Miracle-dz/UniFAR-FTUs huggingface dataset:
Antagonists of growth hormone-releasing hormone (GHRH) reduce prostate size in experimental benign prostatic hyperplasia

Growth hormone-releasing hormone (GHRH), a hypothalamic polypeptide, acts as a potent autocrine/paracrine growth factor in many cancers. Benign prostatic hyperplasia (BPH) is a pathologic proliferation of prostatic glandular and stromal tissues; a variety of growth factors and inflammatory processes are inculpated in its pathogenesis. Previously we showed that potent synthetic antagonists of GHRH strongly inhibit the growth of diverse experimental human tumors including prostate cancer by suppressing various tumoral growth factors. The influence of GHRH antagonists on animal models of BPH has not been investigated. We evaluated the effects of the GHRH antagonists JMR-132 given at doses of 40 μg/d, MIA-313 at 20 μg/d, and MIA-459 at 20 μg/d in testosterone-induced BPH in Wistar rats. Reduction of prostate weights was observed after 6 wk of treatment with GHRH antagonists: a 17.8% decrease with JMR-132 treatment; a 17.0% decline with MIA-313 treatment; and a 21.4% reduction with MIA-459 treatment (P < 0.05 for all). We quantified transcript levels of genes related to growth factors, inflammatory cytokines, and signal transduction and identified significant changes in the expression of more than 80 genes (P < 0.05). Significant reductions in protein levels of IL-1β, NF-κβ/p65, and cyclooxygenase-2 (COX-2) also were observed after treatment with a GHRH antagonist. We conclude that GHRH antagonists can lower prostate weight in experimental BPH. This reduction is caused by the direct inhibitory effects of GHRH antagonists exerted through prostatic GHRH receptors. This study sheds light on the mechanism of action of GHRH antagonists in BPH and suggests that GHRH antagonists should be considered for further development as therapy for BPH.
Sense of coherence; work and family stressors in a metropolitan municipality in South Africa

Background: Not much information is available on the level of the sense of coherence (SOC) of the working population in South Africa. SOC is the disposition of an individual to accept strain as one of the factors that fosters growth and maturity. It develops from infancy through adolescence from the resources available to an individual and could deplete through stressors. Work stressors are those elements in the workplace that could result in harmful behaviour patterns and stress-aversive reactions. While family stressors are those elements in the domestic environment that engender strain and counterproductive behaviour in individuals. Aim: The main aim of the article was to examine the association among SOC and work and family stressors among professional level employees in the South African Public Service. The objectives of this article are (1) to ascertain if the professional level employees investigated had strong or weak sense of coherence (SOC) and (2) To determine the effect of work and family stressors on SOC. Setting: The study was conducted among professional level employees and top management of a municipality in the South African Public Service. Methods: In this pragmatic, cross-sectional study design, a sample of 307 professional level employees born during the apartheid era in South Africa completed the 13-version Orientation to life Questionnaire (OLQ), work stressor and family stressor questionnaires as well as an elementary demographic questionnaire. Additional data was collected from the interview of 11 other top management members. Results and conclusion: The findings refuted the claims that unfavourable environmental conditions could affect the development of a strong SOC in an individual by revealing that professional level employees at the South African Public Service generally had strong SOC. It further revealed that the respondents in comparison with the family stressors were experiencing much work stressors. The findings have implications for workplace practices and management of work and family stressors. Corresponding author: Abe, Ethel Ndidiamaka Email addresses for corresponding author: ethelabe@gmail.com First submission received: 22nd January 2018 Revised submission received: 27th March 2018 Accepted: 21st May 2018
Antimicrobial-Associated Renal Tubular Acidosis

