Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of residential medication management reviews on anticholinergic burden in aged care residents

Abstract Objectives: The primary objective of this study was to investigate the impact of Residential Medication Management Reviews (RMMRs) on anticholinergic burden quantified by seven anticholinergic risk scales. Design: Retrospective analysis. Setting: Accredited pharmacists conducted RMMRs in aged-care facilities (ACFs) in Sydney, Australia. Participants: RMMRs pertained to 814 residents aged 65 years or older. Measurements: Anticholinergic burden was quantified using seven scales at baseline, after pharmacists’ recommendations and after the actual GP uptake of pharmacists’ recommendations. Change in the anticholinergic burden was measured using the Wilcoxon sign rank test. Results: At baseline, depending on the scale used to estimate the anticholinergic burden, between 36% and 67% of patients were prescribed at least one regular anticholinergic medication (ACM). Anticholinergic burden scores were significantly (p < 0.001) lower after pharmacists’ recommendations as determined by each of the seven scales. The reduction in anticholinergic burden was also significant (p < 0.001) after GPs’ acceptance of the pharmacists’ recommendations according to all scales with the exception of one scale which reached borderline significance (p = 0.052). Conclusion: Despite the limitations of the retrospective design and differences in the estimation of anticholinergic burden, this is the first study to demonstrate that RMMRs are effective in reducing ACM prescribing in ACF residents, using a range of measures of anticholinergic burden. Future studies should focus on whether a decrease in anticholinergic burden will translate into improvement in clinical outcomes.
Testing Statebuilding’s ‘Missing Link’: Effects of Government Communications in Colombia

Abstract Research from developed countries indicates that improving how government communicates with the public can increase trust in government and satisfaction with public services. In countries affected by violent conflict, communication has even been described as the ‘missing link’ necessary to rebuild a positive relationship between citizen and state. Does this approach work? This paper presents a field experiment implemented in partnership with a Colombian government agency, to test two communication interventions in statebuilding areas. The results suggest limits to these programmes. One treatment – provision of information on service delivery via text messages – led to a reduction in satisfaction with services. For the second treatment – an invitation for citizens to vote on service provision priorities – we can detect no effect. We find evidence that people’s prior beliefs are strong drivers of these results: both treatments had negative effects among people with low political interest and knowledge, suggesting that informational interventions may backfire among precisely the sub-populations that statebuilders seek to engage. Instead of improving perceptions of service delivery, they may have raised expectations among this otherwise apathetic population.
Improving infant sleep and maternal mental health: a cluster randomised trial

Objectives: To determine whether a community-delivered intervention targeting infant sleep problems improves infant sleep and maternal well-being and to report the costs of this approach to the healthcare system. Design: Cluster randomised trial. Setting: 49 Maternal and Child Health (MCH) centres (clusters) in Melbourne, Australia. Participants: 328 mothers reporting an infant sleep problem at 7 months recruited during October–November 2003. Intervention: Behavioural strategies delivered over individual structured MCH consultations versus usual care. Main outcome measures: Maternal report of infant sleep problem, depression symptoms (Edinburgh Postnatal Depression Scale (EPDS)), and SF-12 mental and physical health scores when infants were 10 and 12 months old. Costs included MCH sleep consultations, other healthcare services and intervention costs. Results: Prevalence of infant sleep problems was lower in the intervention than control group at 10 months (56% vs 68%; adjusted OR 0.58 (95% CI: 0.36 to 0.94)) and 12 months (39% vs 55%; adjusted OR 0.50 (0.31 to 0.80)). EPDS scores indicated less depression at 10 months (adjusted mean difference −1.4 (−2.3 to −0.4) and 12 months (−1.7 (−2.6 to −0.7)). SF-12 mental health scores indicated better health at 10 months (adjusted mean difference 3.7 (1.5 to 5.8)) and 12 months (3.9 (1.8 to 6.1)). Total mean costs including intervention design, delivery and use of non-MCH nurse services were £96.93 and £116.79 per intervention and control family, respectively. Conclusions: Implementing this sleep intervention may lead to health gains for infants and mothers and resource savings for the healthcare system. Trial registration: Current Controlled Trial Registry, number ISRCTN48752250 (registered November 2004).
Axogenic effect of estrogen in male rat hypothalamic neurons involves Ca2+, protein kinase C, and extracellular signal‐regulated kinase signaling

