Pharmacokinetics of Nivolumab and Erythropoietin in a Rat Model of Diet-Induced Obesity.

Purpose: To investigate how obesity affects the pharmacokinetics of biologics in a rat model.

Method: Male Long-Evans rats were fed a high-fat diet from the age of 3 weeks and development of obesity was monitored by measuring body size and composition (fat and lean mass). The animals received nivolumab (1 and 8 mg/kg) or recombinant human erythropoietin (rHuEPO, 1000 IU/kg) by intravenous or subcutaneous injection.

Microstructure response of concentrated suspensions to flow reversal.

We study experimentally at the macroscopic and microstructure scale a dense suspension of non-Brownian neutrally buoyant spherical particles experiencing periodic reversals of flow at constant rate between parallel plates and tracked individually. We first characterize the quasi-steady state reached at the end of half periods. The volume fraction of particles increases from the walls to the center as a result of migration induced by the nonuniform strain rate.

Schizophrenia and retention in HIV care among adults insured through Medicaid in the United States: a population-based retrospective cohort study.

Background: People with schizophrenia spectrum disorders are at elevated risk of HIV, and people with both HIV and schizophrenia are at elevated risk of death compared to individuals with either diagnosis alone. Limited research has assessed the HIV care cascade, and in particular retention in care, among people with HIV (PWH) and schizophrenia in the U.S.

Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.

Intratumoral or Subcutaneous MK-2118, a Non-Cyclic Dinucleotide STING Agonist, With or Without Pembrolizumab for Advanced or Metastatic Solid Tumors or Lymphomas.

Background: We evaluated the non-cyclic dinucleotide stimulator of interferon genes agonist MK-2118 ± pembrolizumab in patients with advanced solid tumors or lymphomas.

Methods: This first-in-human study (NCT03249792) enrolled patients with refractory, advanced solid tumors or lymphomas. Patients received intratumoral (IT) MK-2118 100-20,000 µg (arm 1), IT MK-2118 900-15,000 µg plus intravenous (IV) pembrolizumab 200 mg every 3 weeks (Q3W; arm 2), or subcutaneous (SC) MK-2118 5000-150,000 µg plus IV pembrolizumab 200 mg Q3W (arm 4); arm 3 (visceral injection of MK-2118) was not pursued.

Coupling high-throughput and modeling approaches to streamline early-stage process development for biologics.

Platforms have long been implemented for downstream process development of monoclonal antibodies (mAbs) to streamline development and reduce timelines. These platforms are also increasingly being used for other complex biologics modalities. While development has traditionally been conducted at the lab bench scale in a sequential manner, automated miniaturized and parallelized approaches like RoboColumns and resin plates have also been implemented for chromatographic screening.

Trends and Association between Smoking and the Socio-Demographic Index Among 11 South American Countries, 1990-2019.

Objectives: To examine prevalence trends in the use of smoked tobacco products in 11 South American (SA) countries (i.e., Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Paraguay, Peru, Suriname, Uruguay, and Venezuela) and their association with country-specific socio-demographic index (SDI) over 30 years.

Arv1; a "Mover and Shaker" of Subcellular Lipids.

The composition of eukaryotic membranes reflects a varied but precise amalgam of lipids. The genetic underpinning of how such diversity is achieved or maintained is surprisingly obscure, despite its clear metabolic and pathophysiological impact. The Arv1 protein is represented in all eukaryotes and was initially identified in the model eukaryote as a candidate transporter of lipids from the endoplasmic reticulum.

Efferent compared to afferent neural substrates of the vergence eye movement system evoked via fMRI.

Introduction: The vergence neural system was stimulated to dissect the afferent and efferent components of symmetrical vergence eye movement step responses. The hypothesis tested was whether the afferent regions of interest would differ from the efferent regions to serve as comparative data for future clinical patient population studies.

Methods: Thirty binocularly normal participants participated in an oculomotor symmetrical vergence step block task within a functional MRI experiment compared to a similar sensory task where the participants did not elicit vergence eye movements.

The 2022 ADEA Climate Study in U.S. and Canadian Dental Schools and Allied Dental Programs: Methodological Considerations.

