A Randomized Crossover Trial Evaluating the Impact of Cultural Dexterity Training on Surgical Residents' Knowledge, Cross-Cultural Care, Skills, and Beliefs: The Provider Awareness and Cultural dexterity Training for Surgeons (PACTS) Trial.

OBJECTIVES: This trial examines the impact of the Provider Awareness and Cultural dexterity Toolkit for Surgeons (PACTS) curriculum on surgical residents' knowledge, cross-cultural care, skills, and beliefs. SUMMARY BACKGROUND DATA: Cross-cultural training of providers may reduce healthcare outcome disparities, but its effectiveness in surgical trainees is unknown. METHODS: PACTS focuses on developing skills needed for building trust, working with patients with limited English proficiency, optimizing informed consent, and managing pain. The PACTS trial was a randomized crossover trial of 8 academic general surgery programs in the United States: The Early group ("Early") received PACTS between Periods 1 and 2, while the Delayed group ("Delayed") received PACTS between Periods 2 and 3. Residents were assessed pre- and post-intervention on Knowledge, Cross-Cultural Care, Self-Assessed Skills, and Beliefs. Chi-square and Fisher's exact tests were conducted to evaluate within- and between-intervention group differences. RESULTS: Of 406 residents enrolled, 315 were exposed to the complete PACTS curriculum. Early residents' Cross-Cultural Care (79.6% to 88.2%, P<0.0001), Self-Assessed Skills (74.5% to 85.0%, P<0.0001), and Beliefs (89.6% to 92.4%, P=0.0028) improved after PACTS; Knowledge scores (71.3% to 74.3%, P=0.0661) were unchanged. Delayed resident scores pre- to post-PACTS showed minimal improvements in all domains. When comparing the two groups at Period 2, Early residents had modest improvement in all 4 assessment areas, with statistically significant increase in Beliefs (92.4% vs 89.9%, P=0.0199). CONCLUSION: The PACTS curriculum is a comprehensive tool that improved surgical residents' knowledge, preparedness, skills, and beliefs, which will help with caring for diverse patient populations.

Alterations to metabolic hormones in amyotrophic lateral sclerosis and frontotemporal dementia postmortem human tissue.

Metabolic changes are observed in patients with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although regulation of metabolic processes in the CNS is predominantly carried out within the hypothalamus, extra-hypothalamic CNS areas contain metabolic hormone receptors, including those for leptin (LEPR), insulin (INSR), and neuropeptide Y (NPY), indicating that they may play a role in biological processes underlying pathogenic disease processes. The status of these hormones within regions vulnerable in ALS/FTD is not well described. This study sought to determine whether the expression of these hormones and their receptors is altered in pathology-rich regions in cases of human FTD (superior frontal gyrus and insular cortex) and ALS (primary motor cortex and lumbar spinal cord) with TDP-43 pathology compared to matched healthy controls. LEPR mRNA was increased within the superior frontal gyrus of FTD cases and within primary motor cortex and lumbar spinal cord of ALS cases; INSR mRNA was increased in superior frontal gyrus and insular cortex of FTD cases. NPY protein was decreased in primary motor cortex and lumbar spinal cord of ALS cases. Our results demonstrate that metabolic hormones undergo complex alterations in ALS and FTD and suggest that these hormones could play critical roles in the pathogenesis of these diseases.

Experimental laboratory models as tools for understanding modifiable dementia risk.

Experimental laboratory research has an important role to play in dementia prevention. Mechanisms underlying modifiable risk factors for dementia are promising targets for dementia prevention but are difficult to investigate in human populations due to technological constraints and confounds. Therefore, controlled laboratory experiments in models such as transgenic rodents, invertebrates and in vitro cultured cells are increasingly used to investigate dementia risk factors and test strategies which target them to prevent dementia. This review provides an overview of experimental research into 15 established and putative modifiable dementia risk factors: less early-life education, hearing loss, depression, social isolation, life stress, hypertension, obesity, diabetes, physical inactivity, heavy alcohol use, smoking, air pollution, anesthetic exposure, traumatic brain injury, and disordered sleep. It explores how experimental models have been, and can be, used to address questions about modifiable dementia risk and prevention that cannot readily be addressed in human studies. HIGHLIGHTS: Modifiable dementia risk factors are promising targets for dementia prevention. Interrogation of mechanisms underlying dementia risk is difficult in human populations. Studies using diverse experimental models are revealing modifiable dementia risk mechanisms. We review experimental research into 15 modifiable dementia risk factors. Laboratory science can contribute uniquely to dementia prevention.

