Arm injury in youth baseball players: a 10-year cohort study.

BACKGROUND: Arm injuries are commonly encountered in baseball as young athletes play into adulthood. The purpose of this study was to examine the incidence of arm injury and risk for surgery in adolescent baseball players followed over a 10-year period from scholastic, age-group, and travel baseball leagues through their highest level of competition. METHODS: A prospective study was conducted enrolling middle and high school baseball players in 2010-2012, then followed for 10 years or until retirement from competitive baseball. Players were included if fully participating in team activities at the time of preseason study enrollment. Players with prior arm (shoulder or elbow) surgery or those diagnosed with time loss arm injury within the past year were excluded. Only shoulder and elbow overuse problems resulting in time-loss from sport and medical attention from a sports medicine physician or orthopedic surgeon were documented as injuries in this study. Musculoskeletal overuse injuries were classified based on the orchard injury classification system. Incidence proportion and risk ratio (RR) and 95% confidence intervals (CIs) for initial injury and injuries requiring surgery were calculated. RESULTS: A total of 261 pitchers (age: 14.2 ± 2.6 years; follow-up: 4.2 ± 2.7 years) were enrolled. Twenty percent of the cohort was followed for ≥7 years. The overall injury incidence was 25.6/100 athletes (95% CI 21-31) with a cumulative surgical incidence of 5.4/100 athletes (95% CI 3.2-8.8). The risk of experiencing shoulder injury (n = 25) and elbow injury (n = 38) were similar (n = 38) (RR 0.7, 95% CI 0.4-1.1). The athletes also presented with a similar frequency of requiring surgery regardless of the injured body part. However, the risk of surgery in those playing beyond the high school level was 4.3 times greater (95% CI 1.2-15.0) than those only playing high school. CONCLUSION: This is the first study to follow a large cohort of youth baseball players as they progress, showing a relatively high arm injury incidence. Shoulder and elbow injury incidence was similar but surgical risk increased playing beyond high school, specifically for the elbow. The high injury frequency and burden of care required by young baseball players as reported in this study is concerning, and strategies to reduce injury should be investigated.

Comparative Transcriptomic Analyses of Developing Melanocortin Neurons Reveal New Regulators for the Anorexigenic Neuron Identity.

Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive. We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in mice. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons. Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role of Prdm12 in vivo, we developed and characterized a floxed Prdm12 allele. Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deletion of Prdm12 in adult POMC neurons showed that it is no longer required for Pomc expression or energy balance. Collectively, these findings establish a critical role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Finally, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the hypothalamus whose neurodevelopment remains poorly studied.SIGNIFICANCE STATEMENT POMC and NPY/AgRP neurons are derived from the same hypothalamic progenitors but have opposing effects on food intake. We profiled the transcriptomes of genetically labeled POMC and NPY/AgRP neurons in the developing mouse hypothalamus to decipher the transcriptional codes behind the versus orexigenic neuron identity. Our analyses revealed 29 transcription regulators that are selectively enriched in one of the two populations. We generated new mouse genetic models to selective ablate one of POMC-neuron enriched transcription factors Prdm12 in developing and adult POMC neurons. Our studies establish a previously unrecognized role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis.

CB1Rs in VMH neurons regulate glucose homeostasis but not body weight.

Cannabinoid 1 receptor (CB1R) inverse agonists reduce body weight and improve several parameters of glucose homeostasis. However, these drugs have also been associated with deleterious side effects. CB1R expression is widespread in the brain and in peripheral tissues, but whether specific sites of expression can mediate the beneficial metabolic effects of CB1R drugs, while avoiding the untoward side effects, remains unclear. Evidence suggests inverse agonists may act on key sites within the central nervous system to improve metabolism. The ventromedial hypothalamus (VMH) is a critical node regulating energy balance and glucose homeostasis. To determine the contributions of CB1Rs expressed in VMH neurons in regulating metabolic homeostasis, we generated mice lacking CB1Rs in the VMH. We found that the deletion of CB1Rs in the VMH did not affect body weight in chow- and high-fat diet-fed male and female mice. We also found that deletion of CB1Rs in the VMH did not alter weight loss responses induced by the CB1R inverse agonist SR141716. However, we did find that CB1Rs of the VMH regulate parameters of glucose homeostasis independent of body weight in diet-induced obese male mice.NEW & NOTEWORTHY Cannabinoid 1 receptors (CB1Rs) regulate metabolic homeostasis, and CB1R inverse agonists reduce body weight and improve parameters of glucose metabolism. However, the cell populations expressing CB1Rs that regulate metabolic homeostasis remain unclear. CB1Rs are highly expressed in the ventromedial hypothalamic nucleus (VMH), which is a crucial node that regulates metabolism. With CRISPR/Cas9, we generated mice lacking CB1Rs specifically in VMH neurons and found that CB1Rs in VMH neurons are essential for the regulation of glucose metabolism independent of body weight regulation.

