Clinical features and outcomes of patients with pancreatic cancer requiring unplanned medical ICU admission: A retrospective multicenter study.

BACKGROUND: We sought to describe the reasons for intensive care unit (ICU) admission and outcomes of patients with pancreatic cancer requiring unplanned medical ICU admission. PATIENTS AND METHODS: Retrospective cohort study in five ICUs from 2009 to 2020. All patients with pancreatic cancer admitted to the ICU were included. Patients having undergone recent surgery were excluded (< 4 weeks). RESULTS: 269 patients were included. Tumors were mainly adenocarcinoma (90%). Main reason for admission was sepsis/septic shock (32%) with a biliary tract infection in 44 (51%) patients. Second reason for admission was gastrointestinal bleeding (28%). ICU and 3-month mortality rates were 26% and 59% respectively. Performance status 3-4 (odds ratio OR 3.58), disease status (responsive/stable -ref-, newly diagnosed OR 3.25, progressive OR 5.99), mechanical ventilation (OR 8.03), vasopressors (OR 4.19), SAPS 2 (OR 1.69) and pH (OR 0.02) were independently associated with ICU mortality. Performance status 3-4 (Hazard ratio HR 1.96) and disease status (responsive/stable -ref-, newly diagnosed HR 2.67, progressive HR 4.14) were associated with 3-month mortality. CONCLUSION: Reasons for ICU admissions of pancreatic cancer patients differ from those observed in other solid cancer. Short- and medium-term mortality are strongly influenced by performance status and disease status at ICU admission.

Centrally Acting ACE Inhibitor Use and Physical Performance in Older Adults.

BACKGROUND: There is conflicting evidence regarding the role of angiotensin-converting enzyme inhibitors and physical function. While some studies show improvements in muscle strength and physical function, others show no significant difference or decreased performance. This ambiguity could be due to differential effects of angiotensin-converting enzyme inhibitor subtypes which can be categorized as centrally or peripherally-acting based upon their ability to cross the blood-brain barrier. OBJECTIVE: The objective of this study is to compare physical performance measures among angiotensin-converting enzyme inhibitor subtype users. METHODS: Design: Cross-sectional Setting: Ambulatory Participants: Performed in 364 participants in the Health and Retirement Study cohort who were ≥ 65 years (median age (IQR) 74.00 (69-80) years. MEASUREMENTS: Average difference in hand grip (kg), gait speed(m/s) and peak expiratory flow (L/min). RESULTS: Compared to participants on a peripherally-acting angiotensin-converting enzyme inhibitor (113 (31%)), those on a centrally-acting agent (251(69%)) had stronger grip strength 28.9 ±1.0 vs 26.3±1.0, p=.011 and higher peak expiratory flow rates 316.8±130.4 vs. 280.0±118.5, p= .011 in unadjusted analysis. After multiple adjustments the difference in PEF remained statistically significant (Estimate(CI) 26.5, 95% CI 2.24, 50.5, p = 0.032). CONCLUSION: Our results suggest that in older adults the use of centrally-acting angiotensin-converting enzyme inhibitors compared to a peripherally acting angiotensin-converting enzyme inhibitors was associated with better lung function in older individuals.

Risk factors related to the appearance of umbilical disorders in dairy calves / [Fatores de risco relacionados ao surgimento de afecções umbilicais em bezerros leiteiros]

The objective of this study was to determine the types of calve housing used in dairy farms, the prevalence of umbilical disorders and related risk factors. The 16 farms studied were visited to characterize the types of installation and possible risk factors, as well as information obtained from a questionnaire applied to the farmers. 806 Holstein calves were physically examined, in addition to collecting blood samples for the evaluation of Failures in Passive Immunity Transfer (FPIT), in animals that manifested inflammatory omphalopathies, and were also submitted to ultrasound examination. The prevalence of omphalopathies was assessed by Fisher's test, and multivariate logistic regression to assess risk factors. Eight types of installation were found: tropical house, suspended cage, collective stall, collective picket, Argentinean type, single-story cage, individual stall, and collective picket with chain. Omphalopathies accounted for 6.45% of the calves. Small size farms (up to 99 lactation cows) had high risk for umbilical disorders, ground floor collective calves, without side protection, with sand floor, in closed sheds and without heatstroke were considered risk factors for omphalopathies. Adequate colostrum and umbilical antisepsis are not associated with disease, its appearance being related to the housing conditions of the animals.(AU)

