Faking Psychopathy? An Examination of Response Styles with Antisocial Youth

Journal of Personality Assessment. Feb, 2002  |  Pubmed ID: 11936210

Psychopaths frequently con and manipulate others in an attempt to achieve their own objectives. In the current literature, correlational research has generally found that psychopathy has (a) an inverse relation with social desirability and (b) a positive relation with malingering. Although instructive, these correlational data do not address whether the assessment of psychopathy is vulnerable to specific response styles. This study examined 2 response styles among adolescent offenders in the context of pending adjudication: social desirability and social nonconformity. On 3 measures of psychopathy (i.e., Psychopathy Checklist: Youth Version, Psychopathy Screening Device, and Self-Report of Psychopathy-Second Edition), a simulation design was employed with a realistic scenario, incentives for successful deception, and appropriate manipulation checks. Results indicated moderate to large effect sizes for social desirability and large effect sizes for social nonconformity. The implications of these results for the clinical assessment of psychopathy are discussed.

Measurement of Mitochondrial DNA Synthesis in Vivo Using a Stable Isotope-mass Spectrometric Technique

Journal of Applied Physiology (Bethesda, Md. : 1985). Jun, 2003  |  Pubmed ID: 12562673

We describe here a new stable isotope-mass spectrometric technique for measuring mitochondrial DNA (mtDNA) synthesis. Growing (2-4 mo old) and weight-stable (8-10 mo old) Sprague-Dawley rats were primed with (2)H(2)O (deuterated water) to 2.0-2.5% body water enrichment, via intraperitoneal injection, and then given 4% (2)H(2)O in drinking water for 3-11 wk. Mitochondria were isolated from cardiac and hindlimb muscle, and mtDNA was isolated and enzymatically hydrolyzed to deoxyribonucleosides. PCR confirmed the absence of nuclear DNA contamination. The isotopic enrichment of the deoxyribose moiety of deoxyadenosine was determined by GC-MS analysis, and percent new mtDNA was calculated by comparison to genomic DNA enrichments in a tissue with nearly complete turnover (bone marrow). Initial label incorporation into deoxyadenosine of mtDNA was linear, and turnover of mtDNA was observed in nongrowing adult female rats (1.1-1.3% new mtDNA per day in cardiac and skeletal muscle). Die-away curves of mtDNA after discontinuing (2)H(2)O administration gave a similar turnover rate constant. Human subjects were also given (2)H(2)O for up to 6 wk, and mitochondria from platelets were isolated. Incubation with DNase removed any contaminating genomic DNA; platelet mtDNA exhibited linear incorporation from (2)H(2)O and reached plateau values identical to those in genomic DNA from fully turned over cells (circulating monocytes). In conclusion, replication of mtDNA can be directly measured in vivo in rodents and humans without the use of radioactivity. Use of this technique may allow improved understanding of the regulation of mitochondrial biogenesis in health and disease.

Lutein Interacts with Ascorbic Acid More Frequently Than with Alpha-tocopherol to Alter Biomarkers of Oxidative Stress in Female Zucker Obese Rats

The Journal of Nutrition. Sep, 2003  |  Pubmed ID: 12949374

The influence of dietary lutein, with and without moderate amounts of vitamin C (VC) or vitamin E (VE), on biomarkers of oxidative stress was examined in rats. Nine groups of immature Zucker obese (fa/fa) and lean female rats (8/group) consumed ad libitum for 8 wk the AIN-93G diet (Control) to which was added either dl-alpha-tocopherol acetate (VE) at 0.60 mg/kg or ascorbic acid (VC) at 0.75 mg/kg diet. Each of these diets contained lutein oil (FloraGlo) at 0.5 (Lut0.5) or 1.0 (Lut1.0) mg/kg diet. Weight gain, food efficiency and relative liver weight were higher in obese than in lean rats. Although liver malondialdehyde (MDA) concentrations were significantly higher in obese than in lean rats, levels were significantly lower in obese rats fed VE, VE-Lut and VC-Lut0.5 compared with other obese groups. The accumulation of alpha-tocopherol in liver was 6- and 3-times greater in the VE and VE-Lut1.0 groups, respectively, compared with the obese and lean control groups. Lutein reduced the activity of superoxide dismutase (SOD) in obese rats, independent of VC or VE, and raised the activity of glutathione peroxidase to higher levels in lean rats when combined with VC. Plasma insulin levels were dramatically higher in obese compared with lean rats, but significantly lower in obese rats fed VC-Lut0.5, VE-Lut1.0 and Lut1.0 compared with the Control group. These results suggest that lutein independently reduces the activity of SOD and alters more biomarkers of oxidative stress when combined with vitamin C than with vitamin E, and that vitamin E reduces liver lipid peroxidation in obese rats when the accumulation of liver alpha-tocopherol is very high.

