History and future of leptin: Discovery, regulation and signaling.

The cloning of leptin 30 years ago in 1994 was an important milestone in obesity research. Prior to the discovery of leptin, obesity was stigmatized as a condition caused by lack of character and self-control. Mutations in either leptin or its receptor were the first single gene mutations found to cause severe obesity, and it is now recognized that obesity is caused mostly by a dysregulation of central neuronal circuits. Since the discovery of the leptin-deficient obese mouse (ob/ob) the cloning of leptin (ob aka lep) and leptin receptor (db aka lepr) genes, we have learned much about leptin and its action in the central nervous system. The first hope that leptin would cure obesity was quickly dampened because humans with obesity have increased leptin levels and develop leptin resistance. Nevertheless, leptin target sites in the brain represent an excellent blueprint to understand how neuronal circuits control energy homeostasis. Our expanding understanding of leptin function, interconnection of leptin signaling with other systems and impact on distinct physiological functions continues to guide and improve the development of safe and effective interventions to treat metabolic illnesses. This review highlights past concepts and current emerging concepts of the hormone leptin, leptin receptor signaling pathways and central targets to mediate distinct physiological functions.

Gun-free zones and active shootings in the United States: a matched case-control study.

Background: Most Americans believe that gun-free zones make locations more vulnerable to violent crimes, particularly active shootings. However, there is no empirical evidence regarding the impact of gun-free zones on protecting locations from violence. The objective of this study was to estimate the association between gun-free zones and active shootings. Methods: We used a pair-matched case-control study where cases were all US establishments where active shootings occurred between 2014 and 2020, and controls were randomly selected US establishments where active shootings could have but did not occur, pair-matched by establishment type, year, and county. Gun-free status of included establishments was determined via local laws, company policy, news reporting, Google Maps and posted signage, and calling establishments. Findings: Of 150 active shooting cases, 72 (48.0%) were determined to have occurred in a gun-free zone. Of 150 controls where no active shooting occurred, 92 (61.3%) were determined to be gun-free. After accounting for matched pairs, the conditional odds of an active shooting in gun-free establishments were 0.38 times those in non-gun-free establishments, with a 95% confidence interval of 0.19-0.73 (p-value = 0.0038). Several robustness analyses affirmed these findings. Interpretation: It is unlikely that gun-free zones attract active shooters; gun-free zones may be protective against active shootings. This study challenges the proposition of repealing gun-free zones based on safety concerns. Funding: This work was funded in part by the National Collaborative on Gun Violence Research and the Arnold Foundation.

The Impact of Vacant and Abandoned Property on Health and Well-Being: A Qualitative Inquiry.

This qualitative study explored the role of neglected properties and neighborhood environment characteristics on a sample of New Orleans, Louisiana residents' health and well-being, sense of community, sense of safety, and civic engagement. We hypothesized that residents would identify conditions of their neighborhood's physical environment, including neglected properties, as one factor that impacted their health and other aspects of well-being. Seventy-four (N = 74) participants, including women, men, youth, young adults, and community leaders, took part in 11 focus groups (n = 51) and 23 key informant interviews. Thematic content analysis through inductive and deductive coding cycles of interview transcripts revealed five main categories related to urban neighborhood-built and social environments: 1) health and well-being, 2) sense of community, 3) sense of safety, 4) civic engagement, and 5) youth and family violence. Ten themes were developed and included, for example, the role of neighborhoods in delineating access to health-promoting characteristics and resources; the role of neighborhood social networks as crime prevention strategies; resident-led decision-making in neighborhood improvements; the negative impact of neglected properties; and the role of the local government in improving physical infrastructure. These findings affirm that residents were aware of and impacted by the cyclical nature of built environment neglect on health and well-being, community violence, neighborhood cohesion, civic engagement, and youth violence. Participants recommended improving neighborhood conditions to shift resident mindsets about the health of neighborhoods, reduce violence, and improve quality of life.

Temperature and firearm violence in four US cities: testing competing hypotheses.

