Unexpected and delayed fragmentation dynamics of the organometallic ferrocene induced by ion-collision.

We have investigated the fragmentation dynamics of the organometallic ferrocene molecule after interaction with multiply charged ions using multicoincidence mass spectrometry and quantum chemistry calculations. We observed unexpected fragmentation dynamics of the two-body breakup channels from ferrocene dications revealing a charge screening effect from the iron atom and delayed fragmentation dynamics. These observations are rationalized through the population of a specific long-lived excited state, where one positive charge is located on each cyclopentadienyl ring.

Evaluation of Undiagnosed HIV Estimates Computed from the CD4 Depletion Model in a Rural, Medium-low HIV Prevalence State.

The CD4 depletion model estimates diagnosis delays by approximating infection date from CD4 T-cell count at diagnosis, and back-calculation can compute the proportion of undiagnosed PLWHA. The model assumes the immigration of PLWHA to the U.S. is negligible and counts as a transmission event, which may be impractical outside high prevalence states. Duration of U.S. residency among foreign-born PLWHA and diagnosis delays were compared. The impact on estimates of undiagnosed PLWHA was tested through simulation with different proportions of foreign-born people assumed to have acquired HIV abroad. In 67% of foreign-born people, the mean (SD) years of delay (9.9 (6.3)) exceeded the duration of U.S. residency (2.0 (1.9)). Additionally, inaccuracies in the estimates for proportions of undiagnosed PLWHA were pronounced when foreign-born people who acquired HIV abroad comprised 30% of diagnoses. The CD4 model inadvertently misclassified some diagnoses as in-state transmission events. Consequently, simulated results demonstrated inaccuracies and unstable calculations.

New species of Parasaccocoelium (Haploporidae) and new genus Pseudohaplosplanchnus (Haplosplanchnidae) from mullet fish in the Far East of Russia and Vietnam: morphological and molecular data.

A description and the molecular characterization of two new species in the Haploporidae and Haplosplanchnidae families are provided herein. Parasaccocoelium armatum n. sp. was collected from the intestine of a Mugil cephalus Linnaeus, 1758 from the Primorsky region, Russia, and Pseudohaplosplanchnus catbaensis n. g. n. sp. was collected from Moolgarda seheli (Forsskål, 1775) in the coastal waters of Cat Ba Island, Vietnam. The morphological features of P. armatum n. sp. closely resemble those of Parasaccocoelium polyovum, but these species differ from one another by hermaphroditic sac and vitellaria area length and by maximal egg size. The main difference between P. armatum n. sp. and P. polyovum is the presence of an armed hermaphroditic duct in the new species. Molecular data support the case for inclusion of the studied trematodes in P. armatum n. sp. Worms P. catbaensis n. g. n. sp. from the mullet from Vietnam are morphologically close to Haplosplanchnus (Haplosplosplanchninae). The only difference between P. catbaensis n. g. n. sp. and species of Haplosplanchnus is the presence of few (1-7) large eggs, measuring 135-142 × 92-104 µm, versus numerous small eggs with a maximal size of 75 × 50 µm. Phylogenetic analysis showed that there is a contradiction between the morphological similarity of the worms and their position in the Haplosplanchnidae system, based on the genetic data. Results of this study indicate that P. catbaensis n. g. n. sp. is genetically distant from other representatives of Haplosplanchnus, despite their morphological similarity. According to the molecular data, P. catbaensis n. g. n. sp. is close to Hymenocotta mulli Manter, 1961 (Hymenocottinae). However, these species are considerably different to each other morphologically. Molecular data argue for the possibility of establishing a new subfamily for P. catbaensis n. g. n. sp. However, considering earlier studies of Haplosplanchnidae, we support the view that creating new subfamilies within this family is unreasonable because of the lack of molecular data for most haplosplanchnid species, which are necessary to resolve the problematic systematics and phylogeny of this family.

Sex differences in osteoporosis self-efficacy among community-residing older adults presenting for DXA.

