Miracle-dz/UniFAR-FTUs huggingface dataset:
Biological Effects of Long-Term Caloric Restriction: Adaptation with Simultaneous Administration of Caloric Stress Plus Repeated Immobilization Stress in Rats

In the present study, we have established the biological effects during 8 weeks of (i) caloric restriction (Cal) and (ii) simultaneous administration of Cal plus 2 hr daily immobilization stress using male Sprague-Dawley rats. Animals were divided into three equal groups: (i) ad libitum fed, (ii) 30% restriction of food intake of the ad libitum diet, and (iii) 30% restriction of food intake plus 2 hr daily immobilization stress. Caloric-restricted animals gained only 30% of the total body weight of the unrestricted animals but received 70% of the food of those rats. Cal animals showed a significant loss in their relative liver and thymus weight and a significant gain in their relative adrenal and testis weight as compared to the control animals. Cal animals had almost 2-fold higher levels of plasma corticosterone levels with a dramatic decrease in the total glucocorticoid receptor (GR) levels in the liver, thymus, heart, and testis as compared to ad libitum fed control animals. Interestingly, Cal animals showed higher levels of lipid peroxidation in both the liver and heart, indicating increased oxidative activities in these tissues when compared with the control animals. In addition, Cal animals had increased heat shock protein 70 (HSP 70) content in the testis. Surprisingly, hardly any significant differences were observed in either total body weight gain, organ weights, Plasma corticosterone levels, or lipid peroxidation between Cal animals and Cal plus immobilization-stressed animals. The results obtained suggest that (i) several stress-related responses such as inhibition of total body weight gain, increased adrenal weight, decreased thymus weight, increased plasma corticosterone, and lipid peroxidation levels in the liver and heart are associated with Cal, but (ii) no additional effects were observed on the parameters that were measured when two stress regimens were given simultaneously, suggesting that animals subjected to two stress regimens can protect themselves by controlling their stress-related thresholds of response through adaptation.
Post-Revolutionary Islamism and the Future of Democracy and Human Rights in Egypt

From the backwaters of stagnation in democratization, the Arab Spring countries carried the day and became trailblazers to be replicated by activists all over the world. A couple of seasons after the initial revolution/revolt, Egyptians had transformed their political system, written themselves a constitution, and apparently destroyed the same constitution. While all sectors of society played a role in shaping the revolution, the latter has also affected society. Egypt’s 2012 constitution, one of the outcomes of the revolution, captures a moment in the process and also reflects an attempt to install an Islamist ideology in a constitutional democratic form. The constitution’s attempt to negotiate between Shari‘ah and democracy and its outline of a human rights regime make the future of democracy and human rights ambiguous, as the Islamist stance promulgated has yet to be tested in the real world of politics. As it stands today, the constitution is too ambiguous to allow one to draw a clear picture of the future of constitutional practice. What is clear, however, is that the revolution and subsequent constitution have affected the Islamist discourse about democracy and human rights.
Diagnosis and management of factor V Leiden

ABSTRACT Introduction: The discovery of the factor V Leiden (FVL) missense mutation (Arg506Gln) causing factor V resistance to the anticoagulant action of activated protein C was a landmark that allowed a better understanding of the basis of inherited thrombotic risk. FVL mutation is currently the most common known hereditary defect predisposing to venous thrombosis. Areas covered: Novel data-driven FVL diagnosis and therapeutic approaches in the management of FVL carriers in various clinical settings. Brief conclusions on topics of direct clinical relevance including currently available indications for primary and secondary prophylaxis, the management of female, pediatric carriers and asymptomatic relatives. Latest evidence on the association between FVL and cancer, as well as the possible use of direct oral anticoagulant therapy. Expert commentary: Although FVL diagnosis nowadays is highly accurate, many doubts remain regarding the best management and therapeutic protocols. The main role of clinicians is to tailor therapeutic strategies to carriers and their relatives. High familial penetrance, distinctive aspects of the first thrombotic event (provoked/unprovoked, age, etc.) and laboratory biomarkers can guide the optimal management of secondary antithrombotic prophylaxis, primary prophylaxis in asymptomatic individuals, and whether to screen relatives.
Maturing neurons are selectively sensitive to human immunodeficiency virus type 1 exposure in differentiating human neuroepithelial progenitor cell cultures

Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neuronal injury manifested by dendritic pruning, aberrant neurofilament metabolism, and decreased synaptic density. The central nervous system (CNS) responds to neuronal injury by differentiating new neurons and astrocytes from resident populations of multipotent neuroepithelial progenitor cells (NEP) located in regions such as the subventricular zone or hippocampus. In vitro studies have demonstrated that the HIV-1 virion or envelope glycoprotein gp120 can injure differentiated human neurons and astrocytes, suggesting that HIV-1 proteins could similarly injure NEP or NEP-derived glial and neuronal lineage-committed precursor cells. To answer this question, human fetal brain-derived “neurospheres” containing NEP and NEP-derived precursor cells were cultured in low serum differentiation medium containing lymphotropic HIV-1(SF2), macrophage-tropic HIV-1(SF128A), or recombinant gp120SF2 from HIV-1(SF2). These experiments indicate that exposure to HIV-1 does not affect the ability of the NEP to differentiate into cells expressing either astrocyte-specific or neuron-specific cytoskeletal antigens. However prolonged exposure to HIV-1 does selectively decrease expression of neuronal antigens (microtubule β-III-tubulin and intermediate filament neurofilament-L) but not astrocyte antigens (intermediate filament glial fibrillary acidic protein). The effects of continuous exposure to HIV-1 or gp120 may result from injury to developing neurons and/or impairment of the neuronal developmental process itself. By depressing neuronal microtubule and neurofilament protein expression, HIV-1 and gp120 exposure compromise the potential for postmitotic neuronal dendrite and axon development.
Risk of knee and ankle sprains under various weather conditions in American football.

PURPOSE Previous studies have found conflicting relationships between type of playing surface and injury in American football but have not taken into account possible variations in the surface conditions of outdoor stadiums due to changing weather. METHODS A total of 5910 National Football League team games between 1989 and 1998 inclusive were studied to determine associations between knee and ankle sprains, playing surface, and the weather conditions on the day of the game. RESULTS There was reduced risk of significant ankle sprains (at least 7-d time loss) for games in natural grass stadiums compared with domes (indoor stadiums using AstroTurf) (RR 0.69, 95% CI 0.58-0.83). There was also reduced risk of significant knee sprains on grass compared with domes (RR 0.77, 95% CI 0.66-0.91), although most of this reduction was related to cold and wet weather on grass (RR 0.66, 95% CI 0.47-0.93 compared with hot and dry weather on grass). In open (outdoor) AstroTurf stadiums, cold weather was associated with a lower risk of significant ankle sprains (RR 0.68, 95% CI 0.51-0.91), significant knee sprains (RR 0.60, 95% CI 0.47-0.77) and ACL injuries (RR 0.50, 95% CI 0.31-0.81) compared with hot weather in the same stadiums. Weather did not have any significant effects on the injury risk in domes. The ACL incidence rate was lower during the later (cooler) months of the season in open stadiums (both AstroTurf and natural grass) but not in domes. CONCLUSION Cold weather is associated with lower knee and ankle injury risk in outdoor stadiums (both natural grass and AstroTurf), probably because of reduced shoe-surface traction.
Neuropsychological analyses of impulsiveness in childhood hyperactivity

Background Neuropsychological analyses of impulsiveness are needed to refine assessment of attention-deficit hyperactivity disorder (ADHD). Aims To investigate specific impairments in hyperactive children in a neuropsychological task battery of impulsiveness, the Maudsley Attention and Response Suppression (MARS) task battery, and to identify the neural substrates. Method Impulsiveness was assessed using different tasks of inhibitory control and time management (MARS) in 55 children with ADHD, other diagnoses and controls. Functional magnetic resonance images were obtained from adolescents with and without ADHD during three of the tasks. Results Children with ADHD, but not psychiatric controls, were impaired on tests of response inhibition, but not of motor timing. Reduced right prefrontal activation was observed in hyperactive adolescents during higher level inhibition and delay management, but not during simple sensorimotor coordination. Conclusions Attention-deficit hyperactivity disorder is characterised by specific deficits in tasks of motor response inhibition, but not motor timing, and by dysfunction of frontostriatal brain regions.
Regulatory T Cell–Dependent and –Independent Mechanisms of Immune Suppression by CD28/B7 and CD40/CD40L Costimulation Blockade

