Miracle-dz/UniFAR-FTUs huggingface dataset:
Diadenosine tetraphosphate (Ap4A) – an E. coli alarmone or a damage metabolite?

Under stress, metabolism is changing: specific up‐ or down‐regulation of proteins and metabolites occurs as well as side effects. Distinguishing specific stress‐signaling metabolites (alarmones) from side products (damage metabolites) is not trivial. One example is diadenosine tetraphosphate (Ap4A) – a side product of aminoacyl‐tRNA synthetases found in all domains of life. The earliest observations suggested that Ap4A serves as an alarmone for heat stress in Escherichia coli. However, despite 50 years of research, the signaling mechanisms associated with Ap4A remain unknown. We defined a set of criteria for distinguishing alarmones from damage metabolites to systematically classify Ap4A. In a nutshell, no indications for a signaling cascade that is triggered by Ap4A were found; rather, we found that Ap4A is efficiently removed in a constitutive, nonregulated manner. Several fold perturbations in Ap4A concentrations have no effect, yet accumulation at very high levels is toxic due to disturbance of zinc homeostasis, and also because Ap4A's structural overlap with ATP can result in spurious binding and inactivation of ATP‐binding proteins. Overall, Ap4A met all criteria for a damage metabolite. While we do not exclude any role in signaling, our results indicate that the damage metabolite option should be considered as the null hypothesis when examining Ap4A and other metabolites whose levels change upon stress.
Children, young people and coeliac disease.

Volume I comprises a review of the literature about children and young people with Coeliac Disease, a common autoimmune disease characterised by an immune response to the protein gluten, found in wheat, barley and rye. It also comprises a qualitative research paper detailing interviews with young people that aimed to tap their lived experiences of the disease. The final part of Volume I comprise a public domain briefing paper summarising both the literature review and research paper. The literature review considers the evidence for problems with adherence to treatment (a lifelong diet free from gluten) for young people with Coeliac Disease as well as psychological effects of having the disease in childhood. Studies of parental views were also included. The results suggested that there is some element of psychological distress associated with having CD in childhood, and that adherence to the treatment appears to be influenced by age and gender. Studies of parents’ views about their child’s Coeliac Disease suggested that parents’ belief in their ability to manage the disease is important to how young children adhere to treatment. The research project describes how 5 children and young people were recruited and interviewed about their experiences of living with Coeliac Disease. The resulting data were analysed using Interpretative Phenomenological Analysis and two themes were subsequently identified. These themes related to identity as a young person with Coeliac Disease and to perceptions about food. Volume II comprises five Clinical Practice Reports: Clinical Practice Report 1 describes the “challenging behaviour” of a 42 year old man with learning disabilities. Subsequently, formulations of this behaviour from a behavioural and a systemic perspective are presented. Clinical Practice Report 2 is a service evaluation conducted in the Heart of Birmingham that aimed to measure outcomes for adults with a learning disability, as well as considering outcomes separately for different ethnic groups. Clinical Practice Report 3 is a case study of a 16 year old girl with anger difficulties using CBT within the Solihull Approach model. Clinical Practice Report 4 describes cognitive-behavioural intervention with a 39-year old man suffering with anxiety as a result of residual psychotic symptoms. Clinical Practice Report 5 was an oral presentation of a piece of clinical work completed with staff at a day hospital for older adults, conducted in order to help the staff adjust in their move to a new location.
Association between dietary habits and body mass index to female students college sciences and arts campus 1 at Khamis Mushayt King Khalid University.

