Developmental trajectory of social reward motivation from early adolescence into adulthood in female and male Long-Evans rats.

Most studies of adolescent and adult behavior involved one age group of each, whereas the dynamic changes in brain development suggest that there may be behavioral flux in adolescence. In two studies, we investigated developmental changes in social reward motivation in female and male Long-Evans rats from prepuberty to early adulthood in a social operant conditioning task. Given the earlier onset of puberty in females than in males, we predicted the course of social reward development would differ between the sexes. Overall, the pattern of results from both studies suggests that the trajectory of social motivation across adolescence is characterized by upward and downward shifts that do not depend on the sex of the rats. During training, in both studies, the mean number of social gate openings and percentage of social gate openings was higher at P30 (prepubertal, early adolescence) and P50 (late adolescence) than at P40 (mid adolescence) and P70 (adulthood) irrespective of sex. Nevertheless, the specific age comparisons that were significant depended on the study. In both studies, P30 rats had greater levels of social motivation than did adults in accessing a social reward when increased effort was required (progressive ratio tests). In an extinction test, only P30 and P50 rats continued to show more nose-pokes at the previously social gate than at the nonsocial gate, suggesting resistance to extinction. The results highlight the importance of characterizing behavior at several timepoints in adolescence to understand the neural mechanisms, many of which show similar discontinuities as they develop across adolescence.

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. Evidence suggests that dopaminergic neurotransmission is disrupted by HIV exposure, however, little is known about whether co-exposure to opioids may alter neurotransmitter levels in the striatum and if this in turn influences behavior. Therefore, we assayed motor, anxiety-like, novelty-seeking, exploratory, and social behaviors, and levels of monoamines and their metabolites following 2 weeks and 2 months of Tat and/or morphine exposure in transgenic mice. Morphine decreased dopamine levels, but significantly elevated norepinephrine, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5-hydroxyindoleacetic acid, which typically correlated with increased locomotor behavior. The combination of Tat and morphine altered dopamine, DOPAC, and HVA concentrations differently depending on the neurotransmitter/metabolite and duration of exposure but did not affect the numbers of tyrosine hydroxylase-positive neurons in the mesencephalon. Tat exposure increased the latency to interact with novel conspecifics, but not other novel objects, suggesting the viral protein inhibits exploratory behavior initiation in a context-dependent manner. By contrast, and consistent with prior findings that opioid misuse can increase novelty-seeking behavior, morphine exposure increased the time spent exploring a novel environment. Finally, Tat and morphine interacted to affect locomotor activity in a time-dependent manner, while grip strength and rotarod performance were unaffected. Together, our results provide novel insight into the unique effects of HIV-1 Tat and morphine on monoamine neurochemistry that may underlie their divergent effects on motor and exploratory behavior.

Neurexin-1-dependent circuit activity is required for the maintenance of photoreceptor subtype identity in Drosophila.

In the human and Drosophila color vision system, each photoreceptor neuron (cone cell in humans and R7/R8 photoreceptor cell in Drosophila) makes a stochastic decision to express a single photopigment of the same family with the exclusion of the others. While recent studies have begun to reveal the mechanisms that specify the generation of cone subtypes during development in mammals, nothing is known about how the mosaic of mutually exclusive cone subtypes is maintained in the mammalian retina. In Drosophila, recent work has led to the identification of several intrinsic factors that maintain the identity of R8 photoreceptor subtypes in adults. Whether and how extrinsic mechanisms are involved, however, remain unknown. In this study, we present evidence that supports that the Drosophila transsynaptic adhesion molecule Neurexin 1 (Dnrx-1) is required non-cell autonomously in R8p subtypes for the maintenance of R8y subtype identity. Silencing the activity of R8p subtypes caused a phenotype identical to that in dnrx-1 mutants. These results support a novel role for Nrx-1-dependent circuit activity in mediating the communication between R8 photoreceptor subtypes for maintaining the subtype identity in the retina.

Halogen Bonding in the Decoration of Secondary Coordination Sphere of Zinc(II) and Cadmium(II) Complexes: Catalytic Application in Cycloaddition Reaction of CO2 with Epoxides.

