Depression and anxiety in women with malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST): an analysis of the AGO-CORSETT database.

INTRODUCTION: The intention of this study was to evaluate the level of anxiety and depression of malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) survivors and to identify possible alterable cofactors. METHODS: CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO Studygroup. Women who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate distress. Predictors of distress (type of surgery, chemotherapy, time since diagnosis, recurrence, second tumor, pain) were investigated using multivariate linear regression analysis. RESULTS: 150 MOGCT and SCST patients with confirmed histological diagnosis completed the questionnaire median seven years after diagnosis. They had a HADS total score ≥ 13 indicating severe mental distress in 34% of cases. Patients after fertility-conserving surgery had lower probability of severe mental distress than those without fertility-conserving treatment (ß = - 3.1, p = 0.04). Pain was associated with the level of distress in uni- and multivariate analysis (coef 0.1, p < 0.01, coef. Beta 0.5). DISCUSSION: Severe mental distress was frequent in patients with MOGCT and SCST and the level of pain was associated with the level of distress. Fertility conserving therapy, however, was associated with less mental distress. Screening and treatment of pain and depression is required to improve mental well-being in survivors of MOGCT and SCST.

Impact of Bepanthen® and dexpanthenol on human nasal ciliary beat frequency in vitro.

BACKGROUND: Dexpanthenol-containing ointments/fluids are recommended to restore impaired nasal mucosa. To date, there are no data about the influence of dexpanthenol or formulations including dexpanthenol on ciliary beat frequency (CBF) of nasal epithelial cells. METHODS: We tested the ciliary beat frequency of human nasal epithelial cells in RPMI 1640 cell solution using in vitro high-frequency video microscopy every 60 s over a period of 15 min (min). Bepanthen® solution and dexpanthenol in two clinically relevant concentrations (1.67% and 3.33%) were added to the cells. Addition of sterile water served as control group. To get a better overview, the measurements after 1 min, 5 min and 15 min were combined. RESULTS: The CBF in the control group (n = 17) after 15 min was 7.3 ± 2.6 Hz. In comparison, the CBF after 15 min was 1.8 ± 1.0 Hz in the 3.33% Bepanthen® group (n = 17) and 3.2 ± 1.2 Hz in the 1.67% group, which was statistically significantly lower in both groups (p < 0.001). With regard to the dexpanthenol group (n = 17) a CBF of 6.0 ± 2.6 Hz with 3.33% and 6.1 ± 2.4 Hz with 1.67% dexpanthenol, was detected, which was again statistically significantly lower (p = 0.06) compared to the control group except CBF at 15 min with 1.57% (n = 17; p = 0.04). In general, the effect on CBF was less pronounced with dexpanthenol compared with Bepanthen® with a statistically significant difference between the two formulations. The results were verified by calculating an analysis of variance (ANOVA). CONCLUSIONS: Bepanthen® as an ointment, solution or inhalation is commonly used in ENT for mucosal care. Our results have shown that both substances reduce CBF in clinically relevant concentrations, although the effect was more pronounced with Bepanthen® compared to dexpanthenol solution, which could be related to additives or change of physical properties in the solution. Further research is needed to assess potential clinical relevance.

Neurovascular territories of the canine fossa: Analysis of a South African population.

BACKGROUND: The canine fossa, a depression on the surface of the maxillary bone, is important clinically due to the nexus of the neurovascular elements which occur in this region and supply the superficial and deep structures of the face. While it is known that there is much variation in the neurovascular structures of this region, little is known about sex differences. The aim of this study was to investigate and map the neurovascular branching within the region of the canine fossa of a South African population, with particular reference to any sex differences. METHODS: Sixty hemifaces (n=30 female; n=30 male) of individuals between the ages of 40 and 100years were dissected. The origin, number of branches, connections between branches, origin of connecting branches and the distribution of the neurovascular structures associated with the mid-facial and canine fossa regions were documented. The data obtained was qualitative and was statistically analysed with SPSS v26 statistical analysis software. Frequency and contingency tables, along with Chi-squared analysis and Fischer's Exact test, were used for quantitative data analysis. RESULTS: While high levels of variation in the neurovascular elements were documented, there was no statistically significant variation between the sexes. A sex variation was only observed for the terminal branches of CN VII with females displaying a lower number of buccal nerve terminal branches than males. CONCLUSION: While only one sex difference of significance was found in the highly variable neurovascular structures resident in the region of the canine fossa, the variability of the neurovascular elements is of importance to surgeons.