Objectives: From January 2020 to the end of August 2020, preliminary research gathered data about the need for and the feasibility of an ADEA-led joint Climate Study of dental schools and allied dental programs in the United States and Canada. Informed by these findings, the first ever ADEA-led joint Climate Study took place in 2022. The objectives of this manuscript were to describe the timeline of this climate study and provide information about its methodology, specifically about (a) who participated in this research, (b) what was assessed, (c) how the study was conducted, and (d) how the results were communicated.

Coping is a moderator of relationships between cognitive fatigue and cognitive variability in multiple sclerosis.

Objective: Mean levels of cognitive functioning typically do not show an association with self-reported cognitive fatigue in persons with multiple sclerosis (PwMS), but some studies indicate that has an association with cognitive fatigue. Additionally, coping has been shown to be a powerful moderator of some outcomes in multiple sclerosis (MS). To date, however, coping has not been considered as a possible moderator of the relationship between cognitive fatigue and cognitive in MS.

Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study.

Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 10/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19).

Sleep quality and cognitive functioning among Chinese older adults living in the US: a mixed-effects model analysis.

Background: Racial and ethnic disparities in sleep quality and cognitive health are increasingly recognized, yet little is understood about their associations among Chinese older adults living in the United States. This study aims to examine the relationships between sleep health and cognitive functioning in this population, utilizing data from the Population Study of Chinese Elderly in Chicago (PINE).

Methods: This observational study utilized a two-wave panel design as part of the PINE, including 2,228 participants aged 65 years or older who self-identified as Chinese.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Isolated, severe cerebellar hypoplasia and microcephaly secondary to congenital cytomegalovirus infection in a late preterm neonate.

This case report presents a late preterm infant diagnosed with severe cerebellar hypoplasia and microcephaly secondary to congenital cytomegalovirus (cCMV) infection. Initially suspected to have Dandy-Walker malformation, postnatal MRI revealed significant cerebellar hypoplasia, without other typical cCMV findings. The diagnosis was confirmed by the presence of CMV in serum and urine.

Granulomatous Variant of Giant Centrifugal Miliaria Profunda in an 8-Month-Old Boy: Expanding the Dermatologic Phenotype of Cardiofaciocutaneous Syndrome.

Miliarias are a group of eccrine disorders characterized by sweat retention due to the occlusion of eccrine ducts. Miliaria profunda is the rarest form of miliaria and occurs when eccrine ducts are obstructed at the dermal-epidermal junction. A granulomatous variant of centrifugal miliaria profunda classic findings of granulomatous infiltrate on histology and centrifugal expansion of deep nodules or plaques.

Randomized, Placebo-Controlled, Phase 1 Safety Study of Oral Mucosal Immunotherapy in Peanut Allergic Adults.

Background: Oral Mucosal Immunotherapy (OMIT) uses a specifically formulated toothpaste to deliver allergenic proteins to immunologically active areas of the oral cavity. This represents a new delivery mechanism with several features designed to improve food allergy desensitization. OMIT presents advantages over other approaches to allergy immunotherapy due to its targeted delivery and simplified administration.

Beyond Mentorship: Walking the Talk Through Sponsorship to Support Women in Academic Surgery.

Sponsorship is gaining recognition in academic surgery as an essential advancement beyond mentorship, particularly for women. While mentorship focuses on building the relationship between mentor and mentee to provide guidance, advice, and coaching, sponsorship entails more active involvement and buy-in from the senior towards the performance and growth of the junior. The ABCDs of sponsorship - Amplifying, Boosting, Connecting, and Defending - are powerful, concrete actions that can make a significant impact in the career and life of a future physician.

Exploring the swimming performance and the physical mechanisms oflocomotion.

Tomopterids are mesmerizing holopelagic swimmers. They use two modes of locomotion simultaneously: drag-based metachronal paddling and bodily undulation.has two rows of flexible legs (parapodia) positioned on opposite sides of its body.

REVEAL-CP: Selective Screening of Pediatric Patients for Aromatic L-Amino Acid Decarboxylase Deficiency with a Guthrie Card and Structural Modeling of One Index Case.

The main objective of this prospective, multicenter study (REVEAL-CP) was to test children with cerebral palsy-like signs and symptoms for raised 3--methyldopa (3-OMD) blood levels, a biomarker for aromatic L-amino acid decarboxylase deficiency (AADCd). A secondary objective was to characterize the molecular basis for the defective aromatic L-amino acid decarboxylase (AADC) gene product. Patients were identified in pediatric secondary and tertiary care hospitals through database searches and personal communication.