Effect of Nucleoside Reverse Transcriptase Inhibitors on Mitochondrial DNA Synthesis in Rats and Humans

Journal of Acquired Immune Deficiency Syndromes (1999). Sep, 2004  |  Pubmed ID: 15319672

Nucleoside reverse transcriptase inhibitors (NRTIs) have been hypothesized to inhibit mitochondrial DNA polymerase gamma, resulting in decreased mtDNA synthesis and mitochondrial insufficiency in HIV-1-infected patients. mtDNA synthesis was measured directly using a stable isotope mass spectrometric method following NRTI treatment in rodents. 3'-Azido-3'-deoxythymidine (AZT) was added to water (1 mg/mL) and administered ad libitum to female Sprague-Dawley rats for 1-8 weeks (n = 4 or 5 animals/timepoint). Neither body weight nor food intake was affected by AZT intake. Untreated controls and AZT-treated rats were given 4% H2O as drinking water for 2 weeks. AZT (approximately 100 mg/kg/d) produced a significant (P < 0.05) decrease in cardiac and hindlimb muscle mtDNA fractional synthesis compared with control groups (from 13.8 +/- 4.2% to 7.0 +/- 4.8% and from 7.6 +/- 1.8% to 4.5 +/- 0.4%, respectively) after 4 weeks. Cytochrome c oxidase content in hindlimb muscle was also decreased by 50% compared with controls after 4 weeks of AZT treatment (P < 0.07) and a calculated index of absolute mitochondrial biogenesis rate was significantly reduced by week 2 of AZT (P < 0.05) in hindlimb muscle. In preliminary studies, platelet mtDNA enrichments were compared to monocyte nDNA enrichments (used as a marker of a fully turned over tissue) in healthy human subjects. Fractional synthesis of mtDNA in platelets reached 98 +/- 3% after 5 weeks of H2O labeling. It is concluded that NRTIs decrease mtDNA synthesis and oxidative enzyme content and thus mitochondrial biogenesis in rodents and that the effects of NRTIs on mitochondrial biogenesis in tissues of HIV-1- infected humans can in principle be measured using this approach.

Characterisation of Complex Formation Between Members of the Mycobacterium Tuberculosis Complex CFP-10/ESAT-6 Protein Family: Towards an Understanding of the Rules Governing Complex Formation and Thereby Functional Flexibility

FEMS Microbiology Letters. Sep, 2004  |  Pubmed ID: 15336430

We have previously shown that the secreted M. tuberculosis complex proteins CFP-10 and ESAT-6 form a tight, 1:1 complex, which may represent their functional form. In the work reported here a combination of yeast two-hybrid and biochemical analysis has been used to characterise complex formation between two other pairs of CFP-10/ESAT-6 family proteins (Rv0287/Rv0288 and Rv3019c/Rv3020c) and to determine whether complexes can be formed between non-genome paired members of the family. The results clearly demonstrate that Rv0287/Rv0288 and Rv3019c/3020c form tight complexes, as initially observed for CFP-10/ESAT-6. The closely related Rv0287/Rv0288 and Rv3019c/Rv3020c proteins are also able to form non-genome paired complexes (Rv0287/Rv3019c and Rv0288/Rv3020c), but are not capable of binding to the more distantly related CFP-10/ESAT-6 proteins.

Clinical Comparison of Extended-release Divalproex Versus Delayed-release Divalproex: Pooled Data Analyses from Nine Trials

Epilepsy & Behavior : E&B. Oct, 2004  |  Pubmed ID: 15380129

Divalproex sodium is an effective anticonvulsant, antimanic, and migraine prophylaxis agent. Recently, a new extended-release (ER) formulation of divalproex sodium has become available, which allows for once-daily dosing and provides prolonged therapeutic serum levels. Using data pooled from nine open-label trials involving 321 epilepsy and psychiatry patients, we compared the efficacy and tolerability of divalproex ER with preceding treatment with the older delayed-release (DR) formulation, based on patient reports and analysis by McNemar's test for within-subject paired data. Divalproex ER was associated with superior tolerability with less frequent tremor, weight gain, and gastrointestinal complaints (all P<0.001), but not less hair loss. Divalproex ER also yielded improved seizure control and greater improvement of psychiatric symptoms, and was greatly preferred by patients over divalproex DR. Although the results of the current analyses must be considered highly tentative due to the open-label nature of the trials included, the findings do suggest broad clinical superiority of the new ER preparation.

