Miracle-dz/UniFAR-FTUs huggingface dataset:
Transfer RNA instability as a stress response in Escherichia coli: Rapid dynamics of the tRNA pool as a function of demand

ABSTRACT Production of the translation apparatus of E. coli is carefully matched to the demand for protein synthesis posed by a given growth condition. For example, the fraction of RNA polymerases that transcribe rRNA and tRNA drops from 80% during rapid growth to 24% within minutes of a sudden amino acid starvation. We recently reported in Nucleic Acids Research that the tRNA pool is more dynamically regulated than previously thought. In addition to the regulation at the level of synthesis, we found that tRNAs are subject to demand-based regulation at the level of their degradation. In this point-of-view article we address the question of why this phenomenon has not previously been described. We also present data that expands on the mechanism of tRNA degradation, and we discuss the possible implications of tRNA instability for the ability of E. coli to cope with stresses that affect the translation process.
Does metabolic syndrome impair sexual function in middle- to old-aged women?

INTRODUCTION To date, there are few studies dealing with the impact of metabolic syndrome (MS) on female sexual function, and the association between MS and female sexual dysfunction (FSD) in middle- to old-aged women remains unclear. AIM To evaluate the impact of MS on sexual function in middle- to old-aged women. METHODS From May 2009 to January 2010, we performed a cross-sectional study of sexually active women (≥ 40 years old) who visited a health-screening clinic. Comprehensive history taking, anthropometric measurement, laboratory testing, and questionnaire administration were performed for each of the total 773 women enrolled. MAIN OUTCOME MEASURES The Female Sexual Function Index (FSFI) was used to assess the key dimensions of female sexual function. RESULTS The median age of enrolled subjects was 48 (40-65) years, and the rates of MS and FSD were 12.2% (94/773) and 54.7% (423/773), respectively. We found that the demographics of women with and without MS (P < 0.05) differed significantly from one another in terms of age, menopausal status, body mass index, educational status, household income, and urinary incontinence (UI) symptoms, although their frequency of FSD was similar (52.1% vs. 55.1%). After adjusting clinical confounders, we found that only the pain domain score was significantly different between women with MS and without MS, while the total FSFI score and other constituent domain scores showed little difference between the two groups. However, in the multivariate logistic regression model, MS and most of its components were not associated with FSD; only age, menopausal status, smoking, depression, and symptomatic UI proved to be independent risk factors for FSD (P < 0.05). CONCLUSIONS Our study suggests that MS may have little impact on sexual function in middle- to old-aged women. Further studies with population-based and longitudinal design should be conducted to confirm this finding.
The Psychological, Social, and Economic Impact of Illness Among Patients with Recurrent Cancer

This longitudinal study examined the psychological, social, and economic impact of recurrent cancer and its treatment on an initial sample of 268 patients. Structured interviews were conducted at the initiation of palliative radiation therapy and four and eight months later (n = 161 at final follow-up). Data were obtained on health status, psychological functioning, personality attributes, social support, health care utilization, and finances. Except for medical transportation, most of the patients' concrete needs did not change over time. Economic issues independently predicted psychological outcomes. Patients' perceived stress, role restriction, self-esteem, and total symptoms dccrcased over time, whereas their dispositional pessimism increased.
Chronic administration of udenafil, a selective phosphodiesterase type 5 inhibitor, promotes erectile function recovery in an animal model of bilateral cavernous nerve crush injury.

