Miracle-dz/UniFAR-FTUs huggingface dataset:
Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome

Interneurons are thought to be a primary pathogenic target for several behavioral disorders that arise during development, including schizophrenia and autism. It is not known, however, whether genetic lesions associated with these diseases disrupt established molecular mechanisms of interneuron development. We found that diminished 22q11.2 gene dosage—the primary genetic lesion in 22q11.2 deletion syndrome (22q11.2 DS)—specifically compromises the distribution of early-generated parvalbumin-expressing interneurons in the Large Deletion (LgDel) 22q11.2DS mouse model. This change reflects cell-autonomous disruption of interneuron migration caused by altered expression of the cytokine C-X-C chemokine receptor type 4 (Cxcr4), an established regulator of this process. Cxcr4 is specifically reduced in LgDel migrating interneurons, and genetic analysis confirms that diminished Cxcr4 alters interneuron migration in LgDel mice. Thus, diminished 22q11.2 gene dosage disrupts cortical circuit development by modifying a critical molecular signaling pathway via Cxcr4 that regulates cortical interneuron migration and placement.
Intangible Capital, Volatility Shock, and the Value Premium

This paper extends the canonical, neoclassical investment&#8208;based asset&#8208;pricing model through the incorporation of intangible capital and the formulation of a joint productivity distribution with economic uncertainty shocks at the firm level. The distinctive evolutionary dynamics of intangible capital as opposed to that of physical capital mitigate the negative impact of temporary uncertainty shock on production and serve well to explain the value premium with modest assumptions. The value premium is unconditionally positive, but the realized value spread plummets to negative after major transient second&#8208;moment shocks, for example, the Loma Prieta Earthquake and the 9/11 terrorist&#160;attack.
Modelling the Time-Varying Gold Price Volatility in Malaysia (2005 â€“ 2018)

This study provides new insights into the recent time-varying pattern of gold volatility surrounding the Subprime Global Financial Crisis (GFC) 2008 with special emphasis given to small open economy of Malaysia. Using daily data of gold bullion Kijang Emas issued by the Bank Negara Malaysia from August 2005 till July 2018, the study modelled the gold volatility using different models of ARCH-GARCH family. Under the context of emerging economy, the study found significant enhanced gold volatility during the middle of GFC, signifying that gold price is highly sensitive to specific economic disturbance. Next, our result displayed inverted asymmetry effect where investors interpret gold as a safe-haven investment during good gold returns, hence contributed to enhanced gold volatility. Finally, bilateral exchange rate (MYR/USD) affected volatility with positive sign, indicating that gold investment could be adversely affected during the depreciation of the Malaysian Ringgit.
Functional Convergence of Oxylipin and Abscisic Acid Pathways Controls Stomatal Closure in Response to Drought1[W][OPEN]

Oxylipin affects stomatal closure, functioning most effectively with ABA in response to drought. Membranes are primary sites of perception of environmental stimuli. Polyunsaturated fatty acids are major structural constituents of membranes that also function as modulators of a multitude of signal transduction pathways evoked by environmental stimuli. Different stresses induce production of a distinct blend of oxygenated polyunsaturated fatty acids, “oxylipins. ” We employed three Arabidopsis (Arabidopsis thaliana) ecotypes to examine the oxylipin signature in response to specific stresses and determined that wounding and drought differentially alter oxylipin profiles, particularly the allene oxide synthase branch of the oxylipin pathway, responsible for production of jasmonic acid (JA) and its precursor 12-oxo-phytodienoic acid (12-OPDA). Specifically, wounding induced both 12-OPDA and JA levels, whereas drought induced only the precursor 12-OPDA. Levels of the classical stress phytohormone abscisic acid (ABA) were also mainly enhanced by drought and little by wounding. To explore the role of 12-OPDA in plant drought responses, we generated a range of transgenic lines and exploited the existing mutant plants that differ in their levels of stress-inducible 12-OPDA but display similar ABA levels. The plants producing higher 12-OPDA levels exhibited enhanced drought tolerance and reduced stomatal aperture. Furthermore, exogenously applied ABA and 12-OPDA, individually or combined, promote stomatal closure of ABA and allene oxide synthase biosynthetic mutants, albeit most effectively when combined. Using tomato (Solanum lycopersicum) and Brassica napus verified the potency of this combination in inducing stomatal closure in plants other than Arabidopsis. These data have identified drought as a stress signal that uncouples the conversion of 12-OPDA to JA and have revealed 12-OPDA as a drought-responsive regulator of stomatal closure functioning most effectively together with ABA.
Analysis of the treatment of spontaneous sustained stable ventricular tachycardia.