Background: In the Kingdom of Saudi Arabia (KSA), recent studies revealed increasing consumption of animal products and refined foods in the diet at the expense of vegetables and fruits. These dietary changes were accused of increasing the prevalence of both overweight and obesity observed among Saudi children, adolescences and adults in the last few decades. Objectives: The present study was a cross sectional study aimed at exploring the BMI distribution among students of college of Sciences and Arts for girls Khamis Mushayt Campus 1 at King Khalid University (KKU) and investigated how Dietary habits of students female affected body mass index (BMI). Methods: A total of 240 female students aged 18 - 22 years were about 25% from total students randomly chosen from college of Arts and Science Campus 1 at Khamis Mushayt, King Khalid University, KSA for the present study. A self-reported questionnaire about the student’s dietary habits was conducted and their body mass index (BMI) was measured. Data were analyzed using SPSS statistical software and Chi-square test conducted for variables. Results: About half of the students (47%) were within normal weight, 27.4% were under weight, 16% were overweight and 9.6% were categorized obese. The majority of the students reported eating meals with their family while more than half of sample (58.7%) had eating meals during watching TV. It was worth mentioning that 84.5% of students reported eating snacks such as chocolate and chips 3 or more times per week. There were no significant differences between BMI category and dietary habits. Conclusion and Recommendations: There were no significant difference between body mass index category and dietary habits. Increasing educational programs introduced healthy dietary concepts to improve the dietary habits of female students.
The Prevalence of UTI Pathogens in Urine Specimen Obtained from a Hospital in Rivers State Nigeria

The incidence of urinary tract infections was carried out on patients attending a general hospital in Rivers State, Nigeria. One hundred and fifty urine specimens were collected in 2014, from the 150 specimen 52 were from males and 98 from females. The study was carried out to determine the current status of UTI among patients attending the hospital. Mid-stream urine specimen were collected in sterile universal bottles and analyzed. Urine specimen were examined macroscopically and Combi 9 urinalysis strip was dipped into the urine specimen to check the pH, glucose level and other chemical composition. Each urine sample was streaked onto prepared sterile CLED plates and incubated at 37°C for 24 hours. Results obtained showed that 34.6% of the male specimens were positive and 55.1% were positive from the female specimen. The occurrence of UTI with respect to isolated pathogen showed that Klebsiella sp was the highest occurring followed by E.coli while in both sexes S. aureus was the highest occurring pathogen. The least occurring pathogen was Streptococcus sp 4(4.8%) followed by Candida albicans 3(3.6%). Candida albicans was not found in the male subjects. The highest rate of infection was recorded in patients between the ages of 34-35 and the least was recorded in patients above 46 years. The prevalence of UTI recorded in female subjects was 77.4% and 22.6% in male subjects. UTI has been on the increase, it is recommended that awareness on UTI, factors leading to UTI, prevention and treatment should be increased to reduce the high rate of occurrence.
Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy

Background We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). Methods The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance. Results The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = -0.352 and P < .001 at baseline and r = -0.387 and P = .008 longitudinally) but not with neuropsychological performance. Conclusion The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection.
Risk of fever after pediatric trivalent inactivated influenza vaccine and 13-valent pneumococcal conjugate vaccine.