Infusing geriatrics in Indian Health Service general primary care clinics: Extending VA workforce development training.

As federal partners, the Veterans Health Administration (VA) and the Indian Health Service (IHS) agreed to share resources, such as education. The VA Geriatric Scholars Program, a workforce development program, provides one of its training programs on team-based primary care of elders to clinicians working in IHS and Tribal Health Programs. The practical impact of that training is described. A mixed methods approach was applied to the course's evaluation survey at five clinics in the Northwestern Plains, Southwest, Pacific Coast, and Alaska. Quantitative approaches assessed participants' self-reported intention to improve recognition and assessment of common geriatric syndromes. A qualitative approach applied to open-ended text responses revealed intensions to improve team-based care. Among the 51 respondents in our sample, we found significant improvements in self-reported ability to recognize previously unfamiliar potential risks to elders' health and safety, t(49) = 8.0233, p < .001, as well as increased comfort with conducting geriatric assessments and increased confidence in interprofessional team-based communication. Improvements to team-based care included enhanced clinical skills, organizational factors and the need to train additional employees. This evaluation demonstrates the value of sharing resources among federal partners and its value for participants in IHS and Tribal Health Programs.

Enhancing specialty training in geropsychology competencies: An evaluation of a VA Geriatric Scholars Program advanced topics workshop.

There is a growing need for psychologists with specialized training in geriatric mental health competencies. The Geriatric Scholars Program for Psychologists (GSP-P) was created to address this shortage within a large integrated healthcare system. In 2019, GSP-P piloted an advanced workshop designed to enhance expertise in geriatric mental health competencies among graduates of its foundational competencies core course. The workshop included 3.5 days of expert-led seminars regarding the biopsychosocial needs of older adults with chronic medical illness and was followed by completion of an individualized learning plan. This paper describes the evaluation of the course using a mixed methods with data collected prior to the workshop, immediately post-workshop, and six months post-workshop. Results indicated enthusiasm for the workshop, significant improvements in four geropsychology domains on the Pikes Peak Geropsychology Knowledge and Skill Assessment Tool, and benefit from completion of the independent learning plans. Our findings demonstrate that continued enhancement of geropsychology competencies through advanced coursework is feasible and improves knowledge and skill, particularly when combined with individualized learning plans.

Acute endometriosis-related sigmoid perforation in pregnancy- case report.

BACKGROUND: An acute abdomen is an emergency that requires accurate diagnosis and prompt treatment. In pregnancy, the process is even more challenging and sometimes the radiological findings are unclear. Moreover, endometriosis- related complications are rare, especially in previously unknown endometriosis. CASE PRESENTATION: We report on a case of acute endometriosis-related sigmoid perforation during pregnancy (34 weeks of gestation) due to a previously unknown deep intestinal infiltrating endometriosis with focal ulceration of the affected colonic mucosa. CONCLUSIONS: Despite the low relative risk, clinicians should be aware of possible endometriosis-associated complications in pregnancy with potentially life-threatening events, even in previously unknown endometriosis. Further studies should evaluate intestinal complications during pregnancy in relation to previous treatment of intestinal endometriosis (conservative vs. surgical).

[Reconstruction after facial trauma with dento-alveolar injury]. / Reconstructie na aangezichtstrauma met dentoalveolair letsel.

While abroad, a healthy 36-year-old woman slammed head-on into a rock wall at high speed, resulting in significant facial trauma. The initial trauma care and first aid took place abroad. In the Netherlands, the woman was referred to the Department of Oral and Maxillofacial Surgery (OMFS) for reconstruction of her face and alveolar processes, gingiva and dentition. In view of the seriousness of the injuries, a 3D treatment plan was drawn up in a multidisciplinary collaboration with an OMF surgeon, an implantologist, dentist and dental technician. By making a digital setup of both the top and bottom front in advance, it was possible to work predictably. The first step consisted of bone augmentation by means of an iliac crest graft to reconstruct the major bone defects of the superior and inferior alveolar processes. Implants were then placed in the upper and lower jaws in the ideal position for the suprastructure by means of drill jigs. Within 10 months after the trauma, the implant bridges could be placed on individual zirconia frameworks to optimally restore oral function and aesthetics, completing the reconstruction.