The distribution of cadmium in soil and cacao beans in Peru.

Peru is the eighth largest producer of cacao beans globally, but high cadmium contents are constraining access to international markets which have set upper thresholds for permitted concentrations in chocolate and derivatives. Preliminary data have suggested that high cadmium concentrations in cacao beans are restricted to specific regions in the country, but to date no reliable maps exist of expected cadmium concentrations in soils and cacao beans. Drawing on >2000 representative samples of cacao beans and soils we developed multiple national and regional random forest models to develop predictive maps of cadmium in soil and cacao beans across the area suitable for cacao cultivation. Our model projections show that elevated concentrations of cadmium in cacao soils and beans are largely restricted to the northern parts of the country in the departments of Tumbes, Piura, Amazonas and Loreto, as well as some very localized pockets in the central departments of Huánuco and San Martin. Unsurprisingly, soil cadmium was the by far most important predictor of bean cadmium. Aside from the south-eastern to north-western spatial trend of increasing cadmium values in soils and beans, the most important predictors of both variables in nation-wide models were geology, rainfall seasonality, soil pH and rainfall. At regional level, alluvial deposits and mining operations were also associated with higher cadmium levels in cacao beans. Based on our predictive map of cadmium in cacao beans we estimate that while at a national level <20 % of cacao farming households might be impacted by the cadmium regulations, in the most affected department of Piura this could be as high as 89 %.

Real-Time Student Feedback on the Surgical Learning Environment: Use of a Mobile Application.

OBJECTIVE: Improvements to the medical student surgical learning environment are limited by lack of granular data and recall bias on end-of-clerkship evaluations. The purpose of this study was to identify specific areas for intervention using a novel real-time mobile application. DESIGN: An application was designed to obtain real-time feedback from medical students regarding the learning environment on their surgical clerkship. Thematic analysis of student experiences was performed at the conclusion of 4 consecutive 12-week rotation blocks. SETTING: Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts. RESULTS: Fifty-four medical students at a single institution were asked to participate during their primary clerkship experience. Students submitted 365 responses over 48 weeks. Multiple themes emerged which were dichotomized into positive and negative emotions centered on specific student priorities. Approximately half of responses were associated with positive emotions (52.9%) and half with negative emotions (47.1%). Student priorities included the desire to feel included in the surgical team (resulting in feeling engaged/ignored), to have a positive relationship with members of the team (perceiving kind/rude interactions), to witness compassionate patient care (observing empathy/disrespect for patients), to have a well-planned surgical rotation (experiencing organization/disorganization within teams), and to feel that student well-being is prioritized (reporting opportunities/disregard for student wellness). CONCLUSION: A novel, user-friendly mobile application identified several areas to improve the experience and engagement of students on their surgery clerkship. Allowing clerkship directors and other educational leaders to collect longitudinal data in real time may allow for more targeted, timely improvements to the medical student surgical learning environment.

Identifying the origin of acrylamide in Peruvian panela production to inform strategies for its reduction.

