In JoVE (1)

Other Publications (140)

Articles by David Becker in JoVE

 JoVE Medicine

Inducing Ischemia-reperfusion Injury in the Mouse Ear Skin for Intravital Multiphoton Imaging of Immune Responses

1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, 2Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 3Lee Kong Chian School of Medicine, Nanyang Technological University, 4Centenary Institute for Cancer Medicine and Cell Biology, 5Discipline of Dermatology, University of Sydney, 6Department of Dermatology, Royal Prince Alfred Hospital, 7LSI Immunology Programme, National University of Singapore, 8School of Biological Sciences, Nanyang Technological University

JoVE 54956

Other articles by David Becker on PubMed

Journal of Anatomy. Sep, 2007  |  Pubmed ID: 17848160

Multiphoton Imaging of Chick Retinal Development in Relation to Gap Junctional Communication

The Journal of Physiology. Dec, 2007  |  Pubmed ID: 17932156

Neural progenitor cells in the developing retina extend processes that stretch from the basal vitread surface to the apical ventricular surface. During the cell cycle, the nucleus undergoes interkinetic nuclear migration (INM), moving in a vitread direction during G1, passing through S-phase at its peak and then, on entering G2, returning towards the ventricular surface where it enters M-phase and divides. We have previously shown that individual saltatory movements of the nucleus correlate with transient changes in cytosolic calcium concentration within these progenitor cells and that these events spread to neighbouring progenitors through connexin43 (Cx43) gap junction channels, thereby coordinating the migration of coupled clusters of cells. Disrupting coupling with pharmacological agents, Cx43-specific antisense oligodeoxynucleotides (asODNs) or dominant negative Cx43 (dnCx43) inhibits the sharing of calcium events, reducing the number that each cell experiences and significantly slowing INM. We have developed protocols for imaging migrating progenitor cells by confocal microscopy over relatively short periods, and by multiphoton microscopy over more extended periods that include complete cell cycles. We find that perturbing gap junctional communication not only slows the INM of progenitor cells but also apparently prevents them from changing direction at critical phases of the cell cycle. It also disrupts the migration of young neurons to their appropriate layers after terminal division and leads to their ectopic differentiation. The ability to perform extended time-lapse imaging over 3D volumes in living retina using multiphoton microscopy should now allow fundamental mechanisms governing development of the retinal neuroepithelium to be probed in detail.

Neuroprotective Effect of STAZN, a Novel Azulenyl Nitrone Antioxidant, in Focal Cerebral Ischemia in Rats: Dose-response and Therapeutic Window

Brain Research. Nov, 2007  |  Pubmed ID: 17945201

Stilbazulenyl nitrone (STAZN) is a potent antioxidant that, in a rat model of transient focal cerebral ischemia, confers significant enduring functional and morphological neuroprotection. This study investigated the influence of dose and time of administration on the neuroprotective effects of STAZN in the intraluminal suture model of middle cerebral artery occlusion (MCAo). Dose response: At 2 and 4 h after the onset of MCAo, animals received intravenously either STAZN (low dose=0.07 mg/kg, n=8; medium dose=0.7 mg/kg, n=9; high dose=3.5 mg/kg, n=9), an equivalent volume of vehicle (30% Solutol HS15 and 70% isotonic saline, 0.37 ml/kg, n=5) or saline (0.37 ml/kg, n=5). Only the medium dose improved scores (p<0.05) on a standardized neurobehavioral test at 1, 2 and 3 days after MCAo. Only the medium dose reduced the total infarction (51%, p=0.014) compared to controls. These results indicate that STAZN exhibits maximal neuroprotection at the 0.7 mg/kg dose. Therapeutic window: STAZN (0.6 mg/kg) dissolved in dimethylsulfoxide was given intra-peritoneally at 2 and 4 h (n=11), 3 and 5 h (n=10), 4 and 6 h (n=10) or 5 and 7 h (n=7) after the onset of MCAo. Additional doses were given at 24 and 48 h. Vehicle (dimethylsulfoxide, 2.0 ml/kg, n=6) was administered at 3, 5, 24 and 48 h. STAZN treatment initiated at 2 or 3 h after the onset of MCAo improved neurological scores (p<0.001) and reduced total infarction (42.2%, p<0.05) compared to controls.

Lymph Heart in Chick--somitic Origin, Development and Embryonic Oedema

Development (Cambridge, England). Dec, 2007  |  Pubmed ID: 18003736

The lymph heart is a sac-like structure on either side of avian tail. In some adult birds, it empties the lymph from the copulatory organ; however, during embryonic development, it is thought to circulate extra-embryonic lymph. Very little is known about the origin, innervation and the cellular changes it undergoes during development. Using immunohistochemistry and gene expression profiling we show that the musculature of the lymph heart is initially composed solely of striated skeletal muscle but later develops an additional layer composed of smooth myofibroblasts. Chick-quail fate-mapping demonstrates that the lymph heart originates from the hypaxial compartments of somites 34-41. The embryonic lymph heart is transiently innervated by somatic motoneurons with no autonomic input. In comparison to body muscles, the lymph heart has different sensitivity to neuromuscular junction blockers (sensitive only to decamethonium). Furthermore, its abundant bungarotoxin-positive acetylcholinesterase receptors are unique as they completely lack specific acetylcholinesterase activity. Several lines of evidence suggest that the lymph heart may possess an intrinsic pacing mechanism. Finally, we assessed the function of the lymph heart during embryogenesis and demonstrate that it is responsible for preventing embryonic oedema in birds, a role previously thought to be played by body skeletal muscle contractions.

Neuroprotective Antioxidant STAZN Protects Against Myocardial Ischemia/reperfusion Injury

Biochemical Pharmacology. Jan, 2008  |  Pubmed ID: 17936251

Protecting the myocardium from ischemia-reperfusion injury has significant potential to reduce the complications of myocardial infarction and interventional revascularization procedures. Reperfusion damage is thought to result, in part, from oxidative stress. Here we use a novel method of percutaneous coronary occlusion to show that the potent antioxidant and neuroprotective free-radical scavenger, stilbazulenyl nitrone (STAZN), confers marked cardioprotection when given immediately prior to reperfusion.

[The Evidence-based Invasive Therapy of Stable Angina Pectoris]

Orvosi Hetilap. Feb, 2008  |  Pubmed ID: 18258560

With the spread of invasive cardiology, and with the opening of new home centers today coronarography and the necessary coronary revascularization are accessible for everyone. The indication of invasive investigation of the acute coronary diseases (STEMI, NSTE-ACS) is crystallised by today. At the same time the indication that the invasive strategy of stable coronary disease depends on more factors, this is a complex exercise. This contains the clinical risk stratification (among the analysis of the classic risk factors), and measures the ejection fraction, and the result of the exercise test and the anatomically risk stratification - based on the coronarography. Authors summarised the clinical risk stratification and the indication of the invasive investigation of the stable coronary disease, based on the recent clinical trials and the guidelines.

Immunohistochemical Detection of Connexin36 in Sympathetic Preganglionic and Somatic Motoneurons in the Adult Rat

Autonomic Neuroscience : Basic & Clinical. May, 2008  |  Pubmed ID: 18280223

Gap junctional communication in the adult CNS plays an important role in the synchronization of neuronal activities. In vitro studies have shown evidence of electrotonic coupling through gap junctions between sympathetic preganglionic motoneurons and between somatic motoneurons in the neonatal and adult rat spinal cord. Electrotonic transmission of membrane oscillations might be an important mechanism for recruitment of neurons and result in the generation of rhythmic sympathetic and somato-motor activity at the population level. Gap junctions in the adult spinal cord are constituted principally by connexin36 (Cx36). However, the distribution of Cx36 in specific neuronal populations of the spinal cord is unknown. Here, we identify Cx36-like immunoreactivity in sympathetic preganglionic and somatic motoneurons in thoracic spinal cord segments of the adult rat. For this purpose, double immunostaining against Cx36 and choline acetyltransferase (ChAT) was performed on transverse sections (20 microm) taken from spinal segments T6-T8. Cx36 punctate immunostaining was detected in the majority of ChAT-immunoreactive (-ir) neurons from lamina VII [intermediolateral cell column (IML) and intercalated cell group (IC)], lamina X [central autonomic nucleus (CA)] and in ventral horn neurons from laminae VIII and IX. Cx36 puncta were distributed in the neuronal somata and along dendritic processes. The presence of Cx36 in ChAT-ir neurons is consistent with electrical coupling between sympathetic preganglionic motoneurons and between somatic motoneurons through gap junctions in the adult spinal cord.

Quantification of Retinal Transneuronal Degeneration in Human Glaucoma: a Novel Multiphoton-DAPI Approach

Investigative Ophthalmology & Visual Science. May, 2008  |  Pubmed ID: 18436826

Glaucoma is presumed to result in the selective loss of retinal ganglion cells. In many neural systems, this loss would initiate a cascade of transneuronal degeneration. The quantification of changes in neuronal populations in the middle layers of the retina can be difficult with conventional histologic techniques. A method was developed based on multiphoton imaging of 4',6'-diamino-2-phenylindole (DAPI)-stained tissue to quantify neuron loss in postmortem human glaucomatous retinas.

Correcting, Not Critiquing, the Access-to-care Issue

Journal of the Massachusetts Dental Society. 2008  |  Pubmed ID: 18459669

Simvastatin Vs Therapeutic Lifestyle Changes and Supplements: Randomized Primary Prevention Trial

Mayo Clinic Proceedings. Jul, 2008  |  Pubmed ID: 18613992

To compare the lipid-lowering effects of an alternative regimen (lifestyle changes, red yeast rice, and fish oil) with a standard dose of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin).

Blocking Connexin43 Expression Reduces Inflammation and Improves Functional Recovery After Spinal Cord Injury

Molecular and Cellular Neurosciences. Oct, 2008  |  Pubmed ID: 18617007

After traumatic CNS injury, a cascade of secondary events expands the initial lesion. The gap-junction protein connexin43 (Cx43), which is transiently up-regulated, has been implicated in the spread of 'bystander' damage. We have used an antisense oligodeoxynucleotide (asODN) to suppress Cx43 up-regulation in two rat models of spinal cord injury. Within 24 h of compression injury, rats treated with Cx43-asODN scored higher than sense-ODN and vehicle-treated controls on behavioural tests of locomotion. Their spinal cords showed less swelling and tissue disruption, less up-regulation of astrocytic GFAP, and less extravasation of fluorescently-labelled bovine serum albumin and neutrophils. The locomotor improvement was sustained over at least 4 weeks. Following partial spinal cord transection, Cx43-asODN treatment reduced GFAP immunoreactivity, neutrophil recruitment, and the activity of OX42(+) microglia in and around the lesion site. Cx43 has many potential roles in the pathophysiology of CNS injury and may be a valuable target for therapeutic intervention.

Green Dentistry

Journal of the Massachusetts Dental Society. 2008  |  Pubmed ID: 18705205

Regional Variation in the Denial of Reimbursement for Bone Mineral Density Testing Among US Medicare Beneficiaries

Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. Oct-Dec, 2008  |  Pubmed ID: 18789740

Although the Bone Mass Measurement Act outlines the indications for central dual-energy X-ray absorptiometry (DXA) testing for US Medicare beneficiaries, the specifics regarding the appropriate ICD-9 codes to use for covered indications have not been specified by Medicare and are sometimes ambiguous. We describe the extent to which DXA reimbursement was denied by gender and age of beneficiary, ICD-9 code submitted, time since previous DXA, whether the scan was performed in the physician's office and local Medicare carrier. Using Medicare administrative claims data from 1999 to 2005, we studied a 5% national sample of beneficiaries age > or =65 yr with part A+B coverage who were not health maintenance organization enrollees. We identified central DXA claims and evaluated the relationship between the factors listed above and reimbursement for central DXA (CPT code 76075). Multivariable logistic regression was used to evaluate the independent relationship between DXA reimbursement, ICD-9 diagnosis code, and Medicare carrier. For persons who had no DXA in 1999 or 2000 and who had 1 in 2001 or 2002, the proportion of DXA claims denied was 5.3% for women and 9.1% for men. For repeat DXAs performed within 23 mo, the proportion denied was approximately 19% and did not differ by sex. Reimbursement varied by more than 6-fold according to the ICD-9 diagnosis code submitted. For repeat DXAs performed at <23 mo, the proportion of claims denied ranged from 2% to 43%, depending on Medicare carrier. Denial of Medicare reimbursement for DXA varies significantly by sex, time since previous DXA, ICD-9 diagnosis code submitted, place of service (office vs facility), and local Medicare carrier. Greater guidance and transparency in coding policies are needed to ensure that DXA as a covered service is reimbursed for Medicare beneficiaries with the appropriate indications.

Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE

American Journal of Human Genetics. Nov, 2008  |  Pubmed ID: 18976728

Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date four genes have been established to either cause early-onset autosomal-dominant AD (APP, PSEN1, and PSEN2(1-4)) or to increase susceptibility for late-onset AD (APOE5). However, the heritability of late-onset AD is as high as 80%, (6) and much of the phenotypic variance remains unexplained to date. We performed a genome-wide association (GWA) analysis using 484,522 single-nucleotide polymorphisms (SNPs) on a large (1,376 samples from 410 families) sample of AD families of self-reported European descent. We identified five SNPs showing either significant or marginally significant genome-wide association with a multivariate phenotype combining affection status and onset age. One of these signals (p = 5.7 x 10(-14)) was elicited by SNP rs4420638 and probably reflects APOE-epsilon4, which maps 11 kb proximal (r2 = 0.78). The other four signals were tested in three additional independent AD family samples composed of nearly 2700 individuals from almost 900 families. Two of these SNPs showed significant association in the replication samples (combined p values 0.007 and 0.00002). The SNP (rs11159647, on chromosome 14q31) with the strongest association signal also showed evidence of association with the same allele in GWA data generated in an independent sample of approximately 1,400 AD cases and controls (p = 0.04). Although the precise identity of the underlying locus(i) remains elusive, our study provides compelling evidence for the existence of at least one previously undescribed AD gene that, like APOE-epsilon4, primarily acts as a modifier of onset age.

Weekend Hospitalization and Mortality: a Critical Review

Expert Review of Pharmacoeconomics & Outcomes Research. Feb, 2008  |  Pubmed ID: 20528352

Numerous studies have documented a positive association between weekend hospitalization and mortality. Some researchers have argued that these associations are causal and arise from weekend reductions in hospital staffing. Others have suggested that the observed correlations reflect differences in the unobservable characteristics of weekend versus weekday patients. The existing literature has provided only limited evidence of the specific pathways through which weekend hospitalization might affect health outcomes. This article outlines the limitations of the existing research and highlights the need for in-depth condition-specific studies that acknowledge the potential threat posed by selection bias.

Reduced Efficacy of Rosuvastatin by St. John's Wort

The American Journal of Medicine. Feb, 2009  |  Pubmed ID: 19185075

Successful Management and Long Term Outcome of an Accidental Subclavian Artery Injury with a 9 French Dilator During Pacemaker Implantation with Collagen-based Closure Device

Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. Sep, 2009  |  Pubmed ID: 19266274

Subclavian artery puncture and dilation with 9 Fr dilator during pacemaker implantation is a rare complication. We present a case, where this complication occurred and the injury was sealed with collagen-based closure device without any complications. Long term follow-up and the control angio-CT revealed no further late vascular complications. Therefore, use of a collagen based closure device for treating accidental iatrogenic subclavian artery injury can be a simple, successful alternative therapy when surgical direct vascular repair is not possible or not available.

Pacing Lead Implantation Without Live Fluoroscopy: Feasibility of Acute Success in the Live Canine Model

Journal of Cardiovascular Electrophysiology. Aug, 2009  |  Pubmed ID: 19298557

Fluoroscopic visualization for transvenous pacing lead placement necessitates lead shielding to minimize radiation exposure. An electromagnetic (EM) navigation system that integrates real-time intracardiac tracking within an anatomic navigation environment may provide an effective alternative for lead delivery that obviates live fluoroscopy. We assessed feasibility of pacing lead implantation with electromagnetic tracking guided solely by radiographic virtual navigation and compared this to fluoroscopy-guided implants in a canine model.

Very Late Drug-eluting Stent Thrombosis After Nonsteroidal Anti-inflammatory Drug Treatment Despite Dual Antiplatelet Therapy

The Canadian Journal of Cardiology. Apr, 2009  |  Pubmed ID: 19340348

Drug-eluting coronary stent implantation emerged as a safe and effective therapeutic approach by preventing coronary restenosis and reducing the need for further revascularization. However, in contrast to bare metal stents, recent data suggest a unique underlying pathology, namely late coronary stent thrombosis and delayed endothelial healing.

Life After Coronary Stent Thrombosis

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. May, 2009  |  Pubmed ID: 19396039

Coronary stent thrombosis is a catastrophic complication of percutaneous coronary intervention. There is a paucity of long-term data regarding the clinical outcome of patients who have suffered stent thrombosis.

Health Care Expenditures Associated with Skeletal Fractures Among Medicare Beneficiaries, 1999-2005

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. Dec, 2009  |  Pubmed ID: 19453260

Fractures impose substantial burdens, in terms of both costs and health, on individuals and health care systems. This is particularly true for older Americans and the Medicare system. The objective of this study was to estimate the costs of care associated with selected fractures among Medicare beneficiaries. This was a retrospective, person-level, pre/postfracture analysis using administrative data. The study used Medicare claims data from 1999 through 2005 for a 5% sample of Medicare beneficiaries. The subjects included Medicare beneficiaries, >or=65 yr of age, who had at least 13 mo of both Parts A and B coverage and not enrolled in Medicare Advantage and who experienced a closed fracture of the hip, femur, pelvis, tibia/fibula, ankle, distal forearm, nondistal radius/ulna, humerus, clavicle, spine, or wrist, or any fracture of the distal forearm or ankle during the years 2000 through 2005. The main outcome measures were incremental (greater than baseline) and attributable (directly associated) payments for Medicare-covered services for the first 6 mo after incident fractures. Incremental payments ranged from $7788 (95% CI, $7550-$8025) for distal forearm fractures to $31,310 (95% CI, $31,073-$31,547) for open hip fractures; the attributable payments for distal forearm and hip fractures were $1856 and $18,734, respectively. Fractures are associated with substantial increases in health services utilization and costs among Medicare beneficiaries, but significant proportions of those costs are not directly attributable to fracture treatment. Further research is needed to ascertain other health conditions that are driving costs for Medicare beneficiaries after fractures.

Recovering Unused Information in Genome-wide Association Studies: the Benefit of Analyzing SNPs out of Hardy-Weinberg Equilibrium

European Journal of Human Genetics : EJHG. Dec, 2009  |  Pubmed ID: 19491930

Although the rapid advancements in high throughput genotyping technology have made genome-wide association studies possible, these studies remain an expensive undertaking, especially when considering the large sample sizes necessary to find the small to moderate effect sizes that define complex diseases. It is therefore prudent to utilize all possible information contained in a genome-wide scan. We propose a straightforward analytical approach that tests often unused SNP data without sacrificing statistical validity. We simulate genotype miscalls under a variety of models consistent with observed miscall rates and test for departures from HWE using the standard Pearson's chi(2)-test. We find that true disease susceptibility loci subjected to various patterns of genotype miscalls can be largely out of HWE and, thus, be candidates for removal before association testing. These loci, we demonstrate, can maintain sufficient statistical power even under extreme error models. We additionally show that random miscalls of null SNPs, independent of the phenotype, do not induce bias in case-control or cohort studies, and we suggest that a significant HWE test should not prevent a SNP from being tested when conducting genome-wide association studies in these scenarios. However, association findings for SNPs that are out of HWE must be treated more carefully than 'regular' findings, for example, by re-genotyping the SNP in the same study using a different genotyping technology.

The Future is Now

Journal of the Massachusetts Dental Society. 2009  |  Pubmed ID: 19526906

Red Yeast Rice for Dyslipidemia in Statin-intolerant Patients: a Randomized Trial

Annals of Internal Medicine. Jun, 2009  |  Pubmed ID: 19528562

Red yeast rice is an herbal supplement that decreases low-density lipoprotein (LDL) cholesterol level.

Potential Late-onset Alzheimer's Disease-associated Mutations in the ADAM10 Gene Attenuate {alpha}-secretase Activity

Human Molecular Genetics. Oct, 2009  |  Pubmed ID: 19608551

ADAM10, a member of a disintegrin and metalloprotease family, is an alpha-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated alpha-secretase activity of ADAM10 (>70% decrease), and elevated Abeta levels (1.5-3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD.

Gap-junction Proteins in Retinal Development: New Roles for the "nexus"

Physiology (Bethesda, Md.). Aug, 2009  |  Pubmed ID: 19675353

Gap-junction channels, the cytoplasmic proteins that associate with them, and the transcriptional networks that regulate them are increasingly being viewed as critical communications hubs for cell signaling in health and disease. As a result, the term "nexus," which was the original structural name for these focal intercellular links, is coming back into use with new proteomic and transcriptomic meanings. The retina is better understood than any other part of the vertebrate central nervous system in respect of its developmental patterning, its diverse neuronal types and circuits, and the emergence of its definitive structure-function correlations. Thus, studies of the junctional and nonjunctional nexus roles of gap-junction proteins in coordinating retinal development should throw useful light on cell signaling in other developing nervous tissues.

Comparison of Elimination and Cardiovascular Effects of Adenine Nucleosides Administered Intrapericardially or Intravenously in Anesthetized Dog

Journal of Cardiovascular Pharmacology. Oct, 2009  |  Pubmed ID: 19687746

Intrapericardial (IP) administration of certain cardioactive agents allows investigation of local pharmacological actions on the heart and may carry potential benefit to influence myocardial function. The cardioprotective adenosine (ADO) and inosine (INO) may be the most representative candidates. Elimination and cardiovascular effects of IP and intravenously (IV) applied ADO and INO were compared on anesthetized dogs. Their pericardial and systemic concentrations were measured after consecutive administration of increasing ADO and INO doses. In the case of IP administration at the end of the incubation period, pericardial concentrations of adenine nucleosides significantly exceeded the control values. However, the IV applied ADO and INO were rapidly metabolized in the systemic plasma. As characteristic hemodynamic effects, small but sustained decrease in heart rate (IP ADO) and increase in myocardial contractility (IP INO) were observed. During IV administration, ADO and INO exerted remarkable effects on all hemodynamic variables, which then gradually disappeared in 15 minutes. In summary, the elimination of ADO and INO was significantly slower in the pericardial fluid than in the plasma. Considering the balanced cardiac actions and lack of strong systemic hemodynamic effects, IP administration of adenine nucleosides may suggest a promising approach in the local treatment of the diseased heart.

Leveling the Playing Field

Journal of the Massachusetts Dental Society. 2009  |  Pubmed ID: 19774861

Significance of Off-hours in Centralized Primary Percutaneous Coronary Intervention Network

Croatian Medical Journal. Oct, 2009  |  Pubmed ID: 19839071

To analyze the efficacy of a regionally organized primary percutaneous coronary intervention (PCI) network at the Heart Center, Semmelweis University Budapest, part of the "Budapest model," and the factors that influence it.

Simple Truths

Journal of the Massachusetts Dental Society. 2009  |  Pubmed ID: 19927947

Gap Junction Reduction in Cardiomyocytes Following Transforming Growth Factor-beta Treatment and Trypanosoma Cruzi Infection

Memorias Do Instituto Oswaldo Cruz. Dec, 2009  |  Pubmed ID: 20140368

Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (TGF-beta). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-beta T. cruzi, or SB-431542, an inhibitor of TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta signalling had been shown previously to be highly activated. We demonstrated that TGF-beta treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-beta secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-beta levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease.