Chorioamnionitis induces enteric nervous system injury: effects of timing and inflammation in the ovine fetus.

BACKGROUND: Chorioamnionitis, inflammation of the chorion and amnion, which often results from intrauterine infection, is associated with premature birth and contributes to significant neonatal morbidity and mortality, including necrotizing enterocolitis (NEC). Recently, we have shown that chronic chorioamnionitis is associated with significant structural enteric nervous system (ENS) abnormalities that may predispose to later NEC development. Understanding time point specific effects of an intra-amniotic (IA) infection on the ENS is important for further understanding the pathophysiological processes and for finding a window for optimal therapeutic strategies for an individual patient. The aim of this study was therefore to gain insight in the longitudinal effects of intrauterine LPS exposure (ranging from 5 h to 15 days before premature delivery) on the intestinal mucosa, submucosa, and ENS in fetal lambs by use of a well-established translational ovine chorioamnionitis model. METHODS: We used an ovine chorioamnionitis model to assess outcomes of the fetal ileal mucosa, submucosa and ENS following IA exposure to one dose of 10 mg LPS for 5, 12 or 24 h or 2, 4, 8 or 15 days. RESULTS: Four days of IA LPS exposure causes a decreased PGP9.5- and S100ß-positive surface area in the myenteric plexus along with submucosal and mucosal intestinal inflammation that coincided with systemic inflammation. These changes were preceded by a glial cell reaction with early systemic and local gut inflammation. ENS changes and inflammation recovered 15 days after the IA LPS exposure. CONCLUSIONS: The pattern of mucosal and submucosal inflammation, and ENS alterations in the fetus changed over time following IA LPS exposure. Although ENS damage seemed to recover after prolonged IA LPS exposure, additional postnatal inflammatory exposure, which a premature is likely to encounter, may further harm the ENS and influence functional outcome. In this context, 4 to 8 days of IA LPS exposure may form a period of increased ENS vulnerability and a potential window for optimal therapeutic strategies.

Why do anti-inflammatory signals of bone marrow-derived stromal cells improve neurodegenerative conditions where anti-inflammatory drugs fail?

Neurodegenerative disorders share the final degenerative pathway, the inflammation-induced apoptosis and/or necrosis, irrespective of their etiology, be it of acute and chronic traumatic, vascular and idiopathic origin. Although disease-modifying strategies are an unmet need in these disorders, lately, (pre)clinical studies suggested favorable effects after an intervention with bone marrow-derived stromal cells (bm-SC). Recent interventions with intrathecal transplantation of these cells in preclinical rodent models improved the functional outcome and reduced the inflammation, but not anti-inflammatory drugs. The benefit of bm-SCs was demonstrated in rats with an acute (traumatic spinal cord injury, tSCI) and in mice with a chronic [amyotrophic lateral sclerosis (ALS)-like FUS 1-358 or SOD1-G93-A mutation] neurodegenerative process. Bm-SCs, were found to modify underlying disease processes, to reduce final clinical SCI-related outcome, and to slow down ALS-like clinical progression. After double-blind interventions with bm-SC transplantations, Vehicle (placebo), and (non)steroidal anti-inflammatory drugs (Methylprednisolone, Riluzole, Celecoxib), clinical, histological and histochemical findings, serum/spinal cytokines, markers for spinal microglial activation inclusive, evidenced the cell-to-cell action of bm-SCs in both otherwise healthy and immune-deficient tSCI-rats, as well as wild-type and FUS/SOD1-transgenic ALS-like mice. The multi-pathway hypothesis of the cell-to-cell action of bmSCs, presumably using extracellular vesicles (EVs) as carriers of messages in the form of RNAs, DNA, proteins, and lipids rather than influencing a single inflammatory pathway, could be justified by the reported differences of cytokines and other chemokines in the serum and spinal tissue. The mode of action of bm-SCs is hypothesized to be associated with its dedicated adjustment of the pro-apoptotic glycogen synthase kinase-3ß level towards an anti-apoptotic level whereas their multi-pathway hypothesis seems to be confirmed by the decreased levels of the pro-inflammatory interleukin (IL)-1ß and tumor necrosis factor (TNF) as well as the level of the marker of activated microglia, ionized calcium binding adapter (Iba)-1 level.

