Larger Tumor Size and Elevated Serum Chromogranin A Levels Predict Metastatic Disease on DOTATATE Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

PURPOSE: DOTATATE PET/CT (DOTATATE) is superior to conventional imaging in detecting metastasis for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, limited availability, high-cost, and additive radiation exposure necessitate guidelines for its use. This study seeks to investigate the relationship between clinical characteristics and metastasis on DOTATATE. METHODS: This was a retrospective analysis of 815 patients who underwent DOTATATE at UCLA from 2014 to 2022. After applying inclusion and exclusion criteria, the study cohort consisted of 163 patients with pathologically diagnosed GEP-NETs, who either underwent primary tumor resection within 1-year prior, or had not undergone resection at the time of DOTATATE imaging. The presence of metastasis was determined using DOTATATE. Fisher's exact test, chi-squared test, and Mann-Whitney test were conducted to compare intergroup difference. Multivariate analysis was performed to identify clinical characteristics associated with metastasis on DOTATATE. RESULTS: Of patients with GEP-NETs, 40.5% (n = 66) were diagnosed with metastases by using DOTATATE. Those with metastatic disease were more likely to exhibit a larger primary tumor size (median 3.4 vs. 1.2, cm, P < 0.001), elevated serum chromogranin A level (CgA, median 208 vs. 97, mg/ml, P = 0.005), and higher tumor grade (P < 0.001). Primary tumor size ≥2 cm and serum CgA level ≥150 ng/mL for metastatic disease had a sensitivity and specificity of 64% and 89%, and 72% and 59%, respectively. Multivariate analysis demonstrated that primary tumor size (≥2/<2, cm, odds ratio [OR] 47.90, P < 0.001), tumor functionality (functional/nonfunctional, adjusted OR 10.17 P = 0.008), serum CgA level (≥150/<150, ng/ml, OR 6.25, P = 0.005), and tumor grade G2 (G2/G1, OR 9.6, P < 0.001) were independently associated with metastases on DOTATATE. CONCLUSIONS: Among patients with GEP-NETs, primary tumor size ≥2 cm, serum CgA level ≥150 ng/mL, and tumor grade G2 are associated with an increased risk of metastases on DOTATATE, and these predictors may be helpful to identify patients where DOTATATE is indicated for complete staging.

Modified rush venom immunotherapy in dogs with Hymenoptera hypersensitivity.

BACKGROUND: Hymenoptera envenomation occurs frequently in people and dogs and can trigger anaphylaxis. Venom immunotherapy (VIT) is the only preventive treatment for Hymenoptera hypersensitivity and is indicated for people with severe adverse reactions to insect stings. Rush VIT is an accelerated VIT protocol in people. This has not been reported in dogs. OBJECTIVES: The objective of the study was to evaluate the safety of modified rush VIT. ANIMALS: Twenty client-owned dogs with Hymenoptera hypersensitivity based on a history of adverse reactions to Hymenoptera envenomation and a positive intradermal test to honey bee and/or paper wasp venom. MATERIALS AND METHODS: Dogs received incremental doses of venom via subcutaneous injection one day per week for three consecutive weeks until the maintenance dose was achieved. Vital signs were recorded every 30 min prior to venom administration. Adverse reactions were categorised as localised or grade I-IV systemic reactions. RESULTS: Nineteen of 20 dogs (95%) completed rush VIT. One dog experienced a grade III systemic adverse reaction and was withdrawn from the study. No adverse reactions occurred in 10 of 20 dogs (50%). Localised and grade I-II systemic reactions occurred in nine of 20 dogs (45%), including nausea (n = 5), injection site pruritus (n = 3) and diarrhoea and lethargy (n = 1). CONCLUSIONS AND CLINICAL RELEVANCE: Modified rush VIT in dogs was well-tolerated and should be considered for dogs with Hymenoptera hypersensitivity. Larger studies are needed to evaluate the efficacy of VIT in dogs for preventing hypersensitivity reactions to insect stings.

Comparison of Fidgeting in Adolescents with Attention-Deficit/Hyperactivity Disorder Between Before and After Stimulant Medication Intake.