Maximum levels of acrylamide have been set by the European Commission (EU) 2017/2158 for several food products due to its carcinogenic properties. Although not regulated yet, European buyers are requesting maximum levels of 0.8 mg kg-1 in artisanal panela (raw cane sugar) from northern Peru. Panela in this area is produced by 600 small holder farmers and exportation guarantees a respectable price in an area with a high index of poverty. The objective here was to determine the cause of high acrylamide concentrations in panela to inform cost effective minimisation strategies. We monitored panela production from field to final product to understand the scale of the problem, identify the cause of acrylamide formation, as well as the effect of storage on its concentration. We also determined the utility of rapid kits for asparagine quantification. Our results indicate that high acrylamide levels are a widespread problem (85% of samples analysed) and there was a correlation between acrylamide and asparagine of R2 = 0.58 (p < 0.001), but not with any post-harvest processing variable. We estimate that with a concentration of asparagine of <0.1 g l-1 in sugarcane juice, the threshold set by buyers for acrylamide can be met. Potential solutions to reduce asparagine include varietal selection, improved agronomic practices and the use of asparaginase during panela production. However, any proposed measure should be applicable in the context of the rural Peru. Additionally, we confirm the utility of rapid and low-cost kits for measuring asparagine. This pioneering study provides a baseline for effective management for acrylamide minimization in panela.

Sarm1 knockout modifies biomarkers of neurodegeneration and spinal cord circuitry but not disease progression in the mSOD1G93A mouse model of ALS.

The mechanisms underlying the loss of motor neuron axon integrity in amyotrophic lateral sclerosis (ALS) are unclear. SARM1 has been identified as a genetic risk variant in sporadic ALS, and the SARM1 protein is a key mediator of axon degeneration. To investigate the role of SARM1 in ALS-associated axon degeneration, we knocked out Sarm1 (Sarm1KO) in mSOD1G93ATg (mSOD1) mice. Animals were monitored for ALS disease onset and severity, with motor function assessed at pre-symptomatic and late-stage disease and lumbar spinal cord and sciatic nerve harvested for immunohistochemistry at endpoint (20 weeks). Serum was collected monthly to assess protein concentrations of biomarkers linked to axon degeneration (neurofilament light (NFL) and tau), and astrogliosis (glial fibrillary acidic protein (GFAP)), using single molecule array (Simoa®) technology. Overall, loss of Sarm1 in mSOD1 mice did not slow or delay symptom onset, failed to improve functional declines, and failed to protect motor neurons. Serum NFL levels in mSOD1 mice increased between 8 -12 and 16-20 weeks of age, with the later increase significantly reduced by loss of SARM1. Similarly, loss of SARM1 significantly reduced an increase in serum GFAP between 16 and 20 weeks of age in mSOD1 mice, indicating protection of both global axon degeneration and astrogliosis. In the spinal cord, Sarm1 deletion protected against loss of excitatory VGluT2-positive puncta and attenuated astrogliosis in mSOD1 mice. In the sciatic nerve, absence of SARM1 in mSOD1 mice restored the average area of phosphorylated neurofilament reactivity towards WT levels. Together these data suggest that Sarm1KO in mSOD1 mice is not sufficient to ameliorate functional decline or motor neuron loss but does alter serum biomarker levels and provide protection to axons and glutamatergic synapses. This indicates that treatments targeting SARM1 could warrant further investigation in ALS, potentially as part of a combination therapy.

Pregnancy During Surgical Training: Are Residency Programs Truly Supporting Their Trainees?

