Risk Factors for Major Pregnancy Complications in Female Cardiothoracic Surgeons.

OBJECTIVE: To describe the incidence of and risk factors for pregnancy complications in female cardiothoracic surgeons compared to women of similar sociodemographic profiles. SUMMARY BACKGROUND DATA: Female cardiothoracic surgeons often postpone childbearing, but little is known about their pregnancy outcomes. METHODS: A self-administered survey was distributed to US cardiothoracic surgeons/trainees in 2023. Surgeons with ≥1 live birth were queried on maternal work hours during pregnancy and major antenatal pregnancy complications. Male surgeons answered on behalf of non-surgeon childbearing partners (female non-surgeons). RESULTS: The study included 255 surgeons (63.53% male; 36.47% female). Compared to female surgeons, male surgeons more often had partners who were not employed outside the home (25.64% vs. 13.33%, P<0.001). Female surgeons were older than female non-surgeons at first live birth (34.494.41 vs. 31.454.16, P<0.001), more often worked >60 hours/week during pregnancy (70.33% vs. 14.08%, P<0.001), and more often had pregnancy complications (45.16% vs. 27.16%, P=0.003; OR 1.78, 95%CI:1.01-3.13). Among female surgeons, 18.28% reduced work hours during pregnancy. During their third trimester, 54.84% worked >6 overnight calls/month and 72.04% operated >12 hours/week. Age35yrs (OR 3.28, 95%CI 1.27-8.45) and operating >12 hours/week during the third trimester (OR 3.72, 95%CI 1.04-13.30) were associated with pregnancy complications. CONCLUSIONS: Female cardiothoracic surgeons are more likely to experience major pregnancy complications than non-surgeon partners of their male peers. Long operative hours during pregnancy and older maternal age are significant risk factors for pregnancy complications. To advance gender equity, policies to protect maternal-fetal health and facilitate childbearing during training and early career are needed.

Unspoken Truths: Mental Health Among Academic Surgeons.

OBJECTIVE: To characterize the current state of mental health within the surgical workforce in the United States. BACKGROUND: Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown. METHODS: Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed. RESULTS: Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4%-14.0%), 26.1% (141/539) reported a previous mental health diagnosis. In all, 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P <0.001), anxiety (31.6% vs. 16.2%, P =0.001), PTSD (12.8% vs. 5.6%, P =0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P =0.022). Overall, 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past 2 weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04-3.65, P =0.033) and screening positive for depression (aOR: 4.30, 95% CI: 2.21-8.29, P <0.001) or PTSD (aOR: 3.93, 95% CI: 1.61-9.44, P =0.002) were associated with increased odds of suicidal ideation over the past 12 months. CONCLUSIONS: Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the United States.

Assessing the influence of graft loss on 4-year patient survival after simultaneous pancreas-kidney transplantation: Kaplan-Meier versus Competing Risk Analysis model.

BACKGROUND: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.

Parental Support Policies and Benefits: A Surgical Training Program Report Card of Transparency.

OBJECTIVE: This study aimed to investigate the transparency of parental benefits available to US surgical residency applicants. BACKGROUND: Medical students prioritize work-family balance in specialty selection. Those applying to surgical residency programs also place a significant value on parental leave policies when deciding where to train. However, little is known about the amount of information that surgical training programs publicly offer to potential applicants regarding family support policies. METHODS: Publicly available websites for 264 general surgery training programs were accessed to determine the availability of information on parental benefits. Twenty-six "items of transparency" included types of leave, contract flexibility, salary, lactation, and childcare support. Programs with fewer than the median items of transparency were contacted to inquire about additional public resources. Academic programs were stratified by their associated medical school rankings in the US News & World Report. RESULTS: A total of 144 (54%) programs were academic and 214 (81.4%) had male program directors. The median number of items of transparency was 8 (29.6%). Of the 131 programs contacted, 33 (25.9%) replied, and 2 (6.1%) improved their transparency score. Academic programs associated with medical schools in the upper third of the rankings were more likely to have ≥8 items of transparency (70.8% vs. 45.6%; P =0.002). In the adjusted analysis, academic programs [odds ratio (OR): 3.44, 95% confidence interval (95% CI): 1.87-6.34], those with female program directors (OR: 2.09, 95% CI: 1.01-4.33), and those located in the Western (OR: 3.13, 95% CI: 1.31-7.45) and Southern (OR: 2.45, 95% CI: 1.21-4.98) regions of the country were more likely to have ≥8 items of transparency. CONCLUSIONS: There are significant deficits in publicly available information related to parental benefits for many surgical training programs, which may impact applicants' decision making. Attracting the most talented candidates requires programs to create and share policies that support the integration of professional and personal success.