INTRODUCTION Preservation of the cavernous nerves (CNs) during radical prostatectomy is crucial for the patient's erectile function. Despite advances in operative technique, the majority of men report compromised erectile function postprostatectomy or complete loss of potency due to CN trauma even with nerve-sparing modifications. AIM This study was designed to investigate whether repeated dosing of udenafil, a phosphodiesterase type 5 inhibitor, helps to improve erectile function after CN injury. METHODS Using the CN crush injury model, 8-week-old male Sprague Dawley rats were divided into the following groups; sham-operated group, bilateral CN crush injury exposed to either no udenafil (vehicle) or udenafil (5, 20 mg/kg) daily for two different durations (4 and 8 weeks, p.o.). MAIN OUTCOME MEASURES At both time points, CN electrical stimulation was used to assess erectile function by measuring the intracavernous pressure. The expressions of hypoxia-inducible factor 1-alpha (HIF-1α), transforming growth factor-beta (TGF-β1), nerve growth factor (NGF), endothelin B receptor (ET(B) ), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and sonic hedgehog homolog (SHH) in penile tissue were examined. Immunohistochemical antibody staining was performed for NGF, eNOS, nNOS, CD31, and alpha-smooth muscle actin (α-SMA). Additionally, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay was performed to quantify apoptosis and the tissue slides were stained for Masson's trichrome to assess the smooth muscle/collagen ratio. RESULTS Udenafil improved erectile function in a dose- and time-dependent manner with the maximum erectile function recovery achieved by 20 mg/kg udenafil at an 8-week time point. CN injury increased the expression of HIF-1α, TGF-β1, NGF, and ET(B) , however, decreased the expression of eNOS, nNOS, and SHH. Udenafil significantly suppressed these alterations. The results from the histological analyses show that udenafil markedly reduces apoptosis induced by CN injury and augments the smooth muscle/collagen ratio. CONCLUSIONS CN injury induces significantly impaired erectile function and altered gene/protein expression. Chronic administration of udenafil preserves erectile function and has a beneficial role against the pathophysiological consequences of CN injury.
Functional cortical and subcortical abnormalities in pedophilia: a combined study using a choice reaction time task and fMRI.

INTRODUCTION Pedophiles show sexual interest in prepubescent children but not in adults. Research into the neurofunctional mechanisms of paraphilias has gathered momentum over the last years. AIM To elucidate the underlying neural processing of sexual interest among pedophiles and to highlight the differences in comparison with nonparaphilic sexual interest in adults. METHODS Nine pedophilic patients and 11 nonpedophilic control subjects underwent functional magnetic resonance imaging (fMRI) while viewing pictures of nude (prepubescents, pubescents, and adults) and neutral content, as well as performing a concomitant choice reaction time task (CRTT). MAIN OUTCOME MEASURES Brain blood oxygen level-dependent (BOLD) signals and response latencies in the CRTT during exposure to each picture category. RESULTS Analysis of behavioral data showed group differences in reaction times regarding prepubescent and adult but not pubescent stimuli. During stimulation with pictures displaying nude prepubescents, pedophiles showed increased BOLD response in brain areas known to be involved in processing of visual sexual stimuli. Comparison of pedophilic patients with the control group discovered differences in BOLD responses with respect to prepubescent and adult but not to pubescent stimuli. Differential effects in particular occurred in the cingulate gyrus and insular region. CONCLUSIONS The brain response of pedophiles to visual sexual stimulation by images of nude prepubescents is comparable with previously described neural patterns of sexual processing in nonpedophilic human males evoked by visual stimuli depicting nude adults. Nevertheless, group differences found in the cingulate gyrus and the insular region suggest an important role of these brain areas in pedophilic sexual interest. Furthermore, combining attention-based methods like CRTT with fMRI may be a viable option for future diagnostic procedures regarding pedophilia.
Protective Effect of Ethanolic Extract of Seeds of Moringa oleifera Lam. Against Inflammation Associated with Development of Arthritis in Rats

The present investigation was carried out to study the anti-arthritic activity of ethanolic extract of seeds of Moringa oleifera Lam. (MOEE) in adjuvant-induced arthritis in adult female Wistar rats. During the experimental period, body weight, paw edema volume (primary lesion) and arthritic index (secondary lesion) was observed. On the 21st day, serum from each animal was used for estimation of Rheumatoid Factor (RF) value and levels of selected cytokines (TNFα, IL-1, and IL-6). Whole blood was used for measurement of erythrocyte sedimentation rate (ESR). Liver homogenate was utilized for assessment of oxidative stress and histopathology was performed to measure degree of inflammation in synovial joint. Our results suggest that, percentage reduction in body weight was less, paw edema volume and arthritic index score was decreased significantly as compared to diseased control animals. Serum levels of RF, TNF-α, IL-1, and IL-6 also showed decreased levels as compared to those in the diseased control group. Treatment with MOEE also altered oxidative stress in relation to its anti-inflammatory activity. Histopathological observations showed mild or less infiltration of lymphocytes, angiogenesis and synovial lining thickening. From all above results and observations, it can be concluded that Moringa oleifera possesses promising antiarthritic property.
Trichloroethylene Alters Central and Peripheral Immune Function in Autoimmune-Prone MRL+/+ Mice Following Continuous Developmental and Early Life Exposure