Three new zinc(II) complexes [Zn(H2L3)2(H2O)3] (Zn2), [Zn(H3L2a)(H2O)3]n (Zn3) (H3L2a = 2,4-diiodo-5-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)isophthalate) and [Zn(HL4)(DMF)(H2O)]n (Zn4) were synthesized by the reaction of Zn(II) salts with 5-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl) isophthalic acid (H3L3), 2,4,6-triiodo-5-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl) isophthalic acid (H5L2) (in the presence of NH2OH·HCl) and 5-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)-2,4,6-triiodoisophthalic acid (H3L4), respectively. According to the X-ray structural analysis, the intramolecular resonance-assisted hydrogen bond ring remains intact, with N···O distances of 2.562(5) and 2.573(5) Å in Zn2, 2.603(6) Å in Zn3, and 2.563(8) Å in Zn4. In the crystal packing of Zn3, the cooperation of I···O and I···I types of halogen bonds between tectons leads to a one-dimensional supramolecular polymer, while I···O interactions aggregate 1D chains of coordination polymer Zn4. These new complexes (Zn2, Zn3, and Zn4) and known [Zn(H3L1)(H2O)2]n (Zn1) (H3L1 = 5-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene) hydrazineyl)isophthalate), {[Zn(H3L1)(H2O)3]·3H2O}n (Zn5), [Cd(H3L1)(H2O)2]n (Cd1), {[Cd(HL3)(H2O)2(DMF)]·H2O}n (Cd2), [Cd(H3L3)]n (Cd-3), {[Cd2(µ-H2O)2(µ-H2L4)2(H2L4)2]·2H2O}n (Cd4), and {[Cd(H3L1)(H2O)3]·4H2O}n (Cd5) were tested as catalysts in the cycloaddition reaction of CO2 with epoxides in the presence of tetrabutylammonium halides as the cocatalyst. The halogen-bonded catalyst Zn4 is the most efficient one in the presence of tetrabutylammonium bromide by affording a high yield (85-99%) of cyclic carbonates under solvent-free conditions after 48 h at 40 bar and 80 °C.

Use of Biological Feedback as a Health Behavior Change Technique in Adults: Scoping Review.

BACKGROUND: Recent advancements in personal biosensing technology support the shift from standardized to personalized health interventions, whereby biological data are used to motivate health behavior change. However, the implementation of interventions using biological feedback as a behavior change technique has not been comprehensively explored. OBJECTIVE: The purpose of this review was to (1) map the domains of research where biological feedback has been used as a behavior change technique and (2) describe how it is implemented in behavior change interventions for adults. METHODS: A comprehensive systematic search strategy was used to query 5 electronic databases (Ovid MEDLINE, Elsevier Embase, Cochrane Central Register of Controlled Trials, EBSCOhost PsycINFO, and ProQuest Dissertations & Theses Global) in June 2021. Eligible studies were primary analyses of randomized controlled trials (RCTs) in adults that incorporated biological feedback as a behavior change technique. DistillerSR was used to manage the literature search and review. RESULTS: After removing 49,500 duplicates, 50,287 articles were screened and 767 articles were included. The earliest RCT was published in 1972 with a notable increase in publications after 2000. Biological feedback was most used in RCTs aimed at preventing or managing diabetes (n=233, 30.4%), cardiovascular disease (n=175, 22.8%), and obesity (n=115, 15%). Feedback was often given on multiple biomarkers and targeted multiple health behaviors. The most common biomarkers used were anthropometric measures (n=297, 38.7%), blood pressure (n=238, 31%), and glucose (n=227, 29.6%). The most targeted behaviors were diet (n=472, 61.5%), physical activity (n=417, 54.4%), and smoking reduction (n=154, 20.1%). The frequency and type of communication by which biological feedback was provided varied by the method of biomarker measurement. Of the 493 (64.3%) studies where participants self-measured their biomarker, 476 (96.6%) received feedback multiple times over the intervention and 468 (94.9%) received feedback through a biosensing device. CONCLUSIONS: Biological feedback is increasingly being used to motivate behavior change, particularly where relevant biomarkers can be readily assessed. Yet, the methods by which biological feedback is operationalized in intervention research varied, and its effectiveness remains unclear. This scoping review serves as the foundation for developing a guiding framework for effectively implementing biological feedback as a behavior change technique. TRIAL REGISTRATION: Open Science Framework Registries; https://doi.org/10.17605/OSF.IO/YP5WAd. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/32579.