Objective: Fidgeting is a common symptom in patients with attention-deficit hyperactivity disorder (ADHD). The current study investigated ADHD stimulant medication effects on fidgeting in adolescents with ADHD during a short research study session using wrist-worn accelerometers. Method: Adolescents with ADHD who had been taking stimulant medications (ADHD group) and adolescents without ADHD (control group) participated in the study. Accelerometer data were obtained from both wrists of each participant to track their hand movements during two hearing testing sessions. All subjects in the ADHD group abstained from their stimulant medications for at least 24 hours before their first session (off-med session). The second session (on-med session) was conducted about 60-90 minutes after medication intake. The control group participated in two sessions in a similar time frame. Results: The current study focuses on relationships between hand movements and stimulant medication in adolescents with ADHD. Both conditions were compared to evaluate the relationship of hand movements and stimulant medication. We hypothesized the ADHD group will exhibit less hand movements during the on-medication session in comparison to off-medication session. Conclusion: Wrist-worn accelerometer measures obtained during nonphysical tasks in a short duration may not provide hand movement differences between on-med and off-med conditions in adolescents with ADHD. ClinicalTrials.gov Identifier: NCT04577417.

Mother's physical activity during pregnancy and newborn's brain cortical development.

Background: Physical activity is known to improve mental health, and is regarded as safe and desirable for uncomplicated pregnancy. In this novel study, we aim to evaluate whether there are associations between maternal physical activity during pregnancy and neonatal brain cortical development. Methods: Forty-four mother/newborn dyads were included in this longitudinal study. Healthy pregnant women were recruited and their physical activity throughout pregnancy were documented using accelerometers worn for 3-7 days for each of the 6 time points at 4-10, ∼12, ∼18, ∼24, ∼30, and ∼36 weeks of pregnancy. Average daily total steps and daily total activity count as well as daily minutes spent in sedentary/light/moderate/vigorous activity modes were extracted from the accelerometers for each time point. At ∼2 weeks of postnatal age, their newborns underwent an MRI examination of the brain without sedation, and 3D T1-weighted brain structural images were post-processed by the iBEAT2.0 software utilizing advanced deep learning approaches. Cortical surface maps were reconstructed from the segmented brain images and parcellated to 34 regions in each brain hemisphere, and mean cortical thickness for each region was computed for partial correlation analyses with physical activity measures, with appropriate multiple comparison corrections and potential confounders controlled. Results: At 4-10 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left caudal middle frontal gyrus (rho = 0.48, P = 0.04), right medial orbital frontal gyrus (rho = 0.48, P = 0.04), and right transverse temporal gyrus (rho = 0.48, P = 0.04); mother's daily time in moderate activity mode positively correlated with newborn's cortical thickness in the right transverse temporal gyrus (rho = 0.53, P = 0.03). At ∼24 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left (rho = 0.56, P = 0.02) and right isthmus cingulate gyrus (rho = 0.50, P = 0.05). Conclusion: We identified significant relationships between physical activity in healthy pregnant women during the 1st and 2nd trimester and brain cortical development in newborns. Higher maternal physical activity level is associated with greater neonatal brain cortical thickness, presumably indicating better cortical development.

Fatal disseminated toxoplasmosis in a feline immunodeficiency virus-positive cat receiving oclacitinib for feline atopic skin syndrome.

Toxoplasma gondii is a ubiquitous protozoan, for which felids are the definitive host. Immunocompromised individuals are susceptible to recrudescent toxoplasmosis. This case describes a 6-year-old, feline immunodeficiency virus-positive domestic short hair cat with feline atopic skin syndrome that developed fatal toxoplasmosis after treatment with oclacitinib for five months.

Toxoplasma gondii est un protozoaire ubiquitaire dont les félidés sont l'hôte définitif. Les personnes immunodéprimées sont sensibles à la toxoplasmose recrudescente. Ce cas décrit un chat domestique à poils courts de 6 ans, positif pour le virus de l'immunodéficience féline, atteint du syndrome atopique cutané félin, qui a développé une toxoplasmose mortelle après un traitement à l'oclacitinib pendant cinq mois.

Toxoplasma gondii es un protozoo ubicuo, cuyo huésped definitivo son los felinos. Las personas inmunocomprometidas son susceptibles a la toxoplasmosis recrudescente. Este caso describe un gato doméstico de pelo corto positivo para el virus de la inmunodeficiencia felina de 6 años de edad con síndrome de piel atópica felina, que desarrolló toxoplasmosis fatal después del tratamiento con oclacitinib durante cinco meses.