Real-world characteristics of women with endometriosis-related pain entering a multidisciplinary endometriosis program.

BACKGROUND: Women with endometriosis are commonly treated by their sole provider. In this single-provider model of care, women frequently report long diagnostic delays, unresolved pelvic pain, multiple laparoscopic surgeries, sequential consultations with numerous providers, and an overall dissatisfaction with care. The emergence of multidisciplinary endometriosis centers aims to reduce diagnostic delays, improve pain management, and promote patient satisfaction; however, baseline data at the time of presentation to a multidisciplinary center are lacking. METHODS: A real-world, retrospective, single-site, cross-sectional study of women with surgically confirmed and/or clinically diagnosed endometriosis generated baseline data for a planned longitudinal assessment of multidisciplinary care of endometriosis. The primary objective was to determine the proportion of patients experiencing mild, moderate, or severe pain for dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia at entry into a multidisciplinary endometriosis clinic. Also explored were relationships between pain scores and clinical endpoints obtained from electronic medical records. RESULTS: More than half (59%) of the study participants (n = 638) reported experiencing pelvic pain for ≥ 5 years. Pain intensity was highest for patients reporting dysmenorrhea, followed by NMPP, and dyspareunia. Significant correlations were observed between total pelvic pain and patient age (r = -0.22, p < 0.001, n = 506) and number of previous healthcare providers (r = 0.16, p = 0.006, n = 292); number of previous providers and duration of pain (r = 0.21, p = < 0.0001, n = 279); and duration of pain and years since diagnosis (r = 0.60, p < 0.001, n = 302). Mean pain scores differed significantly by age group for dysmenorrhea (p < 0.001), NMPP (p = 0.005), and total pelvic pain (p < 0.001), but not for dyspareunia (p = 0.06), with the highest mean pain scores reported among those < 30 years of age. CONCLUSION: These real-world data indicate that in the single-provider model of care, unresolved pelvic pain is common among women with endometriosis. Alternative care models, including a multidisciplinary approach, need to be evaluated for improvements in clinical outcomes. These data also highlight the importance of addressing NMPP, which may be particularly troublesome for patients.

Development and internal validation of a humeral torsion prediction model in professional baseball pitchers.

BACKGROUND: Humeral torsion (HT) has been linked to pitching arm injury risk after controlling for shoulder range of motion. Currently measuring HT uses expensive equipment, which inhibits clinical assessment. Developing an HT predictive model can aid clinical baseball arm injury risk examination. Therefore, the purpose of this study was to develop and internally validate an HT prediction model using standard clinical tests and measures in professional baseball pitchers. METHODS: An 11-year (2009-2019) prospective professional baseball cohort was used for this study. Participants were included if they were able to participate in all practices and competitions and were under a Minor League Baseball contract. Preseason shoulder range of motion (external rotation [ER], internal rotation [IR], horizontal adduction [HA]) and HT were collected each season. Player age, arm dominance, arm injury history, and continent of origin were also collected. Examiners were blinded to arm dominance. An a priori power analysis determined that 244 players were needed for accurate prediction models. Missing data was low (<3%); thus, a complete case analysis was performed. Model development followed the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) recommendations. Regression models with restricted cubic splines were performed. Following primary model development, bootstrapping with 2000 iterations were performed to reduce overfitting and assess optimism shrinkage. Prediction model performance was assessed through root mean square error (RMSE), R2, and calibration slope with 95% confidence intervals (CIs). Sensitivity analyses included dominant and nondominant HT. RESULTS: A total of 407 professional pitchers (age: 23.2 [standard deviation 2.4] years, left-handed: 17%; arm history prevalence: 21%) participated. Predictors with the highest influence within the model include IR (0.4, 95% CI 0.3, 0.5; P < .001), ER (-0.3, 95% CI -0.4, -0.2; P < .001), HA (0.3, 95% CI 0.2, 0.4; P < .001), and arm dominance (right-handed: -1.9, 95% CI -3.6, -0.1; P = .034). Final model RMSE was 12, R2 was 0.41, and calibration was 1.00 (95% CI 0.94, 1.06). Sensitivity analyses demonstrated similar model performance. CONCLUSIONS: Every 3° of IR explained 1° of HT. Every 3° of ER explained 1° less of HT, and every 7° of HA explained 1° of HT. Right-handers had 2° less HT. Models demonstrated good predictive performance. This predictive model can be used by clinicians to infer HT using standard clinical test and measures. These data can be used to enhance professional baseball arm injury examination.