Inactivation of bacterial endospores on surfaces by plasma processed air.

AIMS: In case of biological hazards and pandemics, personal protective equipment of rescue forces is currently manually decontaminated with harmful disinfectants, primarily peracetic acid. To overcome current drawbacks regarding supply, handling and disposal of chemicals, the use of plasma processed air (PPA) represents a promising alternative for surface decontamination on site. In this study, the sporicidal efficiency of a portable plasma system, designed for field applications, was evaluated. METHODS AND RESULTS: The developed plasma device is based on a dielectric barrier discharge (DBD) and operated with ambient air as process gas. PPA from the plasma nozzle was flushed into a treatment chamber (volume: 300 l) and bacterial endospores (Bacillus subtilis and Bacillus atrophaeus) dried on different surfaces were treated under variable conditions. Reductions in spores by more than 4 log10 were found within 3 min of PPA exposure. However, the presence of endospores in agglomerates or in an organic matrix as well as the complexity of the respective surface microstructure negatively affected the inactivation efficiency. When endospores were embedded in a dried protein matrix, mechanical wiping with swabs during exposure to PPA increased the inactivation effect significantly. Gaseous ozone alone did not provide a sporicidal effect. Significant spore inactivation was only obtained when water vapour was injected into the PPA stream. CONCLUSION: The results show that endospores dried on surfaces can be reduced by several orders of magnitude within few minutes in a treatment chamber which is flushed with PPA from of a DBD plasma nozzle. SIGNIFICANCE AND IMPACT OF THE STUDY: Plasma processed air generated on site by DBD plasma nozzles could be a suitable alternative for the disinfection of various surfaces in closed rooms.

Socio-ecological determinants of lifestyle behavior of women with overweight or obesity before, during and after pregnancy: qualitative interview analysis in the Netherlands.

BACKGROUND: Maternal overweight and obesity are related to several health risks in the periods before, during and after pregnancy including a higher risk of gestational diabetes mellitus, preeclampsia and preterm birth. At the same time, women's daily life quickly changes in these periods. Therefore, we hypothesize that the value of determinants of lifestyle behavior within different levels of the socio-ecological model differ accordingly and influence lifestyle behavior. These dynamics of determinants of lifestyle behavior in the periods before, during and after pregnancy are unexplored and therefore evaluated in this study. These insights are needed to offer appropriate guidance to improve lifestyle in women of childbearing age. METHODS: Individual semi-structured interviews were conducted before, during or after pregnancy in 26 women with overweight or obesity living in the Netherlands. Questions covered all levels of the socio-ecological model, i.e. intrapersonal, interpersonal, institutional and environmental/societal. All interviews were transcribed and coded. RESULTS: Determinants at all levels of the socio-ecological model were perceived as relevant by women of childbearing age. Various determinants were mentioned including knowledge of a healthy lifestyle, social support, access to customized lifestyle guidance, and distance to healthy lifestyle supporting activities. The importance women attributed to determinants differed between the periods before, during and after pregnancy. Before pregnancy, child's wellbeing as motivator for adopting a healthy lifestyle was mentioned less frequently than during and after pregnancy. Women described that the interplay and balance between determinants varied on a daily basis, and not merely per period. This was often expressed as fluctuation in energy level per day which influences their willingness to put effort in making healthy choices. CONCLUSIONS: Findings of this study confirm the importance of determinants at multiple socio-ecological levels for shaping lifestyle behavior in women of childbearing age. The findings add to current insights that the perceived importance of determinants and their interplay differ before, during and after pregnancy. They influence lifestyle behavior decisions, not only per period but even on a daily basis, in particular in this phase of life. This perspective can be helpful in optimizing lifestyle guidance for women of childbearing age in order to prevent perinatal complications.

Introduction of less invasive surfactant administration (LISA), impact on diagnostic and therapeutic procedures in early life: a historical cohort study.