OBJECTIVES To determine the termination rate of spontaneous sustained stable ventricular tachycardia (SSSVT) as a function of the first and second therapeutic interventions used, and to determine factors associated with successful termination. METHODS A multihospital, retrospective analysis of the treatment of patients with SSSVT was performed. The setting included 2 urban county hospitals, 2 urban private hospitals, and a Veterans Affairs hospital. Cases were identified by discharge diagnosis and ECG characteristics, and confirmed by electrophysiology study or ECG criteria. RESULTS There were 40 cases of SSSVT identified. Excluding adenosine, 35 patients were treated with lidocaine as a first intervention. The rate of termination with lidocaine bolus was 17% (6 of 35) (95% CI 7-34%). Regarding the 35 patients initially treated with lidocaine, the odds of termination of SSSVT were 11 times greater in those without a history of previous myocardial infarction (MI) than in those with a history of MI (95% CI 0.96-551). Of the 29 patients who failed initial lidocaine treatment, 23 were treated with a second lidocaine bolus, with a termination rate of 18% (4 of 22) (95% CI 5-40%). Only 2 patients with sustained ventricular tachycardia had a concurrent MI, and the tachycardia was unresponsive to initial lidocaine bolus in both cases. Fifteen patients received adenosine with no tachycardia terminations and no significant adverse effects. CONCLUSIONS The rate of SSSVT termination with lidocaine was low, particularly in patients with a history of Mi.
Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy.

In this study, we examined the effect of injecting various cytokines. We report here that tumour necrosis factor (TNF)alpha, gamma-interferon and interleukin 2 (IL-2) can, in some circumstances, increase fetal resorption rates in abortion-prone (CBA/J x DBA/2) and non-abortion prone (CBA/J x BALB/c,C3H x DBA/2) matings: 1000 units TNF enhanced resorptions from 43 to 79% in CBA x DBA/2, from 7 to 89% in CBA x BALB/c, from 5 to 47% in C3H x DBA/2. The effect was both gestational age- and dose-dependent. Gamma interferon and R-IL-2 enhanced resorptions from 38 to 68% and 76% respectively in the CBA/J x DBA/2 mating combination, whereas the rates in CBA/J x BALB/c matings were enhanced from 6 to 44% and 55%. Lipopolysaccharide (LPS), which is known to lead to the release of TNF-alpha, had a similar effect, leading to gestational age- and dose-dependent enhancement of resorptions up to 100%. However, cytokines of the CSF family, including IL-3 and GM-CSF, increased the chances of fetal survival when injected into abortion-prone mice, e.g. reducing resorption rates in the abortion-prone CBA/J x DBA/2 mating combination from 55 to 22% (IL-3), and 47 to 8% (GM-CSF). They also increased fetal and placental weight and, in particular, expanded the spongiotrophoblast zone in the placenta. The latter observations may be due to a direct trophic influence on placental cells, perhaps through a cytokine cascade, or an indirect effect due to inhibition of natural killer (NK)-like cells, or both. Whatever the mechanism, these results may find practical application in influencing reproductive outcome in women and other species.
SR 33589, a New Amiodarone‐like Antiarrhythmic Agent: Electrophysiological Effects in Anesthetized Dogs