Blocking of costimulatory CD28/B7 and CD40/CD40L interactions is an experimental approach to immune suppression and tolerance induction. We previously reported that administration of a combination of CTLA-4Ig and MR1 (anti-CD40L mAb) for blockade of these interactions induces tolerance in a fully mismatched allogeneic splenocyte transfer model in mice. We now used this model to study whether regulatory T cells (Tregs) contribute to immune suppression and why both pathways have to be blocked simultaneously. Mice were injected with allogeneic splenocytes, CD4+ T cells, or CD8+ T cells and treated with MR1 mAb and different doses of CTLA-4Ig. The graft-versus-host reaction of CD4+ T cells, but not of CD8+ T cells, was inhibited by MR1. CTLA-4Ig was needed to cover CD8+ T cells but had only a weak effect on CD4+ T cells. Consequently, only the combination provided full protection when splenocytes were transferred. Importantly, MR1 and low-dose CTLA-4Ig treatment resulted in a relative increase in Tregs, and immune suppressive efficacy was abolished in the absence of Tregs. High-dose CTLA-4Ig treatment, in contrast, prevented Treg expansion and activity, and in combination with MR1 completely inhibited CD4+ and CD8+ T cell activation in a Treg-independent manner. In conclusion, MR1 and CTLA-4Ig act synergistically as they target different T cell populations. The contribution of Tregs to immune suppression by costimulation blockade depends on the concentration of CTLA-4Ig and thus on the degree of available CD28 costimulation.
Family discord, parental depression, and psychopathology in offspring: 20-year follow-up.

OBJECTIVE To determine the independent effects of parental depression and family discord on offspring psychopathology among children at high and low risk of depression. METHOD Family discord factors were assessed when subjects were approximately 17 years old, and offspring diagnoses were assessed about 20 years later. Parental and offspring psychopathology was assessed by interviewers blind to parents' clinical status. The following dimensions of family discord were assessed: poor marital adjustment, parent child discord, low family cohesion, affectionless control, and parental divorce. RESULTS Most family discord factors were associated with parental depression. Among children of depressed parents, none of the measures of family discord had a statistically significant association with offspring major depressive disorder or anxiety disorders. Among children of nondepressed parents, parental affectionless control was associated with an almost fivefold increased risk of major depressive disorder (odds ratio [OR] = 4.8; p < or = .05) and with more than a 14-fold increased risk of substance use disorders (OR = 14.3; p < or = .01). CONCLUSIONS Parental depression is associated with family discord and is a consistent risk factor for offspring major depressive disorder and anxiety disorders, as shown over a 20-year follow-up of offspring of depressed and nondepressed parents. Family discord factors may be a risk factor for major depressive disorder and substance use disorders in offspring of nondepressed parents.
No effect of a new second‐generation B‐domain‐deleted recombinant product on lymphocyte transformation in vitro: a study of plasma‐derived and recombinant products

Immunomodulatory effects of various factor VIII and factor IX clotting factor concentrates (CFCs) and of albumin were evaluated by a sensitive assay measuring the incorporation of 3H‐thymidine in phytohaemagglutinin‐stimulated lymphocytes in the presence of monodansylthiacadaverine.
Ketamine-etomidate for children undergoing cardiac catheterization