Linker-Assisted Assembly of Ligand-Bridged CdS/MoS2 Heterostructures: Tunable Light-Harvesting Properties and Ligand-Dependent Control of Charge-Transfer Dynamics and Photocatalytic Hydrogen Evolution.

We used linker-assisted assembly (LAA) to tether CdS quantum dots (QDs) to MoS2 nanosheets via L-cysteine (cys) or mercaptoalkanoic acids (MAAs) of varying lengths, yielding ligand-bridged CdS/MoS2 heterostructures for redox photocatalysis. LAA afforded precise control over the light-harvesting properties of QDs within heterostructures. Photoexcited CdS QDs transferred electrons to molecularly linked MoS2 nanosheets from both band-edge and trap states; the electron-transfer dynamics was tunable with the properties of bridging ligands. Rate constants of electron transfer, estimated from time-correlated single photon counting (TCSPC) measurements, ranged from (9.8 ± 3.8) × 106 s-1 for the extraction of electrons from trap states within heterostructures incorporating the longest MAAs to >5 × 109 s-1 for the extraction of electrons from band-edge or trap states in heterostructures with cys or 3-mercaptopropionic acid (3MPA) linkers. Ultrafast transient absorption measurements revealed that electrons were transferred within 0.5-2 ps or less for CdS-cys-MoS2 and CdS-3MPA-MoS2 heterostructures, corresponding to rate constants ≥5 × 109 s-1. Photoinduced CdS-to-MoS2 electron transfer could be exploited in photocatalytic hydrogen evolution reaction (HER) via the reduction of H+ to H2 in concert with the oxidation of lactic acid. CdS-L-MoS2-functionalized FTO electrodes promoted HER under oxidative conditions wherein H2 was evolved at a Pt counter electrode with Faradaic efficiencies of 90% or higher and under reductive conditions wherein H2 was evolved at the CdS-L-MoS2-heterostructure-functionalized working electrode with Faradaic efficiencies of 25-40%. Dispersed CdS-L-MoS2 heterostructures promoted photocatalytic HER (15.1 µmol h-1) under white-light illumination, whereas free cys-capped CdS QDs produced threefold less H2 and unfunctionalized MoS2 nanosheets produced no measurable H2. Charge separation across the CdS/MoS2 interface is thus pivotal for redox photocatalysis. Our results reveal that LAA affords tunability of the properties of constituent CdS QDs and MoS2 nanosheets and precise, programmable, ligand-dependent control over the assembly, interfacial structure, charge-transfer dynamics, and photocatalytic reactivity of CdS-L-MoS2 heterostructures.

Exploring the Impact of Dawn Phenomenon on Glucose-Guided Eating Thresholds in Individuals With Type 2 Diabetes Using Continuous Glucose Monitoring: Observational Study.

BACKGROUND: Glucose-guided eating (GGE) improves metabolic markers of chronic disease risk, including insulin resistance, in adults without diabetes. GGE is a timed eating paradigm that relies on experiencing feelings of hunger and having a preprandial glucose level below a personalized threshold computed from 2 consecutive morning fasting glucose levels. The dawn phenomenon (DP), which results in elevated morning preprandial glucose levels, could cause typically derived GGE thresholds to be unacceptable or ineffective among people with type 2 diabetes (T2DM). OBJECTIVE: The aim of this study is to quantify the incidence and day-to-day variability in the magnitude of DP and examine its effect on morning preprandial glucose levels as a preliminary test of the feasibility of GGE in adults with T2DM. METHODS: Study participants wore a single-blinded Dexcom G6 Pro continuous glucose monitoring (CGM) system for up to 10 days. First and last eating times and any overnight eating were reported using daily surveys over the study duration. DP was expressed as a dichotomous variable at the day level (DP day vs non-DP day) and as a continuous variable reflecting the percent of days DP was experienced on a valid day. A valid day was defined as having no reported overnight eating (between midnight and 6 AM). ∂ Glucose was computed as the difference in nocturnal glucose nadir (between midnight and 6 AM) to morning preprandial glucose levels. ∂ Glucose ≥20 mg/dL constituted a DP day. Using multilevel modeling, we examined the between- and within-person effects of DP on morning preprandial glucose and the effect of evening eating times on DP. RESULTS: In total, 21 adults (59% female; 13/21, 62%) with non-insulin-treated T2DM wore a CGM for an average of 10.5 (SD 1.1) days. Twenty out of 21 participants (95%) experienced DP for at least 1 day, with an average of 51% of days (SD 27.2; range 0%-100%). The mean ∂ glucose was 23.7 (SD 13.2) mg/dL. People who experience DP more frequently had a morning preprandial glucose level that was 54.1 (95% CI 17.0-83.9; P<.001) mg/dL higher than those who experienced DP less frequently. For within-person effect, morning preprandial glucose levels were 12.1 (95% CI 6.3-17.8; P=.008) mg/dL higher on a DP day than on a non-DP day. The association between ∂ glucose and preprandial glucose levels was 0.50 (95% CI 0.37-0.60; P<.001). There was no effect of the last eating time on DP. CONCLUSIONS: DP was experienced by most study participants regardless of last eating times. The magnitude of the within-person effect of DP on morning preprandial glucose levels was meaningful in the context of GGE. Alternative approaches for determining acceptable and effective GGE thresholds for people with T2DM should be explored and evaluated.