Maximizing the Power of Genome-Wide Association Studies: A Novel Class of Powerful Family-Based Association Tests

Statistics in Biosciences. Nov, 2009  |  Pubmed ID: 22582089

For genome-wide association studies in family-based designs, a new, universally applicable approach is proposed. Using a modified Liptak's method, we combine the p-value of the family-based association test (FBAT) statistic with the p-value for the Van Steen-statistic. The Van Steen-statistic is independent of the FBAT-statistic and utilizes information that is ignored by traditional FBAT-approaches. The new test statistic takes advantages of all available information about the genetic association, while, by virtue of its design, it achieves complete robustness against confounding due to population stratification. The approach is suitable for the analysis of almost any trait type for which FBATs are available, e.g. binary, continuous, time to-onset, multivariate, etc. The efficiency and the validity of the new approach depend on the specification of a nuisance/tuning parameter and the weight parameters in the modified Liptak's method. For different trait types and ascertainment conditions, we discuss general guidelines for the optimal specification of the tuning parameter and the weight parameters. Our simulation experiments and an application to an Alzheimer study show the validity and the efficiency of the new method, which achieves power levels that are comparable to those of population-based approaches.

Tolerability of Red Yeast Rice (2,400 Mg Twice Daily) Versus Pravastatin (20 Mg Twice Daily) in Patients with Previous Statin Intolerance

The American Journal of Cardiology. Jan, 2010  |  Pubmed ID: 20102918

Currently, no consensus has been reached regarding the management of hyperlipidemia in patients who develop statin-associated myalgia (SAM). Many statin-intolerant patients use alternative lipid-lowering therapies, including red yeast rice. The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia. The study was conducted in a community-based setting in Philadelphia, Pennsylvania. A total of 43 adults with dyslipidemia and a history of statin discontinuation because of myalgia were randomly assigned to red yeast rice 2,400 mg twice daily or pravastatin 20 mg twice daily for 12 weeks. All subjects were concomitantly enrolled in a 12-week therapeutic lifestyle change program. The primary outcomes included the incidence of treatment discontinuation because of myalgia and a daily pain severity score. The secondary outcomes were muscle strength and plasma lipids. The incidence of withdrawal from medication owing to myalgia was 5% (1 of 21) in the red yeast rice group and 9% (2 of 22) in the pravastatin group (p = 0.99). The mean pain severity did not differ significantly between the 2 groups. No difference was found in muscle strength between the 2 groups at week 4 (p = 0.61), week 8 (p = 0.81), or week 12 (p = 0.82). The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group. In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins.

Carpe Diem, or Lose Our Voice

Journal of the Massachusetts Dental Society. 2010  |  Pubmed ID: 20225794

Voices from the Field: Part II

Current Problems in Pediatric and Adolescent Health Care. Mar, 2010  |  Pubmed ID: 20230981

The Societal Burden of Osteoporosis

Current Rheumatology Reports. Jun, 2010  |  Pubmed ID: 20425518

Osteoporosis currently affects 10 million Americans and is responsible for more than 1.5 million fractures annually. The financial burden of osteoporosis is substantial, with annual direct medical costs estimated at 17 to 20 billion dollars. Most of these costs are related to the acute and rehabilitative care following osteoporotic fractures, particularly hip fractures. The societal burden of osteoporosis includes these direct medical costs and the monetary (eg, caregiver time) and nonmonetary costs of poor health. The aging of the US population is expected to increase the prevalence of osteoporosis and the number of osteoporotic fractures. Growth of the older adult population will pose significant challenges to Medicare and Medicaid, which bear most of the cost of osteoporosis. Efforts to address the looming financial burden must focus on reducing the prevalence of osteoporosis and the incidence of costly fragility fractures.

Health Services Utilization After Fractures: Evidence from Medicare

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. Sep, 2010  |  Pubmed ID: 20530242

Osteoporosis-related fractures impose a large and growing societal burden, including adverse health effects and direct medical costs. Postfracture utilization of health care services represents an alternative measure of the resource costs associated with these fractures.

Meta-analysis of Cotton Fiber Quality QTLs Across Diverse Environments in a Gossypium Hirsutum X G. Barbadense RIL Population

BMC Plant Biology. Jun, 2010  |  Pubmed ID: 20584292

Cotton fibers (produced by Gossypium species) are the premier natural fibers for textile production. The two tetraploid species, G. barbadense (Gb) and G. hirsutum (Gh), differ significantly in their fiber properties, the former having much longer, finer and stronger fibers that are highly prized. A better understanding of the genetics and underlying biological causes of these differences will aid further improvement of cotton quality through breeding and biotechnology. We evaluated an inter-specific Gh x Gb recombinant inbred line (RIL) population for fiber characteristics in 11 independent experiments under field and glasshouse conditions. Sites were located on 4 continents and 5 countries and some locations were analyzed over multiple years.

Calls to Action

Journal of the Massachusetts Dental Society. 2010  |  Pubmed ID: 20806697

Is Withholding Osteoporosis Medication After Fracture Sometimes Rational? A Comparison of the Risk for Second Fracture Versus Death

Journal of the American Medical Directors Association. Oct, 2010  |  Pubmed ID: 20889095

Undertreatment of osteoporosis is common, even for high-risk patients. Among the reasons for undertreatment may be a clinician's perception of a lack of treatment benefit, particularly in light of patients' expected future mortality. Among US Medicare beneficiaries, we evaluated the risk for second fracture versus death in the 5 years following a hip, clinical vertebral, and wrist/forearm fracture.

Marked Variability of Monacolin Levels in Commercial Red Yeast Rice Products: Buyer Beware!

Archives of Internal Medicine. Oct, 2010  |  Pubmed ID: 20975018

Red yeast rice (RYR) is a widely available dietary supplement used by millions of patients as an alternative therapy for hyperlipidemia. It contains 14 active compounds called monacolins that inhibit hepatic cholesterol synthesis. Although studies have suggested that some formulations of RYR may be effective and safe for lipid lowering, monacolin levels are not standardized among marketed products and are generally not published on labels. We evaluated monacolin levels in 12 commercial RYR formulations and tested for citrinin, a mycotoxin that is nephrotoxic in animals.

Predicting Hip and Major Osteoporotic Fractures Using Administrative Data

Archives of Internal Medicine. Nov, 2010  |  Pubmed ID: 21098356

Are You Doing Your Part?

Journal of the Massachusetts Dental Society. 2010  |  Pubmed ID: 21125928

The Role of Red Yeast Rice for the Physician

Current Atherosclerosis Reports. Feb, 2011  |  Pubmed ID: 21061097

Red yeast rice is an ancient Chinese dietary staple and medication used by millions of patients as an alternative therapy for hypercholesterolemia. In recent years, the use of red yeast rice has grown exponentially due to increased public interest in complementary and alternative medications and the publication of several randomized, controlled trials demonstrating its efficacy and safety in different populations. The most promising role for red yeast rice is as an alternative lipid-lowering therapy for patients who refuse to take statins because of philosophical reasons or patients who are unable to tolerate statin therapy due to statin-associated myalgias. However, there is limited government oversight of red yeast rice products, wide variability of active ingredients in available formulations, and the potential of toxic byproducts. Therefore, until red yeast rice products are regulated and standardized, physicians and patients should be cautious in recommending this promising alternative therapy for hyperlipidemia.

Trying Times

Journal of the Massachusetts Dental Society. 2011  |  Pubmed ID: 21446612

Continuity of Insurance Coverage and Ambulatory Care-sensitive Hospitalizations/ED Visits: Evidence from the Children's Health Insurance Program

Clinical Pediatrics. Oct, 2011  |  Pubmed ID: 21828066

To assess the effects of continuity of insurance coverage on treatment of ambulatory-care sensitive conditions (ACSC).

Functional Gap Junctions Accumulate at the Immunological Synapse and Contribute to T Cell Activation

Journal of Immunology (Baltimore, Md. : 1950). Sep, 2011  |  Pubmed ID: 21844382

Gap junction (GJ) mediates intercellular communication through linked hemichannels from each of two adjacent cells. Using human and mouse models, we show that connexin 43 (Cx43), the main GJ protein in the immune system, was recruited to the immunological synapse during T cell priming as both GJs and stand-alone hemichannels. Cx43 accumulation at the synapse was Ag specific and time dependent, and required an intact actin cytoskeleton. Fluorescence recovery after photobleaching and Cx43-specific inhibitors were used to prove that intercellular communication between T cells and dendritic cells is bidirectional and specifically mediated by Cx43. Moreover, this intercellular cross talk contributed to T cell activation as silencing of Cx43 with an antisense or inhibition of GJ docking impaired intracellular Ca(2+) responses and cytokine release by T cells. These findings identify Cx43 as an important functional component of the immunological synapse and reveal a crucial role for GJs and hemichannels as coordinators of the dendritic cell-T cell signaling machinery that regulates T cell activation.

An "A" for the MDS, but an "F" for the State

Journal of the Massachusetts Dental Society. 2011  |  Pubmed ID: 22128466

Medical Liability and Health Care Reform

Health Matrix (Cleveland, Ohio : 1991). 2011  |  Pubmed ID: 22145523

We examine the impact of the Affordable Care Act (ACA) on medical liability and the controversy over whether federal medical reform including a damages cap could make a useful contribution to health care reform. By providing guaranteed access to health care insurance at community rates, the ACA could reduce the problem of under-compensation resulting from damages caps. However, it may also exacerbate the problem of under-claiming in the malpractice system, thereby reducing incentives to invest in loss prevention activities. Shifting losses from liability insurers to health insurers could further undermine the already weak deterrent effect of the medical liability system. Republicans in Congress and physician groups both pushed for the adoption of a federal damages cap as part of health care reform. Physician support for damages caps could be explained by concerns about the insurance cycle and the consequent instability of the market. Our own study presented here suggests that there is greater insurance market stability in states with caps on non-economic damages. Republicans in Congress argued that the enactment of damages caps would reduce aggregate health care costs. The Congressional Budget Office included savings from reduced health care utilization in its estimates of cost savings that would result from the enactment of a federal damages cap. But notwithstanding recent opinions offered by the CBO, it is not clear that caps will significantly reduce health care costs or that any savings will be passed on to consumers. The ACA included funding for state level demonstration projects for promising reforms such as offer and disclosure and health courts, but at this time the benefits of these reforms are also uncertain. There is a need for further studies on these issues.

Speaking Up for Those Who Can't

Journal of the Massachusetts Dental Society. 2011  |  Pubmed ID: 22308602

The Dental Team's Role in Identifying and Reporting Cases of Child Abuse

Journal of the Massachusetts Dental Society. 2011  |  Pubmed ID: 22308608

The Lipid-lowering Properties of Red Yeast Rice

The Virtual Mentor : VM. Jun, 2011  |  Pubmed ID: 23131404

The Impact of CHIP Coverage on Children with Asthma in Alabama

Clinical Pediatrics. Mar, 2012  |  Pubmed ID: 21890839

This study evaluates the impact of coverage in ALL Kids, the Alabama Child Health Insurance Program (CHIP), by examining asthma-related utilization and outcomes among children continuously enrolled for 3 years (N = 1954)with persistent asthma at enrollment. Outcomes and costs were compared for the first, second, and third years of enrollment using repeated measures analysis of variance and controlling for age, gender, and year fixed-effects. Compared with subsequent years, first year enrollment utilization was higher for asthma-related hospitalizations (6% vs 2% vs 2%; P < .0001) and emergency visits (10% vs 3% vs 2%; P < .0001). Also decreasing were asthma-related outpatient visits (1.46 vs 1.12 vs 0.94; P < .0001), quick-relief prescriptions (2.6 vs 2.2 vs 2.1; P < .0001), and long-term control prescriptions (5.8 vs 5.2 vs 4.4; P < .0001). As a result, significant declines in the mean costs per child were observed. Ongoing ALL Kids coverage is associated with improved disease-management and lower costs for persistent asthma.