OBJECTIVE: Despite recent national improvements in family leave policies, there has been little focus on program-level support for surgical trainees. Trainees who may require clinical duty adjustments during pregnancy, who experience pregnancy loss, or who struggle with balancing work obligations with the demands of a new infant may face stigma when seeking schedule accommodations. The aim of this study was to describe program and colleague support of surgical trainees for pregnancy-related and postpartum health needs. DESIGN: Survey questionnaire. Participants responded to multiple-choice questions about their history of pregnancy loss, their experience with reduction of clinical duties during pregnancy, and their breastfeeding experience. Those who took time off after miscarriages or reduced their clinical duties during pregnancy were asked whether they perceived their colleagues and/or program leadership to be supportive using a 4-point Likert scale (1-strongly agree, 4-strongly disagree) which was dichotomized to agree/disagree. SETTING: Electronically distributed through social media and surgical societies from November 2020 to January 2021. PARTICIPANTS: Female surgical residents and fellows. RESULTS: 258 female surgical residents and fellows were included. Median age was 32 (IQR 30-35) years and 76.74% were white. Of the 52 respondents (20.2%) who reported a miscarriage, 38 (73.1%) took no time off after pregnancy loss, including 5 of 10 women (50%) whose loss occurred after 10 weeks' gestation. Of the 14 residents who took time off after a miscarriage, 4 (28.6%) disagreed their colleagues and/or leadership were supportive of time away from work. Among trainees who reported at least 1 live birth, only 18/114 (15.8%) reduced their work schedule during pregnancy. Of these, 11 (61.1%) described stigma and resentment from colleagues and 14 (77.8%) reported feeling guilty about burdening their colleagues. 100% of respondents reported a desire to breastfeed their infants, but nearly half (46.0%) were unable to reach their breastfeeding goals. 46 (80.7%) cited a lack of time to express breastmilk and 23 (40.4%) cited inadequate lactation facilities as barriers to achieving their breastfeeding goals. CONCLUSIONS: A minority of female trainees takes time off or reduces their clinical duties for pregnancy or postpartum health needs. National parental leave policies are insufficient without complementary program-level strategies that support schedule adjustments for pregnant trainees without engendering a sense of resentment or guilt for doing so. Surgical program leaders should initiate open dialogue, proactively offer clinical duty reductions, and ensure time and space for lactation needs to safeguard maternal-fetal health and improve the working environment for pregnant residents.

Lack of Workplace Support for Obstetric Health Concerns is Associated With Major Pregnancy Complications: A National Study of US Female Surgeons.

OBJECTIVE: We sought to assess whether lack of workplace support for clinical work reductions during pregnancy was associated with major pregnancy complications. BACKGROUND: Surgeons are at high risk of major pregnancy complications. Although rigorous operative schedules pose increased risk, few reduce their clinical duties during pregnancy. METHODS: An electronic survey was distributed to US surgeons who had at least 1 live birth. Lack of workplace support was defined as: (1) desiring but feeling unable to reduce clinical duties during pregnancy due to failure of the workplace/training program to accommodate and/or concerns about financial penalties, burden on colleagues, requirement to make up missed call, being perceived as weak; (2) disagreeing colleagues and/or leadership were supportive of obstetrician-prescribed bedrest. Multivariate logistic regression determined the association between lack of workplace support and major pregnancy complications. RESULTS: Of 671 surgeons, 437 (65.13%) reported lack of workplace support during pregnancy and 302 (45.01%) experienced major pregnancy complications. Surgeons without workplace support were at higher risk of major pregnancy complications than those who had workplace support (odds ratio: 2.44; 95% confidence interval: 1.58-3.75). Bedrest was prescribed to 110/671 (16.39%) surgeons, 38 (34.55%) of whom disagreed that colleagues and/or leadership were supportive. Of the remaining surgeons, 417/560 (74.5%) desired work reductions but were deterred by lack of workplace support. CONCLUSIONS: Lack of workplace support for reduction in clinical duties is associated with adverse obstetric outcomes for surgeons. This is a modifiable workplace obstacle that deters surgeons from acting to optimize their infant's and their own health. To ensure the health of expectant surgeons, departmental policies should support reduction of clinical workload in an equitable manner without creating financial penalties, requiring payback for missed call duties, or overburdening colleagues.

Postpartum Depression in Surgeons and Workplace Support for Obstetric and Neonatal Complication: Results of a National Study of US Surgeons.

