Beyond words: Semantic satiation and the mental accessibility of the concept of suicide.

Disrupting the accessibility of the mental representation of suicide may be a possible pathway to a strategy for suicide prevention. Our study aims to theoretically evaluate this perspective by examining the impact of temporarily disrupting the concept of suicide on perceptions of suicide. Using a within-subject design, we tested the effects of semantic satiation targeting the word "suicide" on the perceptual judgment of suicide-relevant pictures in 104 young adults. On each trial, participants repeated aloud one of the three words (i.e., "accident," "murder," or "suicide") either three times (priming) or 30 times (satiation) and indicated whether a subsequent picture matched with the word. Results indicated that satiation of the word "suicide" slowed the accurate categorization of pictures related to all three words, and satiation of "murder" and "accident" delayed participants' judgment of suicide-relevant pictures. Our findings support that semantic satiation can render the suicide concept temporarily less accessible, thereby providing preliminary support for the strategy of concept disruption in suicide prevention.

Reversal of Obesity by Enhancing Slow-wave Sleep via a Prokineticin Receptor Neural Circuit.

Obese subjects often exhibit hypersomnia accompanied by severe sleep fragmentation, while emerging evidence suggests that poor sleep quality promotes overeating and exacerbates diet-induced obesity (DIO). However, the neural circuit and signaling mechanism underlying the reciprocal control of appetite and sleep is yet not elucidated. Here, we report a neural circuit where prokineticin receptor 2 (PROKR2)-expressing neurons within the parabrachial nucleus (PBN) of the brainstem received direct projections from neuropeptide Y receptor Y2 (NPY2R)-expressing neurons within the lateral preoptic area (LPO) of the hypothalamus. The RNA-Seq results revealed Prokr2 in the PBN is the most regulated GPCR signaling gene that is responsible for comorbidity of obesity and sleep dysfunction. Furthermore, those NPY2R LPO neurons are minimally active during NREM sleep and maximally active during wakefulness and REM sleep. Activation of the NPY2R LPO →PBN circuit or the postsynaptic PROKR2 PBN neurons suppressed feeding of a high-fat diet and abrogated morbid sleep patterns in DIO mice. Further studies showed that genetic ablation of the PROKR2 signaling within PROKR2 PBN neurons alleviated the hyperphagia and weight gain, and restored sleep dysfunction in DIO mice. We further discovered pterostilbene, a plant-derived stilbenoid, is a powerful anti-obesity and sleep-improving agent, robustly suppressed hyperphagia and promoted reconstruction of a healthier sleep architecture, thereby leading to significant weight loss. Collectively, our results unveil a neural mechanism for the reciprocal control of appetite and sleep, through which pterostilbene, along with a class of similarly structured compounds, may be developed as effective therapeutics for tackling obesity and sleep disorders.

Predictors of Listening-Related Fatigue in Adolescents With Hearing Loss.

PURPOSE: Self-reported listening-related fatigue in adolescents with hearing loss (HL) was investigated. Specifically, the extent to which listening-related fatigue is associated with school accommodations, audiologic characteristics, and listening breaks was examined. METHOD: Participants were 144 adolescents with HL ages 12-19 years. Data were collected online via Qualtrics. The Vanderbilt Fatigue Scale-Child was used to measure listening-related fatigue. Participants also reported on their use of listening breaks and school accommodations, including an Individualized Education Program (IEP) or 504 plan, remote microphone systems, closed captioning, preferential seating, sign language interpreters, live transcriptions, and notetakers. RESULTS: After controlling for age, HL laterality, and self-perceived listening difficulty, adolescents with an IEP or a 504 plan reported lower listening-related fatigue compared to adolescents without an IEP or a 504 plan. Adolescents who more frequently used remote microphone systems or notetakers reported higher listening-related fatigue compared to adolescents who used these accommodations less frequently, whereas increased use of a sign language interpreter was associated with decreased listening-related fatigue. Among adolescents with unilateral HL, higher age was associated with lower listening-related fatigue; no effect of age was found among adolescents with bilateral HL. Listening-related fatigue did not differ based on hearing device configuration. CONCLUSIONS: Adolescents with HL should be considered at risk for listening-related fatigue regardless of the type of hearing devices used or the degree of HL. The individualized support provided by an IEP or 504 plan may help alleviate listening-related fatigue, especially by empowering adolescents with HL to be self-advocates in terms of their listening needs and accommodations in school. Additional research is needed to better understand the role of specific school accommodations and listening breaks in addressing listening-related fatigue.

