Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Identification of Mycobacteria to the Species Level Using INNO-LiPA Mycobacteria, a Reverse Hybridization Assay

ABSTRACT INNO-LiPA Mycobacteria (LiPA; Innogenetics, Zwijnaarde, Belgium) is a kit for the simultaneous detection and identification ofMycobacterium species in culture and identifies theMycobacterium tuberculosis complex, the M. avium complex (MAC), and the following Mycobacteriumspecies: M. kansasii, M. avium, M. intracellulare, M. scrofulaceum, M. gordonae, M. xenopi, and the M. chelonae-M. abscessus complex. The assay, which targets the 16S-23S rRNA spacer region, was evaluated on 157 mycobacterial strains that had been identified by conventional techniques and PCR-restriction enzyme analysis of the hsp65 gene (PRA). Forty-seven reference strains consisting of 37 different species and 110 human clinical isolates were submitted to the test, and all were hybridized with theMycobacterium genus probe (MYC) on the LiPA strip (100% sensitivity). Ninety-four isolates hybridized to their corresponding species- or complex-specific probes; only one isolate phenotypically identified as M. gordonae did not react with its specific probe (99.4% accuracy). Thirty-seven MAC strains were phenotypically identified to the complex level and to the species level by LiPA asM. avium (n = 18) or M. intracellulare (n = 7) or as belonging to theM. avium-M. intracellulare-M. scrofulaceum complex (n = 12). Of the last 12 strains, 10 had M. avium PRA patterns and 2 had M. intracellulare PRA patterns. Three isolates that had been identified as a single species by conventional identification were proven to be mixed cultures by the LiPA assay. The whole procedure can be performed in 1 working day, starting with the supernatant of a small amount of bacterial mass that had been treated by freezing and then boiling.
Should the Federal Reserve Pay Competitive Interest on Reserves

In 2008, the Federal Reserve began paying interest on reserves. How should the Fed use this new policy instrument? As the Fed reduces its balance sheet, should it continue to satiate reserve demand and pay competitive interest on reserves? Here, we argue that this may be an inefficient use of the new policy instrument. Using a standard Dynamic Stochastic General Equilibrium model (DSGE), augmented to include a banking sector and an interbank market, our benchmark calibration implies an optimal tax on reserves of about 20 to 40 basis points in the steady state, and a fluctuating tax rate in response to shocks.
Significance of Candida recovered from intraoperative specimens in patients with intra-abdominal perforations.

OBJECTIVE Determine the significance of recovering yeasts from intraoperative specimens from the abdominal cavity and to evaluate the effect of a single intraoperative dose of fluconazole on clinical outcome in patients with intra-abdominal perforations. DESIGN Prospective, randomized, double-blind study. SETTING Multicenter study from 13 hospitals in Norway. PATIENTS One hundred nine patients with intra-abdominal perforations. INTERVENTIONS Patients were randomized to receive either a single 400-mg fluconazole dose or placebo during the operation. MEASUREMENTS AND MAIN RESULTS An intra-abdominal specimen for microbiological culture was obtained at the time of the operation. The primary response variable in the study was death. Secondary response variables were three parameters indicating a complicated postoperative period: mechanical ventilation for > or = 5 days, intensive care treatment for > or = 10 days, and use of a central venous catheter for > or = 10 days. Yeasts were recovered from a intraoperative intra-abdominal specimen from only 1 (3.5%) of 28 patients with perforated appendicitis and from 32 (39.5%) of 81 nonappendicitis patients. Excluding the appendicitis patients, the yeast recovery rate was high both for patients hospitalized at the time of the perforation (45%) and for nonhospitalized patients (32%). The overall mortality was 11% (12 patients). Single-dose intraoperative fluconazole prophylaxis did not reach a statistically significant effect on mortality (4 of 53 patients in the fluconazole group and 8 of 56 patients in the placebo group died [p = .059]). The only two explanatory variables significantly related to death were a intraoperative finding of yeast from an intra-abdominal specimen and the occurrence of a spontaneous perforation in a patient already hospitalized for nonsurgical cancer treatment. Detection of yeast was also a significant explanatory variable for a prolonged period of mechanical ventilation, intensive care treatment, and prolonged use of a central venous catheter. CONCLUSIONS Single-dose intraoperative fluconazole prophylaxis did not have a statistically significant effect on overall mortality (odds ratio = 0.21; 95% confidence interval, 0.04-1.06; p = .059) in patients with intra-abdominal perforation. The recovery rate of yeast from intraoperative specimens from the abdominal cavity was high (>30%) and was associated with death and a complicated postoperative course.
Hepatoprotective effects of DL-α-lipoic acid and α-Tocopherol through amelioration of the mitochondrial oxidative stress in acetaminophen challenged rats

