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Other Publications (199)
- Cardiology in the Young
- Cardiology in the Young
- Cardiology in the Young
- Nature Communications
- Social Security Bulletin
- Journal of Interpersonal Violence
- Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
- Demography
- Acta Neurochirurgica. Supplement
- Eye (London, England)
- Environmental Science & Technology
- Environmental Science & Technology
- The New England Journal of Medicine
- Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco
- Pain Medicine (Malden, Mass.)
- Clinical Pediatrics
- Australian Occupational Therapy Journal
- Environment International
- Addictive Behaviors
- Investigative Ophthalmology & Visual Science
- Investigative Ophthalmology & Visual Science
- Mayo Clinic Proceedings. Mayo Clinic
- Postgraduate Medicine
- Work (Reading, Mass.)
- JAMA : the Journal of the American Medical Association
- Trends in Microbiology
- Genes, Chromosomes & Cancer
- Biophysical Journal
- Virology Journal
- Journal of Medical Microbiology
- Bioorganic & Medicinal Chemistry
- Journal of Bacteriology
- European Journal of Heart Failure
- Clinics in Podiatric Medicine and Surgery
- Journal of Critical Care
- Current Diabetes Reviews
- Archives of Otolaryngology--head & Neck Surgery
- The Journal of Infectious Diseases
- Tuberculosis (Edinburgh, Scotland)
- Journal of Occupational and Environmental Hygiene
- Ophthalmology
- Ophthalmology
- Clinical & Experimental Optometry : Journal of the Australian Optometrical Association
- The Journal of Infectious Diseases
- Veterinary Microbiology
- Chemical Research in Toxicology
- Journal of Natural Products
- Virology
- The Behavioral and Brain Sciences
- Journal of Lipid Research
- Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
- Journal of Family Psychology : JFP : Journal of the Division of Family Psychology of the American Psychological Association (Division 43)
- Schizophrenia Research
- Memórias Do Instituto Oswaldo Cruz
- Molecular Nutrition & Food Research
- Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme
- Platelets
- Virulence
- Clinics in Podiatric Medicine and Surgery
- Molecular and Cellular Biology
- Metabolic Syndrome and Related Disorders
- Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
- Environmental Health Perspectives
- Environment International
- Nature Chemical Biology
- International Journal of Biological Macromolecules
- The Journal of Infectious Diseases
- PloS One
- Addictive Behaviors
- Archives of Dermatology
- Archives of Dermatology
- PloS One
- Ophthalmology
- Journal of Immunology (Baltimore, Md. : 1950)
- Diabetes Technology & Therapeutics
- Journal of Interventional Cardiology
- Open Biology
- Seminars in Respiratory and Critical Care Medicine
- Aquatic Toxicology (Amsterdam, Netherlands)
- Harvard Review of Psychiatry
- Journal of Medical Microbiology
- The Journal of Infectious Diseases
- Inquiry : a Journal of Medical Care Organization, Provision and Financing
- Antiviral Therapy
- Addiction (Abingdon, England)
- Infection and Immunity
- Atherosclerosis
- Biomacromolecules
- Physical Review Letters
- Environmental Health Perspectives
- American Journal of Physiology. Cell Physiology
- Environmental Health Perspectives
- Pediatric Research
- The Journal of Heredity
- PloS One
- Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology
- The Journal of Trauma and Acute Care Surgery
- Cell Metabolism
- BMC Public Health
- The Australasian Journal of Dermatology
- PM & R : the Journal of Injury, Function, and Rehabilitation
- Environmental Science & Technology
- International Journal of Molecular Sciences
- PloS One
- The Australian & New Zealand Journal of Obstetrics & Gynaecology
- International Journal of Cardiology
- PloS One
- BMC Pregnancy and Childbirth
- Bulletin of the NYU Hospital for Joint Diseases
- Cardiology in the Young
- Molecular Therapy. Nucleic Acids
- ACS Synthetic Biology
- Journal of Exposure Science & Environmental Epidemiology
- Midwifery
- Microcirculation (New York, N.Y. : 1994)
- The Pediatric Infectious Disease Journal
- Evidence-based Medicine
- Journal of Biochemical and Molecular Toxicology
- Journal of Emergency Nursing: JEN : Official Publication of the Emergency Department Nurses Association
- Clinics in Podiatric Medicine and Surgery
- Eye & Contact Lens
- Journal of the American Academy of Dermatology
- Journal of Burn Care & Research : Official Publication of the American Burn Association
- Diabetologia
- Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery
- Eye & Contact Lens
- Pediatrics
- The Journal of General Virology
- Medical Physics
- The Science of the Total Environment
- American Journal of Medical Genetics. Part A
- Contact Lens & Anterior Eye : the Journal of the British Contact Lens Association
- Contact Lens & Anterior Eye : the Journal of the British Contact Lens Association
- Letters in Applied Microbiology
- American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
- American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
- Critical Care (London, England)
- Journal of Midwifery & Women's Health
- Current Diabetes Reviews
- Toxicological Sciences : an Official Journal of the Society of Toxicology
- Clinical & Experimental Optometry : Journal of the Australian Optometrical Association
- Journal of Clinical Nursing
- Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists)
- Environmental Health : a Global Access Science Source
- Waste Management (New York, N.Y.)
- Biochemistry
- Journal of Leukocyte Biology
- Environmental Health Perspectives
- Clinics in Podiatric Medicine and Surgery
- Clinics in Podiatric Medicine and Surgery
- The Journal of Biological Chemistry
- Medicine and Science in Sports and Exercise
- Mayo Clinic Proceedings. Mayo Clinic
- PloS One
- Proteome Science
- Environment International
- Diabetes Technology & Therapeutics
- Aquatic Toxicology (Amsterdam, Netherlands)
- Medicine and Science in Sports and Exercise
- Environmental Health Perspectives
- Environmental Science & Technology
- Proceedings of the National Academy of Sciences of the United States of America
- Eye & Contact Lens
- Statistics in Medicine
- JPEN. Journal of Parenteral and Enteral Nutrition
- Addiction Science & Clinical Practice
- Resuscitation
- Neurosurgical Focus
- BMC Pregnancy and Childbirth
- American Journal of Obstetrics and Gynecology
- Cardiovascular Toxicology
- Clinical & Experimental Optometry : Journal of the Australian Optometrical Association
- Addiction (Abingdon, England)
- JAMA Dermatology (Chicago, Ill.)
- Minerva Cardioangiologica
- The Medical Journal of Australia
- Journal of Chromatography. A
- Nucleic Acids Research
- Environmental Toxicology and Pharmacology
- Journal of Immunology (Baltimore, Md. : 1950)
- Public Health Genomics
- BMC Pregnancy and Childbirth
- Clinical & Experimental Optometry : Journal of the Australian Optometrical Association
- Microbiology (Reading, England)
- JAMA Dermatology (Chicago, Ill.)
- Lab on a Chip
- Environment International
- AIDS (London, England)
- Intensive Care Medicine
- Emergency Medicine Journal : EMJ
- Clinical & Experimental Optometry : Journal of the Australian Optometrical Association
- Molecular Therapy. Nucleic Acids
- Addiction (Abingdon, England)
- JAMA Dermatology (Chicago, Ill.)
- The Journal of Biological Chemistry
- World Neurosurgery
- Proceedings of the National Academy of Sciences of the United States of America
- International Journal of Public Health
- American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Articles by Eloise Stapleton in JoVE
Other articles by Eloise Stapleton on PubMed
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Late Catheter Interventions in Hypoplastic Left Heart Syndrome
Cardiology in the Young.
Dec, 2011 |
Pubmed ID: 22152531 Interventional cardiology plays a key role in the diagnosis and management of patients with functionally univentricular physiology after the various stages of surgical palliation. The interventions performed are widely variable in type, including angioplasty of stenotic vessels and implantation of stents in stenotic vessels; closure of defects such as collaterals, leaks in baffles, and fenestrations; creation of fenestration; and more. In the setting of venous hypertension associated with stenosis at the Fontan baffle, conduit, or pulmonary arteries, stent implantation is often preferred, as the aim is to eliminate completely the narrowing, given that relatively mild stenosis can have a significant detrimental hemodynamic effect in patients with functionally univentricular circulation. The procedure is highly successful. In patients who fail after Fontan procedure, creation of a fenestration is often performed, with variable technique depending on the underlying anatomic substrate. To increase chances of patency of the fenestration, implantation of a stent is often required, particularly in the setting of an extracardiac conduit. For those patients with cyanosis and favorable Fontan hemodynamics, closure of the fenestration is performed using atrial septal occluder devices with high success rate. Coils compatible with magnetic resonance imaging are used widely to treat collateral vessels, although on occasion other specific embolization tools are required, such as particles or vascular plugs. Postoperative arch obstruction is successfully managed with angioplasty at a younger age, while implantation of a stent in the aorta is reserved for older patients. Specifics of these interventional procedures as applied to the population of patients with functionally univentricular hearts are described in this manuscript.
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Translating Sexual Assault Prevention from a College Campus to a United States Military Installation: Piloting the Know-your-power Bystander Social Marketing Campaign
Journal of Interpersonal Violence.
May, 2012 |
Pubmed ID: 22080576 One population that shares both similar and different characteristics with traditional college-age students is the U.S. Military. Similarities include a high concentration of 18- to 26-year-olds dealing with new found independence, peer pressure, and the presence of social norms that support violence and hypermasculinity. Sexual violence is a major public health problem in the United States, and because of the similarities in the age group of college and military populations, the problems regarding sexual violence in both constituencies have been well-documented. In the current pilot study we seek to add to both current knowledge about and promising practices of translating prevention strategies from one target audience to another. We describe how we translated, administered, and evaluated a bystander intervention social marketing campaign focused on sexual assault prevention that had been found to significantly affect attitude change on a college campus for a U.S. Army installation in Europe. In addition to demonstrating the process of translating prevention strategies across target audiences, findings from this pilot study contribute to the evaluation data on the effectiveness of sexual violence prevention strategies implemented with members of the U.S. Military. From our analysis, we see that research participants indicate that the degree to which the images resonate with them and the familiarity of the context (i.e., social self-identification) significantly effect the participants' personal responsibility for reducing sexual assault, confidence in acting as a bystander, and reported engagement as a bystander.
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Out of Sight, out of Mind: Including Group Quarters Residents with Household Residents Can Change What We Know About Working-age People with Disabilities
Demography.
Feb, 2012 |
Pubmed ID: 22109082 Information about residents of institutional and noninstitutional group quarters (GQ), particularly those with disabilities, has been limited by gaps in survey data, and statistics based on data that exclude some or all GQ residents are biased as estimates of total population statistics. We used the 2006 and 2007 American Community Survey (ACS) to identify the distribution of working-age populations with and without disabilities by major residence type and to assess the sensitivity of disability statistics to GQ residence. Our findings show that (1) of those with disabilities, about 1 in 13 males and 1 in 33 females live in GQ; (2) GQ rates are higher for individuals reporting mental, self-care, or go-outside-the-home disabilities than for those reporting sensory, physical, or employment disabilities; (3) younger males with disabilities are more likely to reside there, particularly at institutional GQ, reflecting their relatively high incarceration rate; (4) individuals with and without disabilities who are black, American Indian, were never married, or have less than a high school education have higher GQ residence rates; (5) 40% of male and 62% of female GQ residents have a disability; (6) adding GQ residents to household residents increases estimated disability prevalence for males by 6%, and the estimated difference between disability prevalence rates by gender nearly disappears; and (7) inclusion of the GQ population substantially lowers employment rate estimates for young males, blacks, and American Indians.
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Contact Lens-related Microbial Keratitis: How Have Epidemiology and Genetics Helped Us with Pathogenesis and Prophylaxis
Eye (London, England).
Feb, 2012 |
Pubmed ID: 22134592 Contact lens wear is a common predisposing factor in microbial keratitis and is one of the two preventable risk factors for corneal infection in a working age population. Our understanding of the prevention and prophylaxis of contact lens-related corneal infection is informed by recent epidemiological studies describing the incidence of and risk factors for the disease, the effect of causative organism on disease severity, and an appreciation of individual immune profiles in susceptibility to and severity of the disease. Although contemporary contact lenses have not reduced the overall incidence of keratitis, a reduction in morbidity may be achievable through recognition of appropriate risk factors in severe disease, including avoiding delays in presenting for appropriate treatment, and attention to storage case hygiene practise. Severe keratitis is most commonly associated with an environmental causative organism, and daily disposable lenses are associated with less severe disease. Pseudomonas aeruginosa remains the commonest cause of contact lens-related corneal infection probably because of its unique virulence characteristics and ability to survive in the contact lens/storage case/ocular environment. In two recent outbreaks of contact lens-related infections, there has been a strong association demonstrated with particular contact lens solutions. Since the recall of these specific contact lens solutions, the rate of Acanthamoeba keratitis has remained above the expected baseline, indicating unidentified risk factors that may include environmental exposures. Individual differences in susceptibility to microbial keratitis may be partly explained by differences in single-nucleotide polymorphisms in certain cytokine genes, particularly those with a proven protective role in corneal infection.
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Impact of Dust from Multiple Microenvironments and Diet on PentaBDE Body Burden
Environmental Science & Technology.
