Miracle-dz/UniFAR-FTUs huggingface dataset:
Genotype and neuropsychological response inhibition as resilience promoters for attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder under conditions of psychosocial adversity

Whereas child personality, IQ, and family factors have been identified as enabling a resilient response to psychosocial adversity, more direct biological resilience factors have been less well delineated. This is particularly so for child attention-deficit/hyperactivity disorder (ADHD), which has received less attention from a resilience perspective than have associated externalizing disorders. Children from two independent samples were classified as resilient if they avoided developing ADHD, oppositional defiant disorder (ODD), or conduct disorder (CD) in the face of family adversity. Two protective factors were examined for their potential relevance to prefrontal brain development: neuropsychological response inhibition, as assessed by the Stop task, and a composite catecholamine genotype risk score. Resilient children were characterized in both samples by more effective response inhibition, although the effect in the second sample was very small. Genotype was measured in Sample 1, and a composite high risk genotype index was developed by summing presence of risk across markers on three genes expressed in prefrontal cortex: dopamine transporter, dopamine D4 receptor, and noradrenergic alpha-2 receptor. Genotype was a reliable resilience indicator against development of ADHD and CD, but not ODD, in the face of psychosocial adversity. Results illustrate potential neurobiological protective factors related to development of prefrontal cortex that may enable children to avoid developing ADHD and CD in the presence of psychosocial adversity.
A national survey of medical education fellowships

Abstract Purpose: The purpose of our study was to determine the prevalence, focus, time commitment, graduation requirements and programme evaluation methods of medical education fellowships throughout the United States. Medical education fellowships are defined as a single cohort of medical teaching faculty who participate in an extended faculty development programme. Methods: A 26-item online questionnaire was distributed to all US medical schools (n=127) in 2005 and 2006. The questionnaire asked each school if it had a medical education fellowship and the characteristics of the fellowship programme. Results: Almost half (n=55) of the participating schools (n=120, response rate 94.5 %) reported having fellowships. Duration (10–584 hours) and length (<1 month–48 months) varied; most focused on teaching skills, scholarly dissemination and curriculum design, and required the completion of a scholarly project. A majority collected participant satisfaction; few used other programme evaluation strategies. Conclusions: The number of medical education fellowships increased rapidly during the 1990s and 2000s. Across the US, programmes are similar in participant characteristics and curricular focus but unique in completion requirements. Fellowships collect limited programme evaluation data, indicating a need for better outcome data. These results provide benchmark data for those implementing or revising existing medical education fellowships.
The platelet hyporesponsiveness to clopidogrel in acute coronary syndrome patients treated with 75 mg/day clopidogrel may be overcome within 1 month of treatment

Platelets are involved in thrombus formation and inflammation following vascular injury, while clopidogrel exerts antithrombotic and anti-inflammatory actions. We investigated various platelet-derived prothrombotic and proinflammatory mediators as well as the platelet aggregatory response in patients with acute coronary syndromes (ACS) receiving clopidogrel, as a function of the patient responsiveness to drug treatment. Blood samples were obtained from 40 patients with recent (<24 h) ACS before clopidogrel loading 600 mg (followed by a maintenance dose of 75 mg/day) as well as 5-days and 30-days afterwards. Twelve patients exhibited platelet reactivity index (PRI) values higher than 50% evaluated by the Vasodilator Stimulated Phosphoprotein (VASP) test at 5 days and were characterized as nonresponders. The platelet response to adenosine diphosphate (ADP) and thrombin receptor agonist peptide-14 (TRAP) was studied by flow cytometry and light transmission aggregometry. A maximum reduction of ADP- or TRAP-induced platelet aggregation in 28 clopidogrel responding patients was observed at 5 days postclopidogrel loading, whereas in nonresponders, it was achieved at 30-days along with a significant decrease in the PRI values. Similar results were obtained for the membrane expression of CD40L and the production of platelet-derived microparticles. By contrast, the maximum inhibition of P-selectin expression and platelet–leukocyte conjugate formation was observed at 30-days in both patient groups. A maintenance dose of 75 mg clopidogrel differentially affects the platelet aggregation and platelet-derived prothrombotic and proinflammatory mediators in ACS patients within the first month of the treatment, a phenomenon that is highly influenced by the drug response variability. Since these factors may be involved in the major adverse cardiovascular events in ACS patients, especially in those undergoing percutaneous coronary intervention, the above findings may be clinically important.
Maternal Effects on Offspring Mortality in Rhesus Macaques (Macaca mulatta)