The Impact of Metal-Rich Sediments Derived from Mining on Freshwater Stream Life.

Metal-rich sediments have the potential to impair life in freshwater streams and rivers and, thereby, to inhibit recovery of ecological conditions after any remediation of mine water discharges. Sediments remain metal-rich over long time periods and have long-term potential ecotoxicological interactions with local biota, unless the sediments themselves are physically removed or replaced by less metal-rich sediment. Laboratory-derived environmental quality standards are difficult to apply to the field situation, as many complicating factors exist in the real world. Therefore, there is a strong case to consider other, field-relevant, measures of toxic effects as alternatives to laboratory-derived standards and to seek better biological tools to detect, diagnose and ideally predict community-level ecotoxicological impairment. Hence, this review concentrated on field measures of toxic effects of metal-rich sediment in freshwater streams, with less emphasis on laboratory-based toxicity testing approaches. To this end, this review provides an overview of the impact of metal-rich sediments on freshwater stream life, focusing on biological impacts linked to metal contamination.

Task-specific adaptations of postural sway in sitting infants.

When engaging in manual or visual tasks while sitting, infants modify their postural sway based on concurrent task demands. It remains unclear whether these modulations are sensitive to differences in concurrent task demands (holding a toy vs. looking at a toy being held by someone else), and whether the properties of the support surface impact these adaptations. We investigated infants' ability to modify postural sway when holding a toy or visually attending to a toy someone else was holding while sitting on different support surfaces. Twenty-six independently sitting infants sat on solid and compliant surfaces placed on a force plate while looking at or holding a toy. Measures of postural sway were calculated from the center of pressure data. Visually attending to a toy was associated with less sway and lower sway velocity than when holding a toy. Surprisingly, surface compliance did not affect sway and there were no interaction effects. Whereas sway modulations may facilitate infants' performance on both manual and visual concurrent tasks, the visual task placed more constraints on the postural system leading to greater adaptations in postural sway. These findings provide insights into how infants are allocating attention and coordinating perceptual-motor information in developing sitting skills.

Improved Performance of a Rapid Immunochromatographic Assay for Detection of PBP2a in Non-Staphylococcus aureus Staphylococcal Species.

Non-Staphylococcus aureus staphylococcal species (non-SASS) are important pathogens in both animal and human populations. The development of ß-lactam resistance in non-SASS through acquisition and expression of penicillin-binding protein 2a (PBP2a) represents a significant clinical and public health threat. Here, we evaluated the diagnostic performance of two versions of a PBP2a immunochromatographic assay with non-SASS. Our data show that the revised version of the assay, the PBP2a SA culture colony test, has superior diagnostic sensitivity compared to the previous version of the assay, the PBP2a culture colony test, 100% (95% confidence interval [CI], 93.3 to 100%) versus 67.9% (95% CI, 53.7 to 80.1%), respectively, while both assays display a specificity of 100% (95% CI, 92.5 to 100%). Therefore, the PBP2a SA culture colony test offers a rapid, accurate, and relatively inexpensive method for detecting PBP2a-mediated ß-lactam resistance in clinically relevant non-SASS for the management of infections due to these organisms and for antimicrobial stewardship.

The Effect of Holding an Object on Postural Stability and Suprapostural Task Performance.