O objetivo deste estudo foi determinar os tipos de alojamento para bezerros leiteiros, a prevalência de onfalopatias e os fatores de risco relacionados. As 16 fazendas estudadas foram visitadas buscando-se caracterizar os tipos de instalação e os possíveis fatores de risco, além de informações obtidas de um questionário aplicado aos fazendeiros. Foram examinados fisicamente 806 bezerros da raça Holandesa, além da coleta de amostras de sangue, para avaliação da falha de transferência de imunidade passiva (FTIP), nos animais que manifestaram onfalopatias inflamatórias, sendo submetidos também ao exame ultrassonográfico. A prevalência das onfalopatias foi avaliada por teste de Fisher, e foi feita regressão logística multivariada a fim de se avaliarem os fatores de risco. Verificou-se oito tipos de instalação: casinha tropical, gaiola suspensa, baia coletiva, piquete coletivo, bezerreiro tipo argentino, gaiola térrea, baia individual e piquete coletivo com corrente. As onfalopatias corresponderam a 6,45% dos bezerros. Os bezerreiros coletivos térreos, sem proteções laterais, com piso de areia, borracha, concreto ou madeira, em galpões fechados, sem insolação, com alta densidade animal, antissepsia umbilical realizada por três dias e FTIP acima de 50% foram considerados fatores de risco para onfalopatias e possuem relação com o bezerreiro, sendo decisivas para evitar essas condições a colostragem e a antissepsia umbilical adequadas.(AU)

A Nation-Wide Survey of High School Baseball Coaches' Perceptions Indicates their Arm Care Programs Play a Role in Injury Prevention.

BACKGROUND: Arm care programs consisting of upper extremity strengthening and stretching have been recommended for injury prevention for pitchers of all ages. There has been no investigation into high school baseball coaches' usage and perceptions of arm care programs to mitigate physical impairments associated with injuries in baseball players. HYPOTHESIS/PURPOSE: The purpose of this study was to investigate the current usage of arm care programs by high school baseball coaches. The primary objective was to determine if coaches use group-based or individualized arm care programs. The secondary objective sought to determine if the use of arm care programs is influenced by coaches' age, education, and experience level. Finally, this study explored the potential barriers to arm care implementation and high school baseball coaches' current awareness and beliefs of injury prevention. STUDY DESIGN: Descriptive cross-sectional survey. METHODS: A 29-item online survey was emailed to 18,500 high school baseball coaches throughout the United States. Data were collected for three months, and the response rate was 3.7%. RESULTS: A total of 87.3% (n=571/654) of responding coaches use arm care programs with their players. Of coaches performing arm care, only 18.5% of 571 individualize their arm care exercises based on specific player needs. However, older and more experienced coaches are more likely to individualize their programs. Among the 12.7% (n=83/654) of coaches who do not use arm care programs, the two most commonly cited reasons for not implementing arm care were lack of observed benefit (41%) and insufficient staff (31%). Although 42% of 654 coaches recognized reduced shoulder mobility as a major contributor to injury, risk factors such as throwing with a fatigued arm, previous injury history, and throwing > 8 months per year were not consistently identified as primary risk factors. CONCLUSION: The results of this study suggest that the majority high school baseball coaches implement group-based arm care exercise programs to prevent injury. Lack of confidence in the effectiveness and staffing limitations were major barriers to implementation of arm care programming. However, the responding coaches exhibited inconsistent risk factor awareness and dated injury prevention beliefs. Therefore, better educational collaboration between rehabilitation professionals and high school coaches regarding injury risk factors and preventative strategies is warranted. LEVEL OF EVIDENCE: Level 3.

Genetic and commensal induction of IL-18 drive intestinal epithelial MHCII via IFNγ.