17‐β‐Estradiol (E2) stimulates the growth of axons in male‐derived hypothalamic neurons in vitro. This effect is not exerted through the classical intracellular estrogen receptor (ER) but depends on a membrane mechanism involving TrkB. In the present study, we investigate the intracellular signaling cascade that mediates the axogenic effect of E2. Treatment with an intracellular Ca2+ chelator, a Ca2+‐dependent protein kinase C (PKC) inhibitor, or two specific inhibitors of extracellular signal‐regulated kinases (ERK) mitogen‐activated protein kinases (MAPK) completely inhibited the E2‐induced axogenesis. E2 and the membrane‐impermeant construct E2BSA rapidly induced phosphorylation of ERK, which was blocked by the specific inhibitor of the ERK pathway UO126 but not by the ER antagonist ICI 182,780. Decrease of intracellular free Ca2+ or disruption of PKC activation by Ro 32‐0432 attenuated ERK activation, indicating the confluence of signals in the MAPK pathway. Subcellular analysis of ERK demonstrated that the phospho‐ERK signal is augmented in the nucleus after 15 min of E2 stimulation. We have also shown that E2 increased phosphorylation of CREB via ERK signaling. In summary, this study demonstrates that E2, probably via a membrane‐associated receptor, induces axonal growth by activating CREB phosphorylation through ERK signaling by a mechanism involving Ca2+ and PKC activation. © 2007 Wiley‐Liss, Inc.
Molecular Mechanism by Which the K70E Mutation in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confers Resistance to Nucleoside Reverse Transcriptase Inhibitors

ABSTRACT The K70E mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has become more prevalent in clinical samples, particularly in isolates derived from patients for whom triple-nucleoside regimens that include tenofovir (TNV), abacavir, and lamivudine (3TC) failed. To elucidate the molecular mechanism by which this mutation confers resistance to these nucleoside RT inhibitors (NRTI), we conducted detailed biochemical analyses comparing wild-type (WT), K70E, and K65R HIV-1 RT. Pre-steady-state kinetic experiments demonstrate that the K70E mutation in HIV-1 RT allows the enzyme to discriminate between the natural deoxynucleoside triphosphate substrate and the NRTI triphosphate (NRTI-TP). Compared to the WT enzyme, K70E RT showed 2.1-, 2.3-, and 3.5-fold-higher levels of resistance toward TNV-diphosphate, carbovir-TP, and 3TC-TP, respectively. By comparison, K65R RT demonstrated 12.4-, 12.0-, and 13.1-fold-higher levels of resistance, respectively, toward the same analogs. NRTI-TP discrimination by the K70E (and K65R) mutation was primarily due to decreased rates of NRTI-TP incorporation and not to changes in analog binding affinity. The K65R and K70E mutations also profoundly impaired the ability of RT to excise 3′-azido-2′,3′-dideoxythymidine monophosphate (AZT-MP) and other NRTI-MP from the 3′ end of a chain-terminated primer. When introduced into an enzyme with the thymidine analog mutations (TAMs) M41L, L210W, and T215Y, the K70E mutation inhibited ATP-mediated excision of AZT-MP. Taken together, these findings indicate that the K70E mutation, like the K65R mutation, reduces susceptibility to NRTI by selectively decreasing NRTI-TP incorporation and is antagonistic to TAM-mediated nucleotide excision.
Private datacenter infrastructure: “building cost effective ‘YGPDI’ model for real time hands on labs using computing methodologies providing solutions in academic”

In today's world, the technology has emerged as a super power in the industrial world. But the scenario of educational system in Indian universities related with Lab and hands on with Virtualization and Cloud technology is too limited due to lack of resources and other problems [13], [14], [15]. Thus Students lead to lack of technical knowledge in the field of Virtualization, Infrastructure building, Cloud Computing, etc in [16], [17]. Today's industry needs infrastructure related to the technical domain which is a big challenge for the Educational System. For an example Datacenter building and management, Failover and availability, Mission Critical, network security, managing of operations etc remains theoretical only in the books. The proper infrastructure is not there to cater into the practical aspects. So this project comes with the technical solution. This project focuses about the lab infrastructure which cover entire Lab designing and Demonstration. The project aims in the Designing and Implementation process for developing of Lab and Hands on Procedure. The technology used for this is Linux, VMware products. The project results as a hands on and demonstration approach by configuring and building a private cloud required for software defined datacenter and managing it services for a multi-purpose Computing Laboratory using virtualization Technology.
Optimal arrangement of magnetic coils for functional magnetic stimulation of the inspiratory muscles in dogs