Holding an object has been found to reduce postural sway during quiet standing. However, people normally stand to accomplish suprapostural goals, such as fitting a key into a lock. Postural control should therefore be assessed by examining postural outcomes in the context of suprapostural task performance. This study assessed whether holding an object increased standing postural stability and improved the performance of a concurrent precision manual task. A total of 15 young adults performed a precision manual task with their dominant hand while holding or not holding an object in their nondominant hand. Postural stability was assessed using measures of postural sway and time to boundary. Suprapostural task performance was assessed as an error count. Holding did not influence postural sway or suprapostural task performance. Discrepancies among previous studies coupled with the present findings suggest that the effects of holding an object on standing posture are highly sensitive to the experimental context. The authors provide several explanations for their findings and discuss the limitations of previous suggestions that holding an object may have clinical relevance for balance-compromised populations.

Effect of carrying objects on walking characteristics and language abilities in 13- and 24-month-olds.

Learning to walk leads to an increase in language abilities; however, the underlying mechanisms accounting for this relation remain unclear. Investigating the quality of early gait control may offer some insights. The purpose of this study was to (a) quantify how 13-month-olds (n = 39; 39% male) and 24-month-olds (n = 39; 59% male) adapt gait based on task (carrying vs. not carrying objects), object characteristics (size and weight), and environmental constraints (free play vs. structured) and to (b) assess how changes in gait relate to language abilities. To assess gait differences, Midwestern participants engaged in a free-play session and structured task with toys varying in size and weight while wearing motion capture markers. Parents completed an age-appropriate version of the MacArthur-Bates Communicative Development Inventory to measure language abilities. During free play, 13-month-olds were selective when choosing what to carry basing their decisions on object weight over size and adapting their upper-body control based on weight. Neither age group modified lower-body gait due to object characteristics but did reorganize their upper-body control. These upper-body adaptations were dependent upon age, environmental context, and task. Importantly, more mature upper-body control and more time spent in motion during free play were significant predictors of 13-month-olds' language abilities. Gait improvements may offer new opportunities for language learning; increased stability may allow young children to better focus on the objects, potentially enhancing word learning opportunities. Early movements and functional behavior during free play may be important predictors underlying the association between the onset of walking and language development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risky behavior during stair descent for young adults: Differences in men versus women.

Injuries commonly occur on stairs, with high injury rates in young adults, especially young women. High injury rates could result from physiological and/or behavioral differences; this study focuses on behaviors. The purposes of this observational study were (1) to quantify young adult behaviors during stair descent and (2) to identify differences in stair descent behavior for young adult men versus women. Young adult pedestrians (N = 2,400, 1,470 men and 930 women) were videotaped during descent of two indoor campus staircases, a short staircase (2 steps) and a long staircase (17 steps). Behaviors during stair descent were coded by experimenters. Risky behaviors observed on the short staircase included: No one used the handrail, 16.1% used an electronic device, and 16.4% had in-person conversations. On the long staircase: 64.8% of pedestrians did not use the handrail, 11.9% used an electronic device, and 14.5% had in-person conversations. Risky behaviors observed more in women included: less likely to use the handrail (long staircase), more likely to carry an item in their hands (both staircases), more likely to engage in conversation (both staircases), and more likely to wear sandals or heels (both staircases) (p≤0.05). Protective behaviors observed more in women included: less likely to skip steps (both staircases), and more likely to look at treads during transition steps (long staircase) (p≤0.05). The number of co-occurring risky behaviors was higher in women: 1.9 vs 2.3, for men vs women, respectively (p<0.001). Five pedestrians lost balance but did not fall; four of these pedestrians lost balance on the top step and all five had their gaze diverted from the steps at the time balance was lost. The observed behaviors may be related to the high injury rate of stair-related falls in young adults, and young women specifically.

What do macroinvertebrate indices measure? Stressor-specific stream macroinvertebrate indices can be confounded by other stressors.