Major histocompatibility complex class II (MHCII) is dynamically expressed on intestinal epithelial cells (IECs) throughout the intestine, but its regulation remains poorly understood. We observed that spontaneous upregulation of IEC MHCII in locally bred Rag1-/- mice correlated with serum Interleukin (IL)-18, was transferrable via co-housing to commercially bred immunodeficient mice and could be inhibited by both IL-12 and IL-18 blockade. Overproduction of intestinal IL-18 due to an activating Nlrc4 mutation upregulated IEC MHCII via classical inflammasome machinery independently of immunodeficiency or dysbiosis. Immunodeficient dysbiosis increased Il-18 transcription, which synergized with NLRC4 inflammasome activity to drive elevations in serum IL-18. This IL-18-MHCII axis was confirmed in several other models of intestinal and systemic inflammation. Elevated IL-18 reliably preceded MHCII upregulation, suggesting an indirect effect on IECs, and mice with IL-18 overproduction showed activation or expansion of type 1 lymphocytes. Interferon gamma (IFNg) was uniquely able to upregulate IEC MHCII in enteroid cultures and was required for MHCII upregulation in several in vivo systems. Thus, we have linked intestinal dysbiosis, systemic inflammation, and inflammasome activity to IEC MHCII upregulation via an intestinal IL-18-IFNg axis. Understanding this process may be crucial for determining the contribution of IEC MHCII to intestinal homeostasis, host defense, and tolerance.

Low Dose Aspirin in high-risk pregnancies: The volatile effect of acetylsalicylic acid on the inhibition of platelets uncovered by G. Born's light transmission aggregometry.

Preeclampsia still represents a life-threatening pregnancy complication, associated with severe maternal and neonatal morbidity and mortality. Low-dose Aspirin is advised to avoid preeclampsia in high-risk pregnancies worldwide. As Aspirin does not cover all women at risk, the prescription raises questions concerning optimal target population, dosage, and onset of therapy. The aim of this study was to test platelet responsiveness on Aspirin by optical aggegrometry, to gain robust biochemically assessment data of Aspirin in an obstetric cohort. 248 women at high risk for development of preeclampsia were included in the study. Aspirin-prophylaxis was administered either in 100 mg (n = 229) or 150 mg (n = 90) daily. Dosing of 100 mg Aspirin was maintained if testing revealed a sufficient platelet inhibition. If platelet inhibition was insufficient, dosage was increased to 150 mg Aspirin and re-testing was advised. 91 patients (91/229 = 39.7%) presented a sufficient inhibitory Aspirin effect at a dosage of 100 mg, but in 138 patients LTA showed an inadequate Aspirin response (138/229 = 60.3%). In 19 women 150 mg Aspirin was administered as starting dose due to new recommendations. Of all women at 150 mg Aspirin 64 did not properly respond (35.4%). The overall rate of sufficient responding women regardless the Aspirin dose was 64.6%. This study demonstrates still an insufficient inhibition of platelet aggregation in about 1/3 of women even with a dosage of 150 mg Aspirin daily, who might potentially benefit from further increase. These data show, that there is a need for further research to allow a personalized approach for individualized Aspirin therapy, maximizing the preventive benefit for mother and child.

Practical model to identify liver transplant recipients at low risk of postoperative haemorrhage, bile leakage and ascites.

BACKGROUND: This study aimed to identify a subgroup of recipients at low risk of haemorrhage, bile leakage and ascites following liver transplantation (LT). METHODS: Factors associated with significant postoperative ascites (more than 10 ml/kg on postoperative day 5), bile leakage and haemorrhage after LT were identified using three separate multivariable analyses in patients who had LT in 2010-2019. A model predicting the absence of all three outcomes was created and validated internally using bootstrap procedure. RESULTS: Overall, 944 recipients underwent LT. Rates of ascites, bile leakage and haemorrhage were 34.9, 7.7 and 6.0 per cent respectively. The 90-day mortality rate was 7.0 per cent. Partial liver graft (relative risk (RR) 1.31; P = 0.021), intraoperative ascites (more than 10 ml/kg suctioned after laparotomy) (RR 2.05; P = 0.001), malnutrition (RR 1.27; P = 0.006), portal vein thrombosis (RR 1.56; P = 0.024) and intraoperative blood loss greater than 1000 ml (RR 1.39; P = 0.003) were independently associated with postoperative ascites and/or bile leak and/or haemorrhage, and were introduced in the model. The model was well calibrated and predicted the absence of all three outcomes with an area under the curve of 0.76 (P = 0.001). Of the 944 patients, 218 (23.1 per cent) fulfilled the five criteria of the model, and 9.6 per cent experienced postoperative ascites (RR 0.22; P = 0.001), 1.8 per cent haemorrhage (RR 0.21; P = 0.033), 4.1 per cent bile leak (RR 0.54; P = 0.048), 40.4 per cent severe complications (RR 0.70; P = 0.001) and 1.4 per cent 90-day mortality (RR 0.13; P = 0.004). CONCLUSION: A practical model has been provided to identify patients at low risk of ascites, bile leakage and haemorrhage after LT; these patients could potentially qualify for inclusion in non-abdominal drainage protocols.