The Osteoporosis Self Efficacy Scale was determined to equivalently measure calcium and exercise beliefs in both sexes. Despite data illustrating men's and women's similar self-efficacy, gender differences in clinical predictors of self-efficacy imply that efforts to improve care must account for more than self-efficacy. INTRODUCTION: To understand the extent to which the Osteoporosis Self Efficacy (OSE) Scale is reliable for both men and women. A secondary objective was to evaluate sex differences in OSE. METHODS: For this cross-sectional study, we analyzed data collected as part of the Patient Activation after DXA Result Notification (PAADRN) pragmatic trial which enrolled 7749 community-residing adults aged 50 and older reporting for bone densitometry. We used univariable methods, item analysis, exploratory and confirmatory factor analyses, and linear regression to evaluate sex differences in OSE responses and measurement. RESULTS: In this sample, the confirmatory factor analysis model for OSE both overall and within groups indicated a poor fit. The sex differences in the measurement model, however, were minor and reflected configural invariance (i.e., constructs were measuring the same things in both men and women), confirming that the OSE was measuring the same constructs in men and women. Men overall had higher exercise self-efficacy and women higher calcium self-efficacy. Overall, education, hip fracture, and self-reported health status predicted exercise self-efficacy whereas prior DXA, self-reported osteoporosis, and history of pharmacotherapy use did not. Predictors of calcium self-efficacy differed by gender. CONCLUSION: The OSE can be used to measure calcium and exercise self-efficacy in all older adults. However, gender differences in clinical predictors of self-efficacy and the lack of an association of prior DXA with self-efficacy imply that interventions to improve self-efficacy may be insufficient to drive significant improvement in rates of osteoporosis evaluation and treatment. TRIAL REGISTRATION: Patient Activation after DXA Result Notification (PAADRN), NCT01507662, https://clinicaltrials.gov/ct2/show/NCT01507662.

Decorin age-related variations in the distribution of pig extracellular matrix meniscus.

Menisci act like shock absorbers and transmit load across the tibiofemoral joint by increasing congruency during movements or body weight load. This leads to decreasing the resultant stress on the articular cartilages. The meniscus has a dense extracellular matrix (ECM) composed of water, different types of collagens, and proteoglycans, such as decorin, aggrecan and biglycan. Decorin (DCN) regulates collagen fibrillogenesis acting on collagen fibrils diameter and fibrils orientation to achieve the proper assembly of its network. This work investigates the spatial disposition of this fundamental protein in pig meniscus' matrix by immunohistochemistry and western blot analysis. DCN shows an increasing trend, moving from neonatal to adult pig menisci. Adult meniscus, in porcine species, is the only one that could be considered fully mature and functional, and, even if an increasing trend is seen, no precise phenotypical switch points are seen in the age stages considered in this study.

Factors Associated with Receiving Late HIV Testing Among Women Delivering at Hung Vuong Hospital, Ho Chi Minh City, Vietnam, 2014.

HIV testing during pregnancy facilitates timely antiretroviral treatment for HIV-positive women. This study identifies reasons for late HIV testing among pregnant women delivering at a hospital in Ho Chi Minh City. We conducted a case-control study in which 160 cases were women who were tested for HIV late (i.e., at labor and delivery) and 160 controls were women who were tested during antenatal care (ANC). In multivariable logistic regression analysis, six variables were associated with late HIV testing: age less than 30 years, nine or fewer years of education, working as a homemaker or worker/farmer, living 20 km or more from the hospital, having received ANC at a private clinic/hospital only, and not believing that HIV testing is important during pregnancy. We recommend that national programs should provide additional effort for HIV testing during pregnancy to young women, less educated women, homemakers, and those receiving ANC at private clinics and hospitals.

Characterization of different in vitro culture conditions to induce a fibro-chondrogenic differentiation of swine adipose-derived stem cells.