Toxoplasma gondii é um protozoário ubíquo para o qual os felídeos são o hospedeiro definitivo. Indivíduos imunocomprometidos são suscetíveis a toxoplasmose recrudescente. Este relato descreve um caso de um felino doméstico de pelo curto de seis anos de idade, positivo para o vírus da imunodeficiência felina, com síndrome atópica felina, que desenvolveu toxoplasmose fatal após tratamento com oclacitinib por cinco meses.

Reproducible asystole following vagal nerve stimulator lead replacement: a case report.

BACKGROUND: Vagal nerve stimulation (VNS) is approved therapy for the treatment of intractable epilepsy. The stimulation of either nerve, left or right, is effective. However, due to the anatomic and physiological effects of cardiac innervation, the right vagus nerve is typically avoided in order to minimize the risk of cardiac bradyarrhythmias. The location of the VNS lead contacts on the nerve can also have an effect, namely, more distally placed contacts have been associated with lower risk of cardiac arrhythmias, presumably by avoiding vagal cervical cardiac branches; however, our case demonstrates reproducible asystole despite left sided, distal VNS lead placement. CASE PRESENTATION: We report a 28-year-old male patient with pharmacoresistant generalized clonic-tonic seizures. The VNS therapy with 1.5 mA output and 16% duty cycle drastically reduced his seizure burden for several years. The breakthrough seizures along with stabbing pain episodes at the implantable pulse generator (IPG) site have prompted the VNS lead revision surgery with new lead contacts placed more caudally than the old contacts. However, the intraoperative device interrogation with 1 mA output resulted in immediate asystole for the duration of stimulation and it was reproducible until the output was decreased to 0.675 mA. CONCLUSIONS: Our case highlights the possibility of new severe cardiac bradyarrhythmias following surgical VNS lead replacements even in patients without preoperatively known clinical side effects. We suggest preoperative electrocardiography and cardiology consultation for detected abnormalities for all patients undergoing new VNS implantations, as well as revision surgeries for VNS malfunctions. Intraoperatively, the surgeon and anesthesia team should be vigilant of cardiac rhythms and prepared for the immediate management.

Associations Between White Matter Microstructures and Cognitive Functioning in 8-Year-Old Children: A Track-Weighted Imaging Study.

PURPOSE: Quantitative tractography using diffusion-weighted magnetic resonance imaging data is widely used in characterizing white matter microstructure throughout childhood, but more studies are still needed to investigate comprehensive brain-behavior relationships between tract-specific white matter measures and multiple cognitive functions in children. METHODS: In this study, we analyzed diffusion-weighted MRI data of 71 healthy 8-year-old children utilizing white matter tract-specific quantitative measures derived from diffusion-weighted MRI tractography based on a novel track-weighted imaging approach. Track density imaging, average path length map and 4 track-weighted diffusion tensor imaging measures including: mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for 63 white matter tracts. The track-weighted imaging measures were then correlated with a comprehensive set of neuropsychological test scores in different cognitive domains including intelligence, language, memory, academic skills, and executive functions to identify tract-specific brain-behavior relationships. RESULTS: Significant correlations (P < .05, false discovery rate corrected; r = 0.27-0.57) were found in multiple white matter tracts, with a total of 40 correlations identified between various track-weighted imaging measures including average path length map, track-weighted imaging-fractional anisotropy, and neuropsychological test scores and subscales. Specifically, track-weighted imaging measures indicative of better white matter connectivity and/or microstructural development significantly correlated with higher IQ and better language abilities. CONCLUSION: Our findings demonstrate the ability of track-weighted imaging measures in establishing associations between white matter and cognitive functioning in healthy children and can serve as a reference for normal brain/cognition relationships in young school-age children and further aid in identifying imaging biomarkers predictive of adverse neurodevelopmental outcomes.

Pathological treatment response has different prognostic implications for pancreatic cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy.