Metallic Taste After Coronary Artery Stent Implantation

International Journal of Cardiology. Jul, 2012  |  Pubmed ID: 22071040

Connexins in Wound Healing; Perspectives in Diabetic Patients

Biochimica Et Biophysica Acta. Aug, 2012  |  Pubmed ID: 22155211

Skin lesions are common events and we have evolved to rapidly heal them in order to maintain homeostasis and prevent infection and sepsis. Most acute wounds heal without issue, but as we get older our bodies become compromised by poor blood circulation and conditions such as diabetes, leading to slower healing. This can result in stalled or hard-to-heal chronic wounds. Currently about 2% of the Western population develop a chronic wound and this figure will rise as the population ages and diabetes becomes more prevalent [1]. Patient morbidity and quality of life are profoundly altered by chronic wounds [2]. Unfortunately a significant proportion of these chronic wounds fail to respond to conventional treatment and can result in amputation of the lower limb. Life quality and expectancy following amputation is severely reduced. These hard to heal wounds also represent a growing economic burden on Western society with published estimates of costs to healthcare services in the region of $25B annually [3]. There exists a growing need for specific and effective therapeutic agents to improve healing in these wounds. In recent years the gap junction protein Cx43 has been shown to play a pivotal role early on in the acute wound healing process at a number of different levels [4-7]. Conversely, abnormal expression of Cx43 in wound edge keratinocytes was shown to underlie the poor rate of healing in diabetic rats, and targeting its expression with an antisense gel restored normal healing rates [8]. The presence of Cx43 in the wound edge keratinocytes of human chronic wounds has also been reported [9]. Abnormal Cx43 biology may underlie the poor healing of human chronic wounds and be amenable therapeutic intervention [7]. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

Did Copayment Changes Reduce Health Service Utilization Among CHIP Enrollees? Evidence from Alabama

Health Services Research. Aug, 2012  |  Pubmed ID: 22352979

To explore whether health care utilization changed among enrollees in Alabama's CHIP program, ALL Kids, following copayment increases at the beginning of fiscal year 2004.

Overexpression of the Gap Junction Protein Cx43 As Found in Diabetic Foot Ulcers Can Retard Fibroblast Migration

Cell Biology International. Jul, 2012  |  Pubmed ID: 22455314

Poor healing of DFUs (diabetic foot ulcers) is a major clinical problem that can be extremely debilitating and lead to lower limb amputation. In the normal acute wound, the Cx43 (connexin 43) gap junction protein is down-regulated at the wound edge as a precursor to cell migration and healing. In fibroblasts from the human chronic DFU wound edge there was a striking and significant 10-fold elevation of Cx43 protein, as well as a 6-fold increase in N-cadherin and a 2-fold increase in ZO-1 (zonular occludin-1), compared with unwounded skin. In streptozotocin diabetic rats, Cx43 was found to be up-regulated in intact dermal fibroblasts in direct proportion to blood glucose levels and increased 2-fold further in response to wounding of the skin. To mimic diabetes, NIH 3T3 fibroblasts were cultured under different concentrations of glucose or mannitol and Cx43 protein intercellular communication and migration rates were determined. Cultures of fibroblasts in very high (40 mM) glucose conditions showed significantly elevated Cx43 protein levels, as shown by immunostaining and Western blotting, and significantly increasing gap junctional communication, as shown by dye transfer. In scratch wound-healing assays, increased levels of Cx43 from high glucose resulted in repressed filopodial extensions and significantly slower migration rates than in either standard conditions (5.5 mM glucose) or the osmotic control of mannitol. Conversely, when glucose-induced Cx43 up-regulation was prevented with Cx43shRNA (Cx43 short-hairpin RNA) transduction, the fibroblasts extended long filopodia and migrated significantly faster. Cx43 protein was up-regulated in fibroblasts in DFUs as well as after high glucose exposure in culture which correlated with inhibition of fibroblast migration and is likely to contribute to impaired wound healing.

Connexins and Diabetes

Cardiology Research and Practice. 2012  |  Pubmed ID: 22536530

Cell-to-cell interactions via gap junctional communication and connexon hemichannels are involved in the pathogenesis of diabetes. Gap junctions are highly specialized transmembrane structures that are formed by connexon hemichannels, which are further assembled from proteins called "connexins." In this paper, we discuss current knowledge about connexins in diabetes. We also discuss mechanisms of connexin influence and the role of individual connexins in various tissues and how these are affected in diabetes. Connexins may be a future target by both genetic and pharmacological approaches to develop treatments for the treatment of diabetes and its complications.

Direct Formation of the C5'-radical in the Sugar-phosphate Backbone of DNA by High-energy Radiation

The Journal of Physical Chemistry. B. May, 2012  |  Pubmed ID: 22553971

Neutral sugar radicals formed in DNA sugar-phosphate backbone are well-established as precursors of biologically important damage such as DNA strand scission and cross-linking. In this work, we present electron spin resonance (ESR) evidence showing that the sugar radical at C5' (C5'(•)) is one of the most abundant (ca. 30%) sugar radicals formed by γ- and Ar ion-beam irradiated hydrated DNA samples. Taking dimethyl phosphate as a model of sugar-phosphate backbone, ESR and theoretical (DFT) studies of γ-irradiated dimethyl phosphate were carried out. CH(3)OP(O(2)(-))OCH(2)(•) is formed via deprotonation from the methyl group of directly ionized dimethyl phosphate at 77 K. The formation of CH(3)OP(O(2)(-))OCH(2)(•) is independent of dimethyl phosphate concentration (neat or in aqueous solution) or pH. ESR spectra of C5'(•) found in DNA and of CH(3)OP(O(2)(-))OCH(2)(•) do not show an observable β-phosphorus hyperfine coupling (HFC). Furthermore, C5'(•) found in DNA does not show a significant C4'-H β-proton HFC. Applying the DFT/B3LYP/6-31G(d) method, a study of conformational dependence of the phosphorus HFC in CH(3)OP(O(2)(-))OCH(2)(•) shows that in its minimum energy conformation, CH(3)OP(O(2)(-))OCH(2)(•), has a negligible β-phosphorus HFC. On the basis of these results, the formation of radiation-induced C5'(•) is proposed to occur via a very rapid deprotonation from the directly ionized sugar-phosphate backbone, and the rate of this deprotonation must be faster than that of energetically downhill transfer of the unpaired spin (hole) from ionized sugar-phosphate backbone to the DNA bases. Moreover, C5'(•) in irradiated DNA is found to be in a conformation that does not exhibit β-proton or β-phosphorus HFCs.

Targeting Cx43 and N-cadherin, Which Are Abnormally Upregulated in Venous Leg Ulcers, Influences Migration, Adhesion and Activation of Rho GTPases

PloS One. 2012  |  Pubmed ID: 22615994

Venous leg ulcers can be very hard to heal and represent a significant medical need with no effective therapeutic treatment currently available.

Prediction Model to Estimate Presence of Coronary Artery Disease: Retrospective Pooled Analysis of Existing Cohorts

BMJ (Clinical Research Ed.). Jun, 2012  |  Pubmed ID: 22692650

To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations.

Autocrine Adenosine Signaling Promotes Regulatory T Cell-mediated Renal Protection

Journal of the American Society of Nephrology : JASN. Sep, 2012  |  Pubmed ID: 22835488

Regulatory T cells (Tregs) suppress the innate inflammation associated with kidney ischemia-reperfusion injury (IRI), but the mechanism is not well understood. Tregs express CD73, the final enzyme involved in the production of extracellular adenosine, and activation of the adenosine 2A receptor (A(2A)R) on immune cells suppresses inflammation and preserves kidney function after IRI. We hypothesized that Treg-generated adenosine is required to block innate immune responses in kidney IRI and that the Treg-generated adenosine would signal through A(2A)Rs on inflammatory cells and, in an autocrine manner, on Tregs themselves. We found that adoptively transferred wild-type Tregs protected wild-type mice from kidney IRI, but the absence of adenosine generation (CD73-deficient Tregs) or adenosine responsiveness (A(2A)R-deficient Tregs) led to inhibition of Treg function. Pharmacologic stimulation of A(2A)R before adoptive transfer augmented the ability of wild-type and CD73-deficient Tregs to suppress kidney IRI. Microarray analysis and flow cytometry revealed that A(2A)R activation enhanced surface PD-1 expression on Tregs in the absence of any other activation signal. Treatment of Tregs with a PD-1 blocking antibody before adoptive transfer reversed their protective effects, even if pretreated with an A(2A)R agonist. Taken together, these results demonstrate that the simultaneous ability to generate and respond to adenosine is required for Tregs to suppress innate immune responses in IRI through a PD-1-dependent mechanism.

The Times They Are A-changin'

Journal of the Massachusetts Dental Society. 2012  |  Pubmed ID: 22919942

Kr-86 Ion-beam Irradiation of Hydrated DNA: Free Radical and Unaltered Base Yields

Radiation Research. Dec, 2012  |  Pubmed ID: 23106211

This work reports an ESR and product analysis investigation of Kr-86 ion-beam irradiation of hydrated DNA at 77 K. The irradiation results in the formation and trapping of both base radicals and sugar phosphate radicals (DNA backbone radicals). The absolute yields (G, μmol/J) of the base radicals are smaller than the yields found in similarly prepared γ-irradiated DNA samples, and the relative yields of backbone radicals relative to base radicals are much higher than that found in γ-irradiated samples. From these results, we have elaborated our radiation chemical model of the track structure for ion-beam irradiated DNA as it applies to krypton ion-beams. The base radicals, which are trapped as ion radicals or reversibly protonated or deprotonated ion radicals, are formed almost entirely in the track penumbra, a region in which radiation chemical effects are similar to those found in γ-irradiated samples. By comparing the yields of base radicals in ion-beam samples to the yields of the same radicals in γ-irradiated samples, the partition of energy between the low-LET region (penumbra) and the core is experimentally determined. The neutral sugar and other backbone radicals, which are not as susceptible to recombination as are ion radicals, are formed largely in the track core. The backbone radicals show a linear dose response up to very high doses. Unaltered base release yields in Kr-86 irradiated hydrated DNA are equal to sugar radical yields within experimental error limits, consistent with radiation-chemical processes in which all base release originates with sugar radicals. Two phosphorus-centered radicals from fragmentation of the DNA backbone are found in low yields.

[Acute Coronary Syndrome -- 2012]

Orvosi Hetilap. Dec, 2012  |  Pubmed ID: 23248055

The acute coronary syndrome is the most severe form of coronary artery disease. It is an immediate threat of life and the mortality rate can be high without proper therapy and patient management. Based on the first ECG, two different forms can be distinguished: acute coronary syndrome with and without ST elevation. Besides adequate medication, management of these patients is an essential part of treatment. In case of ST elevation, coronarography and percutaneous coronary intervention is needed in general, within 24 hours from the onset of symptoms. When ST elevation is not detected on the ECG, individual ischemic risk factors and predictable mortality of the patient may define the necessity and the date of the invasive examination. The Hungarian hemodynamic laboratory network covers almost the whole country and, therefore, practically each patient may receive a state-of-the-art therapy. Although indicators of cardiovascular diseases are still prominent, the mortality rate of myocardial Infarction is decreasing in Hungary due to the well-organized invasive care.

Ventricular Septal Rupture Caused by Myocardial Bridge, Solved by Interventional Closure Device

Croatian Medical Journal. Dec, 2012  |  Pubmed ID: 23275329

Myocardial bridging is a common coronary anomaly, which is generally described as a benign phenomenon. However, a growing number of studies consider this anomaly a relevant pathophysiological phenomenon with serious pathological consequences. Here we report on the case of an 88-year-old woman suffering from myocardial infarction and ventricular septal rupture, lacking any recognizable coronary disease except for a myocardial bridge causing the systolic compression of the left anterior descending coronary artery. A wide range of diagnostic procedures, including coronarography, echocardiography, and magnetic resonance imaging were used. The septal rupture was finally closed by using a percutaneous closure device. This event indicates that myocardial bridges - at least in some cases - may have notable clinical relevance.