Persistence in a pharmacist-led, same-day PrEP program in Mississippi: a mixed-methods study.

INTRODUCTION: Mississippi has one of the highest rates of HIV in the United States but low PrEP uptake. Understanding patterns of PrEP use can improve PrEP initiation and persistence. METHODS: This is a mixed-method evaluation of a PrEP program in Jackson, Mississippi. Between November 2018-December 2019, clients at high risk for HIV attending a non-clinical testing site were referred to a pharmacist for same-day PrEP initiation. The pharmacist provided a 90-day PrEP prescription and scheduled a follow-up clinical appointment within three months. We linked client records from this visit to electronic health records from the two largest PrEP clinics in Jackson to determine linkage into ongoing clinical care. We identified four distinct PrEP use patterns, which we used for qualitative interview sampling: 1) filled a prescription and linked into care within three months; 2) filled a prescription and linked into care after three months; 3) filled a prescription and never linked into care; and 4) never filled a prescription. In 2021, we purposively sampled patients in these four groups for individual interviews to ascertain barriers and facilitators to PrEP initiation and persistence, using guides informed by the Theory of Planned Behavior. RESULTS: There were 121 clients evaluated for PrEP; all were given a prescription. One-third were less than 25 years old, 77% were Black, and 59% were cisgender men who have sex with men. One-quarter (26%) never filled their PrEP prescription, 44% picked up the prescription but never linked into clinical care, 12% linked into care at some point after three months (resulting in a gap in PrEP coverage), and 18% linked into care within 3 months. We interviewed 26 of 121 clients. Qualitative data revealed that cost, stigmas related to sexuality and HIV, misinformation about PrEP, and perceived side effects were barriers to uptake and persistence. Individuals' desire to stay healthy and the support of PrEP clinic staff were facilitators. CONCLUSIONS: The majority of individuals given a same-day PrEP prescription either never started PrEP or stopped PrEP within the first three months. Addressing noted barriers of stigma and misinformation and reducing structural barriers may increase PrEP initiation and persistence.

Multiple modes of inference reveal less phylogenetic signal in marsupial basicranial shape compared with the rest of the cranium.

Incorporating morphological data into modern phylogenies allows integration of fossil evidence, facilitating divergence dating and macroevolutionary inferences. Improvements in the phylogenetic utility of morphological data have been sought via Procrustes-based geometric morphometrics (GMM), but with mixed success and little clarity over what anatomical areas are most suitable. Here, we assess GMM-based phylogenetic reconstructions in a heavily sampled source of discrete characters for mammalian phylogenetics-the basicranium-in 57 species of marsupial mammals, compared with the remainder of the cranium. We show less phylogenetic signal in the basicranium compared with a 'Rest of Cranium' partition, using diverse metrics of phylogenetic signal (Kmult, phylogenetically aligned principal components analysis, comparisons of UPGMA/neighbour-joining/parsimony trees and cophenetic distances to a reference phylogeny) for scaled, Procrustes-aligned landmarks and allometry-corrected residuals. Surprisingly, a similar pattern emerged from parsimony-based analyses of discrete cranial characters. The consistent results across methods suggest that easily computed metrics such as Kmult can provide good guidance on phylogenetic information in a landmarking configuration. In addition, GMM data may be less informative for intricate but conservative anatomical regions such as the basicranium, while better-but not necessarily novel-phylogenetic information can be expected for broadly characterized shapes such as entire bones. This article is part of the theme issue 'The mammalian skull: development, structure and function'.