Alcohol: Friend or Foe? Alcoholic Beverage Hormesis for Cataract and Atherosclerosis is Related to Plasma Antioxidant Activity

Nonlinearity in Biology, Toxicology, Medicine. Oct, 2004  |  Pubmed ID: 19330151

To correlate the oxidative state of postabsorptive blood plasma after consumption of one or three drinks of different beverages with known J-shaped epidemiological risk curves. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Red wine, lager beer, stout (alcoholic and alcohol-free), with antioxidant activity, and an aqueous solution of alcohol were compared for the plasma antioxidant or pro-oxidant activity in human volunteers following consumption of one or three typical drinks containing equivalent amounts of alcohol (except for an alcohol-free stout used as a control for stout).

Creation of a Stepdown Nurse Internship Program

Journal for Nurses in Staff Development : JNSD : Official Journal of the National Nursing Staff Development Organization. May-Jun, 2005  |  Pubmed ID: 15940028

Within Christiana Care Health System, an opportunity evolved to develop a nurse recruitment strategy for our stepdown units. Being a large teaching system, there was specific need for nursing education at this entry level. Through collaboration of nursing colleagues, the Stepdown Nurse Internship Program was created. The program encompassed clinical orientation and didactic classes. Of notable significance at the completion of the program were the Basic Knowledge Assessment Test score improvement and the nurse retention rate.

Relationship of Mania Symptomatology to Maintenance Treatment Response with Divalproex, Lithium, or Placebo

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Oct, 2005  |  Pubmed ID: 15956987

Euphoric and mixed (dysphoric) manic symptoms have different response patterns to divalproex and lithium in acute mania treatment, but have not been studied in relationship to maintenance treatment outcomes. We examined the impact of initial euphoric or dysphoric manic symptomatology on maintenance outcome. Randomized maintenance treatment with divalproex, lithium, or placebo was provided for 372 bipolar I patients, who met improvement criteria during open phase treatment for an index manic episode. The current analysis grouped patients according to the index manic episode subtype (euphoric or dysphoric), and evaluated the impact on maintenance treatment outcome. The rate of early discontinuation due to intolerance during maintenance treatment was higher for initially dysphoric patients (N=249) than euphoric patients (N=123; 15.7 vs 7.3%, respectively; p=0.032). Both lithium (23.2%) and divalproex (17.1%) were associated with more premature discontinuations due to intolerance than placebo (4.8%; p=0.003 and 0.02, respectively) in the initially dysphoric patients. Among initially euphoric patients, treatment with lithium was associated with significantly more premature discontinuations due to intolerance compared to placebo (18.2 vs 0%; p=0.03), and divalproex was significantly (p=0.05) more effective than lithium, but not placebo in delaying time to a depressive episode. Initial euphoric mania appeared to predispose to better outcomes on indices of depression and overall function with divalproex maintenance than with either placebo or lithium. Dysphoric mania appeared to predispose patients to more side effects when treated with either divalproex or lithium during maintenance therapy.

Measurement of Protein Turnover Rates by Heavy Water Labeling of Nonessential Amino Acids

Biochimica Et Biophysica Acta. May, 2006  |  Pubmed ID: 16567052

In vivo measurements of protein synthesis using isotope-labeled amino acids (AAs) are hampered by the heterogeneity of AA pools and, for slow turnover proteins, the difficulty and expense of long-term labeling. Continuous oral heavy water (2H2O) labeling can safely maintain stable body water 2H enrichments for weeks or months. 2H is metabolically incorporated into C-H bonds of nonessential AAs (NEAAs) and hence into proteins. No posttranslational label exchange occurs, so 2H incorporation into protein NEAAs, in principle, reports on protein synthesis. Here, we show by mass isotopomer distribution analysis (MIDA) of 2H2O-labeled rodent tissue proteins that metabolic 2H flux into C-H bonds of Ala, Gly, or Gln used for protein synthesis is nearly complete. By 2H2O labeling of rodents, turnover of bone and muscle mixed proteins was quantified and stimulation of liver collagen synthesis by CCl4 was detected. Kinetics of several human serum proteins were also measured, reproducing published t1/2 estimates. Plateau enrichments in Ala varied among different proteins. Moderate amounts of protein, isolated chromatographically or electrophoretically, sufficed for kinetic analyses. In conclusion, 2H2O labeling permits sensitive, quantitative, operationally simple measurements of protein turnover in vivo by the rise-to-plateau approach, especially for proteins with slow constitutive turnover.