BACKGROUND: Postpartum depression has well-established long-term adverse effects on maternal and infant health. Surgeons with rigorous operative schedules are at higher risk of obstetric complications, but they rarely reduce their workload during pregnancy. We evaluated whether lack of workplace support for work reductions during difficult pregnancies or after neonatal complications is associated with surgeon postpartum depression. STUDY DESIGN: An electronic survey was sent to practicing and resident surgeons of both sexes in the US. Female surgeons who had at least one live birth were included. Lack of workplace support was defined as: (1) disagreeing that colleagues/leadership were supportive of obstetric-mandated bedrest or time off to care for an infant in the neonatal intensive care unit; (2) feeling unable to reduce clinical duties during pregnancy despite health concerns or to care for an infant in the neonatal intensive care unit. Multivariate logistic regression was used to determine the association of lack of workplace support with postpartum depression. RESULTS: Six hundred ninety-two surgeons were included. The 441 (63.7%) respondents who perceived a lack of workplace support had a higher risk of postpartum depression than those who did not perceive a lack of workplace support (odds ratio 2.21, 95% CI 1.09 to 4.46), controlling for age, race, career stage, and pregnancy/neonatal complications. Of the surgeons with obstetric-related work restrictions, 22.6% experienced loss of income and 38.5% reported >$50,000 loss. CONCLUSION: Lack of workplace support for surgeons with obstetric or neonatal health concerns is associated with a higher risk of postpartum depression. Institutional policies must address the needs of surgeons facing difficult pregnancies to improve mental health outcomes and promote career longevity.

'From soil to chocolate bar': identifying critical steps in the journey of cadmium in a Colombian cacao plantation.

Regulation of maximum levels of cadmium in chocolate is an issue for cacao exportation from many parts of Latin America, including Colombia. These limits are related to the final product, but buyers often request maximum levels of Cd in the beans. However, to date, there is neither a clear understanding of the relationship between the specified levels of Cd in chocolate and cocoa derivatives and levels in harvested beans or soil nor of the effect of post-harvest processes on the levels of Cd in the final product. To address this, the fate of Cd concentration from soil to chocolate bar was followed in a single farm in Santander district, Colombia. The concentration of Cd in soils was measured using ICP-OES and correlated with soil pH, soil organic matter (SOM), and the use of P-based fertilisers. Cd concentrations were also measured in unfermented seeds, fermented and dried beans, shell, nibs, and chocolate. SOM (2.93-3.78%), soil pH (4.7-4.9), soil P concentration (120-132 mg kg-1) affect Cd availability. However, it is still unclear whether Cd concentration of P-based fertilisers (3-30 mg kg-1) is important or not. While post-harvest treatments did not affect the Cd concentration of beans (4.17 ± 0.8 mg kg-1 on average), the removal of the shell (6.57 mg kg-1) from the nibs (3.28 mg kg-1), as well as the percentage of cocoa mass used contributes to a reduction in Cd concentration in the chocolate bar (1.60 mg kg-1). This study provides clear indications on where research into mitigation measures should be focussed, as well as indicating the importance of carrying out analyses for Cd in the nib or cacao mass, rather than the whole bean, reducing Cd concentration by up to 40%.

Cultural Competency Curricula in US Graduate Medical Education: A Scoping Review.

BACKGROUND: Cultural competency training provides participants with knowledge and skills to improve cross-cultural communication and is required for all graduate medical education (GME) training programs. OBJECTIVE: The authors sought to determine what cultural competency curricula exist specifically in GME. METHODS: In April 2020, the authors performed a scoping review of the literature using a multidatabase (PubMed, Ovid, MedEdPORTAL) search strategy that included keywords relevant to GME and cultural competency. The authors extracted descriptive data about the structure, implementation, and analysis of cultural competency curricula and analyzed these data for trends. RESULTS: Sixty-seven articles met criteria for inclusion, of which 61 (91%) were focused exclusively on residents. The most commonly included specialties were psychiatry (n=19, 28.4%), internal medicine (n=16, 23.9%), and pediatrics (n=15, 22.4%). The shortest intervention was a 30-minute online module, while the longest contained didactics, electives, and mentoring programs that spanned the entirety of residency training (4 years). The sample sizes of included studies ranged from 6 to 833 participants. Eight (11.9%) studies utilized OSCEs as assessment tools, while 17 (25.4%) conducted semi-structured interviews or focus groups. Four common themes were unique interventions, retention of learning, trainee evaluation of curricula, and resources required for implementation. CONCLUSIONS: Wide variation exists in the design, implementation, and evaluation of cultural competency curricula for residents and fellows.

