Miracle-dz/UniFAR-FTUs huggingface dataset:
Ethanol reduces lifespan, body weight, and serum alanine aminotransferase level of aldehyde dehydrogenase 2 knockout mouse.

BACKGROUND The aldehyde dehydrogenase 2 (Aldh2) knockout mouse is an animal model of a polymorphism at the human ALDH2 locus (ALDH2*2). To detect differences in the basic phenotype of this animal model, lifespan, body weight (BW), and serum alanine aminotransferase (ALT) level were evaluated. METHODS Aldh2(+/+) , Aldh2(+/-) , and Aldh2(-/-) mice were maintained, from 10 weeks of age, on standard solid food, with liquid supplied as ethanol (EtOH) solution at a concentration of 0 to 20% (forced EtOH consumption). RESULTS For animals provided with water (without EtOH), mice of the distinct genotypes exhibited no difference in lifespan, with the mean values ranging from 90 to 96 weeks for female mice and 97 to 105 weeks for male mice. For animals provided with EtOH, there was a dose-dependent reduction of lifespan in Aldh2(-/-) mice with p for trend <0.001. For example, the mean lifespans of the Aldh2(-/-) females in the 0, 3, 10, and 20% groups were 95, 85, 70, and 29 weeks, respectively. No influence on lifespan was found for Aldh2(+/+) and Aldh2(+/-) mice. BW and ALT level of Aldh2(-/-) mice were significantly lower than those of Aldh2(+/+) mice when the mice were treated with EtOH. While multiple regression analysis suggested that the BW and ALT level in Aldh2(-/-) mice correlated with lifespan, adjustment for EtOH concentration revealed that this correlation was not significant (i.e., reflected EtOH dependence). CONCLUSIONS Aldh2(-/-) mice were unchanged in terms of their basic phenotype under standard laboratory conditions. However, chronic EtOH administration (forced consumption) in these mice resulted in dose-dependent reductions in lifespan, BW, and serum ALT level.
Factors associated with suboptimal compliance to vaccinations in children in developed countries: a systematic review

ABSTRACT Background: The suboptimal compliance to vaccinations continues to be a major public health problem. Scope: We conducted a systematic review (PubMed and Cochrane databases) to evaluate factors associated with suboptimal compliance to vaccinations, focusing on children and adolescents in developed countries. We categorized studies according to whether they used an analytical statistical approach. Results: We identified 553 potentially relevant articles and evaluated in detail 39 with original data. Factors influencing compliance to vaccinations related to parental-childhood characteristics and healthcare structure-professionals characteristics. Specifically, among the various parental-childhood characteristics studied, non-white race, low socioeconomic status, paying for immunization, lack of health insurance, low parental education, older age of the child, younger maternal age, large family size, late birth order, lack of knowledge about disease and vaccination, negative beliefs/attitudes towards immunization, fear of side-effects/risks/contraindications, not remembering vaccination schedules and appointments, sick child delays, and delayed well child visits were statistically significantly associated with suboptimal compliance. Among healthcare structure-professional characteristics were studied. Skepticism/doubts regarding provided medical information, inadequate support from healthcare providers, lack of available health structures, and problems concerning transportation and accessibility to immunization clinics were statistically significantly associated with suboptimal compliance to vaccination. Conclusion: By recognizing and understanding factors associated with suboptimal compliance to vaccinations we can better approach the risk populations and target our efforts at stressing and reinforcing the vital importance of immunizations. Methods to enhance compliance to vaccinations may include reminder calls/mail notification of parents, initiation of health education programs for parents and health professionals, and open communication and trust between care takers of children and physicians.
Late onset postpartum thrombocytosis in preeclampsia

Background. During pregnancy, changes in blood coagulation and fibrinolysis create a hypercoagulable state. In the puerperium this thrombogenicity is even higher, and the chance of developing thromboembolism is 3-5 times higher in this period than during pregnancy. In preeclampsia, platelets are activated and play a substantial role in the pathogenesis of the disease. Systematic information on longitudinal changes in platelet number and size postpartum after normotensive and preeclamptic pregnancies is not available. Methods. We measured platelet number, mean platelet volume and the median volume of the 20% largest platelets in eleven preeclamptic and eleven normotensive pregnant women matched for mode of delivery. The blood samples were taken antepartum and every 2-3 days in the postpartum period until the platelet count decreased/normalized. Results. In the preeclamptic group, the platelet count increased significantly from 240×10 9 /l antepartum to 621×10 9 /l on day 6-14 postpartum (p<0.01). In the control group, the platelet count increased from 214×10 9 /l antepartum to 251×10 9 /l on day 2-5 (p<0.01) and 351×10 9 /l on day 6-14 postpartum (p<0.01). The platelet count was significantly higher in the preeclamptic than in the control group 6-14 days postpartum (p<0.01). Antepartum, mean platelet volume and the median of the 20% largest platelets were significantly higher in the preeclamptic than in the control group. Conclusion. The platelet count is significantly increased postpartum both after normotensive, and 2-3 fold more after preeclamptic pregnancies. The time to peak values is between 6-14 days, usually at a time when patients are discharged from hospital.
Tegaserod in patients with mechanical sensitivity and overlapping symptoms of functional heartburn and functional dyspepsia

