Preoperative Ultrasound-guided Core Biopsy of Axillary Nodes for Staging of Clinically Negative Axilla in Breast Cancer Patients - A Pilot Study.

Objective The aim of the current study is to determine the feasibility and accuracy of ultrasound-guided core biopsy for staging the axilla in clinically node-negative patients with invasive breast cancer. Introduction Historically, in breast cancer patients, axillary lymph node dissection was performed to stage axilla. Because of the high morbidity of axillary lymph node dissection, sentinel lymph node biopsy (SLNB) became the standard of care in patients with clinically node-negative breast cancer.

Structural Features of Nucleoprotein CST/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations.

Telomere comprises the ends of eukaryotic linear chromosomes and is composed of G-rich (TTAGGG) tandem repeats which play an important role in maintaining genome stability, premature aging and onsets of many diseases. Majority of the telomere are replicated by conventional DNA replication, and only the last bit of the lagging strand is synthesized by telomerase (a reverse transcriptase). In addition to replication, telomere maintenance is principally carried out by two key complexes known as shelterin (TRF1, TRF2, TIN2, RAP1, POT1, and TPP1) and CST (CDC13/CTC1, STN1, and TEN1).

Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer).

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models.

HIV infection predominantly affecting children in Sindh, Pakistan, 2019: a cross-sectional study of an outbreak.

Background: In April 2019, an HIV screening camp for all ages was established in response to a report of an unusually large number of paediatric HIV diagnoses in Larkana, Pakistan. We aimed to understand the clinical profile of the children who registered for HIV care.

Methods: In this cross-sectional study, we review the outbreak response from the government, academia, and UN agencies in Larkana, Sindh, Pakistan.

Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration.

Conventional chemotherapeutic regimens are unable to prevent metastasis of non-small cell lung carcinoma (NSCLC) thereby leaving cancer incurable. Cancer stem cells (CSCs) are considered to be the origin of this therapeutic limitation. In the present study we report that the migration potential of NSCLCs is linked to its CSC content.

Culture Conversion at 6 Months in Patients Receiving Delamanid-containing Regimens for the Treatment of Multidrug-resistant Tuberculosis.

Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months. Clinical Trials Registration.

Design, Synthesis, and Biological Evaluation of Novel Fused Spiro-4-Pyran Derivatives as Bacterial Biofilm Disruptor.

This study aims to synthesize novel fused spiro-4-pyran derivatives under green conditions to develop agents having antimicrobial activity. The synthesized compounds were initially screened for in vitro antibacterial activity against two Gram-positive and three Gram-negative bacterial strains, and all the compounds exhibited moderate to potent antibacterial activity. However, compound showed significant inhibition toward all the bacterial strains, particularly against and with minimum inhibitory concentration values of 125 μg/mL for each.

Integrin-EGFR interaction regulates anoikis resistance in colon cancer cells.

Anoikis resistance is an essential property of cancer cells that allow the extra-cellular matrix-detached cells to survive in a suspended state in body fluid in order to metastasize and invade to distant organs. It is known that integrins play an important role in anoikis resistance, but detailed mechanisms are not well understood. Here we report that highly metastatic colon cancer cells showed a higher degree of anoikis resistance than the normal intestinal epithelial cells.

Variation in Chronic Diseases Across Households, Communities, Districts, and States in India.

Introduction: Globally, chronic noncommunicable diseases are the leading cause of death and accounted for 6 million deaths in India in 2016. However, the extent to which variation in chronic disease can be attributed to different population levels in India is unknown, as is whether variation in individual-level factors explains outcome variation at different population levels.

Methods: Cross-sectional data from the District Level Household and Facility Survey 2012-2013 conducted across 21 states, 275 districts, 14,235 villages, 378,487 households, and 1,098,940 individuals aged ≥18 years in India were analyzed in 2018‒2019.

Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia: A Systematic Review and Network Meta-analysis.

Background: Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia.

Purpose: To summarize the comparative efficacy of pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia.

Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO between inception and 28 May 2019 without language restrictions; gray literature; and reference lists scanned from selected studies and systematic reviews.

Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses.

Neuroimmune interactions have emerged as critical modulators of allergic inflammation, and type 2 innate lymphoid cells (ILC2s) are an important cell type for mediating these interactions. Here, we show that ILC2s expressed both the neuropeptide calcitonin gene-related peptide (CGRP) and its receptor. CGRP potently inhibited alarmin-driven type 2 cytokine production and proliferation by lung ILC2s both in vitro and in vivo.

Martini Coarse-Grained Model for Clay-Polymer Nanocomposites.

We have developed a coarse-grained (CG) model of a polymer-clay system consisting of organically modified montmorillonite (oMMT) nanoclay as the nanoparticle in accordance with the MARTINI force field. We have used mechanical properties and cleavage free energy of the clay particle to respectively parameterize bonded and nonbonded interaction parameters for an oMMT clay particle, where intergallery Na ions are replaced by tetramethylammonium (TMA) ions. The mechanical properties were determined from the slope of the stress-strain curve and cleavage free energy was determined by allowing for full surface reconstruction corresponding to a slow equilibrium cleavage process.

A Descriptive Study to Find Possible Correlation between Pituitary Magnetic Resonance Image Findings and Abnormal Pituitary Hormones: A Retrospective Single Centre Study in Saudi Community Based Hospital.