The genetics of primate life histories are poorly understood, but quantitative genetic patterns in other mammals suggest phenotypic differences among individuals early in life can be strongly affected by interactions with mothers or other caretakers. I used generalized linear mixed model extensions of complex pedigree quantitative genetic techniques to explore regression coefficients and variance components for infant and juvenile mortality rates across prereproductive age classes in the semifree ranging Cayo Santiago rhesus macaques. Using a large set of records (maximum n = 977 mothers, 6,240 offspring), strong maternal effects can be identified early in development but they rapidly “burn off” as offspring age and mothers become less consistent buffers from increasingly prominent environmental variation. The different ways behavioral ecologists and animal breeders have defined and studied maternal effects can be subsumed, and even blended, within the quantitative genetic framework. Regression coefficients identify loss of the mother, maternal age, and offspring age within their birth cohort as having significant maternal effects on offspring mortality, while variance components for maternal identity record significant maternal influence in the first month of life. Am. J. Primatol. 75:238‐251, 2013. © 2013 Wiley Periodicals, Inc.
Activation of Cu,Zn-Superoxide Dismutase in the Absence of Oxygen and the Copper Chaperone CCS*

Eukaryotic Cu,Zn-superoxide dismutases (SOD1s) are generally thought to acquire the essential copper cofactor and intramolecular disulfide bond through the action of the CCS copper chaperone. However, several metazoan SOD1s have been shown to acquire activity in vivo in the absence of CCS, and the Cu,Zn-SOD from Caenorhabditis elegans has evolved complete independence from CCS. To investigate SOD1 activation in the absence of CCS, we compared and contrasted the CCS-independent activation of C. elegans and human SOD1 to the strict CCS-dependent activation of Saccharomyces cerevisiae SOD1. Using a yeast expression system, both pathways were seen to acquire copper derived from cell surface transporters and compete for the same intracellular pool of copper. Like CCS, CCS-independent activation occurs rapidly with a preexisting pool of apo-SOD1 without the need for new protein synthesis. The two pathways, however, strongly diverge when assayed for the SOD1 disulfide. SOD1 molecules that are activated without CCS exhibit disulfide oxidation in vivo without oxygen and under copper-depleted conditions. The strict requirement for copper, oxygen, and CCS in disulfide bond oxidation appears exclusive to yeast SOD1, and we find that a unique proline at position 144 in yeast SOD1 is responsible for this disulfide effect. CCS-dependent and -independent pathways also exhibit differential requirements for molecular oxygen. CCS activation of SOD1 requires oxygen, whereas the CCS-independent pathway is able to activate SOD1s even under anaerobic conditions. In this manner, Cu,Zn-SOD from metazoans may retain activity over a wide range of physiological oxygen tensions.
Influenza Viruses with Rearranged Genomes as Live-Attenuated Vaccines

ABSTRACT H5N1 and H9N2 avian influenza virus subtypes top the World Health Organization's list for the greatest pandemic potential. Inactivated H5N1 vaccines induce limited immune responses and, in the case of live-attenuated influenza virus vaccines (LAIV), there are safety concerns regarding the possibility of reassortment between the H5 gene segment and circulating influenza viruses. In order to overcome these drawbacks, we rearranged the genome of an avian H9N2 influenza virus and expressed the entire H5 hemagglutinin open reading frame (ORF) from the segment 8 viral RNA. These vectors had reduced polymerase activities as well as viral replication in vitro and excellent safety profiles in vivo. Immunization with the dual H9-H5 influenza virus resulted in protection against lethal H5N1 challenge in mice and ferrets, and also against a potentially pandemic H9 virus. Our studies demonstrate that rearranging the influenza virus genome has great potential for the development of improved vaccines against influenza virus as well as other pathogens.
Can outcome of pancreatic pseudocysts be predicted? Proposal for a new scoring system.