Summary We compared the electrophysiological effects of a new amiodarone-like agent, SR 33589, with those of amiodarone. Mongrel dogs were anesthetized with chloralose, and electrodes were implanted in right atrium and ventricle for electrical stimulation and regional ECG measurement. Sinus cycle length (CL), AH interval, Wenckebach CL (WCL), atrial, atrioventricular node, and ventricular effective refractory periods (AERP, AVNERP, VERP), and parameters calculated from surface ECG were measured. SR 33589 was administered intravenously (i.v.) at 1, 2.5, or 5 mg/kg followed 60 min later by a second similar dose. The same protocol was followed with amiodarone 5 mg/kg, which reduced heart rate (HR) by 19% (p < 0.05), increased WCL by 31% (p < 0.01), AH interval by 14% (p < 0.05) and AERP, AVNERP, and VERP by 13% (p < 0.05), 19% (p < 0.05), and 11% (p < 0.01) respectively. No effect was observed on HV or PQ intervals. A second administration of 5 mg/kg changed these indexes further. SR 33589 (2.5 mg/kg) reduced HR by 21% (p < 0.001), increased WCL by 44% (p < 0.001), AH interval by 24% (p < 0.01), and AERP, AVNERP, and VERP by 17% (p < 0.001), 63% (p < 0.01), and 15% (p < 0.01) respectively, with an 18% increase in PQ interval (p < 0.05) but no significant effect on HV interval. Higher doses (5 mg/kg) and/or administration of a second dose both resulted in greater changes. Both amiodarone and SR 33589 prolonged VERP more at longer CL than at shorter CL, but the degree of reduction at shorter CL was less with SR 33589 than with amiodarone. Results suggest that acute administration of SR 33589 results in electro-physiological actions similar to those produced by amiodarone.
High Viral Burden Restricts Short-Lived Effector Cell Number at Late Times Postinfection through Increased Natural Regulatory T Cell Expansion

Generating and maintaining a robust CD8+ T cell response in the face of high viral burden is vital for host survival. Further, balancing the differentiation of effectors along the memory precursor effector cell pathway versus the short-lived effector cell (SLEC) pathway may be critical in controlling the outcome of virus infection with regard to clearance and establishing protection. Although recent studies have identified several factors that have the capacity to regulate effector CD8+ T cell differentiation—for example, inflammatory cytokines—we are far from a complete understanding of how cells choose the memory precursor effector cell versus SLEC fate following infection. In this study, we have modulated the infectious dose of the poxvirus vaccinia virus as an approach to modulate the environment present during activation and expansion of virus-specific effector cells. Surprisingly, in the face of a high virus burden, the number of SLECs was decreased. This decrease was the result of increased natural regulatory T cells (Tregs) generated by high viral burden, as depletion of these cells restored SLECs. Our data suggest Treg modulation of differentiation occurs via competition for IL-2 during the late expansion period, as opposed to the time of T cell priming. These findings support a novel model wherein modulation of the Treg response as a result of high viral burden regulates late-stage SLEC number.
Protection against oxidative DNA damage and stress in human prostate by glutathione S‐transferase P1

The pi‐class glutathione S‐transferase (GSTP1) actively protect cells from carcinogens and electrophilic compounds. Loss of GSTP1 expression via promoter hypermethylation is the most common epigenetic alteration observed in human prostate cancer. Silencing of GSTP1 can increase generation of reactive oxygen species (ROS) and DNA damage in cells. In this study we investigated whether loss of GSTP1 contributes to increased DNA damage that may predispose men to a higher risk of prostate cancer. We found significantly elevated (103%; P < 0.0001) levels of 8‐oxo‐2′‐deoxogunosine (8‐OHdG), an oxidative DNA damage marker, in adenocarcinomas, compared to benign counterparts, which positively correlated (r = 0.2) with loss of GSTP1 activity (34%; P < 0.0001). Silencing of GSTP1 using siRNA approach in normal human prostate epithelial RWPE1 cells caused increased intracellular production of ROS and higher susceptibility of cells to H2O2‐mediated oxidative stress. Additionally, human prostate carcinoma LNCaP cells, which contain a silenced GSTP1 gene, were genetically modified to constitutively express high levels of GSTP1. Induction of GSTP1 activity lowered endogenous ROS levels in LNCaP‐pLPCX‐GSTP1 cells, and when exposed to H2O2, these cells exhibited significantly reduced production of ROS and 8‐OHdG levels, compared to vector control LNCaP‐pLPCX cells. Furthermore, exposure of LNCaP cells to green tea polyphenols caused reexpression of GSTP1, which protected the cells from H2O2‐mediated DNA damage through decreased ROS production compared to nonexposed cells. These results suggest that loss of GSTP1 expression in human prostate cells, a process that increases their susceptibility to oxidative stress‐induced DNA damage, may be an important target for primary prevention of prostate cancer. © 2013 Wiley Periodicals, Inc.
Sun protection behaviors of the U.S. white population.

