Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro activity of an aqueous allicin extract and a novel allicin topical gel formulation against Lancefield group B streptococci.

BACKGROUND Studies have shown the efficacy of intra-partum antibiotics in preventing early-onset group B streptococcal sepsis. This approach results in a high intra-partum antibiotic use. Worryingly, the same antibiotics used in prophylaxis are also first-line treatment for neonatal sepsis, and antibiotic exposure in the peri-natal period has been shown to be a risk factor for late-onset serious bacterial infections and allergic disease. Antibiotic exposure in the peri-natal period is becoming a major public health issue; alternative strategies are needed. Garlic has been traditionally used to treat vaginal infections. Allicin is the main antibacterial agent isolated from garlic. OBJECTIVES The aim of the study was to investigate the in vitro activity of a novel allicin extract in aqueous and gel formulation against 76 clinical isolates of Lancefield group B streptococci (GBS). METHODS MICs and MBCs of allicin were determined for 76 GBS isolates by agar dilution and microtitre plate methods. Killing kinetics were determined for a selected 16 of the 76 strains. Agar diffusion tests were compared for allicin liquid and gel (500 mg/L). RESULTS AND CONCLUSIONS MICs and MBCs of allicin liquid were 35 to 95 mg/L and 75 to 315 mg/L, respectively. Time/dose kill curves produced a 2-3 log reduction in cfu/mL within 3 h and no detectable growth at 8 and 24 h. A novel 500 mg/L allicin gel produced an average zone size of 23+/-6 mm compared with 21+/-6 mm for allicin in water. Aqueous allicin is bactericidal against GBS isolates and maintains activity in a novel gel formulation.
First Finding of Melanic Sylvatic Triatoma infestans (Hemiptera: Reduviidae) Colonies in the Argentine Chaco

ABSTRACT Triatoma infestans (Klug), the most important vector of Chagas disease in southern South America, is a highly domiciliated species with well-known sylvatic foci only in the Bolivian Andean valleys and in the Bolivian Chaco, where melanic insects designated as “dark morphs” were found. After the tentative identification of two melanic bugs collected from parrot nests in a forest reserve in the Argentine Chaco as T. infestans, we conducted an intensive search there using mouse-baited sticky traps in summer 2006 and 2007. Four live T. infestans bugs were collected in trees without parrot nests in 288 trap-nights, whereas no bug was collected from inside trees with active parrot nests in 51 trap-nights. To increase bug captures, hollow tree trunks that recently had had Amazona aestiva (Berlepsch) and Aratinga acuticaudata (Vieillot) parrot nests were treated with insecticide fumigant canisters exhibiting strong knockdown power. Four (22%) of 18 trees were positive for T. infestans with a dark phenotype. A fragment of the mitochondrial gene COI of 8 of the 14 triatomine bugs collected was successfully sequenced and confirmed as T. infestans. Most of the bugs were captured from Aspidosperma quebracho-blanco (Schlechter) hollow tree trunks harboring parrot nests. All of the T. infestans collected from the nearest house located at 10 km from the sylvatic foci displayed normal chromatic characters. The repeated finding of T. infestans in sylvatic habitats, albeit at very low density, shows that this species is capable of maintaining viable sylvatic foci in the absence of human hosts and immigration from domestic populations. These are the first confirmed findings of sylvatic T. infestans colonies in Argentina and of dark morphs in the Argentine Chaco.
The effectiveness of skills training for improving outcomes in supported employment.

OBJECTIVE This study evaluated whether a supplementary skills training program improved work outcomes for clients enrolled in supported employment programs. METHODS Thirty-five recently employed clients with severe mental illness who were receiving supported employment services at a free-standing agency were randomly assigned to participate in either the workplace fundamentals program, a skills training program designed to make work more "successful and satisfying," or treatment as usual. Knowledge of workplace fundamentals (for example, identifying workplace stressors, problem solving, and improving job performance) was assessed at baseline and at nine months; employment outcomes and use of additional vocational services were tracked for 18 months. RESULTS Clients in the workplace fundamentals group (N=17) improved more in knowledge of workplace fundamentals than those in the control group (N=18) at the nine-month follow-up, but the two groups did not differ in the number of hours or days worked, salary earned, or receipt of additional vocational services over the 18-month period. In general, clients in this study had higher educational levels and better employment outcomes than clients in most previous studies of supported employment, making it difficult to detect possible effects of the skills training intervention on work. CONCLUSIONS Supplementary skills training did not improve work outcomes for clients who were receiving supported employment.
Predictors of Dropout from Outpatient Mental Health Services; A Study from Rohtak, India