Background: Data on pituitary Magnetic Resonance Imaging (MRI) in patients with abnormal pituitary hormones in Saudi Arabia are very scarce.

Objective: To define the frequency of normal pituitary MRI in patients with abnormal pituitary hormones in a well-defined population.

Design: Retrospective analysis of radiological and hormonal data of patients with pituitary MRI between January 2008 and December 2015.

More acute lymphoid leukemia than acute myeloid leukemia blasts are killed by rabbit antithymocyte globulin.

Rabbit antithymocyte globulin (ATG, thymoglobulin), a polyclonal antibody, is used to prevent graft-versus-host disease (GVHD) and graft failure in the setting of allogeneic hematopoietic cell transplantation (HCT). Recent in vitro studies suggest that ATG also has anti-leukemic activity. Whether acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is more sensitive to ATG is not known.

QSPR Modeling of the Refractive Index for Diverse Polymers Using 2D Descriptors.

In the present work, predictive quantitative structure-property relationship models have been developed to predict refractive indices (RIs) of a set of 221 diverse organic polymers using theoretical two-dimensional descriptors generated on the basis of the structures of polymers' monomer units. Four models have been developed by applying partial least squares (PLS) regression with a different combination of six descriptors obtained via double cross-validation approaches. The predictive ability and robustness of the proposed models were checked using multiple validation strategies.

Chemometric modeling to predict air half-life of persistent organic pollutants (POPs).

We have reported here a quantitative structure-property relationship (QSPR) model for prediction of air half-life of organic chemicals using a dataset of 302 diverse organic chemicals employing only two-dimensional descriptors with definite physicochemical meaning in order to avoid the computational complexity for higher dimensional molecular descriptors. The developed model was rigorously validated using the internationally accepted internal and external validation metrics. The final partial least squares (PLS) regression model obtained at three latent variables comprises six simple and interpretable 2D descriptors.

The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens.

Background: At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens.

Engineering genetically encoded FRET-based nanosensors for real time display of arsenic (As) dynamics in living cells.

Arsenic poisoning has been a major concern that causes severe toxicological damages. Therefore, intricate and inclusive understanding of arsenic flux rates is required to ascertain the cellular concentration and establish the carcinogenetic mechanism of this toxicant at real time. The lack of sufficiently sensitive sensing systems has hampered research in this area.

Evaluation of ellagic acid as an inhibitor of sphingosine kinase 1: A targeted approach towards anticancer therapy.

Sphingosine kinase 1 (SphK1) is one of the central enzymes of sphingolipid metabolism whose high expression level is presumed to be correlated with cancer and other inflammatory diseases. Using a virtual screening approach and in vitro studies, we have identified the ellagic acid (EA), a dietary polyphenol, as a potent inhibitor of SphK1. Molecular docking study has suggested a strong binding affinity of EA to the SphK1.

Identification of α-Mangostin as a Potential Inhibitor of Microtubule Affinity Regulating Kinase 4.

Microtubule affinity regulating kinase 4 (MARK4) is a potential drug target for neuronal disorders and several types of cancers. Filtration of naturally occurring compound libraries using high-throughput screening and enzyme assay suggest α-mangostin is a potential inhibitor of MARK4. Structure-based docking and 100 ns molecular dynamics simulation revealed that the binding of α-mangostin stabilizes the MARK4 structure.

Risk assessment of low arsenic exposure using biomarkers of oxidative and genotoxic stress in a piscine model.

The high level exposure to arsenic induces marked oxidative and genotoxic stress. However, information on the potential of low level arsenic exposure in this context is still scanty. In the present study, the extent of oxidative stress and genetic toxicity induced by low arsenic exposure was explored in freshwater fish Channa punctatus.

Investigation of inhibitory potential of quercetin to the pyruvate dehydrogenase kinase 3: Towards implications in anticancer therapy.

Pyruvate dehydrogenase kinase 3 (PDK3) is a mitochondrial protein, has recently been considered as a potential pharmacological target for varying types of cancer. Here, we report the binding mechanism of quercetin to the PDK3 by using molecular docking, simulation, fluorescence spectroscopy and isothermal titration calorimetric assays. Molecular docking along with simulation provided an in-depth analysis of protein-ligand interactions.

Insight of the Interaction between 2,4-thiazolidinedione and Human Serum Albumin: A Spectroscopic, Thermodynamic and Molecular Docking Study.

Thiazolidinedione derivatives (TZDs) have attracted attention because of their pharmacological effects. For example, certain TZDs have been reported to ameliorate type II diabetes by binding and activating PPARs (peroxisome proliferator-activated receptors). Nonetheless, no information is available on the interaction between the heterocyclic 2, 4-thiazolidinedione (2,4-TZD) moiety and serum albumin, which could affect the pharmacokinetics and pharmacodynamics of TZDs.

Incidence of Anxiety and Depression Among Patients with Type 2 Diabetes and the Predicting Factors.

Introduction Diabetes mellitus (DM) is a chronic, progressive metabolic illness which is commonly complicated by coexistence of depression and anxiety. This study aimed to assess the prevalence of anxiety and depression among diabetic patients and the factors predicting this coexistence. Methods It was a cross-sectional, observational study which included patients of type 2 DM admitted in the hospital due to diabetes-related condition - diabetic foot infections/ulcers, hyperosmotic hyperglycaemic state (HHS), and hypoglycaemic coma/seizure.