OBJECTIVE: To review the literature documenting the association of various antimicrobial medications with the development of renal tubular acidosis (RTA). DATA SOURCES: A search of the English literature via MEDLINE (1966-November 2003) and International Pharmaceutical Abstracts (1970-November 2003) was conducted to identify human reports of RTA associated with various drugs from all available classes of antimicrobial agents. Major search terms included renal tubular acidosis, acidosis, antibiotics, and antimicrobials. Bibliographies of selected articles were also searched to identify additional reports of RTA. STUDY SELECTION AND DATA EXTRACTION: Case reports, observational studies, and experimental studies documenting the association of any antimicrobial agent with the development of RTA were included. DATA SYNTHESIS: Antimicrobial-associated RTA is a relatively uncommon adverse effect, with most reports involving amphotericin B, trimethoprim/sulfamethoxazole, and outdated tetracycline. These agents may induce RTA either through direct tubular toxicity or as a function of their pharmacologic action. The time course for the development of RTA varies depending on the antimicrobial utilized. In most instances, RTA is reversible; however, some patients may experience prolonged recovery after the offending agent is removed. CONCLUSIONS: Given that antimicrobial-associated RTA is a relatively uncommon adverse effect, review of the patient's drug regimen may reveal these agents as otherwise unrecognized causes of RTA. Likewise, underlying causes of RTA other than medications must be ruled out. Diagnosing antimicrobial-induced RTA may be difficult, given many of these agents may be used in combination and some are intrinsically nephrotoxic.
Adolescents and Young Adults With Cancer: Oncology Nurses Report Attitudes and Barriers to Discussing Fertility Preservation.

BACKGROUND Fertility issues have been found to be an important topic for adolescents and young adults (AYAs) with cancer. Medical technology has made fertility preservation (FP) increasingly effective for postpubertal patients whose treatment course may inhibit their future ability to achieve biologic parenthood. Oncology providers' recommendations have been shown to vary, potentially affecting patients' decision-making processes regarding FP. OBJECTIVES This study was designed to assess oncology nurses' recommendations for patients to consider FP options and to explore what patient-related factors may influence discussion of FP with AYAs with cancer. METHODS 116 oncology nurses participated in this study and were randomized to read one of four vignettes about a patient whose proposed treatment course could affect his or her fertility. Participants' recommendations to partake in FP were analyzed to test for differences by patient age and gender. Open-ended responses to questions about their experiences as oncology nurses were analyzed descriptively. FINDINGS Nurses strongly recommended that all patients explore FP options before the start of treatment. Oncology nurses endorsed stronger opinions that young adult female patients should be given independent decision-making power to delay treatment for FP, compared to male and female adolescent patients and young adult male patients. Participants mentioned barriers to discussions that included concerns about exacerbating negative emotions and the decision-making capacity of young patients.
Belatacept and Sirolimus Prolong Nonhuman Primate Islet Allograft Survival: Adverse Consequences of Concomitant Alefacept Therapy

Calcineurin inhibitors (CNI) and steroids are known to promote insulin resistance, and their avoidance after islet transplantation is preferred from a metabolic standpoint. Belatacept, a B7‐specific mediator of costimulation blockade (CoB), is clinically indicated as a CNI alternative in renal transplantation, and we have endeavored to develop a clinically translatable, belatacept‐based regimen that could obviate the need for both CNIs and steroids. Based on the known synergy between CoB and mTOR inhibition, we studied rhesus monkeys undergoing MHC‐mismatched islet allotransplants treated with belatacept and the mTOR inhibitor, sirolimus. To extend prior work on CoB‐resistant rejection, some animals also received CD2 blockade with alefacept (LFA3‐Ig). Nine rhesus macaques were rendered diabetic with streptozotocin and underwent islet allotransplantation. All received belatacept and sirolimus; six also received alefacept. Belatacept and sirolimus significantly prolonged rejection‐free graft survival (median 225 days compared to 8 days in controls receiving basiliximab and sirolimus; p = 0.022). The addition of alefacept provided no additional survival benefit, but was associated with Cytomegalovirus reactivation in four of six animals. No recipients produced donor‐specific alloantibodies. The combination of belatacept and sirolimus successfully prevents islet allograft survival in rhesus monkeys, but induction with alefacept provides no survival benefit and increases the risk of viral reactivation.
Clinical Implications of Cerebral Reorganisation after Primary Digital Flexor Tendon Repair

