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Purpose/objectives: To evaluate rates of clinical complete response (cCR), surgery-free survival, permanent ostomy-free survival, and factors associated with these outcomes in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma., Methods: A retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013 - 2022 with curative intent. All patients received radiation with concurrent capecitabine and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Response rates were determined based on post-treatment MRI and endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Chi-squared analysis compared rates of cCR and surgery by sequence of TNT modality and cell count ratios., Results: Of the 45 patients treated with TNT, most patients had low-lying rectal tumors with a median distance of 4.1 cm from the anal verge (range, 0.0 - 12.0). Overall, 64.4% (n=29) achieved cCR after TNT. 13 patients (28.9%) underwent surgical resection following TNT, 12 of whom had incomplete response and one who elected to undergo surgery after reaching cCR. At median follow up of 32.0 months (range, 7.1 - 86.1), 22.2% (n=10) of patients had a permanent colostomy, with only 2 of these completed for tumor regrowth after cCR. At one and two years, respectively, surgery-free survival was 77.3% and 66.2%, and permanent ostomy-free survival was 90.9% and 78.2%. Rates of cCR were higher in patients who received CRT first compared to those who received chemotherapy first (72.2% vs. 33.3%, p =0.029) and rates of surgery were also lower in patients who received CRT first compared to those who received chemotherapy first (19.4% vs. 66.7%, p=0.005). On Cox regression model, cCR on 6 month post-CRT endoscopy was associated with surgery-free survival (p=0.006) and permanent ostomy-free survival ( p =0.033). Clinical response at earlier follow up points did not predict surgery- nor permanent ostomy-free survival., Conclusion: These results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma who desire organ preservation. In this investigation at a single institution, the treatment response on 6-month post-CRT endoscopy was the best predictor of surgery- and permanent ostomy-free survival, which are outcomes that are important to patient quality of life. CRT followed by consolidation chemotherapy was associated with higher rates of cCR and lower rates of surgery compared to those treated with induction chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Asare, Venner, Batchelor, Sanders, Kunk, Hedrick, Hoang, Reilley, Le, Friel and Janowski.)

Background: The early detection of respiratory infections could improve responses against outbreaks. Wearable devices can provide insights into health and well-being using longitudinal physiological signals., Objective: The purpose of this study was to prospectively evaluate the performance of a consumer wearable physiology-based respiratory infection detection algorithm in health care workers., Methods: In this study, we evaluated the performance of a previously developed system to predict the presence of COVID-19 or other upper respiratory infections. The system generates real-time alerts using physiological signals recorded from a smartwatch. Resting heart rate, respiratory rate, and heart rate variability measured during the sleeping period were used for prediction. After baseline recordings, when participants received a notification from the system, they were required to undergo testing at a Northwell Health System site. Participants were asked to self-report any positive tests during the study. The accuracy of model prediction was evaluated using respiratory infection results (laboratory results or self-reports), and postnotification surveys were used to evaluate potential confounding factors., Results: A total of 577 participants from Northwell Health in New York were enrolled in the study between January 6, 2022, and July 20, 2022. Of these, 470 successfully completed the study, 89 did not provide sufficient physiological data to receive any prediction from the model, and 18 dropped out. Out of the 470 participants who completed the study and wore the smartwatch as required for the 16-week study duration, the algorithm generated 665 positive alerts, of which 153 (23.0%) were not acted upon to undergo testing for respiratory viruses. Across the 512 instances of positive alerts that involved a respiratory viral panel test, 63 had confirmed respiratory infection results (ie, COVID-19 or other respiratory infections detected using a polymerase chain reaction or home test) and the remaining 449 had negative upper respiratory infection test results. Across all cases, the estimated false-positive rate based on predictions per day was 2%, and the positive-predictive value ranged from 4% to 10% in this specific population, with an observed incidence rate of 198 cases per week per 100,000. Detailed examination of questionnaires filled out after receiving a positive alert revealed that physical or emotional stress events, such as intense exercise, poor sleep, stress, and excessive alcohol consumption, could cause a false-positive result., Conclusions: The real-time alerting system provides advance warning on respiratory viral infections as well as other physical or emotional stress events that could lead to physiological signal changes. This study showed the potential of wearables with embedded alerting systems to provide information on wellness measures., (©Zeinab Esmaeilpour, Aravind Natarajan, Hao-Wei Su, Anthony Faranesh, Ciaran Friel, Theodoros P Zanos, Stefani D’Angelo, Conor Heneghan. Originally published in JMIR Formative Research (https://formative.jmir.org), 17.07.2024.)

