Current approaches in CRISPR-Cas system for metabolic disorder.

A new era in genomic medicine has been brought by the development of CRISPR-Cas technology, which presents hitherto unheard-of possibilities for the treatment of metabolic illnesses. The treatment approaches used in CRISPR/Cas9-mediated gene therapy, emphasize distribution techniques such as viral vectors and their use in preclinical models of metabolic diseases like hypercholesterolemia, glycogen storage diseases, and phenylketonuria. The relevance of high-throughput CRISPR screens for target identification in discovering new genes and pathways associated with metabolic dysfunctions is an important aspect of the discovery of new approaches.

Multipronged strategy for protection and motivation of healthcare workers during the COVID-19 pandemic: a real-life study.

Objective: We aimed to assess risk of COVID-19 infection & seroprotection status in healthcare workers (HCWs) in both hospital and community settings following an intensive vaccination drive in India.

Setting: Tertiary Care Hospital.

Methods: We surveyed COVID-19 exposure risk, personal protective equipment (PPE) compliance, vaccination status, mental health & COVID-19 infection rate across different HCW cadres.

A Rare Presentation of Disseminated Peritoneal Leiomyomatosis Following Laparoscopic Hysterectomy and Its Multidisciplinary Management.

Disseminated peritoneal leiomyomatosis (DPL) is a rare entity. It is a benign disease but can mimic disseminated malignancy with extensive disease at multiple sites within the abdominopelvic cavity. The primary contributing factor is postulated to be peritoneal spillage of benign leiomyoma, especially after laparoscopic intervention, although hormonal influences might also play a role.

Perceived Barriers to Leisure-Time Physical Activity Among Physically Active Individuals With Spinal Cord Injury.

Objective: To investigate barriers to leisure-time physical activity (LTPA) for physically active people with spinal cord injury (SCI).

Design: Prospective cross-sectional.

Setting: General community.

Neural Variability and Cognitive Control in Individuals With Opioid Use Disorder.

Importance: Opioid use disorder (OUD) impacts millions of people worldwide. Prior studies investigating its underpinning neural mechanisms have not often considered how brain signals evolve over time, so it remains unclear whether brain dynamics are altered in OUD and have subsequent behavioral implications.

Objective: To characterize brain dynamic alterations and their association with cognitive control in individuals with OUD.

Resilience Informatics in Public Health: Qualitative Analysis of Conference Proceedings.

Background: In recent years, public health has confronted 2 formidable challenges: the devastating COVID-19 pandemic and the enduring threat of climate change. The convergence of these crises underscores the urgent need for resilient solutions. Resilience informatics (RI), an emerging discipline at the intersection of informatics and public health, leverages real-time data integration from health systems, environmental monitoring, and technological tools to develop adaptive responses to multifaceted crises.

Dietary Inflammatory Score and Incident Heart Failure in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Background: Inflammation plays a key role in the development of heart failure (HF), and diet is a known modifiable factor that modulates systemic inflammation. The dietary inflammatory score (DIS) is a tool to quantify the inflammatory components of diet. We sought to determine whether the DIS is associated with incident HF events.

PREVENT and Pooled Cohort Equations in Mortality Risk Prediction: National Health and Nutrition Examination Survey.

Background: The Predicting Risk of CVD Events (PREVENT) equations were developed to address limitations of the Pooled Cohort Equations (PCEs) in predicting atherosclerotic cardiovascular disease (ASCVD) risk. The comparative effectiveness of the PREVENT equations versus the PCEs in predicting mortality risk remains unknown.

Objectives: The purpose of this study was to compare the risk discrimination value of the PREVENT equations with the PCEs for predicting mortality.

Real world data of Ewing sarcoma from a resource-limited setting with poor compliance to treatment leading to poor outcomes.

Background: There is limited data from India on Ewing sarcoma (ES) patients. We analysed the demographic and clinical profile of ES patients, the systemic chemotherapy, local treatment and outcomes in patients with localised, metastatic and recurrent disease.

Methods: Data of ES patients reporting from 2010 to 2019 to a tertiary care referral centre in north India was evaluated.

Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma.

Efficacy and durability remain central shortcomings of T-cell based therapies in multiple myeloma (MM). Here, we employ blood-based transcriptional T-cell profiling to define impaired T-cell fitness as putative biomarker associated with sensitivity to PD1 inhibition in CAR-T refractory MM patients.

Pharmacokinetics and safety of bictegravir in pregnant and postpartum persons with HIV and their infants.

Background: Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.

Setting: Nonrandomized, open-label, multi-center phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.

Methods: Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the 2nd and 3rd trimesters and postpartum was performed.

Synthesis and Reactivity of a Non-Heme μ-Oxodicobalt(IV) Complex.

A mononuclear CoIII complex (1) of a bisamide-bisalkoxide donor ligand was synthesized and thoroughly characterized. The reaction of 1 with 0.5 equiv.

Diffuse Large B-Cell Lymphoma Presenting Primarily as a Cutaneous Leg Lesion: A Case Report and Literature Review.

Primary cutaneous B-cell lymphoma (PCBCL) has three subtypes, among those, the leg type variant is the rarest with the highest rates of relapse and recurrence making it an intriguing focus for researchers. Nevertheless, prior to framing a diagnosis solely based on the lesion's location, it is prudent to reconsider whether it is genuinely a primary cutaneous B-cell lymphoma (PCBCL) or if it aligns more closely with the more prevalent lymphoma variants such as diffuse large B-cell lymphoma (DLBCL) with cutaneous involvement. We are reporting a case of an 85-year-old African American lady, who presented with unilateral left leg DLBCL with cutaneous involvement.

