Preclinical and Clinical Pharmacokinetics of JNJ-75220795, an siRNA Therapeutic Targeting PNPLA3, for Metabolic Dysfunction-Associated Steatohepatitis.

JNJ-75220795 or ARO-PNPLA3 is an investigational small interfering ribonucleic acid agent conjugated with N-acetyl-d-galactosamine that targets the PNPLA3 gene, currently being developed for metabolic dysfunction-associated steatohepatitis (MASH). This study evaluated the pharmacokinetics (PK) profile of single subcutaneous doses of JNJ-75220795 in preclinical species as well as in human subjects with homozygous or heterozygous PNPLA3 I148M mutation in two phase 1 studies-a first-in-human study in the United States and a first-in-Japanese study in Japan. Preclinical PK in rats and non-human primates (NHP) showed a rapid systemic absorption and elimination following single subcutaneous doses.

Sample Preparation for Global Metabolic Profiling of Vaccinia Virus-Infected Primary Human Foreskin Fibroblasts.

Vaccinia virus (VACV), the prototype member of the Poxviridae family, has played a crucial role in medicine as a key component in the development of smallpox vaccines, contributing to the eradication of this deadly disease. Beyond its historical significance, VACV continues to be pivotal in researching metabolic alterations induced by viral infections. Studies have revealed that VACV can impact pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, and lipid metabolism in host cells, offering valuable insights into host-virus interactions and broader cellular metabolism.

Effectiveness of ozone nanobubble treatments on high biomass cyanobacterial blooms: A mesocosm experiment and field trial.

Cyanobacterial harmful algae blooms (cyanoHABs) are a global threat to water resources, and lake managers need effective strategies to suppress or control them. Algaecides may have negative environmental impacts, and their use is becoming restricted. Nanobubble ozone technology (NBOT) is an emerging water treatment option with potentially fewer negative impacts.

Opportunities to advance cervical cancer prevention and care.

Cervical cancer (CaCx) is a major public health issue, with over 600,000 women diagnosed annually. CaCx kills someone every 90 s, mostly in low- and middle-income countries. There are effective yet imperfect mechanisms to prevent CaCx.

The role of convalescent plasma and hyperimmune immunoglobulins in the COVID-19 pandemic, including implications for future preparedness.

Introduction: When Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks.

Methods: A scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment.

cPEPmatch Webserver: A comprehensive tool and database to aid rational design of cyclic peptides for drug discovery.

Cyclic peptides have emerged as versatile scaffolds in drug discovery due to their stability and specificity. Here, we present the cPEPmatch webserver (accessible at https://t38webservices.nat.

The global blood donation index: an imperfect measure of transfusion need.

The optimum number of units of blood and the associated number of blood donors required to meet a given population's needs remain undetermined globally. Typically, a whole blood donation rate of ten donations per 1000 population, at a minimum, is necessary to meet a country's blood needs. This rate is attributed to a WHO recommendation that 1% of a given country's population should donate blood to ensure a blood supply that is sufficient to meet clinical needs.

A review and analysis of outcomes in randomized clinical trials of plasma transfusion in patients with bleeding or for the prevention of bleeding: The BEST collaborative study.

Background: Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence-based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes.

Study Design And Methods: RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023).

Effectiveness of subcutaneous monoclonal antibody treatment in emergency department outpatients with COVID-19.

Objectives: To evaluate whether subcutaneous neutralizing monoclonal antibody (mAb) treatment given in the emergency department (ED) setting was associated with reduced hospitalizations, mortality, and severity of disease when compared to nontreatment among mAb-eligible patients with coronavirus disease 2019 (COVID-19).

Methods: This retrospective observational cohort study of ED patients utilized a propensity score-matched analysis to compare patients who received subcutaneous casirivimab and imdevimab mAb to nontreated COVID-19 control patients in November-December 2021. The primary outcome was all-cause hospitalization within 28 days, and secondary outcomes were 90-day hospitalization, 28- and 90-day mortality, and ED length of stay (LOS).

Exonuclease-enhanced prime editors.

Prime editing (PE) is a powerful gene-editing technique based on targeted gRNA-templated reverse transcription and integration of the de novo synthesized single-stranded DNA. To circumvent one of the main bottlenecks of the method, the competition of the reverse-transcribed 3' flap with the original 5' flap DNA, we generated an enhanced fluorescence-activated cell sorting reporter cell line to develop an exonuclease-enhanced PE strategy ('Exo-PE') composed of an improved PE complex and an aptamer-recruited DNA-exonuclease to remove the 5' original DNA flap. Exo-PE achieved better overall editing efficacy than the reference PE2 strategy for insertions ≥30 base pairs in several endogenous loci and cell lines while maintaining the high editing precision of PE2.

A rare vascular injury in a blood donor after whole blood donation.

Background: Blood donation is a safe process though reactions may still occur. We describe a rare vascular complication in a frequent donor, with improvements in the collection process aimed at avoiding future events.

Methods: A 63-year-old woman presented with local pain and an apparent collection in the left arm 8 days after donation.

The potential of PCNA inhibition as a therapeutic strategy in cervical cancer.

Cervical cancers are the fourth most common and most deadly cancer in women worldwide. Despite being a tremendous public health burden, few novel approaches to improve care for these malignancies have been introduced. We discuss the potential for proliferating cell nuclear antigen (PCNA) inhibition to address this need as well as the advantages and disadvantages for compounds that can therapeutically inhibit PCNA with a specific focus on cervical cancer.

Interactions among human papillomavirus proteins and host DNA repair factors differ during the viral life cycle and virus-induced tumorigenesis.

This review focuses on the impact of human papillomavirus (HPV) oncogenes on DNA repair pathways with a particular focus on how these relationships change as productive HPV infections transition to malignant lesions. We made specific efforts to incorporate advances in the understanding of HPV and DNA damage repair over the last 4 years. We apologize for any articles that we missed in compiling this report.

Narrative-based learning for person-centred healthcare: the Caring Stories learning framework.

This paper describes the learning framework for an innovative narrative-based training platform for healthcare professionals based on older patients' narratives. The aim of Caring Stories is to place patients' desires and needs at the heart of healthcare and by doing so to promote person-centred care (PCC). It is argued that this narrative-based approach to training in healthcare education will provide professionals from different fields with competencies to better understand how to interpret the lifeworlds of older people, as well as facilitate better communication and navigation through increasingly complex care trajectories.

Bell's Palsy in Pregnancy and Postpartum: A Retrospective Case-Control Study of 182 Patients.

Objective: To assess the incidence of Bell's palsy in pregnant and postpartum women. Additionally, to compare facial outcomes in terms of Sunnybrook score following Bell's palsy with regard to corticosteroid treatment and other confounding factors.

Study Design: Retrospective case-control study.

Successful Implementation of Workflow-Embedded Clinical Pathways During the COVID 19 Pandemic.

Background And Objectives: Clinical pathways have been found effective for improving adherence to evidence-based guidelines, thus providing better patient outcomes. As coronavirus disease-2019 (COVID-19) clinical guidance changed rapidly and evolved, a large hospital system in Colorado established clinical pathways within the electronic health record to guide clinical practice and provide the most up-to-date information to frontline providers.

Methods: On March 12, 2020, a system-wide multidisciplinary committee of specialists in emergency medicine, hospital medicine, surgery, intensive care, infectious disease, pharmacy, care management, virtual health, informatics, and primary care was recruited to develop clinical guidelines for COVID-19 patient care based on the limited available evidence and consensus.