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Maladaptive feeding comprises unhealthy eating patterns that jeopardize survival, including over- and underconsumption. These behaviors are often coordinated by endogenous opioid receptors (EORs). Here, we explore the involvement of EORs in obesity and anorexia nervosa (AN), two disorders associated with dysregulated feeding behavior and relevant animal models. While seemingly opposing metabo-psychiatric states, our goal is to highlight common circuit and synaptic mechanisms underlying obesity and AN with a focus on EOR functionality. We examine the neural substrates underlying maladaptive feeding and comorbid conditions including pain, suggesting a role for EOR-driven plasticity in the pathogenesis of both obesity and AN. This review examines the role of endogenous opioid receptors (EORs) in maladaptive feeding, focusing on shared mechanisms between obesity and anorexia nervosa. It highlights EOR-driven neural plasticity, links to pain and substance use, and proposes directions for EOR-targeted therapeutic research.

Oxytocin neurons represent one of the major subsets of neurons in the paraventricular hypothalamus (PVH), a critical brain region for energy homeostasis. Despite substantial evidence supporting a role of oxytocin in body weight regulation, it remains controversial whether oxytocin neurons directly regulate body weight homeostasis, feeding or energy expenditure. Pharmacologic doses of oxytocin suppress feeding through a proposed melanocortin responsive projection from the PVH to the hindbrain. In contrast, deficiency in oxytocin or its receptor leads to reduced energy expenditure without feeding abnormalities. To test the physiological function of oxytocin neurons, we specifically ablated oxytocin neurons in adult mice. Our results show that oxytocin neuron ablation in adult animals has no effect on body weight, food intake or energy expenditure on a regular diet. Interestingly, male mice lacking oxytocin neurons are more sensitive to high fat diet-induced obesity due solely to reduced energy expenditure. In addition, despite a normal food intake, these mice exhibit a blunted food intake response to leptin administration. Thus, our study suggests that oxytocin neurons are required to resist the obesity associated with a high fat diet; but their role in feeding is permissive and can be compensated for by redundant pathways.

The ventromedial hypothalamus (VMH) is a critical neural node that senses blood glucose and promotes glucose utilization or mobilization during hypoglycemia. The VMH neurons that control these distinct physiologic processes are largely unknown. Here, we show that melanocortin 3 receptor (Mc3R)-expressing VMH neurons (VMHMC3R) sense glucose changes both directly and indirectly via altered excitatory input. We identify presynaptic nodes that potentially regulate VMHMC3R neuronal activity, including inputs from proopiomelanocortin (POMC)-producing neurons in the arcuate nucleus. We find that VMHMC3R neuron activation blunts, and their silencing enhances glucose excursion following a glucose load. Overall, these findings demonstrate that VMHMC3R neurons are a glucose-responsive hypothalamic subpopulation that promotes glucose disposal upon activation; this highlights a potential site for targeting dysregulated glycemia.

Background: Variations in systemic inflammatory response biomarker levels have been associated with adverse clinical outcome in various malignancies. This study determined the prognostic significance of preoperative neutrophil:lymphocyte (NLR), platelet:lymphocyte (PLR) and monocyte:lymphocyte (MLR) ratios in endometrial cancer. Methods: Clinicopathological and 5-year follow-up data were obtained for a retrospective series of surgically treated endometrial cancer patients ( n =605). Prognostic significance was determined for overall (OS) and cancer-specific survival (CSS) using Cox proportional hazards models and Kaplan–Meier analysis. Receiver–operator characteristic and log-rank functions were used to optimise cut-offs. NLR, PLR and MLR associations with clinicopathological variables were determined using non-parametric tests. Results: Applying cut-offs of ⩾2.4 (NLR), ⩾240 (PLR) and ⩾0.19 (MLR), NLR and PLR (but not MLR) had independent prognostic significance. Combining NLR and PLR scores stratified patients into low (NLR-low and PLR-low), intermediate (NLR-high or PLR-high) and high risk (NLR-high and PLR-high) groups: multivariable hazard ratio (HR) 2.51; P <0.001 (OS); HR 2.26; P <0.01 (CSS) for high vs low risk patients. Increased NLR and PLR were most strongly associated with advanced stage ( P <0.001), whereas increased MLR was strongly associated with older age ( P <0.001). Conclusion: Both NLR and PLR are independent prognostic indicators for endometrial cancer, which can be combined to provide additional patient stratification.