The Long Road to Parenthood: Assisted Reproduction, Surrogacy, and Adoption Among US Surgeons.

OBJECTIVE: We sought to characterize demographics, costs, and workplace support for surgeons using assisted reproductive technology (ART), adoption, and surrogacy to build their families. SUMMARY BACKGROUND DATA: As the surgical workforce diversifies, the needs of surgeons building a family are changing. ART, adoption, and surrogacy may be used with greater frequency among female surgeons who delay childbearing and surgeons in same-sex relationships. Little is known about costs and workplace support for these endeavors. METHODS: An electronic survey was distributed to surgeons through surgical societies and social media. Rates of ART use were compared between partners of male surgeons and female surgeons and multivariate analysis used to assess risk factors. Surgeons using ART, adoption, or surrogacy were asked to describe costs and time off work to pursue these options. RESULTS: Eight hundred and fifty-nine surgeons participated. Compared to male surgeons, female surgeons were more likely to report delaying children due to surgical training (64.9% vs. 43.5%, P < 0.001), have fewer children (1.9 vs. 2.4, p < 0.001), and use ART (25.2% vs. 17.4%, P = 0.035). Compared to non-surgeon partners of male surgeons, female surgeons were older at first pregnancy (33 vs 31 years, P < 0.001) with age > 35 years associated with greater odds of ART use (odds ratio 3.90; 95% confidence interval 2.74-5.55, P < 0.001). One-third of surgeons using ART spent >$40,000; most took minimal time off work for treatments. Forty-five percent of same-sex couples used adoption or surrogacy. 60% of surgeons using adoption or surrogacy spent >$40,000 and most took minimal paid parental leave. CONCLUSIONS: ART, adoption, or surrogacy is costly and lacks strong workplace support in surgery, disproportionately impacting women and same-sex couples. Equitable and inclusive environments supporting all routes to parenthood ensure recruitment and retention of a diverse workforce. Surgical leaders must enact policies and practices to normalize childbearing as part of an early surgical career, including financial support and equitable parental leave for a growing group of surgeons pursuing ART, surrogacy, or adoption to become parents.

Perceived Discrimination Among Surgical Residents at Academic Medical Centers.

BACKGROUND: Residents of color experience microaggressions in the work environment, are less likely to feel that they fit into their training programs, and feel less comfortable asking for help. Discrimination has been documented among surgical residents, but has not been extensively studied and largely remains unaddressed. We sought to determine the extent of perceived discrimination among general surgery residents. MATERIALS AND METHODS: Residents who were enrolled in a randomized controlled trial investigating a cultural dexterity curriculum completed baseline assessments prior to randomization that included demographic information and the Everyday Discrimination Scale (EDS). Data from the baseline assessments were analyzed for associations of EDS scores with race, ethnicity, sex, socioeconomic level, language ability, and training level. RESULTS: Of 266 residents across seven residency programs, 145 (55%) were men. Racial breakdown was 157 (59%) White, 45 (17%) Asian, 30 (11%) Black, and 12 (5%) Multiracial. The median EDS score was seven (range: 0-36); 58 (22%) fell into the High EDS score group. Resident race, fluency in a language other than English, and median household income were significantly associated with EDS scores. When controlling for other sociodemographic factors, Black residents were 4.2 (95% CI 1.62-11.01, P = 0.003) times as likely to have High EDS scores than their White counterparts. CONCLUSIONS: Black surgical residents experience high levels of perceived discrimination on a daily basis. Institutional leaders should be aware of these findings as they seek to cultivate a diverse surgical training environment.

The role of altered protein acetylation in neurodegenerative disease.