Meniscus repair is still a challenge for orthopaedic surgeons as this tissue has a scarce healing potential due to the limited vascularization and to the lack of progenitor cells. Lately, several tissue engineering strategies combining cells and scaffolds have been developed. Adipose-derived stem cells (ASCs) represent a novel cell source for meniscus repair as they are easy to harvest, and they possess an intrinsic chondrogenic potential. The aim of our study was to analyze and compare the chondrogenic differentiation of swine ASCs cultured in vitro with different supplemented media. We isolated ASCs from swine adipose tissue and we placed in pellet cultures supplemented with either Bone Morphogenetic Protein (BMP)-2 and Transforming Growth Factor (TGF)-ß3 or with Bone Morphogenetic Protein (BMP)-7 and Transforming Growth Factor (TGF)-ß1. Samples were analyzed after 7, 14 or 21 days of culture by biochemical, histological and gene expression analysis. Our preliminary results show that BMP-2 and TGF-ß3 are stronger inducers of chondrogenesis.

Animal models for cartilage repair.

Cartilage lesions still represent an unsolved problem: despite the efforts of the basic and translational research, the regeneration of this tissue is far from being reached (1-3). Articular cartilage lesions can be divided in two main groups: superficial or partial defects and full-thickness defects (4, 5). Partial lesions are not able to self-heal because multipotent cells from the bone marrow cannot reach the area leading to a progressive degeneration of the tissue (6). Conversely, full-thickness injuries possess greater chances to heal because subchondral bone involvement allows for the migration of mesenchymal cells, which fill the damaged area (7, 8). However, healing occurs through the formation of a fibrocartilaginous tissue, which has different biomechanical and biological properties (9). Native hyaline cartilage has indeed specific biomechanical properties, which confer resistance to compressive and shear stresses; the reparative fibrocartilaginous tissue lacks these abilities, therefore, the surrounding healthy cartilage progressively degenerates. In the past years, several therapeutic strategies have been developed to restore the damaged cartilage, bone marrow stimulation (chondroabrasion, drilling, micro- or nano-fractures) and more recently, tissue engineering approaches (10-14). Some of these latter procedures have already been applied in clinical practice such as matrix-induced autologous chondrocyte implantation (MACI) (15) or osteochondral scaffold implantation (16). Generally, tissue engineering approaches are based on the combination of three main elements: cells (i.e. primary chondrocytes or multipotent mesenchymal cells), biocompatible scaffolds (i.e. polymers, composites, ceramics) and signaling molecules (i.e. growth factors). Moreover, several culture conditions (i.e. static or dynamic cultures) and biomechanical stimuli can be applied during the in vitro culture to promote tissue maturation (17-19). However, an in vivo culture is mandatory to validate a new engineered construct as the in vitro phase lacks the essential in vivo environmental stimuli and because the in vivo culture allows for the testing of the biocompatibility and safety of a new material (18, 19). Moreover, preclinical animal models are crucial to understand the molecular mechanisms of cartilage lesions favoring the development of new regenerative strategies (20, 21). in vivo studies on animal models should focus on the analysis of the cellular component, analyzing the maintenance of the cellular phenotype and the tumorigenicity; on the evaluation of the biocompatibility, toxicity and degradation of the biomaterial and on the assessment of the engineered construct. In this manuscript, we will review the most common preclinical animal models, which are used to understand cartilage biology and therefore to develop new tissue engineering strategies. We will focus on both small and large animal models highlighting their peculiarities, advantages and drawbacks.

Validity, reliability, and responsiveness to change of the "Osteoporosis and You" knowledge scale.