The purpose of this study was to determine the effects of combined low-dose ketamine and etomidate on hemodynamics during cardiac catheterization in children with congenital cardiac shunts. Sixty children undergoing routine diagnostic cardiac catheterization were included: 30 had a right-to-left shunt, and 30 had a left-to-right shunt. Both groups were given a single dose of etomidate 0.3 mg·kg−1 with ketamine 1 mg·kg−1. There were no hemodynamic changes in the group with a right-to-left shunt. In cases of left-to-right shunt, there were significant differences in heart rate, right atrial pressure, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, and systemic vascular resistance index. Decreases in pulmonary blood flow and pulmonary-systemic shunt ratio were also observed. Further studies are required with dose titration of this anesthetic combination in pediatric patients with congenital heart disease involving a left-to-right shunt.
Effects of socioeconomic status on the physical activity in adolescents: a systematic review of the evidence

The relationship between physical activity and socioeconomic status (SES) is evident in the adult population, but is much discussed with regard to adolescents. The main objective of this review was, therefore, to clarify whether there is a relationship between physical activity and SES in adolescents. Computerized searches were conducted in the databases PubMed, ISI Web of knowledge and SPORTDiscus to identify all relevant articles up to July 2009. Other review articles, descriptive or theoretical articles and articles where the adolescents in the samples were outside the age group of 13–18 years were excluded. Sixty‐two articles were included in the end. The main results support the hypothesis that there is an association between SES and physical activity among adolescents, and that adolescents with higher SES are more physically active than those with lower SES. The findings are, however, far from uniform. Forty‐two percent of the included studies report no or an opposite relation. There is also an inconsistent use of measures for both variables that complicates explanations and interpretations of the findings. This fortifies the claim that there is no single explanation for a possible difference in physical activity between different socioeconomic groups.
Risk factors for neck and upper limb disorders: results from 24 years of follow up.

OBJECTIVES: To investigate associations between different potential risk factors, related and not related to work, and disorders of the neck and upper extremities occurring up to 24 years later. METHODS: The study comprised 252 women and 232 men, Swedish citizens, 42-59 years of age and in a broad range of occupations. Information about potential risk factors was available from a former study conducted in 1969. Data on disorders of the neck, shoulder, and hand-wrist disorders were obtained retrospectively for the period 1970-93. RESULTS: Risk factors were found to differ between the sexes. Among women over-time work, high mental workload, and unsatisfactory leisure time were associated with disorders in the neck-shoulder region. Interaction was found between high mental workload and unsatisfactory leisure time. Neck symptoms earlier in life were associated with recurrent disorders. Hand and wrist disorders were associated mainly with physical demands at work. Among men blue collar work and a simultaneous presence of high mental workload and additional domestic workload predicted disorders in the neck-shoulder region. CONCLUSIONS: Factors related and not related to work were associated with disorders of the neck, shoulders, and hands and wrist up to 24 years later in life. These included factors related to working hours which previously have not been noted in this context. Interactions between risk factors both related and not related to work were commonly found.
Subclinical atherosclerosis in scleroderma patients

Objective: To investigate subclinical atherosclerosis in patients with systemic sclerosis (SSc). Methods: Sixty-six patients with SSc who met the American College of Rheumatology criteria for the disease were included. The serum levels of total cholesterol (TC), triglycerides, high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were determined in all patients. Carotid artery intima–media thickness (IMT) and carotid plaques were measured. Patients with a history of atherosclerosis, hypertension, smokers, or patients suffering from conditions that affect the lipid profile, such as diabetes mellitus, hypothyroidism, liver or kidney diseases, Cushing's syndrome, obesity, and a history of familial dyslipidaemia, were excluded. Patients receiving medication affecting lipid metabolism were also excluded from the study. Fifty-one age- and sex-matched non-smoking volunteers were used as controls. Results: Sixty patients were investigated. Six were excluded. Of these, two were smokers, two had diabetes mellitus, one hypothyroidism, and one had hypertension treated with diuretics. Patients with SSc exhibited mild dyslipidaemia expressed mainly by low serum levels of HDL-C and high TC (p < 0.001 and p < 0.021, respectively) compared to controls. In addition, the atherogenic ratio LDL-C/HDL-C was significantly higher among SSc patients (p < 0.0001). Common carotid artery IMTs were higher in SSc compared to controls (0.77 ± 0.2 vs. 0.59 ± 0.14, p < 0.0001). No correlation between IMTs and any SSc features were found. Logistic regression analysis showed an independent association of scleroderma with IMTs and TC. Conclusion: The scleroderma patients exhibited an atherogenic lipid profile and subclinical atherosclerosis and have an increased risk for cardiovascular events.
Predictive Genetic Testing for Alzheimer's Disease: Impact upon Risk Perception