After flexor tendon injury, most attention is given to the quality of the tendon repair and postoperative early passive dynamic mobilisation. Schemes for active mobilisation have been developed to prevent tendon adhesions and joint stiffness. This paper describes five patients to demonstrate the cerebral consequences of immobilisation allowing only passive movements, which implies a prolonged absence of actual motor commands. At the end of such immobilisation, PET imaging revealed reduced blood flow in specific motor areas, associated with temporary loss of efficient motor control. Effective motor control was regained after active flexion exercises which was reflected in normalised cerebral activations. This suggests that temporary, reversible cerebral dysfunction may affect the outcome of flexor tendon injuries.
Comparison of prognostic value of red cell distribution width and NT-proBNP for short-term clinical outcomes in acute heart failure patients.

Comparison of the prognostic value of red cell distribution width (RDW) and N-terminal pro B-type natriuretic peptide (NT-proBNP) for short-term clinical outcomes in acute heart failure (AHF) patients has not been fully investigated.A total of 128 patients with AHF were enrolled and followed for 3 months. Primary endpoints were cardiovascular (CV) events, defined as cardiac death and/or readmission for HF. Baseline RDW and NT-proBNP were measured at admission.The 30-day and 90-day CV event rates were 16.4% and 35.9%, respectively. NT-proBNP was higher in people with cardiovascular events at both time points, while RDW was significantly higher only at the 90-day time point. The area under the ROC curve of RDW (area under the ROC curve = 0.695) for the prediction of CV events was higher than that of NT-proBNP (area under the ROC curve = 0.610) at the 90-day time point, but lower at the 30-day time point. Cox hazard analysis revealed RDW and NT-proBNP were independent predictive factors of a 90-day CV event (RDW, hazard ratio, 4.610, 95% confidence interval 1.935-10.981, P = 0.001; NT-proBNP, hazard ratio, 3.661, 95% confi dence interval 1.125-11.907, P = 0.031). Kaplan-Meier survival analysis revealed that patients with an RDW level > 14.5% and NT-proBNP > 1471.5 pg/mL were at highest risk for a CV event (P < 0.001). RDW and NT-proBNP are strong independent predictors of 90-day cardiovascular events in patients hospitalized with AHF. RDW can add prognostic value to NT-proBNP for predicting early cardiovascular events.
Staying in or switching between permanent, temporary and self-employment during 2008–2010: Associations with changing job characteristics and emotional exhaustion

Labour market segmentation theories suggest that permanent and temporary workers are exposed to economic risks to different degrees, and differ in their working life quality and well-being. However, few studies have tested these ideas during times of economic crisis. Also, little is known about how the self-employed compare to permanent and temporary workers and are affected by economic downturns. This study investigated Swedish workers in different labour market segments before and after the financial crisis (2008 and 2010). More specifically, it looked at job characteristics and strain differences between permanent, temporary and self-employed workers. Data (N = 6335) came from SLOSH, a longitudinal representative cohort study of the Swedish workforce. Contradicting segmentation theories, differences between permanent and temporary workers were small. The self-employed stood out with favourable job characteristics, but comparable strain levels. During the crisis, work demands and strain declined for many of the workers studied here.
Involvement of mitochondrial pathway in benzo[a]pyrene-induced neuron apoptosis

Benzo[a]pyrene (B[a]P), a well-known carcinogen, is widespread in the environment. Although the neurotoxic effect of B[a]P has not drawn much attention, toxic effects of B[a]P on learning and memory have been reported. Since it is well known that neuronal apoptosis plays a major role in impairment of learning and memory triggered by many stimuli, an effort has been made to examine whether the B[a]P-induced neurotoxicity occurs through mitochondria-mediated apoptosis. Cultured newborn rat cerebral neurons were used to clarify the apoptosis induced by B[a]P in the study. After incubating with different doses of B[a]P in presence of S9 for 40 h, the apoptotic rates of B[a]P-treated neurons increased in a dose-dependent manner. Further analysis showed that B[a]P-induced apoptosis was accompanied by loss of mitochondrial membrane potential, release of cytochrome c from mitochondria to the cytosol, downregulation of antiapoptotic protein B-cell lymphoma-2 (Bcl-2) levels with concurrent upregulation in proapoptotic Bcl-2-associated X protein (Bax) levels, and increase in the levels and activities of caspases-9 and -3. However, there was no difference in the activity of caspase-8 between B[a]P-exposed neurons and controls. Collectively, these results showed that B[a]P upregulates Bax and downregulates Bcl-2 expression in cultured cerebral neurons, which leads to mitochondrial release of cytochrome c, caspase-3 activation and neuronal apoptotic death.
Size estimation, HIV prevalence and risk behaviours of female sex workers in Pakistan.