BACKGROUND: Pathological treatment effect of resected pancreatic adenocarcinoma after neoadjuvant therapy has prognostic implications. The impact for patients who received chemotherapy alone or chemoradiotherapy is not well defined. METHODS: Patients with localized pancreatic adenocarcinoma who had pancreatectomy after neoadjuvant therapy at 3 centers from 2011 to 2017 were retrospectively analyzed. The chemotherapy and chemoradiotherapy groups were evaluated separately. RESULTS: Of 525 patients, 148 received neoadjuvant chemotherapy and 377 received chemoradiotherapy. The chemoradiotherapy group had a better treatment effect (score 0: 10%, score 1: 30%, score 2: 42%, and score 3: 18%) than the chemotherapy group (score 0: 2%, score 1: 8%, score 2: 35%, and score 3: 55%) (P < .001). Median overall survival was similar between the 2 groups (25.8 vs 26.4 months). Median overall survival for score 0/1, 2, or 3 was 72.2, 38.5, and 20.0 months in the chemotherapy group and 37.9, 24.5, and 19.0 months in the chemoradiotherapy group. Score 2 in the chemotherapy group was associated with better overall survival compared to score 3 (adjusted hazard ratio: 0.49, P = .005), whereas only combined score 0/1 reached significance over score 2 for the chemoradiotherapy group (hazard ratio: 0.63, P = .006). CONCLUSION: The prognostic significance of pathological treatment effect for localized pancreatic adenocarcinoma differs for patients receiving neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy.

The HDR CARE Scale, Inpatient Version: A validated survey instrument to measure environmental affordance for nursing tasks in inpatient healthcare settings.

Rigorous healthcare design research is critical to inform design decisions that improve human experience. Current limitations in the field include a lack of consistent and valid measures that provide feedback about the role of the built environment in producing desirable outcomes. Research findings about nurses' efficiency, quality of care, and satisfaction related to inpatient unit designs have been mixed, and there was previously no validated instrument available to quantitatively measure nurses' ability to work efficiently and effectively in their environment. The objective of this study was to develop, refine, and validate a survey instrument to measure affordance of the care environment to nurse practice, based on various aspects of their work in inpatient units. The HDR Clinical Activities Related to the Environment (CARE) Scale Inpatient Version was developed using item design, refinement, and reliability and validity testing. Psychometric methods from classical test theory and item response theory, along with statistical analyses involving correlations and factor analysis, and thematic summaries of qualitative data were conducted. The four-phase process included (1) an initial pilot study, (2) a content validation survey, (3) cognitive interviews, and (4) a final pilot study. Results from the first three phases of analysis were combined to inform survey scale revisions before the second pilot survey, such as a reduction in the number and rewording of response options, and refinement of scale items. The updated 9-item scale showed excellent internal consistency and improved response distribution and discrimination. The factor analysis revealed a unidimensional measure of nurse practice, as well as potential subscales related to integration, efficiency, and patient care. Within the healthcare design industry, this scale is much needed to generate quantitative and standardized data and will facilitate greater understanding about the aspects of an inpatient healthcare facility that best support nurses' ability to provide quality patient care.

Melanic pigmentation and light preference within and between two Drosophila species.

Environmental adaptation and species divergence often involve suites of co-evolving traits. Pigmentation in insects presents a variable, adaptive, and well-characterized class of phenotypes for which correlations with multiple other traits have been demonstrated. In Drosophila, the pigmentation genes ebony and tan have pleiotropic effects on flies' response to light, creating the potential for correlated evolution of pigmentation and vision. Here, we investigate differences in light preference within and between two sister species, Drosophila americana and D. novamexicana, which differ in pigmentation in part because of evolution at ebony and tan and occupy environments that differ in many variables including solar radiation. We hypothesized that lighter pigmentation would be correlated with a greater preference for environmental light and tested this hypothesis using a habitat choice experiment. In a first set of experiments, using males of D. novamexicana line N14 and D. americana line A00, the light-bodied D. novamexicana was found slightly but significantly more often than D. americana in the light habitat. A second experiment, which included additional lines and females as well as males, failed to find any significant difference between D. novamexicana-N14 and D. americana-A00. Additionally, the other dark line of D. americana (A04) was found in the light habitat more often than the light-bodied D. novamexicana-N14, in contrast to our predictions. However, the lightest line of D. americana, A01, was found substantially and significantly more often in the light habitat than the two darker lines of D. americana, thus providing partial support for our hypothesis. Finally, across all four lines, females were found more often in the light habitat than their more darkly pigmented male counterparts. Additional replication is needed to corroborate these findings and evaluate conflicting results, with the consistent effect of sex within and between species providing an especially intriguing avenue for further research.

NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition.