ABSTRACT Context: Dropout from mental health services is problematic in both developed and developing nations and often leads to poor outcomes. There is a lack of hospital-based studies assessing the factors responsible for treatment dropout from mental health services in Indian settings. This study aims to contribute in that direction by presenting a study done in a tertiary care hospital in North India. Methodology: This was a hospital-based retrospective chart review carried out on randomly selected 139 patients at a tertiary hospital from January 1, 2014, to June 30, 2014. For this chart review, an abstraction form was designed that recorded six sociodemographic variables, nine clinical factors, and two outcome variables (more than one follow-up and active follow-up till 6 months). Results: Out of 139 patients, 53 patients dropped out after the first visit and 105 patients dropped out by the end of 6 months. Lower education status (odds ratio [OR] = 8.2, 95% confidence interval [CI]: 2.30–29.50), severe mental illness (OR = 2.6, 95% CI: 1.05–6.49), and early referral to clinical psychologist (CP) (OR = 7.8, 95% CI: 1.87–6.49) were predictors of better rates of follow-up after first visit. Lower education status (OR = 4.9, 95% CI: 1.45–17.08), early referral to CP (OR = 5.8, 95% CI: 2.09–38.35), and previous treatment history (OR = 8.9, 95% CI: 1.97–17.52) were predictors of better rates of follow-up at the end of 6 months. Conclusion: The findings that education status, diagnosis, utilizing services of CP, and psychiatric services in past are correlated with dropout rates may be helpful in targeting patients who are more vulnerable to dropping out of care in the given setting.
Error adjustments for file linking methods using encrypted unique client identifier (eUCI) with application to recently released prisoners who are HIV+

Incarceration provides an opportunity to test for HIV, provide treatment such as highly active anti‐retroviral therapy, as well as link infected persons to comprehensive HIV care upon their release. A key factor in assessing the success of a program that links released individuals to care is the time from release to receiving care in the community (linkage time). To estimate the linkage time, records from correction systems are linked to Ryan White Clinic data using encrypted Unique Client Identifier (eUCI). Most of the records that were linked using eUCI belong to the same individual; however, in some cases, it may link records incorrectly, or not identify records that should have been linked. We propose a Bayesian procedure that relies on the relationships between variables that appear in either of the data sources, as well as variables that exists in both to identify correctly linked records among all linked records. The procedure generates K datasets in which each pair of linked records is identified as a true link or a false link. The K datasets are analyzed independently, and the results are combined using Rubin's multiple imputation rules. A small validation dataset is used to examine different statistical models and to inform the prior distributions of the parameters. In comparison with previously proposed methods, the proposed method utilizes all of the available data and is both flexible and computationally efficient. In addition, this approach can be applied in other file linking applications. Copyright © 2015 John Wiley & Sons, Ltd.
In Silico Screening for Inhibitors of P-Glycoprotein That Target the Nucleotide Binding Domains

Multidrug resistances and the failure of chemotherapies are often caused by the expression or overexpression of ATP-binding cassette transporter proteins such as the multidrug resistance protein, P-glycoprotein (P-gp). P-gp is expressed in the plasma membrane of many cell types and protects cells from accumulation of toxins. P-gp uses ATP hydrolysis to catalyze the transport of a broad range of mostly hydrophobic compounds across the plasma membrane and out of the cell. During cancer chemotherapy, the administration of therapeutics often selects for cells which overexpress P-gp, thereby creating populations of cancer cells resistant to a variety of chemically unrelated chemotherapeutics. The present study describes extremely high-throughput, massively parallel in silico ligand docking studies aimed at identifying reversible inhibitors of ATP hydrolysis that target the nucleotide-binding domains of P-gp. We used a structural model of human P-gp that we obtained from molecular dynamics experiments as the protein target for ligand docking. We employed a novel approach of subtractive docking experiments that identified ligands that bound predominantly to the nucleotide-binding domains but not the drug-binding domains of P-gp. Four compounds were found that inhibit ATP hydrolysis by P-gp. Using electron spin resonance spectroscopy, we showed that at least three of these compounds affected nucleotide binding to the transporter. These studies represent a successful proof of principle demonstrating the potential of targeted approaches for identifying specific inhibitors of P-gp.
Effective Reduction of Acute Ethanol Withdrawal by the Tetracycline Derivative, Tigecycline, in Female and Male DBA/2J Mice.