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. MSNs in ex vivo slices from male mice were assessed by whole-cell patch-clamp electrophysiology and filled with biocytin to explore the functional and structural effects of progressive Tat and acute morphine exposure. Although the excitability of both D1 and D2 MSNs increased following 48 h of Tat exposure, D1 MSN firing rates decreased below control (Tat-) levels following 2 weeks and 1 month of Tat exposure but returned to control levels after 2 months. D2 neurons continued to display Tat-dependent increases in excitability at 2 weeks, but also returned to control levels following 1 and 2 months of Tat induction. Acute morphine exposure increased D1 MSN excitability irrespective of the duration of Tat exposure, while D2 MSNs were variably affected. That D1 and D2 MSN excitability would return to control levels was unexpected since both subpopulations displayed significant synaptodendritic degeneration and pathologic phospho-tau-Thr205 accumulation following 2 months of Tat induction. Thus, despite frank morphologic damage, D1 and D2 MSNs uniquely adapt to sustained Tat and acute morphine insults.

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. In the present study, we examined the density of dendritic spines in CA1 and CA3 pyramidal neurons, and granule neurons within the dentate gyrus representing the hippocampal trisynaptic pathway after short-term exposure to the HIV transactivator of transcription (Tat) protein and morphine. We exposed inducible male, HIV-1 Tat transgenic mice to escalating doses of morphine (10-40 mg/kg, b.i.d.) and examined synaptodendritic structure in Golgi-impregnated hippocampal neurons. HIV-1 Tat, but not morphine, systematically reduced the density of apical, but not basilar, dendrites of CA1 and CA3 pyramidal neurons, and granule neuronal apical dendrites, suggesting the coordinated loss of specific synaptic interconnections throughout the hippocampal trisynaptic pathway.

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 (GABAA 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). Using whole cell patch-clamp recordings, we detected an outwardly rectifying voltage-dependent current that was impermeable to the large anion methanesulfonate (MsO-). The anionic current was sensitive to the ClC-1 inhibitor 9-anthracenecarboxylic acid (9-AC) and the nonspecific blocker phloretin. The mean fractions of anionic current inhibition by MsO-, 9-AC, and phloretin were not significantly different, indicating that anionic current was caused by active ClC-1-like channels. In addition, we found that Cl- current was not sensitive to the transmembrane protein 16A (TMEM16A; Ano1) inhibitor Ani9 and that the outward Cl- rectification was preserved even at a very high intracellular Ca2+ concentration (2 mM), indicating that TMEM16B (Ano2) did not contribute to the total current. Western blotting and immunohistochemical analyses confirmed the presence of ClC-1 channels in the striatum mainly localized to the somata of striatal neurons. Finally, we found that 9-AC decreased action potential firing frequencies and increased excitability in medium spiny neurons (MSNs) expressing dopamine type 1 (D1) and type 2 (D2) receptors in the brain slices, respectively. We conclude that ClC-1-like channels are preferentially located at the somata of MSNs, are functional, and can modulate neuronal excitability.

Abbreviated Dietary Self-monitoring for Type 2 Diabetes Management: Mixed Methods Feasibility Study.

BACKGROUND: Type 2 diabetes mellitus (T2D) can be managed through diet and lifestyle changes. The American Diabetes Association acknowledges that knowing what and when to eat is the most challenging aspect of diabetes management. Although current recommendations for self-monitoring of diet and glucose levels aim to improve glycemic stability among people with T2D, tracking all intake is burdensome and unsustainable. Thus, dietary self-monitoring approaches that are equally effective but are less burdensome should be explored. OBJECTIVE: This study aims to examine the feasibility of an abbreviated dietary self-monitoring approach in patients with T2D, in which only carbohydrate-containing foods are recorded in a diet tracker. METHODS: We used a mixed methods approach to quantitatively and qualitatively assess general and diet-related diabetes knowledge and the acceptability of reporting only carbohydrate-containing foods in 30 men and women with T2D. RESULTS: The mean Diabetes Knowledge Test score was 83.9% (SD 14.2%). Only 20% (6/30) of participants correctly categorized 5 commonly consumed carbohydrate-containing foods and 5 noncarbohydrate-containing foods. The mean perceived difficulty of reporting only carbohydrate-containing foods was 5.3 on a 10-point scale. Approximately half of the participants (16/30, 53%) preferred to record all foods. A lack of knowledge about carbohydrate-containing foods was the primary cited barrier to acceptability (12/30, 40%). CONCLUSIONS: Abbreviated dietary self-monitoring in which only carbohydrate-containing foods are reported is likely not feasible because of limited carbohydrate-specific knowledge and a preference of most participants to report all foods. Other approaches to reduce the burden of dietary self-monitoring for people with T2D that do not rely on food-specific knowledge could be more feasible.

