GW-9662, a peroxisome proliferator-activated receptor γ (PPARγ) inhibitor, impairs early embryonic development in zebrafish.

Peroxisome proliferator-activated receptor γ (PPARγ) functions as a nuclear transcription factor with primary roles in lipid and glucose metabolism and adipocyte differentiation. Despite intensive research in metabolic contexts, its role during early vertebrate development remains underexplored. Our study focused on understanding PPARγ's developmental role by using a PPARγ antagonist, GW-9662 (GW), in zebrafish embryos.

Disparities During Family-Centered Rounds for Families Using Languages Other Than English.

Background/objective: Patient- and family-centered rounds (PFCR) have become a pediatric standard of care. However, rounds experiences of families using languages other than English (LOE)-particularly languages other than English or Spanish (LOES; eg, Arabic)-receive less focus. We aimed to identify differences in PFCR communication and engagement by language.

Adolescents' perspectives on health literacy interventions for reducing epilepsy misconceptions and stigma, and enhancing epilepsy management in Uganda.

Background: Despite the advancement in medical knowledge, epilepsy is still one of the most highly misunderstood and stigmatized neurological conditions in Sub-Saharan Africa. It is widely believed to be a contagious disease, caused by demonic possession, witchcraft, or other spiritual phenomena, and in some cases attributed to both biologic and supernatural etiologies. These misconceptions and the associated stigma result in social rejection, emotional distress, and feelings of shame.

The time-resolved atomic, molecular and optical science instrument at the Linac Coherent Light Source. Corrigendum.

The name of an author in the article by Walter et al. (2022) [J. Synchrotron Rad.

Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids.

Angelman syndrome is a neurodevelopmental disorder caused by (epi)genetic lesions of maternal UBE3A. Research has focused largely on the role of UBE3A in neurons due to its imprinting in that cell type. Yet, evidence suggests there may be broader neurodevelopmental impacts of UBE3A dysregulation.

Membrane-Active Peptides Derived from Natural Transmembrane Domains Function as Antibiotic Potentiators.

Antimicrobial resistance continues to be a prevailing threat to human health worldwide, largely due to the arsenal of resistance mechanisms bacteria have evolved over years of exposure to traditional antibiotics. As an approach to devising therapeutics that can overcome this resistance, we hypothesized that peptides consisting of single transmembrane (TM) segments of membrane proteins may permeabilize bacterial membranes and thereby facilitate access of antimicrobials to their cytoplasmic targets. Using peptides derived from a natural TM helix from the AcrB component of the AcrAB-TolC efflux protein, we found that AcrB TM8 (wild type sequence: KKKK-FL(Abu)LAALYESWSI-NH) and a "scrambled" analog of identical composition, charge, and overall hydrophobicity (TM8-S: KKKK-FSLEALW(Abu)ISAYL-NH) (Abu = α-aminobutyric acid), resensitize to sublethal doses of the antibiotics cloxacillin and nalidixic acid.

Phase II trial of organ preservation program using short-course radiation and FOLFOXIRI for rectal cancer (SHORT-FOX): Two-Year primary outcome analysis.

Background And Purpose: As patients with rectal cancer with clinical complete response (cCR) after neoadjuvant therapy may be safely spared Total Mesorectal Excision (TME), strategies to maximize cCR are needed.

Materials And Methods: We conducted a single-arm phase II study to determine whether dose-escalated short-course radiotherapy (25 Gy/5 fractions + 5 Gy/1 fraction boost) followed by eight cycles of FOLFOXIRI increased cCR rates among adult patients with > T2N0M0 or low T2N0 rectal cancer.

Results: Between 2020 and 2023, we enrolled 37 patients, of whom 27 (73 %) had at least one high-risk feature (cT4, extramural vascular invasion [EMVI], N2, threatened circumferential resection margin, positive lateral node).

Simplified control of neuromuscular stimulation systems for restoration of reach with limb stiffness as a modifiable degree of freedom.

Brain-controlled functional electrical stimulation (FES) of the upper limb has been used to restore arm function to paralyzed individuals in the lab. Able-bodied individuals naturally modulate limb stiffness throughout movements and in anticipation of perturbations. Our goal is to develop, via simulation, a framework for incorporating stiffness modulation into the currently-used 'lookup-table-based' FES control systems while addressing several practical issues: (1) optimizing stimulation across muscles with overlap in function, (2) coordinating stimulation across joints, and (3) minimizing errors due to fatigue.

Upcycling of post-consumer mixed polyolefin feedstock: An economic and technical evaluation.

This study reports techno-economic and life cycle analyses to evaluate the economic and environmental impacts of mechanically recycled PE/PP blends in the presence of rheology modifiers. Additionally, fiber-reinforced composites derived from the compatibilized blends were prepared and evaluated for their performance compared with virgin plastics. Results suggest that compatibilized PE/PP blends exhibit a 70 % lower selling price compared to virgin PE.