High Infertility Rates and Pregnancy Complications in Female Physicians Indicate a Need for Culture Change.

OBJECTIVE: This survey study aims to determine the prevalence of pregnancy complications and infertility in female physicians in comparison to the general population. Risk factors, workplace environment, and education are also examined. BACKGROUND: Physicians undertake long training and have stressful work environments during optimal childbearing years. While growing literature indicates increased rates of pregnancy complications and infertility in female surgeons, the prevalence in female physicians of all specialties is unknown. METHODS: An anonymous, voluntary survey was distributed to female physicians via private physician social media groups. It queried pregnancy demographics and complications, infertility diagnosis and treatment, workplace environment, and prior education on these topics. Results were compared with general population data, between medical and surgical subspecialties, and between physicians who were and were not educated on the risks of delaying pregnancy. RESULTS: A total of 4533 female physicians completed the survey. Compared with the general population, female physicians were older at first pregnancy, more often underwent infertility evaluation and treatment, and had higher rates of miscarriage and preterm birth. During training, only 8% of those surveyed received education on the risks of delaying pregnancy. Those who were educated were significantly less likely to experience miscarriage or seek infertility evaluation or treatment. Compared with physicians in nonsurgical specialties, surgeons had fewer children, were older at first pregnancy, had more preterm births and fetal growth problems, and were more likely to be discouraged from starting a family during training and practice. CONCLUSIONS: Female physicians, particularly surgeons, have a significantly greater incidence of miscarriage, infertility, and pregnancy complications compared with the general population. The culture of medicine and surgery must continue to evolve to better support women with family planning during their training and careers.

The Challenges of Parenthood for Female Surgeons: The Current Landscape and Future Directions.

Although surgical training programs have nearly reached gender parity, pregnancy and parenthood remain challenging for female surgeons, with obstetric risks related to occupational demands, stigma, inconsistent and brief parental leaves, a paucity of postpartum support for lactation and childcare, and little mentorship on work-family integration. This work environment causes many to postpone starting a family, which leads to higher risks of infertility among female surgeons compared to their male peers. Perception of work-family incompatibility jeopardizes recruitment and retention of our surgical workforce, as it deters medical students from the profession, increases risk of resident attrition, and leads to burnout and career dissatisfaction. The challenges of parenthood for female surgeons was the focus of a Hot Topics session during the 2022 Academic Surgical Congress, the discussion of which is presented herein with recommendations for policy change to better support maternal-fetal health and the needs of surgeons with young children.

Sex Differences among Overweight/Obese Kidney Transplant Recipients Requiring Oxygen Support Amid the COVID-19 Pandemic.

Background and Objectives: Overweight/obesity puts individuals at greater risk for COVID-19 progression and mortality. We aimed to evaluate the impact of overweight/obesity on oxygen (O2) requirement outcomes of male and female kidney transplant recipients (KTRs) during the COVID-19 pandemic. Materials and Methods: We conducted a retrospective analysis of a cohort of KTRs diagnosed with COVID-19. Participants were stratified based on BMI categories, and data on the need for O2 therapy outcome were collected and analyzed separately for male and female KTRs. Results: In total, 284 KTRs (97 males and 187 females) were included in the study. Overweight/obesity was observed in 60.6% of male KTRs and 71% of female KTRs. Strikingly, overweight/obese women had a significantly higher requirement for supplemental O2 (63.3% vs. 41.7%, OR = 2.45, p = 0.03), particularly among older individuals (OR = 1.05, p = 0.04), smokers (OR = 4.55, p = 0.03), those with elevated lactate dehydrogenase (LDH) levels (OR = 1.01, p = 0.006), and those with lower admission and basal estimated glomerular filtration rate (eGFR) levels. Within this cohort, the necessity for O2 supplementation was correlated with more unfavorable outcomes. These included heightened mortality rates, transfers to the intensive care unit, employment of invasive mechanical ventilation, and the emergence of acute kidney injury requiring hemodialysis. On the other hand, although overweight/obese male KTRs had a higher prevalence of hypertension and higher fasting blood glucose levels, no significant association was found with COVID-19-related outcomes when compared to lean male KTRs. Conclusions: Overweight/obesity is highly prevalent in KTRs, and overweight/obese women demonstrated a higher need for supplemental O2. Therefore, the early identification of factors that predict a worse outcome in overweight/obese female KTRs affected by COVID-19 contributes to risk stratification and guides therapeutic decisions.