Jan, 2012 |
Pubmed ID: 22142368 Our objectives were to determine relative contributions of diet and dust exposure from multiple microenvironments to PentaBDE body burden, and to explore the role of handwipes as a measure of personal exposure to PentaBDE. We administered a food frequency questionnaire and collected serum, dust (office, main living area, bedroom, and vehicle), and handwipe samples from 31 participants. ΣPentaBDEs (sum of BDE 28/33, 47, 99, 100, and 153) in handwipes collected in the office environment were weakly correlated with dust collected from offices (r = 0.35, p = 0.06) and bedrooms (r = 0.39, p = 0.04), but not with dust from main living areas (r = -0.05, p = 0.77) or vehicles (r = 0.17, p = 0.47). ΣPentaBDEs in serum were correlated with dust from main living areas (r = 0.42, p = 0.02) and bedrooms (r = 0.49, p = 0.008), but not with dust from offices (r = 0.22, p = 0.25) or vehicles (r = 0.20, p = 0.41). Our final regression model included variables for main living area dust and handwipes, and predicted 55% of the variation in serum ΣPentaBDE concentrations (p = 0.0004). Diet variables were not significant predictors of ΣPentaBDEs in serum. Our research suggests that exposure to dust in the home environment may be the most important factor in predicting PentaBDE body burden in North Americans, and potential exposure pathways may involve PBDE residues on hands.
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Polyfluorinated Compounds in Serum Linked to Indoor Air in Office Environments
Environmental Science & Technology.
Jan, 2012 |
Pubmed ID: 22148395 We aimed to investigate the role of indoor office air on exposure to polyfluorinated compounds (PFCs) among office workers. Week-long, active air sampling was conducted during the winter of 2009 in 31 offices in Boston, MA. Air samples were analyzed for fluorotelomer alcohols (FTOHs), sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs). Serum was collected from each participant (n = 31) and analyzed for 12 PFCs including PFOA and PFOS. In air, FTOHs were present in the highest concentrations, particularly 8:2-FTOH (GM = 9920 pg/m(3)). FTOHs varied significantly by building with the highest levels observed in a newly constructed building. PFOA in serum was significantly correlated with air levels of 6:2-FTOH (r = 0.43), 8:2-FTOH (r = 0.60), and 10:2-FTOH (r = 0.62). Collectively, FTOHs in air significantly predicted PFOA in serum (p < 0.001) and explained approximately 36% of the variation in serum PFOA concentrations. PFOS in serum was not associated with air levels of FOSAs/FOSEs. In conclusion, FTOH concentrations in office air significantly predict serum PFOA concentrations in office workers. Variation in PFC air concentrations by building is likely due to differences in the number, type, and age of potential sources such as carpeting, furniture, and/or paint.
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Measurement of Flame Retardants and Triclosan in Municipal Sewage Sludge and Biosolids
Environment International.
Apr, 2012 |
Pubmed ID: 22280921 As polybrominated diphenyl ethers (PBDEs) face increasing restrictions worldwide, several alternate flame retardants are expected to see increased use as replacement compounds in consumer products. Chemical analysis of biosolids collected from wastewater treatment plants (WWTPs) can help determine whether these flame retardants are migrating from the indoor environment to the outdoor environment, where little is known about their ultimate fate and effects. The objective of this study was to measure concentrations of a suite of flame retardants, and the antimicrobial compound triclosan, in opportunistic samples of municipal biosolids and the domestic sludge Standard Reference Material (SRM) 2781. Grab samples of biosolids were collected from two WWTPs in North Carolina and two in California. Biosolids samples were also obtained during three subsequent collection events at one of the North Carolina WWTPs to evaluate fluctuations in contaminant levels within a given facility over a period of three years. The biosolids and SRM 2781 were analyzed for PBDEs, hexabromobenzene (HBB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB), di(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), the chlorinated flame retardant Dechlorane Plus (syn- and anti-isomers), and the antimicrobial agent 5-chloro-2-(2,4-dichlorophenoxy)phenol (triclosan). PBDEs were detected in every sample analyzed, and ΣPBDE concentrations ranged from 1750 to 6358ng/g dry weight. Additionally, the PBDE replacement chemicals TBB and TBPH were detected at concentrations ranging from 120 to 3749 ng/g dry weight and from 206 to 1631 ng/g dry weight, respectively. Triclosan concentrations ranged from 490 to 13,866 ng/g dry weight. The detection of these contaminants of emerging concern in biosolids suggests that these chemicals have the potential to migrate out of consumer products and enter the outdoor environment.
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Patterns of Drinking-related Protective and Risk Behaviors in College Student Drinkers
Addictive Behaviors.
Apr, 2012 |
Pubmed ID: 22281283 Drinking-related protective (e.g., pacing consumption) and risk (e.g., participating in drinking games) behaviors influence both the amount of alcohol consumed and the consequences experienced by college students. Previous studies of these behaviors have typically examined use and predictors of these constructs separately. In the current study, latent profile analysis (LPA) was used to identify latent subgroups of drinkers with distinct patterns of use of both drinking-related protective and risk behaviors in a sample of college students. A random sample of first year student drinkers (N=229, 59.4% female) at a large, public university in the Northeastern United States completed a web-based assessment of drinking-related protective and risk behaviors, alcohol use, and related consequences. Three patterns of use were identified, including: 1) students who used protective behaviors frequently and seldom engaged in risk behaviors (10%), 2) students who used risk behaviors more frequently and used protective behaviors less often (30%), and 3) students who used both risk and protective behaviors at similar frequencies (60%). Significant differences in the distribution of profiles were observed when considering gender, age of onset of alcohol use, and recent drinking outcomes including weekend alcohol use, heavy-episodic drinking, and alcohol-related problems. Prevention and intervention programs may benefit from a focus on not only increasing protective actions, but on also reducing risk behaviors beyond that of quantity and frequency of alcohol use alone.
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Metabolic Syndrome: Definition and Therapeutic Implications
Postgraduate Medicine.
Jan, 2012 |
Pubmed ID: 22314111 The collection of impaired glucose metabolism, central obesity, elevated blood pressure, and dyslipidemia is identified as metabolic syndrome (MetS). It is estimated that approximately 25% of the world's population has MetS. In the United States, MetS is more common in men and Hispanics, and its incidence increases with age. Metabolic syndrome increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The underlying risk factors include insulin resistance and abdominal obesity. Confusion about MetS exists in part due to the lack of a consensus definition and treatment protocol. Treatment of MetS begins with therapeutic lifestyle changes and then pharmacologic treatment of the syndrome's individual components. Effective interventions include diet modification, exercise, and use of pharmacologic agents to treat risk factors. Weight loss and increasing physical activity significantly improve all aspects of MetS. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with MetS. Physicians can be most effective in advising patients by customizing specific lifestyle recommendations after assessing patients for the presence of risk factors.
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A New Whole Genome Amplification Method for Studying Clonal Evolution Patterns in Malignant Colorectal Polyps
Genes, Chromosomes & Cancer.
May, 2012 |
Pubmed ID: 22334367 To identify the genetic drivers of colorectal tumorigenesis, we applied array comparative genomic hybridization (aCGH) to 13 formalin-fixed paraffin-embedded (FFPE) samples of early, localized human colon adenocarcinomas arising in high-grade adenomas (so-called "malignant polyps"). These lesions are small and hence the amount of DNA is limited. Additionally, the quality of DNA is compromised due to the fragmentation as a consequence of formalin fixation. To overcome these problems, we optimized a newly developed isothermal whole genome amplification system (NuGEN Ovation® WGA FFPE System). Starting with 100 ng of FFPE DNA, the amplification system produced 4.01 ± 0.29 μg (mean ± standard deviation) of DNA. The excellent quality of amplified DNA was further indicated by a high signal-to-noise ratio and a low derivative log(2) ratio spread. Both, the amount of amplified DNA and aCGH performance were independent of the age of the FFPE blocks and the associated degradation of the extracted DNA. We observed losses of chromosome arms 5q and 18q in the adenoma components of the malignant polyp samples, while the embedded early carcinomas revealed losses of 8p, 17p, and 18, and gains of 7, 13, and 20. Aberrations detected in the adenoma components were invariably maintained in the embedded carcinomas. This approach demonstrates that using isothermally whole genome amplified FFPE DNA is technically suitable for aCGH. In addition to demonstrating the clonal origin of the adenoma and carcinoma part within a malignant polyp, the gain of chromosome arm 20q was an indicator for progression from adenoma to carcinoma.
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AMP-activated Protein Kinase β-subunit Requires Internal Motion for Optimal Carbohydrate Binding
Biophysical Journal.
Jan, 2012 |
Pubmed ID: 22339867 AMP-activated protein kinase interacts with oligosaccharides and glycogen through the carbohydrate-binding module (CBM) containing the β-subunit, for which there are two isoforms (β(1) and β(2)). Muscle-specific β(2)-CBM, either as an isolated domain or in the intact enzyme, binds carbohydrates more tightly than the ubiquitous β(1)-CBM. Although residues that contact carbohydrate are strictly conserved, an additional threonine in a loop of β(2)-CBM is concurrent with an increase in flexibility in β(2)-CBM, which may account for the affinity differences between the two isoforms. In contrast to β(1)-CBM, unbound β(2)-CBM showed microsecond-to-millisecond motion at the base of a β-hairpin that contains residues that make critical contacts with carbohydrate. Upon binding to carbohydrate, similar microsecond-to-millisecond motion was observed in this β-hairpin and the loop that contains the threonine insertion. Deletion of the threonine from β(2)-CBM resulted in reduced carbohydrate affinity. Although motion was retained in the unbound state, a significant loss of motion was observed in the bound state of the β(2)-CBM mutant. Insertion of a threonine into the background of β(1)-CBM resulted in increased ligand affinity and flexibility in these loops when bound to carbohydrate. However, these mutations indicate that the additional threonine is not solely responsible for the differences in carbohydrate affinity and protein dynamics. Nevertheless, these results suggest that altered protein dynamics may contribute to differences in the ligand affinity of the two naturally occurring CBM isoforms.
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Long-range Transcriptional Control of an Operon Necessary for Virulence-critical ESX-1 Secretion in Mycobacterium Tuberculosis
Journal of Bacteriology.
May, 2012 |
Pubmed ID: 22389481 The ESX-1 secretion system of Mycobacterium tuberculosis has to be precisely regulated since the secreted proteins, although required for a successful virulent infection, are highly antigenic and their continued secretion would alert the immune system to the infection. The transcription of a five-gene operon containing espACD-Rv3613c-Rv3612c, which is required for ESX-1 secretion and is essential for virulence, was shown to be positively regulated by the EspR transcription factor. Thus, transcription from the start site, found to be located 67 bp upstream of espA, was dependent upon EspR enhancer-like sequences far upstream (between 884 and 1,004 bp), which we term the espA activating region (EAR). The EAR contains one of the known binding sites for EspR, providing the first in vivo evidence that transcriptional activation at the espA promoter occurs by EspR binding to the EAR and looping out DNA between this site and the promoter. Regulation of transcription of this operon thus takes place over long regions of the chromosome. This regulation may differ in some members of the M. tuberculosis complex, including Mycobacterium bovis, since deletions of the intergenic region have removed the upstream sequence containing the EAR, resulting in lowered espA expression. Consequent differences in expression of ESX-1 in these bacteria may contribute to their various pathologies and host ranges. The virulence-critical nature of this operon means that transcription factors controlling its expression are possible drug targets.
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An Update in Incretin-based Therapy: a Focus on Dipeptidyl Peptidase--4 Inhibitors
Current Diabetes Reviews.
May, 2012 |
Pubmed ID: 22429011 Dipeptidyl peptidase -4 inhibitors represent a novel way to augment the incretin system and one of the newest class of medications in the treatment of type 2 diabetes mellitus. Their mechanism of action is to decrease the inactivation of glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide, both of which are involved in maintaining euglycemia subsequent to carbohydrate intake. Currently investigated agents include sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin. Each agent has been shown to provide significant improvements in glycemic control compared to placebo. They are effective when added to other oral diabetes agents and in the cases of sitagliptin, vildagliptin, and alogliptin in addition to insulin. These agents may not provide as significant improvement in glucose concentrations as some other medications including metformin, thiazolidinediones, or glucagon-like peptide 1 agonists. The lack of head to head clinical data comparing the various dipeptidyl peptidase 4 inhibitors does not allow for specific recommendations if one agent is more effective or safer than another within the class. Their side effect profile suggests they are very well tolerated and have few drug interactions. For patients with mildly elevated glucose concentrations, they are therapeutic options in both drug-naive patients as well as those not optimally controlled on other diabetes medications.
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Cortisol and Interleukin-6 Responses During Intermittent Exercise in Two Different Hot Environments with Equivalent WBGT
Journal of Occupational and Environmental Hygiene.