We studied the Osteoporosis and You knowledge scale in 7749 participants enrolled in a clinical trial. Results confirmed its psychometric properties in a diverse audience. Baseline scores were associated with better recall of bone mineral density test results at follow-up; however, the scale was not responsive to knowledge change. INTRODUCTION: The goal of this study was to confirm the measurement properties of the Osteoporosis and You (O&Y) knowledge scale using classic test theory methods in the 7749 men and women participating in the Patient Activation After DXA Result Notification (PAADRN) randomized controlled trial. We hypothesized a simple factor structure that would reflect the four-factor model previously published. METHODS: We conducted psychometric analyses which included item analysis, internal consistency reliability, construct validity using exploratory and confirmatory factor analysis (EFA and CFA), comparing knowledge levels across pre-specified groups, and responsiveness to change. RESULTS: PAADRN participants were predominantly college educated, White females with low bone density, and a moderate level of 10-year fracture risk. EFA revealed four domains closely matching those in two previous reports. While overall scale reliability was minimally acceptable at 0.68, the reliabilities of the domain subscales were unacceptably low (0.59, 0.64, 0.45, and 0.36 for the Biological, Lifestyle, Consequences, and Prevention and Treatment subscales). CFA revealed the data fit the hypothesized model reasonably well with the items loading on their expected latent variable. The scale was not responsive to change, but although not significant, improved knowledge indicated better DXA result recall at 12 and 52 weeks. CONCLUSIONS: In the PAADRN population, the O&Y knowledge scale had psychometric properties similar to those previously reported. Over 12 and 52 weeks, participants did not demonstrate significant changes in knowledge, but those with higher knowledge at baseline were more likely to accurately recall their baseline DXA result.

Distinct neurobiological signatures of brain connectivity in depression subtypes during natural viewing of emotionally salient films.

BACKGROUND: Establishing an evidence-based diagnostic system informed by the biological (dys)function of the nervous system is a major priority in psychiatry. This objective, however, is often challenged by difficulties in identifying homogeneous clinical populations. Melancholia, a biological and endogenous subtype for major depressive disorder, presents a canonical test case in the search of biological nosology. METHOD: We employed a unique combination of naturalistic functional magnetic resonance imaging (fMRI) paradigms - resting state and free viewing of emotionally salient films - to search for neurobiological signatures of depression subtypes. fMRI data were acquired from 57 participants; 17 patients with melancholia, 17 patients with (non-melancholic) major depression and 23 matched healthy controls. RESULTS: Patients with melancholia showed a prominent loss of functional connectivity in hub regions [including ventral medial prefrontal cortex, anterior cingulate cortex (ACC) and superior temporal gyrus] during natural viewing, and in the posterior cingulate cortex while at rest. Of note, the default mode network showed diminished reactivity to external stimuli in melancholia, which correlated with the severity of anhedonia. Intriguingly, the subgenual ACC, a potential target for treating depression with deep brain stimulation (DBS), showed divergent changes between the two depression subtypes, with increased connectivity in the non-melancholic and decreased connectivity in the melancholic subsets. CONCLUSION: These findings reveal neurobiological changes specific to depression subtypes during ecologically valid behavioural conditions, underscoring the critical need to respect differing neurobiological processes underpinning depressive subtypes.

Relationship of galectin-3 with obesity, IL-6, and CRP in women.

PURPOSE: To evaluate the association of galectin-3 (Gal3) with obesity and inflammatory status in a cohort of metabolically healthy, predominantly African-American women with varying cardiovascular disease (CVD) risk as determined by CRP levels. METHODS: We assessed the association between BMI and serum levels of Gal3, IL-6, CRP, and adiponectin in metabolically healthy women (N = 97) to determine the overall association between Gal3, obesity, and inflammation in groups at different CVD risk. RESULTS: Obese women had significantly higher serum Gal3 compared to non-obese participants (P = 0.0016), although Gal3 levels were comparable among different classes of obesity. BMI (R 2 = 0.1406, P = 0.0013), IL-6 (R 2 = 0.0689, P = 0.035), and CRP (R 2 = 0.0468, P = 0.0419), but not adiponectin, positively predicted the variance of Gal3 levels in the total study population. However, the predicting effect of BMI (R 2 = 0.2923, P = 0.0125) and inflammation (R 2 = 0.3138, P = 0.038) on Gal3 was only present in women at low/moderate risk of CVD (CRP ≤ 3 µg/mL). CONCLUSIONS: Gal3 is positively correlated with obesity and inflammation in women, while the presence of elevated CVD risk may disturb the strength of Gal3 as a biomarker of inflammation.

Enhancing classical swine fever virus identification: the advantages of Field-LAMP testing.