The transition from cranial surgery to neurosurgery in East London, 1760-1960.

The emergence of neurosurgery from the practice of cranial surgery between the eighteenth and the twentieth centuries in London, UK, is well documented, including the role of Sir Victor Horsley, the first neurosurgical appointee at the National Hospital Queen Square in 1886. The process of this transition elsewhere in London and the subsequent foundation of other neurosurgical units are less well described. In East London, the status of St. Bartholomew's Hospital (Barts) as the oldest London hospital still active on its original site and its comprehensive archives allow an unusually long history of surgical practice in the specialty to be studied. Using these archives and other primary and secondary sources, this article describes the transition of cranial surgery in East London from the general surgeons, limited to the treatment of brain and skull injury, to the specialized discipline of neurosurgery. We discuss the culmination of this process in the foundation of three neurosurgical units at London Hospital, Whitechapel, by Sir Hugh B. Cairns from 1927; at Barts Hospital, Smithfield, by John E. A. O'Connell from 1937; and at Oldchurch Hospital, Romford, by Leslie C. Oliver from 1945. Two modern neurosurgical units, in Whitechapel and Romford, have taken forward the work begun by this group.

The gene expression profile and cell of origin of canine peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) refers to a heterogenous group of T-cell neoplasms with poor treatment responses and survival times. Canine PTCL clinically and immunophenotypically resembles the most common human subtype, PTCL-not otherwise specified (PTCL-NOS), leading to interest in this canine disease as a naturally occurring model for human PTCL. Gene expression profiling in human PTCL-NOS has helped characterize this ambiguous diagnosis into distinct subtypes, but similar gene expression profiling in canine PTCL is lacking. METHODS: Bulk RNA-sequencing was performed on tumor samples from 33 dogs with either CD4+ (26/33), CD8+ (4/33), or CD4-CD8- (3/33) PTCL as diagnosed by flow cytometry, and sorted CD4+ and CD8+ lymphocytes from healthy control dogs. Following normalization of RNA-seq data, we performed differential gene expression and unsupervised clustering methods. Gene set enrichment analysis was performed to determine the enrichment of canine CD4+ PTCL for human PTCL-NOS, oncogenic pathways, and various stages of T-cell development gene signatures. We utilized gene set variation analysis to evaluate individual canine CD4+ PTCLs for various human and murine T-cell and thymocyte gene signatures. Cultured canine PTCL cells were treated with a pan-PI3K inhibitor, and cell survival and proliferation were compared to DMSO-treated controls. Expression of GATA3 and phosphorylated AKT was validated by immunohistochemistry. RESULTS: While the canine CD4+ PTCL phenotype exhibited a consistent gene expression profile, the expression profiles of CD8+ and CD4-CD8- canine PTCLs were more heterogeneous. Canine CD4+ PTCL had increased expression of GATA3, upregulation of its target genes, enrichment for PI3K/AKT/mTOR signaling, and downregulation of PTEN, features consistent with the more aggressive GATA3-PTCL subtype of human PTCL-NOS. In vitro assays validated the reliance of canine CD4+ PTCL cells on PI3K/AKT/mTOR signaling for survival and proliferation. Canine CD4+ PTCL was enriched for thymic precursor gene signatures, exhibited increased expression of markers of immaturity (CD34, KIT, DNTT, and CCR9), and downregulated genes associated with the T-cell receptor, MHC class II associated genes (DLA-DQA1, DLA-DRA, HLA-DQB1, and HLA-DQB2), and CD25. CONCLUSIONS: Canine CD4+ PTCL most closely resembled the GATA3-PTCL subtype of PTCL-NOS and may originate from an earlier stage of T-cell development than the more conventionally posited mature T-helper cell origin.

The virus be damned: Older adults seek romantic relationships during a pandemic.