Advances in VEGFR Inhibitors: A Comprehensive Review of Novel Anticancer Agents.

Cancer, characterized by aberrant cell growth, presents a formidable health challenge, impacting millions of individuals worldwide each year. Among the myriad mechanisms facilitating tumor progression, Vascular Endothelial Growth Factor receptors (VEGFR) play a pivotal role in driving angiogenesis the process by which tumors develop their own blood supply. This vascularization not only supports tumor nourishment and growth but also facilitates metastasis, enabling cancer to spread to distant sites.

Primary myoepithelial carcinoma of the tibia: a close clinicoradiological mimicker of osteosarcoma.

Myoepithelial tumours are rare and distinct entities with uncertain histogenesis. They occur primarily in major salivary glands and soft tissue around the head and neck. Bony involvement predominantly occurs in facial bones.

Design and synthesis of a carbohydrate-derived chemosensor for selective Ni(II) ion detection: A turn-off approach.

Nickel, an essential transition metal, plays a vital role in biological systems and industries. However, exposure to nickel can cause severe health issues, such as asthma, dermatitis, pneumonitis, neurological disorders, and cancers of the nasal cavity and lungs. Due to nickel's toxicity and extensive industrial use, efficient sensors for detecting Ni ions in environmental and biological contexts are essential.

Genome-wide association mapping for stay-green and stem reserve mobilization traits in wheat (Triticum aestivum L.) under combined heat and drought stress.

Stay-green (SG) and stem reserve mobilization (SRM) are two significant mutually exclusive traits, which contributes to grain-filling during drought and heat stress in wheat. The current research was conducted in a genome-wide association study (GWAS) panel consisting of 278 wheat genotypes of advanced breeding lines to find the markers linked with SG and SRM traits and also to screen the superior genotypes. SG and SRM traits, viz.

Echocardiographic indices probe during dexmedetomidine/midazolam - ketamine anesthesia in dogs undergoing ovariohysterectomy.

Cardiovascular and respiratory alterations during anesthesia are of major concern in canines. Thus, it is essential to understand the potential depressant effects of anesthetic drugs on cardio-vascular system; so that, anesthetic procedures are conducted in the best possible way. The objective of the study was to assess and compare the echocardiographic indices during dex-medetomidine and midazolam anesthesia in dogs undergoing elective ovariohysterectomy.

Single-molecule localisation microscopy (SMLM) is feasible in human and animal formalin fixed paraffin embedded (FFPE) tissues in medical renal disease.

Aims: Establishment of a protocol for routine single-molecule localisation microscopy (SMLM) imaging on formalin fixed paraffin embedded (FFPE) tissue using medical renal disease including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS).

Methods: Protocol for normal and diseased renal FFPE tissue was developed to investigate the clinical diagnostic potential of SMLM. Antibody concentrations were determined for confocal microscopy and transferred to SMLM.

Fragment-based development of small molecule inhibitors targeting cholesterol metabolism.

( ) is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi-(MDR) and extensively-(XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.

Noncanonical PI(4,5)P2 coordinates lysosome positioning through cholesterol trafficking.

In p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 (SREBP-2) pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, new strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport.

PET/CT guided tuberculosis treatment shortening: a randomized trial.

Six months of chemotherapy using current agents is standard of care for pulmonary, drug-sensitive tuberculosis (TB), even though some are believed to be cured more rapidly and others require longer therapy. Understanding what factors determine the length of treatment required for durable cure in individual patients would allow individualization of treatment durations, provide better clinical tools to determine the of appropriate duration of new regimens, as well as reduce the cost of large Phase III studies to determine the optimal combinations to use in TB control programs. We conducted a randomized clinical trial in South Africa and China that recruited 704 participants with newly diagnosed, drug-sensitive pulmonary tuberculosis and stratified them based on radiographic disease characteristics as assessed by FDG PET/CT scan readers.

Up-front dissection of the uterovesical space or "bladder-first approach" reduces hemorrhage and bladder injury during hysterectomy for placenta accreta spectrum: reconfirmed in 78 more cases in a prospective single-center study.

Background: Cesarean hysterectomy for placenta accreta spectrum disorder may be associated with severe hemorrhage because of placental invasion of the myometrium and the uterovesical space or parametrium. It leads to serious complications, such as massive hemorrhage requiring massive transfusion, coagulopathy, bladder and ureteric injuries, need for intensive care unit admission and prolonged hospital stay. To reduce the complications of cesarean hysterectomy for placenta accreta spectrum disorder, ongoing efforts are being made to develop different surgical approaches.

Chronodisruption that dampens output of the central clock abolishes rhythms in metabolome profiles and elevates acylcarnitine levels in the liver of female rats.

Aim: Exposure to light at night and meal time misaligned with the light/dark (LD) cycle-typical features of daily life in modern 24/7 society-are associated with negative effects on health. To understand the mechanism, we developed a novel protocol of complex chronodisruption (CD) in which we exposed female rats to four weekly cycles consisting of 5-day intervals of constant light and 2-day intervals of food access restricted to the light phase of the 12:12 LD cycle.

Methods: We examined the effects of CD on behavior, estrous cycle, sleep patterns, glucose homeostasis and profiles of clock- and metabolism-related gene expression (using RT qPCR) and liver metabolome and lipidome (using untargeted metabolomic and lipidomic profiling).