Acetylation is a key post-translational modification (PTM) involved in the regulation of both histone and non-histone proteins. It controls cellular processes such as DNA transcription, RNA modifications, proteostasis, aging, autophagy, regulation of cytoskeletal structures, and metabolism. Acetylation is essential to maintain neuronal plasticity and therefore essential for memory and learning. Homeostasis of acetylation is maintained through the activities of histone acetyltransferases (HAT) and histone deacetylase (HDAC) enzymes, with alterations to these tightly regulated processes reported in several neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Both hyperacetylation and hypoacetylation can impair neuronal physiological homeostasis and increase the accumulation of pathophysiological proteins such as tau, α-synuclein, and Huntingtin protein implicated in AD, PD, and HD, respectively. Additionally, dysregulation of acetylation is linked to impaired axonal transport, a key pathological mechanism in ALS. This review article will discuss the physiological roles of protein acetylation and examine the current literature that describes altered protein acetylation in neurodegenerative disorders.

Incidence of Infertility and Pregnancy Complications in US Female Surgeons.

Importance: While surgeons often delay pregnancy and childbearing because of training and establishing early careers, little is known about risks of infertility and pregnancy complications among female surgeons. Objective: To describe the incidence of infertility and pregnancy complications among female surgeons in the US and to identify workplace factors associated with increased risk compared with a sociodemographically similar nonsurgeon population. Design, Setting, and Participants: This self-administered survey questionnaire was electronically distributed and collected from November 2020 to January 2021 through multiple surgical societies in the US and social media among male and female attending and resident surgeons with children. Nonchildbearing surgeons were asked to answer questions regarding the pregnancies of their nonsurgeon partners as applicable. Exposures: Surgical profession; work, operative, and overnight call schedules. Main Outcomes and Measures: Descriptive data on pregnancy loss were collected for female surgeons. Use of assisted reproductive technology was compared between male and female surgeons. Pregnancy and neonatal complications were compared between female surgeons and female nonsurgeon partners of surgeons. Results: A total of 850 surgeons (692 women and 158 men) were included in this survey study. Female surgeons with female partners were excluded because of lack of clarity about who carried the pregnancy. Because the included nonchildbearing population was therefore made up of male individuals with female partners, this group is referred to throughout the study as male surgeons. The median (IQR) age was 40 (36-45) years. Of 692 female surgeons surveyed, 290 (42.0%) had a pregnancy loss, more than twice the rate of the general population. Compared with male surgeons, female surgeons had fewer children (mean [SD], 1.8 [0.8] vs 2.3 [1.1]; P < .001), were more likely to delay having children because of surgical training (450 of 692 [65.0%] vs 69 of 158 [43.7%]; P < .001), and were more likely to use assisted reproductive technology (172 of 692 [24.9%] vs 27 of 158 [17.1%]; P = .04). Compared with female nonsurgeon partners, female surgeons were more likely to have major pregnancy complications (311 of 692 [48.3%] vs 43 of 158 [27.2%]; P < .001), which was significant after controlling for age, work hours, in vitro fertilization use, and multiple gestation (odds ratio [OR], 1.72; 95% CI, 1.11-2.66). Female surgeons operating 12 or more hours per week during the last trimester of pregnancy were at higher risk of major pregnancy complications compared with those operating less than 12 hours per week (OR, 1.57; 95% CI, 1.08-2.26). Compared with female nonsurgeon partners, female surgeons were more likely to have musculoskeletal disorders (255 of 692 [36.9%] vs 29 of 158 [18.4%]; P < .001), nonelective cesarean delivery (170 of 692 [25.5%] vs 24 of 158 [15.3%]; P = .01), and postpartum depression (77 of 692 [11.1%] vs 9 of 158 [5.7%]; P = .04). Conclusions and Relevance: This national survey study highlighted increased medical risks of infertility and pregnancy complications among female surgeons. With an increasing percentage of women representing the surgical workforce, changing surgical culture to support pregnancy is paramount to reducing the risk of major pregnancy complications, use of fertility interventions, or involuntary childlessness because of delayed attempts at childbearing.

Effects of TDP-43 overexpression on neuron proteome and morphology in vitro.