Importance: Prenatal diet may be causally related to autism; however, findings are inconsistent, with a limited body of research based on small sample sizes and retrospective study designs., Objective: To investigate the associations of prenatal dietary patterns with autism diagnosis and autism-associated traits in 2 large prospective cohorts, the Norwegian Mother, Father, and Child Cohort Study (MoBa), and the Avon Longitudinal Study of Parents and Children (ALSPAC)., Design, Setting, and Participants: This cohort study used data from MoBa and ALSPAC birth cohort studies conducted across Norway and in the Southwest of England, respectively. Participants were people with singleton pregnancies with self-reported food frequency questionnaire responses. MoBa recruited between 2002 and 2008, and ALSPAC recruited between 1990 and 1992, and children were followed-up until age 8 years or older. Recruitment rates were 41% (95 200 of 277 702 eligible pregnancies) in MoBa and 72% (14 541 of 20 248 eligible pregnancies) in ALSPAC. Data analysis occurred February 1, 2022, to August 1, 2023., Exposure: A healthy prenatal dietary pattern was derived using factor analysis and modeled as low, medium, and high adherence., Main Outcomes and Measures: In MoBa, the offspring outcomes were autism diagnosis and elevated social communication questionnaire score at ages 3 years and 8 years, with further analysis of the social communication difficulties and restrictive and repetitive behaviors subdomains. In ALSPAC, offspring outcomes were elevated social communication difficulties checklist score at age 8 years. Odds ratios (ORs) were estimated using generalized nonlinear models., Results: MoBa included 84 548 pregnancies (mean [SD] age, 30.2 [4.6] years; 43 277 [51.2%] male offspring) and ALSPAC had 11 760 pregnancies (mean [SD] age, 27.9 [4.7] years; 6034 [51.3%] male offspring). In the final adjusted models, high adherence to a healthy dietary pattern, compared with low adherence, was associated with reduced odds of autism diagnosis (OR, 0.78; 95% CI, 0.66-0.92) and social communication difficulties at age 3 years in MoBa (OR 0.76, 95% CI, 0.70-0.82) and age 8 years in ALSPAC (OR, 0.74; 95% CI, 0.55-0.98). There was no consistent evidence of association with the other outcomes., Conclusions and Relevance: In this cohort study of mother-child dyads, adherence to a healthy prenatal dietary pattern was associated with a lower odds of autism diagnosis and social communication difficulties but not restrictive and repetitive behaviors.

Background: Huntington's disease (HD) is an autosomal dominant, neurodegenerative disease that involves dysfunction in the autonomic nervous system (ANS). Heart rate variability (HRV) is a valid and noninvasive measure for ANS dysfunction, yet no study has characterized HRV response to exercise in people with HD., Objective: Characterize HRV response to exercise in individuals with HD and explore its implications for exercise prescription and cardiac dysautonomia mechanisms., Methods: 19 participants with HD were recruited as part of a cohort of individuals enrolled in the Physical Activity and Exercise Outcomes in Huntington's Disease (PACE-HD) study at Teachers College, Columbia University (TC). 13 non-HD age- and gender-matched control participants were also recruited from TC. HRV was recorded with a Polar H10 heart rate (HR) monitor before, during, and after a ramp cycle-ergometer exercise test., Results: Participants with HD showed reduced HR peak (p < 0.01) and HR reserve (p < 0.001) compared with controls. Participants with HD demonstrated reduced root mean square of successive differences between normal-to-normal intervals (RMSSD) and successive differences of normal-to-normal intervals (SDSD) at rest (p < 0.001). Participants with HD also showed differences for low frequency (LF) power (p < 0.01), high frequency (HF) normalized units (nu) (p < 0.05), LF (nu) (p < 0.001), and HF/LF ratio (p < 0.05) compared with controls., Conclusions: We found reduced aerobic exercise capacity and sympathovagal dysautonomia both at rest and during post-exercise recovery in people with HD, suggesting modified exercise prescription may be required for people with HD. Further investigations focusing on cardiac dysautonomia and underlying mechanisms of sympathovagal dysautonomia in people with HD are warranted.