Looking out for the Little Ones

Journal of the Massachusetts Dental Society. 2012  |  Pubmed ID: 23311035

EDIC: a Fine Accomplishment

Journal of the Massachusetts Dental Society. 2012  |  Pubmed ID: 23513341

Evaluating Comorbidity Scores Based on Health Service Expenditures

Medicare & Medicaid Research Review. 2012  |  Pubmed ID: 24800145

To describe the performance of Charlson Comorbidity Index (CCI) specifications among Medicare beneficiaries and subgroups.

The Effects of Premium Changes on ALL Kids, Alabama's CHIP Program

Medicare & Medicaid Research Review. 2012  |  Pubmed ID: 24800149

Describe the trends in enrollment and renewal in the Alabama Children's Health Insurance Plan (CHIP), ALL Kids, since its creation in 1998, and to estimate the effect that an annual premium increase, along with coincident increases in service copays, had on the decision to renew participation.

A Close Examination of Healthcare Expenditures Related to Fractures

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. Apr, 2013  |  Pubmed ID: 23074090

This study evaluated reasons for healthcare expenditures both before and after the occurrence of fractures among Medicare beneficiaries. In a previous study we examined healthcare expenditures in the 6 months before and after fractures. The difference-"incremental" expenditures-provides one estimate of the potentially avoidable costs associated with fractures. We constructed a second estimate of the cost burden-"attributable" expenditures-using only those costs recorded in claims with fracture diagnosis codes. Attributable expenditures accounted for only 24% to 60% of incremental expenditures, depending on the fracture site. We examined health care expenditures between 1999 and 2005 among Medicare beneficiaries who experienced fractures (cases) and among beneficiaries who did not experience fractures (controls), matched to cases on age, race, and sex. We also examined healthcare expenditures for cases and controls for 24 months prior to the fracture index date. When expenditures associated with diagnoses for aftercare, joint pain, and osteoporosis, other musculoskeletal diagnoses, pneumonia, and pressure ulcers were included, the proportion of incremental costs directly attributable to fracture care rose to 72% to 88%. Expenditures prior to fracture were higher for cases than controls, and the rate of increase accelerated over the 12 months prior to the hip fracture. Our findings confirm that the original incremental cost analysis constituted a satisfactory method for estimating avoidable costs associated with fractures. We also conclude that those with fractures had much higher and growing healthcare expenditures in the 12 months prior to the event, compared with age-, race-, and sex-matched controls. This suggests that patterns of healthcare services utilization may provide a means to improve fracture prediction rules.

Favorable Selection, Risk Adjustment, and the Medicare Advantage Program

Health Services Research. Jun, 2013  |  Pubmed ID: 23088500

To examine the effects of changes in payment and risk adjustment on (1) the annual enrollment and switching behavior of Medicare Advantage (MA) beneficiaries, and (2) the relative costliness of MA enrollees and disenrollees.

Importance of Connexin-43 Based Gap Junction in Cirrhosis and Acute on Chronic Liver Failure

Journal of Hepatology. Jan, 2013  |  Pubmed ID: 23376361

BACKGROUND: In cirrhosis, superimposed inflammation often culminates in acute-on chronic liver failure but the mechanism underlying this increased sensitivity is not clear. Cx43 is a ubiquitous gap junction protein that allows transmission of signals between cells at a much higher rate than the constitutively expressed gap junctions. The aims of the study were to test the hypothesis that inflammation drives the increased expression of hepatic Cx43 and to determine its role by Cx43 inhibition. METHODS: Four-weeks after bile duct-ligation (BDL) or sham operation, rats were treated with an anti-TNF antibody, or saline; with or without LPS (1mg/kg); given 3 hrs prior to termination. Biochemistry and cytokines were measured in the plasma and hepatic protein expression (NFkB, TNF-α, iNOS, 4HNE, Cx26, 32 and 43), and confocal microscopy (Cx26, 32 and 43) was performed. The effect of a Cx43-specific inhibitory peptide was studied in a mice BDL model. RESULTS: BDL animals administered with LPS developed typical features of ACLF but the animals administered Infliximab were relatively protected. Cx26/32 expressions were significantly decreased in BDL animals whilst Cx43 was significantly increased which increased further following LPS. Infliximab treatment prevented this increase. However, inhibiting Cx43 in BDL mice produced detrimental effects with markedly greater hepatocellular necrosis. CONCLUSION: The results of this study show for the first time an increased expression of hepatic Cx43 in cirrhosis and ACLF, which was related to the severity of inflammation. This increased Cx43 expression is likely to be an adaptive protective response of the liver to allow better cell-to-cell communication.

Integration of Scaffolds into Full-thickness Skin Wounds: the Connexin Response

Advanced Healthcare Materials. Aug, 2013  |  Pubmed ID: 23417927

Scaffolds have been reported to promote healing of hard-to-heal wounds such as burns and chronic ulcers. However, there has been little investigation into the cell biology of wound edge tissues in response to the scaffolds. Here, we assess the impact of collagen scaffolds on mouse full-thickness wound re-epithelialisation during the first 5 days of healing. We find that scaffolds impede wound re-epithelialisation, inducing a bulbous thickening of the wound edge epidermis as opposed to the thin tongue of migratory keratinocytes seen in normal wound healing. Scaffolds also increase the inflammatory response and the numbers of neutrophils in and around the wound. These effects were also produced by scaffolds made of alginate in the form of fibers and microspheres, but not as an alginate hydrogel. In addition, we find the gap junction protein connexin 43, which normally down-regulates at the wound edge during re-epithelialisation, to be up-regulated in the bulbous epidermal wound edge. Incorporation of connexin 43 antisense oligodeoxynucleotides into the scaffold can be performed to reduce inflammation whilst promoting scaffold biocompatibility.

Can You Hear Me Now?

Journal of the Massachusetts Dental Society. 2013  |  Pubmed ID: 23520687

Long-term Clinical Follow-up After Drug-eluting Stent Implantation for Bare Metal In-stent Restenosis

Journal of Interventional Cardiology. Jun, 2013  |  Pubmed ID: 23586796

We aimed to evaluate the long-term safety and efficacy of drug-eluting stent (DES) implantation in the treatment of diffuse bare metal stent (BMS) restenosis as compared to the treatment of de novo coronary lesions in high restenosis risk patient population.

Connexin Dynamics in the Privileged Wound Healing of the Buccal Mucosa

Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society. Jul-Aug, 2013  |  Pubmed ID: 23627777

Wound closure is fundamental to maintaining tissue homeostasis; a plethora of processes and signals must be coordinated, and gap junctions play a critical role. Some tissues exhibit privileged healing, such as buccal mucosa, repairing more rapidly, but gap junction connexin dynamics during wound healing in such tissues have not been investigated. To determine connexin changes during this rapid healing process, incisional wounds were made in the cheeks of mice and microscopically observed. We discovered that buccal mucosa wound edge keratinocytes do not form a thin tongue of migratory cells like epidermis; instead, a wedge of cells rapidly moves into the wound. The dorsal surfaces of opposing sides of the wounds then touch and join in a "V," which subsequently fills up with cells to form a "delta" that remodels into a flat sheet. Immunostaining showed that connexin26, connexin30, and connexin43 are expressed at significantly higher levels in the buccal mucosa than the epidermis and that, unlike the skin, all three are rapidly down-regulated at the wound edge within 6 hours of wounding. This rapid down-regulation of all three connexins may in part underlie the rapid healing of the buccal mucosa.

[2012 -- the Year of Success in the 20 Year-old Adult Heart Transplant Program of Hungary]

Orvosi Hetilap. Jun, 2013  |  Pubmed ID: 23708987

The Hungarian adult heart transplant program, which started in 1992, has changed gradually in the past 20 years. After the early enthusiasm of the first cases it changed significantly and it became an organized programme. However, low donation activity and moderate referral numbers to the national transplant waiting list slowed down the process therefore, heart transplant numbers did not fulfill expectations in the early years. After a moderate increase in 2007 transplant numbers have dropped again until recently when Hungary partially joined Eurotransplant network. Excess fundamental resources allocated to cardiac transplantation by health care professionals and reorganizing transplant coordination as well as logistics forced dramatic changes in clinical management. In 2011 and 2012 major structural changes had been made at Semmelweis University. The newly established transplant intensive care unit and the initiation of mechanical circulatory support and assist device programme increased transplant numbers by 131% compared to previous years, as well as it resulted an 86.63% 30-day survival rate, hence last year was the most successful year of cardiac transplantation ever.

Effectiveness of Preventive Dental Visits in Reducing Nonpreventive Dental Visits and Expenditures

Pediatrics. Jun, 2013  |  Pubmed ID: 23713098

Although preventive dental visits are considered important for maintaining pediatric oral health, there is relatively little research showing that they reduce subsequent nonpreventive dental visits or costs. At least 1 study seemed to find that early preventive dental care is associated with more restorative and emergency visits. Previous studies are limited by their inability to account for unmeasurable factors that may lead children to "select" into using both more preventive and nonpreventive dental care. We used econometric techniques that minimize selection bias to assess the effectiveness of preventive dental care in reducing subsequent nonpreventive dental service utilization among children.

Co-payments and the Use of Emergency Department Services in the Children's Health Insurance Program

Medical Care Research and Review : MCRR. Oct, 2013  |  Pubmed ID: 23771877

Research suggests that more than half of all emergency department (ED) visits in the United States are for nonurgent conditions, leading to billions of dollars in potentially avoidable spending annually. In this study, we examine the effects of co-payment changes on ED utilization among children enrolled in ALL Kids, Alabama's Children's Health Insurance Program We separately model the effect of the 2003 co-payment increases on the monthly probability of any ED visit, and visits within three severity categories, using linear probability models that control for beneficiary characteristics and time trends that are allowed to vary in the pre- and postperiods. We observe a small decline in the probability of ED visits 1 year after the co-payment increase. However, low-severity visits, which we hypothesize to be more price sensitive, show no significant evidence of a decline. Our study suggests that the modest co-payment changes were not effective in improving the efficiency of ED utilization.

Phytosterols, Red Yeast Rice, and Lifestyle Changes Instead of Statins: a Randomized, Double-blinded, Placebo-controlled Trial

American Heart Journal. Jul, 2013  |  Pubmed ID: 23816039

Many patients who refuse or cannot tolerate statin drugs choose alternative therapies for lipid lowering.

Indicators of Replicative Damage in Equine Tendon Fibroblast Monolayers

BMC Veterinary Research. Sep, 2013  |  Pubmed ID: 24025445

Superficial digital flexor tendon (SDFT) injuries of horses usually follow cumulative matrix microdamage; it is not known why the reparative abilities of tendon fibroblasts are overwhelmed or subverted. Relevant in vitro studies of this process require fibroblasts not already responding to stresses caused by the cell culture protocols. We investigated indicators of replicative damage in SDFT fibroblast monolayers, effects of this on their reparative ability, and measures that can be taken to reduce it.

