Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037).

Background: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

Facile Synthesis of Oxazolidinones as Potential Antibacterial Agents.

An efficient microwave-assisted synthesis route for novel oxazolidinone analogues has been developed. The general synthesis of these compounds began with an L-proline-mediated three-component Mannich reaction between commercially available 3-fluoro-4-morpholinoaniline, aqueous formaldehyde and α-hydroxyacetone. This was followed by a one-step cyclisation to form the core structure of oxazolidinone antibiotics which was subsequently derivatized.

Molecular and spatial analysis of ganglion cells on retinal flatmounts: diversity, topography, and perivascularity.

Diverse retinal ganglion cells (RGCs) transmit distinct visual features from the eye to the brain. Recent studies have categorized RGCs into 45 types in mice based on transcriptomic profiles, showing strong alignment with morphological and electrophysiological properties. However, little is known about how these types are spatially arranged on the two-dimensional retinal surface-an organization that influences visual encoding-and how their local microenvironments impact development and neurodegenerative responses.

Prognostic accuracy of Whole Lung Perfusion Blood Volume as a predictor of 28-day Mortality in Acute Pulmonary Thromboembolism - A prospective study.

Background: The estimated incidence of pulmonary embolism (PE) is around 60-70 cases per 100,000 people annually. The overall mortality rate for massive PE is substantial, ranging from 18% to 65%. We can utilise changes in lung perfusion to stratify patients with PE acutely based on risk, highlighting its diagnostic and prognostic value.

Comparing immunogenicity and safety following transition from reference rituximab to biosimilar rituximab (DRL_RI) in patients with rheumatoid arthritis: a randomized, double-blind, phase 3 study.

Objectives: To assess immunogenicity and safety in patients with active rheumatoid arthritis (RA) transitioning from rituximab [US-licensed rituximab: Reference Product (RP); EU-approved rituximab: Reference Medicinal Product (RMP)] to DRL_RI (proposed rituximab biosimilar), in comparison to those continuing on RP/RMP.

Methods: This double-blind, randomized, Phase 3 study included 140 RA patients having prior exposure to RP/RMP; transitioned to DRL_RI (n = 70) or continued with RP/RMP (n = 70) for two 1000 mg infusions on Days 1 and 15. Assessments included Time-matched Rituximab Concentration (TMRC), anti-drug antibodies (ADAs), neutralizing antibodies (NAbs) and ADA titre over 12 weeks, and safety follow-up till 26 weeks.

Enhancement to effusion: Breast implant-associated anaplastic large cell lymphoma.

Unlabelled: This case is a rare presentation of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), where malignant pericardial effusion (MPE) served as the primary manifestation. A 58-year-old woman, post-breast implant removal, presented with pleuritic chest pain, fever, and chills. Clinical evaluation revealed jugular venous distention, muffled heart sounds, and hemodynamic instability.

Characterization of a novel subfamily 1.4 lipase from Bacillus licheniformis IBRL-CHS2: Cloning and expression optimization.

This study focuses on a novel lipase from Bacillus licheniformis IBRL-CHS2. The lipase gene was cloned into the pGEM-T Easy vector, and its sequences were registered in GenBank (KU984433 and AOT80658). It was identified as a member of the bacterial lipase subfamily 1.

Ciliopathy interacts with neonatal anesthesia to cause non-apoptotic caspase-mediated motor deficits.

Increasing evidence suggests that anesthesia may induce developmental neurotoxicity, yet the influence of genetic predispositions associated with congenital anomalies on this toxicity remains largely unknown. Children with congenital heart disease often exhibit mutations in cilia-related genes and ciliary dysfunction, requiring sedation for their catheter or surgical interventions during the neonatal period. Here we demonstrate that briefly exposing ciliopathic neonatal mice to ketamine causes motor skill impairments, which are associated with a baseline deficit in neocortical layer V neuron apical spine density and their altered dynamics during motor learning.

Comparing Postprandial Glycemic Control Using Fiasp vs Insulin Aspart in Hospitalized Patients With Type 2 Diabetes.

Objective: Hyperglycemia in hospitalized patients is associated with increased morbidity and mortality. Basal-bolus insulin therapy is the treatment of choice for most patients. The efficacy of an ultrarapid vs rapid-acting insulin in hospitalized patients with diabetes has not been evaluated.

Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs.

Immune homeostasis requires a balance of inflammatory and suppressive activities. To design cells potentially useful for local immune suppression, we engineered conventional CD4 T cells with synthetic Notch (synNotch) receptors driving antigen-triggered production of anti-inflammatory payloads. Screening a diverse library of suppression programs, we observed the strongest suppression of cytotoxic T cell attack by the production of both anti-inflammatory factors (interleukin-10, transforming growth factor-β1, programmed death ligand 1) and sinks for proinflammatory cytokines (interleukin-2 receptor subunit CD25).

Is Reconstructive Plastic Surgery Appropriately Valued? Comparison of Reimbursement per Unit Time for Reconstructive versus Aesthetic Procedures.

Background: The work relative value units (wRVUs) system was established as a quantifier of physician labor, technical skill, medical decision-making, and training time required to complete a surgical procedure; hence, more challenging operations should theoretically result in higher reimbursement or compensation. Our purpose was to highlight the discrepancies between insurance-based reconstructive and fee-for-service aesthetic procedures based upon dollar/unit time.

Methods: We analyzed national data from the American College of Surgeons National Surgical Quality Improvement Program, Aesthetic Surgery Databank, and Centers for Medicare and Medicaid Services to compare reimbursement for 8 reconstructive microsurgery and 3 aesthetic procedures and assessed operative times and reimbursement rates, then calculated "relative value unit per unit time" to measure compensation efficiency.

Does a Single Episode of Pain from Impacted Third Molars Necessitate Their Removal?

Background: Pericoronitis induces oxidative stress in the dental follicular (DF) tissue, which can lead to histopathological alterations. It is a fact that an impacted tooth with a history of recurrent pericoronitis should be extracted. But there is a limited research on the levels of nitric oxide (NO) in DF tissues of impacted mandibular third molars with even a single episode of pain, necessitating their removal biochemically at a younger age.

Quantitative mapping of cerebrovascular reactivity amplitude and delay with breath-hold BOLD fMRI when end-tidal CO quality is low.

Cerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in order to regulate blood flow, is a clinically useful measure of cerebrovascular health. CVR is often measured using a breath-hold task to modulate blood CO levels during an fMRI scan. Measuring end-tidal CO (PCO) with a nasal cannula during the task allows CVR amplitude to be calculated in standard units (vascular response per unit change in CO, or %BOLD/mmHg) and CVR delay to be calculated in seconds.

Late Survival and Long-Term Follow-Up After Radical Resection of Advanced Renal Cell Carcinoma With Associated Venous Tumor Thrombus.

Background And Objectives: This study evaluates the prognostic value of venous tumor thrombus (VTT) in patients with advanced renal cell carcinoma (RCC) undergoing radical resection and inferior vena cava (IVC) thrombectomy.

Methods: Retrospective review of patients with radical nephrectomy for RCC and associated VTT (2000-2024). Patients were dichotomized into Neves 0-II (infrahepatic) and Neves III-IV groups (suprahepatic) IVC involvement for univariate analysis.

Tumour mimics in paediatric neuroimaging.

Distinguishing tumours from other conditions is a primary challenge in paediatric neuro-radiology. This paper aims to describe mimics, which are non-neoplastic conditions that have features similar to a neoplastic process caused by a non-neoplastic entity, and chameleons, which are uncommon presentations of brain tumours that are mistaken for other diagnoses. By doing so, we aim to raise awareness of these conditions and prevent inappropriate investigations or treatment in children.

Comparative study of endophytic bacterial strains from non-host crops for enhancing plant growth and managing early blight in tomato.

, , and are potent bacterial endophytes, which typically exhibit host-specific interactions. However, comparative studies of these endophytes and in non-host crops are lacking. Therefore, in this study, we evaluated the potential of endophytes strain HP3d, strain PGSS1, strain A6, and P42, isolated from various crop ecosystems in promoting plant growth and inducing systemic resistance against early blight disease in tomato.

Jammed joints and constricted heart: The science of tribology and missing lubricin. A case report on camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

An autosomal recessively inherited noninflammatory arthropathy known as camptodactyly, arthropathy, coxa vara, and pericarditis (CACP) syndrome was discovered in 1999. It is distinguished by synoviocyte hyperplasia and subcapsular fibrosis of the synovial capsule, which results in a shortage of lubricin production. The resulting lack of joint lubrication induces increased mechanical stress, causing progressive deformities that become evident with weight-bearing and heightened joint activity.

Redefining pancreatic cancer management with tumor-agnostic precision medicine.

Precision oncology and tumor-agnostic drug development provide hope for enhancing outcomes among patients with pancreatic cancer. Tumor-agnostic therapies have emerged across various tumor types, driven by insights into shared biomarkers. In the case of pancreatic cancer, the prevalence of the KRAS gene mutation is noteworthy.

Novel method of calculation of MRI perfusion and comparison of single versus double barrel STA-MCA bypass for revascularisation in Moya Moya disease.

Introduction: Moyamoya disease (MMD) is characterised by supraclinoid internal carotid artery (ICA) narrowing causing cerebral parenchyma to starve. Direct and indirect revascularisation techniques are the treatment norm. We provide a clinicoradiological comparison of single and double barrel superficial temporal artery to middle cerebral artery (STA-MCA) bypass for MMD.