Abstract Acetaminophen (APAP) is known to induce liver mitochondrial dysfunction leading to acute hepatotoxicity. Effect of DL-α-lipoic acid (LA) and α-tocopherol (α-Toc) against the APAP-induced liver mitochondrial damage was evaluated in rats. LA (100 mg/kg, p.o.) and α-Toc (100 mg/kg, p.o.) were given once daily for 15 d, prior to the APAP administration (3 g/kg, p.o). Hepatic damage was confirmed by determining the activities of serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase and alkaline phosphatase, 4 h after the single dose of APAP. To assess the mitochondrial damage, the activities of antioxidant enzymes, Krebs’ cycle dehydrogenases and mitochondrial electron transport chain complexes, and levels of reactive oxygen species (ROS), reduced glutathione, lipid peroxidation (malondialdehyde, MDA) as well as the mitochondrial membrane potential (Δψmt) were evaluated. The activities of mitochondrial enzymes and Δψmt were significantly (p < 0.01) decreased and the level of ROS and MDA were significantly (p < 0.01) increased due to APAP challenge. LA and α-Toc treatment significantly enhanced the activities of mitochondrial enzymes and Δψmt than that of control group; whereas the levels of ROS and MDA were decreased. The results of the study concluded that the liver damage induced by APAP was significantly ameliorated by LA and α-Toc. LA showed more protection than that of α-Toc. The protection can be partially ascribed to their mitochondrial protective effects through their antioxidant activity which could decrease the level of ROS and by direct enhancement of Δψmt.
Troublesome Triad: Trauma, Insomnia, and Alcohol

The objective of this study was to examine the relationships between combat related trauma, insomnia, and alcohol misuse. The author reviewed the standardized tests results from 39 active duty service members, all of whom had recent deployments to either Iraq or Afghanistan. The battery of self-test instruments assessed the effects of military trauma, anxiety, depression, alcohol use, and insomnia. Among the study subjects, the entire group reported significant sleep problems, with bedtime arousals impeding sleep initiation. Male subjects' reported an average AUDIT score of 8.62. Service members with higher trauma scores also reported greater misuse of alcohol. The high trauma scores also correlated with specific pre-sleep cognitive and somatic factors. The findings of this study lend support for the use of standardized instruments for assessing sleep problems, along with similar tests for trauma and substance misuse, which together should help identify high risk military patients.
Vascular Endothelial Growth Factor Induces Abnormal Microvasculature in the Endoglin Heterozygous Mouse Brain

Hereditary hemorrhagic telangiectasia (HHT), associated with brain arteriovenous malformations, is caused by a loss of function mutation in either the endoglin (HHT1) or activin receptor-like kinase 1 gene (ALK-1, HHT2). Endoglin heterozygous (Eng+/−)mice have been proposed as a disease model. To better understand the role of endoglin in vascular malformation development, we examined the effect of vascular endothelial growth factor (VEGF) hyperstimulation on microvessels in adult endoglin heterozygous (Eng+/−) mice using an adenoviral vector to deliver recombinant human VEGF165 cDNA (AdhVEGF) into basal ganglia. VEGF expression was increased in AdhVEGF mice compared with the AdlacZ and saline group (P < 0.05) and localized to multiple cell types (neurons, astrocytes, endothelial cells, and smooth muscle cells) by double-labeled immunostaining. VEGF overexpression increased microvessel count for up to 4 weeks in both the Eng+/+ and Eng+/+ groups (Eng+/+ 185 ± 14 vs. Eng+/− 201 ± 10 microvessels/mm2). Confocal microscopic examination revealed grossly abnormal microvessels in eight of nine Eng+/− mouse brains compared with zero of nine in Eng+/+ mice (P < 0.05). Abnormal microvessels featured enlargement, clustering, twist, or spirals. VEGF receptor Flk-1 and TGF-β receptor 1 (TβR1) expression were reduced in the Eng+/− mouse brain compared with control. Excessive VEGF stimulation may play a pivotal role in the initiation and development of brain vessel malformations in states of relative endoglin insufficiency in adulthood. These observations are relevant to our general understanding of the maintenance of vascular integrity.
The nucleoporin Nup214 sequesters CRM1 at the nuclear rim and modulates NFκB activation in Drosophila