INTRODUCTION: Firearm violence is a major public health issue in the USA. There is growing evidence that firearm violence is associated with higher ambient temperatures. The aim of this study was to test competing hypotheses that could explain associations between temperature and firearm violence: temperature-aggression theory and routine activities theory. METHODS: We examined associations between elevated daily temperatures and shooting incidents in four US cities: Chicago, Illinois; Cincinnati, Ohio; New York, New York and Philadelphia, Pennsylvania. Temperature was operationalised using two different measures: daily maximum temperature and deviations of the daily maximum temperature from 30-year averages. Generalised linear autoregressive moving average models related temperature to shooting incidence while controlling for seasonal effects. RESULTS: As maximum daily temperature deviates from the expected, there was an association with increased shooting incidents in all four cities (eg, New York: b=0.014, 95% CI=0.011 to 0.017). An interaction term created by multiplying daily maximum temperature by the daily difference of maximum temperature from a 30-year average was also found to have a positive association in all four cities (eg, New York: b=0.020, 95% CI=0.016 to 0.025). DISCUSSION: These findings accord with previous studies demonstrating a positive relationship between temperature and firearm violence and further support temperature-aggression theory as the primary causal mechanism.

The association between street construction projects and community violence in New York City.

Introduction: Community violence is a major cause of injury and death in the United States. Empirical studies have identified that some place-based interventions of urban private places, such as remediations of vacant lots and buildings, are associated with reductions in community violence in surrounding areas. The aim of this study was to examine whether routine maintenance and repair of urban public places (e.g., street construction projects) are also associated with reductions in community violence, proxied by violent crime. Method: This staggered adoption difference-in-difference analysis investigated the association between street construction projects and community violence in New York City from 2010-2019, divided into 40 calendar quarters. The units of analysis were street-quarters (n = 155,280). Intervention street-quarters were those with completed projects in 2010-2019; control streets were those where projects were scheduled but not completed before 2019. The outcome of community violence was proxied by counts of crime and violence incidents reported to the New York Police Department, within street-quarters. Results: There were 79,592 street-quarters with any community violence incidents (51.2%). We found that street construction projects were associated with a decrease in reckless endangerment (ATT = -0.013; 95% CI = -0.021, -0.004), robbery (ATT = -0.035; 95% CI = -0.063, -0.007), and weapons offenses (ATT = -0.016; 95% CI = -0.031, -0.001) occurring on street-quarters. Conclusion: Street construction projects may be yet another type of place-based intervention to reduce community violence.

Building a Culture of Health Through the Built Environment: Impact of a Cluster Randomized Trial Remediating Vacant and Abandoned Property on Health Mindsets.

Changing built environment conditions to impact health mindsets and health equity may be a promising target for public health interventions. The present study was a cluster randomized controlled trial to test the impact of remediating vacant and abandoned properties on factors related to health mindset-including well-being, health interconnectedness, social capital markers, neighborhood disorder and worry-as well as direct and indirect violence experiences and the moderating role of racial and income segregation on outcomes. A residential cohort of 405 participants from 194 randomly assigned geographic clusters were surveyed over five waves from 2019 to 2023. Compared to clusters with no treatment, participants in clusters where both vacant lots and abandoned homes were treated experienced significant increases in sense of community (83%, 95% CI=71 to 96%, p=0.01). Among participants in randomization clusters where only vacant lots were treated, there were declines in perceived neighborhood disorder (-55%, 95% CI=-79 to -5, p=0.06) and worry about community violence (-56%, 95% CI=-58 to - 12, p=0.06). There was also a moderating effect of racial and income spatial polarization, with the greatest changes in sense of community observed among more deprived areas with both homes and lots treated; and the largest changes in neighborhood worry and disorder were seen in more deprived areas with only lots treated. Remediation of vacant and abandoned properties may be one approach to change some but not all mindsets around health, and the effects may depend on the type of remediation as well as larger neighborhood conditions such segregation.

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling.

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (Klb Cam2ka ) mice. Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger activation as compared to casein in control-fed mice, whereas casein triggered a larger activation in protein-restricted mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21-KO mice. These data strongly suggest that the increased FGF21 during protein restriction acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.

Systematic disparities in reporting on community firearm violence on local television news in Philadelphia, PA, USA.