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.

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.

Sarcopenia Is Associated With Increased Mortality in Patients With Necrotizing Soft Tissue Infections.

INTRODUCTION: Necrotizing soft tissue infections (NSTIs) are surgical emergencies associated with high morbidity and mortality. Identifying risk factors for poor outcome is a critical part of preoperative decision-making and counseling. Sarcopenia, the loss of lean muscle mass, has been associated with an increased risk of mortality and can be measured using cross-sectional imaging. Our aim was to determine the impact of sarcopenia on mortality in patients with NSTI. We hypothesized that sarcopenia would be associated with an increased risk of mortality in patients with NSTI. METHODS: This is a retrospective cohort study of NSTI patients admitted from 1995 to 2015 to two academic institutions. Operative and pathology reports were reviewed to confirm the diagnosis in all cases. Average bilateral psoas muscle cross-sectional area at L4, normalized for height (Total Psoas Index [TPI]), was calculated using computed tomography (CT). Sarcopenia was defined as TPI in the lowest sex-specific quartile. Primary outcome was in-hospital mortality. Multivariate logistic regression was performed to assess the association between sarcopenia and in-hospital mortality. RESULTS: There were 115 patients with preoperative imaging, 61% male and a median age of 57 y interquartile range (IQR 46.6-67.0). Overall in-hospital mortality was 12.1%. There was no significant difference in sex, body mass index (BMI), comorbidities and American Society of Anesthesiologists classification (Table 1). After multivariate analysis, sarcopenia was independently associated with increased in-hospital mortality (Odds ratio, 3.5; 95% Confidence Interval [CI], 1.05-11.8). CONCLUSIONS: Sarcopenia is associated with increased risk of in-hospital mortality in patients with NSTIs. Sarcopenia identifies patients with higher likelihood of poor outcomes, which can possibly help surgeons in counseling their patients and families.

COVID-19 in Kidney Transplant Recipients With Diabetes Mellitus: A Propensity Score Matching Analysis.

Kidney transplant recipients present higher rates of pre-existing comorbidities, in particular diabetes mellitus (DM), hypertension, and cardiac disease. We aimed to verify the main risk factors related to DM that contribute to COVID-19 progression and mortality in a kidney transplant setting. From March to August 2020, we evaluated 300 kidney transplant recipients affected by COVID-19. We used propensity score matching (PSM) to estimate the impact of DM on COVID-19. After matching, all baseline characteristics were well balanced between those with and without DM (n = 100 in each group). Case fatality rate, the requirement of invasive mechanical ventilation (IMV), and acute kidney injury (AKI) were associated with previous fasting blood glucose, and C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels on admission. These findings were similar in kidney transplant patients with and without DM. Glycemia on admission and estimated glomerular filtration rate (eGFR) either on admission or basal correlated to the need of IMV and development of AKI, respectively. Poor glycaemic control, eGFR, markers of inflammation (CRP) and tissue damage (LDH) were indicative of COVID-19 burden in kidney transplant recipients and may be useful tools for risk-stratifying this population, independently of the DM status, during the pandemic.

The effects of a short-term meditation-based mindfulness protocol in patients receiving hemodialysis.

Mindfulness-based approaches that promote health, improve quality of life, and reduce the impact of comorbidities are key aspects in chronic diseases management. We aimed to verify the impact of a short-term meditation protocol on psychosocial and physiological parameters in chronic hemodialysis patients. We enrolled twenty-two patients, median age of 69.5 years old, into a 12-week meditation protocol that occurred during each hemodialysis session for 10-20 minutes, 3x/week, in a private tertiary hospital. We then evaluated clinical, psychological, and laboratorial parameters pre- and post-meditation. Patients exhibited a better control of serum phosphorus (-0.72 mg/dL; P = 0.002), a decrease in systolic blood pressure (-1.90 mmHg; P = 0.009), a 23% decrease in depressive symptoms (P = 0.014), and an increase of 7% in the self-compassion scale (P = 0.048) after meditation. To note, we observed an increase in 13% of the mindfulness score (P = 0.019). Our preliminary study describes the effects of a short-term meditation protocol in chronic hemodialysis setting. We observed a decrease in depressive symptoms and in blood pressure values, an improvement in self-compassion and serum phosphorous levels. In conjunction with the promising results of meditation in chronic kidney disease setting, this encouraging preliminary study supports the need for additional clinical trials.

Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease.

Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors. This study sought to investigate the benefits of fecal microbiota transplant (FMT) on functional and morphological parameters in a preclinical model of type 2 DM, obesity, and DKD using BTBRob/ob mice. These animals develop hyperglycemia and albuminuria in a time-dependent manner, mimicking DKD in humans. Our main findings unveiled that FMT prevented body weight gain, reduced albuminuria and tumor necrosis factor-α (TNF-α) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBRob/ob mice. Intestinal structural integrity was maintained. Notably, FMT was associated with the abundance of the succinate-consuming Odoribacteraceae bacteria family throughout the intestine. Collectively, our data pointed out the safety and efficacy of FMT in a preclinical model of type 2 DM, obesity, and DKD. These findings provide a basis for translational research on intestinal microbiota modulation and testing its therapeutic potential combined with current treatment for DM.

Hypokalemia in Diabetes Mellitus Setting.

Diabetes mellitus is a public health problem that affects millions of people worldwide regardless of age, sex, and ethnicity. Electrolyte disturbances may occur as a consequence of disease progression or its treatment, in particular potassium disorders. The prevalence of hypokalemia in diabetic individuals over 55 years of age is up to 1.2%. In patients with acute complications of diabetes, such as diabetic ketoacidosis, this prevalence is even higher. Potassium disorders, either hypokalemia or hyperkalemia, have been associated with increased all-cause mortality in diabetic individuals, especially in those with associated comorbidities, such as heart failure and chronic kidney disease. In this article, we discuss the main conditions for the onset of hypokalemia in diabetic individuals, briefly review the pathophysiology of acute complications of diabetes mellitus and their association with hypokalemia, the main signs, symptoms, and laboratory parameters for the diagnosis of hypokalemia, and the management of one of the most common electrolyte disturbances in clinical practice.

COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection.

COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. ACE2 is a key regulator of the renin-angiotensin-aldosterone system (RAAS). SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.

Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity.

Diabetic kidney disease (DKD) is a worldwide microvascular complication of type 2 diabetes mellitus (T2DM). From several pathological mechanisms involved in T2DM-DKD, we focused on mitochondria damage induced by hyperglycemia-driven reactive species oxygen (ROS) accumulation and verified whether mesenchymal stem cells (MSCs) anti-oxidative, anti-apoptotic, autophagy modulation, and pro-mitochondria homeostasis therapeutic potential curtailed T2DM-DKD progression. For that purpose, we grew immortalized glomerular mesangial cells (GMCs) in hyper glucose media containing hydrogen peroxide. MSCs prevented these cells from apoptosis-induced cell death, ROS accumulation, and mitochondria membrane potential impairment. Additionally, MSCs recovered GMCs' biogenesis and mitophagy-related gene expression that were downregulated by stress media. In BTBRob/ob mice, a robust model of T2DM-DKD and obesity, MSC therapy (1 × 106 cells, two doses 4-weeks apart, intra-peritoneal route) led to functional and structural kidney improvement in a time-dependent manner. Therefore, MSC-treated animals exhibited lower levels of urinary albumin-to-creatinine ratio, less mesangial expansion, higher number of podocytes, up-regulation of mitochondria-related survival genes, a decrease in autophagy hyper-activation, and a potential decrease in cleaved-caspase 3 expression. Collectively, these novel findings have important implications for the advancement of cell therapy and provide insights into cellular and molecular mechanisms of MSC-based therapy in T2DM-DKD setting.

Identification of Specific Educational Targets to Improve the Student Surgical Clerkship Experience.

BACKGROUND: This study describes the relationship between medical student perception of surgery, frequency of positive surgery clerkship activities, and overall surgical clerkship experience. METHODS: Medical students at four academic hospitals completed pre- and post-clerkship surveys assessing 1) surgery clerkship activities/experiences and 2) perceptions of surgery during the 2017-2018 academic year. RESULTS: Ninety-one percent of students completed both a pre- and post-clerkship survey (n = 162 of 179). Student perception of surgery significantly improved across the clerkship overall (P < 0.0001) and for 7 of 21 specific items. Eighty-six percent of students agreed that the clerkship was a meaningful experience. Sixty-six percent agreed that the operating room was a positive learning environment. Multivariable logistic regression identified one-on-one mentoring from a resident (OR [95% CI] = 2.12 [1.11-4.04], P = 0.02) and establishing a meaningful relationship with a surgical patient (OR = 2.21 [1.12-4.37], P = 0.02) as activities predictive of student agreement that the surgical clerkship was meaningful. Making an incision (OR = 2.92 [1.54-5.56], P = 0.001) and assisting in dissection (OR = 1.67 [1.03-2.69], P = 0.035) were predictive of student agreement that the operating room was a positive learning environment. Positive student perception of surgery before the clerkship was associated with increased frequency of positive clerkship activities including operative involvement (r = 0.26, P = 0.001) and relationships with surgical attendings (r = 0.20, P = 0.01), residents (r = 0.41, P < 0.0001), and patients (r = 0.24, P = 0.003). CONCLUSIONS: Interventions to improve surgery clerkship quality should target enhancing student relationships with residents and surgical patients as well as providing opportunity for student operative involvement beyond just suturing. In addition, fostering positive perceptions of surgery in the preclinical period may increase meaningfulness and experience with the later surgery clerkship.