BACKGROUND Alcohol use disorder (AUD) is a spectrum disorder characterized by mild to severe symptoms, including potential withdrawal signs upon cessation of consumption. Approximately five hundred thousand patients with AUD undergo clinically relevant episodes of withdrawal annually (New Engl J Med, 2003, 348, 1786). Recent evidence indicates potential for drugs that alter neuroimmune pathways as new AUD therapies. We have previously shown the immunomodulatory drugs, minocycline and tigecycline, were effective in reducing ethanol (EtOH) consumption in both the 2-bottle choice and drinking-in-the-dark paradigms. Here, we test the hypothesis that tigecycline, a tetracycline derivative, will reduce the severity of EtOH withdrawal symptoms in a common acute model of alcohol withdrawal (AWD) using a single anesthetic dose of EtOH in seizure sensitive DBA/2J (DBA) mice. METHODS Naïve adult female and male DBA mice were given separate injections of 4 g/kg i.p. EtOH with vehicle or tigecycline (0, 20, 40, or 80 mg/kg i.p.). The 80 mg/kg dose was tested at 3 time points (0, 4, and 7 hours) post EtOH treatment. Handling-induced convulsions (HICs) were measured before and then over 12 hours following EtOH injection. HIC scores and areas under the curve were tabulated. In separate mice, blood EtOH concentrations (BECs) were measured at 2, 4, and 7 hours postinjection of 4 g/kg i.p. EtOH in mice treated with 0 and 80 mg/kg i.p. tigecycline. RESULTS AWD symptom onset, peak magnitude, and overall HIC severity were reduced by tigecycline drug treatment compared to controls. Tigecycline treatment was effective regardless of timing throughout AWD, with earlier treatment showing greater efficacy. Tigecycline showed a dose-responsive reduction in acute AWD convulsions, with no sex differences in efficacy. Importantly, tigecycline did not affect BECs over a time course of elimination. CONCLUSIONS Tigecycline effectively reduced AWD symptoms in DBA mice at all times and dosages tested, making it a promising lead compound for development of a novel pharmacotherapy for AWD. Further studies are needed to determine the mechanism of tigecycline action.
The Impact of Affect on Out-Group Judgments Depends on Dominant Information-Processing Styles

Two studies tested the affect-as-cognitive-feedback model, in which positive and negative affective states are not uniquely associated with particular processing styles, but rather serve as feedback about currently accessible processing styles. The studies extend existing work by investigating (a) both incidental and integral affect, (b) out-group judgments, and (c) downstream consequences. We manipulated processing styles and either incidental (Study 1) or integral (Study 2) affect and measured perceptions of out-group homogeneity. Positive (relative to negative) affect increased out-group homogeneity judgments when global processing was primed, but under local priming, the effect reversed (Studies 1 and 2). A similar interactive effect emerged on attributions, which had downstream consequences for behavioral intentions (Study 2). These results demonstrate that both incidental and integral affect do not directly produce specific processing styles, but rather influence thinking by providing feedback about currently accessible processing styles.
Functional AR Signaling Is Evident in an In Vitro Mouse Follicle Culture Bioassay That Encompasses Most Stages of Folliculogenesis1