Changes in fecal microbiota with CFTR modulator therapy: A pilot study.

Studies have demonstrated that people with CF with pancreatic insufficiency (PI) have fecal dysbioses. Evidence suggests the causes of these dysbioses are multifactorial, and that important drivers include antibiotic exposure, dietary intake, and CF gastrointestinal tract dysfunction, including nutrient malabsorption. In this pilot study, we tested whether initiation of the CFTR modulator treatments ivacaftor (in a cohort of pancreatic sufficient (PS) people with CF and an R117H CFTR variant) or lumacaftor/ivacaftor (in a cohort of PI people with CF and an F508del variant) changed fecal measures of malabsorption or fecal microbiomes. While we identified no statistically significant fecal changes with either treatment, we detected trends in the PI cohort when initiating lumacaftor/ivacaftor towards decreased fecal fat content and towards fecal microbiomes that more closely resembled the fecal microbiota of people without PI. While these findings support a model in which nutrient malabsorption resulting from CF-induced PI drives fecal dysbiosis, they must be validated in future, larger studies of fecal microbiome and malabsorption outcomes with highly effective CFTR modulator therapies.

Lower cognitive reappraisal capacity is related to impairments in attachment and personality structure in poly-drug use: an fMRI study.

Insecure attachment, impaired personality structure and impaired emotion regulation figure prominently in substance use disorders. While negative emotions can trigger drug-use and relapse, cognitive reappraisal may reduce emotional strain by promoting changes in perspective. In the present study, we explored behavioral and neural correlates of cognitive reappraisal in poly-drug use disorder by testing individuals' capability to generate cognitive reappraisals for aversive events (Reappraisal Inventiveness Test). 18 inpatients with poly-drug use disorder and 16 controls completed the Adult Attachment Scale, the Emotion Regulation Questionnaire, the Brief Symptom Inventory, the Wonderlic Personnel Test, and the Operationalized Psychodynamic Diagnosis Structure Questionnaire, as well as two versions of the Reappraisal Inventiveness Test (during fMRI and outside the lab). Compared to controls, polydrug inpatients reported impaired personality structure, attachment and emotion regulation abilities. In the Reappraisal Inventiveness Test, poly-drug inpatients were less flexible and fluent in generating reappraisals for anger-eliciting situations. Corresponding to previous brain imaging evidence, cognitive reappraisal efforts of both groups were reflected in activation of left frontal regions, particularly left superior and middle frontal gyri and left supplemental motor areas. However, no group differences in neural activation patterns emerged. This suggests that despite cognitive reappraisal impairments on a behavioral level, neural reflections of these deficits in poly-drug use disorder might be more complex.

Pinpointing Neural Correlates of Attachment in Poly-Drug Use: A Diffusion Tensor Imaging Study.

An increasing amount of evidence indicates the significance of attachment in the etiology of poly-drug use disorder (PUD). The aim of this study was to investigate associations between PUD and adult attachment in particular, with a focus on white matter (WM) fiber tract integrity. For this purpose, we selected several regions-of-interest based on previous findings which were examined for their role in PUD and estimated whole-brain associations between adult attachment and WM integrity. A total sample of 144 right-handed males were investigated (Age: M = 27; SD = 4.66). This included a group of patients diagnosed with PUD (n = 70) and a group of healthy controls (HC; n = 74). The Adult Attachment Scales (AAS) was applied to assess attachment attitudes in participants. Diffusion Tensor Imaging was used to investigate differences in WM integrity. The findings suggest substantially less attachment security in PUD patients compared to HC. Furthermore, PUD patients exhibited reduced integrity in WM fiber tracts, most pronounced in the bilateral corticospinal tract, the fronto-occipital fasciculus, and the right inferior longitudinal fasciculus. However, these results were not controlled for comorbid depressiveness. With regard to associations between adult attachment and WM integrity, the results for PUD patients indicate a negative relationship between "Comfort with Closeness" and the structural integrity of a cluster comprising parts of the right anterior thalamic radiation, the inferior fronto-occipital fasciculus and the uncinate fasciculus. Despite being limited by the cross-sectional design of this study, the results emphasize the significance of attachment in PUD etiology, both at a behavioral and a neurological level. Largely in line with previous research, the findings revealed tentative links between adult attachment and WM fiber tracts related to cognitive and affective functions in PUD patients.