Objective: Mental health distress and suicidal ideation are leading contributors to the silent epidemic of physician suicide leading to approximately 300 to 400 physician deaths per year. The Second Trial has illuminated the alarming fact that several of our residents have experienced suicidal thoughts within the last year. Unfortunately, our institution is not an outlier. Suicidal ideation and under- or untreated mental health disorders are increasingly prevalent in the surgical trainee population. Given the major concern for our residents' well-being, our department consulted a licensed mental health professional familiar with resident training and the GME to develop a program to provide access to a mental health professional that is free of cost for trainees, safe and confidential., Design: Implementation of a 30 minute opt-out resident check-in program with a licensed mental health professional and a post-session survey that provided retrospective survey data for analysis., Setting: This program was implemented at the University of Virginia Health System in Charlottesville, VA., Participants: General surgery categorical and preliminary residents participated in this program., Results: Thirty residents participated in the program and an overwhelming majority would like to continue this program at regular intervals. Sessions were 25 minutes on average and 27.7% of participants requested additional sessions., Conclusions: Implementation of this program for our surgical trainees was favorably perceived with request for continuation of the program and provided access to a safe space with a familiar provider., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Microrheology, the study of fluids on micron length-scales, promises to reveal insights into cellular biology, including mechanical biomarkers of disease and the interplay between biomechanics and cellular function. Here a minimally-invasive passive microrheology technique is applied to individual living cells by chemically binding a bead to the surface of a cell, and observing the mean squared displacement of the bead at timescales ranging from milliseconds to 100s of seconds. Measurements are repeated over the course of hours, and presented alongside analysis to quantify changes in the cells' low-frequency elastic modulus, G 0 ' , and the cell's dynamics over the time window ∼10 -2  s to 10 s. An analogy to optical trapping allows verification of the invariant viscosity of HeLa S3 cells under control conditions and after cytoskeletal disruption. Stiffening of the cell is observed during cytoskeletal rearrangement in the control case, and cell softening when the actin cytoskeleton is disrupted by Latrunculin B. These data correlate with conventional understanding that integrin binding and recruitment triggers cytoskeletal rearrangement. This is, to our knowledge, the first time that cell stiffening has been measured during focal adhesion maturation, and the longest time over which such stiffening has been quantified by any means. STATEMENT OF SIGNIFICANCE: Here, we present an approach for studying mechanical properties of live cells without applying external forces or inserting tracers. Regulation of cellular biomechanics is crucial to healthy cell function. For the first time in literature, we can non-invasively and passively quantify cell mechanics during interactions with functionalised surface. Our method can monitor the maturation of adhesion sites on the surface of individual live cells without disrupting the cell mechanics by applying forces to the cell. We observe a stiffening response in cells over tens of minutes after a bead chemically binds. This stiffening reduces the deformation rate of the cytoskeleton, although the internal force generation increases. Our method has potential for applications to study mechanics during cell-surface and cell-vesicle interactions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: While physical activity (PA) is recognized as important in Huntington's disease (HD) disease management, there has been no long-term evaluation undertaken. We aimed to evaluate the feasibility of a nested (within cohort) randomized controlled trial (RCT) of a physical therapist-led PA intervention., Methods: Participants were recruited from six HD specialist centers participating in the Enroll-HD cohort study in Germany, Spain and U.S. Assessments were completed at baseline and 12 months and linked to Enroll-HD cohort data. Participants at three sites (cohort) received no contact between baseline and 12 month assessments. Participants at three additional sites (RCT) were randomized to PA intervention or control group. The intervention consisted of 18 sessions delivered over 12 months; control group participants received no