Trichloroethylene (TCE) is a widespread environmental toxicant known to promote CD4+ T-lymphocyte activation, IFNγ production, and autoimmunity in adult MRL+/+ mice. Because developing tissues may be more sensitive to toxicant exposure, it was hypothesized that continuous TCE exposure beginning at conception might induce even more pronounced CD4+ T-lymphocyte effects and exacerbate the development of autoimmunity in MRL+/+ mice. In the current study, MRL+/+ mice were exposed to occupationally-relevant doses of TCE from conception until adulthood (i.e., 7–8 wk-of-age). The CD4+ T-lymphocyte effects in the thymus and periphery were evaluated, as well as serum antibody levels. TCE exposure altered the number of thymocyte subsets, and reduced the capacity of the most immature CD4−/CD8− thymocytes to undergo apoptosis in vitro. In the periphery, T-lymphocyte IFNγ production was monitored in the blood prior to sacrifice by intracellular cytokine staining and flow cytometry. TCE induced a dose-dependent increase in T-lymphocyte IFNγ as early as 4–5-week-of-age. However, these effects were transient, and not observed in splenic T-lymphocytes in 7–8-week-old mice. In contrast, the serum levels of anti-histone autoantibodies and total IgG2a were significantly elevated in the TCE-exposed offspring. The data illustrated that occupationally-relevant doses of TCE administered throughout development until adulthood affected central and peripheral immune function in association with early signs of autoimmunity. Future studies will address the possibility that early-life exposure to TCE may alter some aspect of self tolerance in the thymus, leading to autoimmune disease later in life.
Mental health care clusters and payment by results: considerations for social inclusion and recovery

Purpose – This paper aims to critically examine the emerging policy agenda of payment by results (PbR) and care clusters in order to identify how to engage with it to ensure it is supportive of social inclusion and recovery.Design/methodology/approach – Care clusters and PbR for mental health care are critically examined.Findings – There is scope in the ongoing development of care clusters and associated pathways to continue the progressive developments towards recovery and social inclusion in the commissioning and delivery of mental health care, but they need to be nurtured and actively pursued.Practical implications – The care clusters and developments building on them provide scope for supporting social inclusion and recovery practice, but also some risks; hence, those with an interest in furthering such practice need to engage now locally and nationally with care clusters developments.Originality/value – PbR is being pursued as a policy for commissioning mental health care in England, based on a model.
Improving the Educational Experience for International Clinical Nurse Specialist Students, Part III: Using Culturally Sensitive Teaching Strategies

This column completes the current series, 1,2 addressing ways to improve the educational experience for international clinical nurse specialist (CNS) students. As noted in the earlier columns, acculturative stress is defined as stress caused by the process of adaptation that accompanies ‘‘a change of cultural environment. ’’ Acculturative stressors are multifactorial and common among students living and studying in a foreign country. Understanding the cultural norms and cultural values specific to the students in your institution can help faculty teach in a more culturally sensitive manner to promote an optimal learning environment for students from other nations. Part 1 of this series discussed the challenges that international students need to overcome when applying to and attending nursing programs in the United States. Last month’s column explored cultural differences in communication from a conceptual and theoretical perspective and identified organizational strategies to improve the student experience at the school and campus level. This month’s column will present classroom and clinical strategies that faculty, and hospital educators, can use to decrease acculturative stress and assist international students to adjust to learning in a different cultural environment.
Pancreatitis in the dog:. dealing with a spectrum of disease