Hemostatic Techniques During Laparoscopic Partial Nephrectomy

Current Opinion in Urology. Sep, 2006  |  Pubmed ID: 16905976

To review the current techniques and technologies being used for hemostatic control during laparoscopic partial nephrectomy.

The Retinal Carotenoids Zeaxanthin and Lutein Scavenge Superoxide and Hydroxyl Radicals: a Chemiluminescence and ESR Study

Molecular Vision. 2006  |  Pubmed ID: 17093397

Carotenoids are present in many biological systems, often decreasing the formation of products of oxidative damage to biological molecules. In the macula their concentration is so high that it has been believed that the yellow color filters out damaging blue light. Recent reports that dietary lutein reduces the risk of cataract in the eye lens suggested that the antioxidant action of carotenoids, which has been inferred from decreased oxidative damage, warranted further direct investigation.

A Randomized, Placebo-controlled, Multicenter Study of Divalproex Sodium Extended Release in the Treatment of Acute Mania

The Journal of Clinical Psychiatry. Oct, 2006  |  Pubmed ID: 17107240

The efficacy and safety of divalproex sodium extended release (divalproex ER) were evaluated in patients hospitalized for acute mania associated with bipolar I disorder, manic or mixed type (DSM-IV-TR criteria).

Relationship of Open Acute Mania Treatment to Blinded Maintenance Outcome in Bipolar I Disorder

Journal of Affective Disorders. Apr, 2008  |  Pubmed ID: 17888516

Most bipolar treatment guidelines recommend that acutely effective therapy be continued as maintenance treatment, unless contraindicated. No published studies have statistically evaluated the relationship between the outcomes in maintenance treatment and the principal acute agent.

Split-face Treatment of Facial Dyschromia: Pulsed Dye Laser with a Compression Handpiece Versus Intense Pulsed Light

Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. May, 2008  |  Pubmed ID: 18318731

Many visible light lasers and intense pulsed light (IPL) devices are available to treat photodamaged skin.

Research Needs Assessment: Nurses' Knowledge, Attitudes, and Practices Related to Research

Journal for Nurses in Staff Development : JNSD : Official Journal of the National Nursing Staff Development Organization. Jan-Feb, 2008  |  Pubmed ID: 18349764

This manuscript demonstrates how one institution used research background information to recommend the use of two survey studies on nurses' knowledge, attitude, and practice related to research as a needs assessment tool to develop research education. The survey results provided in this manuscript helped the staff development specialist members of the nursing research committee develop an organized approach to education development that targeted nurses who need research education. The committee is planning for the future incorporation of research skills into the new nurses' orientation program.

Induction of Vaginal Birth After Cesarean Using Intracervical Foley Bulb

Journal of Midwifery & Women's Health. Nov-Dec, 2008  |  Pubmed ID: 18984513

What's the Treatment for Bacterial Vaginosis?

Nursing. Dec, 2008  |  Pubmed ID: 19033972

A 28-weeks-pregnant patient complained of vaginal irritation and a malodorous white discharge that didn't improve after she used an over-the-counter cream indicated for yeast infections. What's a more effective treatment?

Optimizing Electroporation Conditions in Primary and Other Difficult-to-transfect Cells

Journal of Biomolecular Techniques : JBT. Dec, 2008  |  Pubmed ID: 19183796

Electroporation is a valuable tool for nucleic acid delivery because it can be used for a wide variety of cell types. Many scientists are shifting toward the use of cell types that are more relevant to in vivo applications, including primary cells, which are considered difficult to transfect. The ability to electroporate these cell types with nucleic acid molecules of interest at a relatively high efficiency while maintaining cell viability is essential for elucidating the pathway(s) in which a gene product is involved. We present data demonstrating that by optimizing electroporation parameters, nucleic acid molecules can be delivered in a highly efficient manner. We display transfection results for primary and difficult-to-transfect cell types including human primary fibroblasts, human umbilical vein endothelial cells, Jurkat cells, and two neuroblastoma cell lines [SK-N-SH (human) and Neuro-2A (mouse)] with plasmid DNAs and siRNAs. Our data demonstrate that by determining proper electroporation conditions, glyceraldehyde phosphate dehydrogenase mRNA was silenced in Jurkat cells when compared with negative control siRNA electroporations as early as 4 h post-transfection. Other experiments demonstrated that optimized electroporation conditions using a fluorescently labeled transfection control siRNA resulted in 75% transfection efficiency for Neuro-2A, 93% for human primary fibroblasts, and 94% for HUVEC cells, as analyzed by flow cytometry.

