Integrated Devices: A New Regulatory Pathway to Promote Revolutionary Innovation.

Policy Points Current medical device regulatory frameworks date back half a century and are ill suited for the next generation of medical devices that involve a significant software component. Existing Food and Drug Administration efforts are insufficient because of a lack of statutory authority, whereas international examples offer lessons for improving and harmonizing domestic medical device regulatory policy. A voluntary alternative pathway built upon two-stage review with individual component review followed by holistic review for integrated devices would provide regulators with new tools to address a changing medical device marketplace.

Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer.

Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes.

FGF21 Induces Skeletal Muscle Atrophy and Increases Amino Acids in Female Mice: A Potential Role for Glucocorticoids.

Fibroblast growth factor-21 (FGF21) is an intercellular signaling molecule secreted by metabolic organs, including skeletal muscle, in response to intracellular stress. FGF21 crosses the blood-brain barrier and acts via the nervous system to coordinate aspects of the adaptive starvation response, including increased lipolysis, gluconeogenesis, fatty acid oxidation, and activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Given its beneficial effects for hepatic lipid metabolism, pharmaceutical FGF21 analogues are used in clinical trials treatment of fatty liver disease.

Senolytic treatment does not mitigate oxidative stress-induced muscle atrophy but improves muscle force generation in CuZn superoxide dismutase knockout mice.

Oxidative stress is associated with tissue dysfunctions that can lead to reduced health. Prior work has shown that oxidative stress contributes to both muscle atrophy and cellular senescence, which is a hallmark of aging that may drive in muscle atrophy and muscle contractile dysfunction. The purpose of the study was to test the hypothesis that cellular senescence contributes to muscle atrophy or weakness.

Spatiotemporal characteristics of neurophysiological changes in patients with four-repeat tauopathies.

Introduction: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are the most common four-repeat tauopathies (4RT), and both frequently occur with varying degree of Alzheimer's disease (AD) copathology. Intriguingly, patients with 4RT and patients with AD are at opposite ends of the wakefulness spectrum-AD showing reduced wakefulness and excessive sleepiness whereas 4RT showing decreased homeostatic sleep. The neural mechanisms underlying these distinct phenotypes in the comorbid condition of 4RT and AD are unknown.

Severe Intraventricular Hemorrhage is Associated with Lung Injury in Preterm Infants on Mechanical Ventilation.

Background: The aim of this study was to better understand the relationship between intraventricular hemorrhage and the risk of development of early lung disease in extremely low birth weight infants. We hypothesize that infants with severe intraventricular hemorrhage have higher respiratory severity scores than infants with mild/no intraventricular hemorrhage within the first 7 days of life.

Methods: This was a single center retrospective study conducted on subjects born between 01/01/2018 and 06/30/2021 at the University of Kentucky Children's Hospital NICU.

Predictive value of Hajibandeh index in determining peritoneal contamination in acute abdomen: A cohort study and meta-analysis.

Background: Hajibandeh index (HI), derived from combined levels of C-reactive protein, lactate, neutrophils, lymphocytes and albumin, is a modern predictor of peritoneal contamination and mortality in patients with acute abdominal pathology.

Aim: To validate the performance of HI in predicting the presence and nature of peritoneal contamination in patients with acute abdominal pathology in a larger cohort study and to synthesis evidence in a systematic review and meta-analysis.

Methods: The STROBE guidelines and the PRISMA statement standards were followed to conduct a cohort study (ChiCTR2200056183) and a meta-analysis (CRD42022306018), respectively.

A Pilot Study of Nutritional Supplementation in Soft Tissue Sarcoma Patients.

Background: Wound healing is particularly important for sarcoma patients who undergo neoadjuvant radiation therapy. Previous studies have demonstrated wound complications in this population approaching 35%. With this high rate of wound healing issues, identifying treatment modalities to minimize these complications is of paramount importance.

T* Imaging Assessment of Neoadjuvant Radiation Therapy Combined With Pharmacological Ascorbate in Extremity Soft-Tissue Sarcomas: A Pilot Study.

Background: Extremity soft-tissue sarcomas (STS) are commonly treated with neoadjuvant radiation therapy followed by surgical resection. However, the pathological near-complete response rate is low (9-25%). Noninvasive imaging assessment that predicts treatment response before and during treatment is desirable to optimize treatment regimens.

Mechanical Gains Associated With Virtual Prophylactic Intramedullary Nail Fixation in Femurs With Metastatic Disease.

