Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity and expression of Na(+)-H+ exchanger isoforms 1 and 3 in kidney proximal tubules of hypertensive rats.

Increased activity of the cellular Na(+)-H+ exchangers (NHEs), especially isoform 1 (NHE-1), is a recognized intermediate phenotype of hypertension. NHE activity has been demonstrated to be increased in proximal tubules of the spontaneously hypertensive rat (SHR). However, with the recent cloning of other members of this family of transporters, it is unclear which isoforms may contribute to this increased activity. We have used specific antibodies raised against glutathione-S-transferase fusion proteins of rat NHE-1 and NHE-3 to determine the relative contributions of these isoforms to the NHE activity in freshly isolated and cultured proximal tubule cells from SHR and Wistar-Kyoto (WKY) normotensive control rats. In freshly isolated proximal tubule cells, NHE activity was elevated almost 3-fold in SHR cells (P < .001), and in both rat strains, the contribution from NHE-1 and NHE-3 was approximately equal. Western blots of membranes from these cells showed equal amounts of NHE-1 protein in SHR and WKY cells. However, NHE-3 protein expression was increased 50% in SHR cells (P < .001), and this may account for the elevated activity of this isoform in SHR. The effect of culturing these cells in vitro was then examined. Although total NHE activity in both cell types was decreased during culture, this was mainly due to loss of expression of NHE-3 protein. NHE-1 activity was persistently elevated in the SHR cells in culture. These findings suggest that elevated NHE activity in SHR proximal tubules could be mediated by two mechanisms: (1) increased NHE-1 activity without any increased NHE-1 protein content that persists despite culture and may resemble those changes described for extrarenal tissues and (2) increased NHE-3 activity due to increased expression of NHE-3 protein. Disappearance of NHE-3 during culture implies that our culture conditions did not replicate the in vivo environment and may have removed the factors contributing to the increased NHE-3 expression in SHR cells.
Assessment of sexual risk behaviours of in-school youth: Effect of living arrangement of students; West Gojam zone, Amhara regional state, Ethiopia

Background: Contemporary threats to adolescents' health are primarily the consequence of risk behaviors and their related adverse outcomes. Identifying factors associated with adolescents' risk behaviors is critical for developing effective prevention strategies. A number of risk factors have been identified, including familial environment; however, to the investigator's best knowledge, there have been only one previous study of possible differential vulnerabilities of in-school adolescents to risky sex in reference to parental influences and living arrangements in Ethiopia. Objective: To assess and compare sexual risk behaviours of preparatory students in West Gojam zone, in reference to their living arrangements Methodology: A comparative cross-sectional study was done in ten preparatory schools; West Gojam zone, Amhara National Regional State, Ethiopia. The study participants were selected based on probability proportional to size. A total of 314 students [104 living permanently in the corresponding towns and 210 not], were included in the study. Result: Seventy three (23.2%) respondents had ever had sexual intercourse with an individual of the opposite sex. Disaggregated by sex, 55 (25.0%) of males had had sex compared to 18 (19.4%) of females. Twenty two students (33.3%) reported having had two or more sexual partners in their lifetime (range 1-7, average1.56). In the logistic regression analyses, controlling for observed covariates, age more than 20 years [OR= 2.85; 95%CI= 1.07 to 7.59], having peer pressure to have sex [OR= 4.43; 95%CI= 2.02 to 9.69] and perceived family connectedness [OR= 0.96; 95%CI= 0.92 to 0.99] continued to be significantly and independently associated with sexual activity Conclusion: A greater sense of connectedness to parents decreases the likelihood of sexual activity regardless of living arrangement, Parental monitoring, gender, khat and alcohol consumption, and parental education. Students with peer pressure to have sex are more likely to initiate sexual intercourse.
Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases

Significance Novel advances in viral oncotherapy require effective direct oncolysis and manipulation of the tumor microenvironment, which has proven to be an important target in cancer treatment. The CXCR4 receptor for the CXCL12 chemokine is one of the key stimuli involved in signaling interactions between tumor cells and their microenvironment, suggesting that inhibition of this pathway by oncolytic viruses expressing the CXCR4 antagonist should increase efficacy over that mediated by oncolysis alone. We are unique in demonstrating that targeting CXCR4 signaling through an oncolytic vaccinia virus yields a significant therapeutic impact against primary and metastatic breast cancer. Oncolytic viruses hold promise for the treatment of cancer, but their interaction with the tumor microenvironment needs to be elucidated for optimal tumor cell killing. Because the CXCR4 receptor for the stromal cell-derived factor-1 (SDF-1/CXCL12) chemokine is one of the key stimuli involved in signaling interactions between tumor cells and their stromal microenvironment, we used oncolytic virotherapy with a CXCR4 antagonist to target the CXCL12/CXCR4 signaling axis in a triple-negative 4T1 breast carcinoma in syngeneic mice. We show here that CXCR4 antagonist expression from an oncolytic vaccinia virus delivered intravenously to mice with orthotopic tumors attains higher intratumoral concentration than its soluble counterpart and exhibits increased efficacy over that mediated by oncolysis alone. A systemic delivery of the armed virus after resection of the primary tumor was efficacious in inhibiting the development of spontaneous metastasis and increased overall tumor-free survival. Inhibition of tumor growth with the armed virus was associated with destruction of tumor vasculature, reductions in expression of CXCL12 and VEGF, and decrease in intratumoral numbers of bone marrow-derived endothelial and myeloid cells. These changes led to induction of antitumor antibody responses and resistance to tumor rechallenge. Engineering an oncolytic virus armed with a CXCR4 antagonist represents an innovative strategy that targets multiple elements within the tumor microenvironment. As such, this approach could have a significant therapeutic impact against primary and metastatic breast cancer.
Pharmacokinetics of a cytochrome P450 2E1 probe, chlorzoxazone, and its 6-hydroxy metabolite in poloxamer 407-induced hyperlipidemic rats.

PURPOSE To evaluate the possible changes in CYP2E1 expression and activity in hyperlipidemia (HL), we evaluated the pharmacokinetics of chlorzoxazone (CZX) as a CYP2E1 probe in rats with HL induced by poloxamer 407 (HL rats). METHODS The pharmacokinetics of CZX and its 6-hydroxy metabolite (OH-CZX) were evaluated after intravenous administration of 20 mg/kg CZX to both control and HL rats. We also examined changes in the expression of CYP2E1 and its in vitro metabolic activity in hepatic microsomal fractions from HL rats. RESULTS The total area under the plasma concentration-time curve (AUC) of CZX in the HL rats after its intravenous administration was comparable with that in the controls due to unchanged non-renal clearance (CLNR). The AUC of OH-CZX and AUCOH-CZX/AUCCZX ratios in HL rats also remained unchanged. This was primarily due to the comparable hepatic CLint for metabolism of CZX to OH-CZX via CYP2E1 between the control and HL rats as a result of unchanged expression of CYP2E1 in HL rats. CONCLUSIONS This is the first study to evaluate CYP2E1 expression and activity in HL rats and their effects on the pharmacokinetics of a CYP2E1 probe drug. These findings have potential therapeutic implications assuming that the HL rat model qualitatively reflects similar changes in patients with HL.
Analysis of Backyard Chicken Farmers Socio-Economic and Management Practices in District Quetta, Balochistan

Socio-economic profile of backyard poultry farmers beside the prevailing management practices and flock profile was studied in nine union councils of District Quetta Balochistan; from November, 2016 to March, 2017. Primary data was collected from 99 households randomly selected from study area by using semi-structured questionnaire, while descriptive statistics were used to conclude the data. Study revealed that women were the only prevailing gender (100%) involved in rearing of backyard chicken in the area. Maximum (53%) number of respondents were in the age group of > 40 years, while more than half (58%) of poultry keepers were illiterate. Backyard poultry farming was much popular (79%) in house wives, whereas 75% of them were responsible for primary support of their household. Pashtoon ethnicity was the major (40%) group of respondents. 58% of the respondents reported a family with 10–20 members. 90% of the farmers provided shelter to their birds, made from mud and thatch (kacha). 80% of these birds were fed on kitchen waste and bread remnants. Average flock size was 27 birds, having 48% Desi (Indigenous chicken), 27% Fayoumi, 12 % Rhode Island Red (RIR) and 13% cross bred birds. Flocks were comprised of adult hen (71%), cock (15%) and chicks (14%). Annual egg production was 4190±171 eggs with 217±2.4 eggs produced per bird, whereas the average number of eggs consumed per family was 1314±48 eggs. Backyard poultry rearing offers a real opportunity to alleviate poverty and gender empowerment. The farmers should be further trained to improve the current feeding and management practices of these birds.
Constructing Packings in Grassmannian Manifolds via Alternating Projection