Objective: To better understand how community firearm violence (CFV) is communicated to the public, we aimed to identify systematic differences between the characteristics of shooting victims and events covered on television news and all shootings in Philadelphia, PA, a city with escalating CFV incidence. Methods: We compiled a stratified sample of local television news clips covering shootings that occurred in Philadelphia aired on two randomly selected days per month from January-June 2021 (n = 154 clips). We coded the clips to determine demographic and geographic information about the shooting victims and events and then matched coded shootings with corresponding shootings in the Philadelphia police database. We compared characteristics of shooting victims and shooting event locations depicted in television clips (n = 62) with overall characteristics of shootings in Philadelphia during the study period (n = 1082). Results: Compared to all individuals shot, victims whose shootings were covered on local television news more likely to be children and more likely to be shot in a mass shooting. The average median household income of shooting locations featured on television was significantly higher than the median household income across all shooting locations ($60,302 for television shootings vs. $41,233 for all shootings; p = 0.002). Shootings featured on television occurred in areas with lower rates of income inequality and racialized economic segregation compared to all shooting locations. Conclusions: Television news outlets in Philadelphia systematically over-reported shootings of children, mass shootings, and shootings that occurred in neighborhoods with higher median household income, less socioeconomic inequality, and lower rates of racialized economic segregation.

FGF21 as a mediator of adaptive changes in food intake and macronutrient preference in response to protein restriction.

Free-feeding animals navigate complex nutritional landscapes in which food availability, cost, and nutritional value can vary markedly. Animals have thus developed neural mechanisms that enable the detection of nutrient restriction, and these mechanisms engage adaptive physiological and behavioral responses that limit or reverse this nutrient restriction. This review focuses specifically on dietary protein as an essential and independently defended nutrient. Adequate protein intake is required for life, and ample evidence exists to support an active defense of protein that involves behavioral changes in food intake, food preference, and food motivation, likely mediated by neural changes that increase the reward value of protein foods. Available evidence also suggests that the circulating hormone fibroblast growth factor 21 (FGF21) acts in the brain to coordinate these adaptive changes in food intake, making it a unique endocrine signal that drives changes in macronutrient preference in the context of protein restriction. This article is part of the Special Issue on "Food intake and feeding states".

Physical environmental roadway interventions and injury and death for vulnerable road users: a natural experiment in New York City.

INTRODUCTION: This study examined the effectiveness of three physical environmental roadway interventions (enhanced crossings, speed humps, and turn traffic calming) in preventing crashes involving pedestrian and cyclist injury and mortality in New York City. METHODS: We examined crashes that occurred within a 100-foot radius of intervention and control sites from 2015 to 2019. We used a staggered difference-in-difference design to estimate the association between each intervention type and pedestrian and cyclist crash outcomes. RESULTS: Estimates for enhanced crossings and speed humps included the possibility of no association with crashes, but estimates for turn traffic calming interventions showed reduced odds of crashes involving pedestrian injury by 16% (OR 0.84, 95% CI 0.74 to 0.95) and crashes involving pedestrian fatality by 80% (OR 0.20, 95% CI 0.08 to 0.47). When stratifying by street segment length as a proxy for areas with high speeding risk, turn traffic calming treatments appeared to be most effective at intersections connected to long street segments. DISCUSSION: Turn traffic calming may substantially reduce crash risks for pedestrians. Municipalities can prioritise this physical environmental intervention, especially at turns near long street segments, as a low-cost intervention with substantial public health impact.

Attitudes of women towards intimate partner violence in Guyana: A cross-sectional analytical study.

BACKGROUND: To assess the attitudes of women towards intimate partner violence (IPV) in Guyana. METHODS: We used national data from the publicly available Multiple Indicator Cluster Survey (MICS) conducted in Guyana in 2019 for women aged 15 to 49 years. The prevalence of women who agreed that a husband is justified in beating his wife was analyzed. Respondent reasons included if she: "goes out without telling him", "neglects the children", "argues with him", "refuses sex with him", "burns the food", "has another partner", "stays out late/partying", "refuses to cook or clean", "overspends", and/or "he doesn't have access to her cellphone". Descriptive analyses were carried for all the variables. Logistic regression was used to identify factors associated with these 10 respondent reasons, separately and in combination. RESULTS: The overall prevalence of women's attitudes justifying IPV against women if there was a 'yes' response to any of the 10 reasons was 17.9% (95%CI: 16.6-19.3%), and varied from 2.7% if she "goes out without telling him", "burns the food", or "overspends" to 10.0% if she "has another partner". This prevalence ranged from 10.2% in urban areas to 19.3% in rural areas (p<0.001), and from 16.1% in coastal to 30.1% in interior areas (p<0.001). Similarly, 25.9% of women from the poorest household agreed that a husband has the right in beating his wife for any of the 10 reasons compared to 11.6% of the richest women (11.6%) (p<0.001). Rural place of residence, ethnicity, geographic region, level of education, wealth quintile, ever used of a computer, and frequency of listening to the radio were significant factors associated with women's attitudes justifying IPV against women (p<0.05). CONCLUSION: Over one-sixth of the respondents agreed that a husband was justified in committing IPV against women in Guyana. Public health programs focusing on geographic locations, ethnicity, and economic status must be implemented to change attitudes justifying IPV and reduce this significant public health challenge.