Classical swine fever virus (CSFV) identification has witnessed significant advancements with the development of rapid reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assays. However, conventional RT-LAMP assays for CSFV diagnosis are hindered by a laborious RNA extraction step. Moreover, the need for thermal incubators and expensive micropipettes has limited their application in field settings. Addressing these challenges, our study presents a groundbreaking solution-an electro-free and point-of-care (POC) tool known as the field-LAMP assay-for the rapid clinical detection of CSFV. By eliminating the RNA extraction requirement, advancing the colorimetric read-out and lyophilized reaction reagents, our field-LAMP assay streamlines the diagnostic process, saving valuable time and effort. This novel approach also overcomes the dependency on electric-dependent thermal incubators and expensive micropipettes, making it practical and accessible for use in the field. The successful development of the field-LAMP assay marks a significant milestone in CSFV detection. This electro-free and POC tool offers several advantages, including its ability to deliver rapid results without compromising accuracy, facilitating prompt response and containment measures.

Engagement of a community advisory group to shape and build up participation in TB research.

It is essential that communities at risk from TB are involved in TB research. Community advisory groups (CAGs) are one mechanism for involving communities in research and creating platforms for discussions between researchers and community members. We organised a CAG meeting with community members and people with lived experience in Ho Chi Minh City, Vietnam, to explore the community's knowledge about TB and their perspectives on different diagnostic tests in Vietnam, a low-middle-income country with a high TB burden. Researchers shared basic information and addressed questions about TB. CAG members commented on preference of TB screening tests, and suggested that chest X-rays and blood tests were more acceptable than sputum tests because of the difficulty in sputum expectoration. In addition, clinical studies that required fewer visits to the hospitals would be preferred, even if this meant a greater reliance on blood sampling.

Il est essentiel que les communautés exposées au risque de TB soient impliquées dans la recherche sur la TB. Les groupes consultatifs communautaires (CAG, pour l'anglais « community advisory groups ¼) constituent un mécanisme permettant d'impliquer les communautés dans la recherche et de créer des plateformes de discussion entre les chercheurs et les membres de la communauté. Nous avons organisé une réunion du CAG avec des membres de la communauté et des personnes ayant une expérience vécue à Ho Chi Minh Ville, au Viêt Nam, afin d'explorer les connaissances de la communauté sur la TB et leurs perspectives sur les différents tests de diagnostic au Viêt Nam, un pays à revenu faible et moyen où la charge de la TB est élevée. Les chercheurs ont partagé des informations de base et répondu à des questions sur la TB. Les membres du CAG ont fait part de leur préférence pour les tests de dépistage de la TB et ont suggéré que les radiographies pulmonaires et les analyses de sang étaient plus acceptables que les tests d'expectoration en raison de la difficulté d'expectoration des crachats. En outre, les études cliniques qui nécessitent moins de visites dans les hôpitaux seraient préférées, même si cela implique une plus grande dépendance à l'égard des prélèvements sanguins.

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S ESR1 Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ERα ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ERα breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29's activities in breast cancer cells harboring Y537S ERα. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER+ breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER+ breast cancers.

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S ESR1 Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ERα ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ERα breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29's activities in breast cancer cells harboring Y537S ERα. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER+ breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER+ breast cancers.

Impacts of climate change on rainfall extremes and urban drainage systems: a review.

A review is made of current methods for assessing future changes in urban rainfall extremes and their effects on urban drainage systems, due to anthropogenic-induced climate change. The review concludes that in spite of significant advances there are still many limitations in our understanding of how to describe precipitation patterns in a changing climate in order to design and operate urban drainage infrastructure. Climate change may well be the driver that ensures that changes in urban drainage paradigms are identified and suitable solutions implemented. Design and optimization of urban drainage infrastructure considering climate change impacts and co-optimizing these with other objectives will become ever more important to keep our cities habitable into the future.

Individual-level permethrin exposure biomarkers in U.S. army soldiers: comparison of two treatment formulations for military uniforms.

