Corticostriatal ensemble dynamics across heroin self-administration to reinstatement.

Corticostriatal projection neurons from prelimbic medial prefrontal cortex to the nucleus accumbens core critically regulate drug-seeking behaviors, yet the underlying encoding dynamics whereby these neurons contribute to drug seeking remain elusive. Here we use two-photon calcium imaging to visualize the activity of corticostriatal neurons in mice from the onset of heroin use to relapse. We find that the activity of these neurons is highly heterogeneous during heroin self-administration and seeking, with at least 8 distinct neuronal ensembles that display both excitatory and inhibitory encoding dynamics. These neuronal ensembles are particularly apparent during relapse, where excitatory responses are amplified compared to heroin self-administration. Moreover, we find that optogenetic inhibition of corticostriatal projection neurons attenuates heroin seeking regardless of the relapse trigger. Our results reveal the precise corticostriatal activity dynamics underlying drug-seeking behaviors and support a key role for this circuit in mediating relapse to drug seeking.

Understanding Disparities in the Pediatric ICU: A Scoping Review.

BACKGROUND AND OBJECTIVES: Health disparities are pervasive in pediatrics. We aimed to describe disparities among patients who are likely to be cared for in the PICU and delineate how sociodemographic data are collected and categorized. METHODS: Using MEDLINE as a data source, we identified studies which included an objective to assess sociodemographic disparities among PICU patients in the United States. We created a review rubric, which included methods of sociodemographic data collection and analysis, outcome and exposure variables assessed, and study findings. Two authors reviewed every study. We used the National Institute on Minority Health and Health Disparities Research Framework to organize outcome and exposure variables. RESULTS: The 136 studies included used variable methods of sociodemographic data collection and analysis. A total of 30 of 124 studies (24%) assessing racial disparities used self- or parent-identified race. More than half of the studies (52%) dichotomized race as white and "nonwhite" or "other" in some analyses. Socioeconomic status (SES) indicators also varied; only insurance status was used in a majority of studies (72%) evaluating SES. Consistent, although not uniform, disadvantages existed for racial minority populations and patients with indicators of lower SES. The authors of only 1 study evaluated an intervention intended to mitigate health disparities. Requiring a stated objective to evaluate disparities aimed to increase the methodologic rigor of included studies but excluded some available literature. CONCLUSIONS: Variable, flawed methodologies diminish our understanding of disparities in the PICU. Meaningfully understanding and addressing health inequity requires refining how we collect, analyze, and interpret relevant data.

Barriers to Accessing and Engaging in HIV Preventive Care and Pre-Exposure Prophylaxis Experienced by Transgender Women in Florida.

BACKGROUND: PrEP, a biomedical HIV prevention option, continues to be underutilized among transgender women who could benefit from sustained use, especially women of color and those who identify as Latina and/or reside in the southeastern US. OBJECTIVE: We explored the barriers and facilitators experienced by transgender women who live in Florida regarding accessing, using, and/or staying on PrEP. METHODS: In-depth interviews and focus groups were conducted in either Spanish or English with adult transgender women living in Florida (N = 22). The interviews were audio-recorded, transcribed, and coded in ATLAS.ti using thematic analyses. RESULTS: The mean age of the participants was 42.2 years. Among the participants, 73% were Hispanic/Latina, 59% were foreign-born, and approximately one-third were living with HIV (but had past experience with PrEP). Transgender women cited the following barriers to accessing or considering PrEP: (1) costs and benefits of PrEP use; (2) under-representation in clinical trials resulting in unknown or misinformation regarding PrEP side effects; (3) chronic poverty; and (4) trauma and discrimination. Other stressors, such as behavioral healthcare needs, were identified. CONCLUSIONS: Our analysis revealed interlocking systems of oppression like transphobia, discrimination, and misgendering, which were common barriers experienced by our participants. These synergistically epidemic (i.e., syndemic) barriers contributed to their feelings of being systematically excluded in social spaces, research, public health planning and policies, laws, and social programs related to PrEP. These structural barriers are impediments to HIV preventive care but also act as a source of stress that contributes to mental health problems, financial vulnerability, substance abuse, and other deleterious health outcomes.

