Long-acting nifedipine in the management of essential hypertension: a review for cardiologists.

Calcium channel antagonists, specifically long-acting nifedipine formulations, play a crucial role in treating hypertension and angina. Originally used for angina, nifedipine has been widely employed as an antihypertensive medication for over 40 years. It offers rapid action and oral bioavailability with minimal maternal or fetal side effects, making it suitable for treating hypertensive crises during pregnancy.

In situ RAS:RAF binding correlates with response to KRASG12C inhibitors in KRASG12C--mutant non-small cell lung cancer.

Purpose: Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared to tumors with lower RAS---RAF interaction.

Trastuzumab Deruxtecan Combination Strongly Enhances Responses and Overcomes Sotorasib Resistance in -Mutant NSCLC.

Introduction: Recent advances in the treatment of -mutant non-small cell lung cancer (NSCLC) have led to the development of KRAS inhibitors, such as sotorasib and adagrasib. However, resistance and disease progression remain significant challenges. In this study, we investigated the therapeutic potential of combining trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody-drug conjugate, with sotorasib in -mutant NSCLC, while also evaluating HER2 expression in NSCLC samples.

Discovery of fossil avian footprints from Late Holocene sediments of Allahbund uplift in Great Rann of Kachchh of Western India.

The Great Rann of Kachchh is a sabkha terrain with a thick succession of Quaternary to Late Holocene sediments, deposited during high sea level after the Last Glacial Maxima. Geomorphologically, the Great Rann of Kachchh is subdivided into Bet Zone, Linear Trench Zone, Great Barren Zone, and Banni Plain. The Bet zone is a slightly elevated flat surface comprising a complex network of bets and interbet channels-the geomorphic entities developed as complex interplay of sea level and coseismic tectonic activity during the Holocene.

Distinct properties and activation of hexameric and heptameric Pannexin 1 channel concatemers.

Pannexin 1 (PANX1) is a member of a topologically related and stoichiometrically diverse family of large pore membrane ion channels that support the flux of signaling metabolites (e.g., ATP) and fluorescent dyes.

Peripheral edema induced by isosorbide mononitrate in an elderly patient: A case study of dose-related risks and drug interactions.

Adverse drug reactions (ADRs) in elderly patients are frequently attributed to age-related altered pharmacokinetics and the complexities of polypharmacy to manage multiple chronic conditions, making elderly patients more susceptible to ADRs. The following is a case report of an 80-year-old female patient with systemic symptoms of chest pain, low blood sugar, mouth ulcers, and concentrates on peripheral edema due to nitrate vasodilator isosorbide mononitrate (ISMN). She had hypertension, diabetes, ischemic heart disease, and chronic obstructive pulmonary disease (COPD).

Constitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects in microglia.

CX3CR1-Cre mouse lines have produced important advancements in our understanding of microglial biology. Recent studies have demonstrated the adverse effects of tamoxifen-induced CX3CR1-Cre expression during development, which include changes in microglial density, phenotype, and DNA damage, as well as anxiety-like behavior. However, the unintended effects of constitutive CX3CR1-BAC-Cre expression remain unexplored.

Expert Opinion on the Role of Sacubitril/Valsartan in the Management of Hypertension in India.

Hypertension, a key modifiable risk factor for cardiovascular diseases (CVD), significantly contributes to premature death and morbidity worldwide. Despite stabilization in age-adjusted global prevalence, the absolute number of hypertensive individuals doubled from 2000 to 2010, largely due to increases in low- and middle-income countries. In 2021, only 21% of hypertensive individuals globally had effective blood pressure (BP) control.

Circulating microRNAs associated with bronchodilator response in childhood asthma.

Background: Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.

Green Protocol for the Synthesis of Luminescent Carbon Nanodots Derived from Murraya Koenigii Leaves and Urea: Enhancing Photoluminescence for Advanced Bioimaging.

We have synthesized Murraya Koenigii leaves powder-derived carbon nanodots (CNDs) by hydrothermal method. A tribute to our commitment to environmental sustainability is the unique composition of our CNDs, which are made entirely of natural carbon sources and a green solvent, water. Our further efforts to improve performance led us to start making nitrogen-doped CNDs.

Biologics in Asthma: Emerging Biologics.

Advances in our understanding of asthma pathophysiology have led to the advent of multiple targeted asthma therapies such as biologics. However, partial response to biologics occurs, indicating residual disease activity in some patients. Hence, there exists a need for new therapies that focus on novel pathways, alongside perhaps evaluation of combination biologic therapies and modulators of downstream cytokine activation.

Emerging Role of Low-dose Loop Diuretics in the Management of Heart Failure Patients to Maintain Euvolemia.

The current scenario of employing loop diuretics in combination with guideline-directed medical therapy (GDMT) demonstrates a comprehensive approach to improving clinical outcomes in individuals with heart failure (HF). GDMT uses four types of drugs: angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Torsemide, furosemide, and bumetanide are common loop diuretics used to control fluid overload in HF and provide symptomatic relief.

Integrated Physical-Mental Healthcare Services in Specialist Settings to Improve Outcomes for Older People Living With Mental Health Diagnoses: A Systematic Review.

Background: Many older people are now living with co-occurring physical and mental health disorders, but these often managed separately. The aim of this systematic review was to explore integrated physical-mental health care services available internationally for older people living with mental health diagnoses, and whether these result in improved health outcomes.

Methods: Medline, Embase, CINAHL, PsycINFO and Scopus were searched with a predefined search strategy (PROSPERO: CRD42022383824), generating 6210 articles.

Identification of MicroRNAs in children with increased asthma bronchodilator usage in genetics of asthma in Costa Rica Study.

Introduction: Uncontrolled or severe asthma results in symptomatic usage of short-acting ß2-agonist (SABA) usage. MicroRNAs (miRNAs) are posttranslational regulators that can influence asthma biology. This study aims to identify miRNAs that are associated with increased SABA usage.

Nickel allergy does not correlate with function after total knee arthroplasty.

Purpose: The purpose of this study is to determine if there is a relationship between clinical outcomes and nickel allergy by evaluating asymptomatic total knee arthroplasty (TKA) patients with well-functioning implants through quantitative metal allergy (MA) testing.

Methods: A prospective case series was performed on 50 patients with well-functioning TKA of various implant types. Inclusion criteria included primary TKA with a minimum 12-month follow-up and Oxford knee score (OKS) ≥ 40.

Virtual reality use in pediatric patients for orthopedic clinical procedures: A randomized prospective trial of efficacy.

Background: Distraction therapy use such as virtual reality is novel in the pediatric orthopedic field. In this study, we use subjective and objective metrics to evaluate virtual reality efficacy to reduce anxiety and pain in a pediatric orthopedic cohort.

Methods: A prospective randomized controlled trial included patients between age 5 and 17 years, presenting to a tertiary care pediatric orthopedic clinic.

Dissecting the Spatially Restricted Effects of Microenvironment-Mediated Resistance on Targeted Therapy Responses.

The response of tumors to anti-cancer therapies is defined not only by cell-intrinsic therapy sensitivities but also by local interactions with the tumor microenvironment. Fibroblasts that make tumor stroma have been shown to produce paracrine factors that can strongly reduce the sensitivity of tumor cells to many types of targeted therapies. Moreover, a high stroma/tumor ratio is generally associated with poor survival and reduced therapy responses.

Intranasal delivery of doxepin: enhancing brain targeting efficiency utilizing nanostructured lipid carriers for a biopharmaceutics drug disposition classification system class-I drug.

Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box-Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery.

Use of Patient-Specific Interbody Cages Through a Minimally Invasive Lateral Approach for Unstable Lumbar Spondylodiskitis.

Background And Objectives: Patients with diskitis/osteomyelitis who do not respond to medical treatment or develop spinal instability/deformity may warrant surgical intervention. Irregular bony destruction due to the infection can pose a challenge for spinal reconstruction. The authors report a lateral approach using patient-specific interbody cages combined with posterior or lateral instrumentation to achieve spinal reconstruction for spinal instability/deformity from spondylodiskitis.

Vague Presentation of Cat Scratch Disease in a Child.

Prolonged fever for more than a week or fever of unknown origin in pediatric patients with or without soft tissue infection should raise suspicion for infection. A 10-year-old female presented to urgent care with a "bug bite" on the left ring finger, cough, and 2 to 3 days of low-grade fever. Ten days later, her symptoms progressed to soft tissue swelling of the left elbow without fracture on radiograph.

Patellar Tendon Reconstruction Using Tibialis Posterior Allograft for Treatment of Patellar Tendon Rupture After Bone-Patellar Tendon-Bone Anterior Cruciate Ligament Reconstruction.

Bone-patellar tendon-bone (BPTB) autografts are often used to treat anterior cruciate ligament (ACL) tears in young, highly active patients. These grafts are robust and provide adequate stability, allowing for return to sport and optimal functional outcomes in athletes. Patellar tendon rupture following BPTB ACL reconstruction is rare and can be difficult to treat.

L-Arginine Doped Carbon Nanodots from Cinnamon Bark for Improved Fluorescent Yeast Cell Imaging.

In this study, we present an economical and efficient synthesis method for carbon nanodots (CNDs) derived from cinnamon bark wood powder, with the incorporation of L-arginine as a dopant at varying ratios (Cinnamon : L-Arginine - 1:0.25, 1:0.5) via a hydrothermal reaction.