TDP-43 is pathologically and genetically with associated amyotrophic lateral sclerosis and frontotemporal lobar degeneration. These diseases are characterized by significant neurite defects, including cytoskeletal pathology. The involvement of TDP-43 in the degeneration of neurons in these diseases are not yet well understood, however accumulating evidence shows involvement in neurite outgrowth, remodelling and in regulation of many components of the neuronal cytoskeleton. In order to investigate how alterations to TDP-43 expression levels may exert effects on the neuronal cytoskeleton, primary cortical neurons from transgenic mice overexpressing one or two copies of human wildtype TDP-43 under the prion promoter were examined. Label-free quantitative proteomic analysis, followed by functional annotation clustering to identify protein families that clustered together within up- or down-regulated protein groups, revealed that actin-binding proteins were significantly more abundant in neurons overexpressing TDP-43 compared to wildtype neurons. Morphological analysis demonstrated that during early development neurons expressing one copy of human TDP-43 had an increased number of neurite branches and alterations to growth cone morphology, while no changes were observed in neurons expressing two copies of TDP-43. These developmental processes require specific expression and organization of the cytoskeleton. The results from these studies provide further insight into the normal function of TDP-43 and how alterations in TDP-43 expression may impact the cytoskeleton.

Habitat Quality Differentiation and Consequences for Ecosystem Service Provision of an Amazonian Hyperdominant Tree Species.

Ecosystem services of Amazonian forests are disproportionally produced by a limited set of hyperdominant tree species. Yet the spatial variation in the delivery of ecosystem services by individual hyperdominant species across their distribution ranges and corresponding environmental gradients is poorly understood. Here, we use the concept of habitat quality to unravel the effect of environmental gradients on seed production and aboveground biomass (AGB) of the Brazil nut, one of Amazonia's largest and most long-lived hyperdominants. We find that a range of climate and soil gradients create trade-offs between density and fitness of Brazil nut trees. Density responses to environmental gradients were in line with predictions under the Janzen-Connell and Herms-Mattson hypotheses, whereas tree fitness responses were in line with resource requirements of trees over their life cycle. These trade-offs resulted in divergent responses in area-based seed production and AGB. While seed production and AGB of individual trees (i.e., fitness) responded similarly to most environmental gradients, they showed opposite tendencies to tree density for almost half of the gradients. However, for gradients creating opposite fitness-density responses, area-based seed production was invariable, while trends in area-based AGB tended to mirror the response of tree density. We conclude that while the relation between environmental gradients and tree density is generally indicative of the response of AGB accumulation in a given area of forest, this is not necessarily the case for fruit production.

TDP-43 mislocalization drives neurofilament changes in a novel model of TDP-43 proteinopathy.

Mislocalization of the TAR DNA-binding protein 43 (TDP-43) from the nucleus to the cytoplasm is a common feature of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The downstream in vivo cellular effects of this mislocalization are not well understood. To investigate the impact of mislocalized TDP-43 on neuronal cell bodies, axons and axonal terminals, we utilized the mouse visual system to create a new model of TDP-43 proteinopathy. Mouse (C57BL/6J) retinal ganglion cells (RGCs) were transduced with GFP-tagged human wildtype TDP-43 (hTDP-WT-GFP) and human TDP-43 with a mutation in the nuclear localization sequence (hTDP-ΔNLS-GFP), to cause TDP-43 mislocalization, with ∼60% transduction efficiency achieved. Expression of both hTDP-WT-GFP and hTDP-ΔNLS-GFP resulted in changes to neurofilament expression, with cytoplasmic TDP-43 being associated with significantly (p<0.05) increased neurofilament heavy expression in the cell soma, and both forms of altered TDP-43 leading to significantly (p<0.05) decreased numbers of neurofilament-positive axons within the optic nerve. Alterations to neurofilament proteins were associated with significantly (p<0.05) increased microglial density in the optic nerve and retina. Furthermore expression of hTDP-WT-GFP was associated with a significant (p<0.05) increase in pre-synaptic input into RGCs in the retina. The current study has developed a new model allowing detailed examination of alterations to TDP-43 and will contribute to the knowledge of TDP-43-mediated neuronal alterations and degeneration.