Differences in Perceived Versus Actual Sensory Perception in Avoidant/Restrictive Food Intake Disorder.

Background: Individuals with avoidant/restrictive food intake disorder (ARFID) self-report heightened sensitivity to taste and smell, but neither phenomenon has been systematically explored in the laboratory. We hypothesized that, compared to healthy controls (HC, n = 34), children, adolescents, and adults with full/subthreshold ARFID (n = 100; ages 9 to 23 years) would self-report heightened response to taste/smell stimuli and exhibit stronger bitter taste perception and heightened smell perception in performance-based tasks, and these differences would be especially prominent in those with the ARFID-sensory sensitivity presentation.

Method: We measured self-reported sensitivity to taste/smell with the adolescent/adult sensory profile (AASP).

Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5.

People living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), even though combination antiretroviral therapy (cART) suppresses HIV replication. HIV-1 transactivator of transcription (HIV-1 Tat) contributes to the development of HAND through neuroinflammatory and neurotoxic mechanisms. C-C chemokine 5 receptor (CCR5) is important in immune cell targeting and is a co-receptor for HIV viral entry into CD4+ cells.

Sex related differences in cognitive deficits: Disrupted Arc/Arg3.1 signaling in an HIV model.

Combined and highly active anti-retroviral therapies (cART) have transitioned HIV into a more chronic disease. Roughly half of people living with HIV (PLWH) still experience neurocognitive disorders, albeit less severely than in the pre-cART era. Sex-related effects on memory/cognition remain understudied, although the percentage of PLWH that are female has increased.

Novel voltage-dependent Cl channels in striatal medium spiny neurons are unrelated to ClC-1 or other known Ca-induced Cl channel/transporter types.

Intracellular chloride (Cl) homeostasis is a critical regulator of neuronal excitability. Voltage-dependent neuronal Cl channels remain the least understood in terms of their role as a source of Cl entry controlling excitability. We have shown recently that striatal medium spiny neurons (MSNs) express a functional Cl conducting ClC-1-like channel with properties similar but not identical to native ClC-1 channels (Yarotskyy, V.

Examining the effects of the HIV-1 protein Tat and morphine on antiretroviral accumulation and distribution within the brain.

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro-acquired HIV (neuroHIV) remains a significant problem and approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury and synaptodendritic culling, viral replication, and potentially altering antiretroviral concentrations within the brain. The present study examined the effects of HIV and morphine co-exposure on the accumulation and spatial distribution of antiretroviral drugs across multiple regions within the brain in an HIV-1 Tat transgenic mouse model by using infrared-matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI MSI).

Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1P receptor-mediated G-protein activation in a mouse model of sciatic nerve injury.

Sphingosine-1-phosphate (S1P) receptor (S1PR) agonists, such as fingolimod (FTY720), alleviate nociception in preclinical pain models by either activation (agonism) or inhibition (functional antagonism) of S1PR type-1 (S1PR1). However, the dose-dependence and temporal relationship between reversal of nociception and modulation of S1PR1 signaling has not been systematically investigated. This study examined the relationship between FTY720-induced antinociception and S1PR1 adaptation using a sciatic nerve chronic constriction injury (CCI) model of neuropathic pain in male and female C57Bl/6J mice.

Noninvasive Technologies for the Diagnosis of Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Early cutaneous squamous cell carcinoma (cSCC) diagnosis is essential to initiate adequate targeted treatment. Noninvasive diagnostic technologies could overcome the need of multiple biopsies and reduce tumor recurrence. To assess performance of noninvasive technologies for cSCC diagnostics, 947 relevant records were identified through a systematic literature search.

Sustained fentanyl exposure inhibits neuronal activity in dissociated striatal neuronal-glial cocultures through actions independent of opioid receptors.

Besides having high potency and efficacy at the µ-opioid (MOR) and other opioid receptor types, fentanyl has some affinity for some adrenergic receptor types, which may underlie its unique pathophysiological differences from typical opioids. To better understand the unique actions of fentanyl, we assessed the extent to which fentanyl alters striatal medium spiny neuron (MSN) activity via opioid receptors or α-adrenoceptors in dopamine type 1 or type 2 receptor (D1 or D2)-expressing MSNs. In neuronal and mixed-glial cocultures from the striatum, acute fentanyl (100 nM) exposure decreased the frequency of spontaneous action potentials.

Amphibian mast cells serve as barriers to chytrid fungus infections.

Global amphibian declines are compounded by deadly disease outbreaks caused by the chytrid fungus, (). Much has been learned about the roles of amphibian skin-produced antimicrobial components and microbiomes in controlling , yet almost nothing is known about the roles of skin-resident immune cells in anti- defenses. Mammalian mast cells reside within and serve as key immune sentinels in barrier tissues like skin.

Arabidopsis CaLB1 undergoes phase separation with the ESCRT protein ALIX and modulates autophagosome maturation.

Autophagy is relevant for diverse processes in eukaryotic cells, making its regulation of fundamental importance. The formation and maturation of autophagosomes require a complex choreography of numerous factors. The endosomal sorting complex required for transport (ESCRT) is implicated in the final step of autophagosomal maturation by sealing of the phagophore membrane.