In an attempt to maximize inspiratory pressure and volume, the optimal position of a single or of dual magnetic coils during functional magnetic stimulation (FMS) of the inspiratory muscles was evaluated in twenty-three dogs. Unilateral phrenic magnetic stimulation (UPMS) or bilateral phrenic magnetic stimulation (BPMS), posterior cervical magnetic stimulation (PCMS), anterior cervical magnetic stimulation (ACMS) as well as a combination of PCMS and ACMS were performed. Trans-diaphragmatic pressure (Pdi), flow, and lung volume changes with an open airway were measured. Transdiaphragmatic pressure was also measured with an occluded airway. Changes in inspiratory parameters during FMS were compared with 1) electrical stimulation of surgically exposed bilateral phrenic nerves (BPES) and 2) ventral root electrical stimulation at C5-C7 (VRES C5-C7). Relative to the Pdi generated by BPES of 36.3/spl plusmn/4.5 cm H/sub 2/O (Mean /spl plusmn/ SEM), occluded Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and a combined PCMS + ACMS were 51.7%, 61.5%, 22.4%, 100.3%, and 104.5% of the maximal Pdi, respectively. Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and combined ACMS + PCMS were 38.0%, 45.2%, 16.5%, 73.8%, and 76.8%, respectively, of the Pdi induced by VRES (C5-C7) (48.0/spl plusmn/3.9 cm H/sub 2/O). The maximal Pdi(s) generated during ACMS and combined PCMS + ACMS were higher than the maximal Pdi(s) generated during UPMS, BPMS, or PCMS (p<0.05). ACMS alone induced 129.8% of the inspiratory flow (73.0/spl plusmn/9.4 L/min) and 77.5% of the volume (626/spl plusmn/556 ml) induced by BPES. ACMS and combined PCMS + ACMS produce a greater inspiratory pressure than UPMS, BPMS or PCMS. ACMS can be used to generate sufficient inspiratory pressure, flow, and volume for activation of the inspiratory muscles.
N′-(5-Fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene)benzenesulfonohydrazide

The molecule of the title compound, C14H10FN3O3S, consists of an indole unit and a phenylsulfonyl unit that are disposed in an approximately trans orientation relative to the N—N single bond. Two molecules are arranged about a center of inversion, forming a hydrazide–carbonyl N—H⋯O hydrogen-bonded dimer; the dimers are linked by an indole–sulfonyl N—H⋯O hydrogen bond into a ribbon.
Interaction with the Histone Chaperone Vps75 Promotes Nuclear Localization and HAT Activity of Rtt109 In Vivo

Modification of histones is critical for the regulation of all chromatin‐templated processes. Yeast Rtt109 is a histone acetyltransferase (HAT) that acetylates H3 lysines 9, 27 and 56. Rtt109 associates with and is stabilized by Nap1 family histone chaperone Vps75. Our data suggest Vps75 and Nap1 have some overlapping functions despite their different cellular localization and histone binding specificity. We determined that Vps75 contains a classical nuclear localization signal and is imported by Kap60–Kap95. Rtt109 nuclear localization depends on Vps75, and nuclear localization of the Vps75–Rtt109 complex is not critical for Rtt109‐dependent functions, suggesting Rtt109 may be able to acetylate nascent histones before nuclear import. To date, the effects of VPS75 deletion on Rtt109 function had not been separated from the resulting Rtt109 degradation; thus, we used an Rtt109 mutant lacking the Vps75‐interaction domain that is stable without Vps75. Our data show that in addition to promoting Rtt109 stability, Vps75 binding is necessary for Rtt109 acetylation of the H3 tail. Direct interaction of Vps75 with H3 likely allows Rtt109 access to the histone tail. Furthermore, our genetic interaction data support the idea of Rtt109‐independent functions of Vps75. In summary, our data suggest that Vps75 influences chromatin structure by regulating histone modification and through its histone chaperone functions.
VALIDITY OF F-H PUZZLE IN PAKISTAN ECONOMY: A TIME SERIES STUDY