Most Common Causes of Natural and Injury-related Deaths in Addis Ababa, Ethiopia

Pathology, Research and Practice. 2009  |  Pubmed ID: 19321271

In Ethiopia, like many developing countries, autopsy is rare unless conducted in the medico-legal arena, making vital statistics that include pathological diagnoses sparse. To determine the most common factors contributing to death among individuals who died from natural or injury-related events in Ethiopia 200 consecutive autopsies were conducted in 2006 at the Forensic Medico-legal Pathology Department, Menelik II Hospital, Addis Ababa, Ethiopia. The results describe significant pathological observations, putative cause of death, age distribution, and gender ratios. Eighty-one percent of the cases were male, and the mean age was 38.9 (+/-15.5 years). Fifty-two percent of the individuals died from natural causes, including infections, and 48% died from injury-related events. In the natural deaths group, as determined by gross examination at autopsy pulmonary complications were the most commonly reported cause of death, with suspected tuberculosis accounting for 12%. Tuberculosis (21, 8%) and liver disease (14, 5%) were the most common histopathological findings in the natural and injury-related causes groups, respectively. In the injury-related group, automobile accident was the most common cause of accidental death (80%), and homicide by beating was the most common cause of death in the intentional injury group (31%). These data provide valuable unbiased analyses of causes of death among individuals in Addis Ababa, Ethiopia.

The Remnants of Galaxy Formation from a Panoramic Survey of the Region Around M31

Nature. Sep, 2009  |  Pubmed ID: 19727194

In hierarchical cosmological models, galaxies grow in mass through the continual accretion of smaller ones. The tidal disruption of these systems is expected to result in loosely bound stars surrounding the galaxy, at distances that reach 10-100 times the radius of the central disk. The number, luminosity and morphology of the relics of this process provide significant clues to galaxy formation history, but obtaining a comprehensive survey of these components is difficult because of their intrinsic faintness and vast extent. Here we report a panoramic survey of the Andromeda galaxy (M31). We detect stars and coherent structures that are almost certainly remnants of dwarf galaxies destroyed by the tidal field of M31. An improved census of their surviving counterparts implies that three-quarters of M31's satellites brighter than M(v) = -6 await discovery. The brightest companion, Triangulum (M33), is surrounded by a stellar structure that provides persuasive evidence for a recent encounter with M31. This panorama of galaxy structure directly confirms the basic tenets of the hierarchical galaxy formation model and reveals the shared history of M31 and M33 in the unceasing build-up of galaxies.

Exopolysaccharides Produced by Bifidobacterium Longum IPLA E44 and Bifidobacterium Animalis Subsp. Lactis IPLA R1 Modify the Composition and Metabolic Activity of Human Faecal Microbiota in PH-controlled Batch Cultures

International Journal of Food Microbiology. Nov, 2009  |  Pubmed ID: 19735956

Exopolysaccharides (EPS) isolated from two Bifidobacterium strains, one of human intestinal origin (Bifidobacterium longum subsp. longum IPLA E44) and the other from dairy origin (Bifidobacterium animalis subsp. lactis IPLA R1), were subjected to in vitro chemically simulated gastrointestinal digestion, which showed the absence of degradation of both polymers in these conditions. Polymers were then used as carbon sources in pH-controlled faecal batch cultures and compared with the non-prebiotic carbohydrate glucose and the prebiotic inulin to determine changes in the composition of faecal bacteria. A set of eight fluorescent in situ hybridisation oligonucleotide probes targeting 16S rRNA sequences was used to quantify specific groups of microorganisms. Growth of the opportunistic pathogen Clostridium histolyticum occurred with all carbohydrates tested similarly to that found in negative control cultures without added carbohydrate and was mainly attributed to the culture conditions used rather than enhancement of growth by these substrates. Polymers E44 and R1 stimulated growth of Lactobacillus/Enterococcus, Bifidobacterium, and Bacteroides/Prevotella in a similar way to that seen with inulin. The EPS R1 also promoted growth of the Atopobium cluster during the first 24h of fermentation. An increase in acetic and lactic acids was found during early stages of fermentation (first 10-24h) correlating with increases of Lactobacillus, Bifidobacterium, and Atopobium. Propionic acid concentrations increased in old cultures, which was coincident with the enrichment of Clostridium cluster IX in cultures with EPS R1 and with the increases in Bacteroides in cultures with both microbial EPS (R1 and E44) and inulin. The lowest acetic to propionic acid ratio was obtained for EPS E44. None of the carbohydrates tested supported the growth of microorganisms from Clostridium clusters XIVa+b and IV, results that correlate with the poor butyrate production in the presence of EPS. Thus, EPS synthesized by bifidobacteria from dairy and intestinal origins can modulate the intestinal microbiota in vitro, promoting changes in some numerically and metabolically relevant microbial populations and shifts in the production of short chain fatty acids.

