Antipsychotics possess anti-glioblastoma activity by disrupting lysosomal function and inhibiting oncogenic signaling by stabilizing PTEN.

The repurposing of medications developed for central nervous system (CNS) disorders, possessing favorable safety profiles and blood-brain barrier permeability, represents a promising strategy for identifying new therapies to combat glioblastoma (GBM). In this study, we investigated the anti-GBM activity of specific antipsychotics and antidepressants in vitro and in vivo. Our results demonstrate that these compounds share a common mechanism of action in GBM, disrupting lysosomal function and subsequently inducing lysosomal membrane rupture and cell death.

Beta Blockers in Contemporary Cardiology: Is It Better to Cast Them Out?

Beta blockers are one of the commonest prescription drugs in medicine and they have been thought to revolutionize the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) in the last century. In addition to HFrEF, they are prescribed for a variety of diseases in cardiology from hypertension to HF, angina, and stable coronary artery disease (CAD). The increased prescription of beta blockers in conditions like HF with preserved ejection fraction (HFpEF), and stable CAD may be doing more harm than good as per the data we have so far.

miRNA-194-3p represses NF-κB in gliomas to attenuate iPSC genes and proneural to mesenchymal transition.

Severe tumor heterogeneity drives the aggressive and treatment refractory nature of glioblastomas (GBMs). While limiting GBM heterogeneity offers promising therapeutic potential, the underlying mechanisms that regulate GBM plasticity remain poorly understood. We utilized 14 patient-derived and four commercially available cell lines to uncover miR-194-3p as a key epigenetic determinant of stemness and transcriptional subtype in GBM.

Electrocardiographic lead reversals.

Misplacement of cables during the recording of a 12-lead electrocardiogram [ECG] poses a non-negligible risk of creating panic and confusion at the bedside in daily clinical practice. Clinical awareness about the manifestations of commonly encountered electrode misplacements is imperative for avoiding misdiagnosis. A basic understanding of the electrophysiology behind these anomalous ECG tracings is likely to aid in prompt suspicion, accurate detection, and appropriate rectification in most cases.

Does Cardiac Arrhythmia Predict Worse Outcome in Mild or Moderate Covid-19 Infection?

Covid-19 is a multisystem disease with the lungs being predominantly affected. Cardiac involvement is mostly seen as a rise in troponins, arrhythmias, and ventricular dysfunction. This study aimed to estimate the incidence of arrhythmias seen in Covid-19 infection and assess if arrhythmias predict worsening or mortality Prospective observational study involving patients with mild to moderate Covid illness admitted in a tertiary care centre.

Early dose of Adenosine, postRadiofrequency abLation of accessory pathwaY in determining acute procedural success (EARLY study).

Introduction: Post ablation of the accessory pathway (AP), the patient is observed in the catheterization laboratory for a variable period for resumption of pathway conduction. Aim of the study was to determine whether the administration of intravenous adenosine at 10 min after ablation of AP would have the same diagnostic accuracy as waiting for 30 min in predicting the resumption of AP conduction.

Methods: This was a prospective interventional study conducted in two centers.

A Pilot Study of Electrocardiographic Features in Patients with Obesity from a Tertiary Care Centre in Southern India (Electron).

Obesity is associated with increased all-cause mortality and cardiovascular disease (CVD). An electrocardiogram (ECG) may be used to screen for subtle signs of CVD or altered cardiac morphology in the obese. This observational cross-sectional analysed ECG changes in patients with obesity at a tertiary care centre in southern India.

Atrial depolarization abnormalities in pulmonary sarcoidosis.

Background: Cardiac sarcoidosis, often manifested as sudden death, can be the first manifestation of sarcoidosis. Since 12-lead electrocardiogram (ECG) is recommended as an initial screening tool for cardiac sarcoidosis, the recognition of subtle abnormalities assumes utmost significance. The objective of this study was to identify the electrocardiographic abnormalities in patients with pulmonary sarcoidosis.

Altered Gemcitabine and Nab-paclitaxel Scheduling Improves Therapeutic Efficacy Compared with Standard Concurrent Treatment in Preclinical Models of Pancreatic Cancer.

Purpose: Concurrent gemcitabine and nab-paclitaxel treatment is one of the preferred chemotherapy regimens for metastatic and locally advanced pancreatic ductal adenocarcinoma (PDAC). Previous studies demonstrate that caveolin-1 (Cav-1) expression is critical for nab-paclitaxel uptake into tumors and correlates with response. Gemcitabine increases nab-paclitaxel uptake by increasing Cav-1 expression.

