Tumors, Treatments, and Trust: Cancer Characteristics, Outcomes, and Screening Uptake in Transgender and Gender-Diverse Patients.

BACKGROUND: More than 2.5 million adults in the United States identify as transgender or gender-diverse (TGD), but little data exist on cancer screening and care for this population. We examined cancer characteristics, screening adherence, genetic testing, and provider inclusive language for TGD patients with cancer. METHODS: This single institution retrospective cohort study identified TGD patients with cancer between 2000 and 2022. Demographic, clinicopathological, treatment, and screening data were collected, as well as data on gender-affirming care (GAC) and use of patients' personal pronouns in medical records. Descriptive statistics and regression analyses were used to report outcomes. RESULTS: Sixty unique patients with 69 cancer diagnoses were included: 63.3% were transgender women, 21.7% transgender men, 6.7% nonbinary, and 8.3% were genderqueer. Sixty-five percent had a family history of cancer. Only 46.2% of those who met genetic testing criteria were referred. On review of recommended cancer screening, colorectal screening had the greatest uptake (62%), followed by breast (48.3%), lung (35.7%), cervical (33.3%), and prostate (32%); 8.5% of cancers were diagnosed on screening. Individuals with Medicare had reduced odds of screening uptake (OR 0.07, 95% CI 0.01-0.58) versus private insurance. With respect to GAC, 73.3% used gender-affirming hormone therapy and 41% had gender-affirming surgery. After initiating GAC and asserting personal pronouns, 75% were referred to by incorrect name/pronouns in provider documentation. CONCLUSIONS: Our TGD cancer patient cohort had low rates of disease-specific cancer screening and inadequate genetic referrals. Many providers did not use appropriate patient names/pronouns. Provider and patient interventions are needed to ensure inclusive preventative and oncologic care for this marginalized population.

Early-life sodium deprivation programs long-term changes in ingestive behaviors and energy expenditure in C57BL/6J mice.

Postnatal growth failure remains a significant problem for infants born prematurely, despite aggressive efforts to improve perinatal nutrition. Though often dysregulated in early life when children are born preterm, sodium (Na) homeostasis is vital to achieve optimal growth. We hypothesize that insufficient Na supply in this critical period contributes to growth restriction and programmed risks for cardiometabolic disease in later adulthood. Thus, we sought to ascertain the effects of prolonged versus early-life Na depletion on weight gain, body composition, food and water intake behaviors, and energy expenditure in C57BL/6J mice. In one study, mice were provided a low (0.04%)- or normal/high (0.30%)-Na diet between 3 and 18 wk of age. Na-restricted mice demonstrated delayed growth and elevated basal metabolic rate. In a second study, mice were provided 0.04% or 0.30% Na diet between 3 and 6 wk of age and then returned to standard (0.15%)-Na diet through the end of the study. Na-restricted mice exhibited growth delays that quickly caught up on return to standard diet. Between 6 and 18 wk of age, previously restricted mice exhibited sustained, programmed changes in feeding behaviors, reductions in total food intake, and increases in water intake and aerobic energy expenditure while maintaining normal body composition. Although having no effect in control mice, administration of the ganglionic blocker hexamethonium abolished the programmed increase in basal metabolic rate in previously restricted mice. Together these data indicate that early-life Na restriction can cause programmed changes in ingestive behaviors, autonomic function, and energy expenditure that persist well into adulthood.

Risk of post-vasectomy infections in 133,044 vasectomies from four international vasectomy practices.

OBJECTIVES: To estimate the risk of post-vasectomy infections in various settings and across various surgical techniques and sanitization practices. PATIENTS AND METHODS: Retrospective review of the records of 133,044 vasectomized patients from four large practices/network of practices using the no-scalpel vasectomy (NSV) technique in Canada (2011-2021), Colombia (2015-2020), New Zealand (2018-2021), and the United Kingdom (2006-2019). We defined infection as any mention in medical records of any antibiotics prescribed for a genital or urinary condition following vasectomy. RESULTS: Post-vasectomy infection risks were 0.8% (219 infections/26,809 procedures), 2.1% (390/18,490), 1.0% (100/10,506), and 1.3% (1,007/77,239) in Canada, Colombia, New Zealand, and the UK, respectively. Audit period comparison suggests a limited effect on the risk of infection of excising a short vas segment, applying topical antibiotic on scrotal opening, wearing a surgical mask in Canada, type of skin disinfectant, and use of non-sterile gloves in New Zealand. Risk of infection was lower in Colombia when mucosal cautery and fascial interposition [FI] were used for vas occlusion compared to ligation, excision, and FI (0.9% vs. 2.1%, p<0.00001). Low level of infection certainty in 56% to 60% of patients who received antibiotics indicates that the true risk might be overestimated. Lack of information in medical records and patients not consulting their vasectomy providers might have led to underestimation of the risk. CONCLUSION: Risk of infection after vasectomy is low, about 1%, among international high-volume vasectomy practices performing NSV and various occlusion techniques. Apart from vasectomy occlusion technique, no other factor modified the risk of post-vasectomy infection.