Emerging evidence suggests that intratumoral interferon (IFN) signaling can trigger targetable vulnerabilities. A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its extensively reprogrammed metabolic network, in which nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are critical cofactors. Here, we show that IFN signaling, present in a subset of PDAC tumors, substantially lowers NAD(H) levels through up-regulating the expression of NAD-consuming enzymes PARP9, PARP10, and PARP14. Their individual contributions to this mechanism in PDAC have not been previously delineated. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD salvage pathway, a dominant source of NAD in cancer cells. We found that IFN-induced NAD consumption increased dependence upon NAMPT for its role in recycling NAM to salvage NAD pools, thus sensitizing PDAC cells to pharmacologic NAMPT inhibition. Their combination decreased PDAC cell proliferation and invasion in vitro and suppressed orthotopic tumor growth and liver metastases in vivo.

Postoperative Physician Phone Calls as a Method to Decrease Urgent Care and Emergency Department Returns After Ambulatory General Surgery.

Unplanned returns after ambulatory surgery pose a burden to patients and health care providers alike. We hypothesized that a postoperative phone call by a physician would decrease avoidable returns to urgent care (UC) or the emergency department (ED) in the week after anorectal (AR), laparoscopic cholecystectomy (LC), inguinal hernia repair (IHR), and umbilical hernia repair (UHR) operations. A retrospective analysis from 1/2011 to 12/2015 across 14 Kaiser hospitals was conducted to determine baseline UC/ED return rates of patients pre-call. Between 10/2017 and 06/2019, physicians placed phone calls to patients within postoperative days (PODs) 1-4. The cohorts were compared using chi-squared analysis with significance determined at P < .05. In total, 276 patients received a call, with the majority placed on PODs 1-3. There were no statistically significant differences in return rates between the pre- and post-call groups. All of the AR, 50.0% of LC, 66.7% of IHR, and 50.0% of UHR patients returned prior to phone call placement. Our data indicate that a physician phone call does not help in decreasing UC/ED returns. However, it is noteworthy that many of the returns occurred pre-call placement. Future directions should be aimed at placing earlier postoperative phone calls.

Impact of resection margin status on survival in pancreatic cancer patients after neoadjuvant treatment and pancreatoduodenectomy.

BACKGROUND: Resection margin status has been recognized as an independent prognostic factor on overall survival in pancreatic cancer patients undergoing surgical resection. However, its impact after neoadjuvant treatment remains uncertain. METHODS: We analyzed 305 patients with resectable or borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatoduodenectomy at 3 tertiary referral centers between 2010 and 2017. Positive resection margin was defined as 1 or more cancer cells at any margin. Overall survival was measured from the date of surgery until death or last follow-up. RESULTS: One hundred and seventy-eight patients received neoadjuvant chemotherapy and 127 received neoadjuvant chemoradiotherapy. The median overall survival was 29.8 months. The 1-, 3-, and 5-year overall survival rates were 79.2%, 44.0%, and 23.5%, respectively. Negative margin was achieved in 275 (90.2%) patients. Negative margin resection patients had a significantly longer overall survival than positive resection margin patients (31.3 vs 16.3 months, P < .001). In univariate analyses, overall survival was associated with age, margin status, histologic grade, ypT, number of positive lymph nodes, perineural invasion, treatment effect, postoperative carbohydrate antigen 19-9, and adjuvant therapy. Positive margin resection, poorly differentiated carcinoma, treatment effect score of 3, postoperative carbohydrate antigen 19-9 of 37 U/mL or higher, and lack of adjuvant therapy were predictive of poor overall survival in multivariate Cox regression analysis. CONCLUSION: Margin status was an independent predictor of overall survival in patients treated with neoadjuvant therapy and pancreatoduodenectomy, supporting the use of a negative margin resection as a surrogate of adequate oncological resection in this setting. Our findings may also have significant implications for patient stratification in future randomized trials.

Histone deacetylase inhibition is synthetically lethal with arginine deprivation in pancreatic cancers with low argininosuccinate synthetase 1 expression.