From neighborhood to household: connections between neighborhood vacant and abandoned property and family violence.

Rates of family violence, including intimate partner violence (IPV) and child maltreatment, remain high in the U.S. and contribute to substantial health and economic costs. How neighborhood environment may influence family violence remains poorly understood. We examine the association between neighborhood vacant and abandoned properties and family violence, and the role collective efficacy may play in that relationship. Data were used from a longitudinal cohort of 218 maternal-child dyads in a southern U.S. city known for elevated rates of violence. Women were matched on their propensity score, for living in a neighborhood with elevated vacant and cited properties. Analyses accounting for clustering in neighborhood and matched groups were conducted to examine the association between neighborhood vacant and abandoned property and family violence, and the potential mediating relationship of collective efficacy. The likelihood of experiencing child maltreatment at 12-months of age was more than twice as high for children living in neighborhoods with a high vacant and cited property rates compared to women living in neighborhoods with fewer vacant and cited properties (OR=2.11, 95% CI=1.03, 4.31). Women living in neighborhoods characterized by high levels of vacant and cited properties were also more than twice as likely to report IPV (OR=2.52, 95% CI=1.21, 5.25). Associations remained mostly stable after controlling for key covariates. Collective efficacy did not act as a mediator in the relationship between vacant and cited properties and family violence. Reducing neighborhood vacant and cited properties may be an important target for interventions focused on reducing family violence.

Hepatic interoception in health and disease.

The liver is a large organ with crucial functions in metabolism and immune defense, as well as blood homeostasis and detoxification, and it is clearly in bidirectional communication with the brain and rest of the body via both neural and humoral pathways. A host of neural sensory mechanisms have been proposed, but in contrast to the gut-brain axis, details for both the exact site and molecular signaling steps of their peripheral transduction mechanisms are generally lacking. Similarly, knowledge about function-specific sensory and motor components of both vagal and spinal access pathways to the hepatic parenchyma is missing. Lack of progress largely owes to controversies regarding selectivity of vagal access pathways and extent of hepatocyte innervation. In contrast, there is considerable evidence for glucose sensors in the wall of the hepatic portal vein and their importance for glucose handling by the liver and the brain and the systemic response to hypoglycemia. As liver diseases are on the rise globally, and there are intriguing associations between liver diseases and mental illnesses, it will be important to further dissect and identify both neural and humoral pathways that mediate hepatocyte-specific signals to relevant brain areas. The question of whether and how sensations from the liver contribute to interoceptive self-awareness has not yet been explored.

Trends in police complaints and arrests on New York City subways, 2018 to 2023: an interrupted time-series analysis.

BACKGROUND: Public transportation use is influenced by perceptions of safety. Concerns related to crime on New York City (NYC) transit have risen following NYC's COVID-19 pandemic state of emergency declaration in 2020, leading to declines in subway ridership. In response, the most recent mayoral administration implemented a Subway Safety Plan in 2022. This study aimed to quantify the effects of the COVID-19 pandemic and the Subway Safety Plan on rates of complaints to and arrests by the New York City Police Department (NYPD) Transit Bureau. METHODS: Using publicly available data on complaints and arrests, we conducted interrupted time-series analyses using autoregressive integrated moving average models applied to monthly data for the period from September 2018 to August 2023. We estimated changes in the rates of complaints to and arrests by the NYPD Transit Bureau before and after: (1) the COVID-19 pandemic state of emergency declaration (i.e., March 2020), and (2) the announcement of the Subway Safety Plan (i.e., February 2022). We also examined trends by complaint and arrest type as well as changes in proportion of arrests by demographic and geographic groups. RESULTS: After the COVID-19 pandemic declaration, there was an 84% increase (i.e., an absolute increase of 6.07 per 1,000,000 riders, CI 1.42, 10.71) in complaints to the NYPD Transit Bureau, including a 99% increase (0.91 per 1,000,000 riders, CI 0.42, 1.41) in complaints for assault and a 125% increase in complaints for harassment (0.94 per 1,000,000 riders, CI 0.29, 1.60). Following the Subway Safety Plan there was an increase in the rate of arrests for harassment (0.004 per 1,000,000 riders, CI 0.001, 0.007), as well as decreases in the proportion of arrests for individuals racialized as White (- 0.02, CI - 0.04, - 0.01) and proportion of arrests in the borough of Manhattan (- 0.13, CI - 0.17, - 0.09). CONCLUSIONS: The increased rates of complaints to the NYPD Transit Bureau following the onset of the COVID-19 pandemic remained elevated following the enactment of the Subway Safety Plan. Further evaluation efforts can help identify effective means of promoting safety on public transportation.