BACKGROUND The spontaneous resolution rate of pancreatic pseudocysts (PPs) is 86%, and the serious complication rate is 3-9%. The aim of the present study was to develop a scoring system that would predict spontaneous resolution of PPs. METHODS Medical records of 70 patients were retrospectively reviewed. Two patients were excluded. Demographic data and laboratory measurements were obtained from patient records. RESULTS Mean age of the 68 patients included was 56.6 years. Female:male ratio was 1.34:1. Causes of pancreatitis were stones (48.5%), alcohol consumption (26.5%), and unknown etiology (25%). Mean size of PP was 71 mm. Pseudocysts disappeared in 32 patients (47.1%). With univariate analysis, serum direct bilirubin level (>0.95 mg/dL), cyst carcinoembryonic antigen (CEA) level (>1.5), and cyst diameter (>55 mm) were found to be significantly different between patients with and without spontaneous resolution. In multivariate analysis, these variables were statistically significant. Scores were calculated with points assigned to each variable. Final scores predicted spontaneous resolution in approximately 80% of patients. CONCLUSION The scoring system developed to predict resolution of PPs is simple and useful, but requires validation.
What makes a good reviewer and a good review for a general medical journal?

CONTEXT Selecting peer reviewers who will provide high-quality reviews is a central task of editors of biomedical journals. OBJECTIVES To determine the characteristics of reviewers for a general medical journal who produce high-quality reviews and to describe the characteristics of a good review, particularly in terms of the time spent reviewing and turnaround time. DESIGN, SETTING, AND PARTICIPANTS Surveys of reviewers of the 420 manuscripts submitted to BMJ between January and June 1997. MAIN OUTCOME MEASURES Review quality was assessed independently by 2 editors and by the corresponding author using a newly developed 7-item review quality instrument. RESULTS Of the 420 manuscripts, 345 (82%) had 2 reviews completed, for a total of 690 reviews. Authors' assessments of review quality were available for 507 reviews. The characteristics of reviewers had little association with the quality of the reviews they produced (explaining only 8% of the variation), regardless of whether editors or authors defined the quality of the review. In a logistic regression analysis, the only significant factor associated with higher-quality ratings by both editors and authors was reviewers trained in epidemiology or statistics. Younger age also was an independent predictor for editors' quality assessments, while reviews performed by reviewers who were members of an editorial board were rated of poorer quality by authors. Review quality increased with time spent on a review, up to 3 hours but not beyond. CONCLUSIONS The characteristics of reviewers we studied did not identify those who performed high-quality reviews. Reviewers might be advised that spending longer than 3 hours on a review on average did not appear to increase review quality as rated by editors and authors.
Cyclofenil versus placebo in progressive systemic sclerosis. A one-year double-blind crossover study of 27 patients.

Cyclofenil was evaluated versus placebo in the treatment of progressive systemic sclerosis (PSS, scleroderma) in a 2 x 6-month double-blind crossover study. The mean duration of disease was six years. Of 38 patients entering the study, 27 completed both periods. Reasons for drop-outs were very high liver transaminases in three cases, cardiac death in two, and drug allergy, alcoholic problems, suspected congestive heart failure, reactivation of tuberculosis, arteriosclerotic heart disease, and lethal progression of PSS in one case each. No fatality was attributed to cyclofenil. Liver enzyme abnormalities were seen in 13 of 35 active drug periods and in 5 of 30 placebo periods. Cutaneous and visceral involvement were assessed by a large battery of subjective parameters and objective tests. Overall improvement was seen during 17 drug periods and nine placebo periods (N.S.), but a paired comparison of the status at the end of each treatment period resulted in the following distribution: 15 were improved at the end of the drug period, four at the end of placebo period (p less than 0.01) and eight were unchanged. In patients with a disease duration of five years or less, joint stiffness and pain were less on drug than on placebo treatment (p less than 0.05). In the whole group, oesophageal peristalsis improved (p less than 0.05). Blood folate increased (p less than 0.01). Working capacity was lower after the drug period than after the placebo period (p less than 0.05). Several other parameters, however, did not change significantly. Cyclofenil appears to be a promising drug in the treatment of PSS and should be tested further in controlled long-term studies.
Identification of New Epitopes from Four Different Tumor-Associated Antigens: Recognition of Naturally Processed Epitopes Correlates with HLA-A∗0201-Binding Affinity1