Evaluation of the Amblyopia tracker app.

PURPOSE: The Amblyopia tracker app has been developed to be a tool for parents to monitor changes in vision at home during amblyopia treatment. The aims of this study were to evaluate the feasibility and repeatability of parents testing their children at home and to compare home test results to an assessment in clinic by an orthoptist. METHODS: Children (age < 18 years) with amblyopia (interocular acuity difference of ≥ 0.2logMAR) were recruited. Parents were asked to test their child with the app three times during a two week period followed by an online questionnaire about the usability. Participants also tested within 48 h of their appointment where the measurement was repeated by an orthoptist. RESULTS: Out of 277 potential participants contacted, 37 completed three home measurements, mean age 6.8 years (SD 2.94). Home tests comparisons were made between test two and three to ensure familiarity with the process. Paired t-tests showed no statistically significant difference for either eye or the interocular acuity difference (IAD). However, 29% had a difference in IAD of more than 0.1logMAR on repeated testing, with a maximum of 0.4logMAR difference in the IAD. Questionnaire responses from the parents who participated were predominantly positive with 97% of respondents saying they would use it if were available. Comparison of home and clinical measurements (n = 23, mean age 6.72 SD 2.60) showed no statistically significant differences for either eye or interocular acuity difference (paired t-test, p > 0.3 in all cases). CONCLUSION: Results show no statistically significant differences for the Amblyopia tracker app when used by parents at home on repeated testing, or between the home test by a parent and the test by a clinician. However, variability in the results does indicate that further improvements are required to ensure the results can be used as a reliable clinical tool.

Restoration of a paraventricular thalamo-accumbal behavioral suppression circuit prevents reinstatement of heroin seeking.

Lack of behavioral suppression typifies substance use disorders, yet the neural circuit underpinnings of drug-induced behavioral disinhibition remain unclear. Here, we employ deep-brain two-photon calcium imaging in heroin self-administering mice, longitudinally tracking adaptations within a paraventricular thalamus to nucleus accumbens behavioral inhibition circuit from the onset of heroin use to reinstatement. We find that select thalamo-accumbal neuronal ensembles become profoundly hypoactive across the development of heroin seeking and use. Electrophysiological experiments further reveal persistent adaptations at thalamo-accumbal parvalbumin interneuronal synapses, whereas functional rescue of these synapses prevents multiple triggers from initiating reinstatement of heroin seeking. Finally, we find an enrichment of µ-opioid receptors in output- and cell-type-specific paraventricular thalamic neurons, which provide a mechanism for heroin-induced synaptic plasticity and behavioral disinhibition. These findings reveal key circuit adaptations that underlie behavioral disinhibition in opioid dependence and further suggest that recovery of this system would reduce relapse susceptibility.

Case Series: Cemiplimab and Nivolumab Immunotherapy as Promising Treatment in Advanced or Metastatic Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Surgery is usually curative; however, some locally advanced or metastatic CSCC may be unresectable. Current novel therapeutic options with immune checkpoint inhibition (ICI) of programmed-death receptor 1 (PD-1) such as cemiplimab and nivolumab have demonstrated promising and sustained results with good tolerability in patients with CSCC. This study looks at 2 cases of CSCC treated with cemiplimab and nivolumab, respectively, demonstrating dramatic response within 2 cycles with significant reduction in tumour size and minimal toxicities or adverse outcomes reported. Immunotherapy has shown positive results as an effective treatment option for unresectable, recurrent, or metastatic CSCC. It is currently approved for use in the USA and Europe.

Detection of SARS-CoV-2 in high-efficiency particulate air (HEPA) filters of low-cost air purifiers in community-based organizations.