ABSTRACT Background: While functional heartburn (FH) and functional dyspepsia (FD) are recognized clinical entities, symptoms often overlap across both disorders. Despite their frequency, little is known of the underlying pathophysiology of overlapping symptoms. This study evaluated the effect of the 5-HT4 agonist, tegaserod, on visceral sensitivity and symptom improvement in patients with overlapping symptoms of FH and FD. Research design and methods: Patients with overlapping symptoms of FH and FD (ROME II) and mechanical hypersensitivity (Barostat examination) were randomized to tegaserod 6 mg bid or placebo for 2 weeks with treatment crossover after a 2-week washout period. Esophageal and gastric Barostat sensory tests were performed and patients rated their overall symptoms at study end. When carry-over was detected, data were presented for period 1 only. Safety was also assessed. Results: Sixty patients were screened of whom 30 were randomized and 25 completed. Mechanical hypersensitivity was reported by 83% of 47 patients completing esophageal and gastric baseline Barostat examinations. Tegaserod did not significantly alter balloon volume to pain (primary variable); however, pressure to gastric pain increased (p = 0.044 vs. placebo). The severity of heartburn, regurgitation, early fullness, and bloating was significantly lower following tegaserod vs. placebo treatment (p = 0.026, p = 0.021, p = 0.016, and p = 0.030). Overall symptom improvement was reported by 52% tegaserod vs. 32% placebo patients (p = 0.275), and treatment was well tolerated. Conclusions: Results suggest that tegaserod may increase the gastric pain threshold and decrease the severity of individual symptoms in patients with overlapping FH and FD. However, these findings must be considered within the context of the study limitations, including the small number of subjects, potential for and presence of a carry-over effect, along with the impact of Barostat balloon use on the assessment of gastric function.
Individual Consistency in Behavioral State Profiles in Human Fetuses Between 38 and 40 Weeks Gestation

The purpose of this pilot study was to determine the degree of consistency in individual state profiles for 12 normal human fetuses examined on three separate occasions between 38 and 40 weeks gestation. For each fetus, heart rate and eye and gross body movements were monitored continuously for two consecutive 120-min periods on each of 3 days. Fetal behavioral states were assigned using the criteria of Nijhuis et al. [1]. The percent time spent in each behavioral state and in transition and insertion periods was determined for each of the three 4-hr study sessions; a within-subject analysis of variance (ANOVA) was performed to obtain an objective measure of state profile consistency for each fetus. For the study population as a whole, there was a large range in the distribution of the state profile consistency statistic (F): two fetuses exhibited no consistency in their state profiles (F = 2.5, F = 11.2), the within-subject state profiles for three fetuses were virtually identical over the three study se.
Intensive Case Management and Rehospitalization: A Survival Analysis

This study evaluated the efficacy of an intensive-case management program in extending community tenure and reducing rates of rehospitalization for mentally ill outpatients. The study group was composed of 196 individuals with a history of state psychiatric hospitalization. One subgroup of subjects was composed of all clients currently receiving intensive case management (ICM) services (n = 108). A second subgroup, the control group, was made up of randomly selected clients (n = 88) eligible for intensive case management services. Survival analysis models were tested to derive a model that contained the maximum number of significant covariates predictive of community tenure (survival) until rehospitalization. After statistically controlling for these covanates, clients in the control group were 41.2% less likely to be rehospitalized (survival). Clients most at risk of rehospitalization were ICM clients who received shorter intervals of intensive case management; higher levels of services per month; and had experienced brief, frequent prior hospitalizations.
Social isolation rearing increases nucleus accumbens dopamine and norepinephrine responses to acute ethanol in adulthood.