OBJECTIVE To provide size estimation and to determine risky behaviours and HIV prevalence among female sex workers in Pakistan, which has progressed from a low to concentrated level of HIV epidemic. METHODS A cross-sectional study (geographic mapping and integrated behavioural and biological survey-IBBS) was conducted between August 2005 to January 2006 in Karachi, Hyderabad and Sukkur. A detailed questionnaire and dry blood spot (DBS) specimen for HIV testing were collected by trained interviewers after informed consent. The study was ethically approved by review boards in Canada and Pakistan. RESULTS About 14,900 female sex workers were estimated to be functional in Sindh. A total of 1158 of them were interviewed for the study. Average age of sex workers was 27.4 +/- 6.7 years, and the majority 787 (67.9%) were married, and uneducated 764 (65.9%). Sindhi (26.4%) was the predominant ethnicity. Mean number of paid clients was 2.1 +/- 1.2. three workers were confirmed HIV positive (0.75%, 95 percent CI 0.2-2.2%) from Karachi. Condom use at last sexual act was highest (68%) among brothel-based workers from Karachi, and the lowest in Sukkur where only 1.3% street-based workers reported using a condom at last sexual act. Overall use of illicit drugs through injections was negligible. CONCLUSION HIV prevalence among female sex workers in Sindh, Pakistan is low but risky behaviours are present. Well organised service delivery programmes can help promoting safer practices.
Causal Attributions and Parents’ Acceptance of Their Homosexual Sons

This Internet-based study examined the association between Israeli parents’ attributions regarding the cause of their son’s homosexuality and their level of acceptance of their homosexual son. The sample (N = 57) was recruited via Internet Web sites (gay forums and support groups). Findings suggest that more essentialist (versus constructivist) causal attributions were associated with higher levels of parental acceptance. Length of time parents knew of their son’s homosexual orientation predicted the degree to which their attributions were essentialist. Implications are discussed.
Acoustic Thoracic Images for Transmitted Glottal Sounds

Sound transmission has been of interest for many years in an attempt to study the structure of the lung and different researches have shown that artificial sounds produce a lateralization of sound information at the thoracic surface. Most of these studies have use non-simultaneous recording and input sounds introduced at the mouth or other thoracic points. In this paper, we present acoustic thoracic images, for transmitted glottal sounds, formed by a multichannel system with an array of 5times5 microphones. The study was done using 4 healthy subjects and 4 subjects having diffuse interstitial pneumonia. In both groups of subjects, it was found that the thorax behaves as a lowpass filter depending on the physical properties of its components, and that the transmitted acoustic thoracic imaging (TATHI) could reflect such properties. In most of the healthy subjects right to left asymmetries and heterogeneous apical to basal distribution were found. In patients the lateral dominance was lost and an intensity increment in the frequency band of 300 to 600 Hz was revealed. We conclude that TATHI permits to observe easily the spatial extension of the disease through sound transmission.
Expression of vesicular glutamate transporters, VGLUT1 and VGLUT2, in cholinergic spinal motoneurons