This study aims to investigate the presence of SARS-CoV-2 in public spaces and assess the utility of inexpensive air purifiers equipped with high-efficiency particulate air (HEPA) filters for viral detection. Samples were collected from six community-based organizations in underserved minority neighborhoods in Northwest Miami, Florida, from February to May 2022. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect SARS-CoV-2 in air purifier filters and surface swabs. Among 32 filters tested, three yielded positive results, while no positive surface swabs were found. Notably, positive samples were obtained exclusively from child daycare centers. These findings highlight the potential for airborne transmission of SARS-CoV-2 in indoor air, particularly in child daycare centers. Moreover, the study demonstrates the effectiveness of readily available HEPA filters in detecting the virus. Improving indoor ventilation and implementing air filtration systems are crucial in reducing COVID-19 transmission where people gather. Air filtration systems incorporating HEPA filters offer a valuable approach to virus detection and reducing transmission risks. Future research should explore the applicability of this technology for early identification and mitigation of viral outbreaks.

Acute inhibition of hunger-sensing AgRP neurons promotes context-specific learning in mice.

OBJECTIVE: An environmental context, which reliably predicts food availability, can increase the appetitive food drive within the same environment context. However, hunger is required for the development of such a context-induced feeding (CIF) response, suggesting the neural circuits sensitive to hunger link an internal energy state with a particular environment context. Since Agouti related peptide (AgRP) neurons are activated by energy deficit, we hypothesised that AgRP neurons are both necessary and sufficient to drive CIF. METHODS: To examine the role of AgRP neurons in the CIF process, we used fibre photometry with GCaMP7f, chemogenetic activation of AgRP neurons, as well as optogenetic control of AgRP neurons to facilitate acute temporal control not permitted with chemogenetics. RESULTS: A CIF response at test was only observed when mice were fasted during context training and AgRP population activity at test showed an attenuated inhibitory response to food, suggesting increased food-seeking and/or decreased satiety signalling drives the increased feeding response at test. Intriguingly, chemogenetic activation of AgRP neurons during context training did not increase CIF, suggesting precise temporal firing properties may be required. Indeed, termination of AgRP neuronal photostimulation during context training (ON-OFF in context), in the presence or absence of food, increased CIF. Moreover, photoinhibition of AgRP neurons during context training in fasted mice was sufficient to drive a subsequent CIF in the absence of food. CONCLUSIONS: Our results suggest that AgRP neurons regulate the acquisition of CIF when the acute inhibition of AgRP activity is temporally matched to context exposure. These results establish acute AgRP inhibition as a salient neural event underscoring the effect of hunger on associative learning.

Salinity and total suspended solids control mercury speciation in a tidal river: Comparisons with a photochemical mercury model.

Daytime volatilization of gaseous elemental mercury (Hg(0)aq) is a significant mechanism for mercury removal from aquatic systems and potentially limits the production and bioaccumulation of methylmercury. Changes in incoming solar radiation (in the ultraviolet range), dissolved organic matter, salinity, and total suspended particles were investigated concurrently with several mercury species (Hg(0)aq, dissolved total mercury (THg), easily reducible mercury (ERM), and mercury associated with total suspended solids (THgTSS)) during daylight hours near the mouth of a hypertidal river. There were no predictable temporal changes observed for Hg(0)aq in unfiltered surface water. Hg(0)aq ranged from 0 to 12 pg L-1, THg ranged from 0 to 492 pg L-1, ERM ranged from 13 to 381 pg L-1, and THgTSS ranged from <1.58 ng g-1 to 261.32 ng g-1. The range of Hg(0)aq predicted by the empirical model was similar to measured ERM concentrations, but it was shown that ERM did not significantly predict in-situ photoreducible Hg(II) (Hg(II)RED). Production of Hg(0)aq appears to largely be suppressed by suspended solids, which limits ultraviolet radiation transmission through surface water. Comparison of these results to an empirical model developed for this site to predict Hg(0)aq indicates that significantly more mercury is available for photoreduction near the mouth of the tidal river, and that Hg(II) will likely photoreduce quickly when TSS levels decrease with ocean mixing.

An Intensive Care Unit peer support group: Participants' views on format, content and the impact on recovery journeys.