The quality of life in type I diabetic patients with end-stage kidney disease before and after simultaneous pancreas-kidney transplantation: a single-center prospective study.

Simultaneous pancreas-kidney transplantation (SPKT) aimed at increasing the life expectancy for diabetic patients with end-stage kidney disease (ESKD). However, the risks of surgery complications and immunosuppression therapy make it unclear if the SPKT positively impacts patient's quality of life (QoL). Using the Kidney Disease Quality of Life-Short-Form Health Survey (KDQOL-SF36) and Problems Areas in Diabetes (PAID) measurement tools, we compared the QoL of 57 patients on the pretransplant waiting list with that of 103 patients who had undergone SPKT. Posttransplantation patients were assessed within different time intervals (<1, 1-3, and >3 years). Mean KDQOL-SF36 scores were better among posttransplantation patients in the SF36 and KDQOL domains. It was also observed patients' stress reduction in PAID mean score (P = 0.011) after SPKT. We concluded that patients receiving SPKT had a better perception of QoL than did patients on the waiting list, and this positive perception remained almost entirely comparable over the three different intervals of the posttransplantation time. These positive results showed better outcomes when excluding patients that lost pancreas graft function. Further research is needed to compare diabetic patients with kidney transplant alone using specific measurement tools to evaluate patient's QoL.

Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-ß-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-ß-hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-ß-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.

Interaction between neuronal nitric oxide synthase signaling and temperature influences sarcoplasmic reticulum calcium leak: role of nitroso-redox balance.

RATIONALE: Although nitric oxide (NO) signaling modulates cardiac function and excitation-contraction coupling, opposing results because of inconsistent experimental conditions, particularly with respect to temperature, confound the ability to elucidate NO signaling pathways. Here, we show that temperature significantly modulates NO effects. OBJECTIVE: To test the hypothesis that temperature profoundly affects nitroso-redox equilibrium, thereby affecting sarcoplasmic reticulum (SR) calcium (Ca(2+)) leak. METHODS AND RESULTS: We measured SR Ca(2+) leak in cardiomyocytes from wild-type (WT), NO/redox imbalance (neuronal nitric oxide synthase-deficient mice-1 [NOS1(-/-)]), and hyper S-nitrosoglutathione reductase-deficient (GSNOR(-/-)) mice. In WT cardiomyocytes, SR Ca(2+) leak increased because temperature decreased from 37°C to 23°C, whereas in NOS1(-/-) cells, the leak suddenly increased when the temperature surpassed 30°C. GSNOR(-/-) cardiomyocytes exhibited low leak throughout the temperature range. Exogenously added NO had a biphasic effect on NOS1(-/-) cardiomyocytes; reducing leak at 37°C but increasing it at subphysiological temperatures. Oxypurinol and Tempol diminished the leak in NOS1(-/-) cardiomyocytes. Cooling from 37°C to 23°C increased reactive oxygen species generation in WT but decreased it in NOS1(-/-) cardiomyocytes. Oxypurinol further reduced reactive oxygen species generation. At 23°C in WT cells, leak was decreased by tetrahydrobiopterin, an essential NOS cofactor. Cooling significantly increased SR Ca(2+) content in NOS1(-/-) cells but had no effect in WT or GSNOR(-/-). CONCLUSIONS: Ca(2+) leak and temperature are normally inversely proportional, whereas NOS1 deficiency reverses this effect, increasing leak and elevating reactive oxygen species production because temperature increases. Reduced denitrosylation (GSNOR deficiency) eliminates the temperature dependence of leak. Thus, temperature regulates the balance between NO and reactive oxygen species which in turn has a major effect on SR Ca(2+).