BACKGROUND Early-life stress is associated with increased vulnerability to alcohol addiction. However, the neural substrates linking chronic childhood/adolescent stress and increased risk of alcohol addiction are not well understood. In the nucleus accumbens (NAc), dopamine (DA) and norepinephrine (NE) signaling can be profoundly influenced by stress, anxiety, and drugs of abuse, including ethanol (EtOH). Here, we employed a rodent model of early-life stress that results in enduring increases in behavioral risk factors of alcoholism to gain a better understanding of how chronic adolescent stress may impact the EtOH sensitivity of DA and NE release in the NAc. METHODS Male Long-Evans rats were either group housed (GH; 4 rats/cage) or socially isolated (SI; 1 rat/cage) for 6 weeks beginning on postnatal day 28. SI and GH rats were tested in adulthood for anxiety-like behaviors (elevated plus maze), and the effects of EtOH (1 and 2 g/kg; intraperitoneally.) on NAc DA and NE were assessed by microdialysis. RESULTS SI animals showed increased anxiety-like behavior compared to GH animals. Although SI had no effect on baseline levels of DA or NE, baseline DA levels were positively correlated with anxiety measures. In addition, while no significant differences were observed with 1 g/kg EtOH, the 2 g/kg dose induced significantly greater DA release in SI animals. Moreover, EtOH (2 g/kg) only elevated NAc NE levels in SI rats. CONCLUSIONS These results suggest that chronic early-life stress sensitizes accumbal DA and NE release in response to an acute EtOH challenge. A greater EtOH sensitivity of DA and NE release dynamics in the NAc may contribute to increases in behavioral risk factors of alcoholism, like greater EtOH self-administration, that are observed in SI rats.
Basal anxiety negatively correlates with vulnerability to ethanol-induced behavioral sensitization in DBA/2J mice: modulation by diazepam.

BACKGROUND Anxiety disorders predispose individuals to the development of alcohol dependence in humans. Surprisingly, whether anxiety is a trait influencing the development of alcohol-related behaviors in rodents remains controversial. Here, we addressed the hypothesis of a relationship between basal anxiety levels and the development of ethanol (EtOH)-induced behavioral sensitization (EIBS), a model of neuroadaptations occurring after repeated EtOH exposure which is proposed to play a role in early and recurring steps of addiction. METHODS EtOH-naïve DBA/2J mice were submitted to the elevated plus maze and light/dark box tests to evaluate their basal anxiety levels. Then, mice received daily intraperitoneal injection of saline or 2 g/kg EtOH for 10 days and locomotor activity was immediately monitored. Mice were then split into resistant and sensitized phenotypes based on their increase in locomotion. The relationship between basal anxiety and the development of sensitization was investigated. In addition, we tested the effect of an 8-day-long treatment with 4 mg/kg diazepam, a broad-spectrum benzodiazepine anxiolytic, on the expression of sensitization in both resistant and sensitized mice. RESULTS For the first time, we showed that vulnerability to EIBS is negatively correlated with basal anxiety. Moreover, a diazepam treatment during EIBS procedure increased EtOH-induced hyperlocomotion of resistant mice after 1 week of withdrawal (but not immediately after) without any effect in the group of sensitized mice. CONCLUSIONS This study shows that, in mice, basal anxiety predicts the vulnerability to EIBS. Mice exhibiting low basal anxiety will develop higher EIBS than mice with elevated anxiety levels. Modulation of anxiety by a diazepam treatment during the development of EIBS enhances its expression after 1 week postinduction. Altogether, we demonstrated an inverse relationship between basal anxiety-like behaviors and EIBS vulnerability and that resistance to EIBS vanishes after anxiolytic treatment.
Binge drinking and eating problems in Russian adolescents.

BACKGROUND Binge drinking may be linked to problematic eating behavior, although as yet, little research has been conducted on this association. The objective of this study was to examine the relationship between binge drinking and eating problems in Russian adolescents. METHODS Data were drawn from the Social and Health Assessment, a cross-sectional school-based survey of 6th to 10th grade students (aged 12 to 17 years old) carried out in Arkhangelsk, Russia. Information was collected on various eating problems (worries about weight, feeling fat, excessive eating, fasting and excessive exercise, and purging behaviors) and binge drinking (5 or more drinks in a row). Logistic regression analysis was used to examine the relationship between binge drinking and eating problems. RESULTS Among the 2,488 adolescents included in the statistical analysis, nearly 50% of girls expressed worries about their weight, while 35.0 and 41.5% of adolescent boys and girls reported excessive eating, respectively. The prevalence of purging behaviors (vomiting/using laxatives) was, however, much lower among both sexes (females—2.6%; males—3.3%). In a regression model adjusted for demographic factors and depressive symptoms, among girls, binge drinking was associated with 5 of the 6 eating problems with odds ratios (ORs) ranging from 1.21 (upset about weight gain) to 1.68 (excessive eating). For boys, binge drinking was linked to feeling overweight (OR: 1.47, confidence interval [CI]: 1.20 to 1.81) and vomiting/used laxatives (OR: 4.13, CI: 1.58 to 10.80). CONCLUSIONS Many adolescents in Russia report problematic eating attitudes and behaviors, and eating problems are associated with binge drinking. More research is now needed in this setting to better understand adolescent eating problems and their association with alcohol misuse, so that contextually suitable interventions can be implemented to reduce these behaviors and mitigate their potentially detrimental effects.
Vascular adhesion protein-1 is elevated in primary sclerosing cholangitis, is predictive of clinical outcome and facilitates recruitment of gut-tropic lymphocytes to liver in a substrate-dependent manner