intervention, however both groups completed monthly exercise/falls diaries and 6-month assessments., Results: 274 participants were screened, 204 met inclusion criteria and 116 were enrolled (59 in cohort; 57 in RCT). Retention rates at 12-months were 84.7% (cohort) and 79.0% (RCT). Data completeness at baseline ranged from 42.3 to 100% and at 12-months 19.2-85.2%. In the RCT, there was 80.5% adherence, high intervention fidelity, and similar adverse events between groups. There were differences in fitness, walking endurance and self-reported PA at 12 months favoring the intervention group, with data completeness >60%. Participants in the cohort had motor and functional decline at rates comparable to previous studies., Conclusion: Predefined progression criteria indicating feasibility were met. PACE-HD lays the groundwork for a future, fully-powered within cohort trial, but approaches to ensure data completeness must be considered., Clinicaltrials: GOV: NCT03344601., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Prenatal nutrition is associated with offspring autism spectrum disorder (herein referred to as autism), yet, it remains unknown if the association is causal. Triangulation may improve causal inference by integrating the results of conventional multivariate regression with several alternative approaches that have unrelated sources of bias. We systematically reviewed the literature on the relationship between prenatal multivitamin supplements and offspring autism, and evidence for the causal approaches applied. Six databases were searched up to 8 June 2020, by which time we had screened 1309 titles/abstracts, and retained 12 articles. Quality assessment was guided using Newcastle-Ottawa in individual studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) for the body of evidence. The effect estimates from multivariate regression were meta-analysed in a random effects model and causal approaches were narratively synthesised. The meta-analysis of prenatal multivitamin supplements involved 904,947 children (8159 cases), and in the overall analysis showed no robust association with offspring autism; however, a reduced risk was observed in the subgroup of high-quality observational studies (RR 0.77, 95% CI (0.62, 0.96), I 2 = 62.4%), early pregnancy (RR 0.76, 95% CI (0.58; 0.99), I 2 = 79.8%) and prospective studies (RR 0.69, 95% CI (0.48, 1.00), I 2 = 95.9%). The quality of evidence was very low, and triangulation was of limited utility because alternative methods were used infrequently and often not robustly applied.

Background: Clostridioides difficile infection is reported to occur after 2.2% of colorectal operations and is associated with longer length of hospital stay, greater overall healthcare cost, and significant morbidity and mortality. The incidence of Clostridioides difficile infection is greatest after elective stoma reversal. The purpose of this study was to evaluate the effect of prior Clostridioides difficile infection on patients undergoing stoma reversal. We hypothesized that patients with a history of Clostridioides difficile infection who underwent stoma reversal will be at an increased risk of postoperative Clostridioides difficile infection compared with patients without a history of Clostridioides difficile infection., Methods: This was an observational cohort study of patients undergoing elective stoma reversal surgery by colorectal surgeons at a single academic institution during a 10-year period. A prospectively maintained institutional database was queried to identify 454 patients who underwent stoma reversal surgery between January 1, 2007 and December 31, 2017. The primary outcomes were Clostridioides difficile infection after stoma reversal and time to Clostridioides difficile infection after bowel refunctionalization. Secondary outcomes included postoperative complications, length of hospital stay, discharge destination, and 30-day readmission rate. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with Clostridioides difficile infection after stoma reversal., Results: A total of 445 patients were identified who underwent elective stoma reversal, 42 of whom had a history of Clostridioides difficile infection before the stoma reversal. There were no significant differences in patient age, number of days diverted, or use of perioperative antibiotics between patients with and without a history of Clostridioides difficile infection. The incidence of postreversal Clostridioides difficile infection was 23.4% in patients with a history of Clostridioides difficile infection compared with 9.6% in patients with no Clostridioides difficile infection history (P = .004); however, time to Clostridioides difficile infection after reversal did not differ. History of