BACKGROUND Sun protection behaviors are recommended to prevent skin cancer, which has increased in incidence. This study measured the prevalence of sun protection behaviors and determined personal characteristics associated with them. METHODS Data from 10,048 white respondents to the 1992 National Health Interview Survey Cancer Control Supplement were analyzed. Multiple logistic regression models were constructed to relate personal characteristics to specific behaviors. RESULTS Fifty-three percent of respondents reported they were "very likely" to use sunscreen, wear protective clothing, or seek shade if they were outside on a sunny day for more than 1 hr. Proportions for the individual behaviors were 32, 28, and 30%, respectively. Compared with people who do not burn, those reporting severe sunburn after 1 hr of sun exposure reported more use of sunscreens (odds ratio [OR] = 2.4, 95% confidence interval [CI] 2.0, 2.9), shade (OR = 1.8, 95% CI 1.5, 2.1), and protective clothing (OR = 2.2, 95% CI 1.9, 2.7). Other factors associated with practicing protection behaviors included a personal history of skin cancer, older age, and female sex. CONCLUSIONS A large percentage of white U.S. adults did not protect themselves from sun exposure. Additional education of the general public and persons at higher risk for skin cancer is needed.
SOD1 gene polymorphisms in sudden sensorineural hearing loss

Abstract Conclusion The results suggest that SOD1 rs4998557 could be associated with susceptibility to SSNHL in the Japanese population. Objectives To assess the gene association with sudden sensorineural hearing loss (SSNHL). Methods A two-stage case control study was conducted to explore the relationship of the candidate genes to SSNHL. The 192 gene samples from SSNHL patients registered in the intractable inner ear disease gene bank were enrolled. As the candidate genes, 39 SNPs from 31 genes were selected for the first stage study. The second stage study examined whether the SOD1 gene polymorphisms, defined by significant differences between cases and controls in the first stage study, are associated with SSNHL. Results Significant differences were observed in four SNPs from three genes, Glutathione-S-transferase pai 1 (GSTP1), proteine kinase C heta (PRKCH), and superoxide dismutase 1 (SOD1), in terms of allele frequency between SSNHL patients and HapMap controls. In the SOD1 gene, a significant difference was observed in the dominant model study of the SNP rs4998557 in the second stage study. Furthermore, as a result of dividing SSNHL patients based on the clinical data, the difference was more apparent in the case of the over 60 dB group and the tinnitus–positive group.
A study on the clinico-epidemiological profile and the outcome of snake bite victims in a tertiary care centre in southern India.

BACKGROUND Snake bite is a common medical emergency and an occupational hazard, more so in tropical India, where farming is a major source of employment. The available data on the epidemiology of snake bite from the Indian subcontinent are sparse. Snake bite is a neglected disease that afflicts the most impoverished inhabitants of the rural areas in the tropical developing countries. AIMS This study was carried out to describe the epidemiology, arrival delays, clinical features, complications, and the outcome of snakebites which were seen in a tertiary care hospital of southern India. SETTING Sri Chamarajendra District Hospital which is attached to the Hassan Institute of Medical Sciences, Hassan, Karnataka, India. STUDY DESIGN A record-based, retrospective, descriptive study. MATERIALS AND METHODS One hundred eighty patients of snake bite were studied from January 2010 to December 2011. The data on the demographic factors, clinical features and complications, details of the treatment which was received and the outcome of the snake bite victims were recorded and analyzed. RESULTS Among a total 180 cases of snake bite, there were 108 cases of viper bite which presented with haematotoxic manifestations and 74 elapid bites had neuroparalytic manifestations. The victims were predominantly males (60.5%) and they were aged 20-40 years. A majority of the victims are from the rural areas (81.1%) and most of the bites occurred during the day time (70.5%), mainly on the lower limbs (67.2%). The highest number of cases occurred during July- September. Most of the victims were farmers (54.4%) and plantation workers (30.5%), which suggested that snake bite was an occupational hazard. A reaction to the ASV was noted in 12.7% of the patients and the mortality rate in our study was 3.8%. CONCLUSION In the tropics, snake bite is a rural and an occupational hazard among farmers, plantation workers, herders and hunters. Regular public health programmes regarding the prevention, pre -hospital management (first aid) and the importance of the early transfer to the hospital should be emphasized.
Angiotensin II and monocrotaline-induced pulmonary hypertension: effect of losartan (DuP 753), a nonpeptide angiotensin type 1 receptor antagonist.