CRM1-mediated protein export is an important determinant of the nuclear accumulation of many gene regulators. Here, we show that the NFκB transcription factor Dorsal is a substrate of CRM1 and requires the nucleoporin Nup214 for its nuclear translocation upon signaling. Nup214 bound to CRM1 directly and anchored it to the nuclear envelope. In nup214 mutants CRM1 accumulated in the nucleus and NES-protein export was enhanced. Nup214 formed complexes with Nup88 and CRM1 in vivo and Nup214 protected Nup88 from degradation at the nuclear rim. In turn, Nup88 was sufficient for targeting the complex to the nuclear pores. Overexpression experiments indicated that Nup214 alone attracts a fraction of CRM1 to the nuclear envelope but does not interfere with NES-GFP export. By contrast, overexpression of the Nup214-Nup88 complex trapped CRM1 and Dorsal to cytoplasmic foci and inhibited protein export and immune response activation. We hypothesize that variation in levels of the Nup214-Nup88 complex at the pore changes the amount of NPC-bound CRM1 and influences the relative strength and duration of NFκB signaling responses.
Proteomic Characterization of Inhibitory Synapses Using a Novel pHluorin-tagged γ-Aminobutyric Acid Receptor, Type A (GABAA), α2 Subunit Knock-in Mouse*

The accumulation of γ-aminobutyric acid receptors (GABAARs) at the appropriate postsynaptic sites is critical for determining the efficacy of fast inhibitory neurotransmission. Although we know that the majority of synaptic GABAAR subtypes are assembled from α1–3, β, and γ2 subunits, our understanding of how neurons facilitate their targeting to and stabilization at inhibitory synapses is rudimentary. To address these issues, we have created knock-in mice in which the pH-sensitive green fluorescent protein (GFP) and the Myc epitope were introduced to the extracellular domain of the mature receptor α2 subunit (pHα2). Using immunoaffinity purification and mass spectroscopy, we identified a stable complex of 174 proteins that were associated with pHα2, including other GABAAR subunits, and previously identified receptor-associated proteins such as gephyrin and collybistin. 149 of these proteins were novel GABAAR binding partners and included G-protein-coupled receptors and ion channel subunits, proteins that regulate trafficking and degradation, regulators of protein phosphorylation, GTPases, and a number of proteins that regulate their activity. Notably, members of the postsynaptic density family of proteins that are critical components of excitatory synapses were not associated with GABAARs. Crucially, we demonstrated for a subset of these novel proteins (including cullin1, ephexin, potassium channel tetramerization domain containing protein 12, mitofusin2, metabotropic glutamate receptor 5, p21-activated kinase 7, and Ras-related protein 5A) bind directly to the intracellular domains of GABAARs, validating our proteomic analysis. Thus, our experiments illustrate the complexity of the GABAAR proteome and enhance our understanding of the mechanisms neurons use to construct inhibitory synapses.
Early integrin binding to Arg-Gly-Asp peptide activates actin polymerization and contractile movement that stimulates outward translocation