Enhanced Habituation and Decreased Anxiety by Environmental Enrichment and Possible Attenuation of These Effects by Chronic Alpha-tocopherol (vitamin E) in Aging Male and Female Rats

Pharmacology, Biochemistry, and Behavior. Feb, 2010  |  Pubmed ID: 19941885

Middle-aged 330-day-old male and female hooded rats were group-housed for nearly 5 months in either standard cages, or in cages containing objects. Each cage also provided either pure water, or a solution of vitamin E (DL-alpha-tocopherol acetate) for drinking. Records were kept of averages for each cage of the rats' body weights and the volume of fluid/100g average body weight drunk. The average daily dose of tocopherol was approximately 162 and 173mg/kg for males and females respectively. Males (but not females) kept in enriched cages weighed less than those from standard cages. They also drank less fluid than females who also drank more tocopherol solution than males. When 490+days old, for rats provided with water, enrichment led to decreased open-field ambulation and increased within-session decrements in the response (habituation). Enrichment also led to decreased occupancy of the center of the apparatus for males only and, for all rats combined, increased grooming behavior. It was concluded that the effects of enrichment on aged rats were due to increased within-session habituation to novelty and decreased anxiety similar to what has been suggested for younger animals. Tocopherol appeared to interfere with effects of enrichment possibly because of pro-oxidant-related increased anxiety.

Using Continuous ST-segment Monitoring

Nursing. 2010  |  Pubmed ID: 20168199

Expression Patterns of Hormones, Signaling Molecules, and Transcription Factors During Adenohypophysis Development in the Chick Embryo

Developmental Dynamics : an Official Publication of the American Association of Anatomists. Apr, 2010  |  Pubmed ID: 20175188

The chick embryo is an ideal model to study pituitary cell-type differentiation. Previous studies describing the temporal appearance of differentiated pituitary cell types in the chick embryo are contradictory. To resolve these controversies, we used RT-PCR to define the temporal onset and in situ hybridization and immunohistochemistry to define the spatial localization of hormone expression within the pituitary. RT-PCR detected low levels of Fshbeta (gonadotropes) and Pomc (corticotropes, melanotropes) mRNA at E4 and Gh (somatotropes), Prl (lactotropes), and Tshbeta (thyrotropes) mRNA at E8. For all hormones, sufficient accumulation of mRNA and/or protein to permit detection by in situ hybridization or immunohistochemistry was observed approximately 3 days later and in all cases corresponded to a notable increase in RT-PCR product. We also describe the expression patterns of signaling (Bmp2, Bmp4, Fgf8, Fgf10, Shh) and transcription factors (Pitx1, Pitx2, cLim3) known to be important for pituitary organogenesis in other model organisms.

A Randomized, Placebo-controlled, Multicenter Study of Divalproex Sodium Extended-release in the Acute Treatment of Mania

The Journal of Clinical Psychiatry. Apr, 2010  |  Pubmed ID: 20361904

Divalproex sodium extended-release (ER) was examined for the treatment of acute mania in adults in 2 randomized, placebo-controlled clinical trials. One study demonstrated statistically significant improvements in mania symptoms compared to placebo, while an earlier study did not. Results of the earlier study are presented here.

Recurrent Ovarian Cancer: Use of Contrast-enhanced CT and PET/CT to Accurately Localize Tumor Recurrence and to Predict Patients' Survival

Radiology. Oct, 2010  |  Pubmed ID: 20697116

To compare accuracy and interobserver variability in the detection and localization of recurrent ovarian cancer with contrast material-enhanced (CE) computed tomography (CT) and positron emission tomography (PET)/CT and determine whether imaging findings can be used to predict survival.

Unleashing Animal-assisted Therapy

Nursing. Oct, 2010  |  Pubmed ID: 20844386

Comparison of Two Methods for Ranking Applicants for Residency

Journal of the American College of Radiology : JACR. Dec, 2010  |  Pubmed ID: 21129688