BACKGROUND: In preterm infants with Respiratory Distress Syndrome (RDS), Less Invasive Surfactant Administration (LISA) has been established to reduce the need of mechanical ventilation and might improve survival rates without bronchopulmonary dysplasia. The aim of this study was to investigate whether NICU care has changed after introduction of less invasive surfactant administration (LISA), with regard to diagnostic and therapeutic procedures in the first week of life. METHODS: Infants with gestational age < 32 weeks who received surfactant by LISA (June 2014 - December 2017, n = 169) were retrospectively compared to infants who received surfactant after intubation (January 2012 - May 2014, n = 155). Local protocols on indication for surfactant, early onset sepsis, blood transfusions and enteral feeding did not change between both study periods. Besides, as secondary outcome complications of prematurity were compared. Data was collected from electronic patient files and compared by univariate analysis through Students T-test, Mann Whitney-U test, Pearson Chi-Square test or Linear by Linear Association. RESULTS: All baseline characteristics of both groups were comparable. Compared to controls, LISA patients received a higher total surfactant dose (208 vs.160 mg/kg; p < 0.001), required redosing more frequently (32.5% vs. 21.3%; p = 0.023), but needed less mechanical ventilation (35.5% vs. 76.8%; p < 0.001). After LISA, infants underwent fewer X-rays (1.0 vs. 3.0, p < 0.001), blood gas examinations (3.0 vs. 5.0, p < 0.001), less inotropic drugs (9.5% vs. 18.1%; p = 0.024), blood transfusions (24.9% vs. 41.9%, p = 0.003) and had shorter duration of antibiotic therapy for suspected early onset sepsis (3.0 vs. 5.0 days, p < 0.001). Moreover, enteral feeding was advanced faster (120 vs. 100 mL/kg/d, p = 0.048) at day seven. There were no differences in complications of prematurity. CONCLUSION: The introduction of LISA is associated with significantly fewer diagnostic and therapeutic procedures in the first week of life, which emphasizes the beneficial effects of LISA.

[Stimulatory and inhibitory signaling pathways of the T cell-APC interaction and the effect of TLR agonists on APCs]. / Stimulierende und inhibierende Signalwege der APZ- und T-Zell-Interaktion sowie Einfluss von TLR-Agonisten auf APZ.

BACKGROUND: CD8+ cells are key players in the identification and elimination of cancer cells. Cancers can escape an effective T cell response by inducing an exhausted cell state, which limits the cytotoxic capacity of the effector cells. Among other mechanisms, new checkpoint inhibitors reactivate exhausted, dysfunctional T cells. CD8+ T cells can eliminate tumor cells after presentation of tumor-specific antigens via antigen-presenting cells (APCs). APC-mediated tumor recognition is mainly stimulated by Toll-like receptors (TLRs). OBJECTIVE: This study investigates the effect of TLR agonists on APCs as well as stimulatory and inhibitory signaling pathways of the T cell-APC interaction. MATERIALS AND METHODS: Gene expression of interleukin (IL)12 and programmed death ligand 1 (PD-L1) was analyzed by quantitative polymerase chain reaction (qPCR) after 0, 8, 24, and 48 h of CD14+ cell stimulation with CpG. Protein expression of inhibitor of nuclear factor kappa B (IκBα) after CpG stimulation was investigated by western blot. CD8+ T cells were stimulated for 72 h with or without programmed cell death protein 1 (PD-1) checkpoint blockade and analyzed for expression of PD­1, Tim­3, CTLA4, and Lag3 by flow cytometry. RESULTS: TLR stimulation (by unmethylated CpG DNA) of APCs upregulates immunostimulatory signals such as IL12 expression but also activates immunoinhibitory signaling pathways such as PD-L1 expression. This signaling is NF-κB dependent. After blockade of the PD-1/PD-L1 signaling pathway, overexpression of other immune checkpoint inhibitory receptors was observed-a potential explanation for lacking therapeutic responses after TLR stimulation with PD­1 checkpoint blockade. CONCLUSION: TLR stimulation causes APCs in the tumor microenvironment to upregulate PD-L1 in an NF-κB-mediated fashion, thereby contributing to CD8+ T cell exhaustion. The effect of PD­1 blockade after TLR stimulation might be impaired due to upregulation of other checkpoint inhibitors.

Developing a program to increase geropsychology competencies of Veterans Health Administration (VHA) psychologists.