On 03 February 2022, SpaceX launched 49 Starlink satellites, 38 of which re‐entered the atmosphere on or about 07 February 2022 due to unexpectedly high atmospheric drag. We use empirical model (NRLMSIS, JB08, and HASDM) outputs as well as solar extreme ultraviolet occultation and high‐fidelity accelerometer data to show that thermospheric density was at least 20%–30% higher at 210 km relative to the 9 days prior to the launch due to consecutive geomagnetic storms related to solar eruptions from NOAA AR12936 on 29 January 2022. We model the orbital altitude and in‐track position of a Starlink‐like satellite in a low‐drag configuration at 200 km during minor (G1) and extreme (G5) geomagnetic storms to show that an extreme storm would have at least a factor of two higher impact, with cumulative in‐track errors on the order of 10,000 km after a 5‐day duration extreme storm. Comparison of the JB08 and NRL MSIS models relative to the HASDM model during modeled historical minor and extreme geomagnetic storms shows that in‐track errors on the order of 100 km per day at 250 km, decreasing to cumulative errors on the order of 1 km per day at 550 km during geomagnetic storms. We conclude that full‐physics, data assimilative, coupled models of the magnetosphere and upper atmosphere, as well as new operational satellite missions providing “nowcasting” data to launch controllers, space traffic coordinators, and satellite operators, are needed to prevent similar—or worse—orbital system impacts during future geomagnetic storms.

Background The prevalence of smoking among cervical cancer survivors is high and evidence-based smoking cessation interventions are critically needed. This paper describes the study design, methods, and data analysis plans for a randomized clinical trial (RCT) designed to evaluate the efficacy of a novel, personally tailored SMS-delivered text-based digital treatment adjuvant designed to enhance the long-term efficacy of a “ M otivation A nd P roblem- S olving” ( MAPS ) approach for smoking cessation among individuals with a history of cervical intraepithelial neoplasia (CIN) or cervical cancer. MAPS is a phone counseling approach designed to facilitate long-term abstinence that comprises 6 counseling calls over 12 months. The current trial is evaluating the efficacy of MAPS+ , which comprises all MAPS components plus a 24-month digital treatment adjuvant. This trial represents a logical extension of our previous RCT, which compared the efficacy of MAPS to a quitline control condition and found that MAPS resulted in greater than a 2-fold increase in smoking abstinence at 12 months (i.e., 26.4% vs. 11.9%). This treatment effect was no longer significant at 18 months, suggesting that efficacy dissipated as time from the end of treatment increased. The primary aim of the current trial is to compare the efficacy of MAPS + and ST in facilitating long-term abstinence. Methods Individuals who smoke and have a history of cervical cancer or CIN (N = 340) are recruited throughout Florida and randomly assigned to Standard Treatment [ ST ] or MAPS+ . ST participants are electronically connected with the Florida Quitline. MAPS + consists of 6 proactive MAPS-based counseling calls over 12 months plus the novel, personally tailored, text message-based treatment adjuvant delivered over 24 months. All participants receive 12 weeks of combination nicotine replacement therapy (patch and lozenge) and are followed for 24 months. Participant recruitment commenced in December 2022 and is ongoing. Discussion This study builds on promising results from our recent trial which found that MAPS was associated with substantially higher abstinence from smoking at the end of the 12-month treatment period. Finding that this low-burden, personally tailored digital treatment adjuvant improves the long-term efficacy of MAPS would have important clinical and public health implications. Trial registration Clinical Trials Registry NCT05645146; https://clinicaltrials.gov/ct2/show/NCT05645146 ; Registered on December 9, 2022.