[Assessment of a newly-implemented blended teaching of intensive care and emergency medicine at Paris-Diderot University]. / Évaluation d'un enseignement multimodal intégrant du e-learning dans l'apprentissage de la réanimation et de la médecine d'urgence au cours du second cycle des études médicales.

INTRODUCTION: Blended-learning methods could be a response to student nonattendance. Non-compulsory teaching combining e-learning/interactive face-to-face sessions has been implemented at Paris-Diderot Medical School for the teaching of intensive care and emergency medicine during the 2018/2019 university period. The aim of the study was to assess this newly-implemented blended teaching. METHODS: Questionnaire submitted to the 388 DFASM3 medical students present at the faculty exam of intensive care/emergency medicine. Attendance at a teaching modality was defined by the follow-up of more than half of this teaching modality. Correlations between attendance at e-learning and/or interactive face-to-face sessions, and grade were performed. RESULTS: A total of 358/388 (92%) students participated in this survey. A quarter of the students (88/321 - 25%) reported they usually attended at traditional lectures. Regarding blended-learning, 210/317 (67%) students reported having attended at e-learning courses and 84/321 (27%) attended at interactive face-to-face sessions. The distribution of students according to their attendance at e-learning and/or interactive face-to-face sessions was significantly different (P<0.01). There was a significant correlation (P<0.001) between attendance at e-learning and grade obtained at the faculty exam. Nevertheless, this correlation was also found for these students in another course taught traditionally. Overall, 309/315 (98%) students were satisfied with the blended teaching, 297/318 (93%) wanted its extent to the whole medical school's curriculum. CONCLUSION: The use of combined learning methods reached more students than traditional teachings and allowed the University to focus on its role of knowledge transfer.

Management of liver failure in general intensive care unit.

OBJECTIVE: To produce French guidelines on Management of Liver failure in general Intensive Care Unit (ICU). DESIGN: A consensus committee of 23 experts from the French Society of Anesthesiology and Critical Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Association for the Study of the Liver (Association française pour l'étude du foie, AFEF) was convened. A formal conflict-of-interest (COI) policy was developed at the start of the process and enforced throughout. The entire guideline process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of the quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Some recommendations were ungraded. METHODS: Two fields were defined: acute liver failure (ALF) and cirrhotic patients in general ICU. The panel focused on three questions with respect to ALF: (1) Which etiological examinations should be performed to reduce morbidity and mortality? (2) Which specific treatments should be initiated rapidly to reduce morbidity and mortality? (3) Which symptomatic treatment should be initiated rapidly to reduce morbidity and mortality? Seven questions concerning cirrhotic patients were addressed: (1) Which criteria should be used to guide ICU admission of cirrhotic patients in order to improve their prognosis? (2) Which specific management of kidney injury should be implemented to reduce morbidity and mortality in cirrhotic ICU patients? (3) Which specific measures to manage sepsis in order to reduce morbidity and mortality in cirrhotic ICU patients? (4) In which circumstances, human serum albumin should be administered to reduce morbidity and mortality in cirrhotic ICU patients? (5) How should digestive haemorrhage be treated in order to reduce morbidity and mortality in cirrhotic ICU patients? (6) How should haemostasis be managed in order to reduce morbidity and mortality in cirrhotic ICU patients? And (7) When should advice be obtained from an expert centre in order to reduce morbidity and mortality in cirrhotic ICU patients? Population, intervention, comparison and outcome (PICO) issues were reviewed and updated as required, and evidence profiles were generated. An analysis of the literature and recommendations was then performed in accordance with the GRADE® methodology. RESULTS: The SFAR/AFEF Guidelines panel produced 18 statements on liver failure in general ICU. After two rounds of debate and various amendments, a strong agreement was reached on 100% of the recommendations: six had a high level of evidence (Grade 1 ±), seven had a low level of evidence (Grade 2 ±) and six were expert judgments. Finally, no recommendation was provided with respect to one question. CONCLUSIONS: Substantial agreement exists among experts regarding numerous strong recommendations on the optimum care of patients with liver failure in general ICU.