Sexually Dimorphic Effects of CYP2B6 in the Development of Fasting-Mediated Steatosis in Mice: Role of the Oxylipin Products 9-HODE and 9-HOTrE.

: Cytochrome P450 2B6 (CYP2B6) is a sexually dimorphic, anti-obesity CYP enzyme responsible for the metabolism of xeno- and endobiotics, including the metabolism of polyunsaturated fatty acids (PUFAs) into 9-hydroxyoctadecadienoic acid (9-HODE) and 9-hydroxyoctadecatrienoic acid (9-HOTrE). However, humanized CYP2B6 transgenic (hCYP2B6-Tg) mice are sensitive to diet-induced hepatic steatosis despite their resistance to obesity. The purpose of this study was to determine if 9-HODE, 9-HOTrE, or other factors contribute to the sexually dimorphic steatosis observed in hCYP2B6-Tg mice.

Influence of Patient Gender and Race on Obstructive Sleep Apnea in Perioperative Medicine.

Obstructive sleep apnea (OSA), a disorder of upper airway collapse during sleep, has long been recognized as an important risk factor for patients undergoing anesthesia. This article explores gender and racial disparities in the diagnosis and treatment of OSA, and how these inequities may impact care in the perioperative period.

Case report: use of pleural dialysis as an alternate means of renal replacement therapy in three cats.

Objective: The objective of this case series is to describe the indications, methodology, and short-term outcomes of three cats with severe azotemia managed with pleural dialysis.

Case Summary: Three cats were presented separately to the emergency room (ER) on referral for severe azotemia of varying etiologies. Despite aggressive medical and/or surgical management, none of the cats showed improvement in their blood urea nitrogen (BUN) or creatinine values.

Further Probing the Properties of a Unique Sponge-derived Alkaloid Through the Isolation of a New (-)-(5)-(8)-(14)-Mycothiazole Analogue.

Scale-up isolation of (+)-(5)-(8)-(14)-mycothiazole () from Vanuatu specimens of to semisynthesize (+)-(5)-(8)-8--acetyl-(14)-mycothiazole () revealed a new diastereomer, (-)-(5)-(8)-(14)-mycothiazole (). The structure of was determined using HRMS, NMR, and comparing optical rotation to (-)-(5)-(8)-(14)-mycothiazole () and . The maximum tolerated dose of in mice was 0.

Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors (EEs) enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus-specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci.

NF1 miniswine model the cellular disruptions and behavioral presentations of NF1-associated cognitive and motor impairment.

Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1 miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology.

Creating Culturally Adapted Multilingual Materials for Research.

Patients who speak languages other than English are frequently excluded from research. This exclusion exacerbates inequities, biases results, and may violate federal regulations and research ethics. Language justice is the right to communicate in an individual's preferred language to address power imbalances and promote equity.

Cost Savings of Whole Blood Versus Component Therapy at a Community Level 1 Trauma Center.

Background: Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe.

Methods: This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021.

Investigating impacts of the mycothiazole chemotype as a chemical probe for the study of mitochondrial function and aging.

Small molecule inhibitors of the mitochondrial electron transport chain (ETC) hold significant promise to provide valuable insights to the field of mitochondrial research and aging biology. In this study, we investigated two molecules: mycothiazole (MTZ) - from the marine sponge C. mycofijiensis and its more stable semisynthetic analog 8-O-acetylmycothiazole (8-OAc) as potent and selective chemical probes based on their high efficiency to inhibit ETC complex I function.

Abatacept Decreases Renal T-cell Infiltration and Renal Inflammation and Ameliorates Progressive Renal Injury in Obese Dahl Salt-sensitive Rats Before Puberty.

Prepubertal obesity is growing at an alarming rate and is now considered a risk factor for renal injury. Recently, we reported that the early development of renal injury in obese Dahl salt-sensitive (SS) leptin receptor mutant (SS LepR mutant) rats was associated with increased T-cell infiltration and activation before puberty. Therefore, the current study investigated the effect of inhibiting T-cell activation with abatacept on the progression of renal injury in young obese SS LepR mutant rats before puberty.

Web-Based Scaffolds: The Feasibility of a Constructivist Approach to Oncology Fellow Learning.

In this 2-institution feasibility pilot, oncology fellows used and updated freely available web-based learning tools (scaffolds) in a constructivist fashion.

Lumbar vertebral bone density is decreased in horses with pituitary pars intermedia dysfunction.

Background: Pathological fractures have been reported in equids with pituitary pars intermedia dysfunction (PPID) but their prevalence and pathogenesis is unknown.

Objectives: To compare: (1) bone mineral density (BMD) in weight bearing and nonweight bearing bones in PPID equids and aged and young PPID controls; and (2) biomechanical properties of the fourth lumbar vertebral body in PPID equids and aged PPID equids.

Study Design: Case-control study: five PPID equids and six aged and four young PPID control horses.