Abstract Androgens have distinct physiological functions within the ovary. The biological action of androgens is primarily exerted through transcriptional regulation by the nuclear androgen receptor (AR), but the molecular cascades governed by AR remain largely unknown. At present, there is imminent concern that environmental man-made chemicals with antiandrogenic properties, among others, are capable of modulating hormonal responses, thereby interfering with normal physiological processes that are critical to fertility. In the present study, we aimed to further characterize a standardized and reproducible follicle culture system in terms of AR expression during in vitro folliculogenesis to be able to use it as a bioassay to study effects of antiandrogens on follicular and oocyte growth, steroid secretion profile, and oocyte meiotic maturation capacity. Immunohistochemical analysis revealed that cytoplasmic AR protein was translocated to the nucleus of granulosa and theca cells in response to endogenous androgen production in theca cells during preantral follicular development. During the antral phase in vitro, AR was differentially expressed in mural and cumulus cells, implying an oocyte-mediated regulation. Treatment of follicles with hydroxyflutamide or bicalutamide, two model antiandrogenic compounds, resulted in reduced follicular growth during the preantral phase, altered steroidogenic environment, and arrest in oocyte meiotic maturation in response to human chorionic gonadotropin. Androgen receptor expression in the culture model corresponded well to what is described in vivo, and this system revealed several ovarian functions targeted by AR antagonists that can be further investigated using more in-depth molecular techniques.
Expression of Macrophage Migration Inhibitory Factor by Neuroblastoma Leads to the Inhibition of Antitumor T Cell Reactivity In Vivo1

Neuroblastomas and many other solid tumors produce high amounts of macrophage migration inhibitory factor (MIF), which appears to play a role in tumor progression. We found that MIF expression in neuroblastoma inhibits T cell proliferation in vitro, raising the possibility that MIF promotes tumorigenesis, in part, by suppressing antitumor immunity. To examine whether tumor-derived MIF leads to suppression of T cell immunity in vivo, we generated MIF-deficient neuroblastoma cell lines using short hairpin small interfering RNAs (siRNA). The MIF knockdown (MIFKD) AGN2a neuroblastoma cells were more effectively rejected in immune-competent mice than control siRNA-transduced or wild-type AGN2a. However, the increased rejection of MIFKD AGN2a was not observed in T cell-depleted mice. MIFKD tumors had increased infiltration of CD8+ and CD4+ T cells, as well as increased numbers of macrophages, dendritic cells, and B cells. Immunization with MIFKD AGN2a cells significantly increased protection against tumor challenge as compared with immunization with wild-type AGN2a, and the increased protection correlated with elevated frequencies of tumor-reactive CD8+ T cells in the lymphoid tissue of treated animals. Increased numbers of infiltrating tumor-reactive CD8+ T cells were also observed at the site of tumor vaccination. In vitro, treatment of AGN2a-derived culture supernatants with neutralizing MIF-specific Ab failed to reverse T cell suppressive activity, suggesting that MIF is not directly responsible for the immune suppression in vivo. This supports a model whereby MIF expression in neuroblastoma initiates a pathway that leads to the suppression of T cell immunity in vivo.
Weak Organic Acids Decrease Borrelia burgdorferi Cytoplasmic pH, Eliciting an Acid Stress Response and Impacting RpoN- and RpoS-Dependent Gene Expression

The spirochete Borrelia burgdorferi survives in its tick vector, Ixodes scapularis, or within various hosts. To transition between and survive in these distinct niches, B. burgdorferi changes its gene expression in response to environmental cues, both biochemical and physiological. Exposure of B. burgdorferi to weak monocarboxylic organic acids, including those detected in the blood meal of fed ticks, decreased the cytoplasmic pH of B. burgdorferi in vitro. A decrease in the cytoplasmic pH induced the expression of genes encoding enzymes that have been shown to restore pH homeostasis in other bacteria. These include putative coupled proton/cation exchangers, a putative Na+/H+ antiporter, a neutralizing buffer transporter, an amino acid deaminase and a proton exporting vacuolar-type VoV1 ATPase. Data presented in this report suggested that the acid stress response triggered the expression of RpoN- and RpoS-dependent genes including important virulence factors such as outer surface protein C (OspC), BBA66, and some BosR (Borrelia oxidative stress regulator)-dependent genes. Because the expression of virulence factors, like OspC, are so tightly connected by RpoS to general cellular stress responses and cell physiology, it is difficult to separate transmission-promoting conditions in what is clearly a multifactorial and complex regulatory web.
Activation of Interferon Response Genes and of Plasmacytoid Dendritic Cells in HIV-1 Positive Subjects with GB Virus C Co-Infection