Purpose:The objective of this paper is to examine the validity of F-H puzzle in the context of Pakistan. In this study the Feldstein-Horioko puzzle investigated in Pakistan which states that the existence of relationship between saving and investment is the indication of capital immobility. Methodology:The data of gross domestic product saving, capital formation and current account from 1980 to 2016 collected from State Bank of Pakistan, IMF outlook data base and Economic Survey of Pakistan.The ADF and PP test used to find out the stationarity of the variables. Famous Johansen cointegration used to check the long run relationship between saving and investment and between current account and investment. Findings:The results of unit root test indicate that all the variables are stationary at their first difference. The empirical results of cointegration test shows that there is no long run relation exist between saving and investment and long run relationship exist between current account and investment which does not support the findings of F-H puzzle and shows that capital is perfectly mobile in case of Pakistani economy.
Pharmacological Preconditioning by Low Dose Cobalt Protoporphyrin Induces Heme Oxygenase-1 Overexpression and Alleviates Retinal Ischemia-Reperfusion Injury in Rats

Purpose: Retinal ischemia-induced neuronal death plays a crucial role in certain severe visual impairment diseases. The aims of this study were to investigate the effects of low dose cobalt protoporphyrin IX (CoPP), an inducer of heme oxygenase-1 (HO-1), on the retina of rats against ischemia-reperfusion (IR) injury. Methods: Retinal IR was achieved in rats by raising intraocular pressure for 60 min. CoPP (1 mg/ kg) was injected intraperitoneally 24 hr before IR. Retinal injury was assessed by the number of retinal ganglion cells (RGCs) seven days after reperfusion. TUNEL assay was used to detect the appearance of apoptotic cells 24 hr after reperfusion. The expressions of the HO-1 and Bax proteins were evaluated by Western blot. Results: Both HO-1 expression, examined by Western blot, and enzyme activity were increased strongly after CoPP administration. Rats treated with CoPP before IR had more RGCs (p = 0.034) and less apoptotic cells (p = 0.04) together with downregulated Bax protein levels (p = 0.03) compared to ischemic rats without CoPP. The protective effects of CoPP were HO-1 dependent because the upregulation of HO-1 and the RGC protection were both abolished by the HO-1 inhibitor tin protoporphyrin (SnPP). Conclusions: In this study, we demonstrated that induction of HO-1 expression by low dose CoPP ameliorated retinal damage from IR injury. The favorable effect appears to be related with modulations of the apoptotic pathway.
Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study.

BACKGROUND Multisite ventricular pacing has recently been proposed as an additional treatment for patients with severe congestive heart failure. To further assess the potential value of this technique, we compared the acute hemodynamic changes associated with pacing the right ventricular apex (RVA) or outflow tract (RVOT) alone, the left ventricle (LV) alone, or biventricular (BIV) pacing of the RVA and LV together. METHODS AND RESULTS Acute hemodynamic findings were measured in 27 patients with severe heart failure despite optimal therapy and either first-degree AV block and/or an intraventricular conduction defect. In the 23 patients with a high pulmonary capillary wedge pressure (PCWP) (>15 mm Hg), data were collected after transvenous pacing at different ventricular sites in either the VDD mode (AV delay=100 ms) or the VVI mode in patients with atrial fibrillation (n=6). The mean baseline cardiac index was 1.82 L x min(-1) x m(-2). Mean+/-SD baseline systolic blood pressure (SBP) (118.5+/-15.2 mm Hg), PCWP (26.4+/-6.6 mm Hg), and V-wave amplitude (39.1+/-14.6 mm Hg) were similar before and after either RVA or RVOT pacing. In contrast, LV-based pacing (either LV alone or BIV pacing) resulted in higher SBP (P<.03) and lower PCWP (P<.01) and V-wave amplitude (P<.001) than either baseline or RV pacing measurements. With LV pacing alone, SBP, PCWP, and V waves were 126.5+/-15.1, 20.7+/-5.9, and 25.5+/-8.1 mm Hg, respectively. The results with LV pacing alone were similar to those obtained with BIV pacing. CONCLUSIONS In patients with severe congestive heart failure, both LV pacing alone and BIV pacing resulted in a similar and significant acute improvement in SBP, PCWP, and V-wave amplitude compared with baseline measurements and RV pacing alone. These results provide a strong basis for initiating long-term studies examining the chronic effects of LV-based pacing in patients with medically refractory congestive heart failure.
Liver Fatty Acid-binding Protein Targets Fatty Acids to the Nucleus