Background: Peer support groups reduce psychological morbidity and increase social support for Intensive Care Unit (ICU) survivors. Group formats differ and research, although emerging, is limited. This study explores a continuously running ICU Expert by Experience group, which has a dual role of support and service-user consultative, from attendees' perspectives. Methods: A thematic analysis was conducted on interviews with current and past members of an ICU Expert by Experience group. 11 participants took part in online and telephone interviews. Three provided written responses. Final themes were created following a process of data validation with participants. Results: Four main themes emerged: (1) Support in the difficult recovery journey (2) Relationships and shared experiences (3) Value of professional facilitation (4) Practical considerations. Conclusion: Patients highlighted the help gained from the group as an integral part of their recovery journey. Results also identified practical implications for those considering setting up similar support groups.

Effectiveness of systematically delivered evidence-based home safety promotion to improve child home safety practices: a controlled before-and-after study.

OBJECTIVE: Evaluate the effectiveness of systematically delivered evidence-based home safety promotion for improving child home safety practices. DESIGN: Controlled before-and-after study. SETTING: Nine electoral wards in Nottingham, UK. PARTICIPANTS: 361 families with children aged 2-7 months at recruitment living in four intervention wards with high health, education and social need; and 401 in five matched control wards. INTERVENTION: Evidence-based home safety promotion delivered by health visiting teams, family mentors and children's centres including 24 monthly safety messages; home safety activity sessions; quarterly 'safety weeks'; home safety checklists. OUTCOMES: Primary: composite measure comprising having a working smoke alarm, storing poisons out of reach and having a stairgate. Secondary: other home safety practices; medically attended injuries. Parents completed questionnaires at 12 and 24 months after recruitment plus optional three monthly injury questionnaires. RESULTS: At 24 months there was no significant difference between groups in the primary outcome (55.8% vs 48.8%; OR 1.58, 95% CI 0.98 to 2.55) or medically attended injury rates (incidence rate ratio 0.89, 95% CI 0.51 to 1.56), but intervention families were more likely to store poisons safely (OR 1.81, 95% CI 1.06 to 3.07), have a fire escape plan (OR 1.81, 95% CI 1.06 to 3.08), use a fireguard or have no fire (OR 3.17, 95% CI 1.63 to 6.16) and perform more safety practices (ß 0.46, 95% CI 0.13 to 0.79). CONCLUSIONS: Systematic evidence-based home safety promotion in areas with substantial need increases adoption of some safety practices. Funders should consider commissioning evidence-based multicomponent child home safety interventions. TRIAL REGISTRATION NUMBER: ISRCTN31210493.

Mercury photoreduction and photooxidation kinetics in estuarine water: Effects of salinity and dissolved organic matter.

Net photoreduction of divalent mercury (Hg(II)) and volatilization of photoreduction products (i.e., elemental mercury (Hg(0))/dissolved gaseous mercury (DGM)) is a mechanism by which mercury burdens in ecosystems are lessened. The effects of salinity on mercury photoreactions were investigated while controlling the concentration of DOM (>1 kDa) using natural surface water from the tidal Jijuktu'kwejk (Cornwallis River) and processed with a tangential ultrafiltration-dilution technique. Pseudo first-order rate constants in estuarine water salinity dilutions ranged between 0.22 h-1 and 0.73 h-1. The amount of mercury available for photoreduction (Hg(II)RED) ranged between 67.2 and 265.9 pg. Pseudo first-order rate constants decreased with increasing salinity treatments (0-13.5 g L-1), with minimal change in rate constants occurring in higher salinity treatments (e.g. 20.3 or 26.8 g L-1), while Hg(II)RED increased with salinity. In lower salinity treatments, DOM was more photoactive. Taken together, results suggest changes in the mercury photoreduction mechanism from DOM-bound electron transfer to photochemically produced secondary reduction products with increasing salinity. Experiments examining photooxidation showed decreases in Hg (0) with longer exposure time, suggesting transformation of Hg(II)RED into a non-reducible form. This research highlights the importance of salinity and DOM interactions in estuarine surface water and their effects on mercury photochemistry.

Identification of a Stress-Sensitive Anorexigenic Neurocircuit From Medial Prefrontal Cortex to Lateral Hypothalamus.