IMPORTANCE An observational study found an increased risk of febrile seizure on the day of or 1 day after vaccination (days 0-1) with trivalent inactivated influenza vaccine (TIV) in the 2010-2011 season; risk was highest with simultaneous vaccination with TIV and 13-valent pneumococcal vaccine (PCV13) in children who were 6 to 23 months old. Text messaging is a novel method for surveillance of adverse events after immunization that has not been used for hypothesis-driven vaccine safety research. OBJECTIVE To prospectively evaluate whether children receiving TIV and PCV13 simultaneously had higher rates of fever on days 0 to 1 than those receiving either product without the other. DESIGN, SETTING, AND PARTICIPANTS Prospective observational cohort study of parents of children 6 to 23 months old recruited from 3 medical center-affiliated clinics in New York City from November 1, 2011, through April 5, 2012. A total of 530 of 614 eligible participants (86.3%) were enrolled. Parents were texted on the night of vaccination (day 0) and the 7 subsequent nights (days 1-7) to report their child's temperature. We used log-binomial regression to calculate adjusted relative risks (aRRs) and excess risk for fever on days 0 to 1, adjusted for age group, past influenza vaccination and simultaneous receipt of selected inactivated vaccines. EXPOSURES Receipt of TIV and/or PCV13. MAIN OUTCOME(S) AND MEASURE(S) Temperature of 38°C or higher on days 0 to 1 after vaccination. RESULTS On days 0 to 1, children receiving TIV and PCV13 simultaneously had higher rates (37.6%) of fever (temperature ≥38°C) than those receiving TIV (7.5%; aRR, 2.69; 95% CI, 1.30-5.60) or PCV13 (9.5%; aRR, 2.67; 95% CI, 1.25-5.66). The excess risk of fever after TIV and PCV13 was 20 and 23 per 100 vaccinations compared with TIV without PCV13 and PCV13 without TIV, respectively. Fever rates for days 2 to 7 were similar across groups. For days 0 to 1, 74.8% of the text messages were confirmed delivered; for another 9.0%, delivery status was unknown. Response rates were 95.1% and 90.9% for days 0 and 1 for confirmed delivered messages, respectively. CONCLUSIONS AND RELEVANCE Simultaneous TIV and PCV13 administration was associated with higher transient increased fever risk than administration of either vaccine without the other product. Text messaging to prospectively assess a specific vaccine adverse event has potential for enhancing prelicensure and postlicensure monitoring of adverse events after immunization and deserves further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01467934.
Sestrin2 facilitates glutamine‐dependent transcription of PGC‐1α and survival of liver cancer cells under glucose limitation

Differential utilization of metabolites and metabolic plasticity can confer adaptation to cancer cells under metabolic stress. Glutamine is one of the vital and versatile nutrients that cancer cells consume avidly for their proliferation, and therefore mechanisms related to glutamine metabolism have been identified as targets. Recently, sestrin2 (SESN2), a stress‐inducible protein, has been reported to regulate survival in glutamine‐depleted cancer cells; based on this, we explored if SESN2 could regulate glutamine metabolism during glucose starvation. This report highlights the role of SESN2 in the regulation of glutamine‐dependent activation of the mitochondrial biogenesis marker peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) under glucose scarcity in liver cancer cells (HepG2). We demonstrate that down‐regulation of SESN2 induces a decrease in the levels of intracellular glutamine and PGC‐1α under glucose deprivation, concomitant with a decline in cell survival, but no effect was observed on the invasive or migration potential of the cells. Under similar metabolic conditions, SESN2 forms a complex with c‐Jun N‐terminal kinase (JNK) and forkhead box protein O1 (FOXO1). Absence of SESN2 or inhibition of JNK reduces nuclear translocation of FOXO1, consequently causing transcriptional inhibition of PGC‐1α. Notably, our observations demonstrate a reduction in cell viability under high glutamine and low glucose conditions during SESN2 down‐regulation that could be rescued on JNK inhibition. To recover from acetaminophen‐induced mitochondrial damage, SESN2 was crucial for glutamine‐mediated activation of PGC‐1α in HepG2 cells. Collectively, we demonstrate a novel role of SESN2 in mediating activation of PGC‐1α by modulating glutamine metabolism that facilitates cancer cell survival under glucose‐limited metabolic conditions.
Nottingham study of sexuality & ageing (NoSSA I). Attitudes regarding sexuality and older people: a review of the literature

Abstract Attitudes regarding sexuality and older people is a relatively under-researched area, despite its topical relevance as people live longer, remain healthy, and are better educated and well informed. The first part of the literature review examines the attitudes different age groups have about sexuality and old people. The second part describes the existing literature, which has investigated the attitudes of health professionals, in particular doctors and nurses. The last part discusses current knowledge regarding attitudes of staff from nursing and residential homes regarding sexuality and old age.
Assessment of Metabolic Syndrome in a sample of Central and South Americans living in the Washington, D.C. area