COVID-19 was concerning for older adults because they faced greater health risks from the virus and generally experience higher rates of isolation and loneliness. Single older adults are of particular concern because they also lack a cohabiting partner for social connection, so they may face greater levels of loneliness. Many older adults have been using technology to develop and maintain social connections, including romantic connections, to mitigate these feelings of loneliness and isolation. This research explores how feelings of loneliness connect to use of online dating sites during a pandemic, how older adults decided to and rationalized dating at a time when meeting in-person and social interactions were discouraged and dangerous, and how experiences differed between men and women. I interviewed 50 men and 50 women, ages 60-83, about their experiences seeking partners and dating during the pandemic. All respondents were single, heterosexual, and recruited from online dating websites, but varied by race, education level, marital experience, employment status, and geographic location. Single older adults relied on feelings of loneliness and isolation, the ubiquity of online dating sites, and particularly for women, adherence to safety measures while on a date as motivation for seeking and meeting romantic partners during a pandemic. Single older adults seeking new romantic interactions during a pandemic, when health risks were greater, illustrates the importance of intimate relationships even into older age and how loneliness and isolation are powerful drivers in seeking romantic relationships.

Variables Associated With Resolution and Persistence of Ovarian Cysts.

OBJECTIVE: To estimate surveillance intervals of incident ovarian cysts, and describe variables associated with cyst resolution times. METHODS: The UK-OCST (University of Kentucky Ovarian Cancer Screening Trial) was a prospective cohort that enrolled 47,762 individuals over 30 years, including 2,638 individuals with incident cysts. Cyst diameter and structure and patient age, body mass index, use of hormone therapy (HT), family history of ovarian cancer, and menopausal status were examined as variables associated with cyst resolution using t tests, χ 2 test, Kaplan Meier, and Cox multiple regression. RESULTS: Of 2,638 individuals with incident cysts, 1,667 experienced resolution (63.2%) within 1.2 years, and 971 experienced persistence (36.8%). Within 1 year, unilocular and septated cysts had similar resolution rates (35.4% and 36.7%, respectively, P >.05), but time to resolution was shorter for unilocular cysts compared with septated cysts (mean 1.89 years vs 2.58 years, respectively, P <.001). Both unilocular and septated cysts smaller than 3 cm resolved faster than cysts larger than 6 cm ( P <.001). Variables associated with percent resolution included being of younger age, premenopausal status (but not for synchronous bilateral cysts), and those reporting a family history of ovarian cancer ( P <.05). Variables associated with a faster cyst resolution rate included being older than age 70 years and not using hormone therapy. Body mass index and family history were not associated with cyst resolution time. CONCLUSION: Different surveillance times may be appropriate depending on cyst structure and size and patient age and HT use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04473833.

GenPup-M: A novel validated owner-reported clinical metrology instrument for detecting early mobility changes in dogs.

OBJECTIVE: To use a previously validated veterinary clinical examination sheet, Liverpool Osteoarthritis in Dogs (LOAD) questionnaire, combined with kinetic and kinematic gait analysis in dogs with/without mobility problems to demonstrate the capacity of a novel clinical metrology instrument ("GenPup-M") to detect canine mobility impairments. DESIGN: Quantitative study. ANIMALS: 62 dogs (31 with mobility impairments and 31 without mobility impairments). PROCEDURE: The dogs' clinical history was obtained from owners and all dogs underwent a validated orthopaedic clinical examination. Mobility impairments were diagnosed in the mobility impaired group based on clinical history and orthopaedic examination. Owners were asked to complete GenPup-M along with a previously validated mobility questionnaire (Liverpool Osteoarthritis in Dogs (LOAD)) to identify construct validity. As a test of criterion validity, the correlation between instrument scores and the overall clinical examination scores, along with force-platform obtained peak vertical forces (PVF) were calculated. GenPup-M underwent internal consistency and factor analysis. Spatiotemporal parameters were calculated for dogs with/without mobility impairments to define the gait differences between these two groups. RESULTS: Principal Component Analysis identified GenPup-M had two components with Eigenvalues >1 ("stiffness/ease of movement" and "willingness to be active/exercise"). Cronbach's α was used to test internal consistency of GenPup-M and was found to be "good" (0.87). There was a strong, positive correlation between GenPup-M and LOAD responses (r2 = 0.69, p<0.001) highlighting construct validity. Criterion validity was also shown when comparing GenPup-M to clinical examination scores (r2 = 0.74, p<0.001) and PVF (r2 = 0.43, p<0.001). Quantitative canine gait analysis showed that there were statistically significant differences between peak vertical forces (PVF) of mobility impaired and non-mobility impaired dogs (p<0.05). Analyses of PVF showed that non-mobility impaired dogs more evenly distributed their weight across all thoracic and pelvic limbs when compared to mobility impaired dogs. There were also consistent findings that mobility impaired dogs moved slower than non-mobility impaired dogs. CONCLUSION AND CLINICAL RELEVANCE: GenPup-M is a clinical metrology instrument (CMI) that can be completed by dog owners to detect all mobility impairments, including those that are early in onset, indicating the versatility of GenPup-M to assess dogs with and without mobility impairments. Results of the study found that GenPup-M positively correlated with all three objective measures of canine mobility and consequently showed criterion and construct validity. Owner-reported CMIs such as GenPup-M allow non-invasive scoring systems which veterinary surgeons and owners can use to allow communication and longitudinal assessment of a dog's mobility. It is anticipated that GenPup-M will be used by owners at yearly vaccinations/health checks, allowing identification of any subtle mobility changes, and enabling early intervention.