PANCREATITIS - whether it be acute or chronic - is a relatively common, but often misdiagnosed, problem in dogs. It is associated with a systemic inflammatory response which, in severe cases, can result in the development of multiorgan failure, diffuse intravascular coagulation and death. Classical acute pancreatitis is often straightforward to diagnose, but this only represents one end of a wide spectrum of disease. Milder and/or more chronic forms of the condition are not so easily recognised, but can cause significant pain and reduce the quality of life of an animal. There is no single diagnostic test with 100 per cent sensitivity and specificity for the disease, apart from biopsy which is relatively invasive and, hence, not often indicated. Treatment recommendations depend on the severity of the disease and range from conservative management at home to referral for intensive care. The causes of pancreatitis in dogs are usually unknown. Therefore, therapy tends to be symptomatic and non-specific. The potential long-term sequelae of chronic pancreatitis in dogs are largely uninvestigated, but can include the development of diabetes mellitus and/or exocrine pancreatic insufficiency. This article discusses the potential causes, diagnosis and treatment of acute and chronic pancreatitis in dogs.
Changes in Provider Perceptions of Family Presence During Resuscitation

Purpose/Objectives: The purpose of this study was to measure changes in perceptions of healthcare providers (HCPs) in the cardiac intensive care unit (CICU) before and after an implementation of an educational program that included approval of a unit-based guideline for family presence (FP) during resuscitation and invasive procedures. Design: A descriptive pretest and posttest design was used to measure changes in perception for FP during resuscitation and invasive procedures. Setting: The setting for this study was a CICU of a large academic medical center. Sample: A convenient sample of HCPs who work in a CICU was included in this study. Methods: Healthcare providers completed the FP scales for confidence and risk-benefit for resuscitation and invasive procedure before and after the implementation of an FP educational program. The program included presentations, discussions, and collaborative guideline development approval with CICU HCPs. Findings: There were 43 HCPs before and 40 HCPs after the FP educational program who completed the FP Confidence and Risk-Benefit Scales. There was improvement in FP Risk Benefit Scale for resuscitation (P < .01), although there was no change in the invasive procedure scale. There was no significant change in confidence for FP for resuscitation or invasive procedures, although there was a trend toward improved scores. There was a significant increase in the number of family members present during resuscitation after the educational program (P < .02). Implications: The conduct of FP educational program and the approval of a unit-based guideline improved HCPs’ perception of risk and benefit of FP during resuscitation and the actual presence of family during resuscitation. This effort provided the infrastructure for FP in the CICU and support for further FP efforts.
Re‐evaluation of hepatitis B virus clinical phases by systems biology identifies unappreciated roles for the innate immune response and B cells

To identify immunological mechanisms that govern distinct clinical phases of a chronic hepatitis B virus (HBV) infection—immune tolerant (IT), immune active (IA), inactive carrier (IC), and hepatitis B e antigen (HBeAg)‐negative (ENEG) hepatitis phases—we performed a systems biology study. Serum samples from untreated chronic HBV patients (n = 71) were used for multiplex cytokine measurements, quantitative hepatitis B surface antigen (HBsAg), HBeAg levels, HBV genotype, and mutant analysis. Leukocytes were phenotyped using multicolor flow cytometry, and whole‐blood transcriptome profiles were generated. The latter were compared with liver biopsy transcriptomes from IA (n = 16) and IT (n = 3) patients. HBV viral load as well as HBeAg and HBsAg levels (P < 0.001), but not leukocyte composition, differed significantly between distinct phases. Serum macrophage chemotactic protein 1, interleukin‐12p40, interferon (IFN)‐gamma‐inducible protein 10, and macrophage inflammatory protein 1 beta levels were different between two or more clinical phases (P < 0.05). Comparison of blood transcriptomes identified 64 differentially expressed genes. The gene signature distinguishing IA from IT and IC patients was predominantly composed of highly up‐regulated immunoglobulin‐encoding genes. Modular repertoire analysis using gene sets clustered according to similar expression patterns corroborated the abundant expression of B‐cell function‐related genes in IA patients and pointed toward increased (ISG) transcript levels in IT patients, compared to subsequent phases. Natural killer cell activities were clustered in clinical phases with biochemical liver damage (IA and ENEG phases), whereas T‐cell activities were higher in all phases, compared to IT patients. B‐cell‐related transcripts proved to be higher in biopsies from IA versus IT patients. Conclusion: HBV clinical phases are characterized by distinct blood gene signatures. Innate IFN and B‐cell responses are highly active during the IT and IA phases, respectively. This suggests that the presumed immune tolerance in chronic HBV infections needs to be redefined. (Hepatology 2015;62:87‐100)
Mercury modulates interplay between IL-1β, TNF-α, and gap junctional intercellular communication in keratinocytes: mitigation by lycopene