Title of Document: Assessment of Metabolic Syndrome in a sample of Central and South Americans living in the Washington, D.C. area Regina Marie Gill Master of Science 2010 Directed By: Robert T. Jackson, Ph.D., R.D. Professor Department of Nutrition and Food Science The Central/South American population is growing rapidly in the U.S., but little is known about the health status. The purpose of this study was 1) to estimate the prevalence of MS and its individual components, 2) compare risk factors among Hispanic sub-groups, and 3) examine how metabolic syndrome (MS) prevalence estimates have changed from 1993-1994 to 2008-2009 in a sample of Central/South Americans living in the D.C. area. In this cross-sectional, medical recor d xtraction survey, data from 1993-1994 were compared with data from 2008-2009 on 1,042 male and female adults collected by questionnaire. 28% of our subjects had MS. The most prevalent MS components were low HDL (43.2% men; 50.7% women), elevated triglycerides (37%), and high BMI ≥ 25 kg/m (75.6%). Among Central/South Americans, Salvadorans had the highest prevalence of MS (30.7%). MS prevalence was significantly greater for the 2008-2009 subjects (27.9%) compared with 1993-1994 subjects (19.7%) ( p ≤ 0.05).
Risk factors for peripherally inserted central venous catheter complications in children.

IMPORTANCE Peripherally inserted central venous catheters (PICCs) are prone to infectious, thrombotic, and mechanical complications. These complications are associated with morbidity, so data are needed to inform quality improvement efforts. OBJECTIVES To characterize the epidemiology of and to identify risk factors for complications necessitating removal of PICCs in children. DESIGN Cohort study. SETTING Johns Hopkins Children's Center, Baltimore, Maryland. PARTICIPANTS Hospitalized children who had a PICC inserted outside of the neonatal intensive care unit (ICU) from January 1, 2003, through December 31, 2009. MAIN OUTCOME MEASURES Complications necessitating PICC removal as recorded by the PICC Team. RESULTS During the study period, 2574 PICCs were placed in 1807 children. Complications necessitating catheter removal occurred in 534 PICCs (20.8%) during 46 021 catheter-days (11.6 complications per 1000 catheter-days). These included accidental dislodgement (4.6%), infection (4.3%), occlusion (3.7%), local infiltration (3.0%), leakage (1.5%), breakage (1.4%), phlebitis (1.2%), and thrombosis (0.5%). From 2003 to 2009, complications decreased by 15% per year (incidence rate ratio [IRR], 0.85; 95% CI, 0.81-0.89). In adjusted analysis, all noncentral PICC tip locations-midline (IRR 4.59, 95% CI, 3.69-5.69), midclavicular (2.15; 1.54-2.98), and other (3.26; 1.72-6.15)-compared with central tip location were associated with an increased risk of complications. Pediatric ICU exposure and age younger than 1 year were independently associated with complications necessitating PICC removal. CONCLUSIONS AND RELEVANCE Noncentral PICC tip locations, younger age, and pediatric ICU exposure were independent risk factors for complications necessitating PICC removal. Despite reductions in PICC complications, further efforts are needed to prevent PICC-associated complications in children.
Genetic variation in oxytocin rs2740210 and early adversity associated with postpartum depression and breastfeeding duration

Mothers vary in duration of breastfeeding. These individual differences are related to a variety of demographic and individual maternal factors including maternal hormones, mood and early experiences. However, little is known about the role of genetic factors. We studied single‐nucleotide polymorphisms (SNPs) in the OXT peptide gene (rs2740210; rs4813627) and the OXT receptor gene (OXTR rs237885) in two samples of mothers from the Maternal adversity, Vulnerability and Neurodevelopment study (MAVAN), a multicenter (Hamilton and Montreal, Canada) study following mothers and their children from pregnancy until 7 years of age. Data from the Hamilton site was the primary sample (n = 201) and data from Montreal was the replication sample (n = 151). Breastfeeding duration, maternal mood (measured by the CES‐D scale) and early life adversity (measured by the CTQ scale) were established during 12 months postpartum. In our primary sample, polymorphisms in OXT rs2740210, but not the other SNPs, interacted with early life adversity to predict variation in breastfeeding duration (overall F8,125 = 2.361, P = 0.021; interaction effect b = −8.12, t = −2.3, P = 0.023) and depression (overall F8,118 = 5.751, P ≤ 0.001; interaction effect b = 6.06, t = 3.13, P = 0.002). A moderated mediation model showed that higher levels of depression mediated the inverse relation of high levels of early life adversity to breastfeeding duration, but only in women possessing the CC genotype [effect a′ = −3.3401, 95% confidence interval (CI) = −7.9466 to −0.0015] of the OXT SNP and not in women with the AA/AC genotype (a′ = −1.2942, ns). The latter findings (moderated mediation model) were replicated in our Montreal sample (a′ = −0.277, 95% CI = −0.7987 to −0.0348 for CC; a′ = −0.1820, ns for AA/AC).
Morphine intake and the effects of naltrexone and buprenorphine on the acquisition of methamphetamine intake