2012 |
Pubmed ID: 22482790 Blood marker concentrations such as cortisol (COR) and interleukin (IL)-6 are commonly used to evaluate the physiological strain associated with work in the heat. It is unclear, however, if hot environments of an equivalent thermal stress, as defined by a similar wet bulb globe temperature (WBGT), result in similar response patterns. This study examined markers of neuroendocrine (COR) and immune (IL-6) responses, as well as the cardiovascular and thermal responses, relative to changes in body heat content measured by whole-body direct calorimetry during work in two different hot environments with equivalent WBGT. Eight males performed a 2-hr heavy intermittent exercise protocol (six 15-min bouts of cycling at a constant rate of metabolic heat production (360W) interspersed by 5-min rest periods) in Hot/Dry (46°C, 10% relative humidity [RH]) and Warm/Humid (33°C, 60% RH) conditions (WBGT ∼ 29°C). Whole-body evaporative and dry heat exchange, change in body heat content (ΔH(b)), rectal temperature (T(re)), and heart rate were measured continuously. Venous blood was obtained at rest (PRE) and the end of each exercise bout for the measurement of changes in plasma volume (PV), plasma protein (an estimate of plasma water changes), COR, and IL-6. Ratings of perceived exertion and thermal sensation were measured during the last minute of each exercise bout. No differences existed for ΔH(b), heart rate, T(re),%ΔPV, plasma protein concentration, perceptual strain (thermal sensation, perceived exertion), and COR between the Hot/Dry and Warm/Humid conditions. IL-6 exhibited an interaction effect (p = 0.041), such that greater increases were observed in the Hot/Dry (Δ = 1.61 pg·mL(-1)) compared with the Warm/Humid (Δ = 0.64 pg·mL(-1)) environment. These findings indicate that work performed in two different hot environments with equivalent WBGT resulted in similar levels of thermal, cardiovascular, and perceptual strain, which support the use of the WBGT stress index. However, the greater IL-6 response in the Hot/Dry requires further research to elucidate the effects of different hot environments and work intensities.
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In Vitro Metabolism of the Brominated Flame Retardants 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and Bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) in Human and Rat Tissues
Chemical Research in Toxicology.
Jul, 2012 |
Pubmed ID: 22575079 Due to the phaseout of polybrominated diphenyl ether (PBDE) flame retardants, new chemicals, such as 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH), have been used as replacements in some commercial flame retardant mixtures. Both chemicals have been detected in indoor dust at concentrations approaching the concentrations of PBDEs; however, little is known about their fate, metabolism, or toxicity. The goal of this study was to investigate the potential metabolism of these two brominated flame retardants in human and rat tissues by conducting in vitro experiments with liver and intestinal subcellular fractions. In all the experiments, TBB was consistently metabolized to 2,3,4,5-tetrabromobenzoic acid (TBBA) via cleavage of the 2-ethylhexyl chain without requiring any added cofactors. TBBA was also formed in purified porcine carboxylesterase but at a much faster rate of 6.29 ± 0.58 nmol min(-1) mg protein(-1). The estimated K(m) and V(max) values for TBB metabolism in human microsomes were 11.1 ± 3.9 μM and 0.644 ± 0.144 nmol min(-1) mg protein(-1), respectively. A similar K(m) of 9.3 ± 2.2 μM was calculated for porcine carboxylesterase, indicating similar enzyme specificity. While the rapid formation of TBBA may reduce the bioaccumulation potential of TBB in mammals and may be useful as a biomarker of TBB exposure, the toxicity of this brominated benzoic acid is unknown and may be a concern based on its structural similarity to other toxic pollutants. In contrast to TBB, no metabolites of TBPH were detected in human or rat subcellular fractions. However, a metabolic product of TBPH, mono(2-ethylhexyl) tetrabromophthalate (TBMEHP), was formed in purified porcine carboxylesterase at an approximate rate of 1.08 pmol min(-1) mg protein(-1). No phase II metabolites of TBBA or TBMEHP were observed. More research is needed to understand the in vivo toxicokinetics and health effects of these compounds given their current ubiquitous presence in most US households and the resulting probability of chronic exposure, particularly to young children.
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Tsc2, a Positional Candidate Gene Underlying a Quantitative Trait Locus for Hepatic Steatosis
Journal of Lipid Research.
Aug, 2012 |
Pubmed ID: 22628617 Nonalchoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction and is associated with metabolic diseases, including obesity, insulin resistance, and type 2 diabetes. We mapped a quantitative trait locus (QTL) for NAFLD to chromosome 17 in a cross between C57BL/6 (B6) and BTBR mouse strains made genetically obese with the Lep(ob/ob) mutation. We identified Tsc2 as a gene underlying the chromosome 17 NAFLD QTL. Tsc2 functions as an inhibitor of mammalian target of rapamycin, which is involved in many physiological processes, including cell growth, proliferation, and metabolism. We found that Tsc2(+/-) mice have increased lipogenic gene expression in the liver in an insulin-dependent manner. The coding single nucleotide polymorphism between the B6 and BTBR strains leads to a change in the ability to inhibit the expression of lipogenic genes and de novo lipogenesis in AML12 cells and to promote the proliferation of Ins1 cells. This difference is due to a different affinity of binding to Tsc1, which affects the stability of Tsc2.
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Perceived Partner Support in Pregnancy Predicts Lower Maternal and Infant Distress
Journal of Family Psychology : JFP : Journal of the Division of Family Psychology of the American Psychological Association (Division 43).
Jun, 2012 |
Pubmed ID: 22662772 Maternal postpartum emotional distress is quite common and can pose significant risk to mothers and infants. The current study investigated mothers' relationships with their partners during pregnancy and tested the hypotheses that perception of prenatal partner support is a significant predictor of changes in maternal emotional distress from midpregnancy to postpartum, and contributes to maternal ratings of infant distress to novelty. Using a prospective longitudinal design, 272 adult pregnant women were interviewed regarding their partner support, relationship satisfaction, and interpersonal security (attachment style and willingness to seek out support), and they completed standardized measures of prenatal symptoms of depression and anxiety (distress). At 6 to 8 weeks' postpartum, mothers reported these symptoms again and completed measures of their infants' temperament. Structural equation modeling (SEM) was used to test direct and indirect contributions of partner support, relationship satisfaction, and interpersonal security to maternal and infant postpartum distress. Mothers who perceived stronger social support from their partners midpregnancy had lower emotional distress postpartum after controlling for their distress in early pregnancy, and their infants were reported to be less distressed in response to novelty. Partner support mediated the effects of mothers' interpersonal security and relationship satisfaction on maternal and infant outcomes. A high-quality, supportive partner relationship during pregnancy may contribute to improved maternal and infant well-being postpartum, indicating a potential role for partner relationships in mental health interventions, with possible benefits for infants as well.
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Premorbid Multivariate Markers of Neurodevelopmental Instability in the Prediction of Adult Schizophrenia-spectrum Disorder: a High-risk Prospective Investigation
Schizophrenia Research.
Aug, 2012 |
Pubmed ID: 22664169 The authors examined whether multiple childhood indicators of neurodevelopmental instability known to relate to schizophrenia-spectrum disorders could predict later schizophrenia-spectrum outcomes. A standardized battery of neurological and intellectual assessments was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Adult diagnostic information was available for 244 members of the sample. Participants were grouped into three categories indicating level of genetic risk: children with a parent with schizophrenia (n=94); children with a parent with a non-psychotic mental health diagnosis (n=84); and children with a parent with no records of psychiatric hospitalization (n=66). Variables measured included minor physical anomalies (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were assessed through psychiatric interviews in 1992, as well as through a scan of the national psychiatric registry through 2007. Through a combination of multiple childhood predictors, the model correctly classified 73% (24 of 33) of the participants who eventually developed a schizophrenia-spectrum outcome in adulthood. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing a schizophrenia-spectrum disorder. Genetic risk, MPAs, and other markers of neurodevelopmental instability may be useful for comprehensive prediction models.
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Effect of Chromium Dinicocysteinate Supplementation on Circulating Levels of Insulin, TNF-α, Oxidative Stress, and Insulin Resistance in Type 2 Diabetic Subjects: Randomized, Double-blind, Placebo-controlled Study
Molecular Nutrition & Food Research.
Aug, 2012 |
Pubmed ID: 22674882 Chromium and cysteine supplementation have been shown to improve glucose metabolism in animal studies. This study examined the hypothesis that chromium dinicocysteinate (CDNC), a complex of chromium and l-cysteine, is beneficial in lowering oxidative stress, vascular inflammation, and glycemia in type 2 diabetic subjects.
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Body Heat Storage During Intermittent Work in Hot-dry and Warm-wet Environments
Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme.
Oct, 2012 |
Pubmed ID: 22686402 We examined heat balance using an American Conference of Governmental Industrial Hygienists threshold limit value allocated exercise protocol in hot-dry (HD; 46 °C, 10% relative humidity (RH)) and warm-wet (WW; 33 °C, 60% RH) environments of equivalent WBGT (29 °C) for different clothing ensembles. Whole-body heat exchange and changes in body heat content (ΔH(b)) were measured using simultaneous direct whole-body and indirect calorimetry. Eight males performed six 15-min cycling periods at a constant rate of metabolic heat production (360 W) interspersed by 5-min rest periods for six experimental trials: HD and WW environments for a seminude control (CON), modified work uniform (MWU, moisture permeable top and work pants), and standard work uniform (SWU, work coveralls and cotton undergarments). Whole-body evaporative and dry heat exchange, rectal temperature (T(re)), and heart rate were measured continuously. The cumulative ΔH(b) during the 2 h intermittent exercise protocol was similar between HD and WW environments for each of the clothing ensembles (CON, 387 ± 55 vs. 435 ± 49 kJ; MWU, 485 ± 58 vs. 531 ± 61 kJ; SWU, 585 ± 74 vs. 660 ± 54 kJ, respectively). Similarly, no differences in T(re) (CON, 37.67 ± 0.07 vs. 37.48 ± 0.08 °C; MWU, 37.73 ± 0.08 vs. 37.53 ± 0.09 °C; SWU, 38.01 ± 0.09 vs. 37.94 ± 0.05 °C) or heat rate (CON, 93 ± 3 vs. 84 ± 3 beats·minâ»Â¹; MWU, 102 ± 5 vs. 95 ± 9 beats·minâ»Â¹; SWU, 119 ± 8 vs. 110 ± 9 beats·minâ»Â¹) were observed at the end of the 2 h intermittent exercise protocol in HD vs. WW environments, respectively. We showed similar levels of thermal and cardiovascular strain for intermittent work performed in high heat stress conditions of varying environmental conditions but similar WBGT.
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GATA6 is Required for Proliferation, Migration, Secretory Cell Maturation, and Gene Expression in the Mature Mouse Colon
Molecular and Cellular Biology.
Sep, 2012 |
Pubmed ID: 22733991 Controlled renewal of the epithelium with precise cell distribution and gene expression patterns is essential for colonic function. GATA6 is expressed in the colonic epithelium, but its function in the colon is currently unknown. To define GATA6 function in the colon, we conditionally deleted Gata6 throughout the epithelium of small and large intestines of adult mice. In the colon, Gata6 deletion resulted in shorter, wider crypts, a decrease in proliferation, and a delayed crypt-to-surface epithelial migration rate. Staining techniques and electron microscopy indicated deficient maturation of goblet cells, and coimmunofluorescence demonstrated alterations in specific hormones produced by the endocrine L cells and serotonin-producing cells. Specific colonocyte genes were significantly downregulated. In LS174T, the colonic adenocarcinoma cell line, Gata6 knockdown resulted in a significant downregulation of a similar subset of goblet cell and colonocyte genes, and GATA6 was found to occupy active loci in enhancers and promoters of some of these genes, suggesting that they are direct targets of GATA6. These data demonstrate that GATA6 is necessary for proliferation, migration, lineage maturation, and gene expression in the mature colonic epithelium.
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Brominated and Chlorinated Flame Retardants in San Francisco Bay Sediments and Wildlife
Environment International.
Oct, 2012 |
Pubmed ID: 22766500 Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted in the use of alternative flame retardants in consumer products to comply with flammability standards. In contrast to PBDEs, information on the occurrence and fate of these alternative compounds in the environment is limited, particularly in the United States. In this study, a survey of flame retardants in San Francisco Bay was conducted to evaluate whether PBDE replacement chemicals and other current use flame retardants were accumulating in the Bay food web. In addition to PBDEs, brominated and chlorinated flame retardants (hexabromocyclododecane (HBCD) and Dechlorane Plus (DP)) were detected in Bay sediments and wildlife. Median concentrations of PBDEs, HBCD, and DP, respectively, were 4.3, 0.3, and 0.2 ng gâ»Â¹ dry weight (dw) in sediments; 1670,
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Factors Affecting Hatch Success of Hawksbill Sea Turtles on Long Island, Antigua, West Indies
PloS One.
2012 |
Pubmed ID: 22802928 Current understanding of the factors influencing hawksbill sea turtle (Eretmochelys imbricata) hatch success is disparate and based on relatively short-term studies or limited sample sizes. Because global populations of hawksbills are heavily depleted, evaluating the parameters that impact hatch success is important to their conservation and recovery. Here, we use data collected by the Jumby Bay Hawksbill Project (JBHP) to investigate hatch success. The JBHP implements saturation tagging protocols to study a hawksbill rookery in Antigua, West Indies. Habitat data, which reflect the varied nesting beaches, are collected at egg deposition, and nest contents are exhumed and categorized post-emergence. We analyzed hatch success using mixed-model analyses with explanatory and predictive datasets. We incorporated a random effect for turtle identity and evaluated environmental, temporal and individual-based reproductive variables. Hatch success averaged 78.6% (SD: 21.2%) during the study period. Highly supported models included multiple covariates, including distance to vegetation, deposition date, individual intra-seasonal nest number, clutch size, organic content, and sand grain size. Nests located in open sand were predicted to produce 10.4 more viable hatchlings per clutch than nests located >1.5 m into vegetation. For an individual first nesting in early July, the fourth nest of the season yielded 13.2 more viable hatchlings than the initial clutch. Generalized beach section and inter-annual variation were also supported in our explanatory dataset, suggesting that gaps remain in our understanding of hatch success. Our findings illustrate that evaluating hatch success is a complex process, involving multiple environmental and individual variables. Although distance to vegetation and hatch success were inversely related, vegetation is an important component of hawksbill nesting habitat, and a more complete assessment of the impacts of specific vegetation types on hatch success and hatchling sex ratios is needed. Future research should explore the roles of sand structure, nest moisture, and local weather conditions.