Monitoring programmes worldwide use biota to assess the "health" of water bodies. Indices based on biota are used to describe the change in status of sites over time, to identify progress against management targets and to diagnose the causes of biological degradation. A variety of numerical stressor-specific biotic indices have been developed based on the response of biota to differences in stressors among sites. Yet, it is not clear how variation in pressures within sites, over what time period, and in what combination has the greatest impact on different biotic groups. An understanding of how temporal variation in pressures influences biological assessment indices would assist in setting achievable targets and help focus catchment-scale mitigation strategies to ensure that they deliver the desired improvements in biological condition.Hydrochemical data provided by a network of high-frequency (15 or 30 min) automated monitoring stations over 3 years were matched to replicated biological data to understand the influence of spatio-temporal variation in pollution pressures on biological indices. Hydrochemical data were summarised in various ways to reflect central tendency, peaks, troughs and variation over 1-90 days before the collection of each biological sample. An objective model selection procedure was used to determine which hydrochemical determinand, and over what time period, best explained variation in the biological indices.Stressor-specific indices derived from macroinvertebrates which purportedly assess stress from low flows, excess fine sediment, nutrient enrichment, pesticides and organic pollution were significantly inter-correlated and reflected periods of low oxygen concentration, even though only one index (ASPTWHPT, average score per taxon) was designed for this purpose. Changes in community composition resulting from one stressor frequently lead to confounding effects on stressor-specific indices.Variation in ASPTWHPT was best described by dissolved oxygen calculated as Q5 over 10 days, suggesting that low oxygen events had most influence over this period. Longer-term effects were apparent, but were masked by recovery. Macroinvertebrate abundance was best described by Q95 of stream velocity over 60 days, suggesting a slower recovery in numbers than in the community trait reflected by ASPTWHPT.Although use of ASPTWHPT was supported, we recommend that additional independent evidence should be used to corroborate any conclusions regarding the causes of degradation drawn from the other stressor-specific indices. The use of such stressor-specific indices alone risks the mistargeting of management strategies if the putative stressor-index approach is taken to be more reliable than the results herein suggest.

Juvenile social subjugation induces a sex-specific pattern of anxiety and depression-like behaviors in adult rats.

Child abuse is the most significant environmental risk factor for the development of mood disorders, which occur twice as frequently in women as in men. To determine whether juvenile social subjugation (JSS) of rats induces mood disorder-like symptoms, we exposed 28 day-old male and female rats to daily aggressive acts from aggressive male residents. Each rat received pins, kicks, and dominance postures from the resident for 10 min per day for 10 days. When the rats were adults, we tested their anxiety- and depression-like behaviors. In addition, we measured circulating basal and stress-evoked corticosterone (CORT) levels, and weighed the adrenal glands. Although the amount of JSS was indistinguishable between males and females, females were nonetheless more severely affected by the experience. Subjugated females became immobile more quickly during forced swim tests, and made fewer investigatory approaches during the social interaction test than control females. Juvenile social subjugation increased closed arm time in the elevated plus maze of males and females, but the effect of social subjugation was greater in females. Finally, stress-evoked CORT levels were significantly higher, and adrenal gland weights were significantly heavier, in subjugated females relative to their controls and to subjugated males. Our results demonstrate that JSS increases depression- and anxiety-like behaviors and sensitizes the stress response system in a sex-specific manner.

Dietary emulsifier consumption alters gene expression in the amygdala and paraventricular nucleus of the hypothalamus in mice.

Dietary emulsifier consumption promotes systemic low-grade inflammation, metabolic deregulation, and possibly an anxiety-like phenotype. The latter finding suggests that dietary emulsifiers impact brain areas that modulate stress responses. The goal of the current study was to test whether emulsifier consumption is associated with changes in gene expression in the amygdala and the paraventricular nucleus of the hypothalamus (PVN), two brain areas that are involved in behavioral and neuroendocrine responses to stress. Using RNA-Seq, we compared groups consuming either carboxymethylcellulose or polysorbate 80 for 12-weeks. A total of 243 genes were differentially expressed in the amygdala and PVN of emulsifier-treated mice compared to controls. There was minimal overlap of differentially expressed genes in CMC- and P80-treated animals, suggesting that each emulsifier acts via distinct molecular mechanisms to produce an anxiety-like phenotype. Furthermore, gene ontology and pathway analysis revealed that various stress, metabolic, and immune terms and pathways were altered by emulsifiers. These findings are the first to demonstrate that emulsifier consumption changes gene expression in brain regions that are critical for stress responding, providing possible molecular mechanisms that may underly the previously observed anxiety-like phenotype.

Normalized Isometric Shoulder Strength as a Predictor of Ball Velocity in Youth Baseball Players.

