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.

National Academies of Sciences, Engineering, and Medicine Standing Committee on Primary Care: An Objective Venue to Inform Policy.

The 2021 National Academies of Sciences, Engineering, and Medicine (NASEM) report outlined an implementation framework with recommendations for federal, state, and local policy makers, health systems, educational institutions, the interprofessional workforce, and others across the health care ecosystem to ensure that high-quality primary care is available for everyone in the United States. Based on 1 of the report's recommendations, the Department of Health and Human Services, in collaboration with the Department of Veterans Affairs and the Department of Agriculture, launched the in 2021 to coordinate and prioritize primary care activities across the federal government. Formation of this federal coordinating body is a critical step for improving primary care in the US, but it is equally important to enable external primary care policy experts, researchers, and working clinicians to provide input on urgent primary care needs and priorities as primary care policy evolves.

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.

Characterizing hospitalists' comfort and familiarity with LGBTQ clinical topics.

Objectives: Evidence has shown that lesbian, gay, bisexual, queer (LGBQ) and transgender patients (LGBTQ) experience disparities in health care delivery and clinical outcomes. As the predominant U.S.

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.

Placental Methylglyoxal in Preeclampsia: Vascular and Biomarker Implications.

Background: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction.

Methods: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies.

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.

An analysis of WHO's Temporary Recommendations on international travel and trade measures during Public Health Emergencies of International Concern.

During Public Health Emergencies of International Concern (PHEICs), The International Health Regulations (IHR) require the WHO to issue Temporary Recommendations on the use of international travel and trade measures. During the COVID-19 pandemic, WHO's initial recommendation against 'any travel or trade restriction' has been questioned, and virtually all countries subsequently used international travel measures. WHO's Recommendations to States Parties also changed over the course of the pandemic.

Depressive-like Behavior Is Accompanied by Prefrontal Cortical Innate Immune Fatigue and Dendritic Spine Losses after HIV-1 Tat and Morphine Exposure.

Opioid use disorder (OUD) and HIV are comorbid epidemics that can increase depression. HIV and the viral protein Tat can directly induce neuronal injury within reward and emotionality brain circuitry, including the prefrontal cortex (PFC). Such damage involves both excitotoxic mechanisms and more indirect pathways through neuroinflammation, both of which can be worsened by opioid co-exposure.

Casein Kinase 2 Mediates HIV- and Opioid-Induced Pathologic Phosphorylation of TAR DNA Binding Protein 43 in the Basal Ganglia.

HIV/HIV-1 Tat and morphine independently increase pathologic phosphorylation of TAR DNA binding protein 43 in the striatum. HIV- and opioid-induced pathologic phosphorylation of TAR DNA binding protein 43 may involve enhanced CK2 activity and protein levels.

A novel nano-iron supplement versus standard treatment for iron deficiency anaemia in children 6-35 months (IHAT-GUT trial): a double-blind, randomised, placebo-controlled non-inferiority phase II trial in The Gambia.

Background: Iron deficiency anaemia (IDA) is the leading cause of years lost to disability in most sub-Saharan African countries and is especially common in young children. The IHAT-GUT trial assessed the efficacy and safety of a novel nano iron supplement, which is a dietary ferritin analogue termed iron hydroxide adipate tartrate (IHAT), for the treatment of IDA in children under 3 years of age.

Methods: In this single-country, randomised, double-blind, parallel, placebo-controlled, non-inferiority Phase II study in The Gambia, children 6-35 months with IDA (7≤Hb < 11 g/dL and ferritin<30 μg/L) were randomly assigned (1:1:1) to receive either IHAT, ferrous sulphate (FeSO) or placebo daily for 3 months (85 days).

Persistent sensory changes and sex differences in transgenic mice conditionally expressing HIV-1 Tat regulatory protein.

HIV-associated sensory neuropathies (HIV-SN) are prevalent in >50% of patients aged over 45 years many of which report moderate to severe chronic pain. Previous preclinical studies have investigated the mechanisms by which HIV-1 causes sensory neuropathies and pain-like behaviors. The aim of the present study is to delineate the role of chronic HIV-1 trans-activator of transcription protein (Tat) exposure in the development of neuropathy in mice.

Progressive Degeneration and Adaptive Excitability in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons Exposed to HIV-1 Tat and Morphine.

The striatum is especially vulnerable to HIV-1 infection, with medium spiny neurons (MSNs) exhibiting marked synaptodendritic damage that can be exacerbated by opioid use disorder. Despite known structural defects in MSNs co-exposed to HIV-1 Tat and opioids, the pathophysiological sequelae of sustained HIV-1 exposure and acute comorbid effects of opioids on dopamine D1 and D2 receptor-expressing (D1 and D2) MSNs are unknown. To address this question, Drd1-tdTomato- or Drd2-eGFP-expressing reporter and conditional HIV-1 Tat transgenic mice were interbred.

Neurodegeneration Within the Amygdala Is Differentially Induced by Opioid and HIV-1 Tat Exposure.