Ranking radiology residency applicants is a complex process. Multiple factors, such as the variability in evaluation of candidates and the sometimes excessive subjectivity experienced, may influence the final outcome. To address inconsistencies, Yale University's selection committee integrated a mathematical model of ranking. The goal is to compare the mathematically generated rank list with the traditional committee-derived list to identify applicants with discrepancies between the two rank orders as a safety net to ensure that the final rank order list reflects true committee consensus. For three consecutive years, beginning with the 2006-2007 interview season, three rank order lists were compiled. The subjective list was developed by committee consensus on appropriate rank for each applicant. The mathematical list was developed using an equation to assign a score from each of an applicant's three interviewers, which were then averaged and arranged in descending order. These two lists were compared to identify applicants who had differences of 10 rank order positions. Identified applicants were reassessed and reassigned if necessary, forming the National Resident Matching Program (final) list submitted for the match. Over three years, 224 applicants were ranked in total, with 109 being reevaluated (49%) and 24 ultimately reassigned (11%). Discrepancies in rank on the two lists were identified and discussed. In some but not all cases, the discrepancies were remedied. Reasons for discrepancies are discussed. The mathematical method used in parallel with the subjective method has proved useful in identifying misplaced applicants and provided assurance that the final rank list reflects the committee's evaluation of each applicant.

The Impacts of Short Break Provision on Families with a Disabled Child: an International Literature Review

Health & Social Care in the Community. Jul, 2011  |  Pubmed ID: 21175907

There are widespread assumptions about the potential impacts of short breaks on family carers and disabled children. This review aims to evaluate the existing international research evidence concerning the impacts of short breaks on families with a disabled child. Electronic literature searches were conducted using ASSIA, PsycInfo, CINAHL, and Web of Science, and requests for information were sent to selected email lists. Of 60 articles or reports identified for inclusion in the review, the vast majority of studies were cross-sectional, with only eight studies using quasi-experimental pre-post designs or longitudinal designs. Nonetheless, the consistency with which some findings have been reported suggests that short breaks appear to have the potential to positively impact on not only the well-being of carers, but also the children receiving short breaks and their families as a whole. Additional research is warranted in a number of areas. First, research needs to consider the impact of short breaks on fathers. Second, there is a need to consider in more depth how short breaks can impact on the siblings of disabled children. Third, research could consider how best short breaks can be combined with other interventions to maximise the impact for disabled children and their families. Fourth, research needs to look at the longer term impact of short breaks on outcomes for disabled children and their families. What is needed is evidence on what type of short breaks are best for children and families with particular characteristics at particular times during the course of the child's maturation towards adulthood.

Effect of Dextransucrase Cellobiose Acceptor Products on the Growth of Human Gut Bacteria

Journal of Agricultural and Food Chemistry. Apr, 2011  |  Pubmed ID: 21395323

The selective fermentation by human gut bacteria of gluco-oligosaccharides obtained from the reaction between the glucosyl group of sucrose and cellobiose, catalyzed by dextransucrases (DSR) from Leuconostoc mesenteroides , has been evaluated. Oligosaccharides were fractionated according to their molecular weight, and their effect on the growth of different bacterial groups was studied. To determine the structure (position and configuration of glycosidic linkages)-function relationship, their properties were compared to those of DSR maltose acceptor products (DSRMal) and of recognized prebiotic carbohydrates (fructo-oligosaccharides, FOS). Cellobiose acceptor products (DSRCel) showed bifidogenic properties similar to those of FOS. However, no significant differences related to molecular weight or isomeric configurations were found for DSRCel and DSRMal products.

Y-STR Loci Diversity in Native Alaskan Populations

International Journal of Legal Medicine. Jul, 2011  |  Pubmed ID: 21448665

Y chromosome short tandem repeat (Y-STR) loci are important genetic markers for forensic biological evidence analyses. However, paternal inheritance, reduced effective population size, and lack of independence between loci can reduce Y-STR diversity and may yield greater population substructure effects on a locus-by-locus basis compared with the autosomal STR loci. Population studies are necessary to assess the genetic variation of forensically relevant markers so that proper inferences can be made about the rarity of DNA profiles. This study examined 16 Y-STRs in three sampled populations of Native Americans from Alaska: Inupiat, Yupik, and Athabaskan. Population genetic and statistical issues addressed were: (1) the degree of diversity at locus and haplotype levels, (2) determination of the loci that contribute more so to haplotype diversity, and (3) the effects of population substructure on forensic statistical calculations of the rarity of a Y-STR profile. All three population samples were highly polymorphic at the haplotype level for the 16 Y-STR markers; however, the Native Americans demonstrated reduced genetic diversity compared with major US populations. The degree of substructure indicated that the three populations were related and admixed in terms of paternal lineage. The examination of more polymorphic loci may be needed to increase the power of discrimination of Y-STR systems in these populations.