This paper describes a numerical method for finding good packings in Grassmannian manifolds equipped with various metrics. This investigation also encompasses packing in projective spaces. In each case, producing a good packing is equivalent to constructing a matrix that has certain structural and spectral properties. By alternately enforcing the structural condition and then the spectral condition, it is often possible to reach a matrix that satisfies both. One may then extract a packing from this matrix. This approach is both powerful and versatile. In cases in which experiments have been performed, the alternating projection method yields packings that compete with the best packings recorded. It also extends to problems that have not been studied numerically. For example, it can be used to produce packings of subspaces in real and complex Grassmannian spaces equipped with the Fubini–Study distance; these packings are valuable in wireless communications. One can prove that some of the novel configurations constructed by the algorithm have packing diameters that are nearly optimal.
Acute Pancreatitis Following a Single Dose of Codeine Phosphate : A Case Report

Several drugs have previously been implicated to cause acute pancreatitis. We report the rare case of codeine induced acute pancreatitis. A 43-year-old woman developed the symptoms and clinical signs of acute pancreatitis 90 minutes after the ingestion of codeine phosphate. The diagnosis was proved both biochemically and radiologically which excluded other potential causes. The likely underlying pathophysiology is codeine-induced spasm of the sphincter of oddi. Noor Obeid1*, Lucy Fletcher2 and Ian CC King1 1Department of General Surgery, Queen Victoria Hospital, UK 2Department of General Surgery, Royal Victoria Infirmary, UK Noor Obeid, et al., Annals of Clinical Case Reports Surgery Remedy Publications LLC. , | http://anncaserep.com/ 2016 | Volume 1 | Article 1146 2 most recent paper on this topic was by Turkmen et al. [4] in 2015 in which they reported a case of drug induced pancreatitis in a patient with a previous cholecystectomy. The patient developed symptoms of pancreatitis 60 minutes after taking 30mg of codeine for mild muscle aches. It has been suggested that the pathophysiology of codeineinduced pancreatitis is likely due to constriction of the sphincter of Oddi which has been demonstrated to be induced by subcutaneous injection with therapeutic doses of codeine and morphine [8]. Positive re-challenge has previously been documented further proving codeine as a cause for AP [5]. Further oral challenge of codeine in this index patient was not performed due to ethical reasons. The majority of previous case reports are very similar to the case described above with onset of symptoms approximately 1-3 hours post ingestion of codeine [6]. Studies have shown that injection of therapeutic doses of opioid cause rapid onset of constriction of the sphincter of Oddi, lasting for approximately two hours which correlates with reported symptoms [9]. AP should be considered as a potential side effect when prescribing codeine particularly in patients who has previously undergone cholecystectomy [7]. These patients are possibly more likely to suffer from codeine associated AP due to smooth-muscle hyperplasia or fibrosis increasing sphincter of Oddi spasm postcholecystectomy [7]. However, in contrast to the majority of previous reports our case shows that codeine induced AP is not exclusive to the post-cholecystectomy patient population. In conclusion we have identified a case of codeine induced AP in a middle-aged woman. Similar cases should be more regularly reported to understand more accurately incidence and improve education on this condition. Increasing the awareness of codeine as a cause of AP, will enable clinicians to make a more informed decision when prescribing codeine in preventing this condition. Prescribing codeine as a form of analgesia in patients presenting with AP should be done with care so as not to exacerbate the existing condition. In future medical professionals should be mindful of the association of codeine and AP when patients present clinically, biologically and radiologically with AP.
Gender in Jeopardy!: The Role of Opponent Gender in High-Stakes Competition