Clostridioides difficile infection was also associated with greater risk of postoperative complications (26.2% vs 9.4%, P < .01), increased length of stay (3 vs 5 days postoperatively, P < .01), increased likelihood of discharge to a skilled-care facility (11.9% vs 6.2%, P < .01), and readmission (13.7 vs 31.0%, P < .01) within 30 days. In a multivariable logistic regression model, history of Clostridioides difficile infection, increased length of hospital stay, and discharge to a skilled facility were associated with increased risk of Clostridioides difficile infection after reversal, while proton pump inhibitors use was associated with decreased risk of Clostridioides difficile infection., Conclusion: Patients with a prior history of Clostridioides difficile infection who underwent stoma reversal exhibited higher rates of postoperative Clostridioides difficile infection and were at greater risk of postoperative complications, discharge to a skilled facility, and 30-day readmission. Furthermore, research into interventions aimed at improving outcomes in this unique, high-risk population is needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Shift work is associated with risk for adverse health outcomes including cardiovascular disease, type 2 diabetes, cancer, and obesity. Short sleep duration combined with disruptions to the circadian system may alter factors involved with the behavioral regulation of energy intake and expenditure. We aimed to determine how shift work affects sleep, food intake, and physical activity. Methods: This was a field-based observational study using objective assessments of sleep and physical activity and a 24-hour dietary recall in shift workers. Day (n = 12) and night (n = 12) hospital shift workers (nurses and technicians) who were women had their free-living sleep and physical activity tracked via accelerometry, and completed a computer-assisted 24-hour food recall, during a series of work shifts. Results: Compared to day workers, night workers had significantly shorter sleep duration and reported more premature awakenings and feeling less refreshed upon awakening. Daily self-reported energy and macronutrient intakes were not different between groups, although the night shift workers reported a significantly longer total daily eating duration window than day workers. Objectively recorded physical activity levels were not different between groups. Conclusions: The present findings confirm that sleep is disturbed in women night workers, while there are relatively less effects on objectively recorded physical activity and self-reported food intake. We also observed a prolonged daily eating duration in night vs. day workers. These observations can help inform the design of novel behavioral interventions, including, potentially, time restricted feeding approaches (e.g., by limiting daily eating episodes to within a 10-12 h window), to optimize weight management in shift workers.

Objective: We hypothesize the Distressed Communities Index (DCI), a composite socioeconomic ranking by ZIP code, will predict risk-adjusted outcomes after surgery., Summary of Background Data: Socioeconomic status affects surgical outcomes; however, the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) database does not account for these factors., Methods: All ACS NSQIP patients (17,228) undergoing surgery (2005 to 2015) at a large academic institution were paired with the DCI, which accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies. Developed by the Economic Innovation Group, DCI scores range from 0 (no distress) to 100 (severe distress). Multivariable regressions were used to evaluate ACS NSQIP predicted risk-adjusted effect of DCI on outcomes and inflation-adjusted hospital cost., Results: A total of 4522 (26.2%) patients came from severely distressed communities (top quartile). These patients had higher rates of medical comorbidities, transfer from outside hospital, emergency status, and higher ACS NSQIP predicted risk scores (all P < 0.05). In addition, these patients had greater resource utilization, increased postoperative complications, and higher short- and long-term mortality (all P < 0.05). Risk-adjustment with multivariate regression demonstrated that DCI independently predicts postoperative complications (odds ratio 1.1, P = 0.01) even after accounting for ACS NSQIP predicted risk score. Furthermore, DCI independently predicted inflation-adjusted cost (+$978/quartile, P < 0.0001) after risk adjustment., Conclusions: The DCI, an established metric for socioeconomic distress, improves ACS NSQIP risk-adjustment to predict outcomes and hospital cost. These findings highlight the impact of socioeconomic status on surgical outcomes and should be integrated into ACS NSQIP risk models.