The aim of this study was to determine the impact on risk perceptions of disclosing genetic test results used to estimate the risk of Alzheimer's disease (AD). Adult children (n= 149) of people with AD were randomized to one of two groups—Intervention group: lifetime risk estimates of AD based on age, gender, family history, and Apolipoprotein E (APOE) genotype; Control group: lifetime risk estimates of AD based on the same risk factors excluding APOE genotype. Perceptions of personal risk (PPR) for AD were assessed six weeks after risk assessments. PPR were correlated with actual lifetime risk estimates (r= 0.501; p < 0.0001). After controlling for lifetime risks communicated to participants, age, and number of affected relatives, PPR scores among those with an ɛ4‐positive test result (the test result associated with increased AD susceptibility) (adjusted mean: 3.4 (SD: 0.7)) were not different from the PPR scores in the Control group (adjusted mean: 3.4 (SD: 0.7) (F(1,91)= 1.98; p= 0.162). Again, controlling for lifetime risk estimates, age, and number of affected relatives, the PPR score of those receiving an ɛ4‐negative test result was significantly lower (adjusted mean: 3.1 (SD: 0.8)) than those in the Control group (adjusted mean: 3.4 (SD: 0.7) (F(1,95)= 6.23; p= 0.014). Perceptions of risk of developing AD are influenced by genetic test disclosure in those receiving ɛ4‐negative, but not those receiving ɛ4‐positive test results. Despite the reduced perceptions of risk in the former group, there was no evidence of false reassurance (i.e., perceiving risks as equal to or lower than population risks of AD), although this possibility should be assessed in other testing contexts.
Safety, immunogenicity, and transmissibility in humans of CVD 1203, a live oral Shigella flexneri 2a vaccine candidate attenuated by deletions in aroA and virG

We evaluated the safety and immunogenicity of attenuated Shigella flexneri 2a vaccine candidate CVD 1203, which harbors precise deletions in the plasmid gene virG and in the chromosomal gene aroA. CVD 1203 invades epithelial cells but undergoes minimal intracellular proliferation and cell-to-cell spread. Fasting healthy volunteers, aged 18 to 40 years, were randomly allocated (double-blind design) to receive either CVD 1203 vaccine or placebo, along with sodium bicarbonate buffer, on days 0 and 14, as follows. At the time of the first inoculation, 10 subjects received placebo (group 1) and 22 subjects received either 1.5 x 10(8) (group 2; 11 subjects) or 1.5 x 10(9) (group 3; 11 subjects) CFU of CVD 1203. Fourteen days later, subjects from group 1 received 1.2 x 10(6) CFU of CVD 1203 and subjects from groups 2 and 3 received 1.2 x 10(8) vaccine organisms. Clinical tolerance was dose dependent. After a single dose of CVD 1203 at 10(6), 10(8), or 10(9) CFU, self-limited (<48-h duration) objective reactogenicity (fever, diarrhea, or dysentery) developed in 0, 18, and 72% of subjects, respectively, and in no placebo recipients. CVD 1203 induced immunoglobulin G seroconversion to S. flexneri 2a lipopolysaccharide (LPS) in 30, 45, and 36% of subjects from groups 1, 2, and 3, respectively, and stimulated immunoglobulin A-producing anti-LPS antibody-secreting cells in 60, 91, and 100% of subjects, respectively. After vaccination, significant rises in tumor necrosis factor alpha concentration in serum (groups 1, 2, and 3) and stool (group 2) samples were observed. We conclude that engineered deletions in virG and aroA markedly attenuate wild-type S. flexneri but preserve immunogenicity; however, less reactogenic vaccines are needed.