Using 4,279 episodes of the popular US game show Jeopardy! , we analyze whether the opponents' gender is able to explain the gender gap in competitive behavior. Our findings indicate that gender differences disappear when women compete against men. This result is surprising, but emerges with remarkable consistency for the probability to (i) respond, (ii) respond correctly, and (iii) respond correctly in high-stakes situations. Even risk preferences in wagering decisions, where gender differences are especially pronounced, do not differ across gender once a woman competes against males. Using a fixed-effects framework, and therefore exploiting within-player variation only, confirms these findings. These results, derived from a large real-life setting, suggest that gender differences in performance and risk attitudes are not gender-inherent, but rather emerge in distinct social environments.
Effects of a semi-rigid ankle brace on ankle joint loading during landing on inclined surfaces

ABSTRACT Ankle bracing is commonly used to prevent ankle sprain occurrences. The present study investigated the effects of a semi-rigid ankle brace on the ankle joint complex during landing on inclined surfaces. Seventeen recreational athletes performed a single leg landing task onto three different surface alignments (everted, neutral, inverted), with and without the brace. Ground reaction forces (GRF), kinematics, and brace pressure were recorded. Six two-way repeated measures MANOVA tested for differences in GRF, talocrural and subtalar kinematics and kinetics. Participants landed with a significantly less plantar flexed (P < 0.001) and more everted (P = 0.001) foot during the braced condition. Although no differences were observed for the joint moments, an increased subtalar compression force (P = 0.009) was observed with the brace. Landing on the inverted surface resulted in significantly higher peak magnitudes of the vertical and the mediolateral GRF and the talocrural inversion moment compared to landing on the neutral surface. Ankle bracing altered ankle kinematics by restricting the ROM of the ankle joint complex. This study confirmed that landing on inverted surfaces may increase the risk for lateral ankle ligaments injuries. The significantly higher subtalar compression force during the brace condition might contribute to overuse injuries.
Fresh frozen plasma reduces edema in skeletal muscle following combined limb ischemia-reperfusion injury and hemorrhagic shock in rats

BACKGROUND Exsanguination from extremity vascular injuries is the most common potentially survivable injury on the battlefield. Advances in treatment have dramatically improved survival, increasing the need to address associated morbidities including ischemia-reperfusion injury and extremity compartment syndrome. Despite advances, hemorrhagic shock (HS) requiring fluid resuscitation is common. Plasma-based resuscitation for the treatment of HS has been shown to reduce edema and injury in tissues other than muscle. The objective of this study was to determine if fresh frozen plasma (FFP) resuscitation offered protection in a rat model of combined HS and skeletal muscle ischemia-reperfusion injury. METHODS Anesthetized Sprague-Dawley rats underwent 37.5% arterial hemorrhage, producing HS, followed by 3 hours of tourniquet application. Animals were not resuscitated or resuscitated with either FFP (equal to the shed blood volume) or lactated Ringer’s solution (three times shed volume) after 30 minutes of ischemia. They were euthanized 24 hours later, and their muscles were analyzed for edema (wet weight-dry weight). Routine histology was performed on muscle cross-sections stained with hematoxylin and eosin and graded using a semiquantitative grading system. RESULTS All animals developed HS; the mortality rate was 50% in no resuscitation rats. FFP reduced edema by 13% (p = 0.02) compared with lactated Ringer’s solution. Pathology scores were not different between treatment groups. CONCLUSION FFP resuscitation reduces edema following muscle injury, decreasing the risk of developing extremity compartment syndrome.
IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist

The functional role of IL-1 family member 10, recently renamed IL-38, remains unknown. In the present study we aimed to elucidate the biological function of IL-38 and to identify its receptor. Heat-killed Candida albicans was used to stimulate memory T-lymphocyte cytokine production in freshly obtained human peripheral blood mononuclear cells from healthy subjects. The addition of recombinant IL-38 (152 amino acids) inhibited the production of T-cell cytokines IL-22 (37% decrease) and IL-17 (39% decrease). The reduction in IL-22 and IL-17 caused by IL-38 was similar to that caused by the naturally occurring IL-36 receptor antagonist (IL-36Ra) in the same peripheral blood mononuclear cells cultures. IL-8 production induced by IL-36γ was reduced by IL-38 (42% decrease) and also was reduced by IL-36Ra (73% decrease). When human blood monocyte-derived dendritic cells were used, IL-38 as well as IL-36Ra increased LPS-induced IL-6 by twofold. We screened immobilized extracellular domains of each member of the IL-1 receptor family, including the IL-36 receptor (also known as “IL-1 receptor-related protein 2”) and observed that IL-38 bound only to the IL-36 receptor, as did IL-36Ra. The dose–response suppression of IL-38 as well as that of IL-36Ra of Candida-induced IL-22 and IL-17 was not that of the classic IL-1 receptor antagonist (anakinra), because low concentrations were optimal for inhibiting IL-22 production, whereas higher concentrations modestly increased IL-22. These data provide evidence that IL-38 binds to the IL-36R, as does IL-36Ra, and that IL-38 and IL-36Ra have similar biological effects on immune cells by engaging the IL-36 receptor.
Myocardial Free Fatty Acid and Glucose Use After Carvedilol Treatment in Patients With Congestive Heart Failure

Background—Use of &bgr;-adrenoreceptor blockade in the treatment of heart failure has been associated with a reduction in myocardial oxygen consumption and an improvement in myocardial energy efficiency. One potential mechanism for this beneficial effect is a shift in myocardial substrate use from increased free fatty acid (FFA) oxidation to increased glucose oxidation. Methods and Results—We studied the effect of carvedilol therapy on myocardial FFA and glucose use in 9 patients with stable New York Heart Association functional class III ischemic cardiomyopathy (left ventricular ejection fraction ≤35%) using myocardial positron emission tomography studies and resting echocardiograms before and 3 months after carvedilol treatment. Myocardial uptake of the novel long chain fatty acid metabolic tracer 14(R, S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA) was used to determine myocardial FFA use, and [18F]fluoro-2-deoxy-glucose ([18F]-FDG) was used to determine myocardial glucose use. After carvedilol treatment, the mean myocardial uptake rate for [18F]-FTHA decreased (from 20.4±8.6 to 9.7±2.3 mL · 100 g−1 · min−1;P <0.005), mean fatty acid use decreased (from 19.3±7.0 to 8.2±1.8 &mgr;moL · 100 g−1 · min−1;P <0.005), the mean myocardial uptake rate for [18F]-FDG was unchanged (from 1.4±0.4 to 2.4±0.8 mL · 100 g−1 · min−1;P =0.14), and mean glucose use was unchanged (from 11.1±3.1 to 18.7±6.0 &mgr;moL · 100 g−1 · min−1;P =0.12). Serum FFA and glucose concentrations were unchanged, and mean left ventricular ejection fraction improved (from 26±2% to 37±4%;P <0.05). Conclusions—Carvedilol treatment in patients with heart failure results in a 57% decrease in myocardial FFA use without a significant change in glucose use. These metabolic changes could contribute to the observed improvements in energy efficiency seen in patients with heart failure.
Fatal Attraction: Salience, Naivete, and Sophistication in Experimental Hide-and-Seek Games

"Hide-and-seek" games are zero-sum two-person games in which one player wins by matching the other's decision and the other wins by mismatching. Although such games are often played on cultural or geographic "landscapes" that frame decisions nonneutrally, equilibrium ignores such framing. This paper reconsiders the results of experiments by Rubinstein, Tversky, and others whose designs model nonneutral landscapes, in which subjects deviate systematically from equilibrium in response to them. Comparing alternative explanations theoretically and econometrically suggests that the deviations are well explained by a structural nonequilibrium model of initial responses based on "level-k" thinking, suitably adapted to nonneutral landscapes. (JEL C72, C92)