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GB Virus C Envelope Protein E2 Inhibits TCR-induced IL-2 Production and Alters IL-2-signaling Pathways
Journal of Immunology (Baltimore, Md. : 1950).
Sep, 2012 |
Pubmed ID: 22844114 GB virus type C (GBV-C) viremia is associated with reduced CD4+ T cell expansion following IL-2 therapy and with a reduction in T cell activation in HIV-infected individuals. The mechanism(s) by which GBV-C might alter T cell activation or IL-2 signaling have not been studied. In this study, we assess IL-2 release, IL-2R expression, IL-2 signaling, and cell proliferation in tet-off Jurkat cells expressing the GBV-C envelope glycoprotein (E2) following activation through the TCR. TCR activation was induced by incubation in anti-CD3/CD28 Abs. IL-2 release was measured by ELISA, STAT5 phosphorylation was assessed by immunoblot, and IL-2Rα (CD25) expression and cell proliferation were determined by flow cytometry. IL-2 and IL-2Rα steady-state mRNA levels were measured by real-time PCR. GBV-C E2 expression significantly inhibited IL-2 release, CD25 expression, STAT5 phosphorylation, and cellular proliferation in Jurkat cells following activation through the TCR compared with control cell lines. Reducing E2 expression by doxycycline reversed the inhibitory effects observed in the E2-expressing cells. The N-terminal 219 aa of E2 was sufficient to inhibit IL-2 signaling. Addition of purified recombinant GBV-C E2 protein to primary human CD4+ and CD8+ T cells inhibited TCR activation-induced IL-2 release and upregulation of IL-2Rα expression. These data provide evidence that the GBV-C E2 protein may contribute to the block in CD4+ T cell expansion following IL-2 therapy in HIV-infected individuals. Furthermore, the effects of GBV-C on IL-2 and IL-2-signaling pathways may contribute to the reduction in chronic immune activation observed in GBV-C/HIV-coinfected individuals.
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An Update in Incretin-based Therapy: a Focus on Glucagon-like Peptide-1 Receptor Agonists
Diabetes Technology & Therapeutics.
Oct, 2012 |
Pubmed ID: 22845681 The glucagon-like peptide-1 receptor agonists, exenatide and liraglutide, offer a unique mechanism in the treatment of type 2 diabetes mellitus (T2DM) as part of the incretin system. Their mechanism of action is to increase insulin secretion, decrease glucagon release, reduce food intake, and slow gastric emptying. They target postprandial blood glucose values and have some effect on fasting levels as well. In addition, they promote weight loss and may help to preserve β-cell function, both major problems in T2DM patients. Changes in hemoglobin A1c are similar to those produced by other T2DM agents, including thiazolidinediones, low-dose metformin, and sulfonylureas, and better than those caused by α-reductase inhibitors and dipeptidyl peptidase-4 inhibitors. These agents have been safely studied in combination with metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin therapy. Overall, data are limited for head-to-head comparisons, but it appears that liraglutide may have better efficacy and tolerability compared with exenatide; however, more studies are needed. They are overall well tolerated, with the main adverse events being similar to those with metformin (gastrointestinal intolerances that are transient and dose dependent). However, patients must be monitored for pancreatitis as a rare but possible side effect. For T2DM patients willing to use an injectable agent, exenatide and liraglutide offer another therapeutic option to control hyperglycemia with the potential for weight loss and may be combined with other agents safely.
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Systems Analysis of Transcription Factor Activities in Environments with Stable and Dynamic Oxygen Concentrations
Open Biology.
Jul, 2012 |
Pubmed ID: 22870390 Understanding gene regulation requires knowledge of changes in transcription factor (TF) activities. Simultaneous direct measurement of numerous TF activities is currently impossible. Nevertheless, statistical approaches to infer TF activities have yielded non-trivial and verifiable predictions for individual TFs. Here, global statistical modelling identifies changes in TF activities from transcript profiles of Escherichia coli growing in stable (fixed oxygen availabilities) and dynamic (changing oxygen availability) environments. A core oxygen-responsive TF network, supplemented by additional TFs acting under specific conditions, was identified. The activities of the cytoplasmic oxygen-responsive TF, FNR, and the membrane-bound terminal oxidases implied that, even on the scale of the bacterial cell, spatial effects significantly influence oxygen-sensing. Several transcripts exhibited asymmetrical patterns of abundance in aerobic to anaerobic and anaerobic to aerobic transitions. One of these transcripts, ndh, encodes a major component of the aerobic respiratory chain and is regulated by oxygen-responsive TFs ArcA and FNR. Kinetic modelling indicated that ArcA and FNR behaviour could not explain the ndh transcript profile, leading to the identification of another TF, PdhR, as the source of the asymmetry. Thus, this approach illustrates how systematic examination of regulatory responses in stable and dynamic environments yields new mechanistic insights into adaptive processes.
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Species Specific Differences in the in Vitro Metabolism of the Flame Retardant Mixture, Firemaster® BZ-54
Aquatic Toxicology (Amsterdam, Netherlands).
Nov, 2012 |
Pubmed ID: 22889877 Firemaster(®) BZ-54 is a flame retardant additive and consists of a brominated benzoate (2-ethylhexyl 2,3,4,5-tetrabromobenzoate; TBB) and a brominated phthalate (bis (2-ethylhexyl) 2,3,4,5-tetrabromophthalate; TBPH). Previous research has shown that fathead minnows exposed in vivo to Firemaster(®) BZ-54 accumulate TBB and TBPH. This study examined the in vitro biotransformation potential of TBB and TBPH in hepatic subcellular fractions (i.e., S9, microsomes and cytosol) in the fathead minnow, common carp, mouse and snapping turtle. Metabolism was evaluated by measuring the loss of the parent TBB or TBPH and identifying potential metabolites in the sample extracts. Metabolic loss of TBPH was measured for all species, while TBB loss was observed for all species except for the snapping turtle. Several metabolites were observed in all of the incubations except for snapping turtle. Metabolites observed appeared to be derived from TBB, given their structures and lack of appearance in the snapping turtle incubations. One of these metabolites, 2,3,4,5-tetrabromomethylbenzoate has been identified for the first time in a biological system. When metabolized, TBB and TBPH loss was found in each subcellular fraction suggesting that the enzyme(s) involved are present in both soluble and membrane-bound forms. It can be concluded that a broad range of species are capable of metabolizing TBB and TBPH to various metabolites and further research should be carried out to ascertain the specific products formed from metabolism of TBB and TBPH.
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Addressing Sexual and Relationship Violence in the LGBT Community Using a Bystander Framework
Harvard Review of Psychiatry.
Jul-Aug, 2012 |
Pubmed ID: 22894729 Sexual and relationship violence are two major public health issues that affect an alarming number of undergraduate students. As a result, many colleges and universities have protocols to serve victims of these forms of violence. Despite federal legislation stating that all students should have equitable experiences, current protocols and programs focus primarily on heterosexual students. College student victims of sexual and relationship violence who identify as lesbian, gay, bisexual, or transgender can face particular challenges, including disclosure of their sexual and gender orientations, and revictimization when seeking services. In recent years an increasing number of campuses have adopted bystander prevention strategies to address sexual and relationship violence. These strategies seek to engage community members in the prevention of sexual and relationship violence by training them to identify and safely intervene in situations where sexual or relationship violence is about to occur, is occurring, or has occurred. In this article we review published bystander prevention strategies that focus on preventing sexual and relationship violence in the campus community, and discuss how bystander strategies are addressing or can address relationship and sexual violence in the LGBT community.
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Evaluation of Two Multiplex Real-time PCR Screening Capabilities for the Detection of Bacillus Anthracis, Francisella Tularensis and Yersinia Pestis in Blood Samples Generated from Murine Infection Models
Journal of Medical Microbiology.
Nov, 2012 |
Pubmed ID: 22899777 Two multiplex PCR screening capabilities (TaqMan Array Cards and FilmArray) were evaluated for their ability to detect Bacillus anthracis, Francisella tularensis and Yersinia pestis in blood samples obtained from respective murine infection models. Blood samples were obtained from infected mice at 24 h intervals after exposure. Multiplex PCR results were compared with standard blood culture and singleplex real-time PCR. Across all three models, 71 mice were tested in total, within which a subset of 43 samples was shown to contain an infecting agent by at least one of the detection technologies. Within this subset of positive samples, for each model studied, the detection rates of each technology were compared. The B. anthracis model blood culture (14 of 15 agent-containing samples tested) and FilmArray PCR (12 of 15) were shown to have equivalent detection rates, which were significantly higher (at the 95 % confidence level) than singleplex (five of 14) or Array Card (two of 14) PCRs. The F. tularensis model blood culture (12 of 12) was shown to have a significantly higher (at 95 % confidence level) detection rate than all PCR technologies, with FilmArray (seven of 11) and singleplex (seven of 12) PCRs shown to have significantly higher (at 95 % confidence level) detection rates than the Array Card PCR (two of 11). Within the Y. pestis model, there was no significant difference in detection rates between blood culture (10 of 16), singleplex PCR (14 of 16), Array Card PCR (10 of 16) and FilmArray PCR (10 of 13).
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Escherichia Coli Isolates That Carry Vat, FyuA, ChuA, and YfcV Efficiently Colonize the Urinary Tract
Infection and Immunity.
Dec, 2012 |
Pubmed ID: 22966046 Extraintestinal Escherichia coli (ExPEC), a heterogeneous group of pathogens, encompasses avian, neonatal meningitis, and uropathogenic E. coli strains. While several virulence factors are associated with ExPEC, there is no core set of virulence factors that can be used to definitively differentiate these pathotypes. Here we describe a multiplex of four virulence factor-encoding genes, yfcV, vat, fyuA, and chuA, highly associated with uropathogenic E. coli strains that can distinguish three groups of E. coli: diarrheagenic and animal-associated E. coli strains, human commensal and avian pathogenic E. coli strains, and uropathogenic and neonatal meningitis E. coli strains. Furthermore, human intestinal isolates that encode all four predictor genes express them during exponential growth in human urine and colonize the bladder in the mouse model of ascending urinary tract infection in higher numbers than human commensal strains that do not encode the four predictor genes (P = 0.02), suggesting that the presence of the predictors correlates with uropathogenic potential.
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Relationship Between Hydrogen Sulfide Levels and HDL-cholesterol, Adiponectin, and Potassium Levels in the Blood of Healthy Subjects
Atherosclerosis.
Nov, 2012 |
Pubmed ID: 22989474 Hydrogen sulfide (H(2)S) is an important signaling molecule whose blood levels have been shown to be lower in certain disease states. Increasing evidence indicates that H(2)S plays a potentially significant role in many biological processes and that malfunctioning of H(2)S homeostasis may contribute to the pathogenesis of vascular inflammation and atherosclerosis. This study examined the fasting blood levels of H(2)S, HDL-cholesterol, LDL-cholesterol, triglycerides, adiponectin, resistin, and potassium in 36 healthy adult volunteers. There was a significant positive correlation between blood levels of H(2)S and HDL-cholesterol (r = 0.49, p = 0.003), adiponectin (r = 0.36, p = 0.04), and potassium (r = 0.34, p = 0.047), as well as a significant negative correlation with LDL/HDL levels (r = -0.39, p = 0.02). This is the first demonstration of an association of circulating levels of H(2)S with the HDL, LDL, and adiponectin homeostasis in the blood of healthy humans.
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Molecular Insights into Glycogen α-particle Formation
Biomacromolecules.
Nov, 2012 |
Pubmed ID: 23004915 Glycogen, a hyperbranched complex glucose polymer, is an intracellular glucose store that provides energy for cellular functions, with liver glycogen involved in blood-glucose regulation. Liver glycogen comprises complex α particles made up of smaller β particles. The recent discovery that these α particles are smaller and fewer in diabetic, compared with healthy, mice highlights the need to elucidate the nature of α-particle formation; this paper tests various possibilities for binding within α particles. Acid hydrolysis effects, examined using dynamic light scattering and size exclusion chromatography, showed that the binding is not simple α-(1→4) or α-(1→6) glycosidic linkages. There was no significant change in α particle size after the addition of various reagents, which disrupt disulfide, protein, and hydrogen bonds and hydrophobic interactions. The results are consistent with proteinaceous binding between β particles in α particles, with the inability of protease to break apart particles being attributed to steric hindrance.
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Single Fiber Analyses of Glycogen-related Proteins Reveal Their Differential Association with Glycogen in Rat Skeletal Muscle
American Journal of Physiology. Cell Physiology.