Hydrocephalus in patients with vestibular schwannoma.

BACKGROUND: Hydrocephalus (HC) is common in patients with vestibular schwannoma (VS). This can be managed with a cerebrospinal fluid (CSF) diversion procedure prior to VS resection or with VS resection, keeping CSF diversion in reserve unless required postoperatively. No clear consensus exists as to which approach is superior. This study identifies factors predictive of the development of HC, and analyses outcomes for those managed with primary CSF resection versus tumour resection. METHODS: Single-centre retrospective cohort study of 204 consecutive adult patients with a unilateral VS from May 2009 to June 2021. Data was collected on patient and tumour demographics, management, and outcome. RESULTS: 204 patients, with a mean age at presentation of 59.5 (21-83), with 50% female, and a mean follow-up of 7.5 years (1.8-13.9) were included. 119 were managed conservatively, 36 with stereotactic radiosurgery only, and 49 with surgery. 30 (15%) patients had radiological HC, of which 23 (77%) were obstructive, and 7 (23%) were communicating. Maximum intracranial tumour diameter and Koos grade were higher in patients with HC. Of the patients with HC the majority (20, 67%) were managed initially with CSF diversion, with 12 patients undergoing subsequent tumour resection, and three patients avoiding primary resection. Nine (30%) were managed with primary surgical resection, of whom three required subsequent CSF diversion. Complication rates and Modified Rankin Scale (MRS) were comparable or lower in the CSF diversion group (8%, MRS ≤2 = 83%), versus the primary resection group (67%, MRS ≤2 = 67%), and the primary surgical resection without HC group (25%, MRS ≤2 = 86%). CONCLUSIONS: CSF diversion prior to tumour resection is a safe and acceptable strategy compared to primary VS resection, with improved outcomes and reduced surgical complications. Randomized studies and national databases are needed to determine the long-term outcomes of patients treated with CSF diversion versus primary resection.

Aberrant Arterial Anatomy at the Floor of the Third Ventricle: Video Case Report.

A 65-year-old woman presented with a 2-month progressive history of forgetfulness, headaches, and decline in mobility. Imaging showed a large, enhancing pineal region tumor with triventricular hydrocephalus. She underwent an endoscopic third ventriculostomy and biopsy after appropriate consent was gained. Video 1 demonstrates the endoscopic procedure during which 2 aberrant arteries were identified at the floor of the third ventricle. The endoscopic third ventriculostomy was performed between these 2 arteries with great care to preserve them. The patient improved postoperatively with resolution of the hydrocephalus. Histology showed a metastatic malignant melanoma. To the best of our knowledge, no similar anatomy has been shown in an endoscopic procedure. We speculate that these are perforating arteries from the posterior communicating artery (premamillary artery) or a branch from the first part of the posterior cerebral artery P1 (thalamoperforators). Other options include perforators from the ophthalmic segment of the internal carotid artery, the communicating segment of the internal carotid artery, the superior hypophyseal artery, or a branch of the medial posterior choroidal arteries. We look at each in turn.

The management of symptomatic hyperostotic bilateral spheno-orbital meningiomas: patient series.