Some common genetic factors appear to influence risk for drug dependence across multiple drugs of abuse. In previous research, mice that were selectively bred for higher amounts of methamphetamine consumption, using a two‐bottle choice methamphetamine drinking procedure, were found to be less sensitive to the locomotor stimulant effects of morphine and of the more selective μ‐opioid receptor agonist fentanyl, compared to mice that were bred for low methamphetamine consumption. This suggested that μ‐opioid receptor‐mediated pathways may influence genetic risk for methamphetamine consumption. We hypothesized that these differences in opioid sensitivity would impact opioid intake in the methamphetamine drinking lines and that drugs with μ‐opioid receptor activity would impact methamphetamine intake. Consumption of morphine was examined in 2, two‐bottle choice studies, one that compared morphine to quinine consumption and another that used a saccharin fading procedure. Next, naltrexone (0, 0.5, 1, 2, 5, 10 and 20 mg/kg), a μ‐opioid receptor antagonist, and buprenorphine (0, 1, 2 or 4 mg/kg), a μ‐opioid receptor partial agonist, were each examined for their effects on the acquisition of methamphetamine consumption. Low methamphetamine drinking mice consumed more morphine compared to high methamphetamine drinking mice. Naltrexone did not alter methamphetamine consumption in either selected line; however, buprenorphine reduced methamphetamine intake in the high methamphetamine drinking line. These data show that greater sensitivity to opioids is associated with greater opioid intake and warrant further investigation of drugs with μ‐opioid receptor‐specific agonist activity in genetically determined differences in methamphetamine consumption.
Plasma MicroRNA Levels Are Associated With Hepatitis B e Antigen Status and Treatment Response in Chronic Hepatitis B Patients

Background Hepatitis B virus (HBV) modulates microRNA (miRNA) expression to support viral replication. The aim of this study was to identify miRNAs associated with hepatitis B e antigen (HBeAg) status and response to antiviral therapy in patients with chronic hepatitis B (CHB) , and to assess if these miRNAs are actively secreted by hepatoma cells. Methods Plasma miRNA levels were measured by reverse-transcription quantitative polymerase chain reaction in healthy controls (n = 10) and pretreatment samples of an identification cohort (n = 24) and a confirmation cohort (n = 64) of CHB patients treated with peginterferon/nucleotide analogue combination therapy. Levels of HBV-associated miRNAs were measured in cells, extracellular vesicles, and hepatitis B surface antigen (HBsAg) particles of hepatoma cell lines. Results HBeAg-positive patients had higher plasma levels of miR-122-5p, miR-125b-5p, miR-192-5p, miR-193b-3p, and miR-194-5p compared to HBeAg-negative patients, and levels of these miRNAs were associated with HBV DNA and HBsAg levels. Pretreatment plasma levels of miR-301a-3p and miR-145-5p were higher in responders (combined response or HBsAg loss) compared to nonresponders. miR-192-5p, miR-193b-3p, and miR-194-5p were present in extracellular vesicles and HBsAg particles derived from hepatoma cells. Conclusions We identified miRNAs that are associated with HBeAg status, levels of HBV DNA and HBsAg, and treatment response in CHB patients. We demonstrated that several of these miRNAs are present in extracellular vesicles and HBsAg particles secreted by hepatoma cells.