Background: Many patients with metastatic bone disease (MBD) of the femur undergo prophylactic surgical fixation for impending pathologic fractures; intramedullary nailing (IMN) being the most common fixation type. However, surgeons often question if IMN fixation provides sufficient improvements in mechanical strength for particular metastatic lesions. Our goal was to use patient-specific finite element (FE) modeling to computationally evaluate the effects of simulated IMN fixation on the mechanics of femurs affected with MBD.

Deconvoluting Nonlinear Catalyst-Substrate Effects in the Intramolecular Dirhodium-Catalyzed C-H Insertion of Donor/Donor Carbenes Using Data Science Tools.

Interactions between catalysts and substrates can be highly complex and dynamic, often complicating the development of models to either predict or understand such processes. A dirhodium(II)-catalyzed C-H insertion of donor/donor carbenes into 2-alkoxybenzophenone substrates to form benzodihydrofurans was selected as a model system to explore nonlinear methods to achieve a mechanistic understanding. We found that the application of traditional methods of multivariate linear regression (MLR) correlating DFT-derived descriptors of catalysts and substrates leads to poorly performing models.

17α-Estradiol alleviates high-fat diet-induced inflammatory and metabolic dysfunction in skeletal muscle of male and female mice.

17α-estradiol (17α-E2) is a naturally occurring nonfeminizing diastereomer of 17β-estradiol that has life span-extending effects in rodent models. To date, studies of the systemic and tissue-specific benefits of 17α-E2 have largely focused on the liver, brain, and white adipose tissue with far less focus on skeletal muscle. Skeletal muscle has an important role in metabolic and age-related disease.

Dominance Analysis of Bright and Dark Dispositional Predictors of Socially Desirable Responding.

Although the role of so-called dark traits in the prediction of maladaptive behavior has seen a large increase in interest by researchers, the Big Five still maintain their ubiquity in the prediction of most behaviors. This study uses measures of the Dark Tetrad and the Big Five personality traits to predict a very specific form of maladaptive behavior: the impression management form of socially desirable responding. In regression-based dominance analysis, results suggest that not all of the Big Five nor the Dark Tetrad provide statistically significant incremental validity but as a block, the Big Five dominate the Dark Tetrad in the prediction of the purposeful misrepresentation of one's self to others on self-report inventories.

Novel avenues of tau research.

Introduction: The pace of innovation has accelerated in virtually every area of tau research in just the past few years.

Methods: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation.

Results: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research.

Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.

Mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms.

Human tendon-on-a-chip for modeling vascular inflammatory fibrosis.

Understanding vascular inflammation and myofibroblast crosstalk is critical to developing therapies for fibrotic diseases. Here we report the development of a novel human Tendon-on-a-Chip (hToC) to model this crosstalk in peritendinous adhesions, a debilitating fibrotic condition affecting flexor tendon, which currently lacks biological therapies. The hToC enables cellular and paracrine interactions between a vascular compartment harboring endothelial cells and monocytes with a tissue hydrogel compartment containing tendon fibroblasts and macrophages.

A naturally occurring variant of SHLP2 is a protective factor in Parkinson's disease.

Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate the functional role of a PD-associated mtSNP that impacts the mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.

Adaptation of commodity purchase tasks to identify substitutable substance-free alternative activities for alcohol use.

Behavioral economic frameworks emphasize the importance of contextual influences on alcohol use; therefore, identifying relative demand for alcohol versus other commodities is of importance. Cross-commodity purchase tasks allow participants to make choices across multiple concurrently available commodities and can thereby pinpoint interactions among those commodities. These tasks may help identify relevant substance-free alternative activities to target in alcohol treatment by determining whether the activity functions as a substitute for alcohol use.

Meta-analysis of a family history of diabetes in schizophrenia.

Objective: Type 2 diabetes (T2DM) is common in patients with schizophrenia and non-affective psychosis. These patients also have an increased prevalence of a family history of T2DM. We performed a systematic review and meta-analysis of the association between a family history of T2DM and schizophrenia.

The impact of hostile abortion legislation on the United States maternal mortality crisis: a call for increased abortion education.

The growing restrictive abortion policies nationwide and the Supreme Court decision on place increasing barriers to abortion access in the United States. These restrictions disproportionately affect low-income people of color, immigrants, and non-English speakers, and have the potential to exacerbate already existing racial inequities in maternal and neonatal outcomes. The United States is facing a Black maternal health crisis where Black birthing people are more than twice as likely to experience maternal mortality and severe maternal morbidity compared to White birthing people.

Computational drug discovery of an inhibitor of APOBEC3B as a treatment for epithelial cancers.

Cancer is one of the leading causes of death in the U.S., and tumorous cancers such as cervical, lung, breast, and ovarian cancers are the most common types.