Manipulating Claudin Expression in Avian Embryos

Methods in Molecular Biology (Clifton, N.J.). 2011  |  Pubmed ID: 21717358

Since the discovery of Claudin-1 and -2 by Tsukita and colleagues in the late 1990s [Furuse et al. J Cell Biol 141:1539-50,1998], claudin family members have been found to have critical roles in maintaining the integrity of epithelial and endothelial tight junctions [Furuse and Moriwaki Ann N Y Acad Sci 1165:58-61, 2009; Morita et al. Proc Natl Acad Sci USA 96:511-6, 1999; Tsukita and Furuse Ann N Y Acad Sci 915:129-35, 2000; Turksen and Troy J Cell Sci 117:2435-47, 2004]. The properties of distinct claudin family members in tight junction permeability and specificity have been extensively studied in vitro using cell culture models. In vivo, claudin family members are dynamically regulated during embryogenesis and alterations in their expression patterns can have detrimental effects on the formation and physiological function of the tissues in which they are expressed. The chick embryo provides an excellent system to dissect the roles of specific family members in vivo and to explore the effects of modulating claudin expression during the epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions that are associated with tissue morphogenesis and differentiation. We are using the chick embryo to understand the roles of the claudin family of tight junction proteins during gastrulation and left-right patterning during embryogenesis. Here, we describe methodologies for manipulating claudin gene expression in specific target tissues during chick embryogenesis.

Challenges of Drug Discovery in Novel Target Space. The Discovery and Evaluation of PF-3893787: a Novel Histamine H4 Receptor Antagonist

Bioorganic & Medicinal Chemistry Letters. Nov, 2011  |  Pubmed ID: 21920751

We describe the development of novel benzimidazoles as small molecule histamine H4 receptor (H4R) antagonists and their profiling in rat early toxicity studies. The discovery and optimisation of a second series of pyrimidine based antagonists is then described culminating in the identification of the clinical development candidate 13 (PF-3893787). The pre-clinical profile of 13 (PF-3893787) is presented including the development of a translatable biomarker. Our pragmatic approach to target selection, safety assessment, and testing for efficacy faced numerous challenges and we share a number of lessons which the team learned and which will assist us and others in future drug discovery projects.

In Vitro Fermentation of Lactulose-Derived Oligosaccharides by Mixed Fecal Microbiota

Journal of Agricultural and Food Chemistry. Feb, 2012  |  Pubmed ID: 22292561

Fermentation properties of oligosaccharides derived from lactulose (OsLu) and lactose (GOS) have been assessed in pH-controlled anaerobic batch cultures using lactulose and Vivinal-GOS as reference carbohydrates. Changes in gut bacterial populations and their metabolic activities were monitored over 24 h by fluorescent in situ hybridization (FISH) and by measurement of short-chain fatty acid (SCFA) production. Lactulose-derived oligosaccharides were selectively fermented by Bifidobacterium and lactic acid bacterial populations producing higher SCFA concentrations compared to GOS. The highest total SCFA production was from Vivinal-GOS > lactulose > OsLu > GOS. Longer incubation periods produced a selective fermentation of OsLu when they were used as a carbon source reaching the highest selective index scores. The new oligosaccharides may constitute a good alternative to lactulose, and they could belong to a new generation of prebiotics to be used as a functional ingredient for improving the composition of gut microflora.

Claudin-5 Expression in the Vasculature of the Developing Chick Embryo

Gene Expression Patterns : GEP. Feb, 2012  |  Pubmed ID: 22326481

The claudin family of proteins are integral components of tight junctions and are responsible for determining the ion specificity and permeability of paracellular transport within epithelial and endothelial cell layers. Studies in human, mouse, Xenopus, and zebrafish have shown that only a limited number of claudins are expressed in endothelial cells. Here, we report the expression pattern of Claudin-5 during chick development. Between HH stage 4 and 6 Claudin-5 expression was observed exclusively in extraembryonic tissue. Claudin-5 expression was not observed in the embryo until HH stage 8, coincident with the onset of embryonic vascularization. Claudin-5 expression was maintained in the developing vasculature in the embryonic and extraembryonic tissue throughout organogenesis (HH stage 19-35), including the vasculature of the ectoderm and of organs derived from the mesoderm and endoderm lineages. These data describe a conserved expression pattern for Claudin-5 in the endothelial tight junction barrier and is the first report of the onset of Claudin-5 expression in a vertebrate embryo.

Efficacy and Safety of the Novel α(4)β (2) Neuronal Nicotinic Receptor Partial Agonist ABT-089 in Adults with Attention-deficit/hyperactivity Disorder: a Randomized, Double-blind, Placebo-controlled Crossover Study

Psychopharmacology. Feb, 2012  |  Pubmed ID: 21748252

α(4)β(2) Neuronal nicotinic receptors (NNRs) are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD).