Safety, tolerability, and pharmacokinetics of a novel anti-influenza agent ZX-7101A tablets in healthy chinese participants: A first-in-human phase I clinical study.

Background: We investigated the safety, tolerability, and pharmacokinetics of ZX-7101A tablets, a novel cap-dependent endonuclease inhibitor, in healthy participants in a first-in-human study.

Methods: The single ascending dose (SAD) part of the study included 40, 80, 160, 240, and 320 mg dose cohorts with10 participants in each dose cohort (8 participants received ZX-7101A tablets and 2 participants received placebo). The food effect (FE) part of the study was a randomised, 2-cycle, 2-way crossover design, which enrolled 16 participants to receive a single oral dose of 80 mg ZX-7101A tablets.

Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth.

Deeper understanding of the crosstalk between host cells and (Mtb) provides crucial guidelines for the rational design of novel intervention strategies against tuberculosis (TB). Mycobacteria possess a unique complex cell wall with arabinogalactan (AG) as a critical component. AG has been identified as a virulence factor of Mtb which is recognized by host galectin-9.

Evaluation and application of population pharmacokinetic models for optimising linezolid treatment in non-adherence multidrug-resistant tuberculosis patients.

Background: Population pharmacokinetic (popPK) models can optimise linezolid dosage regimens in patients with multidrug-resistant tuberculosis (MDR-TB); however, unknown cross-centre precision and poor adherence remain problematic. This study aimed to assess the predictive ability of published models and use the most suitable model to optimise dosage regimens and manage compliance.

Methods: One hundred fifty-eight linezolid plasma concentrations from 27 patients with MDR-TB were used to assess the predictive performance of published models.

Long-term survival after unrelated donor marrow transplantation for aplastic anaemia after optimized conditioning regimen: a retrospective multicentre cohort study.

Background: Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50 mg/kg (150, 100, 50, 0 mg/kg) in combination with total body irradiation (TBI) 2 Gy, anti-thymocyte globulin (ATG) and fludarabine.

Effects of individualized positive end-expiratory pressure on intraoperative oxygenation and postoperative pulmonary complications in patients requiring pneumoperitoneum with Trendelenburg position: A systematic review and meta-analysis.

Background: Whether individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and reduces postoperative pulmonary complications (PPCs) remains unclear. This systematic review and meta-analysis examined whether individualized PEEP is associated with improved intraoperative oxygenation and reduce PPCs for patients needing pneumoperitoneum with the Trendelenburg position during surgery.

Methods: Medline, Embase, the Cochrane Library, and www.

Primary caregiver burden and undiagnosed mental health illness in out-patients with inflammatory bowel disease-A multicentric prospective survey from the IBD Emerging Nations' Consortium.

Background: Mental health is an overlooked aspect of inflammatory bowel disease (IBD) patient care with limited data from the developing world. The primary caregiver burden is expected to be high, but has not been evaluated.

Methods: We conducted a questionnaire-based survey of consecutive out-patients with no diagnosed mental health illness (n = 289) and their primary caregivers (n = 247) from 10 centers across eight countries (Bangladesh, India, Iran, Malaysia, Myanmar, Nepal, Pakistan, Thailand) of IBD-Emerging Nations' Consortium (ENC).

MIFEPRISTON IN OBSTETRICS - WHY NOT?

Cervical ripening is a critical component of normal parturition. There are substantial variations in labour induction (IOL) techniques around the world. Mifepristone causes the termination of unwanted pregnancies, but there is a lack of consensus on its use for labour induction.

Performance Evaluation of SARS-CoV-2 Rapid Antigen Test Among Symptomatic and Asymptomatic Patients in the Emergency Department of a Tertiary Care Hospital.

The aim of this study was to evaluate the diagnostic performance of the SARS-CoV-2 rapid antigen test (RAT) for the diagnosis of COVID-19 among symptomatic and asymptomatic patients. This retrospective study was done from 15th November 2021 to 15th December 2021, at National Medical Centre, Karachi, Pakistan. Two parallel nasopharyngeal swabs were collected from each patient, and SARS-CoV-2 RAT and SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) were done.

Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy.

Introduction: Immune checkpoint blockade (ICB) improved clinical outcomes in renal and bladder cancer patients, but the response rates remain limited especially in metastatic disease. While STAT3 transcription factor is well-known master regulator of tumor immune evasion, little is known about the role of STAT3 in the resistance of renal or bladder cancers to immunotherapy.

Methods: To better understand immune alterations associated with ICB resistance, we assessed blood biomarkers in renal cancer patients classified as responders or non-responders to first line nivolumab/ipilimumab immunotherapy.

Mutations in PGRN gene associated with the risk of psoriasis in Pakistan: a case control study.

Background: Psoriasis is a chronic, autoimmune, papulosquamous skin disorder, characterized by the formation of drop-like papules and silvery-white plaques surrounded by reddened or inflamed skin, existing predominantly on the scalp, knees and elbows. The characteristic inflammation and hyperproliferation of keratinocytes in psoriasis is regulated by progranulin (PGRN), which suppresses the expression and release of inflammatory cytokines, such as TNF-α.

Methodology: In this study mutation analysis of the PGRN gene was performed by extracting the genomic DNA from blood samples of 171 diagnosed psoriasis patients and controls through standard salting-out method, followed by amplification and sequencing of the targeted region of exon 5-7 of PGRN gene.

In vivo evaluation of new adjuvant systems based on combination of Salmonella Typhi porins with particulate systems: Liposomes versus polymeric particles.

Subunit vaccines that have weak immunogenic activity require adjuvant systems for enhancedcellular and long-acting humoral immune responses. Both lipid-based and polymeric-based particulate adjuvants have been widely investigated to induce the desired immune responses against the subunit vaccines. The adjuvant efficacy of these particulate adjuvants depends upon their physicochemical properties such as particle size, surface charge, shape and their composition.

Dermatoscopic Patterns in Childhood Vitiligo and Their Association With Reflectance Confocal Microscopy Findings.

Introduction: The diagnosis of vitiligo is mainly based on clinical findings. However, dermoscopy or reflectance confocal microscopy (RCM) could be useful for assessing its progression (stability, pigmen-tation, or depigmentation).

Objectives: To evaluate the correlation of dermatological findings by dermoscopy and RCM in pediatric vitiligo.

Utilization of an ultra-low-field, portable magnetic resonance imaging for brain tumor assessment in lower middle-income countries.

Background: Access to neuroimaging is limited in low-middle-income countries (LMICs) due to financial and resource constraints. A new, ultra-low-field, low-cost, and portable magnetic resonance imaging (pMRI) device could potentially increase access to imaging in LMICs.

Case Description: We have presented the first brain tumor case scanned using an Ultra-low-field pMRI at Aga Khan University Hospital in Karachi, Pakistan.

Intraoperative use of ultra-low-field, portable magnetic resonance imaging - first report.

Background: Intraoperative use of portable magnetic resonance imaging (pMRI) has become a valuable tool in a surgeon's arsenal since its inception. It allows intraoperative localization of tumor extent and identification of residual disease, hence maximizing tumor resection. Its utility has been widespread in high-income countries for the past 20 years, but in lower-middle-income countries (LMIC), it is still not widely available due to several reasons, including cost constraints.

Enhancing Equitable Access to Rare Disease Diagnosis and Treatment around the World: A Review of Evidence, Policies, and Challenges.

This document provides a comprehensive summary of evidence on the current situation of rare diseases (RDs) globally and regionally, including conditions, practices, policies, and regulations, as well as the challenges and barriers faced by RD patients, their families, and caregivers. The document builds on a review of academic literature and policies and a process of validation and feedback by a group of seven experts from across the globe. Panelists were selected based on their academic merit, expertise, and knowledge regarding the RD environment.

Dual targeting of CD19 and CD22 with bicistronic CAR-T cells in patients with relapsed/refractory large B-cell lymphoma.

Relapse after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multiantigen targeting and programmed cell death protein-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in relapsed/refractory LBCL (NCT03289455).

9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea.

Background: With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis.

Methods: In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea.

Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy.

Neuroglial apoptosis and neuroinflammation play an important role in epileptogenesis. The aim of this study is to evaluate neuronal and glial apoptosis in association with neuroinflammation in brain epileptic focus and inflammatory changes in blood in patients with focal drug-resistant epilepsy (DRE). Pathological changes in the temporal lobe in epilepsy (histology, transmission electron microscopy), levels of apoptotic and neuroinflammatory proteins: active caspase-3 (immunohistochemistry), full-length form caspase-3, caspase-9, FAS, FAS-L, NF-kB, TNF-α, p53 (Western blot), and cytokine levels in blood: IL-1β, IL-2, IL-4, IL-7, TNF-α, etc.

The effect of the national scaling program on tooth loss: a claim-based matched large cohort study in Korea.

Objective: Tooth loss affects quality of life. Scaling is a measure to prevent periodontal disease and tooth loss. This study aimed to determine the effect of scaling on tooth loss.