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. Changes in sociability are also associated with dysregulation of hypothalamic neuropeptides such as oxytocin or corticotropin releasing factor (CRF) in the prefrontal cortico-hippocampal-amygdalar circuit. Accordingly, we hypothesized that the interaction of HIV-1 Tat and morphine would impair inter-male social interactions and disrupt oxytocin and CRF within the PFC and associated circuitry. Male mice were exposed to HIV-1 Tat for 8 weeks and administered saline or escalating doses of morphine twice daily (s.c.) during the last 2 weeks of HIV-1 Tat exposure. Tat attenuated aggressive interactions with an unknown intruder, whereas morphine decreased both non-aggressive and aggressive social interactions in the resident-intruder test. However, there was no effect of Tat or morphine on non-reciprocal interactions in the social interaction and novelty tests. Tat, but not morphine, decreased oxytocin levels in the PFC and amygdala, whereas both Tat and morphine decreased the percentage of oxytocin-immunoreactive neurons in the hypothalamic paraventricular nucleus (PVN). In Tat(+) or morphine-exposed mice, regional levels of CRF and oxytocin correlated with alterations in behavior in the social interaction and novelty tests. Overall, decreased expression of oxytocin in the prefrontal cortico-hippocampal-amygdalar circuit is associated with morphine- and HIV-Tat-induced deficits in social behavior.

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 ex vivo slices during recordings to begin to assess the initial pharmacokinetic consequences of opioid withdrawal. Tat expression reduced hippocampal CA1 pyramidal neuronal excitability at lower stimulating currents. Pyramidal cell firing rates were unaffected by continuous morphine exposure. Behaviorally, exposure to Tat or high dosages of morphine impaired spatial memory Exposure to Tat and steady-state levels of morphine appeared to have largely independent effects on pyramidal neuron structure and function, a response that is distinct from other vulnerable brain regions such as the striatum. By contrast, acutely withholding morphine (from morphine-tolerant ex vivo slices) revealed unique and selective neuroadaptive shifts in CA1 pyramidal neuronal excitability and dendritic plasticity, including some interactions with Tat. Collectively, the results show that opioid-HIV interactions in hippocampal area CA1 are more nuanced than previously assumed, and appear to vary depending on the outcome assessed and on the pharmacokinetics of morphine exposure.

Is there any gender difference in epidemiology, clinical presentation and co-morbidities of non-functioning pituitary adenomas? A prospective survey of a National Referral Center and review of the literature.

PURPOSE: Gender differences in patients diagnosed with non-functioning Pituitary Adenomas (NFPA) in a National Referral Center for Pituitary Tumors at the Federico II University of Naples, Italy. METHODS: Patients newly diagnosed with non-functioning sellar masses found on pituitary Magnetic Resonance Imaging from January 1st 2016 to December 31th 2018 underwent anthropometric measurements, basal evaluation of pituitary function, and metabolic assessment. Fatty live index (FLI) and visceral adiposity index (VAI) were calculated. RESULTS: Seventy-three patients (35 males, 51.1 ± 17.0 years; 38 females, 41.8 ± 18.1 years) presented with NFPA. Lesions > 1 cm (85.7% vs. 47.3%; χ2 = 10.26, p = 0.001) and hypopituitarism (77.1% vs. 7.9%; χ2 = 33.29, p = 0.001) were more frequent in males than females. The highest sizes of pituitary adenomas were significantly associated with male gender (OR = 1.05, p = 0.049; R2 = 0.060; IC 1.00-1.10). Headache (62.8% vs. 31.6%; χ2 = 5.96, p = 0.015) and visual field deficits (57.1% vs. 26.3%; χ2 = 5.93, p = 0.015) were significantly more frequent in males than in females. There was no sex difference in obesity prevalence, but the metabolic syndrome was more common among males than females (60.6% vs. 26.3%; χ2 = 7.14, p = 0.001). FLI was also higher in males (69.6 ± 27.3 vs. 49.2 ± 31.3; p < 0.001), while there were no differences in VAI. CONCLUSIONS: Apart from the possible delay in the diagnosis induced by the gender differences in symptom presentation, the higher prevalence of macroadenomas amongst NFPA in males compared with females let to hypothesize a key role of the sex hormone profile as predictive factors of their biological behavior and metabolic profile. Further studies are, however, mandatory to better support the influence of gender differences on onset, progression, and metabolic consequences of NFPA.