Purpose: To determine whether theory-based physical activity (PA) interventions for overweight and obese female cancer survivors lead to increased PA and improved health., Methods: This systematic review examined randomized controlled trials analyzing the impact of theory-based PA interventions on overweight and obese female cancer survivors through December 2016. Searches of 5 electronic databases revealed 10 articles that included 1351 participants who met the inclusion criteria., Results: Participants were primarily non-Hispanic white (74%-100%) breast or endometrial cancer survivors. Intervention characteristics and PA assessment tools varied greatly. Adherence (68%-99%) and retention (79%-100%) were relatively high. Social cognitive theory was utilized as the theoretical construct in 9 of the 10 studies. Home-based interventions led to small improvements in PA (Cohen's d range = 0.25-0.31), whereas home-based plus center-based interventions led to moderate to large improvements (Cohen's d range = 0.45-1.02). Only three of the studies assessed psychosocial behavioral processes associated with PA, and the results were mixed. Health-related outcomes included improvements in aerobic fitness (Cohen's d = 0.32-1.1 in 5 studies), large absolute decreases in waist circumferences (>6 cm in 3 of 5 studies; Cohen's d = -0.31 to -1.02), and no change in inflammatory biomarkers (in 2 studies). Only one serious adverse event (pelvic stress fracture) was attributed to the interventions., Conclusions: Theory-based PA interventions are safe and feasible for overweight and obese female cancer survivors. Interventions that include a center-based component showed moderate to large effect sizes for PA. Future studies should evaluate behavioral variables and more health-related clinical outcomes.

Objective: Endometrial cancer survivors are the least physically active of all cancer survivor groups and exhibit up to 70% obesity. While studies suggest lifestyle interventions result in improved health outcomes, recruitment and availability of these programs are limited. The purpose was to evaluate the acceptability and validity of the Fitbit Alta™ physical activity monitor (Fitbit) for socioculturally diverse endometrial cancer survivors., Methods: Thirty endometrial cancer survivors were given wrist-worn Fitbits to wear for 30 days. Participants then returned the Fitbits, completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ), Technology Acceptance Questionnaire, and answered qualitative prompts. Correlations between daily Fitbit step counts, demographic factors, body mass index (BMI), and GLTEQ Index, were analyzed using Stata 13.0. Concordance Correlation Coefficient using U statistics was used to examine convergent validity., Results: Twenty-five participants completed the study. Mean age was 62 ± 9 years. Mean BMI was 32 ± 9 kg·m -2 . Self-identified race/ethnicity was 36% Hispanic, 36% non-Hispanic white, 16% non-Hispanic black and 12% Asian. Participants wore the Fitbits a median of 93% of possible days. Median daily Fitbit step count was 5325 (IQR: 3761-8753). Mean Technology Acceptance score was 2.8 ± 0.5 out of 4.0. Younger (<65 years) and employed participants were more likely to achieve at least 6000 daily steps (p < 0.05). There was no correlation (CCC = 0.00, p = 0.99) between step count and GLTEQ Index. Most free responses reflected positive experiences., Conclusions: The Fitbits were well accepted in this sample. Self-reported physical activity was not associated with steps recorded. The physical activity data indicate an insufficiently active population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

As agricultural acreage expanded and came to dominate landscapes across the world, viruses gained opportunities to move between crop and wild native plants. In the Midwestern USA, virus exchange currently occurs between widespread annual Poaceae crops and remnant native perennial prairie grasses now under consideration as bioenergy feedstocks. In this region, the common aphid species Rhopalosiphum padi L. (the bird cherry-oat aphid) transmits several virus species in the family Luteoviridae, including Barley yellow dwarf virus (BYDV-PAV, genus Luteovirus) and Cereal yellow dwarf virus (CYDV-RPV and -RPS, genus Polerovirus). The yellow dwarf virus (YDV) species in these two genera share genetic similarities in their 3'-ends, but diverge in the 5'-regions. Most notably, CYDVs encode a P0 viral suppressor of RNA silencing (VSR) absent in BYDV-PAV. Because BYDV-PAV has been reported more frequently in annual cereals and CYDVs in perennial non-crop grasses, we examine the hypothesis that the viruses' genetic differences reflect different affinities for crop and non-crop hosts. Specifically, we ask (i) whether CYDVs might persist within and affect a native non-crop grass more strongly than BYDV-PAV, on the grounds that the