Mammalian spinal motoneurons are cholinergic neurons that have long been suspected to use also glutamate as a neurotransmitter. We report that VGLUT1 and VGLUT2, two subtypes of vesicular glutamate transporters, are expressed in rat spinal motoneurons. Both proteins are present in somato‐dendritic compartments as well as in axon terminals in primary cultures of immunopurified motoneurons and sections of spinal cord from adult rat. However, VGLUT1 and VGLUT2 are not found at neuromuscular junctions of skeletal muscles. After intracellular injection of biocytin in motoneurons, VGLUT2 is observed in anterogradely labelled terminals contacting Renshaw inhibitory interneurons. These VGLUT2‐ and VGLUT1‐positive terminals do not express VAChT, the vesicular acetylcholine transporter. Overall, our study establishes for the first time that (i) mammalian spinal motoneurons express vesicular glutamate transporters, (ii) these motoneurons have the potential to release glutamate (in addition to acetylcholine) at terminals contacting Renshaw cells, and finally (iii) the VGLUTs are not present at neuromuscular synapses of skeletal muscles.
Methods of Blood Pressure Measurement in the ICU*

Objective:Minimal clinical research has investigated the significance of different blood pressure monitoring techniques in the ICU and whether systolic vs. mean blood pressures should be targeted in therapeutic protocols and in defining clinical study cohorts. The objectives of this study are to compare real-world invasive arterial blood pressure with noninvasive blood pressure, and to determine if differences between the two techniques have clinical implications. Design:We conducted a retrospective study comparing invasive arterial blood pressure and noninvasive blood pressure measurements using a large ICU database. We performed pairwise comparison between concurrent measures of invasive arterial blood pressure and noninvasive blood pressure. We studied the association of systolic and mean invasive arterial blood pressure and noninvasive blood pressure with acute kidney injury, and with ICU mortality. Setting:Adult intensive care units at a tertiary care hospital. Patients:Adult patients admitted to intensive care units between 2001 and 2007. Interventions:None. Measurements and Main Results:Pairwise analysis of 27,022 simultaneously measured invasive arterial blood pressure/noninvasive blood pressure pairs indicated that noninvasive blood pressure overestimated systolic invasive arterial blood pressure during hypotension. Analysis of acute kidney injury and ICU mortality involved 1,633 and 4,957 patients, respectively. Our results indicated that hypotensive systolic noninvasive blood pressure readings were associated with a higher acute kidney injury prevalence (p = 0.008) and ICU mortality (p < 0.001) than systolic invasive arterial blood pressure in the same range (⩽70 mm Hg). Noninvasive blood pressure and invasive arterial blood pressure mean arterial pressures showed better agreement; acute kidney injury prevalence (p = 0.28) and ICU mortality (p = 0.76) associated with hypotensive mean arterial pressure readings (⩽60 mm Hg) were independent of measurement technique. Conclusions:Clinically significant discrepancies exist between invasive and noninvasive systolic blood pressure measurements during hypotension. Mean blood pressure from both techniques may be interpreted in a consistent manner in assessing patients’ prognosis. Our results suggest that mean rather than systolic blood pressure is the preferred metric in the ICU to guide therapy.
A Novel Isoform of the Secretory Pathway Ca2+,Mn2+-ATPase, hSPCA2, Has Unusual Properties and Is Expressed in the Brain*

Unlike lower eukaryotes, mammalian genomes have a second gene, ATP2C2, encoding a putative member of the family of secretory pathway Ca2+,Mn2+-ATPases, SPCA2. Human SPCA2 shares 64% amino acid identity with the protein defective in Hailey Hailey disease, hSPCA1. We show that human SPCA2 (hSPCA2) has a more limited tissue distribution than hSPCA1, with prominent protein expression in brain and testis. In primary neuronal cells, endogenous SPCA2 has a highly punctate distribution that overlaps with vesicles derived from the trans-Golgi network and is thus different from the compact perinuclear distribution of hSPCA1 seen in keratinocytes and nonpolarized cells. Heterologous expression in a yeast strain lacking endogenous Ca2+ pumps reveals further functional differences from hSPCA1. Although the Mn2+-specific phenotype of hSPCA2 is similar to that of hSPCA1, Ca2+ ions are transported with much poorer affinity, resulting in only weak complementation of Ca2+-specific yeast phenotypes. These observations suggest that SPCA2 may have a more specialized role in mammalian cells, possibly in cellular detoxification of Mn2+ ions, similar to that in yeast. We point to the close links between manganese neurotoxicity and Parkinsonism that would predict an important physiological role for SPCA2 in the brain.