In silico inspired design of urea noscapine congeners as anticancer agents: Chemical synthesis and experimental evaluation using breast cancer cells and a xenograft mouse model.

A series of semisynthetic noscapine-urea congeners (7a-7h) as potential tubulin-binding agents are being developed by integrating a urea pharmacophore at the C-9 position of the noscapine scaffold. Their binding affinity to tubulin was predicted through molecular docking, molecular dynamics (MD) simulations, and the MM-PBSA approach. These molecules were subsequently chemically synthesized and assessed using breast cancer cell lines (MCF-7 and MDA-MB-231) and normal human embryonic kidney cells (HEK).

Risk of Silent Myocardial Infarction in Prediabetic Patients: A Case-Control Study in a Veteran Population.

Objectives: In the management of cardiovascular disease, it is important to identify patients at risk early on, to provide interventions to prevent the disease and its complications. The goal of our study was to investigate the association between glucose levels and silent myocardial infarction (SMI) among patients, who consisted of veterans within the Veterans Affairs clinical system.

Methods: Among the group of patients with an initially normal electrocardiogram, a cohort of patients with a subsequent diagnosis of SMI was selected as the case cohort, whereas 4 patients for each study subject, without evidence of coronary artery disease and normal electrocardiogram within the previous 6 months, were identified and constituted the control cohort.

Response to pegylated interferon in a COVID-19 positive male with metastatic jejunal neuroendocrine tumor treated with everolimus.

A 61-year-old male on everolimus had chronic SARS-CoV-2 infection. Addition of pegylated interferon cleared viral RNA and supports combination therapy with everolimus plus interferon for COVID-19.

Response to pegylated interferon in a COVID-19-positive elderly woman with primary myelofibrosis treated with ruxolitinib.

An 83-year-old female had asymptomatic SARS-CoV-2 infection while taking ruxolitinib. She remained RT-PCR positive for viral RNA for >120 days, and Pegylated interferon for 4 weeks led to viral RNA clearance. The observations support combination therapy of ruxolitinib + interferon for COVID-19.

Trends in Appendicitis Among Pregnant Women, the Risk for Cardiac Arrest, and Maternal-Fetal Mortality.

Background: Appendicitis is the most common extra-uterine surgical emergency requiring immediate intervention during pregnancy. However, risks for mortality and morbidity among pregnant women with appendicitis remain poorly understood. This study was conducted to determine the temporal trends of appendicitis in pregnant women, and to calculate the risk of maternal-fetal mortality and near-miss marker (i.

Post-earthquake Zika virus surge: Disaster and public health threat amid climatic conduciveness.

A recent major earthquake (M7.8), coupled with appropriate climatic conditions, led to significant destruction in Ecuador. Temperature variations, which may be induced by anthropogenic climate change, are often associated with changes in rainfall, humidity and pressure.

Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses.

Aim: We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes.

Methods: At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA.

Syphilis and HIV/Syphilis Co-infection Among Men Who Have Sex With Men (MSM) in Ecuador.

There is a reemergence of syphilis in the Latin American and Caribbean region. There is also very little information about HIV/Syphilis co-infection and its determinants. The aim of this study is to investigate knowledge, attitudes, and practices regarding sexually transmitted infections (STIs), in particular syphilis infection and HIV/Syphilis co-infection, as well as to estimate the prevalence of syphilis among men who have sex with men (MSM) in a city with one of the highest HIV prevalence rates in Ecuador.

Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells.

Despite the impressive rates of clinical response to programmed death 1 (PD-1) blockade in multiple cancers, the majority of patients still fail to respond to this therapy. The CT26 tumor in mice showed similar heterogeneity, with most tumors unaffected by anti-PD-1. As in humans, response of CT26 to anti-PD-1 correlated with increased T- and B-cell infiltration and IFN expression.

Community-based fortified dietary intervention improved health outcomes among low-income African-American women.

Poor dietary exposure disproportionately affects African-Americans and contributes to the persistence of disparities in health outcomes. In this study, we hypothesized that fortified dietary intervention (FDI) will improve measured dietary and related health outcomes and will be acceptable among low-income African-American women living in Tampa, FL. These objectives were tested using a prospective experimental study using pretest and posttest design with a control group, using a community-based participatory research approach.

Risk Factors Associated With HIV Among Men Who Have Sex With Men (MSM) in Ecuador.

The Joint United Nations Program on HIV/AIDS estimates that between 0.3% and 0.7% of adults aged 15 to 49 years were living with HIV in Ecuador in 2013.

Orientation of Dental Professionals in India towards Integrative Medicine: A Cross-Sectional Survey.

Introduction: There is a growing demand on our health care system, including Dentistry, to shift from a bio-medical approach to Integrative model of care. The attitudes of health professionals towards Integrative Medicine (IM) are an important factor that influences this transition.

Aim: The aim of this study was to evaluate and compare the orientation of the dental professionals in India towards the principles and practice of Integrative Medicine.

Usp9X Is Required for Lymphocyte Activation and Homeostasis through Its Control of ZAP70 Ubiquitination and PKCβ Kinase Activity.

To achieve a durable adaptive immune response, lymphocytes must undergo clonal expansion and induce a survival program that enables the persistence of Ag-experienced cells and the development of memory. During the priming phase of this response, CD4(+)T lymphocytes either remain tolerized or undergo clonal expansion. In this article, we show that Usp9X functions as a positive regulatory switch during T lymphocyte priming through removal of inhibitory monoubiquitination from ZAP70.