The Use of Connexin-based Therapeutic Approaches to Target Inflammatory Diseases

Methods in Molecular Biology (Clifton, N.J.). 2013  |  Pubmed ID: 24029957

Alterations in Connexin43 (Cx43) expression levels have been shown to play a role in inflammatory processes including skin wounding and neuroinflammation. Cx43 protein levels increase following a skin wound and can inhibit wound healing. Increased Cx43 has been observed following stroke, epilepsy, ischemia, optic nerve damage, and spinal cord injury with gap junctional communication and hemichannel opening leading to increased secondary damage via the inflammatory response. Connexin43 modulation has been identified as a potential target for protection and repair in neuroinflammation and skin wound repair. This review describes the use of a Cx43 specific antisense oligonucleotide (Cx43 AsODN) and peptide mimetics of the connexin extracellular loop domain to modulate Cx43 expression and/or function in inflammatory disorders of the skin and central nervous system. An overview of the role of connexin43 in inflammatory conditions, how antisense and peptide have allowed us to elucidate the role of Cx43 in these diseases, create models of diseases to test interventions and their potential for use clinically or in current clinical trials is presented. Antisense oligonucleotides are applied topically and have been used to improve wound healing following skin injury. They have also been used to develop ex vivo models of neuroinflammatory diseases that will allow testing of intervention strategies. The connexin mimetic peptides have shown potential in a number of neuroinflammatory disorders in ex vivo models as well as in vivo when delivered directly to the injury site or when delivered systemically.

The Spirit of Cooperation

Journal of the Massachusetts Dental Society. 2013  |  Pubmed ID: 24073513

Patient Perceptions of Nonmelanoma Skin Cancer Before Diagnosis

Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. Oct, 2013  |  Pubmed ID: 24090260

There is a paucity of data regarding patient perceptions of nonmelanoma skin cancer (NMSC).

Something for Everyone

Journal of the Massachusetts Dental Society. 2013  |  Pubmed ID: 24428023

Bitter Pill Indeed

Journal of the Massachusetts Dental Society. 2013  |  Pubmed ID: 24494257

Characteristics of Low-severity Emergency Department Use Among CHIP Enrollees

The American Journal of Managed Care. Dec, 2013  |  Pubmed ID: 24512087

To describe patient characteristics among those utilizing the emergency department (ED) for low-severity conditions (ie, conditions potentially treatable or manageable in a primary care setting).

Measuring Prevention More Broadly: an Empirical Assessment of CHIPRA Core Measures

Medicare & Medicaid Research Review. 2013  |  Pubmed ID: 24800161

To assess limitations of using select Children's Health Insurance Program Reauthorization Act (CHIPRA) core claims-based measures in capturing the preventive services that may occur in the clinical setting.

Characterization and Remediation of Chlorinated Volatile Organic Contaminants in the Vadose Zone: An Overview of Issues and Approaches

Vadose Zone Journal : VZJ. Nov, 2013  |  Pubmed ID: 25383058

Contamination of vadose-zone systems by chlorinated solvents is widespread, and poses significant potential risk to human health through impacts on groundwater quality and vapor intrusion. Soil vapor extraction (SVE) is the presumptive remedy for such contamination, and has been used successfully for innumerable sites. However, SVE operations typically exhibit reduced mass-removal effectiveness at some point due to the impact of poorly accessible contaminant mass and associated mass-transfer limitations. Assessment of SVE performance and closure is currently based on characterizing contaminant mass discharge associated with the vadose-zone source, and its impact on groundwater or vapor intrusion. These issues are addressed in this overview, with a focus on summarizing recent advances in our understanding of the transport, characterization, and remediation of chlorinated solvents in the vadose zone. The evolution of contaminant distribution over time and the associated impacts on remediation efficiency will be discussed, as will the potential impact of persistent sources on groundwater quality and vapor intrusion. In addition, alternative methods for site characterization and remediation will be addressed.

Exploring In-hospital Death from Myocardial Infarction in Eastern Europe: from the International Registry of Acute Coronary Syndromes in Transitional Countries (ISACS-TC); on the Behalf of the Working Group on Coronary Pathophysiology & Microcirculation of the European Society of Cardiology

Current Vascular Pharmacology. 2014  |  Pubmed ID: 23607683

The aim of the current study was to investigate the outcomes of coronary reperfusion therapies and ST-segment elevation myocardial infarction (STEMI) in patients of Eastern countries with economies in transition. Federation, and Serbia. The overall population consisted of 23,486 consecutive patients admitted to hospitals from January 1(st) to December 31(st) 2009. Registry data and statistics from the Organization for Economic Cooperation and Development (OECD) countries for the same period were used for comparison (2009-2010). In-hospital mortality was between 4% and 5% in the Western countries. In comparison mortality data were significantly larger in Serbia (10.8%) and Bosnia and Herzegovina (11.2%), intermediate in Russian Federation (7.2%) and similar in Hungary (5.0%). The rates of primary percutaneous coronary intervention (primary PCI) were very low in Bosnia and Herzegovina (18.3%), low in Russian Federation (20.6%) and Serbia (22%), and high in Hungary (70%). Major risk factors for death appear to be lack of reperfusion therapy, longer time delay from symptoms onset to hospital presentation as well as the higher percentage of patients with clinical presentation in Killip class III/IV.

Trends in the Utilization and Outcomes of Medicare Patients Hospitalized for Hip Fracture, 2000-2008

Journal of Aging and Health. Apr, 2014  |  Pubmed ID: 24401322

This study examines temporal trends in hip fracture related utilization and outcomes among elderly fee-for-service Medicare beneficiaries.

Wound Healing Activity and Mechanisms of Action of an Antibacterial Protein from the Venom of the Eastern Diamondback Rattlesnake (Crotalus Adamanteus)

PloS One. 2014  |  Pubmed ID: 24551028

Basic phospholipase A2 was identified from the venom of the eastern diamondback rattlesnake. The Crotalus adamanteus toxin-II (CaTx-II) induced bactericidal effects (7.8 µg/ml) on Staphylococcus aureus, while on Burkholderia pseudomallei (KHW), and Enterobacter aerogenes were killed at 15.6 µg/ml. CaTx-II caused pore formation and membrane damaging effects on the bacterial cell wall. CaTx-II was not cytotoxic on lung (MRC-5), skin fibroblast (HEPK) cells and in mice. CaTx-II-treated mice showed significant wound closure and complete healing by 16 days as compared to untreated controls (**P<0.01). Histological examination revealed enhanced collagen synthesis and neovascularization after treatment with CaTx-II versus 2% Fusidic Acid ointment (FAO) treated controls. Measurement of tissue cytokines revealed that interleukin-1 beta (IL-1β) expression in CaTx-II treated mice was significantly suppressed versus untreated controls. In contrast, cytokines involved in wound healing and cell migration i.e., monocyte chemotactic protein-1 (MCP-1), fibroblast growth factor-basic (FGF-b), chemokine (KC), granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly enhanced in CaTx-II treated mice, but not in the controls. CaTx-II also modulated nuclear factor-kappa B (NF-κB) activation during skin wound healing. The CaTx-II protein highlights distinct snake proteins as a potential source of novel antimicrobial agents with significant therapeutic application for bacterial skin infections.

Patterns and Predictors of Osteoporosis Medication Discontinuation and Switching Among Medicare Beneficiaries

BMC Musculoskeletal Disorders. Apr, 2014  |  Pubmed ID: 24684864

Low adherence to bisphosphonate therapy is associated with increased fracture risk. Factors associated with discontinuation of osteoporosis medications have not been studied in-depth. This study assessed medication discontinuation and switching patterns among Medicare beneficiaries who were new users of bisphosphonates and evaluated factors possibly associated with discontinuation.


Journal of the Massachusetts Dental Society. 2014  |  Pubmed ID: 24941541

Can Increases in CHIP Copayments Reduce Program Expenditures on Prescription Drugs?

Medicare & Medicaid Research Review. 2014  |  Pubmed ID: 24967148

The primary aim is to explore whether prescription drug expenditures by enrollees changed in Alabama's CHIP program, ALL Kids, after copayment increases in fiscal year 2004. The subsidiary aim is to explore whether non-pharmaceutical expenditures also changed.


Journal of the Massachusetts Dental Society. 2014  |  Pubmed ID: 25226764

Efficacy of Drug-eluting Balloon in Patients with Bare-metal or Drug-eluting Stent Restenosis

Hellenic Journal of Cardiology : HJC = Hellenike Kardiologike Epitheorese. Sep-Oct, 2014  |  Pubmed ID: 25243435

In spite of improving results, the treatment of in-stent restenosis (ISR) of bare-metal stents (BMS), and particularly drug-eluting stents (DES), is a challenging clinical problem. There are promising but limited follow-up data concerning drug-eluting balloons in the treatment of BMS and DES restenosis. The goal of this real-world registry was to assess the long-term safety and efficacy of drug-eluting balloons in the treatment of BMS and DES restenosis.

Effect of Cardiac Resynchronization Therapy with Implantable Cardioverter Defibrillator Versus Cardiac Resynchronization Therapy with Pacemaker on Mortality in Heart Failure Patients: Results of a High-volume, Single-centre Experience

European Journal of Heart Failure. Dec, 2014  |  Pubmed ID: 25379962

There are limited and contradictory data on the effects of CRT with implantable cardioverter defibrillator (CRT-D) on mortality as compared with CRT with pacemaker (CRT-P).

Superbugs? No Thanks!

Journal of the Massachusetts Dental Society. 2014  |  Pubmed ID: 25509494

Ultrastructure and Composition of Thrombi in Coronary and Peripheral Artery Disease: Correlations with Clinical and Laboratory Findings

Thrombosis Research. Apr, 2015  |  Pubmed ID: 25686880

Fibrin structure and cellular composition of thrombi profoundly affect the clinical outcomes in ischemic coronary and peripheral artery disease. Our study addressed the interrelations of structural features of thrombi and routinely measured laboratory parameters.

Stimuli-responsive Liposomes for the Delivery of Nucleic Acid Therapeutics

Nanomedicine : Nanotechnology, Biology, and Medicine. Aug, 2015  |  Pubmed ID: 25819885

Nucleic acid therapeutics (NATs) are valuable tools in the modulation of gene expression in a highly specific manner. So far, NATs have been actively pursued in both pre-clinical and clinical studies to treat diseases such as cancer, infectious and inflammatory diseases. However, the clinical application of NATs remains a considerable challenge owing to their limited cellular uptake, low biological stability, off-target effect, and unfavorable pharmacokinetics. One concept to address these issues is to deliver NATs within stimuli-responsive liposomes, which release their contents of NATs upon encountering environmental changes such as temperature, pH, and ion strength. In this case, before reaching the targeted tissue/organ, NATs are protected from degradation by enzymes and immune system. Once at the area of interest, localized and targeted delivery can be achieved with minimal influence to other parts of the body. Here, we discuss the latest developments and existing challenges in this field.

Enrollment, Expenditures, and Utilization After CHIP Expansion: Evidence from Alabama

Academic Pediatrics. May-Jun, 2015  |  Pubmed ID: 25906697

In October 2009, Alabama expanded eligibility in its Children's Health Insurance Program (CHIP), known as ALL Kids, from 200% to 300% of the federal poverty level (FPL). We examined the expenditures, utilization, and enrollment behavior of expansion enrollees relative to traditional enrollees (100-200% FPL) and assessed the impact of expansion on total program expenditures.

Clinical Predictors of Mortality Following Rotational Atherectomy and Stent Implantation in High-risk Patients: A Single Center Experience

Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. Oct, 2015  |  Pubmed ID: 26032270

Our aim was to assess the procedural success and determine the clinical predictors of postprocedure mortality, following rotational atherectomy (RA) and stenting in high-risk patients.

Let There Be Light

Journal of the Massachusetts Dental Society. 2015  |  Pubmed ID: 26168524

Trends in Mortality and Recurrent Coronary Heart Disease Events After an Acute Myocardial Infarction Among Medicare Beneficiaries, 2001-2009

American Heart Journal. Aug, 2015  |  Pubmed ID: 26299221

Few contemporary studies examine trends in recurrent coronary heart disease (CHD) events and mortality after acute myocardial infarction (AMI) and whether these trends vary by race or sex.