Angiotensin in the Arcuate: Mechanisms Integrating Cardiometabolic Control: The 2022 COH Mid-Career Award for Research Excellence.

The American Heart Association has identified obesity as a primary impediment to ongoing improvements in cardiovascular diseases, including hypertension. Although drugs, exercise, diets, and surgeries can each cause weight loss, few subjects maintain a reduced weight over the long term. Dysfunctional integrative control (ie, adaptation) of resting metabolic rate (RMR) appears to underlie this failed weight maintenance, yet the neurobiology of physiological and pathophysiological RMR control is poorly understood. Here, we review recent insights into the cellular and molecular control of RMR by Ang-II (angiotensin II) signaling within the arcuate nucleus of the hypothalamus. Within a unique subset of agouti-related peptide neurons, AT1R (Ang-II type 1 receptors) are implicated in the integrative control of RMR. Furthermore, a spontaneous G protein signal switch of AT1R within this neuron type appears to underlie the pathogenesis of RMR adaptation by qualitatively changing the cellular response to AT1R activation from a ß-arrestin-1/Gαi (heterotrimeric G protein, α i subtype)-mediated inhibitory response to a Gαq (heterotrimeric G protein, α q subtype)-mediated stimulatory response. We conclude that therapeutic approaches to obesity are likely hampered by the plasticity of the signaling mechanisms that mediate the normal integrative control of energy balance. The same stimulus that would increase RMR in the normal physiological state may decrease RMR during obesity due to qualitative changes in second-messenger coupling. Understanding the mechanisms that regulate interactions between receptors such as AT1R and its various second messenger signaling cascades will provide novel insights into the pathogenesis of RMR adaptation and potentially point toward new therapeutic approaches for obesity and hypertension.

Differences in Fluid, Electrolyte, and Energy Balance in C57BL/6J Mice (Mus musculus) in Metabolic Caging at Thermoneutral or Standard Room Temperatures.

The Guide for the Care and Use of Laboratory Animals recommends mice be pair or group housed and provided with nesting materials. These provisions support social interactions and are also critical for thermoregulatory behaviors such as huddling and burrowing. However, studies of fluid and electrolyte balance and digestive function may involve use of metabolic caging (MC) systems in which mice are housed individually on wire-mesh floors that permit quantitative collection of urine and feces. MC housing prevents mice from performing their typical huddling and burrowing behaviors. Housing in MC can cause weight loss and behavioral changes in rodents. Here, we tested the hypothesis that MC housing of mice at standard room temperature (SRT, 22 to 23 °C) exposes them to cold stress, which causes metabolic changes in the mice as compared with standard housing. We hypothesized that performing MC studies at a thermoneutral temperature (TNT, 30 °C) would minimize these changes. Fluid, electrolyte, and energy balance and body composition were assessed in male and female C57BL/6J mice housed at SRT or TNT in MC, static microisolation cages, or a multiplexed metabolic phenotyping system designed to mimic static microisolation cages (Promethion, Sable Systems International). In brief, as compared with MC housing at SRT, MC housing at TNT was associated with lower food intake and energy expenditure, absence of weight loss, and lower urine and fecal corticosterone levels. These results indicate that housing in MC at SRT causes cold stress that can be mitigated if MC studies are performed at TNT.

Cardiometabolic Effects of DOCA-Salt in Mice Depend on Ambient Temperature.

BACKGROUND: Mice prefer warmer environments than humans. For this reason, behavioral and physiological thermoregulatory responses are engaged by mice in response to a standard room temperature of 22 to 24 °C. Autonomic mechanisms mediating thermoregulatory responses overlap with mechanisms activated in hypertension, and, therefore, we hypothesized that housing at thermoneutral temperatures (TNs; 30 °C) would modify the cardiometabolic effects of deoxycorticosterone acetate (DOCA)-salt in mice. METHODS: The effects of DOCA-salt treatment upon ingestive behaviors, energy expenditure, blood pressure, heart rate (HR), and core temperature were assessed in C57BL/6J mice housed at room temperature or TN. RESULTS: Housing at TN reduced food intake, energy expenditure, blood pressure, and HR and attenuated HR responses to acute autonomic blockade by chlorisondamine. At room temperature, DOCA-salt caused expected increases in fluid intake, sodium retention in osmotically inactive pools, blood pressure, core temperature, and also caused expected decreases in fat-free mass, total body water, and HR. At TN, the effects of DOCA-salt upon fluid intake, fat gains, hydration, and core temperature were exaggerated, but effects on energy expenditure and HR were blunted. Effects of DOCA-salt upon blood pressure were similar for 3 weeks and exaggerated by TN housing in the fourth week. CONCLUSIONS: Ambient temperature robustly influences behavioral and physiological functions in mice, including metabolic and cardiovascular phenotype development in response to DOCA-salt treatment. Studying cardiometabolic responses of mice at optimal ambient temperatures promises to improve the translational relevance of rodent models.

A better way: training for direct observations in healthcare.