Gene Expression Patterns Associated with Survival in Glioblastoma.

The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (COL1A2, IGFBP3, NGFR, and WIF1) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank p-value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank p-value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.

Interstate Highway Connections and Traced Gun Transfers Between the 48 Contiguous United States.

Importance: Interstate gun flow has critical implications for gun violence prevention, as gun transfers across state lines can undermine local gun control policies. Objective: To identify possible gun trafficking routes along interstate highways in the US. Design, Setting, and Participants: This repeated-measures, ecological, cross-sectional study used data from the Bureau of Alcohol, Tobacco, Firearms and Explosives from January 1, 2010, to December 31, 2019, to examine associations between interstate connections via 13 highways that each spanned at least 1000 miles and interstate traced gun transfer counts for the 48 contiguous United States. Analyses were completed in November 2023. Exposures: Characteristics of the origin states and the transportation connections between the destination state and the origin states. Main Outcomes and Measures: The main outcome was the total count of guns used in crimes in each destination state per year that were originally purchased in the origin state. Bayesian conditional autoregressive Poisson models were used to examine associations between the count of guns used in crime traced to interstate purchases and interstate highway connections between origin and destination states. Results: Between 2010 and 2019, 526 801 guns used in crimes in the contiguous 48 states were traced to interstate purchases. Northbound gun transfers along the Interstate 95 corridor were greater than expected to New Jersey (incidence rate ratio [IRR], 2.80; 95% credible interval [CrI], 1.01-7.68) and Maryland (IRR, 3.07; 95% CrI, 1.09-8.61); transfers were similarly greater along Interstate 15 southbound, Interstate 25 southbound, Interstate 35 southbound, Interstate 75 northbound and southbound, Interstate 10 westbound, and Interstate 20 eastbound and westbound. Conclusions and Relevance: This repeated-measures, ecological, cross-sectional study identified that guns used in crimes traced to interstate purchases moved routinely between states along multiple major transportation routes. Interstate gun transfers are a major contributor to gun crime, injury, and death in the US. National policies and interstate cooperation are needed to address this issue.

Defining Spatial Epidemiology: A Systematic Review and Re-orientation.

BACKGROUND: Spatial epidemiology has emerged as an important subfield of epidemiology over the past quarter century. We trace the origins of spatial epidemiology and note that its emergence coincided with technological developments in spatial statistics and geography. We hypothesize that spatial epidemiology makes important contributions to descriptive epidemiology and analytic risk-factor studies but is not yet aligned with epidemiology's current focus on causal inference and intervention. METHODS: We conducted a systematic review of studies indexed in PubMed that used the term "spatial epidemiolog*" in the title, abstract, or keywords. Excluded articles were not written in English, examined disease in animals, or reported biologic pathogen distribution only. We coded the included papers into five categories (review, demonstration of method, descriptive, analytic, and intervention) and recorded the unit of analysis (i.e., individual vs. ecological). We additionally examined articles coded as analytic ecologic studies using scales for lexical content. RESULTS: A total of 482 articles met the inclusion criteria, including 76 reviews, 117 demonstrations of methods, 122 descriptive studies, 167 analytic studies, and 0 intervention studies. Demonstration studies were most common from 2006 to 2014, and analytic studies were most common after 2015. Among the analytic ecologic studies, those published in later years used more terms relevant to spatial statistics (incidence rate ratio =1.3; 95% confidence interval [CI] = 1.1, 1.5) and causal inference (incidence rate ratio =1.1; 95% CI = 1.1, 1.2). CONCLUSIONS: Spatial epidemiology is an important and growing subfield of epidemiology. We suggest a re-orientation to help align its practice with the goals of contemporary epidemiology.