Forty-two wild-type and analogue peptides derived from p53, carcinoembryonic Ag, Her2/neu, and MAGE2/3 were screened for their capacity to induce CTLs, in vitro, capable of recognizing tumor target lines. All the peptides bound HLA-A*0201 and two or more additional A2 supertype alleles with an IC50 of 500 nM or less. A total of 20 of 22 wild-type and 9 of 12 single amino acid substitution analogues were found to be immunogenic in primary in vitro CTL induction assays, using normal PBMCs and GM-CSF/IL-4-induced dendritic cells. These results suggest that peripheral T cell tolerance does not prevent, in this system, induction of CTL responses against tumor-associated Ag peptides, and confirm that an HLA class I affinity of 500 nM or less is associated with CTL epitope immunogenicity. CTLs generated by 13 of 20 of the wild-type epitopes, 6 of 9 of the single, and 2 of 5 of the double substitution analogues tested recognized epitopes generated by endogenous processing of tumor-associated Ags and expressed by HLA-matched cancer cell lines. Further analysis revealed that recognition of naturally processed Ag was correlated with high HLA-A2.1-binding affinity (IC50 = 200 nM or less; p = 0.008), suggesting that high binding affinity epitopes are frequently generated and can be recognized as a result of natural Ag processing. These results have implications for the development of cancer vaccines, in particular, and for the process of epitope selection in general.
A comparative study of breast cell proliferation during hormone replacement therapy: effects of tibolone and continuous combined estrogen–progestogen treatment

Objective To use the fine-needle aspiration (FNA) biopsy technique to compare the effects of tibolone, conventional hormone replacement therapy (HRT) and placebo on breast cell proliferation in postmenopausal women. Methods A total of 91 women were randomized to receive either estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA), tibolone 2.5 mg or placebo for 6 months in a prospective double-blind trial. Breast cell proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody. Results From the 83 women who completed the study, a total of 166 FNA biopsies were obtained, and 118 of these aspirates (71%) were evaluable for MIB-1 content. Women with assessable biopsies were younger, had a lower body mass index, and had higher levels of sex hormone binding globulin and insulin-like growth factor-I than women in whom the cell yield was insufficient. During treatment with E2/NETA, there was an increase in proliferation (percentage of MIB-1) from a mean value of 2.2 to 6.4% after 6 months (p < 0.01). No significant changes were recorded during treatment with tibolone or placebo. There was a negative association between proliferation and serum levels of total (rs = −0.29, p < 0.05) and free (rs = −0.31, p < 0.03) testosterone. Conclusions Tibolone seems to have little influence on breast cell proliferation.
Ultrasound-guided embryo transfer: a prospective randomized controlled trial.

BACKGROUND Recent reports suggested that ultrasound guidance during embryo transfer might improve the pregnancy rate. METHODS A prospective randomized controlled trial was performed to compare embryo transfer under ultrasound guidance versus the clinical touch method. A total of 800 embryo transfers was studied; 400 were randomized to ultrasound-guided transfers and 400 were randomized to the clinical touch group. Of these, 441 were fresh cycles and 359 were frozen-thawed cycles. RESULTS The clinical pregnancy rate was 26.0% in the ultrasound-guided group and 22.5% in the clinical touch group; the difference was not statistically significant. The ongoing pregnancy rate was 23.5% in the ultrasound-guided group compared with 19.0% in the clinical touch group and the difference was again not statistically significant. The implantation rate was slightly higher in the ultrasound-guided group (15.3%) than the clinical touch group (12.0%) (P = 0.048). There were no differences in the incidences of ectopic pregnancy, miscarriage and multiple pregnancy between the two groups. CONCLUSIONS A significant improvement in implantation rate was observed following the use of ultrasound guidance during embryo transfer. The extent of improvement in the pregnancy rate may depend on the specific techniques and methods of embryo transfer used in individual centres.
Echocardiographic evaluation of cardiac function in the fetus