BACKGROUND: Evidence suggests that wearing permethrin-treated military uniforms is not associated with current adverse health conditions. However, exposure through this route results in permethrin biomarker concentrations considerably higher than those in the U.S. POPULATION: The U.S. Army is exploring different methods of uniform treatment that reduce exposure while maintaining effective protection from insect vector-borne diseases. OBJECTIVE: To compare permethrin exposure when wearing two types of permethrin-treated military uniforms. METHODS: Eight male soldiers participated in a 32-day crossover design study to compare permethrin exposure when wearing the current Army uniform (CurrU) and a uniform with a new applied fabric treatment (NewU). Each soldier wore the uniforms for designated 8 h/day time periods over 3 consecutive days separated by a 'wash-out' week of no exposure. Permethrin exposure was assessed from the urinary concentrations of 3-phenoxybenzoic acid (3-PBA) and of the sum of cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (∑DCCA). Estimated dose was determined based on ∑DCCA concentrations. RESULTS: Permethrin exposure biomarkers were 21% (3-PBA, p = 0.025) and 35% (∑DCCA, p < 0.001) lower when wearing the NewU compared to the CurrU; the dose was 33% lower (p = 0.05). SIGNIFICANCE: Findings suggest the new treatment reduces human permethrin exposure biomarkers resulting from wearing-treated military uniforms.

Assessment of bowel movement dysfunction following laparoscopic low anterior resection for rectal cancer: a single-center study from Vietnam.

OBJECTIVE: Postoperative bowel movement dysfunction is a challenging problem greatly affecting patients' quality of life after low anterior resection. We aimed to evaluate the bowel movement function of patients undergoing laparoscopic low anterior resection for rectal cancer. PATIENTS AND METHODS: This retrospective study recruited 82 rectal cancer patients undergoing laparoscopic low anterior resection from July 2018 to July 2020 at 108 Military Central Hospital, Hanoi, Vietnam. RESULTS: The patients' mean age was 62.3±11.6 (28-84) years, 54 (65.9%) were males, and 28 (34.1%) were females. Bowel movement function changed significantly after one year: the average score for low anterior resection syndrome (LARS) after three months, six months, and one year was 17.6, 14.0, and 10.6, respectively. The rate of patients with major LARS decreased from 26.8% after three months to 14.6% after one year. The Wexner score also decreased from 5.9 after three months to 3.4 after one year. The rate of patients with normal bowel movement increased from 28.0% after three months to 46.3% after one year. The rate of patients with complete fecal incontinence decreased from 11.0% after three months to 7.3% after one year. Preoperative chemoradiotherapy (p=0.017), tumor location (p=0.02), method of anastomosis (p=0.01), and anastomosis location (p=0.000) were risk factors associated with major LARS after surgery. CONCLUSIONS: Bowel movement dysfunction in rectal cancer patients undergoing laparoscopic low anterior resection is a common and persistent problem after surgery. However, bowel function gradually recovers over time. Therefore, patients should be monitored and supported for a better quality of life.

Biomedical doctoral students' research practices when facing dilemmas: two vignette-based randomized control trials.

Our aim was to describe the research practices of doctoral students facing a dilemma to research integrity and to assess the impact of inappropriate research environments, i.e. exposure to (a) a post-doctoral researcher who committed a Detrimental Research Practice (DRP) in a similar situation and (b) a supervisor who did not oppose the DRP. We conducted two 2-arm, parallel-group randomized controlled trials. We created 10 vignettes describing a realistic dilemma with two alternative courses of action (good practice versus DRP). 630 PhD students were randomized through an online system to a vignette (a) with (n = 151) or without (n = 164) exposure to a post-doctoral researcher; (b) with (n = 155) or without (n = 160) exposure to a supervisor. The primary outcome was a score from - 5 to + 5, where positive scores indicated the choice of DRP and negative scores indicated good practice. Overall, 37% of unexposed participants chose to commit DRP with important variation across vignettes (minimum 10%; maximum 66%). The mean difference [95%CI] was 0.17 [- 0.65 to 0.99;], p = 0.65 when exposed to the post-doctoral researcher, and 0.79 [- 0.38; 1.94], p = 0.16, when exposed to the supervisor. In conclusion, we did not find evidence of an impact of postdoctoral researchers and supervisors on student research practices.Trial registration: NCT04263805, NCT04263506 (registration date 11 February 2020).