BACKGROUND: Despite increased awareness of factors related to athletic performance and injury prevention, youth and adolescent baseball players continue to report injuries at alarming rates. Upper extremity muscle strength is an integral part of physical assessment and injury prevention in baseball players, however minimal data exists in youth populations. Changes in anthropometric measures, inherent in physically developing athletes, have been shown to impact strength measures, however normalization methodology is rarely reported. PURPOSE: The purposes of this study were to 1) compare the measurement properties of five potential methods for normalizing isometric shoulder strength in a cohort of 9-12 year old male baseball players and 2) examine the relationship between normalized isometric shoulder strength and ball velocity in a cohort of 9-12 year old male baseball players. STUDY DESIGN: Prospective cohort study (n=159). METHODS: Baseline and follow up height, weight and bilateral ulnar length measurements were assessed followed by isometric strength in both the dominant and non-dominant shoulders. Strength measures included scapular plane abduction (scaption), external rotation (ER) at 0°, ER and internal rotation (IR) at 90°. Ball velocity was assessed as a measure of throwing performance. Intraclass correlation coefficients (ICC2,1), standard errors of measurement (SEM) and minimal detectable change (MDC95) were calculated for all strength measures. Repeated measures ANOVA were conducted comparing changes in normalized strength using five separate anthropometric measures: weight, height, body mass index, ulnar length and % of non-dominant shoulder strength. Linear regression models were used to examine the relationships between normalized isometric shoulder strength and ball velocity. Statistical significance was set a priori at α=0.05. RESULTS: Shoulder strength normalized using ulnar length was the only method that demonstrated excellent reliability (ICC2,1 0.98-0.99) and detected significant changes between strength in each of the four measures tested (SEM 0.39-0.69 Nm). Modest but significant correlations were observed between scaption and ball velocity (r2 = 0.27, p < 0.001) and ER at 0° and ball velocity (r2 = 0.23, p < 0.001). CONCLUSION: Ulnar length was the most stable and reliable normalization method for assessing isometric shoulder strength in youth baseball players. In addition, normalized scaption strength was the most significant predictor of ball velocity, followed by ER at 0° strength in this population. LEVEL OF EVIDENCE: Level 2b (etiology).

Delineating a serotonin 1B receptor circuit for appetite suppression in mice.

Triptans are a class of commonly prescribed antimigraine drugs. Here, we report a previously unrecognized role for them to suppress appetite in mice. In particular, frovatriptan treatment reduces food intake and body weight in diet-induced obese mice. Moreover, the anorectic effect depends on the serotonin (5-HT) 1B receptor (Htr1b). By ablating Htr1b in four different brain regions, we demonstrate that Htr1b engages in spatiotemporally segregated neural pathways to regulate postnatal growth and food intake. Moreover, Htr1b in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) contributes to the hypophagic effects of HTR1B agonists. To further study the anorexigenic Htr1b circuit, we generated Htr1b-Cre mice. We find that ARH Htr1b neurons bidirectionally regulate food intake in vivo. Furthermore, single-nucleus RNA sequencing analyses revealed that Htr1b marks a subset of AgRP neurons. Finally, we used an intersectional approach to specifically target these neurons (Htr1bAgRP neurons). We show that they regulate food intake, in part, through a Htr1bAgRP→PVH circuit.

Lasting effects of maternal behaviour on the distribution of a dispersive stream insect.

1. Predicting population dynamics at large spatial scales requires integrating information about spatial distribution patterns, inter-patch movement rates and within-patch processes. Advective dispersal of aquatic species by water movement is considered paramount to understanding their population dynamics. Rivers are model advective systems, and the larvae of baetid mayflies are considered quintessential dispersers. Egg laying of baetids along channels is patchy and reflects the distribution of oviposition sites, but larvae are assumed to drift frequently and far, thereby erasing patterns created during oviposition. Dispersal kernels are often overestimated, however, and empirical tests of such assumptions are warranted because of the pivotal role distribution patterns can have on populations. 2. We tested empirically whether the egg distribution patterns arising from oviposition behaviours persisted and were reflected in the distribution patterns of larval Baetis rhodani. In field surveys, we tested for associations between egg mass and larval densities over 1 km lengths of four streams. A control species, the mayfly Ephemerella ignita, was employed to test for covarying environmental factors. We estimated drift rates directly to test whether larvae dispersed between riffles (patches of high egg mass density) and whether drift rates were density-dependent or density-related - expected outcomes if drift erases patterns established by maternal behaviours. 3. Positive associations between egg masses and larval benthic densities were found for neonate and mid-stage larvae of Baetis, but not the control species, suggesting persistence of the patchy distribution patterns established at oviposition. Drift rates were high, and riffles were net exporters of neonate and mid-stage larvae, but drift rates were unrelated to benthic densities and few drifters reached the next riffle. Riffles were sinks for large larvae, suggesting ontogenetic shifts in habitat use, but little long-distance dispersal. 4. Overall, the results suggest that most neonate and mid-stage larvae of B. rhodani remain close to the natal riffle, and late-stage larvae disperse shorter distances than routinely assumed. The persistence of maternal effects on distribution patterns well into juvenile life of an allegedly iconic disperser suggests that traditional models of how dispersal influences the population dynamics of many lotic invertebrates may be incorrect.