Effects of heat stroke on surface ECG: a study on clinical outcomes.

Aims: Classic heat stroke is associated with high in-hospital mortality and morbidity. The relation between the ECG findings in heat stroke and the clinical outcomes of these patients has not been studied. The aim of this study was to describe the electrocardiographic features in patients with classic heat stroke and to determine if there is any correlation of ECG findings with in-hospital outcomes.

Cells isolated from residual intracranial tumors after treatment express iPSC genes and possess neural lineage differentiation plasticity.

Background: The goal of this study is to identify and characterize treatment resistant tumor initiating cells (TRTICs) using orthotopic xenografts.

Methods: TRTICs were enriched from GBM cell lines using mouse xenografts treated with fractionated doses of radiation and temozolomide. TRTICs were characterized by neurosphere clonogenicity and self-renewal, serial xenotransplantation, differentiation potential, and mRNA & miRNA transcriptomic profiling.

Devil is in the detail.

A 15-year-old girl of Asian origin, hailing from a rural agrarian background, presented with history of multiple episodes of dizziness for 3 years. The episodes were precipitated mostly by emotional and/or physical stress and relieved on lying down, with a few episodes culminating in transient loss of consciousness. As preliminary cardiac and neurological evaluation were normal, she was being treated by the primary physician as a case of probable psychogenic syncope, supported by the consistent association of the episodes with emotional stress.

Left ventricular structure and diastolic function by cardiac magnetic resonance imaging in hypertrophic cardiomyopathy.

Objective: Diastolic dysfunction is common in hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD), but its relationships with left ventricular (LV) parameters have not been well studied. Our objective was to assess the relationship of various measures of diastolic function, and maximum left ventricular wall thickness (MLVWT) and left ventricular mass index (LVMI) in HCM, HHD and normal controls using cardiac magnetic resonance imaging (CMR). We also assessed LV parameters and diastolic function in relation to late gadolinium enhancement (LGE) and right ventricular (RV) hypertrophy in HCM.

Lack of Constitutively Active DNA Repair Sensitizes Glioblastomas to Akt Inhibition and Induces Synthetic Lethality with Radiation Treatment in a p53-Dependent Manner.

Treatment refractory glioblastoma (GBM) remains a major clinical problem globally, and targeted therapies in GBM have not been promising to date. The Cancer Genome Atlas integrative analysis of GBM reported the striking finding of genetic alterations in the p53 and PI3K pathways in more than 80% of GBMs. Given the role of these pathways in making cell-fate decisions and responding to genotoxic stress, we investigated the reliance of these two pathways in mediating radiation resistance.

NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability.

To identify potential molecular hubs that regulate oncogenic kinases and target them to improve treatment outcomes for glioblastoma patients. Data mining of The Cancer Genome Atlas datasets identified nicotinamide-N-methyl transferase (NNMT) as a prognostic marker for glioblastoma, an enzyme linked to the reorganization of the methylome. We tested our hypothesis that NNMT plays a crucial role by modulating protein methylation, leading to inactivation of tumor suppressors and activation of oncogenes.

Methionine and Kynurenine Activate Oncogenic Kinases in Glioblastoma, and Methionine Deprivation Compromises Proliferation.

Purpose: We employed a metabolomics-based approach with the goal to better understand the molecular signatures of glioblastoma cells and tissues, with an aim toward identifying potential targetable biomarkers for developing more effective and novel therapies.

Experimental Design: We used liquid chromatography coupled with mass spectrometry (LC-MS/Q-TOF and LC-MS/QQQ) for the discovery and validation of metabolites from primary and established glioblastoma cells, glioblastoma tissues, and normal human astrocytes.

Results: We identified tryptophan, methionine, kynurenine, and 5-methylthioadenosine as differentially regulated metabolites (DRM) in glioblastoma cells compared with normal human astrocytes (NHAs).

Decrement Evoked Potential Mapping: Basis of a Mechanistic Strategy for Ventricular Tachycardia Ablation.

Background: Substrate-based mapping for ventricular tachycardia (VT) ablation is hampered by its inability to determine critical sites of the VT circuit. We hypothesized that those potentials, which delay with a decremental extrastimulus (decrement evoked potentials or DEEPs), are more likely to colocalize with the diastolic pathways of VT circuits.

Methods And Results: DEEPs were identified in intraoperative left ventricular maps from 6 patients with ischemic cardiomyopathy (total 9 VTs) and were compared with late potential (LP) and activation maps of the diastolic pathway for each VT.