BACKGROUND: The occurrence of hyperostotic bilateral spheno-orbital meningiomas (BSOMs) is very rare. Patients present with bilateral symptoms and require bilateral treatment. This series describes 6 patients presenting to 2 UK neurosurgical units and includes a literature review. To the best of the authors' knowledge, this is the largest series documented. OBSERVATIONS: This is a retrospective review of patients with BSOMs presenting between 2006 and 2023. Six females, whose mean age was 43 (range: 36-64) years, presented with features of visual disturbance. Bilateral sphen-oorbital meningiomas were identified. All patients underwent bilateral staged resections. The patients had an initial improvement in their symptoms. Extensive genetic testing was performed in 4 patients, with no variants in the NF2, LZTR1, SMARCB1, SMARCE1, and SMARCA4 genes or other variants detected. The mean follow-up was 100.3 (range: 64-186) months. Sixty-seven percent of patients had good long-term visual acuity. The progression rate was 75% and was particularly aggressive in 1 patient. Four patients required radiation therapy, and 2 needed further surgery. LESSONS: Hyperostotic BSOMs are extensive, challenging tumors causing significant disability. They can recur, with significant patient impact. Multidisciplinary management and indefinite long-term follow-up are essential. The biology of these tumors remains unclear. As molecular testing expands, the understanding of BSOM oncogenesis and potential therapeutic targets is likely to improve.

Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial.

INTRODUCTION: The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT. METHODS AND ANALYSIS: We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress. ETHICS AND DISSEMINATION: This study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group. TRIAL REGISTRATION NUMBER: ISRCTN41647111.

Pain, mental health and healthcare utilization: Impact of the COVID-19 pandemic on youth with chronic pain, parents and siblings.

BACKGROUND: Paediatric chronic pain was a public health emergency before the novel coronavirus (COVID-19) pandemic, and this problem is predicted to escalate. Pain tends to occur intergenerationally in families, and youth with chronic pain and their parents have high rates of mental health issues, which can further exacerbate pain. Siblings of youth with chronic pain have been largely overlooked in research, as well as the impact of the pandemic on posttraumatic stress disorder (PTSD) symptoms and healthcare utilization. METHODS: This cross-sectional study examined pain, mental health and healthcare utilization in three groups: youth with chronic pain (n = 357), parents of youth with chronic pain (n = 233) and siblings of youth with chronic pain (n = 156) during the COVID-19 pandemic in Canada. RESULTS: More so than with pain symptoms, the results revealed high levels of mental health symptoms (i.e. anxiety, depressive, and PTSD), particularly in individuals more personally impacted by the pandemic. The largest effect was seen on PTSD symptoms for all groups. For parents with chronic pain, greater personal COVID-19 impact was related to worse pain interference. Reported rates of healthcare utilization were strikingly high, with youth with chronic pain, parents (reporting on behalf of their children with chronic pain), and siblings of youth with chronic pain reporting that most consultations were due to pain. CONCLUSIONS: Longitudinal research assessing these outcomes across continued waves of the pandemic is needed to ensure timely, tailored and equitable access to pain and mental health assessment and treatment. SIGNIFICANCE: This study examined pain, mental health, substance use and healthcare utilization in youth with chronic pain, siblings and parents during the COVID-19 pandemic. Greater personal impact of the pandemic was not largely associated with poorer pain outcomes; however, it was associated with mental health, with the largest effect on PTSD symptoms. The high rates and significant association of COVID-19 impact with PTSD symptoms underscore the importance of including PTSD assessment as part of routine screening practices in pain clinics.

Laterality indices consensus initiative (LICI): A Delphi expert survey report on recommendations to record, assess, and report asymmetry in human behavioural and brain research.

Laterality indices (LIs) quantify the left-right asymmetry of brain and behavioural variables and provide a measure that is statistically convenient and seemingly easy to interpret. Substantial variability in how structural and functional asymmetries are recorded, calculated, and reported, however, suggest little agreement on the conditions required for its valid assessment. The present study aimed for consensus on general aspects in this context of laterality research, and more specifically within a particular method or technique (i.e., dichotic listening, visual half-field technique, performance asymmetries, preference bias reports, electrophysiological recording, functional MRI, structural MRI, and functional transcranial Doppler sonography). Experts in laterality research were invited to participate in an online Delphi survey to evaluate consensus and stimulate discussion. In Round 0, 106 experts generated 453 statements on what they considered good practice in their field of expertise. Statements were organised into a 295-statement survey that the experts then were asked, in Round 1, to independently assess for importance and support, which further reduced the survey to 241 statements that were presented again to the experts in Round 2. Based on the Round 2 input, we present a set of critically reviewed key recommendations to record, assess, and report laterality research for various methods.