Dec, 2012 |
Pubmed ID: 23015546 To understand how glycogen affects skeletal muscle physiology, we examined enzymes essential for muscle glycogen synthesis and degradation using single fibers from quiescent and stimulated rat skeletal muscle. Presenting a shift in paradigm, we show these proteins are differentially associated with glycogen granules. Protein diffusibility and/or abundance of glycogenin, glycogen branching enzyme (GBE), debranching enzyme (GDE), phosphorylase (GP), and synthase (GS) were examined in fibers isolated from rat fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscle. GDE and GP proteins were more abundant (~10- to 100-fold) in fibers from EDL compared with SOL muscle. GS and glycogenin proteins were similar between muscles while GBE had an approximately fourfold greater abundance in SOL muscle. Mechanically skinned fibers exposed to physiological buffer for 10 min showed ~70% total pools of GBE and GP were diffusible (nonbound), whereas GDE and GS were considerably less diffusible. Intense in vitro stimulation, sufficient to elicit a ~50% decrease in intracellular glycogen, increased diffusibility of GDE, GP, and GS (~15-60%) and decreased GBE diffusibility (~20%). Amylase treatment, which breaks α-1,4 linkages of glycogen, indicated differential diffusibilities and hence glycogen associations of GDE and GS. Membrane solubilization (1% Triton-X-100) allowed a small additional amount of GDE and GS to diffuse from fibers, suggesting the majority of nonglycogen-associated GDE/GS is associated with myofibrillar/contractile network of muscle rather than membranes. Given differences in enzymes required for glycogen metabolism, the current findings suggest glycogen particles have fiber-type-dependent structures. The greater catabolic potential of glycogen breakdown in fast-twitch fibers may account for different contraction induced rates of glycogen utilization.
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Novel and High Volume Use Flame Retardants in US Couches Reflective of the 2005 PentaBDE Phase Out
Environmental Science & Technology.
Dec, 2012 |
Pubmed ID: 23186002 California's furniture flammability standard Technical Bulletin 117 (TB 117) is believed to be a major driver of chemical flame retardant (FR) use in residential furniture in the United States. With the phase-out of the polybrominated diphenyl ether (PBDE) FR mixture PentaBDE in 2005, alternative FRs are increasingly being used to meet TB 117; however, it was unclear which chemicals were being used and how frequently. To address this data gap, we collected and analyzed 102 samples of polyurethane foam from residential couches purchased in the United States from 1985 to 2010. Overall, we detected chemical flame retardants in 85% of the couches. In samples purchased prior to 2005 (n = 41) PBDEs associated with the PentaBDE mixture including BDEs 47, 99, and 100 (PentaBDE) were the most common FR detected (39%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCPP; 24%), which is a suspected human carcinogen. In samples purchased in 2005 or later (n = 61) the most common FRs detected were TDCPP (52%) and components associated with the Firemaster550 (FM 550) mixture (18%). Since the 2005 phase-out of PentaBDE, the use of TDCPP increased significantly. In addition, a mixture of nonhalogenated organophosphate FRs that included triphenyl phosphate (TPP), tris(4-butylphenyl) phosphate (TBPP), and a mix of butylphenyl phosphate isomers were observed in 13% of the couch samples purchased in 2005 or later. Overall the prevalence of flame retardants (and PentaBDE) was higher in couches bought in California compared to elsewhere, although the difference was not quite significant (p = 0.054 for PentaBDE). The difference was greater before 2005 than after, suggesting that TB 117 is becoming a de facto standard across the U.S. We determined that the presence of a TB 117 label did predict the presence of a FR; however, lack of a label did not predict the absence of a flame retardant. Following the PentaBDE phase out, we also found an increased number of flame retardants on the market. Given these results, and the potential for human exposure to FRs, health studies should be conducted on the types of FRs identified here.
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Impairment of Coronary Arteriolar Endothelium-dependent Dilation After Multi-walled Carbon Nanotube Inhalation: a Time-course Study
International Journal of Molecular Sciences.
2012 |
Pubmed ID: 23203034 Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24-168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed.
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GB Virus C Infection is Associated with Altered Lymphocyte Subset Distribution and Reduced T Cell Activation and Proliferation in HIV-infected Individuals
PloS One.
2012 |
Pubmed ID: 23209780 GBV-C infection is associated with prolonged survival and with reduced T cell activation in HIV-infected subjects not receiving combination antiretroviral therapy (cART). The relationship between GBV-C and T cell activation in HIV-infected subjects was examined. HIV-infected subjects on cART with non-detectable HIV viral load (VL) or cART naïve subjects were studied. GBV-C VL and HIV VL were determined. Cell surface markers of activation (CD38(+)/HLA-DR(+)), proliferation (Ki-67+), and HIV entry co-receptor expression (CCR5+ and CXCR4+) on total CD4+ and CD8+ T cells, and on naïve, central memory (CM), effector memory (EM), and effector CD4+ and CD8+ subpopulations were measured by flow cytometry. In subjects with suppressed HIV VL, GBV-C was consistently associated with reduced activation in naïve, CM, EM, and effector CD4+ cells. GBV-C was associated with reduced CD4+ and CD8+ T cell surface expression of activation and proliferation markers, independent of HIV VL classification. GBV-C was also associated with higher proportions of naïve CD4+ and CD8+ T cells, and with lower proportions of EM CD4+ and CD8+ T cells. In conclusion, GBV-C infection was associated with reduced activation of CD4+ and CD8+ T cells in both HIV viremic and HIV RNA suppressed patients. Those with GBV-C infection demonstrated an increased proportion of naive T cells and a reduction in T cell activation and proliferation independent of HIV VL classification, including those with suppressed HIV VL on cART. Since HIV pathogenesis is thought to be accelerated by T cell activation, these results may contribute to prolonged survival among HIV infected individuals co-infected with GBV-C. Furthermore, since cART therapy does not reduce T cell activation to levels seen in HIV-uninfected people, GBV-C infection may be beneficial for HIV-related diseases in those effectively treated with anti-HIV therapy.
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A New Anti-fibrotic Drug Attenuates Cardiac Remodeling and Systolic Dysfunction Following Experimental Myocardial Infarction
International Journal of Cardiology.
Dec, 2012 |
Pubmed ID: 23219315 BACKGROUND: Pathological deposition of extracellular matrix in the non-infarct zone (NIZ) of the ventricle post myocardial infarction (MI) is a key contributor to cardiac remodeling and heart failure. FT011, a novel antifibrotic compound, was evaluated for its efficacy in neonatal cardiac fibroblasts (NCF) and in an experimental MI model. METHODS AND RESULTS: Collagen synthesis in NCF was determined by (3)H-proline incorporation following stimulation with TGF-β or angiotensin II (Ang II). FT011 inhibited collagen synthesis to both agents in a dose dependent manner. In vivo, Sprague Dawley rats underwent left anterior descending coronary artery ligation or sham surgery and were randomized one week later to receive either FT011 (200mg/kg/day) or vehicle for a further 4weeks. Echocardiography and cardiac catheterization were performed, and tissues were collected for histological analysis of collagen, myocyte hypertrophy, interstitial macrophage accumulation and Smad2 phosphorylation. mRNA expression of collagens I and III and TGF-β was measured using in situ hybridization and RT-PCR, respectively. FT011 treatment was associated with improved cardiac function (increased ejection fraction, fraction shortening and preload recruitable stroke work) and myocardial remodeling (reduced left ventricular diameter and volume at both end diastolic and systolic) compared with vehicle treatment. FT011 significantly reduced collagen matrix deposition, myocyte hypertrophy and interstitial macrophage infiltration, and mRNA expression of collagens I and III in NIZ compared with vehicle treatment. CONCLUSION: Anti-fibrotic therapy with FT011 in MI rats attenuated fibrosis and preserved systolic function.
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Associations Between Serum Levels of Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Environmental and Behavioral Factors in Pregnant Women
Journal of Exposure Science & Environmental Epidemiology.
Mar, 2013 |
Pubmed ID: 22760441 Polybrominated diphenyl ethers (PBDE) are flame retardants that were previously used in upholstery, fabrics, and household appliances. PBDEs have been linked to adverse health outcomes, including neurotoxicity, thyroid hormone dysregulation, endocrine disruption, and poor semen quality. Because PBDEs pass into placental circulation, maternal exposures can approximate fetal exposures. Our objectives were to determine whether diet and specific human behaviors were significantly associated with PBDE exposures in a cohort of pregnant women. Women between the 34th and 38th week of pregnancy were given a questionnaire about behavioral, environmental, and dietary factors and asked to provide blood samples. Serum PBDE levels were measured using GS-MS and lipid adjusted. An adjusted ordinary least squares regression model was run to identify potential associations between behaviors and serum PBDE levels. Serum concentrations of BDEs 47, 99, 100, and 153 were found above the limit of detection in at least 50% of study participants and used in our models. Associations with serum PBDEs were observed with self-reported hand-to-mouth behaviors, including biting nails and licking fingers. Serum BDE levels of 47, 99, 153, and total PBDEs were also significantly higher in those individuals owning a large-screen TV compared with those who did not. Serum PBDE levels were comparable to levels reported in the general population. Hand-to-mouth behaviors may influence serum PBDE concentrations in adults. Household electronics such as large-screen TVs appear to serve as a significant source of PBDEs in pregnant women. Together, hand-to-mouth behaviors and TV ownership may serve as a route of exposure to PBDEs in adults.
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Effect of Human Skin Grafts on Whole-body Heat Loss During Exercise Heat Stress: a Case Report
Journal of Burn Care & Research : Official Publication of the American Burn Association.
Jul-Aug, 2013 |
Pubmed ID: 23202874 When exposed to heat stress, increases in cutaneous blood flow and sweating in well-healed grafted skin are severely attenuated, which could impair whole-body heat loss if skin grafts cover a large portion of total body surface area (TBSA). It is unknown to what extent whole-body heat loss is impaired when skin grafts cover a significant (eg, >50%) proportion of TBSA. The authors examined whole-body heat exchange during and after 60 min of cycling exercise in the heat (35°C; 25% relative humidity), at a fixed rate of metabolic heat production (~400 W) in a woman (age, 36 years; mass, 78.2 kg) with well-healed (17+ years) skin grafts covering 75% of TBSA. Her responses were compared with two noninjured control subjects. Whole-body evaporative and dry heat exchange were measured by direct calorimetry. While exercising in the same ambient conditions and at the same rate of heat production, relative evaporative heat loss of nongrafted skin in the grafted subject (ie, evaporative heat loss per m) was nearly twice that of the control subjects. However, total rate of evaporative heat loss reached only 59% of the amount required for heat balance in the skin-grafted subject compared with 92 ± 3% in controls. Thus, the increase in core temperature was 2-fold greater for the grafted (1.22°C) vs control (0.61 ± 0.19°C) individuals. This case study demonstrates that a large area of grafted skin greatly diminishes maximum evaporative heat loss during exercise in the heat, making a compensable environment for control subjects uncompensable for skin-grafted individuals.
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Chimpanzee GB Virus C and GB Virus A E2 Envelope Glycoproteins Contain a Peptide Motif That Inhibits Human Immunodeficiency Virus Type 1 Replication in Human CD4⺠T-cells
The Journal of General Virology.
Apr, 2013 |
Pubmed ID: 23288422 GB virus type C (GBV-C) is a lymphotropic virus that can cause persistent infection in humans. GBV-C is not associated with any disease, but is associated with reduced mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Related viruses have been isolated from chimpanzees (GBV-Ccpz) and from New World primates (GB virus type A, GBV-A). These viruses are also capable of establishing persistent infection. We determined the nucleotide sequence encoding the envelope glycoprotein (E2) of two GBV-Ccpz isolates obtained from the sera of captive chimpanzees. The deduced GBV-Ccpz E2 protein differed from human GBV-C by 31 % at the amino acid level. Similar to human GBV-C E2, expression of GBV-Ccpz E2 in a tet-off human CD4(+) Jurkat T-cell line significantly inhibited the replication of diverse HIV-1 isolates. This anti-HIV-replication effect of GBV-Ccpz E2 protein was reversed by maintaining cells in doxycycline to reduce E2 expression. Previously, we found a 17 aa region within human GBV-C E2 that was sufficient to inhibit HIV-1. Although GBV-Ccpz E2 differed by 3 aa differences in this region, the chimpanzee GBV-C 17mer E2 peptide inhibited HIV-1 replication. Similarly, the GBV-A peptide that aligns with this GBV-C E2 region inhibited HIV-1 replication despite sharing only 5 aa with the human GBV-C E2 sequence. Thus, despite amino acid differences, the peptide region on both the GBV-Ccpz and the GBV-A E2 protein inhibit HIV-1 replication similar to human GBV-C. Consequently, GBV-Ccpz or GBV-A infection of non-human primates may provide an animal model to study GB virus-HIV interactions.
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Associations Between Brominated Flame Retardants in House Dust and Hormone Levels in Men
The Science of the Total Environment.
Feb, 2013 |
Pubmed ID: 23333513 Brominated flame retardants (BFRs) are used in the manufacture of a variety of materials and consumer products in order to meet fire safety standards. BFRs may persist in the environment and have been detected in wildlife, humans and indoor dust and air. Some BFRs have demonstrated endocrine and reproductive effects in animals, but human studies are limited. In this exploratory study, we measured serum hormone levels and flame retardant concentrations [31 polybrominated diphenyl ether (PBDE) congeners and 6 alternate flame retardants] in house dust from men recruited through a US infertility clinic. PBDE congeners in dust were grouped by commercial mixtures (i.e. penta-, octa- and deca-BDE). In multivariable linear regression models adjusted by age and body mass index (BMI), significant positive associations were found between house dust concentrations of pentaBDEs and serum levels of free T4, total T3, estradiol, and sex hormone binding globulin (SHBG), along with an inverse association with follicle stimulating hormone (FSH). There were also positive associations of octaBDE concentrations with serum free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone and an inverse association of decaBDE concentrations with testosterone. Hexabromocyclododecane (HBCD) was associated with decreased SHBG and increased free androgen index. Dust concentrations of bis-tribromophenoxyethane (BTBPE) and tetrabromo-diethylhexylphthalate (TBPH) were positively associated with total T3. These findings are consistent with our previous report of associations between PBDEs (BDE 47, 99 and 100) in house dust and hormone levels in men, and further suggest that exposure to contaminants in indoor dust may be leading to endocrine disruption in men.