There is an alarming supply and demand gap for geropsychology expertise within the United States. Health policy experts called for increasing geriatric mental health competencies for all mental health providers, including within Veterans Health Administration (VHA), to address this problematic gap. The VHA Geriatrics Scholar Program (GSP) Psychology Track was developed because there were no commercially available trainings in geropsychology for licensed psychologists. Developing the GSP Psychology Track was based on an evidence-based educational model for the VHA primary care workforce; and included a stepwise curriculum design, pilot implementation, and program evaluation. The educational program was pilot tested with eight VHA psychologists. Evaluation results demonstrated feasibility of implementing an innovative integrated multimodal educational program in geropsychology. Furthermore, this program was associated with reports of increased confidence in geropsychology competencies and self-reported implementation of geropsychology knowledge, indicating the potential for this educational model to improve mental health care for older Veterans.

Iatrogenic endometriosis harbors somatic cancer-driver mutations.

STUDY QUESTION: Does incisional endometriosis (IE) harbor somatic cancer-driver mutations? SUMMARY ANSWER: We found that approximately one-quarter of IE cases harbor somatic-cancer mutations, which commonly affect components of the MAPK/RAS or PI3K-Akt-mTor signaling pathways. WHAT IS KNOWN ALREADY: Despite the classification of endometriosis as a benign gynecological disease, it shares key features with cancers such as resistance to apoptosis and stimulation of angiogenesis and is well-established as the precursor of clear cell and endometrioid ovarian carcinomas. Our group has recently shown that deep infiltrating endometriosis (DE), a form of endometriosis that rarely undergoes malignant transformation, harbors recurrent somatic mutations. STUDY DESIGN, SIZE, DURATION: In a retrospective study comparing iatrogenically induced and endogenously occurring forms of endometriosis unlikely to progress to cancer, we examined endometriosis specimens from 40 women with IE and 36 women with DE. Specimens were collected between 2004 and 2017 from five hospital sites in either Canada, Germany or the Netherlands. IE and DE cohorts were age-matched and all women presented with histologically typical endometriosis without known history of malignancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Archival tissue specimens containing endometriotic lesions were macrodissected and/or laser-capture microdissected to enrich endometriotic stroma and epithelium and a hypersensitive cancer hotspot sequencing panel was used to assess for presence of somatic mutations. Mutations were subsequently validated using droplet digital PCR. PTEN and ARID1A immunohistochemistry (IHC) were performed as surrogates for somatic events resulting in functional loss of respective proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, we detected somatic cancer-driver events in 11 of 40 (27.5%) IE cases and 13 of 36 (36.1%) DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA and CTNNB1. Heterogeneous PTEN loss occurred at similar rates in IE and DE (7/40 vs 5/36, respectively), whereas ARID1A loss only occurred in a single case of DE. While rates of detectable somatic cancer-driver events between IE and DE are not statistically significant (P > 0.05), KRAS activating mutations were more prevalent in DE. LIMITATIONS, REASONS FOR CAUTION: Detection of somatic cancer-driver events were limited to hotspots analyzed in our panel-based sequencing assay and loss of protein expression by IHC from archival tissue. Whole genome or exome sequencing, or epigenetic analysis may uncover additional somatic alterations. Moreover, because of the descriptive nature of this study, the functional roles of identified mutations within the context of endometriosis remain unclear and causality cannot be established. WIDER IMPLICATIONS OF THE FINDINGS: The alterations we report may be important in driving the growth and survival of endometriosis in ectopic regions of the body. Given the frequency of mutation in surgically displaced endometrium (IE), examination of similar somatic events in eutopic endometrium, as well as clinically annotated cases of other forms of endometriosis, in particular endometriomas that are most commonly linked to malignancy, is warranted. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a Canadian Cancer Society Impact Grant [701603, PI Huntsman], Canadian Institutes of Health Research Transitional Open Operating Grant [MOP-142273, PI Yong], the Canadian Institutes of Health Research Foundation Grant [FDN-154290, PI Huntsman], the Canadian Institutes of Health Research Project Grant [PJT-156084, PIs Yong and Anglesio], and the Janet D. Cottrelle Foundation through the BC Cancer Foundation [PI Huntsman]. D.G. Huntsman is a co-founder and shareholder of Contextual Genomics Inc., a for profit company that provides clinical reporting to assist in cancer patient treatment. R. Aguirre-Hernandez, J. Khattra and L.M. Prentice have a patent MOLECULAR QUALITY ASSURANCE METHODS FOR USE IN SEQUENCING pending and are current (or former) employees of Contextual Genomics Inc. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Unexpected malignant uterine pathology: Incidence, characteristics and outcome in a large single-center series of hysterectomies for presumed benign uterine disease.