polerovirus VSR could better moderate the defenses of a well-defended perennial, and (ii) whether the opposite pattern of effects might occur in a less defended annual crop. Because previous work found that the VSR of CYDV-RPS possessed greater silencing suppressor efficiency than that of CYDV-RPV, we further explored (iii) whether a novel grass-associated CYDV-RPS isolate would influence a native non-crop grass more strongly than a comparable CYDV-RPV isolate. In growth chamber studies, we found support for this hypothesis: only grass-associated CYDV-RPS stunted the shoots and crowns of Panicum virgatum L. (switchgrass), a perennial native North American prairie grass, whereas crop-associated BYDV-PAV (and coinfection with BYDV-PAV and CYDV-RPS) most stunted annual Avena sativa L. (oats). These findings suggest that some of the diversity in grass-infecting Luteoviridae reflects viral capacity to modulate defenses in different host types. Intriguingly, while all virus treatments also reduced root production in both host species, only crop-associated BYDV-PAV (or co-infection) reduced rooting depths. Such root effects may increase host susceptibility to drought, and indicate that BYDV-PAV pathogenicity is determined by something other than a P0 VSR. These findings contribute to growing evidence that pathogenic crop-associated viruses may harm native species as well as crops. Critical next questions include the extent to which crop-associated selection pressures drive viral pathogenesis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Diverting stomas are employed for various clinical indications and easier to revert than end stomas. General, plastic, and colorectal surgeons continue to debate whether a diverting loop stoma adequately diverts stool, preventing spillage into the distal limb, which does not receive stool. A retrospective, descriptive study was conducted involving all patients who underwent loop ostomy surgery (colostomy or ileostomy) - defined by current procedural terminology (CPT) codes 44187, 44188, 44153, and 44155-44158 - between April 1, 2002 and October 12, 2010. The purpose of the study was to determine if a diverting loop stoma is completely diverting with no efflux into the distal limb by examining the rate of distal limb contamination. Two surgeons identified patients at the University of Virginia who had loop ostomy surgery and subsequently underwent computed tomography (CT) scan with oral contrast for clinical suspicion of abnormal pathology. A radiologist reviewed these images to evaluate the presence or absence of oral contrast in the ostomy distal limb. Distal progression of oral contrast was deemed adequate if oral contrast was visualized within the ostomy bag or if contrast was intraluminal distal to the loop ostomy. The loop ostomy was considered diverting if oral contrast was only visualized in the ostomy bag with no oral contrast distally. Of the 202 eligible patients, 26 (13%) underwent 41 postoperative CT scans of the abdomen/pelvis. Four (4) were excluded due to inadequate exam or confounding contrast (rectal contrast, contrast retention from preoperative scan). Of the remaining 22 patients with 35 CT scans (median age 54 [range 26-82] years, 10 men, 18 Caucasian, 18 having elective surgery), no patient (0%) had evidence of distal contrast. In this and other studies, loop stomas were found to provide adequate diversion without spillage into the nonfunctional limb for the vast majority of patients and should strongly be considered as the procedure of choice for temporary diversion.

Background: With the advent of laparoscopy, many traditional junior-level cases now require advanced laparoscopic skill. We sought to ascertain the implications of laparoscopy on residency training through the use of a large national database., Methods: American College of Surgeons National Surgical Quality Improvement Program data were gathered for patients undergoing elective open and laparoscopic inguinal herniorrhaphy, appendectomy, and partial colectomy during 2005 and 2006. Cases were stratified by resident level and compared using univariate analysis., Results: A total of 14,729 cases were performed during the study period. For inguinal hernia repair, 72% of open repairs were performed by postgraduate year 3 residents or below versus 41% of laparoscopic repairs (P < .0001). Similarly, 61% of open appendectomies were performed by postgraduate year 3 residents or below compared with 48% of laparoscopic appendectomies (P < .0001). Forty-six percent of open colectomies were performed by postgraduate year 3 and postgraduate year 4 residents versus 33% of laparoscopic resections (P < .0001)., Conclusions: These data show an upward shift in cases traditionally performed by junior-level residents. The implications of this shift are unknown but may lead to decreased surgical experience during the early years of training.