Understanding the neural components modulating feeding-related behavior and energy expenditure is crucial to combating obesity and its comorbidities. Neurons within the paraventricular nucleus of the hypothalamus (PVH) are a key component of the satiety response; activation of the PVH decreases feeding and increases energy expenditure, thereby promoting negative energy balance. In contrast, PVH ablation or silencing in both rodents and humans leads to substantial obesity. Recent studies have identified genetically-defined PVH subpopulations that control discrete aspects of energy balance (e.g. oxytocin (OXT), neuronal nitric oxide synthase 1 (NOS1), melanocortin 4-receptor (MC4R), prodynorphin (PDYN)). We previously demonstrated that non-OXT NOS1 PVH neurons contribute to PVH-mediated feeding suppression. Here, we identify and characterize a non-OXT, non-NOS1 subpopulation of PVH and peri-PVH neurons expressing insulin-receptor substrate 4 (IRS4 PVH ) involved in energy balance control. Using Cre-dependent viral tools to activate, trace and silence these neurons, we highlight the sufficiency and necessity of IRS4 PVH neurons in normal feeding and energy expenditure regulation. Furthermore, we demonstrate that IRS4 PVH neurons lie within a complex hypothalamic circuitry that engages distinct hindbrain regions and is innervated by discrete upstream hypothalamic sites. Overall, we reveal a requisite role for IRS4 PVH neurons in PVH-mediated energy balance which raises the possibility of developing novel approaches targeting IRS4 PVH neurons for anti-obesity therapies.

Background Incidence of skin cancer has been increasing among U.S. Hispanics, who often are diagnosed with larger lesions and at later stage disease. Behaviors to decrease exposure to ultraviolet radiation can reduce risk of skin cancer. We describe skin cancer prevention behaviors and psychosocial variables among Hispanic participants recruited into a skin cancer prevention trial. Methods Self-reported Hispanic participants from eight primary care clinics in Tampa, Florida and Ponce, Puerto Rico were recruited into a randomized controlled prevention trial. Information on demographics, sun-related behaviors, and psychosocial variables were collected before intervention materials were provided. Multivariable regression models were used to compare baseline sun-related behaviors and psychosocial variables across groups defined by geographic location and language preference. Results Participants reported low levels of intentional outdoor tanning, weekday and weekend sun exposure, and very low levels of indoor tanning. However, only a minority of participants practiced sun-protective behaviors often or always, and about 30% experienced a sunburn in the past year. Participants had low levels of recent worry and concern about skin cancer, modest levels of perceived risk and severity, and high levels of response efficacy and self-efficacy. When comparing across groups defined by geographic location and language preference, English-preferring Tampa residents (hereafter referred to as Tampeños) had the highest proportion who were sunburned (35.9%) and tended toward more risky behavior but also had higher protective behavior than did Spanish-preferring Tampeños or Puerto Ricans. Spanish-preferring Puerto Ricans had higher recent concern about skin cancer, comparative chance of getting skin cancer, and response efficacy compared to either English- or Spanish-preferring Tampeños. Spanish-preferring Tampeños had the highest levels of familism and recent distress about skin cancer. Conclusions Our results mirror previous observations of low levels of sun-protective behavior among U.S. Hispanics compelling the need for culturally appropriate and translated awareness campaigns targeted to this population. Because Hispanics in Tampa and Puerto Rico reported modest levels of perceived risk and severity, and high levels of response efficacy and self-efficacy, interventions aiming to improve skin cancer prevention activities that are anchored in Protection Motivation Theory may be particularly effective in this population subgroup.

The Abstinence-Related Motivational Engagement (ARME) scale was developed to assess motivation to remain abstinent after a smoking cessation attempt. The ARME demonstrated reliability and validity among a small sample of ex-smokers. This study expands the psychometric evaluation of the ARME and tests the ARME as a predictor of smoking status among a sample of participants quitting smoking. The parent trial tested the efficacy of a self-help smoking cessation intervention (N = 1874), with assessments every 6 months. Internal consistency and factor structure of the ARME was evaluated at each assessment to confirm use of the measure as designed. Discriminant validity was assessed by comparing the ARME to the Situation-specific Abstinence Self-Efficacy (SSE) scale via inter-correlations and prediction of future smoking status. Finally, the trajectories of both the ARME and SSE were compared among continuous abstainers and continuous smokers. A single-factor structure was observed at each assessment. Cronbach’s alphas ranged from 0.88–0.91 for the total sample. Correlations between the ARME and the SSE ranged from 0.38–0.47 ( p s <0.001) among smokers; and from 0.09–0.15 (most p s > 0.05) among abstainers. Among current smokers, the ARME and SSE were independent positive predictors of subsequent abstinence (AORs 1.28–2.29, p s <0.001). For those currently abstinent, only the SSE predicted subsequent abstinence (AORs 1.69–2.60, p s <0.05). GEE analyses showed different trajectories for the two measures, as well as between abstainers and smokers. In conclusion, the ARME is a reliable, valid measure with unique predictive utility for current smokers and a distinct trajectory among those who have successfully quit.