BACKGROUND: A greater understanding of how the brain controls appetite is fundamental to developing new approaches for treating diseases characterized by dysfunctional feeding behavior, such as obesity and anorexia nervosa. METHODS: By modeling neural network dynamics related to homeostatic state and body mass index, we identified a novel pathway projecting from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) in humans (n = 53). We then assessed the physiological role and dissected the function of this mPFC-LH circuit in mice. RESULTS: In vivo recordings of population calcium activity revealed that this glutamatergic mPFC-LH pathway is activated in response to acute stressors and inhibited during food consumption, suggesting a role in stress-related control over food intake. Consistent with this role, inhibition of this circuit increased feeding and sucrose seeking during mild stressors, but not under nonstressful conditions. Finally, chemogenetic or optogenetic activation of the mPFC-LH pathway is sufficient to suppress food intake and sucrose seeking in mice. CONCLUSIONS: These studies identify a glutamatergic mPFC-LH circuit as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake.

Participation in a yoga intervention is associated with improved mental health among Latinx adolescents.

Latinx youth with mental health disorders have worse outcomes when compared to their White (non-Hispanic) counterparts. Latinx youth also have less access to and lower utilization of mental health services. Emerging research supports the psychological and physical benefits of engaging in yoga and yoga may function as a complimentary treatment option for patients with mental health challenges. However, research assessing the efficacy of yoga and mindfulness is particularly sparse among Latinx youth, who may particularly benefit from mind body awareness activities given barriers to more traditional health approaches. The objective of this quasi-experimental study was to examine the effects of a 12-week Vinyasa flow-based yoga group intervention on anxiety, depression, empathy, and life satisfaction among adolescents receiving outpatient mental health treatment. Adolescents (n = 186; 12-17 years old) were recruited to an active intervention condition (Yoga); a subsequent group of participants (n = 91) were recruited in the same manner to an assessment-only comparison control condition (Comparison). The Yoga group participated in culturally and developmentally tailored group yoga classes for 12 weeks. Structural equation modelling was used to evaluate the main effect intervention response between participants in the two conditions. At the post-intervention assessment, after controlling for baseline levels of outcome variables (i.e., depression, anxiety, empathy, and life satisfaction), on average participants in the yoga condition reported: less depression symptoms (B = -1.54, p = 0.008), less anxiety symptoms (B = -0.75, p = 0.048), greater empathy (B = 1.32, p = 0.025) and greater life satisfaction (B = 0.30, p = 0.013) as compared to the Comparison condition. Yoga interventions can be an acceptable and feasible modality for promoting well-being and reducing mental health problems among Latinx youth.

An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice.

Suppression of dangerous or inappropriate reward-motivated behaviors is critical for survival, whereas therapeutic or recreational opioid use can unleash detrimental behavioral actions and addiction. Nevertheless, the neuronal systems that suppress maladaptive motivated behaviors remain unclear, and whether opioids disengage those systems is unknown. In a mouse model using two-photon calcium imaging in vivo, we identify paraventricular thalamostriatal neuronal ensembles that are inhibited upon sucrose self-administration and seeking, yet these neurons are tonically active when behavior is suppressed by a fear-provoking predator odor, a pharmacological stressor, or inhibitory learning. Electrophysiological, optogenetic, and chemogenetic experiments reveal that thalamostriatal neurons innervate accumbal parvalbumin interneurons through synapses enriched with calcium permeable AMPA receptors, and activity within this circuit is necessary and sufficient for the suppression of sucrose seeking regardless of the behavioral suppressor administered. Furthermore, systemic or intra-accumbal opioid injections rapidly dysregulate thalamostriatal ensemble dynamics, weaken thalamostriatal synaptic innervation of downstream neurons, and unleash reward-seeking behaviors in a manner that is reversed by genetic deletion of thalamic µ-opioid receptors. Overall, our findings reveal a thalamostriatal to parvalbumin interneuron circuit that is both required for the suppression of reward seeking and rapidly disengaged by opioids.