REDUCING PMTCT ATTRITION: PERSPECTIVES OF HIV+ WOMEN ON THE PREVENTION OF MOTHER-TO-CHILD HIV SERVICES IN ADDIS ABABA, ETHIOPIA.

Background: Only 41% of eligible Ethiopian women completed (PMTCT) therapy in 2012, with MTCT rate of 20%.

Objective: This study elicited the perspectives of HIV positive mothers on the situation and the unique beliefs, attitudes, cultural norms and individuals who have influence over them during their pregnancy.

Methods: The mixed-methods parent study included community level surveys, focus groups and in-depth individual interviews of HIV positive women with a child at least one year of age in Addis Ababa, Ethiopia: only focus group and interview data are presented here.

Industry-Related Injuries in the United States From 1998 to 2011: Characteristics, Trends, and Associated Health Care Costs.

Objective: To describe the trends, correlates, and healthcare costs associated with industry-related injuries across the United States between 1998 and 2011.

Methods: A retrospective, cross-sectional analysis of hospital discharges was conducted using the National Inpatient Sample. We used the International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify accidents occurring in industrial settings.

NF-κB Essential Modulator Deficiency Leading to Disseminated Cutaneous Atypical Mycobacteria.

NF-κB essential modulator (NEMO) is a kinase integral to the macrophage TNF-α pathway, which leads to the intracellular destruction of Mycobacteria species. Defects in the NEMO pathway result in spectrum of diseases, including but not limited to ectodermal dysplasia, Mendelian susceptibility to mycobacterial diseases, and incontinentia pigmenti. In addition, paucity of NEMO can lead to the inability to mount a proper immune response against opportunistic pyogenic and mycobacterial infections, leading to dissemination to various organ systems.

Association between maternal symptoms of sleep disordered breathing and fetal telomere length.

Study Objectives: Our investigation aims to assess the impact of symptoms of maternal sleep-disordered breathing, specifically sleep apnea risk and daytime sleepiness, on fetal leukocyte telomere length.

Participants And Setting: Pregnant women were recruited upon hospital delivery admission.

Interventions: Sleep exposure outcomes were measured using the Berlin Questionnaire to quantify sleep apnea and the Epworth Sleepiness Scale to measure daytime sleepiness.

Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X.

The T cell hyperproliferation and autoimmune phenotypes that manifest in mice lacking E3 ubiquitin ligases such as Cbl, ITCH, or GRAIL highlight the importance of ubiquitination for the maintenance of peripheral T cell tolerance. Less is known, however, about the deubiquitinating enzymes that regulate T cell proliferation and effector function. Here, we define a cell intrinsic role for the deubiquitinase Usp9X during proximal TCR signaling.

Estimating benchmark exposure for air particulate matter using latent class models.

We performed benchmark exposure (BME) calculations for particulate matter when multiple dichotomous outcome variables are involved using latent class modeling techniques and generated separate results for both the extra risk and additional risk. The use of latent class models in this study is advantageous because it combined several outcomes into just two classes (namely, a high-risk class and a low-risk class) and compared these two classes to obtain the BME levels. This novel approach addresses a key problem in risk estimation--namely, the multiple comparisons problem, where separate regression models are fitted for each outcome variable and the reference exposure will rely on the results of the best-fitting model.

Preterm birth in the first pregnancy and risk of neonatal death in the second pregnancy: a propensity score-weighted matching approach.

The study purpose was to assess the relationship between various grades of preterm birth (moderate preterm: 33-36 weeks; severe preterm: 27-32 weeks; extreme preterm: ≤ 26 weeks) in the first pregnancy and neonatal mortality (death within 28 days of birth; early: 0-7 days; late: 8-28 days) in the second pregnancy. Using the Missouri maternally-linked dataset (1989-2005), a population-based, retrospective cohort analysis with propensity score-weighted matching was conducted on mothers with two consecutive singleton live births (n = 310,653 women). Women with a prior preterm birth were more likely to subsequently experience neonatal death.

Human immunodeficiency virus in a tribal family: Issues and challenges.

A 35-year-old married tribal female presented with well-defined crusted ulcers with purulent exudates on the right side of the face involving both lips and right forearm since last 6 months. On investigation, she turned out to be human immunodeficiency virus (HIV) positive with CD4 count of 7 cell/mm(3) and also having probable abdominal tuberculosis (TB) as suggested by ultrasonography abdomen. Her husband and son were also found to be HIV positive.

Pro-apoptotic BIM is an essential initiator of physiological endothelial cell death independent of regulation by FOXO3.

The growth of new blood vessels by angiogenesis is essential for normal development, but can also cause or contribute to the pathology of numerous diseases. Recent studies have shown that BIM, a pro-apoptotic BCL2-family protein, is required for endothelial cell apoptosis in vivo, and can contribute to the anti-angiogenic effect of VEGF-A inhibitors in certain tumor models. Despite its importance, the extent to which BIM is autonomously required for physiological endothelial apoptosis remains unknown and its regulation under such conditions is poorly defined.

Profile of HIV seroconcordant/discordant couples a clinic based study at Vadodara, India.

Background: Heterosexual transmission of HIV among married couples is the commonest mode of transmission seen in India. Intramarital transmission is associated with several challenges which need to be further researched.

Aim: To study level of seroconcordance and serodiscordance among HIV positive couples and factors affecting intramarital sexual transmission in terms of safe sexual practice, and the presence of Sexually transmitted infections (STI)/circumcision.