Although unesterified long chain fatty acids interact with peroxisome proliferator-activated receptors to initiate transcription within the nucleus, almost nothing is known regarding factors regulating long chain fatty acid distribution to the nucleus of living cells. The possibility that the liver fatty acid-binding protein (L-FABP) may function in this role was addressed in transfected L-cell fibroblasts overexpressing L-FABP using a series of fluorescent fatty acids differing in chain length and unsaturation. After 30 min of incubation, oxidation of BODIPY-, NBD-, and cis-parinaric acids was undetectable in L-cells. Likewise, L-cells very poorly esterified these fluorescent fatty acids in the following order: 0% BODIPY-C5, NBD-C6 (short chain length) < 0–3% NBD-C18, BODIPY-C16, cis-parinaric acid (long chain length) < 11% BODIPY-C12 (medium chain length). Real time confocal and multiphoton laser scanning microscopy (CLSM and MPLSM) showed that these fluorescent fatty acids were generally taken up in the following order: long chain (BODIPY-C16, NBD-C18) > medium chain (BODIPY-C12) ≫ short chain (BODIPY-C5, NBD-C6). The fluorescent fatty acids were imaged in the nucleus, primarily associated with the nuclear envelope, at levels about 2–3-fold lower than outside the nucleus. CLSM and MPLSM showed that L-FABP expression enhanced by 2–4-fold the initial rate and/or average maximal uptake of the long and medium chain but not the short chain fluorescent fatty acids in living cells. Furthermore, L-FABP expression increased the targeting of long and medium but not short chain fluorescent fatty acids to the nucleus by 2.9–4.4-fold and increased the proportion (i.e.nuclear:cytoplasm ratio) of medium and long chain but not short chain fatty acids by 2–3.6-fold. In summary, these results showed for the first time the presence of unesterified fatty acids in the nucleus of living cells and demonstrated that expression of a fatty acid-binding protein, L-FABP, specifically enhanced uptake and intracellular targeting of long and medium chain fatty acids to the nucleus.
Identifying patterns of situational antecedents to heavy drinking among college students

Abstract Background: Emerging adults have the highest prevalence of heavy drinking as compared to all other age groups. Given the negative consequences associated with such drinking, additional research efforts focused on at-risk consumption are warranted. The current study sought to identify patterns of situational antecedents to drinking and to examine their associations with drinking motivations, alcohol involvement, and mental health functioning in a sample of heavy drinking college students. Method: Participants were 549 (65.8% women) college student drinkers. Results: Latent profile analysis identified three classes based on likelihood of heavy drinking across eight situational precipitants. The ‘High Situational Endorsement’ group reported the greatest likelihood of heavy drinking in most situations assessed. This class experienced the greatest level of alcohol-related harms as compared to the ‘Low Situational Endorsement’ and ‘Moderate Situational Endorsement’ groups. The Low Situational Endorsement class was characterized by the lowest likelihood of heavy drinking across all situational antecedents and they experienced the fewest alcohol-related harms, relative to the other classes. Class membership was related to drinking motivations with the ‘High Situational Endorsement’ class endorsing the highest coping- and conformity-motivated drinking. The ‘High Situational Endorsement’ class also reported experiencing more mental health symptoms than other groups. Conclusions: The current study contributed to the larger drinking literature by identifying profiles that may signify a particularly risky drinking style. Findings may help guide intervention work with college heavy drinkers.
Hepatitis E virus capsid protein assembles in 4M urea in the presence of salts

The hepatitis E virus (HEV) capsid protein has been demonstrated to be able to assemble into particles in vitro. However, this process and the mechanism of protein–protein interactions during particle assembly remain unclear. In this study, we investigated the assembly mechanism of HEV structural protein subunits, the capsid protein p239 (aa368–606), using analytical ultracentrifugation. It was the first to observe that the p239 can form particles in 4M urea as a result of supplementation with salt, including ammonium sulfate [(NH4)2SO4], sodium sulfate (Na2SO4), sodium chloride (NaCl), and ammonium chloride (NH4Cl). Interestingly, it is the ionic strength that determines the efficiency of promoting particle assembly. The assembly rate was affected by temperature and salt concentration. When (NH4)2SO4 was used, assembling intermediates of p239 with sedimentation coefficient values of approximately 5 S, which were mostly dodecamers, were identified for the first time. A highly conserved 28‐aa region (aa368–395) of p239 was found to be critical for particle assembly, and the hydrophobic residues Leu372, Leu375, and Leu395of p239 was found to be critical for particle assembly, which was revealed by site‐directed mutagenesis. This study provides new insights into the assembly mechanism of native HEV, and contributes a valuable basis for further investigations of protein assembly by hydrophobic interactions under denaturing conditions.