Opioid use disorder (OUD) is a critical problem that contributes to the spread of HIV and may intrinsically worsen neuroHIV. Despite the advent of combined antiretroviral therapies (cART), about half of persons infected with HIV (PWH) experience cognitive and emotional deficits that can be exacerbated by opioid abuse. HIV-1 Tat is expressed in the central nervous system (CNS) of PWH on cART and is thought to contribute to neuroHIV.

HIV-1 Tat reduces apical dendritic spine density throughout the trisynaptic pathway in the hippocampus of male transgenic mice.

Nearly one-third of persons infected with HIV-1 (PWH) develop HIV-associated neurocognitive disorders (HAND), which can be exacerbated by exposure to opioids. The impact of opioids on HIV-induced alterations in neuronal plasticity is less well understood. Both morphine exposure and HIV have been shown to disrupt synaptic growth and stability in the hippocampus suggesting a potential site of convergence for their deleterious effects.

Chloride channels with ClC-1-like properties differentially regulate the excitability of dopamine receptor D1- and D2-expressing striatal medium spiny neurons.

Dynamic chloride (Cl) regulation is critical for synaptic inhibition. In mature neurons, Cl influx and extrusion are primarily controlled by ligand-gated anion channels (GABA and glycine receptors) and the potassium chloride cotransporter K-Cl cotransporter 2 (KCC2), respectively. Here, we report for the first time, to our knowledge, a presence of a new source of Cl influx in striatal neurons with properties similar to chloride voltage-gated channel 1 (ClC-1).

Determinants of Mortality Among Severely Malnourished Children in Northern Nigeria.

Objectives: Severe Acute Malnutrition is a significant cause of mortality in children under the age of 5 years in low-resource settings, including Northern Nigeria. The study aimed to determine the associations between selected risk factors and mortality outcomes in children admitted with SAM in a facility in Katsina State, Northern Nigeria.

Methods: A prospective observational cohort of 201 children aged 6 to 59 months who were admitted with severe acute malnutrition (SAM) in stabilization centers in Katsina State, Northern Nigeria between May 18, 2021, and July 20, 2021, (63 days) were assessed followed up.

Restoration of KCC2 Membrane Localization in Striatal Dopamine D2 Receptor-Expressing Medium Spiny Neurons Rescues Locomotor Deficits in HIV Tat-Transgenic Mice.

People infected with HIV (PWH) are highly susceptible to striatal and hippocampal damage. Motor and memory impairments are common among these patients, likely as behavioral manifestations of damage to these brain regions. GABAergic dysfunction from HIV infection and viral proteins such as transactivator of transcription (Tat) have been well documented.

HIV-1 Tat and morphine decrease murine inter-male social interactions and associated oxytocin levels in the prefrontal cortex, amygdala, and hypothalamic paraventricular nucleus.

Many persons infected with HIV-1 (PWH) and opioid-dependent individuals experience deficits in sociability that interfere with daily living. Sociability is regulated by the prefrontal cortico-hippocampal-amygdalar circuit. Within this circuit HIV-1 trans-activator of transcription (HIV-1 Tat) and opioids can increase dendritic pathology and alter neuronal firing.

Oncologic Errors in Diagnostic Radiology: A 10-Year Analysis Based on Medical Malpractice Claims.

Purpose: To retrospectively analyze the nature and extent of oncology-related errors accounting for malpractice allegations in diagnostic radiology.

Methods: The Comparative Benchmarking System of the Controlled Risk Insurance Company, a database containing roughly 30% of medical malpractice claims in the United States, was searched retrospectively for the period 2008 to 2017. Claims naming radiology as a primary service were identified and were stratified and compared by oncologic versus nononcologic status, allegation type (diagnostic versus nondiagnostic), and imaging modality.

Monoacylglycerol Lipase Inhibition Using JZL184 Attenuates Paw Inflammation and Functional Deficits in a Mouse Model of Inflammatory Arthritis.

Patients with rheumatoid arthritis (RA) experience joint swelling and cartilage destruction resulting in chronic pain, functional disability, and compromised joint function. Current RA treatments, including glucocorticoid receptor agonists, produce adverse side effects and lack prolonged treatment efficacy. Cannabinoids (i.

HIV-1 Tat and Morphine Differentially Disrupt Pyramidal Cell Structure and Function and Spatial Learning in Hippocampal Area CA1: Continuous versus Interrupted Morphine Exposure.

About half the people infected with human immunodeficiency virus (HIV) have neurocognitive deficits that often include memory impairment and hippocampal deficits, which can be exacerbated by opioid abuse. To explore the effects of opioids and HIV on hippocampal CA1 pyramidal neuron structure and function, we induced HIV-1 transactivator of transcription (Tat) expression in transgenic mice for 14 d and co-administered time-release morphine or vehicle subcutaneous implants during the final 5 d (days 9-14) to establish steady-state morphine levels. Morphine was withheld from some slices during recordings to begin to assess the initial pharmacokinetic consequences of opioid withdrawal.