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Positive Effects of Short Course Androgen Therapy on the Neurodevelopmental Outcome in Boys with 47,XXY Syndrome at 36 and 72 Months of Age
American Journal of Medical Genetics. Part A.
Mar, 2013 |
Pubmed ID: 23345253 The effects of early androgen treatment on neurodevelopmental performance in pre-pubertal boys with 47,XXY have not been well investigated. The influence of hormones on brain development in humans suggests that a positive effect on neurodevelopmental outcome in young boys with XXY may be plausible with hormone replacement therapy. The aim of the study was to investigate retrospectively if an early course of androgen treatment (three injections of testosterone enanthate, 25 mg, each) had an impact on specific domains of neurodevelopmental function in boys with 47,XXY at 36 and 72 months of age. One hundred one boys with a karyotype of 47,XXY had neurodevelopmental assessments. The retrospective chart review resulted in one group (n = 34) who had received androgen treatment during infancy and the second group was untreated (N = 67). Statistical analysis was completed to determine if there was a positive effect from treatment observed at 36 and at 72 months on multiple domains of development. There were significant differences in multiple cognitive domains in the group who received androgen treatment, including multiple measures of language, intellectual, and neuromotor skills. Improved function was observed in neurodevelopmental outcome in boys with 47,XXY at 36 and 72 months who had been treated with a short course of androgen treatment in infancy. Continued research is underway to expand our understanding of the relationship of androgen, brain function, and neurobehavioral and neurodevelopmental outcome in boys with 47,XXY.
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The Potential Impact of Washing Machines on Laundry Malodour Generation
Letters in Applied Microbiology.
Apr, 2013 |
Pubmed ID: 23350695 A multidisciplinary approach has been adopted to investigate and identify the source of malodour in washing machines and the potential for cross-contamination of laundry. Four washing machines were olfactively graded, and the number of colony-forming units (CFUs) bacteria was determined in four specific locations. Then, samples of terry-towel and fleece were washed, without the use of detergent, in the machines, and the occurrence of malodour over a 52-h period was assessed. Analysis of the scrapings from the four locations in the two malodorous machines identified a plethora of volatile organic compounds (VOCs) by either olfactory detection or mass spectral identification post-gas chromatographic separation. In addition, microbiological analysis from the swabs from the four locations within all four washing machines was carried out. Quantitative analysis of VOCs from 66 microbiological isolates from either the washing machines or fabrics was carried out. In total, 10 VOCs were identified: dimethyl disulfide, 3-methyl-1-butanol, 2,4-dithiapentane, dimethyl trisulfide, 2-tridecanone, indole, 2-phenylethanol, isovaleric acid, isobutyric acid and 1-undecene.
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Is It All the X: Familial Learning Dysfunction and the Impact of Behavioral Aspects of the Phenotypic Presentation of XXY?
American Journal of Medical Genetics. Part C, Seminars in Medical Genetics.
Feb, 2013 |
Pubmed ID: 23359595 The behavioral phenotype of children with XXY has not been extensively studied until recently and this research has been confounded by insufficient study populations and ascertainment biases. The aim of the study was to expand the behavioral aspect of the XXY phenotype as well as investigate the role of existing familial learning disabilities (FLD) on behavioral problems. Behavioral phenotype of XXY includes social anxiety, ADHD, social communication, and atypical peer interactions. The Child Behavior Checklist (CBCL), Social Responsiveness Scale (SRS), and Gilliam Autism Rating Scale (GARS) were completed by the parents of 54 boys with XXY who had not received hormonal replacement prior to participation. Our findings suggest fewer behavioral deficits and lower severity in the general 47,XXY population than previously published and found significant differences between the groups with a positive FLD on the behavioral assessments. Findings demonstrate that boys with FLD exhibit an increased incidence and severity of behavioral problems. Our study expands on the findings of Samango-Sprouse et al. [Samango-Sprouse et al. (2012b) J Intellect Disabil Res] and the significant influence that FLD has on not only neurodevelopment, but also behavioral deficits. Our study suggests that part of the XXY phenotypic profile may be modulated by FLD. Further study is underway to examine the interaction between the many salient factors effecting behavioral and neurodevelopmental progression in XXY and variant forms. © 2013 Wiley Periodicals, Inc.
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Musculoskeletal Anomalies in a Large Cohort of Boys with 49, XXXXY
American Journal of Medical Genetics. Part C, Seminars in Medical Genetics.
Feb, 2013 |
Pubmed ID: 23359596 49, XXXXY is a rare aneuploidy and variant of Klinefelter syndrome, occurring in 1 per 80,000-100,000 live births. We present a cohort of 40 affected males, focusing on musculoskeletal problems. Subjects were participants in an annual 49er family support group meeting. Children were examined in a multidisciplinary clinic by a pediatric neurologist and geneticist, a pediatric orthopedist, a neurodevelopmentalist, and two physical therapists. The patient data were collected from this clinic from 2004 to 2012. All patients were required to have karyotypes that confirmed the presence of XXXXY. There was a high prevalence of musculoskeletal disorders, particularly hypotonia (34 patients [85%]), radioulnar synostosis (30 [75%]), pes planus (26 [65%]), asymmetric hip rotation (27 [67.5%]), and clinodactyly (24 [60%]). Other, less common lower-extremity disorders, included, 5 patients (12.5%) with unilateral club foot, 5 boys (12.5%) with pes cavus, 10 patients (25%) genu valgum and 2 children with genu varus (5%). To our knowledge, this is the first large cohort of boys with 49, XXXXY that focuses on musculoskeletal disorders. There was an increased incidence of hypotonia, clubfoot, avascular necrosis of the femoral head, radioulnar synostosis, and pes planus compared to the normative population. Boys with 49, XXXXY would benefit from multidisciplinary evaluations, particularly from pediatric orthopedists, physical therapists, neurologists, and geneticists for appropriate medical care.
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Aryl Phosphate Esters Within a Major PentaBDE Replacement Product Induce Cardiotoxicity in Developing Zebrafish Embryos: Potential Role of the Aryl Hydrocarbon Receptor
Toxicological Sciences : an Official Journal of the Society of Toxicology.
May, 2013 |
Pubmed ID: 23377616 Firemaster 550 (FM550) is an additive flame retardant formulation of brominated and aryl phosphate ester (APE) components introduced as a major replacement product for the commercial polybrominated diphenyl ether mixture (known as PentaBDE) used primarily in polyurethane foam. However, little is known about the potential effects of FM550-based ingredients during early vertebrate development. Therefore, we first screened the developmental toxicity of each FM550 component using zebrafish as an animal model. Based on these initial screening assays, we found that exposure to the brominated components as high as 10µM resulted in no significant effects on embryonic survival or development, whereas exposure to triphenyl phosphate (TPP) or mono-substituted isopropylated triaryl phosphate (mono-ITP)-two APEs comprising almost 50% of FM550-resulted in targeted effects on cardiac looping and function during embryogenesis. As these cardiac abnormalities resembled aryl hydrocarbon receptor (AHR) agonist-induced phenotypes, we then exposed developing embryos to TPP or mono-ITP in the presence or absence of an AHR antagonist (CH223191) or AHR2-specific morpholino. Based on these studies, we found that CH223191 blocked heart malformations following exposure to mono-ITP but not TPP, whereas AHR2 knockdown failed to block the cardiotoxic effects of both components. Finally, using a cell-based human AHR reporter assay, we found that mono-ITP (but not TPP) exposure resulted in a significant increase in human AHR-driven luciferase activity at similar nominal concentrations as a potent reference AHR agonist (β-naphthoflavone). Overall, our findings suggest that two major APE components of FM550 induce severe cardiac abnormalities during early vertebrate development.
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What Do Clinical Optometrists Like About Their Job?
Clinical & Experimental Optometry : Journal of the Australian Optometrical Association.
Feb, 2013 |
Pubmed ID: 23379690 BACKGROUND: There are few publications describing what optometrists like about clinical work. The purpose of this paper is to explore what optometrists in practice find satisfying with their work and what they find stressful. METHODS: Sixty Australian optometrists participated in a 30-minute semi-structured telephone or face-to-face interview during the period August 2009 to March 2010. The interviews covered a range of topics related to ergonomics and physical comfort, including three questions related to satisfaction with clinical optometry, job satisfaction and self-perceived work-stress. These data were subject to qualitative and quantitative analysis. RESULTS: Participants reported that they liked clinical optometry because of work-related factors (for example, clinical challenge) (n = 47, 78 per cent), people-related factors (e.g. helping people) (n = 29, 48 per cent) and relationships with patients (n = 28, 47 per cent). Clinical freedom was the most frequently cited reason for participants liking their current job (n = 18, 30 per cent). Self-employed participants were more likely to value relationships with their patients (Chi-square, p < 0.01). Employee and locum participants were more likely to value relationships with staff (Chi-square, p < 0.05) and colleagues (Chi-square, p < 0.05). There were 32 participants (53 per cent) who perceived their work as stressful, most commonly related to clinical issues (n = 25, 42 per cent), workload demands (n = 20, 33 per cent) and management tasks (n = 15, 25 per cent). Clinical issues were a stressor for employee and locum participants (Chi-square, p < 0.01) and urban practitioners (Chi-square, p < 0.05). Management tasks were a stressor for independently practising participants (Chi-square, p < 0.01). CONCLUSION: Understanding what clinical optometrists like and find stressful about their work is important for employers, industry and the profession, as these are key elements of employment satisfaction. The information presented in this paper can be used as a basis for developing quantitative tools for assessing job satisfaction and job stress more extensively in the optometric profession.
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Zn(II) Stimulation of Fe(II)-activated Repression in the Iron-dependent Repressor from Mycobacterium Tuberculosis
Biochemistry.
Mar, 2013 |
Pubmed ID: 23432191 Thermodynamic measurements of Fe(II) binding and activation of repressor function in the iron-dependent repressor from Mycobacterium tuberculosis (IdeR) are reported. IdeR, a member of the diphtheria toxin repressor family of proteins, regulates iron homeostasis and contributes to the virulence response in M. tuberculosis. Although iron is the physiological ligand, this is the first detailed analysis of iron binding and activation in this protein. The results showed that IdeR binds 2 equiv of Fe(II) with dissociation constants that differ by a factor of 25. The high- and low-affinity iron binding sites were assigned to physical binding sites I and II, respectively, using metal binding site mutants. IdeR was also found to contain a high-affinity Zn(II) binding site that was assigned to physical metal binding site II through the use of binding site mutants and metal competition assays. Fe(II) binding was modestly weaker in the presence of Zn(II), but the coupled metal binding-DNA binding affinity was significantly stronger, requiring 30-fold less Fe(II) to activate DNA binding compared to Fe(II) alone. Together, these results suggest that IdeR is a mixed-metal repressor, where Zn(II) acts as a structural metal and Fe(II) acts to trigger the physiologically relevant promoter binding. This new model for IdeR activation provides a better understanding of IdeR and the biology of iron homeostasis in M. tuberculosis.
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Regulatory B Cell Frequency Correlates with Markers of HIV Disease Progression and Attenuates Anti-HIV CD8⺠T Cell Function in Vitro
Journal of Leukocyte Biology.
May, 2013 |
Pubmed ID: 23434518 HIV infection is associated with elevated expression of IL-10 and PD-L1, contributing to impairment of T cell effector functions. In autoimmunity, tumor immunology, and some viral infections, Bregs modulate T cell function via IL-10 production. In this study, we tested the hypothesis that during HIV infection, Bregs attenuate CD8(+) T cell effector function, contributing to immune dysfunction. We determined that in vitro, TLR2-, TLR9-, and CD40L-costimulated Bregs from HIV(-) individuals exhibited a high frequency of cells expressing IL-10 and PD-L1. Compared with Bregs from HIV(-) individuals, a significantly higher percentage of Bregs from HIV(+) individuals spontaneously expressed IL-10 (P=0.0218). After in vitro stimulation with HIV peptides, Breg-depleted PBMCs from HIV(+) individuals exhibited a heightened frequency of cytotoxic (CD107a(+); P=0.0171) and HIV-specific CD8(+) T cells compared with total PBMCs. Furthermore, Breg depletion led to enhanced proliferation of total CD8(+) and CD107a(+)CD8(+) T cells (P=0.0280, and P=0.0102, respectively). In addition, augmented CD8(+) T cell effector function in vitro was reflected in a 67% increased clearance of infected CD4(+) T cells. The observed Breg suppression of CD8(+) T cell proliferation was IL-10-dependent. In HIV(+) individuals, Breg frequency correlated positively with viral load (r=0.4324; P=0.0095), immune activation (r=0.5978; P=0.0005), and CD8(+) T cell exhaustion (CD8(+)PD-1(+); r=0.5893; P=0.0101). Finally, the frequency of PD-L1-expressing Bregs correlated positively with CD8(+)PD-1(+) T cells (r=0.4791; P=0.0443). Our data indicate that Bregs contribute to HIV-infection associated immune dysfunction by T cell impairment, via IL-10 and possibly PD-L1 expression.
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Mechanism of [4Fe-4S](Cys)4 Cluster Nitrosylation is Conserved Among NO-responsive Regulators
The Journal of Biological Chemistry.