The development of high‐resolution ultrasound has allowed detailed examination of the fetal heart. The accuracy of fetal echocardiography in the diagnosis of malformations of the fetal heart has been established in the second trimester and, more recently, at a much earlier stage in gestation (Allan et al., 1980 ; Allan et al., 1981 ; Simpson, 2000 ; Huggon et al., 2002 ). Confirmation of structural abnormalities has usually been by autopsy or by postnatal investigation. This is certainly sufficient for confirmation of structural malformations, but functional evaluation of the fetal heart is far more difficult to validate. Post‐mortem studies, by their very nature give little insight into cardiac function and postnatal studies, whilst permitting functional evaluation of the heart, do so under entirely different conditions compared to the circulation in utero. Prior to the advent of ultrasound, fetal data was drawn from invasive animal studies (Pohlman, 1909 ; Dawes et al., 1954 ; Barcroft, 1936 ; Rudolph, 1985 ). There have been very few invasive studies in the human fetus including some conducted on exteriorised fetuses undergoing termination by hysterotomy (Nyberg and Westin, 1962 ; Rudolph et al., 1971 ). Pressure data has been obtained from the human fetus for normal human hearts and in cardiac disease (Johnson et al., 2000 ; Johnson et al., 1992 ; Johnson, 1992 ). However, the vast majority of cardiac functional data in the human fetus has been obtained by non‐invasive means, which has almost exclusively been by echocardiography. This article will review some of the techniques that may be used to evaluate fetal cardiac function and will also emphasise some of the limitations of such techniques. Copyright © 2004 John Wiley & Sons, Ltd.
Effect of stress on biofilm formation by icaA positive and negative strains of methicillin resistant Staphylococcus aureus.

OBJECTIVE To determine the effect of physical and chemical stress factors e.g. antibiotics, NaCl, glucose, heat shock, cold shock and sonic waves on biofilm formation by icaA positive and negative strains of Methicillin resistant Staphylococcus (S.) aureus. STUDY DESIGN Experimental study. PLACE AND DURATION OF STUDY Microbiological Analytical Centre, Pakistan Council of Scientific and Industrial Research (PCSIR) Laboratories Complex, Karachi, from January to December 2010. METHODOLOGY One strain of Staphylococcus aureus labelled as FA was isolated from a food sample and the other strain labelled as CL was a clinical strain. Biofilm assays were performed in brain-heart infusion (BHI) medium and in BHI supplemented with 7% NaCl, 5% glucose, or sub-inhibitory concentrations of Vancomycin, Oxacillin, Ampicillin, Tetracycline, Erythromycin, Rifampicin and Ciprofloxacin. Polymerase chain reaction (PCR) was used for screening of the icaA and mecA genes. RESULTS The FA and CL were identified as MRSA carrying mecA gene. The strain FA showed biofilm formation without any treatment and was found to carry icaA gene contrary to CL, that does not contain this gene therefore, is unable to produce biofilm under normal conditions without any stress. The use of sub-lethal doses of cell wall active antibiotics, exposure to 7% NaCl, sonication, and heat shock were found to augment biofilm quantity in FA, an icaA positive strain and induce biofilm mode of growth in CL, an icaA negative strain. Anti-protein synthesis antibiotics did not show any effect on biofilm formation process in icaA positive or negative strains. CONCLUSION There is a role of anti-cell wall factors i.e. sonication, heat shock, NaCl and antibiotics in the induction of biofilm mode of growth in MRSA and Methicillin sensitive S. aureus. The factors which partially damage bacterial cell wall, equally, induce biofilm formation in icaA positive or negative S. aureus.