As part of our program to develop novel ligands for the estrogen receptor, we synthesized the series of isomeric 17alpha-(trifluoromethyl)phenylvinyl estradiols using our solid-phase organic synthesis methodology. The compounds were evaluated for their relative binding affinity (RBA) using the ERalpha-LBD and in vivo potency using the immature rat uterotrophic growth assay. The ortho-isomer had the highest RBA values, 48-223, and the highest estrogenicity in vivo. The other isomers had significantly lower affinities and were weaker agonists in the uterotrophic assay. The results suggest that introduction of substituents at the 17alpha-position of estradiol is tolerated by the ER-LBD and permit agonist responses in the intact animal, however, the effect is sensitive to the position of groups on the phenyl ring. This study demonstrates that the 17alpha-position of estradiol is a reasonable site for modification but the position and physicochemical properties of such modifications may significantly affect the affinity and efficacy of the ligand.

Background: The regulation of leptin in patients with critical illness is poorly understood. Sex, diet, body mass, and cytokines may all play a role., Objective: The aims of this study were to determine the factors influencing leptin concentrations in hospitalized patients beginning total parenteral nutrition (TPN) and whether a 3-d regimen of TPN would further increase plasma leptin concentrations above baseline., Design: Twenty-six patients requiring TPN were enrolled in this prospective, nonintervention study. Only 20 (11 women and 9 men) completed all 3 d of TPN., Results: Baseline plasma leptin in the TPN patients ranged from 62.5 to 1625 pmol/L ( +/- SD: 419 +/- 387; n = 26) and was not significantly different between men (444 +/- 494 pmol/L) and women (363 +/- 244 pmol/L). Baseline plasma insulin ranged from 76 to 695 pmol/L (271 +/- 188; n = 26) and was not correlated with plasma leptin. Leptin concentrations increased after 3 d of TPN, from 356 +/- 300 to 794 +/- 600 pmol/L (P < 0.05) in parallel with an increase in insulin from 257 +/- 187 to 979 +/- 917 pmol/L (P < 0.01) in the 20 patients who completed the study; however, the changes were not correlated when expressed as percentages. Although the men and women had insulin responses to feeding that were not significantly different, leptin concentrations did not increase significantly in men but increased 3-fold in women (to 1094 +/- 638 pmol/L; P < 0.01)., Conclusions: Leptin regulation in patients with a critical illness differs substantially from that in healthy persons. The importance of glucose and insulin in leptin secretion remains unclear, especially in men.

Differences in agonist responses of the novel estrogen receptor ligands (17alpha,20Z)-(p-methoxyphenyl)vinyl estradiol (1), (17alpha, 20Z)-(o-alpha,alpha,alpha-trifluoromethylphenyl)vinyl estradiol (2), and (17alpha,20Z)-(o-hydroxymethylphenyl)vinyl estradiol (3) led us to investigate their solution conformation. In competitive binding assay studies, we observed that several phenyl-substituted (17alpha, 20E/Z)-(X-phenyl)vinyl estradiols exhibited significant estrogen receptor binding, but with variation (RBA (1) = 20; RBA (2) = 23; RBA (3) = 140 where estradiol RBA = 100) depending on the phenyl substitution pattern. Because the 17alpha-phenylvinyl substituent interacts with the key helix-12 of the ligand binding domain, we considered that differences in the preferred conformation of 1-3 could account for their varying binding affinity. 2D NMR experiments at 500 MHz allowed the complete assignment of the (13)C and (1)H spectra of 1-3. The conformations of these compounds in solution were established by 2D and 1D NOESY spectroscopy. A statistical approach of evaluating contributing conformers of 1-3 from predicted (13)C shifts correlated quite well with the NOE data. The 17alpha substituents of 1 and 2 exist in similar conformational equilibria with some differences in relative populations of conformers. In contrast, the 17alpha substituent of 3 exists in a different conformational equilibrium. The similarity in solution conformations of 1 and 2 suggests they occupy a similar receptor volume, consistent with similar RBA values of 20 and 23. Conversely, the different conformational equilibria of 3 may contribute to the significant binding affinity (RBA = 140) of this ligand.

Mental health professionals are increasingly concerned with the consequences of clinical judgement errors. Such concern has led to an increase in requests for specialist advice from forensic mental health care teams. Consequently, the demand for forensic community mental health nurses (FCMHNs) to provide specialist advice and reports has increased. Such advice can be significant in planning and delivering care.