Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content.

Introduction: Extracellular vesicles (EVs) can potently inhibit inflammation yet there is a lack of understanding about the impact of donor characteristics on the efficacy of EVs. The goal of this study was to determine whether the sex and age of donor platelet-derived EVs (PEV) affected their ability to inhibit viral myocarditis.

Methods: PEV, isolated from men and women of all ages, was compared to PEV obtained from women under 50 years of age, which we termed premenopausal PEV (pmPEV).

Vertical pelvic movement asymmetry and lameness location in ipsilateral combined forelimb and hindlimb lameness cases.

Background: Compensatory vertical head and pelvis movement asymmetry may occur in trotting horses with a primary cause of lameness in one end of the body due to the weight shifting between limbs, leading to apparent combined forelimb and hindlimb lameness (CFHL). Little is known about CFHL patterns observed with body-mounted inertial sensors (BMIS) and regardless of their underlying mechanisms, compensatory and secondary lameness may complicate the definitive identification of the primary causes of lameness.

Objective: Determine associations between vertical pelvic movement asymmetry and location of primary lameness in ipsilateral CFHL cases where hindlimb lameness is solely impact or push-off type.

Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial.

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab.

The Safety, Tolerability, and Preliminary Efficacy of a Gemcitabine-releasing Intravesical System (TAR-200) in American Urological Association-defined Intermediate-risk Non-muscle-invasive Bladder Cancer Patients: A Phase 1b Study.

Background And Objective: Patients with intermediate-risk non-muscle-invasive bladder cancer (IR NMIBC) have a high risk of recurrence and need effective therapies to reduce the risk of disease recurrence or progression. This phase 1b study (NCT02720367) assessed the safety and tolerability of TAR-200, an intravesical drug delivery system, in participants with IR NMIBC.

Methods: Participants with recurrent IR NMIBC were eligible.

Has recombination changed during the recent evolution of the guppy Y chromosome?

Genome sequencing and genetic mapping of molecular markers have demonstrated nearly complete Y-linkage across much of the guppy (Poecilia reticulata) XY chromosome pair. Predominant Y-linkage of factors controlling visible male-specific coloration traits also suggested that these polymorphisms are sexually antagonistic (SA). However, occasional exchanges with the X are detected, and recombination patterns also appear to differ between natural guppy populations, suggesting ongoing evolution of recombination suppression under selection created by partially sex-linked SA polymorphisms.

Large-scale genomic data reveal the phylogeny and evolution of owlet moths (Noctuoidea).

The owlet moths (Noctuoidea; ~43-45K described species) are one of the most ecologically diverse and speciose superfamilies of animals. Moreover, they comprise some of the world's most notorious pests of agriculture and forestry. Despite their contributions to terrestrial biodiversity and impacts on ecosystems and economies, the evolutionary history of Noctuoidea remains unclear because the superfamily lacks a statistically robust phylogenetic and temporal framework.

Reconstituted Extracellular Vesicles from Human Platelets Decrease Viral Myocarditis in Mice.

Patients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease-specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice.

Phase I evaluation of CycloSam (Sm-153-DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma.

Sm-DOTMP (CycloSam ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression.

Innovative Strategies for Remotely Sampling Hard-to-Reach Populations: Assessing Phone Versus Internet Respondent-Driven Sampling Approaches Among Venezuelan Refugees and Migrants in Colombia.

It is challenging to quantitatively measure the health vulnerability and risk factors of refugees and migrants residing outside of formal settlement settings. For hard-to-reach populations without available sampling frames, researchers have increasingly turned to novel sampling and statistical methods, like respondent-driven sampling (RDS). "Standard" RDS is typically conducted face-to-face at fixed sites.

Safety, Tolerability, and Preliminary Efficacy of TAR-200 in Patients With Muscle-invasive Bladder Cancer Who Refused or Were Unfit for Curative-intent Therapy: A Phase 1 Study.

Purpose: Half of patients with muscle-invasive bladder cancer worldwide may not receive curative-intent therapy. Elderly or frail patients are most affected by this unmet need. TAR-200 is a novel, intravesical drug delivery system that provides sustained, local release of gemcitabine into the bladder over a 21-day dosing cycle.

Prevalence and clinical significance of increasing head height asymmetry as a measure of forelimb lameness in horses when trotting in a straight line after palmar digital nerve block.

Background: Some horses increase in forelimb lameness, measured as vertical head height asymmetry, or differences in maximums and minimums of head heights (HDmax, HDmin), after a palmar digital nerve (PDN) block. The prevalence of this finding, or what it means clinically, has not been reported in peer-reviewed literature.

Objectives: To estimate the prevalence of increasing head height asymmetry after a PDN block and determine if this is associated with cause of forelimb lameness.

Assessing the impact of the COVID-19 pandemic among Venezuelan refugees and migrants in Colombia using respondent-driven sampling (RDS).

Objectives: To determine factors associated with adherence to COVID-19 mitigation measures, related symptoms and testing, as well as pandemic-related income loss among Venezuelan refugee and migrant adults in urban and border areas of Colombia.