GB virus C (GBV-C) coinfection has a protective role in Human Immunodeficiency Virus (HIV) infection, and increases the duration of suppression of HIV-1 viremia in patients under Highly Active Anti-Retroviral Therapy (HAART). Since innate antiviral response may be involved in the protection, we analyzed the possible role of GBV-C as activator of innate immunity. To this aim, we measured the extent of activation of the interferon (IFN) system and of circulating Dendritic Cells (DC) in vivo, and the ability of GBV-C to activate these functions in vitro. Activation of IFN system and of circulating DC was compared in GBV-positive and -negative HIV-1 co-infected patients with HAART-driven suppression of HIV-1 viremia. Endogenous levels of IFN-γ and RNA-dependent protein kinase (PKR) mRNA were significantly higher in peripheral blood mononuclear cells (PBMC) from GBV-C-positive when compared to GBV-C-negative patients. IFN-γ expression was correlated with all the Interferon response genes (IRGs) and with GBV-C viremia. The frequency of circulating plasmacytoid DC (pDC) expressing the CD80 activation marker was increased in GBV-C-positive patients, and was correlated with GBV-C viral load. In vitro experiments indicated that GBV-C is able to induce IFN-γ expression in PBMC. In addition, in PBMC cultures GBV-C induced an increase of CD80 expression by pDC, that was reduced by antibody to IFN-γ. Our data indicate that in HIV-positive patients GBV-C coinfection promotes the activation of IFN-γ and downstream IRG expression, as well as with the activation/maturation of circulating pDC. GBV-C-driven IFN-γ activation is, at least in part, responsible for the increased maturation of pDC. This crosstalk may suggest a role for GBV-C coinfection in boosting the innate antiviral response to HIV infection.
Effects of endurance exercise on nocturnal hormone concentrations in males.

A preliminary study was conducted to evaluate the change in nocturnal concentrations of testosterone, luteinizing hormone, growth hormone, prolactin, thyroxine, and cortisol following a control day (no exercise) and on a day in which exercise was performed. Exercise consisted of 90 min of cycling at 70% of each subject's maximal oxygen uptake. The exercise occurred from 1630 to 1800 hr on the exercise day while a comparable period of rest took place on the control day. Hormonal concentrations were evaluated at 2-hr intervals for a 12-hr period each night (2000-0800 hr). The subjects slept from 2255 (+/- 20 min [X +/- S.E.M.]) until 0715 (+/- 15) during each night. All hormone responses were plotted and integrated for the 12-hr period. Analysis indicated that a significant augmentation of the prolactin and thyroxine responses occurred, while concurrently an attenuation of the growth hormone and cortisol responses were observed. Contrastingly, no significant effects were found for the testosterone and luteinizing hormones responses. The physiological significance of these findings remained to be determined, but the results do suggest that further research is warranted in the area.
Alterations of myocardial presynaptic sympathetic innervation in patients with multi-vessel coronary artery disease but without history of myocardial infarction

In patients with myocardial infarction, left ventricular sympathetic denervation exceeds the size of the scar tissue. However, little is known about the regional innervation in patients with coronary artery disease (CAD) but no myocardial infarction. Using positron emission tomography (PET) with 13N-ammonia and 11C-hydroxyephedrine (HED), resting perfusion and presynaptic sympathetic innervation were studied in eight patients (seven males, one female; 58±9 years) with multi-vessel CAD and no history of myocardial infarction. Using polar map analysis of the PET data, the results were regionally compared with normal databases. The mean HED retention was 8.0%±2.0%·min−1. Myocardial resting perfusion was normal in 23 of 24 vascular territories. Despite normal resting perfusion, significantly reduced HED retention, indicating dysinnervation, was found in 14 of 23 (61%) vascular territories (six of eight patients). Of the dysinnervated territories, 11 (79%) showed angiographically severe stenosis (⩾90% of native vessel/coronary artery bypass graft), eight (57%) showed ischaemia (myocardial perfusion scintigraphy/stress-electrocardiogram) and 12 (86%) had been revascularized. Of the nine segments with normal innervation, two (22%) revealed severe stenosis, two (22%) showed ischaemia and seven (78%) had been revascularized. It can be concluded that, in patients with advanced CAD and normal left ventricular function, dysinnervation can occur in the absence of myocardial infarction. This is consistent with the hypothesis that sympathetic neurones are more susceptible than myocytes to ischaemic damage.