High-Performance Capacitive Deionization Disinfection of Water with Graphene Oxide-graft-Quaternized Chitosan Nanohybrid Electrode Coating

ACS Nano. Oct, 2015  |  Pubmed ID: 26389519

Water disinfection materials should ideally be broad-spectrum-active, nonleachable, and noncontaminating to the liquid needing sterilization. Herein, we demonstrate a high-performance capacitive deionization disinfection (CDID) electrode made by coating an activated carbon (AC) electrode with cationic nanohybrids of graphene oxide-graft-quaternized chitosan (GO-QC). Our GO-QC/AC CDID electrode can achieve at least 99.9999% killing (i.e., 6 log reduction) of Escherichia coli in water flowing continuously through the CDID cell. Without the GO-QC coating, the AC electrode alone cannot kill the bacteria and adsorbs a much smaller fraction (<82.8 ± 1.8%) of E. coli from the same biocontaminated water. Our CDID process consists of alternating cycles of water disinfection followed by electrode regeneration, each a few minutes duration, so that this water disinfection process can be continuous and it only needs a small electrode voltage (2 V). With a typical brackish water biocontamination (with 10(4) CFU mL(-1) bacteria), the GO-QC/AC electrodes can kill 99.99% of the E. coli in water for 5 h. The disinfecting GO-QC is securely attached on the AC electrode surface, so that it is noncontaminating to water, unlike many other chemicals used today. The GO-QC nanohybrids have excellent intrinsic antimicrobial properties in suspension form. Further, the GO component contributes toward the needed surface conductivity of the CDID electrode. This CDID process offers an economical method toward ultrafast, contaminant-free, and continuous killing of bacteria in biocontaminated water. The proposed strategy introduces a green in situ disinfectant approach for water purification.

Controlled Release of Drugs in Electrosprayed Nanoparticles for Bone Tissue Engineering

Advanced Drug Delivery Reviews. Nov, 2015  |  Pubmed ID: 26415888

Generating porous topographic substrates, by mimicking the native extracellular matrix (ECM) to promote the regeneration of damaged bone tissues, is a challenging process. Generally, scaffolds developed for bone tissue regeneration support bone cell growth and induce bone-forming cells by natural proteins and growth factors. Limitations are often associated with these approaches such as improper scaffold stability, and insufficient cell adhesion, proliferation, differentiation, and mineralization with less growth factor expression. Therefore, the use of engineered nanoparticles has been rapidly increasing in bone tissue engineering (BTE) applications. The electrospray technique is advantageous over other conventional methods as it generates nanomaterials of particle sizes in the micro/nanoscale range. The size and charge of the particles are controlled by regulating the polymer solution flow rate and electric voltage. The unique properties of nanoparticles such as large surface area-to-volume ratio, small size, and higher reactivity make them promising candidates in the field of biomedical engineering. These nanomaterials are extensively used as therapeutic agents and for drug delivery, mimicking ECM, and restoring and improving the functions of damaged organs. The controlled and sustained release of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides from nanoparticles has been well developed in nanomedicine. This review provides an insight into the preparation of nanoparticles by electrospraying technique and illustrates the use of nanoparticles in drug delivery for promoting bone tissue regeneration.

Adverse Selection in the Children's Health Insurance Program

Inquiry : a Journal of Medical Care Organization, Provision and Financing. Jul, 2015  |  Pubmed ID: 26428203

This study investigates whether new enrollees in the Alabama Children's Health Insurance Program have different claims experience from renewing enrollees who do not have a lapse in coverage and from continuing enrollees. The analysis compared health services utilization in the first month of enrollment for new enrollees (who had not been in the program for at least 12 months) with utilization among continuing enrollees. A second analysis compared first-month utilization of those who renew immediately with those who waited at least 2 months to renew. A 2-part model estimated the probability of usage and then the extent of usage conditional on any utilization. Claims data for 826 866 child-years over the period from 1999 to 2012 were used. New enrollees annually constituted a stable 40% share of participants. Among those enrolled in the program, 13.5% renewed on time and 86.5% of enrollees were late to renew their enrollment. In the multivariate 2-part models, controlling for age, gender, race, income eligibility category, and year, new enrollees had overall first-month claims experience that was nearly $29 less than continuing enrollees. This was driven by lower ambulatory use. Late renewals had overall first-month claims experience that was $10 less than immediate renewals. However, controlling for the presence of chronic health conditions, there was no statistically meaningful difference in the first-month claims experience of late and early renewals. Thus, differences in claims experience between new and continuing enrollees and between early and late renewals are small, with greater spending found among continuing and early renewing participants. Higher claims experience by early renewals is attributable to having chronic health conditions.

The Value of Volunteering

Journal of the Massachusetts Dental Society. 2015  |  Pubmed ID: 26455076

The Action of Mimetic Peptides on Connexins Protects Fibroblasts from the Negative Effects of Ischemia Reperfusion

Biology Open. Oct, 2015  |  Pubmed ID: 26471768

Connexins have been proposed as a target for therapeutic treatment of a variety of conditions. The main approaches have been by antisense or small peptides specific against connexins. Some of these peptides enhance communication while others interfere with connexin binding partners or bind to the intracellular and extracellular loops of connexins. Here, we explored the mechanism of action of a connexin mimetic peptide by evaluating its effect on gap junction channels, connexin protein levels and hemichannel activity in fibroblast cells under normal conditions and following ischemia reperfusion injury which elevates Cx43 levels, increases hemichannel activity and causes cell death. Our results showed that the effects of the mimetic peptide were concentration-dependent. High concentrations (100-300 μM) significantly reduced Cx43 protein levels and GJIC within 2 h, while these effects did not appear until 6 h when using lower concentrations (10-30 μM). Cell death can be reduced when hemichannel opening and GJIC were minimised.

Identification of Therapeutic Targets of Inflammatory Monocyte Recruitment to Modulate the Allogeneic Injury to Donor Cornea

Investigative Ophthalmology & Visual Science. Nov, 2015  |  Pubmed ID: 26544793

We sought to test the hypothesis that monocytes contribute to the immunopathogenesis of corneal allograft rejection and identify therapeutic targets to inhibit monocyte recruitment.

Role of Right Ventricular Global Longitudinal Strain in Predicting Early and Long-Term Mortality in Cardiac Resynchronization Therapy Patients

PloS One. 2015  |  Pubmed ID: 26700308

Right ventricular (RV) dysfunction has been associated with poor prognosis in chronic heart failure (HF). However, less data is available about the role of RV dysfunction in patients with cardiac resynchronization therapy (CRT). We aimed to investigate if RV dysfunction would predict outcome in CRT.

The Opioid Crisis and Dentistry

Journal of the Massachusetts Dental Society. 2015  |  Pubmed ID: 26727809

The Ratio of the Neutrophil Leucocytes to the Lymphocytes Predicts the Outcome After Cardiac Resynchronization Therapy

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. May, 2016  |  Pubmed ID: 25972301

The low lymphocyte counts and high neutrophil leucocyte fractions have been associated with poor prognosis in chronic heart failure. We hypothesized that the baseline ratio of the neutrophil leucocytes to the lymphocytes (NL ratio) would predict the outcome of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT).

Topical Dihydrotestosterone to Treat Micropenis Secondary to Partial Androgen Insensitivity Syndrome (PAIS) Before, During, and After Puberty - a Case Series

Journal of Pediatric Endocrinology & Metabolism : JPEM. Feb, 2016  |  Pubmed ID: 26352087

X-linked partial androgen insensitivity syndrome (PAIS) causes under-virilization at all stages of development. In two thirds of males, this results in micropenis. Dihydrotestosterone (DHT) is a potent androgen that is critical for male genital development, which when applied topically, has been shown to increase penile length with micropenis of varying etiologies. We present the first case series using topical DHT gel to treat micropenis in 46,XY males with PAIS, before, during, and after puberty.

Translating Connexin Biology into Therapeutics

Seminars in Cell & Developmental Biology. Feb, 2016  |  Pubmed ID: 26688335

It is 45 years since gap junctions were first described. Universities face increasing commercial pressures and declining federal funding, with governments and funding foundations showing greater interest in gaining return on their investments. This review outlines approaches taken to translate gap junction research to clinical application and the challenges faced. The need for commercialisation is discussed and key concepts behind research patenting briefly described. Connexin channel roles in disease and injury are also discussed, as is identification of the connexin hemichannel as a therapeutic target which appears to play a role in both the start and perpetuation of the inflammasome pathway. Furthermore connexin hemichannel opening results in vascular dieback in acute injury and chronic disease. Translation to human indications is illustrated from the perspective of one connexin biotechnology company, CoDa Therapeutics, Inc.

Burden of Coronary Heart Disease Rehospitalizations Following Acute Myocardial Infarction in Older Adults

Cardiovascular Drugs and Therapy. Jun, 2016  |  Pubmed ID: 26898407

Studies of prognosis following acute myocardial infarction (AMI) conventionally examine the first recurrent coronary heart disease (CHD) event which may not adequately characterize the full burden of CHD hospitalizations. We therefore examined the cumulative number of CHD rehospitalizations following AMI among older adults in the United States.

Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy

Disease Markers. 2016  |  Pubmed ID: 26903690

Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction.

Preventive Dental Care and Long-Term Dental Outcomes Among ALL Kids Enrollees

Health Services Research. Dec, 2016  |  Pubmed ID: 26927421

To investigate whether early or regular preventive dental visit (PDV) reduces restorative or emergency dental care and costs for low-income children.

Evaluation of Human Papillomavirus As a Risk Factor for Preterm Birth or Pregnancy-Related Hypertension

Obstetrics and Gynecology. Feb, 2016  |  Pubmed ID: 26942348

To compare rates of preterm birth and pregnancy-related hypertension in women with and without human papillomavirus (HPV) infection.

The Great Recession of 2007-2009 and Public Insurance Coverage for Children in Alabama: Enrollment and Claims Data from 1999-2011

Public Health Reports (Washington, D.C. : 1974). Mar-Apr, 2016  |  Pubmed ID: 26957670

This study examined the impact of the Great Recession of 2007-2009 on public health insurance enrollment and expenditures in Alabama. Our analysis was designed to provide a framework for other states to conduct similar analyses to better understand the relationship between macroeconomic conditions and public health insurance costs.

Survey of Expert Opinion on Intelligence: Causes of International Differences in Cognitive Ability Tests

Frontiers in Psychology. 2016  |  Pubmed ID: 27047425

Following Snyderman and Rothman (1987, 1988), we surveyed expert opinions on the current state of intelligence research. This report examines expert opinions on causes of international differences in student assessment and psychometric IQ test results. Experts were surveyed about the importance of culture, genes, education (quantity and quality), wealth, health, geography, climate, politics, modernization, sampling error, test knowledge, discrimination, test bias, and migration. The importance of these factors was evaluated for diverse countries, regions, and groups including Finland, East Asia, sub-Saharan Africa, Southern Europe, the Arabian-Muslim world, Latin America, Israel, Jews in the West, Roma (gypsies), and Muslim immigrants. Education was rated by N = 71 experts as the most important cause of international ability differences. Genes were rated as the second most relevant factor but also had the highest variability in ratings. Culture, health, wealth, modernization, and politics were the next most important factors, whereas other factors such as geography, climate, test bias, and sampling error were less important. The paper concludes with a discussion of limitations of the survey (e.g., response rates and validity of expert opinions).

[The Role of Therapeutic Hypothermia in Post-resuscitation Care - Review of the Literature and Personal Experience]

Orvosi Hetilap. Apr, 2016  |  Pubmed ID: 27063428

In the last fifteen years mild therapeutic hypothermia became an accepted and widespread therapeutic method in the treatment of successfully resuscitated patients due to sudden cardiac death. Based on the available evidence therapeutic hypothermia is part of the resuscitation guidelines, however, many aspects of its therapeutic use are based on empirical facts. In particular, the subjects of intense debate are the ideal target temperature and the benefit of hypothermia in patients found with non-shockable rhythm. Hypothermia affects almost all organ systems and, therefore, early detection and treatment of side effects are essential. The aim of the authors is to summarize the clinical role and pathophysiologic effects of therapeutic hypothermia in the treatment of resuscitated patients based on current evidence and their practical experience.