Design: Phone-based respondent-driven sampling SETTING: Bogotá and Norte de Santander, Colombia.

Participants: 605 adult Venezuelan refugees and migrants residing in Bogotá (n=305) and Norte de Santander (n=300), who arrived in Colombia after 2014 and completed the survey in August and September 2020.

Anti-nociceptive efficacy of the soluble epoxide hydrolase inhibitor t-TUCB in horses with mechanically induced lameness.

Introduction: Soluble epoxide hydrolase (sEH) inhibitors are novel anti-inflammatory and analgesic agents that could improve pain management in horses. The objective of the present study was to evaluate the anti-nociceptive effect of a single-dose intravenous administration of the sEH inhibitor trans-4-{4-[3-(4-trifluro-methoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB) using an adjustable heart bar shoe (a-HBS) model of lameness. We hypothesized that t-TUCB would improve objective and subjective lameness measures compared to the control.

The Scope and Impact of the COVID-19 Pandemic on Neuroemergent Patient Transfers, Clinical Care and Patient Outcomes.

Introduction: The SARS-CoV-2 (COVID-19) pandemic continues to substantially alter previously established clinical practice patterns and has transformed patient care in American healthcare. However, studies to evaluate the impact of COVID-19 on neuroemergent patient care and associated clinical outcomes are limited. Herein, we describe the impact of COVID-19 on the Neuroemergency Transfer Program (NTP) - a novel, urban, high volume interhospital patient transfer program.

The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial.

Objectives: Neoadjuvant chemotherapy and radical cystectomy (RC) are underutilized standards of care for the treatment of muscle-invasive bladder cancer (MIBC) due to high patient burden from systemic toxicities and postoperative complications, respectively. TAR-200 is a novel intravesical drug delivery system developed to release gemcitabine into the bladder urine continuously, resulting in distribution of drug into stromal layers of the bladder. The primary aim of the TAR-200-101 study was to evaluate the safety of TAR-200 in patients with MIBC prior to RC (NCT02722538).

Long term cost comparisons of radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer.

Background: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC).

Alternate delivery platforms and implementation models for bringing evidence-based behavioral interventions to scale for youth facing adversity: a case study in West Africa.

Background: Youth Functioning and Organizational Success for West African Regional Development (Youth FORWARD) was launched as an implementation science collaboration focused on scaling out evidence-based mental health interventions for youth exposed to war and other adversities through novel delivery platforms. This implementation science case study examines the use of a collaborative team approach (CTA) as a scale-out strategy to foster the integration of an evidence-based group mental health intervention, the Youth Readiness Intervention, into youth employment programs tied to regional economic development in Sierra Leone.

Methods: A case study methodology is used to explore the feasibility and acceptability of integrating an evidence-based intervention, the Youth Readiness Intervention (YRI), into youth entrepreneurship programs (ENTR) in Sierra Leone, facilitated by the CTA.

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders).

How did the guppy Y chromosome evolve?

The sex chromosome pairs of many species do not undergo genetic recombination, unlike the autosomes. It has been proposed that the suppressed recombination results from natural selection favouring close linkage between sex-determining genes and mutations on this chromosome with advantages in one sex, but disadvantages in the other (these are called sexually antagonistic mutations). No example of such selection leading to suppressed recombination has been described, but populations of the guppy display sexually antagonistic mutations (affecting male coloration), and would be expected to evolve suppressed recombination.

A retrospective comparison of radiographic and clinical outcomes in single-level degenerative lumbar disease undergoing anterior versus transforaminal lumbar interbody fusion.

Background: Single-level lumbar degenerative disc disease (DDD) remains a significant cause of morbidity in adulthood. Anterior lumbar interbody fusion (ALIF) and Transforaminal lumbar interbody fusion (TLIF) are surgical techniques developed to treat this condition. With limited studies on intermediate term outcomes in a single cohort, we compare radiographic and clinical outcomes in patients undergoing ALIF and TLIF.

Differential effect of body mass index by gender on oncological outcomes in patients with renal cell carcinoma.

Objectives: To investigate the relationship between gender, body mass index (BMI), and prognosis in renal cell carcinoma (RCC) patients.

Materials And Methods: We retrospectively reviewed 1353 patients with RCC who underwent a partial or radical nephrectomy between 1988 and 2015. The association among sex, BMI, stage, grade, overall survival (OS), and recurrence-free survival (RFS) was analyzed.

Transforaminal lumbar interbody fusion using a novel minimally invasive expandable interbody cage: patient-reported outcomes and radiographic parameters.

Objective: The goal of this study was to evaluate the clinical and radiographic outcomes of a novel multidirectional in situ expandable minimally invasive surgery (MIS) transforaminal lumbar interbody fusion (TLIF) cage.

Methods: A retrospective analysis of 69 consecutive patients undergoing a 1- or 2-level MIS TLIF using an expandable cage was performed over a 2-year period. Standard MIS techniques with pedicle screw fixation were used in all cases.