Administration of the pyrrolizidine alkaloid monocrotaline (MCT) to rats results in hypertensive pulmonary vascular disease characterized by a structurally based increase in pulmonary vascular resistance and right ventricular hypertrophy. Alterations in lung angiotensin converting enzyme activity in MCT-treated rats have suggested a role for angiotensin II (AII) in the pathogenesis of this model of hypertensive pulmonary vascular disease. To determine if increases in AII contribute to the development of pulmonary hypertension in MCT-treated rats, we examined the effect of chronic administration of the nonpeptide AII receptor antagonist Losartan on indices of pulmonary hypertension, Losartan (DuP 753; 10 mg/kg s.c.) administration for 21 days did not prevent the development of hypertensive pulmonary vascular disease in MCT-treated rats. However, 18 hr after the last dose of Losartan, AII (0.1 micrograms/kg i.v.)-induced pressor responses were inhibited by 63% in Losartan-treated rats. Losartan administration in MCT-treated rats did not prevent increases in pulmonary artery pressure or development of right ventricular hypertrophy. Additionally, increases in medial arterial thickness in pulmonary artery vessels (less than 50 microns and 50-100 microns external diameter) from MCT-treated rats were still evident in Losartan-treated rats. However, Losartan administration decreased medial pulmonary artery thickness of 50 to 100 microns external diameter vessels in control rats. These results demonstrate that AII. acting at the AT1 receptor subtype, does not contribute to pulmonary hypertension in this animal model.
Etelcalcetide for the treatment of secondary hyperparathyroidism

ABSTRACT Introduction: Calcium sensing receptor is an important target for the treatment of secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is a novel peptide calcimimetic agent that has a similar mechanism of action as cinacalcet hydrochloride. Clinical trials of etelcalcetide have been performed in the US, Europe, and Japan, and these trials demonstrated the safety and efficacy of etelcalcetide in dialysis patients. Etelcalcetide has recently been approved in Europe, the US and Japan. Areas covered: We review the development, pharmacokinetics, and clinical efficacy and safety of etelcalcetide for the treatment of SHPT in hemodialysis patients. We also summarize the clinical evidence regarding cinacalcet to forecast the potential clinical benefit of etelcalcetide. Expert opinion: Etelcalcetide is an injectable calcimimetic with a longer elimination half-life than cinacalcet. The injectable formulation improves adherence and reduces pill burden, while the frequency of gastrointestinal adverse events has been comparable between cinacalcet and etelcalcetide. The longer half-life of etelcalcetide reduces the fluctuation of biochemical markers of mineral and bone metabolism, but it remains to be determined whether such a sustained effect results in improved outcomes. Further studies are needed to determine the impact of etelcalcetide on clinical outcomes, particularly in comparison with the conventional calcimimetic cinacalcet.
Impact of the first eight months of orthodontic treatment with a fixed appliance on the families of adolescent patients.

OBJECTIVE To evaluate the impact of the first 8 months of orthodontic treatment with a fixed appliance on the families of adolescent patients and to examine the evaluative properties of the Family Impact Scale (FIS). MATERIALS AND METHODS The study involved a sample of 94 parents/caregivers of adolescents undergoing orthodontic treatment with a fixed appliance. The participants were asked to answer the Brazilian version of the FIS before treatment (T1) and 8 months after the bonding of the fixed appliance (T2). Statistical analysis was carried out using the Wilcoxon signed rank test and the Bonferroni correction for the overall score and FIS subscales. Responsiveness of the measure and the minimal clinically important difference (MCID) were also assessed. RESULTS Among the 94 participants initially admitted to the present study, two were excluded as a result of treatment dropout and failure to return the second questionnaire. Thus, a sample of 92 parents/caregivers participated (response rate: 97.8%). Among the 92 participants, 70 were the mothers of patients, 16 were fathers, and six were other family members. Statistically significant improvements were found in the overall score (P < .001) as well as in both parental activity and parental emotions subscales (P < .001). The reductions in scores were associated with effect sizes showing moderate clinically meaningful changes in the overall FIS and in the parental/family activity, parental emotions, and family conflict subscales. The MCID was 2.66 for the overall FIS. CONCLUSION The first 8 months of orthodontic treatment with a fixed appliance had a positive impact on the families of adolescents.