A comparative study of incidence, mortality and disability adjusted life years (DALYs) for leading cancers in BRICS countries.

Background: While cancer stands as a prominent global contributor to mortality, the BRICS countries, which contribute a considerable proportion of the world's economy, also account for a substantial proportion of global cancer-related deaths. The study aims to compile data on the incidence, mortality and disability-adjusted life years (DALYs) of leading cancers in BRICS countries to assess any variations in these parameters.

Methods: Indicators such as the age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR) were abstracted from GLOBOCAN 2022.

Evaluation of outcomes of clinical phenotyping-based treatment for bladder pain syndrome/interstitial cystitis.

Introduction: Bladder pain syndrome/Interstitial cystitis (BPS/IC) is clinically of diverse types because different causes contribute to the development of their symptoms. It is important to classify patients into various groups based on the possible etiopathogenesis of their condition. Treatment may be tailored to each specific group according to the possible cause.

The effects of omega-3, DHA, EPA, Souvenaid® in Alzheimer's disease: A systematic review and meta-analysis.

Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. Omega-3 fatty acids (n-3-PUFA) are essential to normal neural development and function. Souvenaid®, a medical supplement that contains n-3-PUFA's: eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), has emerged as an alternative, slowing cognitive decline in AD patients.

PHF2 regulates genome topology and DNA replication in neural stem cells via cohesin.

Cohesin plays a crucial role in the organization of topologically-associated domains (TADs), which influence gene expression and DNA replication timing. Whether epigenetic regulators may affect TADs via cohesin to mediate DNA replication remains elusive. Here, we discover that the histone demethylase PHF2 associates with RAD21, a core subunit of cohesin, to regulate DNA replication in mouse neural stem cells (NSC).

BHLHE40 Regulates Myeloid Cell Polarization through IL-10-Dependent and -Independent Mechanisms.

Better understanding of the host responses to Mycobacterium tuberculosis infections is required to prevent tuberculosis and develop new therapeutic interventions. The host transcription factor BHLHE40 is essential for controlling M. tuberculosis infection, in part by repressing Il10 expression, where excess IL-10 contributes to the early susceptibility of Bhlhe40-/- mice to M.

Targeting Dysregulated Lipid Metabolism in Cancer with Pharmacological Inhibitors.

Metabolic plasticity is recognised as a hallmark of cancer cells, enabling adaptation to microenvironmental changes throughout tumour progression. A dysregulated lipid metabolism plays a pivotal role in promoting oncogenesis. Oncogenic signalling pathways, such as PI3K/AKT/mTOR, JAK/STAT, Hippo, and NF-kB, intersect with the lipid metabolism to drive tumour progression.

Heterogeneity of synaptic connectivity in the fly visual system.

Visual systems are homogeneous structures, where repeating columnar units retinotopically cover the visual field. Each of these columns contain many of the same neuron types that are distinguished by anatomic, genetic and - generally - by functional properties. However, there are exceptions to this rule.

BRD4 isoforms have distinct roles in tumour progression and metastasis in rhabdomyosarcoma.

BRD4, a bromodomain and extraterminal (BET) protein, is deregulated in multiple cancers and has emerged as a promising drug target. However, the function of the two main BRD4 isoforms (BRD4-L and BRD4-S) has not been analysed in parallel in most cancers. This complicates determining therapeutic efficacy of pan-BET inhibitors.

A novel home-based method for preparing suspensions of anti-TB drugs.

Tablets are the most widely available dosage form for the treatment of TB; however, adult tablets fail to meet the needs of young children who cannot swallow these tablets or require dose titration. We tested a new, simple device (XTEMP-R) and the methodology for converting tablets of TB drugs into a homogeneous suspension for home use by children and caregivers. XTEMP-R is a new device used for converting tablets into liquid preparations.

Nebulised fentanyl, dexmedetomidine and magnesium sulphate for attenuation of haemodynamic response to laryngoscopy and tracheal intubation: A double-blinded, randomised comparative study.

Background And Aims: Direct laryngoscopy and tracheal intubation cause an increase in heart rate (HR) and blood pressure, called as pressor response. This study aimed to compare nebulised forms of fentanyl, dexmedetomidine and magnesium sulphate to attenuate the haemodynamic response to laryngoscopy and tracheal intubation.

Methods: This double-blinded, randomised study was conducted on 90 patients undergoing elective surgery requiring endotracheal intubation.

Single-nucleus multiomic mapping of mA methylomes and transcriptomes in native populations of cells with sn-m6A-CT.

N-methyladenosine (mA) RNA modification plays important roles in the governance of gene expression and is temporally regulated in different cell states. In contrast to global mA profiling in bulk sequencing, single-cell technologies for analyzing mA heterogeneity are not extensively established. Here, we developed single-nucleus m6A-CUT&Tag (sn-m6A-CT) for simultaneous profiling of mA methylomes and transcriptomes within a single nucleus using mouse embryonic stem cells (mESCs).

BRD4 isoforms have distinct roles in tumor progression and metastasis in embryonal rhabdomyosarcoma.

BRD4, a bromodomain and extraterminal (BET) protein, is deregulated in multiple cancers and has emerged as a promising drug target. However, the function of the two main BRD4 isoforms (BRD4-L and BRD4-S) has not been analyzed in parallel in most cancers. This complicates determining therapeutic efficacy of pan-BET inhibitors.

MPT51 and MPT64-based antigen detection assay for the diagnosis of extrapulmonary tuberculosis from urine samples.

In view of WHO's "End-TB" strategy, we developed a non-invasive, urine-based ELISA, targeting 2 Mycobacterium tuberculosis antigens namely MPT51 and MPT64 for extrapulmonary TB (EPTB) diagnosis. Suspected EPTB patients (n = 137) [Pleural TB, Abdominal TB and Tuberculous meningitis] were categorized in "Definite" EPTB (n = 10) [Xpert-MTB/RIF and/or culture-positive], "Probable" EPTB (n = 77) and "Non-EPTB" (n = 50) groups using defined composite reference standards. ROC-curves were generated using ELISA results of "Definite" EPTB and "Non-EPTB" groups for both antigens independently and cut-off values were selected to provide 86.

An Alternative Approach to Tablet Splitting and Grinding for Medication Administration.

Tablet formulations fail to meet the needs of patients unable to swallow tablets such as pediatric, elderly, and patients that must receive medications via feeding tubes. Our objective was to develop and test a new, simple device (XTEMP-R) and the methodology for converting tablets into a homogeneous suspension for medication administration. We developed a new device comprised of a flexible receptacle, a tight-fitting cap, and a suction cup bottom to convert tablets into liquid preparations.

Review of Neurological Manifestations of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect any part of the neuraxis. Many neurological conditions have been attributed to be caused by SARS-CoV-2, namely encephalopathy (acute necrotizing encephalopathy and encephalopathy with reversible splenial lesions), seizures, stroke, cranial nerve palsies, meningoencephalitis, acute disseminated encephalomyelitis (ADEM), transverse myelitis (long and short segment), Guillain-Barré syndrome (GBS) and its variants, polyneuritis cranialis, optic neuritis (ON), plexopathy, myasthenia gravis (MG), and myositis. The pathophysiology differs depending on the time frame of presentation.

Fed- and Fasted-State Performance of Pretomanid Amorphous Solid Dispersions Formulated with an Enteric Polymer.

Weakly acid polymers with pH-responsive solubility are being used with increasing frequency in amorphous solid dispersion (ASD) formulations of drugs with low aqueous solubility. However, drug release and crystallization in a pH environment where the polymer is insoluble are not well understood. The aim of the current study was to develop ASD formulations optimized for release and supersaturation longevity of a rapidly crystallizing drug, pretomanid (PTM), and to evaluate a subset of these formulations in vivo.

Steady-state memory-phenotype conventional CD4 T cells exacerbate autoimmune neuroinflammation in a bystander manner via the Bhlhe40/GM-CSF axis.

Memory-phenotype (MP) CD4 T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4 T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4 T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Stable, compounded bedaquiline suspensions to support practical implementation of pediatric dosing in the field.

Bedaquiline (BDQ) tablets are indicated as part of a combination regimen for the treatment of multidrug-resistant TB in adults, adolescents and children. A dispersible tablet formulation is now approved but is not currently available in all settings. The aim of this study was to develop stable extemporaneous liquid formulations of BDQ that can be stored at room temperature or 30°C for several weeks, to support pragmatic pediatric dosing in the field and reduce wastage.

Sugar and sugar-free liquid formulations of delamanid for patients with rifampicin-resistant TB.

Delamanid (DLM) tablets are recommended for the treatment of rifampicin-resistant TB. However, no liquid or dispersible tablet formulation of DLM is currently commercially available for patients with challenges ingesting these tablets. The aim of this study was to develop stable extemporaneous liquid formulations of DLM that can be stored at room temperature for several weeks.