Arginine (Arg) deprivation is a promising therapeutic approach for tumors with low argininosuccinate synthetase 1 (ASS1) expression. However, its efficacy as a single agent therapy needs to be improved as resistance is frequently observed. Methods: A tissue microarray was performed to assess ASS1 expression in surgical specimens of pancreatic ductal adenocarcinoma (PDAC) and its correlation with disease prognosis. An RNA-Seq analysis examined the role of ASS1 in regulating the global gene transcriptome. A high throughput screen of FDA-approved oncology drugs identified synthetic lethality between histone deacetylase (HDAC) inhibitors and Arg deprivation in PDAC cells with low ASS1 expression. We examined HDAC inhibitor panobinostat (PAN) and Arg deprivation in a panel of human PDAC cell lines, in ASS1-high and -knockdown/knockout isogenic models, in both anchorage-dependent and -independent cultures, and in multicellular complex cultures that model the PDAC tumor microenvironment. We examined the effects of combined Arg deprivation and PAN on DNA damage and the protein levels of key DNA repair enzymes. We also evaluated the efficacy of PAN and ADI-PEG20 (an Arg-degrading agent currently in Phase 2 clinical trials) in xenograft models with ASS1-low and -high PDAC tumors. Results: Low ASS1 protein level is a negative prognostic indicator in PDAC. Arg deprivation in ASS1-deficient PDAC cells upregulated asparagine synthetase (ASNS) which redirected aspartate (Asp) from being used for de novo nucleotide biosynthesis, thus causing nucleotide insufficiency and impairing cell cycle S-phase progression. Comprehensively validated, HDAC inhibitors and Arg deprivation showed synthetic lethality in ASS1-low PDAC cells. Mechanistically, combined Arg deprivation and HDAC inhibition triggered degradation of a key DNA repair enzyme C-terminal-binding protein interacting protein (CtIP), resulting in DNA damage and apoptosis. In addition, S-phase-retained ASS1-low PDAC cells (due to Arg deprivation) were also sensitized to DNA damage, thus yielding effective cell death. Compared to single agents, the combination of PAN and ADI-PEG20 showed better efficacy in suppressing ASS1-low PDAC tumor growth in mouse xenograft models. Conclusion: The combination of PAN and ADI-PEG20 is a rational translational therapeutic strategy for treating ASS1-low PDAC tumors through synergistic induction of DNA damage.

Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion.

Functional lysosomes mediate autophagy and macropinocytosis for nutrient acquisition. Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit high basal lysosomal activity, and inhibition of lysosome function suppresses PDAC cell proliferation and tumor growth. However, the codependencies induced by lysosomal inhibition in PDAC have not been systematically explored. We performed a comprehensive pharmacological inhibition screen of the protein kinome and found that replication stress response (RSR) inhibitors were synthetically lethal with chloroquine (CQ) in PDAC cells. CQ treatment reduced de novo nucleotide biosynthesis and induced replication stress. We found that CQ treatment caused mitochondrial dysfunction and depletion of aspartate, an essential precursor for de novo nucleotide synthesis, as an underlying mechanism. Supplementation with aspartate partially rescued the phenotypes induced by CQ. The synergy of CQ and the RSR inhibitor VE-822 was comprehensively validated in both 2D and 3D cultures of PDAC cell lines, a heterotypic spheroid culture with cancer-associated fibroblasts, and in vivo xenograft and syngeneic PDAC mouse models. These results indicate a codependency on functional lysosomes and RSR in PDAC and support the translational potential of the combination of CQ and RSR inhibitors.

An assessment of chlorine stain and collegiate swimmers.

Background: Swimming is known worldwide as one of the healthiest, low-impact forms of exercise that promotes a strong body, heart, and mind. However, several studies have suggested that swimming pool chlorination is responsible for dental erosion, calculus formation, and stain in competitive and recreational swimmers, a phenomenon known as swimmer's mouth. The purpose of this observational study was to assess chlorine stain on the dentition of competitive female swimmers and divers from a university team and to determine if dental preventive practices affected chlorine stains. Methods: Swimmers were recruited from the University of New Mexico Swimming and Diving Team for this IRB-approved study (#17-481). Participants completed a questionnaire regarding individual oral habits and frequency of preventive visits. Following the questionnaire, an oral screening was completed to evaluate for stain. Fisher exact tests, nonparametric Wilcoxon tests, and descriptive statistics were used to analyse the data. Additionally, a cross-sectional analysis was used to compare the chlorine stain between divers and swimmers. Results: Twenty-one females, with a mean age of 20.5 years, participated in the study. One hundred percent of these subjects had staining of the teeth, despite the fact that 85% of them reported brushing their teeth 2 to 3 times per day, and 81% reported receiving regular dental prophylaxis. All participants swam 5 or more times every week, with practice length ranging from 1 to 2 hours. There were no differences in stain between collegiate swimmers and divers. Conclusion: Within this study sample, extrinsic staining of the teeth was identified on all swimmers and divers and the presence of stain was not prevented by the frequency of tooth brushing or professional stain removal. Additional oral hygiene regimens should be explored to facilitate the prevention or complete removal of swimmer stain.