Trajectory of ghrelin and PYY around a test meal in males and females with avoidant/restrictive food intake disorder versus healthy controls.

Disruptions in appetite-regulating hormones may contribute to the development and/or maintenance of avoidant/restrictive food intake disorder (ARFID). No study has previously assessed fasting levels of orexigenic ghrelin or anorexigenic peptide YY (PYY), nor their trajectory in response to food intake among youth with ARFID across the weight spectrum. We measured fasting and postprandial (30, 60, 120 minutes post-meal) levels of ghrelin and PYY among 127 males and females with full and subthreshold ARFID (n = 95) and healthy controls (HC; n = 32).

A Comparison of Clinical Outcomes of Colectomies for Pediatric and Adult Patients With Inflammatory Bowel Disease.

Crohn's disease (CD) and ulcerative colitis (UC) are prevalent in adult and pediatric populations, but their differences are not well studied using national data. We compared the clinical outcomes of these patients using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) databases. Colectomy cases for CD and UC, the 2 major forms of inflammatory bowel disease (IBD), were compared between adult and pediatric patients using the 2017-2019 ACS NSQIP databases.

Intranasal Oxytocin for Obesity.

Background: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity.

Methods: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks.

HIV-1 Tat and morphine interactions dynamically shift striatal monoamine levels and exploratory behaviors over time.

Despite the advent of combination anti-retroviral therapy (cART), nearly half of people infected with HIV treated with cART still exhibit HIV-associated neurocognitive disorders (HAND). HAND can be worsened by co-morbid opioid use disorder. The basal ganglia are particularly vulnerable to HIV-1 and exhibit higher viral loads and more severe pathology, which can be exacerbated by co-exposure to opioids.

Fentanyl dysregulates neuroinflammation and disrupts blood-brain barrier integrity in HIV-1 Tat transgenic mice.

Opioid overdose deaths have dramatically increased by 781% from 1999 to 2021. In the setting of HIV, opioid drug abuse exacerbates neurotoxic effects of HIV in the brain, as opioids enhance viral replication, promote neuronal dysfunction and injury, and dysregulate an already compromised inflammatory response. Despite the rise in fentanyl abuse and the close association between opioid abuse and HIV infection, the interactive comorbidity between fentanyl abuse and HIV has yet to be examined in vivo.

Dermatologist-like explainable AI enhances trust and confidence in diagnosing melanoma.

Artificial intelligence (AI) systems have been shown to help dermatologists diagnose melanoma more accurately, however they lack transparency, hindering user acceptance. Explainable AI (XAI) methods can help to increase transparency, yet often lack precise, domain-specific explanations. Moreover, the impact of XAI methods on dermatologists' decisions has not yet been evaluated.

What Matters Most: The Documented Goals, Values and Motivators of Advanced Cancer Patients.

Background: Goals of care conversations are essential to delivery of goal concordant care. Infrequent and inconsistent goals of care documentation potentially limit delivery of goal concordant care.

Methods: At Kaiser Permanente San Francisco Cancer Center, a standardized documentation template was designed and implemented to increase goals of care documentation by oncologists.

Membrane-specific and calcium-dependent binding of the Arabidopsis C2 domain protein CaLB revealed by ATR-FTIR spectroscopy.

C2 domain-containing proteins bind to cellular membranes and mediate diverse cellular processes. Although many of these membrane-interacting proteins have been identified, the molecular mechanisms of protein-membrane interactions and conformational dynamics are often poorly understood and remain to be investigated with appropriate methods. Here, we used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and biomimetic membrane systems to analyse CalB, a yet uncharacterized Arabidopsis C2 domain protein.

COVID-19 Pandemic Effects on Clinical Outcomes of Hip Fractures Among Pediatric and Adult Patients.

Background: Little is known about the distribution and outcomes of hip fractures in pediatric patients during the COVID-19 pandemic.

Objective: To study the clinical outcomes of both pediatric and adult patients who underwent hip fracture surgeries and determine the effects of changes surrounding the COVID-19 pandemic.

Methods: Both pediatric and adult surgical hip fracture cases were analyzed from the pandemic year (2020) and the control year (2019) using the American College of Surgeons National Surgical Quality Improvement Program database.

Time is of the Essence: Why Goals-of-Care Conversations and Prognosis Documentation Matters in Advanced Cancer Patients in an Integrated Health System.

Advanced cancer patients benefit less from aggressive therapies and more from goal-directed palliative management. Early and clearly documented goals-of-care discussions, including end-of-life decision making, are essential in this patient population. Integrated healthcare systems are comprehensive care models associated with improved quality of care and lower mortality compared to other healthcare models.

Identifying and Overcoming the Sampling Challenges in Relative Binding Free Energy Calculations of a Model Protein:Protein Complex.

Relative alchemical binding free energy calculations are routinely used in drug discovery projects to optimize the affinity of small molecules for their drug targets. Alchemical methods can also be used to estimate the impact of amino acid mutations on protein:protein binding affinities, but these calculations can involve sampling challenges due to the complex networks of protein and water interactions frequently present in protein:protein interfaces. We investigate these challenges by extending a graphics processing unit (GPU)-accelerated open-source relative free energy calculation package (Perses) to predict the impact of amino acid mutations on protein:protein binding.