Improved Outcomes with Dose-dense Paclitaxel-based Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Carcinoma

Gynecologic Oncology. Jul, 2016  |  Pubmed ID: 27130405

We compared tolerability, toxicity, response, and interval debulking surgery (IDS) outcomes between patients who received weekly dose-dense paclitaxel (DDP) and every three-week platinum to standard every three-week taxane plus platinum neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC).

Cardiac Allograft Vasculopathy: Optical Coherence Guided Innovative Treatment Options with the Bioresorbable Vascular Scaffold: Proof of Concept

Minerva Cardioangiologica. Aug, 2016  |  Pubmed ID: 27152623

The aim of our work was to assess a novel interventional therapy option in cardiac allograft vasculopathy (CAV), a complex form of coronary disease presenting only in heart transplant (HTx) recipients. It is typically a rapidly progressing phenomenon, affecting the entire coronary circulation causing diffuse, severe coronary lesions and has no one unique cause. Treatment options are limited, but where eligible, palliation via percutaneous revascularization (PCI) mainly using new generation drug eluting stents (DES) is recommended. Our working group sought to assess outcomes of CAV PCI using an Absorb (Abbott Vascular, Santa Clara, CA, USA) fully bioresorbable, everolimus eluting vascular scaffold (BVS), under optical coherence tomography (OCT) guidance. Our initial, proof-of-concept case showed a late CAV, macrophage and foam-cell rich lesion, with typical asymmetric intimal hyperplasia and contralateral thin-cap fibroatheroma formation. Post-PCI OCT showed underexpansion, requiring aggressive postdilatation. Ninety-day follow-up CT angiogram identified the scaffold and displayed a patent lumen of the device. BVS use thus seems eligible in CAV, yet needs proper, meticulous implantation. Use may also delay CAV progression as lesion healing is promoted, with restoration of vasomotion and a natural increase in vascular lumen. Furthermore, the chronically present vascular irritation surrounding stent/scaffold struts may subside, as no permanent metal is present as an increased substrate for inflammation. To assess full efficacy, further studies will be needed.

Health Expenditure Concentration and Characteristics of High-Cost Enrollees in CHIP

Inquiry : a Journal of Medical Care Organization, Provision and Financing. 2016  |  Pubmed ID: 27166411

Devising effective cost-containment strategies in public insurance programs requires understanding the distribution of health care spending and characteristics of high-cost enrollees. The aim was to characterize high-cost enrollees in a state's public insurance program and determine whether expenditure inequality changes over time, or with changes in cost-sharing policies or program eligibility. We use 1999-2011 claims and enrollment data from the Alabama Children's Health Insurance Program, ALL Kids. All children enrolled in ALL Kids were included in our study, including multiple years of enrollment (N = 1,031,600 enrollee-months). We examine the distribution of costs over time, whether this distribution changes after increases in cost sharing and expanded eligibility, patient characteristics that predict high-cost status, and examine health services used by high-cost children to identify what is preventable. The top 10% (1%) of enrollees account for about 65.5% (24.7%) of total program costs. Inpatient and outpatient costs are the largest components of costs incurred by high-cost utilizers. Non-urgent emergency department costs are a relatively small portion. Average expenditure increases over time, particularly after expanded eligibility, and the share of costs incurred by the top 10% and 1% increases slightly. Multivariable logistic regression results indicate that infants and older teens, Caucasian children, and those with chronic conditions are more likely to be high-cost utilizers. Increased cost sharing does not reduce cost concentration or average expenditure among high-cost utilizers. These findings suggest that identifying and targeting potentially preventable costs among high-cost utilizers are called for to help reduce costs in public insurance programs.


Journal of the Massachusetts Dental Society. 2016  |  Pubmed ID: 27197357

Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing

Advanced Healthcare Materials. Jul, 2016  |  Pubmed ID: 27253638

Antisense oligodeoxynucleotides targeting the mRNA of the gap junction protein Cx43 promote tissue repair in a variety of different wounds. Delivery of the antisense drug has most often been achieved by a thermoreversible hydrogel, Pluronic F-127, which is very effective in the short term but does not allow for sustained delivery over several days. For chronic wounds that take a long time to heal, repeated dosing with the drug may be desirable but is not always compatible with conventional treatments such as the weekly changing of compression bandages on venous leg ulcers. Here the coating of collagen scaffolds with antisense oligonucleotides is investigated and a way to provide protection of the oligodeoxynucleotide drug is found in conjunction with sustained release over a 7 d period. This approach significantly reduces the normal foreign body reaction to the scaffold, which induces an increase of Cx43 protein and an inhibition of healing. As a result of the antisense integration into the scaffold, inflammation is reduced with the rate of wound healing and contracture is significantly improved. This coated scaffold approach may be very useful for treating venous leg ulcers and also for providing a sustained release of any other types of oligonucleotide drugs that are being developed.

Detailed Heart Rate Variability Analysis in Athletes

Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. Aug, 2016  |  Pubmed ID: 27271053

Heart rate variability (HRV) analysis has been used to evaluate patients with various cardiovascular diseases. While the vast majority of HRV studies have focused on pathological states, our study focuses on the less explored area of HRV analysis across different training intensity and sports. We aimed to measure HRV in healthy elite and masters athletes and compare to healthy, but non-athletic controls.

Working Together

Journal of the Massachusetts Dental Society. 2016  |  Pubmed ID: 27400547

Impact of CT-apelin and NT-proBNP on Identifying Non-responders to Cardiac Resynchronization Therapy

Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals. Aug, 2016  |  Pubmed ID: 27471876

Assessment of response to cardiac resynchronization therapy (CRT) is essential.

Connexins in Endothelial Barrier Function - Novel Therapeutic Targets Countering Vascular Hyperpermeability

Thrombosis and Haemostasis. Oct, 2016  |  Pubmed ID: 27488046

Prolonged vascular hyperpermeability is a common feature of many diseases. Vascular hyperpermeability is typically associated with changes in the expression patterns of adherens and tight junction proteins. Here, we focus on the less-appreciated contribution of gap junction proteins (connexins) to basal vascular permeability and endothelial dysfunction. First, we assess the association of connexins with endothelial barrier integrity by introducing tools used in connexin biology and relating the findings to customary readouts in vascular biology. Second, we explore potential mechanistic ties between connexins and junction regulation. Third, we review the role of connexins in microvascular organisation and development, focusing on interactions of the endothelium with mural cells and tissue-specific perivascular cells. Last, we see how connexins contribute to the interactions between the endothelium and components of the immune system, by using neutrophils as an example. Mounting evidence of crosstalk between connexins and other junction proteins suggests that we rethink the way in which different junction components contribute to endothelial barrier function. Given the multiple points of connexin-mediated communication arising from the endothelium, there is great potential for synergism between connexin-targeted inhibitors and existing immune-targeted therapeutics. As more drugs targeting connexins progress through clinical trials, it is hoped that some might prove effective at countering vascular hyperpermeability.

Rotational Atherectomy of Undilatable Coronary Stents: Stentablation, a Clinical Perspective and Recommendation

EuroIntervention : Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. Aug, 2016  |  Pubmed ID: 27497363

Our aim was to examine procedural viability and midterm outcomes following the use of rotational atherectomy (RA) on malapposed, crippled, otherwise non-salvageable metallic stents (i.e., stentablation [SA]), and convey important procedural pointers for practitioners encountering such situations.

Coronary Artery Manifestation of Ormond Disease: The "Mistletoe Sign"

Radiology. Aug, 2016  |  Pubmed ID: 27548369

A 69-year-old woman presented with symptoms of presumed cardiac involvement of idiopathic retroperitoneal fibrosis, otherwise known as Ormond disease. Distinct pericoronary tissue proliferations were depicted at cardiac magnetic resonance (MR) imaging and coronary computed tomographic (CT) angiography. On images, the coronary manifestation was termed the "mistletoe sign." The presence of the mistletoe sign on cardiac MR and coronary CT angiographic images is probably rare, but it might be a characteristic manifestation of retroperitoneal fibrosis. With the increasing number of noninvasive cardiac imaging tests performed worldwide, the recognition of the mistletoe sign could be helpful in diagnosing retroperitoneal fibrosis. (©) RSNA, 2016 Online supplemental material is available for this article.

Connexin 43 is Overexpressed in Human Fetal Membrane Defects After Fetoscopic Surgery

Prenatal Diagnosis. Oct, 2016  |  Pubmed ID: 27568096

We examined whether surgically induced membrane defects elevate connexin 43 (Cx43) expression in the wound edge of the amniotic membrane (AM) and drives structural changes in collagen that affects healing after fetoscopic surgery.

[Current Therapy of the Acute Coronary Syndrome - 2016]

Orvosi Hetilap. Sep, 2016  |  Pubmed ID: 27640615

Acute coronary syndrome is a life threatening disease with high mortality rate without optimal therapy. Due to the continuous development in the treatment of the disease, the prognosis has dramatically improved over the last 30 years. Apart from the improvement of the medication, the most important factor is the availability of an immediate coronary intervention for everyone, at any time. Currently, nineteen interventional centers provide this care in Hungary, 24 hours a day. Thanks to the European guidelines, the care system is now more efficient in determining who and when needs the treatment. This article summarises the principles of the treatment currently in use. Orv. Hetil., 2016, 157(38), 1500-1506.

Gamma and Ion-Beam Irradiation of DNA: Free Radical Mechanisms, Electron Effects, and Radiation Chemical Track Structure

Radiation Physics and Chemistry (Oxford, England : 1993). Nov, 2016  |  Pubmed ID: 27695205

The focus of our laboratory's investigation is to study the direct-type DNA damage mechanisms resulting from γ-ray and ion-beam radiation-induced free radical processes in DNA which lead to molecular damage important to cellular survival. This work compares the results of low LET (γ-) and high LET (ion-beam) radiation to develop a chemical track structure model for ion-beam radiation damage to DNA. Recent studies on protonation states of cytosine cation radicals in the N1-substituted cytosine derivatives in their ground state and 5-methylcytosine cation radicals in ground as well as in excited state are described. Our results exhibit a radical signature of excitations in 5-methylcytosine cation radical. Moreover, our recent theoretical studies elucidate the role of electron-induced reactions (low energy electrons (LEE), presolvated electrons (epre(-)), and aqueous (or, solvated) electrons (eaq(-))). Finally DFT calculations of the ionization potentials of various sugar radicals show the relative reactivity of these species.

Epidermal Grafting for Wound Healing: a Review on the Harvesting Systems, the Ultrastructure of the Graft and the Mechanism of Wound Healing

International Wound Journal. Oct, 2016  |  Pubmed ID: 27785878

Epidermal grafting for wound healing involves the transfer of the epidermis from a healthy location to cover a wound. The structural difference of the epidermal graft in comparison to the split-thickness skin graft and full-thickness skin graft contributes to the mechanism of effect. While skin grafting is an epidermal transfer, little is known about the precise mechanism of wound healing by epidermal graft. This paper aims to explore the evolution of the epidermal graft harvesting system over the last five decades, the structural advantages of epidermal graft for wound healing and the current hypotheses on the mechanism of wound healing by epidermal graft. Three mechanisms are proposed: keratinocyte activation, growth factor secretion and reepithelialisation from the wound edge. We evaluate and explain how these processes work and integrate to promote wound healing based on the current in vivo and in vitro evidence. We also review the ongoing clinical trials evaluating the efficacy of epidermal graft for wound healing. The epidermal graft is a promising alternative to the more invasive conventional surgical techniques as it is simple, less expensive and reduces the surgical burden for patients in need of wound coverage.

TCT-228 Rotational Atherectomy of Malapposed, Undilatable Coronary Stents: Fact or Fiction?

Journal of the American College of Cardiology. Nov, 2016  |  Pubmed ID: 27970405

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