Direct observation is valuable for identifying latent threats and elucidating system complexity in clinical environments. This approach facilitates prospective risk assessment and reveals workarounds, near-misses and recurrent safety problems difficult to diagnose retrospectively or via outcome data alone. As observers are an instrument of data collection, developing effective and comprehensive observer training is critical to ensuring the reliability of the data collection and reproducibility of the research. However, methodological rigour for ensuring these data collection properties remains a key challenge in direct observation research in healthcare. Although prior literature has offered key considerations for observational research in healthcare, operationalising these recommendations may pose a challenge and unless guidance is also provided on observer training. In this article, we offer guidelines for training non-clinical observers to conduct direct observations including conducting a training needs analysis, incorporating practice observations and evaluating observers and inter-rater reliability. The operationalisation of these guidelines is described in the context of a 5-year multisite observational study investigating technology integration in the operating room. We also discuss novel tools developed during the course our project to support data collection and examine inter-rater reliability among observers in direct observation studies.

Room Size Influences Flow in Robotic-Assisted Surgery.

The introduction of surgical technology into existing operating rooms (ORs) can place novel demands on staff and infrastructure. Despite the substantial physical size of the devices in robotic-assisted surgery (RAS), the workspace implications are rarely considered. This study aimed to explore the impact of OR size on the environmental causes of surgical flow disruptions (FDs) occurring during RAS. Fifty-six RAS procedures were observed at two academic hospitals between July 2019 and January 2021 across general, urologic, and gynecologic surgical specialties. A multiple regression analysis demonstrated significant effects of room size in the pre-docking phase (t = 2.170, df = 54, ß = 0.017, p = 0.035) where the rate of FDs increased as room size increased, and docking phase (t = -2.488, df = 54, ß = -0.017, p = 0.016) where the rate of FDs increased as room size decreased. Significant effects of site (pre-docking phase: p = 0.000 and docking phase: p = 0.000) were also demonstrated. Findings from this study demonstrate hitherto unrecognized spatial challenges involved with introducing surgical robots into the operating domain. While new technology may provide benefits towards patient safety, it is important to consider the needs of the technology prior to integration.

TeoNAM: A Nested Association Mapping Population for Domestication and Agronomic Trait Analysis in Maize.

Recombinant inbred lines (RILs) are an important resource for mapping genes controlling complex traits in many species. While RIL populations have been developed for maize, a maize RIL population with multiple teosinte inbred lines as parents has been lacking. Here, we report a teosinte nested association mapping (TeoNAM) population, derived from crossing five teosinte inbreds to the maize inbred line W22. The resulting 1257 BC1S4 RILs were genotyped with 51,544 SNPs, providing a high-density genetic map with a length of 1540 cM. On average, each RIL is 15% homozygous teosinte and 8% heterozygous. We performed joint linkage mapping (JLM) and a genome-wide association study (GWAS) for 22 domestication and agronomic traits. A total of 255 QTL from JLM were identified, with many of these mapping near known genes or novel candidate genes. TeoNAM is a useful resource for QTL mapping for the discovery of novel allelic variation from teosinte. TeoNAM provides the first report that PROSTRATE GROWTH1, a rice domestication gene, is also a QTL associated with tillering in teosinte and maize. We detected multiple QTL for flowering time and other traits for which the teosinte allele contributes to a more maize-like phenotype. Such QTL could be valuable in maize improvement.

Risk of post-vasectomy infections in 133,044 vasectomies from four international vasectomy practices

ABSTRACT Objectives: To estimate the risk of post-vasectomy infections in various settings and across various surgical techniques and sanitization practices. Patients and Methods: Retrospective review of the records of 133,044 vasectomized patients from four large practices/network of practices using the no-scalpel vasectomy (NSV) technique in Canada (2011-2021), Colombia (2015-2020), New Zealand (2018-2021), and the United Kingdom (2006-2019). We defined infection as any mention in medical records of any antibiotics prescribed for a genital or urinary condition following vasectomy. Results: Post-vasectomy infection risks were 0.8% (219 infections/26,809 procedures), 2.1% (390/18,490), 1.0% (100/10,506), and 1.3% (1,007/77,239) in Canada, Colombia, New Zealand, and the UK, respectively. Audit period comparison suggests a limited effect on the risk of infection of excising a short vas segment, applying topical antibiotic on scrotal opening, wearing a surgical mask in Canada, type of skin disinfectant, and use of non-sterile gloves in New Zealand. Risk of infection was lower in Colombia when mucosal cautery and fascial interposition [FI] were used for vas occlusion compared to ligation, excision, and FI (0.9% vs. 2.1%, p<0.00001). Low level of infection certainty in 56% to 60% of patients who received antibiotics indicates that the true risk might be overestimated. Lack of information in medical records and patients not consulting their vasectomy providers might have led to underestimation of the risk. Conclusion: Risk of infection after vasectomy is low, about 1%, among international high-volume vasectomy practices performing NSV and various occlusion techniques. Apart from vasectomy occlusion technique, no other factor modified the risk of post-vasectomy infection.