Integrin-mediated adhesions are critical for stem cell differentiation, cancer metastasis, and the immune response [Hynes RO (2009) Science 326:1216–1219]. However, the mechanisms of early adhesion formation remain unclear, especially the effects of lateral clustering of integrins and the role of the Src family kinases. Using mobile Arg–Gly–Asp (RGD) peptide ligands on lipid bilayers with nano-fabricated physical barriers [Salaita K, et al. (2010) Science 327:1380–1385], we observe surprising long-range lateral movements of ligated integrins during the process of cell spreading. Initially, RGD-activated integrin clusters stimulate actin polymerization that radiates from the clusters. Myosin II contraction of actin from adjacent clusters produces contractile pairs that move toward each other against barriers. Force generated by myosin II stimulates a Src kinase-dependent lamellipodial extension and outward movement of clusters. Subsequent retraction by myosin II causes inward movement of clusters. The final cell spread area increases with the density of periodic barriers. Early integrin clustering recruits adhesion proteins, talin, paxillin, and FAK, irrespective of force generation. However, recruitment of vinculin is only observed upon contraction. Thus, we suggest that integrin activation and early clustering are independent of lateral forces. Clustering activates Src-dependent actin polymerization from clusters. Myosin contraction of clusters to lines stimulates active spreading with outward forces from actin polymerization followed by a second wave of contraction. Many of these early mechanical steps are not evident in cells spreading on immobilized matrices perhaps because of the low forces involved. These observations can provide new targets to control integrin-dependent adhesion and motility.
Costs and Consequences: A Review of Discharge Opioid Prescribing for ongoing Management of Acute Pain

Over recent years there has been a growing need for patients to be sent home from hospital with prescribed opioids for ongoing management of their acute pain. Increasingly complex surgery is being performed on a day-stay or 23-hour-stay basis and inpatients after major surgery and trauma are now discharged at a much earlier stage than in the past. However, prescription of opioids to be self-administered at home is not without risk. In addition to the potential for acute adverse effects, including opioid-induced ventilatory impairment and impairment of driving skills, a review of the literature shows that opioid use continues in some patients for some years after surgery. There are also indications that over-prescription of discharge opioids occur with a significant amount not consumed, resulting in a potentially large pool of unused opioid available for later use by either the patient or others in the community. Concerns about the potential for harm arising from prescription of opioids for ongoing acute pain management after discharge are relatively recent. However, at a time when serious problems resulting from the non-medical use of opioids have reached epidemic proportions in the community, all doctors must be aware of the potential risks and be able to identify and appropriately manage patients where there might be a risk of prolonged opioid use or misuse. Anaesthetists are ideally placed to exercise stewardship over the use of opioids, so that these drugs can maintain their rightful place in the post-discharge analgesic pharmacopoeia.
Daughters Providing Poststroke Care

Stroke is a leading cause of disability and dependence on the family, specifically daughter caregivers. The quality of the parent–child relationship can influence the experiences and well-being of daughters. Little is known about this in the context of stroke caregiving. We aimed to explore daughters’ perceptions of changes in the relationship with their parent and how these changes contribute to their well-being. We used a qualitative descriptive design. Twenty-three daughters completed one in-depth interview that was transcribed, reviewed, coded, and categorized to generate themes. The parent–child relationship was central to each of the three themes: It (a) led daughters to take on the caregiving role, (b) changed as a result of caregiving, and (c) contributed to daughters’ physical and emotional health. Targeted counseling that addresses changes in the parent–child relationship can help mitigate losses in communication and intimacy between daughters and parents. Insight into temporal relationship changes is needed.
Autoregressive spectral modeling of Motor Unit Action Potentials: Preliminary findings

Autoregressive (AR) spectral modeling of Motor Unit Action Potentials (MUAPs) has been suggested in the past but not thoroughly investigated. In this study AR spectral modeling was applied on MUAPs recorded from the biceps muscle. The AR parameters were estimated using the Yule-Walker, Burg, and Modified Covariance methods. Findings suggest that a similar spectral envelope was obtained by the Burg and the Modified Covariance methods of order 12.
Differences in insulin resistance do not predict weight loss in response to hypocaloric diets in healthy obese women.