Apr, 2013 |
Pubmed ID: 23471974 The Fumarate nitrate reduction (FNR) regulator from Escherichia coli controls expression of >300 genes in response to O2 through reaction with its [4Fe-4S] cluster cofactor. FNR is the master switch for the transition between anaerobic and aerobic respiration. In response to physiological concentrations of nitric oxide (NO), FNR also regulates genes, including the nitrate reductase (nar) operon, a major source of endogenous cellular NO, and hmp, which encodes an NO-detoxifying enzyme. Here we show that the [4Fe-4S] cluster of FNR reacts rapidly in a multiphasic reaction with eight NO molecules. Oxidation of cluster sulfide ions (S(2-)) to sulfane (S(0)) occurs, some of which remains associated with the protein as Cys persulfide. The nitrosylation products are similar to a pair of dinuclear dinitrosyl iron complexes, [Fe(I)2(NO)4(Cys)2](0), known as Roussin's red ester. A similar reactivity with NO was reported for the Wbl family of [4Fe-4S]-containing proteins found only in actinomycetes, such as Streptomyces and Mycobacteria. These results show that NO reacts via a common mechanism with [4Fe-4S] clusters in phylogenetically unrelated regulatory proteins that, although coordinated by four Cys residues, have different cluster environments. The reactivity of E. coli FNR toward NO, in addition to its sensitivity toward O2, is part of a hierarchal network that monitors, and responds to, NO, both endogenously generated and exogenously derived.
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Whole-Body Heat Loss During Exercise in the Heat Is Not Impaired in Type 1 Diabetes
Medicine and Science in Sports and Exercise.
Mar, 2013 |
Pubmed ID: 23475170 Purpose: To determine if individuals with type 1 diabetes exhibit impairments in local and whole-body heat loss responses that could impact core temperature regulation during exercise in the heat compared to matched, non-diabetic individuals. Methods: Twelve otherwise healthy individuals with type 1 diabetes (HbA1c = 7.7±0.3%) and 12 controls matched for age, sex, body surface area, and physical fitness cycled continuously for 60-min at a set rate of metabolic heat production (∼400W) in a whole-body direct calorimeter (35 °C and 20% relative humidity). Local sweat rate (ventilated capsule) was measured on the back and skin blood flow (SkBF, laser-Doppler velocimetry) on the forearm. Core (rectal and esophageal) and mean skin temperatures and heart rate were measured continuously. Whole-body heat exchange and change in body heat content were measured using simultaneous direct whole-body and indirect calorimetry. Results: The change (mean±SE) in body heat content was similar between groups during exercise (Diabetes: 409±27; Control: 386±33 kJ, p=0.584) and recovery (Diabetes:-115±16; Control:-93±24 kJ, p=0.457). Local heat loss responses of sweating (p=0.783) and SkBF (p=0.078), as well as rectal temperature (Diabetes: 37.87±0.10; Control: 37.85±0.13 °C, p=0.977) and heart rate (Diabetes: 130±9 vs. Control: 127±7 beats·min, p=0.326) were comparable at the end of the exercise period. Conclusion: During light-to-moderate intensity exercise performed under conditions permitting full sweat evaporation, otherwise healthy type 1 diabetic individuals did not show impaired heat loss responses during heat exposure when compared to matched individuals without diabetes.
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A Spinal Cord Window Chamber Model for in Vivo Longitudinal Multimodal Optical and Acoustic Imaging in a Murine Model
PloS One.
2013 |
Pubmed ID: 23516432 In vivo and direct imaging of the murine spinal cord and its vasculature using multimodal (optical and acoustic) imaging techniques could significantly advance preclinical studies of the spinal cord. Such intrinsically high resolution and complementary imaging technologies could provide a powerful means of quantitatively monitoring changes in anatomy, structure, physiology and function of the living cord over time after traumatic injury, onset of disease, or therapeutic intervention. However, longitudinal in vivo imaging of the intact spinal cord in rodent models has been challenging, requiring repeated surgeries to expose the cord for imaging or sacrifice of animals at various time points for ex vivo tissue analysis. To address these limitations, we have developed an implantable spinal cord window chamber (SCWC) device and procedures in mice for repeated multimodal intravital microscopic imaging of the cord and its vasculature in situ. We present methodology for using our SCWC to achieve spatially co-registered optical-acoustic imaging performed serially for up to four weeks, without damaging the cord or induction of locomotor deficits in implanted animals. To demonstrate the feasibility, we used the SCWC model to study the response of the normal spinal cord vasculature to ionizing radiation over time using white light and fluorescence microscopy combined with optical coherence tomography (OCT) in vivo. In vivo power Doppler ultrasound and photoacoustics were used to directly visualize the cord and vascular structures and to measure hemoglobin oxygen saturation through the complete spinal cord, respectively. The model was also used for intravital imaging of spinal micrometastases resulting from primary brain tumor using fluorescence and bioluminescence imaging. Our SCWC model overcomes previous in vivo imaging challenges, and our data provide evidence of the broader utility of hybridized optical-acoustic imaging methods for obtaining multiparametric and rich imaging data sets, including over extended periods, for preclinical in vivo spinal cord research.
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Predictors of Tris(1,3-dichloro-2-propyl) Phosphate Metabolite in the Urine of Office Workers
Environment International.
May, 2013 |
Pubmed ID: 23523854 Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is a flame retardant widely used in furniture containing polyurethane foam. It is a carcinogen, endocrine disruptor, and potentially neurotoxic. Our objectives were to characterize exposure of adult office workers (n=29) to TDCPP by measuring its primary metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), in their urine; measuring TDCPP in dust from their homes; offices and vehicles; and assessing possible predictors of exposure. We identified TDCPP in 99% of dust (GM=4.43μg/g) and BDCPP in 100% of urine samples (GM=408pg/mL). Concentrations of TDCPP were significantly higher in dust from vehicles (GM=12.5μg/g) and offices (GM=6.06μg/g) than in dust from the main living area (GM=4.21μg/g) or bedrooms (GM=1.40μg/g) of worker homes. Urinary BDCPP concentrations among participants who worked in a new office building were 26% of those who worked in older buildings (p=0.01). We found some evidence of a positive trend between urinary BDCPP and TDCPP in office dust that was not observed in the other microenvironments and may be related to the timing of urine sample collection during the afternoon of a workday. Overall our findings suggest that exposure to TDCPP in the work environment is one of the contributors to the personal exposure for office workers. Further research is needed to confirm specific exposure sources (e.g., polyurethane foam), determine the importance of exposure in other microenvironments such as homes and vehicles, and address the inhalation and dermal exposure pathways.
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Do Heat Events Pose a Greater Health Risk for Individuals with Type 2 Diabetes?
Diabetes Technology & Therapeutics.
Jun, 2013 |
Pubmed ID: 23530578 Chronic medical conditions such as type 2 diabetes may alter the body's normal response to heat. Evidence suggests that the local heat loss response of skin blood flow (SkBF) is affected by diabetes-related impairments in both endothelium-dependent and non-endothelium-dependent mechanisms, resulting in lower elevations in SkBF in response to a heat or pharmacological stimulus. Thermoregulatory sweating may also be diminished by type 2 diabetes, impairing the body's ability to transfer heat from its core to the environment. Diabetes-associated co-morbidities and the medications (particularly those affecting fluid balance) required to treat these conditions may exacerbate the risk of heat-related illness by decreasing SkBF and sweating further. Unfortunately, the majority of studies measure local heat loss responses in the hands and feet and lack measures of core temperature. Therefore, the impact of these impairments on whole-body heat loss remains unknown. This review addresses heat-related vulnerability in individuals with type 2 diabetes by examining the literature related to heat loss responses in this population. Type 2 diabetes, its associated co-morbidities, and the medications required in their treatment may cause dehydration, lower SkBF, and reduced sweating, which could consequently impair thermoregulation. This effect is most evident in individuals with poor blood glucose control. Although type 2 diabetes can be associated with impairments in SkBF and sweating, more physically active individuals requiring fewer medications and having good blood glucose control may be able to tolerate heat as well as those of similar age and body composition.
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Using Whole Mount in Situ Hybridization to Examine Thyroid Hormone Deiodinase Expression in Embryonic and Larval Zebrafish: a Tool for Examining OH-BDE Toxicity to Early Life Stages
Aquatic Toxicology (Amsterdam, Netherlands).
May, 2013 |
Pubmed ID: 23531416 Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish. The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression. While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible. For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo. While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development. In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized. To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100nM 6-OH-BDE-47. Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment. Our results demonstrate effects of OH-BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages.
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Older Adults with Type 2 Diabetes Store More Heat During Exercise
Medicine and Science in Sports and Exercise.
Mar, 2013 |
Pubmed ID: 23542894 It is unknown if diabetes-related reductions in local skin blood flow (SkBF) and sweating (LSR) measured during passive heat stress translate into greater heat storage during exercise in the heat in individuals with type 2 diabetes (T2D) compared to non-diabetic control (CON) subjects. PURPOSE: To examine the effects of T2D on whole-body heat exchange during exercise in the heat. METHODS: Ten (6 males and 4 females) adults with T2D and 10 adults (6 males and 4 females) without diabetes matched for age, sex, body surface area, and fitness cycled continuously for 60 min at a fixed rate of metabolic heat production (∼370 W) in a whole-body direct calorimeter (30°C and 20% RH). Upper back LSR, forearm SkBF and rectal temperature (Tre) and heart rate were measured continuously. Whole-body heat loss and changes in body heat content (ΔHb) were determined using simultaneous direct whole-body and indirect calorimetry. RESULTS: Whole-body heat loss was significantly attenuated from 15 min throughout the remaining exercise with the differences becoming more pronounced over time for T2D relative to CON (p=0.004). This resulted in a significantly greater ΔHb in T2D (360±33; CON: 265±28 kJ, p=0.013). No differences were measured during recovery (T2D: -87±22; CON: -132±21 kJ, p=0.076). By the end of the 60-min recovery, the T2D group lost only 21% (79 kJ) of the total heat gained during exercise whereas their non-diabetic counterparts lost in excess of 55% (131 kJ). No differences were observed in LSR (p=0.361), SkBF (p=0.528), Tre (p=0.388) or heart rate (p=0.179) during exercise or recovery. CONCLUSION: Older adults with T2D have a reduced capacity to dissipate heat during exercise resulting a greater heat storage and therefore level of thermal strain.
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Investigating a Novel Flame Retardant Known As V6: Measurements in Baby Products, House Dust, and Car Dust
Environmental Science & Technology.
May, 2013 |
Pubmed ID: 23565680 With the phase-out of polybrominated diphenyl ether (PBDE) flame retardants, the use of new and alternate flame retardants has been increasing. 2,2-bis(chloromethyl)propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate, known as V6, is a flame retardant applied to polyurethane foam commonly found in furniture and automobile foam. However, to the authors' knowledge, no research has been conducted on V6 levels in the environment. The intention of this study was to measure the concentration of V6 in foam collected from baby products where it was recently detected and measure levels in dust samples collected from homes and automobiles in the Boston, MA area. To accomplish this, a pure V6 commercial standard was purchased from a Chinese manufacturer and purified (>98%). An analytical method to measure V6 in dust samples using liquid chromatography tandem mass spectrometry (LC/MS-MS) was developed. Extraction was conducted using accelerated solvent extraction (ASE) and extracts were purified using an ENVI-Florisil SPE column (500 mg, 3 mL). V6 was measured in foam samples collected from baby products with a concentration ranging from 24,500,000 to 59,500,000 ng/g of foam (n = 12, average ± sd: 46,500,000 ± 12,000,000 ng/g; i.e., on average, 4.6% of the foam mass was V6). V6 was also detected in 19 of 20 car dust samples and 14 of 20 house dust samples analyzed. The concentration of V6 in the house dust ranged from
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Biomimetic Model to Reconstitute Angiogenic Sprouting Morphogenesis in Vitro
Proceedings of the National Academy of Sciences of the United States of America.
Apr, 2013 |
Pubmed ID: 23569284 Angiogenesis is a complex morphogenetic process whereby endothelial cells from existing vessels invade as multicellular sprouts to form new vessels. Here, we have engineered a unique organotypic model of angiogenic sprouting and neovessel formation that originates from preformed artificial vessels fully encapsulated within a 3D extracellular matrix. Using this model, we screened the effects of angiogenic factors and identified two distinct cocktails that promoted robust multicellular endothelial sprouting. The angiogenic sprouts in our system exhibited hallmark structural features of in vivo angiogenesis, including directed invasion of leading cells that developed filopodia-like protrusions characteristic of tip cells, following stalk cells exhibiting apical-basal polarity, and lumens and branches connecting back to the parent vessels. Ultimately, sprouts bridged between preformed channels and formed perfusable neovessels. Using this model, we investigated the effects of angiogenic inhibitors on sprouting morphogenesis. Interestingly, the ability of VEGF receptor 2 inhibition to antagonize filopodia formation in tip cells was context-dependent, suggesting a mechanism by which vessels might be able to toggle between VEGF-dependent and VEGF-independent modes of angiogenesis. Like VEGF, sphingosine-1-phosphate also seemed to exert its proangiogenic effects by stimulating directional filopodial extension, whereas matrix metalloproteinase inhibitors prevented sprout extension but had no impact on filopodial formation. Together, these results demonstrate an in vitro 3D biomimetic model that reconstitutes the morphogenetic steps of angiogenic sprouting and highlight the potential utility of the model to elucidate the molecular mechanisms that coordinate the complex series of events involved in neovascularization.