Gap junctional intercellular communication (GJIC) is used to control cell proliferation. It is not surprising then that a lack of GJIC (i.e., during loss of contact inhibition among adjacent cells) is associated with cancer promotion/progression. There also seems to be a link between ineffective GJIC and increases in inflammatory events. Interestingly, many cytokines released during an inflammatory response also have critical roles in cancer cell survival. Specifically, TNFα and IL-1β are important for initiating/augmenting CD8+- and NK-cell mediated killing; however, in what appears counterintuitive, each—at times—can act to protect cancer cells against apoptosis, a major mechanism for cell killing from within. It is thus plausible to assume that certain toxicants might act as cancer promoters in manners distinct from/augmentive of direct effects on DNA, i.e., by concurrently altering GJIC and cytokine formation in host or microenvironment of a cancer cell. Our research has evaluated effects of many toxicants upon keratinocytes; in particular, we have examined effects of mercury on GJIC and on TNFα and IL-1β levels in (and secretion by) these cells. In the studies here, a tomato preparation (i.e., an oleoresin) bearing the antioxidant carotenoid lycopene was examined for its effects on GJIC and cytokine formation by keratinocytes in general, and its potential ability to mitigate/reverse the toxic effects of mercury in the cells in particular. It was shown that a 4-hr treatment with the oleoresin (containing 56, 6 nM lycopene) re-established GJIC among—and increased the formation of IL-1β and TNFα that had been significantly reduced within—keratinocytes that had been pre-treated for 24 hr with 10 nM HgCl2. These results show that effects of mercury likely depend on some level of oxidative stress and that its potential effects on keratinocyte GJIC and cytokine concentrations could, in an exposed host, be mitigated/reversed by increased dietary intake of carotenoids like lycopene.
Ledipasvir‐sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens

Patients who fail to achieve sustained virological response (SVR) after treatment with sofosbuvir (SOF) plus ribavirin (RBV) with or without pegylated interferon (Peg‐IFN) do not have established retreatment options. We conducted an open‐label trial to assess the efficacy and safety of ledipasvir (LDV)‐SOF plus RBV in patients with genotype 1 hepatitis C virus (HCV) who did not achieve SVR after treatment in phase II and III trials of SOF regimens. We enrolled 51 patients at 24 sites in the United States. All patients received the fixed‐dose combination tablet of LDV‐SOF once‐daily plus weight‐based RBV (1,000 or 1,200 mg/day) for 12 weeks. The efficacy endpoint was the proportion of patients with SVR 12 weeks after discontinuation of therapy (SVR12). Of the 51 patients enrolled, 25 (49%) had previously received SOF plus Peg‐IFN‐RBV, 20 (39%) had received SOF‐RBV, 5 (10%) had received SOF placebo plus Peg‐IFN‐RBV, and 1 (2%) received GS‐0938 monotherapy. Fourteen (27%) had compensated cirrhosis at baseline, and 47 (92%) had non‐CC interleukin‐28B genotypes. SVR12 was achieved by 50 of the 51 patients (98%) treated. Among the 45 patients who received SOF in earlier treatment, 44 (98%) achieved SVR12. The only patient who did not achieve SVR12 was a patient with genotype 3a HCV who had been incorrectly genotyped as 1a in the previous study. Given the high rates of SVR12, no differences among patient subgroups were discernible. Of 51 patients, 41 (80%) experienced at least one adverse event (AE), but most events were mild to moderate in severity. The most common AEs were fatigue, headache, and diarrhea. One patient discontinued treatment because of an unrelated AE (bipolar disorder). Conclusion: Twelve weeks of LDV‐SOF plus RBV was an effective and safe treatment for patients who have not achieved SVR with earlier regimens that included SOF. (Hepatology 2015;61:1793–1797)