Contexte: La natation est reconnue partout dans le monde comme l'une des formes d'exercice physique les plus saines et ayant le moins d'impact, qui renforce le corps, le coeur et l'esprit. Cependant, plusieurs études ont suggéré que la chloration des piscines cause l'érosion dentaire et la formation de tartre et de taches chez les nageurs compétitifs et récréatifs; un phénomène appelé la bouche de nageur. L'objectif de cette étude d'observation était d'évaluer les taches de chlore sur la dentition de nageuses et de plongeuses de compétition d'une équipe universitaire et de déterminer si les habitudes dentaires en matière de prévention influençaient les taches de chlore. Méthodologie: Les nageuses ont été recrutées de l'équipe de natation et de plongeon de l'Université du Nouveau-Mexique pour effectuer cette étude approuvée par le comité d'éthique médicale (#17-481). Les participantes ont répondu à un questionnaire à l'égard des habitudes buccodentaires personnelles et de la fréquence de leurs visites dentaires préventives. À la suite du questionnaire, un dépistage buccal a été effectué pour évaluer les taches. Les tests exacts de probabilité de Fisher, les tests non paramétriques de Wilcoxon et les statistiques descriptives ont été employées pour analyser les données. De plus, une analyse en coupe a servi à comparer les taches de chlore chez les plongeuses et les nageuses. Résultats: Vingt-et-une femmes âgées en moyenne de 20,5 ans ont participé à l'étude. La totalité des sujets avait des taches sur les dents, malgré le fait que 85 % d'entre elles ont signalé avoir brossé leurs dents 2 à 3 fois par jour et 81 % d'entre elles ont rapporté recevoir régulièrement des prophylaxies dentaires. Toutes les participantes ont nagé 5 fois ou plus par semaine et la durée de leur entraînement variait d'une à deux heures. Les nageuses et les plongeuses universitaires n'ont démontré aucune différence dans leur taux de taches. Conclusion: Parmi cet échantillon de l'étude, des taches extrinsèques ont été décelées sur les dents de toutes les nageuses et plongeuses, et la fréquence du brossage de dents ou l'élimination professionnelle des taches n'a pas empêché la présence de taches. Des mesures supplémentaires d'hygiène buccodentaire devraient être explorées afin de faciliter la prévention ou l'élimination complète des taches chez les nageurs.

Reducing emergency hospital admissions: a population health complex intervention of an enhanced model of primary care and compassionate communities.

BACKGROUND: Reducing emergency admissions to hospital has been a cornerstone of healthcare policy. Little evidence exists to show that systematic interventions across a population have achieved this aim. The authors report the impact of a complex intervention over a 44-month period in Frome, Somerset, on unplanned admissions to hospital. AIM: To evaluate a population health complex intervention of an enhanced model of primary care and compassionate communities on population health improvement and reduction of emergency admissions to hospital. DESIGN AND SETTING: A cohort retrospective study of a complex intervention on all emergency admissions in Frome Medical Practice, Somerset, compared with the remainder of Somerset, from April 2013 to December 2017. METHOD: Patients were identified using broad criteria, including anyone giving cause for concern. Patient-centred goal setting and care planning combined with a compassionate community social approach was implemented broadly across the population of Frome. RESULTS: There was a progressive reduction, by 7.9 cases per quarter (95% confidence interval [CI] = 2.8 to 13.1, P = 0.006), in unplanned hospital admissions across the whole population of Frome during the study period from April 2013 to December 2017, a decrease of 14.0%. At the same time, there was a 28.5% increase in admissions per quarter within Somerset, with a rise in the number of unplanned admissions of 236 per quarter (95% CI = 152 to 320, P<0.001). CONCLUSION: The complex intervention in Frome was associated with highly significant reductions in unplanned admissions to hospital, with a decrease in healthcare costs across the whole population of Frome.