OBJECTIVE: Hysterectomy is a frequently used therapeutic option for benign gynecological conditions. The purpose of this study was to investigate the incidence and characteristics of unforeseen malignant pathologies of the uterine corpus in a large population-based, single center cohort. METHODS: Patients who underwent hysterectomy for presumed benign conditions between 2003 and 2016 were identified. In cases of unexpected malignancies of the uterine corpus (UUM), available tissue samples were collected and a specialized gynecopathological review was performed. RESULTS: A total of 10,756 patients underwent hysterectomy for benign indications. After chart and gynecopathological review, 45/10,756 (0.42%) cases of unexpected uterine malignancies were confirmed. 33/45 (73.3%) were endometrial carcinomas (UEC) and 12/45 (26.7%) were uterine sarcomas (UUS). 27/33 (81.8%) UEC were FIGO IA, 5/33 (15.2%) FIGO IB and 1/33 (3%) FIGO stage II disease. Endometrioid and serous histotype were present in 31/33 (93.9%) and in 2/33 (6.1%) cases, respectively. 8/12 (66.7%) USS were early stage (FIGO IA or IB); only 3/12 (25.0%) were diagnosed at an advanced stage (≥FIGO II). Fatal outcome was observed in 1 patient diagnosed with UEC and 3 patients diagnosed with UUS. CONCLUSION: Our study shows that diagnosis of UUM is rare (0.42%). The majority of UUM tend to be early stage, making preoperative diagnosis difficult. In case of UEC, patient outcome is generally favorable. Nevertheless, the appropriate surgical approach for hysterectomy for a benign indication should be chosen carefully, taking all preoperative findings into account. Patients should always be informed about the residual risk of UUM.

The rural interdisciplinary team training program: a workforce development workshop to increase geriatrics knowledge and skills for rural providers.

The Rural Interdisciplinary Team Training Program (RITT) is a team-based educational component of the Veterans Health Administration (VHA) Office of Rural Health Geriatric Scholars Program. It is a workforce development program to enhance the geriatrics knowledge and skills of VA primary care clinicians and staff caring for older veterans in rural communities. The RITT workshop, accredited for 6.5 hours, is interactive and multi-modal with didactic mini-lectures, interactive case discussions and role play demonstrations of assessments. Clinic teams also develop and implement a small quality improvement project based on common challenges faced by older persons. This report is an evaluation of the effect of the RITT Program on geriatrics knowledge and team development as well as success in developing and implementing the quality improvement projects in 80 VHA rural outpatient clinics in 38 states.

Impact of spontaneous donor hypothermia on graft outcomes after kidney transplantation.

A previous donor intervention trial found that therapeutic hypothermia reduced delayed graft function (DGF) after kidney transplantation. This retrospective cohort study nested in the randomized dopamine trial (ClinicalTrials.gov identifier: NCT000115115) investigates the effects of spontaneous donor hypothermia (core body temperature <36°C) on initial kidney graft function, and evaluates 5-year graft survival. Hypothermia assessed by a singular measurement in the intensive care unit 4-20 hours before procurement was associated with less DGF after kidney transplantation (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.34-0.91). The benefit was greater when need for more than a single posttransplant dialysis session was analyzed (OR 0.48, 95%CI 0.28-0.82). Donor dopamine ameliorated dialysis requirement independently from hypothermia in a temporal relationship with exposure (OR 0.93, 95%CI 0.87-0.98, per hour). A lower core body temperature in the donor was associated with lower serum creatinine levels before procurement, which may reflect lower systemic inflammation and attenuated renal injury from brain death. Despite a considerable effect on DGF, our study failed to demonstrate a graft survival advantage (hazard ratio [HR] 0.83, 95%CI 0.54-1.27), whereas dopamine treatment was associated with improved long-term outcome (HR 0.95, 95%CI 0.91-0.99 per hour).