Is physical pain causally related to suicidal behavior: An experimental test.

Existing evidence suggests a link between physical pain and suicide, but the nature of this relationship remains unknown. To address this critical gap in knowledge, the present study leveraged a validated virtual reality (VR) suicide paradigm to experimentally examine the causal effects of physical pain on subsequent virtual suicidal behaviors. Based on previous findings, we hypothesized that physical pain would causally drive virtual suicidal behavior only if suicide was conceptualized as having desirable anticipated consequences (e.g., a means of escaping from current pain; an opportunity to avoid future pain). We tested this by randomizing 326 participants across four different conditions: a physical pain condition, an anticipated escape condition, an anticipated avoidance condition, and a control condition. As predicted, physical pain alone did not result in statistically significant increases in VR suicide rates; however, the anticipation that virtual suicidal behavior would result in the avoidance of future physical pain had a large causal effect on VR suicide rates (B = 1.61, p < .001, IRR = 5.01). We failed to find evidence that anticipating that VR suicide would provide an escape from currently experienced physical pain increases the likelihood of VR suicide. Our findings add to a growing body of evidence suggesting that the anticipated consequences of suicide (e.g., avoidance of future physical pain) may serve as primary causes of suicidal behavior.

Identification of a GABAergic neural circuit governing leptin signaling deficiency-induced obesity.

The hormone leptin is known to robustly suppress food intake by acting upon the leptin receptor (LepR) signaling system residing within the agouti-related protein (AgRP) neurons of the hypothalamus. However, clinical studies indicate that leptin is undesirable as a therapeutic regiment for obesity, which is at least partly attributed to the poorly understood complex secondary structure and key signaling mechanism of the leptin-responsive neural circuit. Here, we show that the LepR-expressing portal neurons send GABAergic projections to a cohort of α3-GABAA receptor expressing neurons within the dorsomedial hypothalamic nucleus (DMH) for the control of leptin-mediated obesity phenotype. We identified the DMH as a key brain region that contributes to the regulation of leptin-mediated feeding. Acute activation of the GABAergic AgRP-DMH circuit promoted food intake and glucose intolerance, while activation of post-synaptic MC4R neurons in the DMH elicited exactly opposite phenotypes. Rapid deletion of LepR from AgRP neurons caused an obesity phenotype which can be rescued by blockage of GABAA receptor in the DMH. Consistent with behavioral results, these DMH neurons displayed suppressed neural activities in response to hunger or hyperglycemia. Furthermore, we identified that α3-GABAA receptor signaling within the DMH exerts potent bi-directional regulation of the central effects of leptin on feeding and body weight. Together, our results demonstrate a novel GABAergic neural circuit governing leptin-mediated feeding and energy balance via a unique α3-GABAA signaling within the secondary leptin-responsive neural circuit, constituting a new avenue for therapeutic interventions in the treatment of obesity and associated comorbidities.

Computer Prompt Software to Reduce Sedentary Behavior and Promote Physical Activity Among Desk-Based Workers: A Systematic Review.

OBJECTIVE: Do computer prompt software programs at the workplace reduce sitting time and/or increase physical activity at work? BACKGROUND: Many products are promoted and being used in the workplace; however, their effectiveness and use are unknown or the evidence base that they work to change behavior is lacking. METHOD: We searched for relevant papers published between 2005 and 2020. The inclusion criteria were computer prompt software programs installed as behavioral change interventions; interventions implemented during work hours and delivered through a work personal computer or laptop; and measures of sedentary behavior and/or physical activity. To minimize risk of bias, three recommended best-evidence synthesis criteria were used: random assignment, sample size, and external validity. Based on these criteria, articles were selected and evaluated. RESULTS: Six publications met the quality threshold for review. Seven articles did not meet the quality threshold. Four of the six included publications found that computer prompt software programs decreased sedentary behavior and/or increased physical activity. Two publications reported inconsistent results. CONCLUSIONS: The promising results from this systematic review indicate that there is potential for computer prompt software programs to improve the health of desk-based workers. For conclusive findings, more high-quality, scientific studies are needed. APPLICATION: The best-evidence publications in this review can serve as a guide in selecting and implementing computer prompt software programs at the workplace to decrease sedentary behavior and increase physical activity.