A Pharmacist-Led, Same-Day, HIV Pre-Exposure Prophylaxis Initiation Program to Increase PrEP Uptake and Decrease Time to PrEP Initiation.

Mississippi has one of the highest rates of HIV in the United States, but has low pre-exposure prophylaxis (PrEP) uptake, particularly among black men who have sex with men (MSM) and women. From November 2018 to May 2019, patients at high risk of HIV who tested negative for HIV at a nonclinical testing center in Jackson, Mississippi, were referred to an on-site clinical pharmacist for same-day PrEP initiation. The pharmacist evaluated patients for medical contraindications to PrEP, but no baseline labs were obtained. The pharmacist provided a PrEP prescription and scheduled a clinical appointment for patients within 6 weeks, at which time they were evaluated by a clinician and completed baseline labs. The pharmacist evaluated 69 patients for PrEP; 57% were MSM, 77% were black, and 65% were uninsured. All patients received a PrEP prescription; 83% received the prescription the same day and 97% received it within 5 days. Fifty-three (77%) of 69 clients filled the prescription; 87% of whom filled it within 1 week. Only 23 (43%) of 53 clients who filled their prescription attended their initial clinical appointment within 6 weeks of obtaining PrEP. There were no differences in PrEP initiation or retention by patient sex/gender. This pilot program suggests that an on-site pharmacist working in a nonclinical testing center in the southern United States can successfully initiate PrEP among predominately low-income black MSM. Future efforts should seek to better integrate laboratory testing into this demedicalized model of PrEP and to improve retention in care.

What does soil-transmitted helminth elimination look like? Results from a targeted molecular detection survey in Japan.

BACKGROUND: Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures. The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized. Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections. Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs. METHODS: Stool samples were collected from 682 preschool- and school-aged children from six localities of Japan with previously high prevalence of STH. Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination. For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura. RESULTS: Among the 682 children, no positive samples were identified, and participants reported high standards of WASH. CONCLUSIONS: To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection. The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas. These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible. Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.

Carotid foramen size in the human skull tracks developmental changes in cerebral blood flow and brain metabolism.

OBJECTIVES: In humans, neuronal processes related to brain development elevate the metabolic rate of brain tissue relative to the body during early childhood. This phenomenon has been hypothesized to contribute to slow somatic growth in preadolescent Homo sapiens. The uncoupling of the brain's metabolic rate from brain size during development complicates the study of the evolutionary emergence of these traits in the fossil record. Here, we extend a method previously developed to predict interspecific differences in cerebral blood flow (a correlate of cerebral glucose use) to predict ontogenetic changes in human brain metabolism. MATERIALS AND METHODS: Radii of the carotid foramen from an ontogenetic series of modern human crania were used to predict blood flow rates through the internal carotid arteries (ICA), which were compared to empirically measured ICA flow and brain metabolism values. RESULTS: Predictions of both absolute ICA blood flow rates and perfusion (ICA blood flow rates relative to brain size) generally match measured values in infancy and childhood. Maximum predicted ICA blood flow rates and perfusion were found to occur between ages 5 and 8, which roughly correspond to the age of maximum measured ICA blood flow rate and absolute and brain mass-specific rate of whole brain glucose uptake. DISCUSSION: These findings suggest that, during human growth and development, the size of the carotid foramen corresponds well to blood flow requirements through the ICA, and the method tested here may provide new opportunities for studying developmental changes in brain metabolism using osteological samples, including fossil hominins.