The current study was initiated to determine whether insulin resistance and/or hyperinsulinemia affected the ability of obese individuals to lose weight in response to hypocaloric diets. Thirty-one obese, nondiabetic women, with values for body mass index ranging from 28.0-35.0 kg/m2, volunteered for this program. Resistance to insulin-mediated glucose disposal was assessed by determining their steady state plasma insulin and glucose concentration during the last 30 min of a 180-min infusion of somatostatin, insulin, and glucose. The total integrated insulin response to breakfast and lunch was also determined. After the baseline measurements, volunteers were placed on a hypocaloric diet calculated to lead to a minimum weekly loss of 1% of ideal body weight. Individuals who met the criteria after 30 days of dieting were defined as weight loss successes (n = 20) and continued on the diet for another 30 days. Individuals not meeting the criteria were designated as weight loss failures (n = 12) and were discharged from the study. There was a mean (+/-SEM) weight loss at 60 days of 9.2 +/- 0.4 kg in the 20 individuals defined as weight loss successes, but there was no correlation between weight loss and either steady state plasma glucose or the total integrated insulin response (r < 0.1; P > 0.83). Furthermore, using the same criteria to define insulin sensitivity and insulin resistance as those for therapeutic successes, the therapeutic failures comprised six insulin-sensitive and five insulin-resistant subjects. In summary, insulin-mediated glucose disposal varied widely in nondiabetic, obese women, and there was no relationship between baseline insulin resistance or total integrated insulin response and weight loss. It is concluded that the ability to lose weight on a calorie-restricted diet over a short time period does not vary in obese, healthy women as a function of insulin resistance or hyperinsulinemia.
Best Practices for QSAR Model Development, Validation, and Exploitation

After nearly five decades “in the making”, QSAR modeling has established itself as one of the major computational molecular modeling methodologies. As any mature research discipline, QSAR modeling can be characterized by a collection of well defined protocols and procedures that enable the expert application of the method for exploring and exploiting ever growing collections of biologically active chemical compounds. This review examines most critical QSAR modeling routines that we regard as best practices in the field. We discuss these procedures in the context of integrative predictive QSAR modeling workflow that is focused on achieving models of the highest statistical rigor and external predictive power. Specific elements of the workflow consist of data preparation including chemical structure (and when possible, associated biological data) curation, outlier detection, dataset balancing, and model validation. We especially emphasize procedures used to validate models, both internally and externally, as well as the need to define model applicability domains that should be used when models are employed for the prediction of external compounds or compound libraries. Finally, we present several examples of successful applications of QSAR models for virtual screening to identify experimentally confirmed hits.
The dexmedetomidine “augmented” sedato analgesic cocktail: An effective approach for sedation in prolonged endoscopic retrograde cholangio-pancreatography

Background and Aims: In absence of any published standard guideline for sedation or anesthesia practice for prolonged therapeutic “endoscopic retrograde cholangio-pancreatography (ERCP)”, safe and cost-effective sedation protocol is the need of the hour. Our study aims to evaluate the efficacy of a dexmedetomidine as an add-on for prolonged deep sedation for ERCP and to compare three deep sedation regimens regarding safety and efficacy. Material and Methods: Forty-five consecutively enrolled patients planned for therapeutic ERCP and assumed to have prolonged procedural duration (>50 min) were divided into three groups in a randomized assessor blinded fashion. Group 1 received propofol and midazolam, Group 2 received the sedato-analgesic cocktail containing ketamine-propofol-midazolam-pentazocine, and the Group 3 received sedate-analgesic cocktail plus dexmedetomidine infusion under monitoring of vital parameters and according to the judgment of the concerned anesthesiologist. Total propofol requirement, episodes of gagging, oxygen desaturation, changes in mean blood pressure (MBP), recovery and satisfaction score of endoscopist, anesthetist and patient were noted and analyzed statistically using one way ANOVA with Bonferroni correction and Chi-square test. Results: Mean propofol requirement, incidences of gagging and oxygen desaturation was significantly less in Group 2 and 3 compared to Group 1. MBP was more stable and recovery was faster in Group 3. Anesthetist's satisfaction was more with Group 2 and even more with Group 3. Conclusions: The sedato-analgesic cocktail was superior to the conventional propofol-midazolam regimen, dexmedetomidine as add-on increased the efficacy and safety of sedate-analgesic cocktail. It reduces propofol requirement, helps to maintain the patient in a safe and more stable level of sedation and increases satisfaction of the anesthetist.