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Parenteral Fish Oil Lipid Emulsions in the Critically Ill: A Systematic Review and Meta-Analysis
JPEN. Journal of Parenteral and Enteral Nutrition.
Apr, 2013 |
Pubmed ID: 23609773 Introduction: ω-3 Polyunsaturated fatty acids contained in fish oils (FO) possess major anti-inflammatory, antioxidant, and immunologic properties that could be beneficial during critical illness. We hypothesized that parenteral FO-containing emulsions may improve clinical outcomes in the critically ill. Methods: We searched computerized databases from 1980-2012. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated FO-containing emulsions, either in the context of parenteral nutrition (PN) or enteral nutrition (EN). Results: A total of 6 RCTs (n = 390 patients) were included; the mean methodological score of all trials was 10 (range, 6-13). When the results of these studies were aggregated, FO-containing emulsions were associated with a trend toward a reduction in mortality (risk ratio [RR], 0.71; 95% confidence interval [CI], 0.49-1.04; P = .08; heterogeneity I(2) = 0%) and a reduction in the duration of mechanical ventilation (weighted mean difference in days [WMD], -1.41; 95% CI, -3.43 to 0.61; P = .17). However, this strategy had no effect on infections (RR, 0.76; 95% CI, 0.42-1.36; P = .35) and intensive care unit length of stay (WMD, -0.46; 95% CI, -4.87 to 3.95; P = .84, heterogeneity I(2) = 75%). Conclusion: FO-containing lipid emulsions may be able to decrease mortality and ventilation days in the critically ill. However, because of the paucity of clinical data, there is inadequate evidence to recommend the routine use of parenteral FO. Large, rigorously designed RCTs are required to elucidate the efficacy of parenteral FO in the critically ill.
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Pulmonary Cerium Dioxide Nanoparticle Exposure Differentially Impairs Coronary and Mesenteric Arteriolar Reactivity
Cardiovascular Toxicology.
May, 2013 |
Pubmed ID: 23645470 Cerium dioxide nanoparticles (CeO2 NPs) are an engineered nanomaterial (ENM) that possesses unique catalytic, oxidative, and reductive properties. Currently, CeO2 NPs are being used as a fuel catalyst but these properties are also utilized in the development of potential drug treatments for radiation and stroke protection. These uses of CeO2 NPs present a risk for human exposure; however, to date, no studies have investigated the effects of CeO2 NPs on the microcirculation following pulmonary exposure. Previous studies in our laboratory with other nanomaterials have shown impairments in normal microvascular function after pulmonary exposures. Therefore, we predicted that CeO2 NP exposure would cause microvascular dysfunction that is dependent on the tissue bed and dose. Twenty-four-hour post-exposure to CeO2 NPs (0-400 μg), mesenteric, and coronary arterioles was isolated and microvascular function was assessed. Our results provided evidence that pulmonary CeO2 NP exposure impairs endothelium-dependent and endothelium-independent arteriolar dilation in a dose-dependent manner. The CeO2 NP exposure dose which causes a 50 % impairment in arteriolar function (EC50) was calculated and ranged from 15 to 100 μg depending on the chemical agonist and microvascular bed. Microvascular assessments with acetylcholine revealed a 33-75 % reduction in function following exposure. Additionally, there was a greater sensitivity to CeO2 NP exposure in the mesenteric microvasculature due to the 40 % decrease in the calculated EC50 compared to the coronary microvasculature EC50. CeO2 NP exposure increased mean arterial pressure in some groups. Taken together, these observed microvascular changes may likely have detrimental effects on local blood flow regulation and contribute to cardiovascular dysfunction associated with particle exposure.
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Does Thyroid Disruption Contribute to the Developmental Neurotoxicity of Chlorpyrifos?
Environmental Toxicology and Pharmacology.
Apr, 2013 |
Pubmed ID: 23686008 Although organophosphate pesticides are not usually characterized as "endocrine disruptors," recent work points to potential, long-term reductions of circulating thyroid hormones after developmental exposures to chlorpyrifos that are devoid of observable toxicity. We administered chlorpyrifos to developing rats on gestational days 17-20 or postnatal days 1-4, regimens that produce distinctly different, sex-selective effects on neurobehavioral performance. The prenatal regimen produced a small, but statistically significant reduction in brain thyroxine levels from juvenile stages through adulthood; in contrast, postnatal exposure produced a transient elevation in young adulthood. However, in neither case did we observe the sex-selectivity noted earlier for neurobehavioral outcomes of these specific treatment regimens, or as reported earlier for effects on serum T4 in developing mice. Thus, although chlorpyrifos has the potential to disrupt thyroid status sufficiently to alter brain thyroid hormone levels, the effect is small, and any potential contribution to neurobehavioral abnormalities remains to be proven.
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Personal Consequences of Work-related Physical Discomfort: an Exploratory Study
Clinical & Experimental Optometry : Journal of the Australian Optometrical Association.
May, 2013 |
Pubmed ID: 23701021 BACKGROUND: Work-related physical discomfort has been reported in Australian optometrists. The purpose of this paper is to explore the personal consequences of work-related discomfort. METHODS: Forty-seven optometrists with self-reported work-related discomfort participated in a 30-minute telephone or face-to-face interview related to ergonomics and physical comfort. Self-employed, employee, locum and retired optometrists participated. Four avenues were investigated; namely, description of discomfort, non-work contributing factors, whether the participant has ever stopped work due to discomfort, and the treatments accessed to alleviate discomfort. These data were subject to qualitative and quantitative analyses. RESULTS: Reported discomfort ranged from mild to severe. Eight participants (17 per cent) ascribed their discomfort entirely to work and seven (15 per cent) cited non-work factors as the cause. Many participants (32, 68 per cent) reported that non-work factors, for example, sport and driving, aggravated existing work-related discomfort and for some, their discomfort impacted on home and leisure activities. There were 15 participants (32 per cent), who have stopped work because of discomfort, including two who have ceased working as an optometrist and two who now work reduced hours. The majority (32) continue to work despite discomfort. Many participants (31, 66 per cent) seek treatment to alleviate discomfort, with seven participants (15 per cent) reporting that they receive multiple therapies per week. Work-related discomfort was generally viewed as a personal issue, with most participants accessing treatment in their own time (27, 57 per cent) and funding it personally or with private health insurance. Only four participants have received funding through workers' compensation or income protection insurance. CONCLUSIONS: Work-related discomfort has significant financial and personal costs for some Australian optometrists. These qualitative data can be used to develop quantitative tools for assessing the impact of discomfort on quality of life for optometrists and their families. The results also highlight the need for preventative action to reduce work-related discomfort within the optometric profession.
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Linguistic Acculturation and Skin Cancer-related Behaviors Among Hispanics in the Southern and Western United States
JAMA Dermatology (Chicago, Ill.).
Jun, 2013 |
Pubmed ID: 23752366 OBJECTIVE To examine the association between linguistic acculturation (assessed using the Language Use and Linguistic Preference subscales from the Bidimensional Acculturation Scale for Hispanics) and skin cancer-related behaviors among US Hispanic adults to determine whether, compared with Hispanics denoted as Spanish-acculturated, English-acculturated Hispanics would report less frequent shade seeking and use of sun protective clothing and higher rates of sunscreen use, sunbathing, and indoor tanning. DESIGN Online survey study conducted in September 2011. SETTING Five southern and western US states. PARTICIPANTS A population-based sample of 788 Hispanic adults drawn from a nationally representative web panel. MAIN OUTCOME MEASURES Self-reported sunscreen use, shade seeking, use of sun protective clothing, sunbathing, and indoor tanning. RESULTS Multivariate regression analyses were conducted to examine predictors of the skin cancer-related behaviors. As hypothesized, English-acculturated Hispanics had lower rates of shade seeking and use of sun protective clothing and reported higher rates of sunbathing and indoor tanning than Spanish-acculturated Hispanics. English-acculturated Hispanics and bicultural Hispanics (ie, those with high Spanish and high English acculturation) reported comparably high rates of sunbathing and indoor tanning. Results suggested that bicultural Hispanics seek shade and wear sun protective clothing less often than Spanish-acculturated Hispanics but more often than English-acculturated Hispanics. Acculturation was not associated with sunscreen use. CONCLUSIONS Hispanic adults do not routinely engage in behaviors that reduce their risk of skin cancer. Bicultural and English-acculturated Hispanics are particularly in need of skin cancer prevention interventions.
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Microfluidics Embedded Within Extracellular Matrix to Define Vascular Architectures and Pattern Diffusive Gradients
Lab on a Chip.
Aug, 2013 |
Pubmed ID: 23787488 Gradients of diffusive molecules within 3D extracellular matrix (ECM) are essential in guiding many processes such as development, angiogenesis, and cancer. The spatial distribution of factors that guide these processes is complex, dictated by the distribution and architecture of vasculature and presence of surrounding cells, which can serve as sources or sinks of factors. To generate temporally and spatially defined soluble gradients within a 3D cell culture environment, we developed an approach to patterning microfluidically ported microchannels that pass through a 3D ECM. Micromolded networks of sacrificial conduits ensconced within an ECM gel precursor solution are dissolved following ECM gelation to yield functional microfluidic channels. The dimensions and spatial layout of channels are readily dictated using photolithographic methods, and channels are connected to external flow via a gasket that also serves to house the 3D ECM. We demonstrated sustained spatial patterning of diffusive gradients dependent on the architecture of the microfluidic network, as well as the ability to independently populate cells in either the channels or surrounding ECM, enabling the study of 3D morphogenetic processes. To highlight the utility of this approach, we generated model vascular networks by lining the channels with endothelial cells and examined how channel architecture, through its effects on diffusion patterns, can guide the location and morphology of endothelial sprouting from the channels. We show that locations of strongest gradients define positions of angiogenic sprouting, suggesting a mechanism by which angiogenesis is regulated in vivo and a potential means to spatially defining vasculature in tissue engineering applications. This flexible 3D microfluidic approach should have utility in modeling simple tissues and will aid in the screening and identification of soluble factor conditions that drive morphogenetic events such as angiogenesis.
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Associations Between PBDEs in Office Air, Dust, and Surface Wipes
Environment International.
Jun, 2013 |
Pubmed ID: 23797055 Increased use of flame-retardants in office furniture may increase exposure to PBDEs in the office environment. However, partitioning of PBDEs within the office environment is not well understood. Our objectives were to examine relationships between concurrent measures of PBDEs in office air, floor dust, and surface wipes. We collected air, dust, and surface wipe samples from 31 offices in Boston, MA. Correlation and linear regression were used to evaluate associations between variables. Geometric mean (GM) concentrations of individual BDE congeners in air and congener specific octanol-air partition coefficients (Koa) were used to predict GM concentrations in dust and surface wipes and compared to the measured concentrations. GM concentrations of PentaBDEs in office air, dust, and surface wipes were 472pg/m(3), 2411ng/g, and 77pg/cm(2), respectively. BDE209 was detected in 100% of dust samples (GM=4202ng/g), 93% of surface wipes (GM=125pg/cm(2)), and 39% of air samples. PentaBDEs in dust and air were moderately correlated with each other (r=0.60, p=0.0003), as well as with PentaBDEs in surface wipes (r=0.51, p=0.003 for both dust and air). BDE209 in dust was correlated with BDE209 in surface wipes (r=0.69, p=0.007). Building (three categories) and PentaBDEs in dust were independent predictors of PentaBDEs in both air and surface wipes, together explaining 50% (p=0.0009) and 48% (p=0.001) of the variation respectively. Predicted and measured concentrations of individual BDE congeners were highly correlated in dust (r=0.98, p
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Ca2+ Release-activated Ca2+ Channel Blockade As a Potential Tool in Antipancreatitis Therapy
Proceedings of the National Academy of Sciences of the United States of America.
Jul, 2013 |
Pubmed ID: 23878235 Alcohol-related acute pancreatitis can be mediated by a combination of alcohol and fatty acids (fatty acid ethyl esters) and is initiated by a sustained elevation of the Ca(2+) concentration inside pancreatic acinar cells ([Ca(2+)]i), due to excessive release of Ca(2+) stored inside the cells followed by Ca(2+) entry from the interstitial fluid. The sustained [Ca(2+)]i elevation activates intracellular digestive proenzymes resulting in necrosis and inflammation. We tested the hypothesis that pharmacological blockade of store-operated or Ca(2+) release-activated Ca(2+) channels (CRAC) would prevent sustained elevation of [Ca(2+)]i and therefore protease activation and necrosis. In isolated mouse pancreatic acinar cells, CRAC channels were activated by blocking Ca(2+) ATPase pumps in the endoplasmic reticulum with thapsigargin in the absence of external Ca(2+). Ca(2+) entry then occurred upon admission of Ca(2+) to the extracellular solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A, inhibited store-operated Ca(2+) entry in a concentration-dependent manner within the range of 1 to 50 μM (IC50 = 3.4 μM), but had little or no effect on the physiological Ca(2+) spiking evoked by acetylcholine or cholecystokinin. Palmitoleic acid ethyl ester (100 μM), an important mediator of alcohol-related pancreatitis, evoked a sustained elevation of [Ca(2+)]i, which was markedly reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced trypsin and protease activity as well as necrosis were almost abolished by blocking CRAC channels. There is currently no specific treatment of pancreatitis, but our data show that pharmacological CRAC blockade is highly effective against toxic [Ca(2+)]i elevation, necrosis, and trypsin/protease activity and therefore has potential to effectively treat pancreatitis.
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