Neighborhood Walkability, Historical Redlining, and Childhood Obesity in Denver, Colorado.

Childhood obesity is a precursor to future health complications. In adults, neighborhood walkability is inversely associated with obesity prevalence. Recently, it has been shown that current urban walkability has been influenced by historical discriminatory neighborhood disinvestment. However, the relationship between this systemic racism and obesity has not been extensively studied. The objective of this study was to evaluate the association of neighborhood walkability and redlining, a historical practice of denying home loans to communities of color, with childhood obesity. We evaluated neighborhood walkability and walkable destinations for 250 participants of the Healthy Start cohort, based in the Denver metropolitan region. Eligible participants attended an examination between ages 4 and 8. Walkable destinations and redlining geolocations were determined based on residential addresses, and a weighting system for destination types was developed. Sidewalks and trails in Denver were included in the network analyst tool in ArcMap to calculate the precise walkable environment for each child. We implemented linear regression models to estimate associations between neighborhood characteristics and child body mass index (BMI) z-scores and fat mass percent. There was a significant association between child BMI and redlining (ß: 1.36, 95% CI: 0.106, 2.620). We did not find an association between walkability measures and childhood obesity outcomes. We propose that cities such as Denver pursue built environment policies, such as inclusionary zoning and direct investments in neighborhoods that have been historically neglected, to reduce the childhood health impacts of segregated poverty, and suggest further studies on the influences that redlining and urban built environment factors have on childhood obesity.

Testosterone's Role in COVID-19.

COVID-19 consistently displays a higher mortality in males. This sex-specific difference in outcomes is seen not only in the current COVID-19 pandemic, but also in prior viral epidemics and pandemics. Sex hormones, such as testosterone, play a clear role in modulating the immune response, providing a clue that may illuminate the underpinnings of these outcomes. Developing a deeper understanding of these epidemiological findings permits a more effective response to the disease. This article summarizes the sex-specific COVID-19 outcomes, the role of androgens in generating these outcomes, and the potential role of modifying testosterone levels as a form of treatment of COVID-19. Auerbach JM, Khera M. Testosterone's Role in COVID-19. J Sex Med 2021;18:843-848.

Mathematical modeling reveals kinetics of lymphocyte recirculation in the whole organism.

The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours). Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism.

Post-Operative Order Set Decreases Opioid Prescriptions and Increases Efficiency.

BACKGROUND: Opioid addiction remains a public health crisis. We aimed to create an electronic medical record (EMR) based protocol to decrease post-operative prescribing of opioid medications and streamline the ordering process while maintaining adequate pain control. METHODS: An order set was created to minimize opioid prescriptions. The post-operative prescribing practices for minor urologic procedures (MUOs) over 6-week periods at three time points were compared: one period before and two periods after implementation of the order set. RESULTS: 72 MUOs were performed in the pre-implementation, 52 in post-implementation, and 60 in the long-term period. Opioid medications were prescribed for 66 patients (91.7%) pre-implementation, 23 patients (44.2%) post-implementation, and 45 patients (75.0%) at the long-term time point (P < .0001 and P = .015 respectively). The mean morphine milligram equivalent (MME) prescribed was 81.52 units before implementation, 38.74 units after, and 24.21 units at the long-term time point (P = .0002 and P < .0001 respectively). DISCUSSION: The integration of a post-operative prescribing order set into our EMR substantially decreased opioid prescribing after MUO while streamlining the ordering process to improve efficiency.

Testosterone replacement therapy and cardiovascular disease.

The use of testosterone therapy has a complex history of apprehension and questions regarding its safety. Despite an eventual consensus that testosterone therapy was safe and effective, several studies relating to cardiovascular risks emerged in the last decade, rekindling skepticism regarding the safety of testosterone therapy. Given the utility of testosterone therapy in treating the symptoms of hypogonadism, it remains crucial to closely examine the safety of testosterone therapy. The present article synthesizes the current evidence regarding cardiovascular risks that may be associated with testosterone therapy, the potential mechanisms regarding testosterone's efficacy, and future directions in evaluating the safety of its use.

Evaluating incidence, prevalence, and treatment trends in adult men with hypogonadism in the United States.