Objective Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of IBD. This clinical association is linked pathologically to the recruitment of mucosal T cells to the liver, via vascular adhesion protein (VAP)-1-dependent enzyme activity. Our aim was to examine the expression, function and enzymatic activation of the ectoenzyme VAP-1 in patients with PSC. Design We examined VAP-1 expression in patients with PSC, correlated levels with clinical characteristics and determined the functional consequences of enzyme activation by specific enzyme substrates on hepatic endothelium. Results The intrahepatic enzyme activity of VAP-1 was elevated in PSC versus immune-mediated disease controls and non-diseased liver (p<0.001). The adhesion of gut-tropic α4β7+lymphocytes to hepatic endothelial cells in vitro under flow was attenuated by 50% following administration of the VAP-1 inhibitor semicarbazide (p<0.01). Of a number of natural VAP-1 substrates tested, cysteamine—which can be secreted by inflamed colonic epithelium and gut bacteria—was the most efficient (yielded the highest enzymatic rate) and efficacious in its ability to induce expression of functional mucosal addressin cell adhesion molecule-1 on hepatic endothelium. In a prospectively evaluated patient cohort with PSC, elevated serum soluble (s)VAP-1 levels predicted poorer transplant-free survival for patients, independently (HR: 3.85, p=0.003) and additively (HR: 2.02, p=0.012) of the presence of liver cirrhosis. Conclusions VAP-1 expression is increased in PSC, facilitates adhesion of gut-tropic lymphocytes to liver endothelium in a substrate-dependent manner, and elevated levels of its circulating form predict clinical outcome in patients.
Behavioral Impulsivity and Risk-Taking Trajectories Across Early Adolescence in Youths With and Without Family Histories of Alcohol and Other Drug Use Disorders.

BACKGROUND Youths with family histories of alcohol and other drug use disorders (FH+) are at increased susceptibility for developing substance use disorders relative to those without such histories (FH-). This vulnerability may be related to impaired adolescent development of impulse control and elevated risk-taking. However, no previous studies have prospectively examined impulse control and risk-taking in FH+ youth across adolescence. METHODS A total of 386 pre-adolescents (305 FH+, 81 FH-; aged 10 to 12) with no histories of regular alcohol or other drug use were compared on behavioral measures of impulsivity including delay discounting, response initiation (Immediate Memory Task), response inhibition impulsivity (GoStop Impulsivity Paradigm), and risk-taking (Balloon Analogue Risk Task-Youth). Youths completed these laboratory tasks every 6 months, allowing for the examination of 10- to 15-year-olds. Hierarchical linear modeling was used to characterize the development of impulse control and risk-taking as shown in performance of these tasks throughout adolescence. RESULTS We found that (i) FH+ youths had increased levels of delay discounting and response inhibition impulsivity at study entry; (ii) regardless of FH status, all youths had relatively stable delay discounting across time, improvements in response inhibition and response initiation impulsivity, and increased risk-taking; and (iii) although FH+ youths had increased response inhibition impulsivity at pre-adolescence, these differences were negligible by mid-adolescence. CONCLUSIONS Heightened delay discounting in FH+ pre-adolescents coupled with normal adolescent increases in risk-taking may contribute to their increased susceptibility toward problem substance use in adolescence.
A cost-effective memory-based real-valued FFT and Hermitian symmetric IFFT processor for DMT-based wire-line transmission systems

This paper presents an efficient computation scheme for the memory-based FFT/IFFT processor used in DMT (discrete multi-tone) systems. Only half-size FFT/IFFT is required to transform real-valued data and Hermitian symmetric data. That is, the cost in processing elements and memory can be reduced by two. Finally, a variable-size radix-4 memory-based FFT/IFFT processor with block scaling scheme is designed for DMT systems.
Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials

Objective Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). Design We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. Results 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments. Conclusions Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib. Trial registration numbers NCT01393626 and NCT01393899.