The atypical antipsychotic risperidone targets hypothalamic melanocortin 4 receptors to cause weight gain.

Atypical antipsychotics such as risperidone cause drug-induced metabolic syndrome. However, the underlying mechanisms remain largely unknown. Here, we report a new mouse model that reliably reproduces risperidone-induced weight gain, adiposity, and glucose intolerance. We found that risperidone treatment acutely altered energy balance in C57BL/6 mice and that hyperphagia accounted for most of the weight gain. Transcriptomic analyses in the hypothalamus of risperidone-fed mice revealed that risperidone treatment reduced the expression of Mc4r. Furthermore, Mc4r in Sim1 neurons was necessary for risperidone-induced hyperphagia and weight gain. Moreover, we found that the same pathway underlies the obesogenic effect of olanzapine-another commonly prescribed antipsychotic drug. Remarkably, whole-cell patch-clamp recording demonstrated that risperidone acutely inhibited the activity of hypothalamic Mc4r neurons via the opening of a postsynaptic potassium conductance. Finally, we showed that treatment with setmelanotide, an MC4R-specific agonist, mitigated hyperphagia and obesity in both risperidone- and olanzapine-fed mice.

Accumulation of trace metals in freshwater macroinvertebrates across metal contamination gradients.

Historical mining activities cause widespread, long-term trace metal contamination of freshwater ecosystems. However, measuring trace metal bioavailability has proven difficult, because it depends on many factors, not least concentrations in water, sediment and habitat. Simple tools are needed to assess bioavailabilities. The use of biomonitors has been widely advocated to provide a realistic measure. To date there have been few attempts to identify ubiquitous patterns of trace metal accumulation within and between freshwater biomonitors at geographical scales relevant to trace metal contamination. Here we address this through a nationwide collection of freshwater biomonitors (species of Gammarus, Leuctra, Baetis, Rhyacophila, Hydropsyche) from 99 English and Welsh stream sites spanning a gradient of high to low trace metal loading. The study tested for inter-biomonitor variation in trace metal body burden, and for congruence amongst accumulations of trace metals within taxa and between taxa across the gradient. In general, significant differences in trace metal body burden occurred between taxa: Gammarus sp. was the most different compared with insect biomonitors. Bivariate relationships between trace metals within biomonitors reflected trace metal profiles in the environment. Strong correlations between some trace metals suggested accumulation was also influenced by physiological pathways. Bivariate relationships between insect biomonitors for body burdens of As, Cu, Mn and Pb were highly consistent. Our data show that irrespective of taxonomic or ecological differences, there is a commonality of response amongst insect taxa, indicating one or more could provide consistent measures of trace metal bioavailability.

Ingestion of probiotic (Lactobacillus helveticus and Bifidobacterium longum) alters intestinal microbial structure and behavioral expression following social defeat stress.

Social stress exacerbates anxious and depressive behaviors in humans. Similarly, anxiety- and depressive-like behaviors are triggered by social stress in a variety of non-human animals. Here, we tested whether oral administration of the putative anxiolytic probiotic strains Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces the striking increase in anxiety-like behavior and changes in gut microbiota observed following social defeat stress in Syrian hamsters. We administered the probiotic at two different doses for 21 days, and 16S rRNA gene amplicon sequencing revealed a shift in microbial structure following probiotic administration at both doses, independently of stress. Probiotic administration at either dose increased anti-inflammatory cytokines IL-4, IL-5, and IL-10 compared to placebo. Surprisingly, probiotic administration at the low dose, equivalent to the one used in humans, significantly increased social avoidance and decreased social interaction. This behavioral change was associated with a reduction in microbial richness in this group. Together, these results demonstrate that probiotic administration alters gut microbial composition and may promote an anti-inflammatory profile but that these changes may not promote reductions in behavioral responses to social stress.