No extensive studies have investigated current diagnosis and treatment trends of hypogonadism (HG) in adult men in the United States. Using a comprehensive commercial insurance database, we surveyed current trends in incidence, prevalence, and treatment of hypogonadism in the United States. We analyzed insurance claims data from 2008-2017 using the IBM MarketScan™ Commercial Claims and Encounters database for men ≥18. Overall, we estimated annual incidence at 16.1 cases per 100,000 person-years, with the highest incidence seen among men 35-44 years at 21.5 cases per 100,000 person-years (IRR 1.83; 95% CI 1.63, 2.06, p < 0.001) and among those living in the Southern United States at 22.6 cases per 100,000 person-years (IRR 1.96; 95% CI 1.76, 2.18, p < 0.001). The prevalence of HG across the study period increased from 0.78% to 5.4%, while treatment rates decreased from 32.9% to 20.8%. These study findings provide a large-scale view of current diagnosis rates and treatment of hypogonadism in adult men in the United States. Despite the increase in prevalence of disease, there is an observed decline in treatment rates after diagnosis. Further investigations are needed to identify factors driving the observed decline in healthcare utilization among men with hypogonadism.

Local network connectivity optimization: an evaluation of heuristics applied to complex spatial networks, a transportation case study, and a spatial social network.

Optimizing global connectivity in spatial networks, either through rewiring or adding edges, can increase the flow of information and increase the resilience of the network to failures. Yet, rewiring is not feasible for systems with fixed edges and optimizing global connectivity may not result in optimal local connectivity in systems where that is wanted. We describe the local network connectivity optimization problem, where costly edges are added to a systems with an established and fixed edge network to increase connectivity to a specific location, such as in transportation and telecommunication systems. Solutions to this problem maximize the number of nodes within a given distance to a focal node in the network while they minimize the number and length of additional connections. We compare several heuristics applied to random networks, including two novel planar random networks that are useful for spatial network simulation research, a real-world transportation case study, and a set of real-world social network data. Across network types, significant variation between nodal characteristics and the optimal connections was observed. The characteristics along with the computational costs of the search for optimal solutions highlights the need of prescribing effective heuristics. We offer a novel formulation of the genetic algorithm, which outperforms existing techniques. We describe how this heuristic can be applied to other combinatorial and dynamic problems.

Hypogonadism management and cardiovascular health.

In the early days of its use, testosterone therapy faced skepticism regarding its safety and efficacy. After a converging consensus that testosterone therapy was safe and effective for the treatment of hypogonadism, several recent studies showed adverse cardiovascular outcomes associated with testosterone treatment, ultimately resulting in a mandated FDA label warning about the unknown safety of testosterone therapy. Given the clear efficacy of testosterone therapy in the treatment of hypogonadism, establishing the safety of this therapeutic tool is essential. This article summarizes the current evidence regarding the cardiovascular safety of testosterone therapy for the management of hypogonadism, as well as the proposed mechanisms that may explain testosterone's underlying effects.

Convergence to consensus in heterogeneous groups and the emergence of informal leadership.

When group cohesion is essential, groups must have efficient strategies in place for consensus decision-making. Recent theoretical work suggests that shared decision-making is often the most efficient way for dealing with both information uncertainty and individual variation in preferences. However, some animal and most human groups make collective decisions through particular individuals, leaders, that have a disproportionate influence on group decision-making. To address this discrepancy between theory and data, we study a simple, but general, model that explicitly focuses on the dynamics of consensus building in groups composed by individuals who are heterogeneous in preferences, certain personality traits (agreeability and persuasiveness), reputation, and social networks. We show that within-group heterogeneity can significantly delay democratic consensus building as well as give rise to the emergence of informal leaders, i.e. individuals with a disproportionately large impact on group decisions. Our results thus imply strong benefits of leadership particularly when groups experience time pressure and significant conflict of interest between members (due to various between-individual differences). Overall, our models shed light on why leadership and decision-making hierarchies are widespread, especially in human groups.

Thermodynamic characterization of dissociation rate variations of human leukocyte antigen and peptide complexes.

Stability of minor histocompatibility antigen-MHC molecule complexes is a major requirement for the successful presentation of the antigen to T cell receptors. In this letter we show thermodynamic features of the complexes made of a peptide antigen and its three variants to explain molecular basis of variable stability of the complexes. Our analysis suggests that enthalpy is a major factor in determining the stability of the complexes. We also found that the dissociation of the peptides from the complexes exhibits enthalpy-entropy compensation. Two structural features of the complexes, noncovalent chemical bondings and flexibility of the peptides in the complexes, are in a good agreement with our thermodynamic analysis. We expect thermodynamic investigation of peptide antigen-MHC protein complexes will provide valuable information on the stability.