ComBat harmonization for radiomic features in independent phantom and lung cancer patient computed tomography datasets.

This work seeks to evaluate the combatting batch effect (ComBat) harmonization algorithm's ability to reduce the variation in radiomic features arising from different imaging protocols and independently verify published results. The Gammex computed tomography (CT) electron density phantom and Quasar body phantom were imaged using 32 different chest imaging protocols. 107 radiomic features were extracted from 15 spatially varying spherical contours between 1.5 cm and 3 cm in each of the lung300 density, lung450 density, and wood inserts. The Kolmogorov-Smirnov test was used to determine significant differences in the distribution of the features and the concordance correlation coefficient (CCC) was used to measure the repeatability of the features from each protocol variation class (kVp, pitch, etc) before and after ComBat harmonization. P-values were corrected for multiple comparisons using the Benjamini-Hochberg-Yekutieli procedure. Finally, the ComBat algorithm was applied to human subject data using six different thorax imaging protocols with 135 patients. Spherical contours of un-irradiated lung (2 cm) and vertebral bone (1 cm) were used for radiomic feature extraction. ComBat harmonization reduced the percentage of features from significantly different distributions to 0%-2% or preserved 0% across all protocol variations for the lung300, lung450 and wood inserts. For the human subject data, ComBat harmonization reduced the percentage of significantly different features from 0%-59% for bone and 0%-19% for lung to 0% for both. This work verifies previously published results and demonstrates that ComBat harmonization is an effective means to harmonize radiomic features extracted from different imaging protocols to allow comparisons in large multi-institution datasets. Biological variation can be explicitly preserved by providing the ComBat algorithm with clinical or biological variables to protect. ComBat harmonization should be tested for its effect on predictive models.

The relationship between "Eyes Reading" ability and verbal memory in bipolar disorder.

In psychiatric disorders, neurocognitive impairments are prevalent and have been associated with poor outcome. Deficits in Theory of Mind (ToM, "mentalising") have also been observed in bipolar disorder (BD); however, the literature shows inconsistent data. The aim of this study was to explore ToM performance in a well-characterized sample of euthymic individuals with BD and its relationship with neurocognitive function. One hundred sixteen euthymic patients with BD between 18 and 74 years (mean age = 42.4, SD = 13.8) and 79 healthy controls (mean age = 39.8, SD = 16.5) were investigated with an extensive neurocognitive test battery (Trail Making Test A/B, d2 Test of Attention, Stroop Color-Word Test, California Verbal Learning Test, Multiple Choice Vocabulary Test). Additionally, all participants were given the Reading the Mind in the Eyes Test (RMET) to measure affective ToM, the ability to make assumptions about other people´s feelings. Overall, "Eyes Reading" performance was not impaired in individuals with BD compared with controls. However, a significant relationship between RMET and verbal memory in BD was shown, particularly in males. Data showed worse RMET performance in patients with memory deficits compared to patients without memory deficits and controls. Due to cross-sectional data, no conclusions can be made with respect to cause and effect.

Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors.

The cell adhesion molecule neuroligin2 (NLGN2) regulates GABAergic synapse development, but its role in neural circuit function in the adult hippocampus is unclear. We investigated GABAergic synapses and hippocampus-dependent behaviors following viral-vector-mediated overexpression of NLGN2. Transducing hippocampal neurons with AAV-NLGN2 increased neuronal expression of NLGN2 and membrane localization of GABAergic postsynaptic proteins gephyrin and GABAARγ2, and presynaptic vesicular GABA transporter protein (VGAT) suggesting trans-synaptic enhancement of GABAergic synapses. In contrast, glutamatergic postsynaptic density protein-95 (PSD-95) and presynaptic vesicular glutamate transporter (VGLUT) protein were unaltered. Moreover, AAV-NLGN2 significantly increased parvalbumin immunoreactive (PV+) synaptic boutons co-localized with postsynaptic gephyrin+ puncta. Furthermore, these changes were demonstrated to lead to cognitive impairments as shown in a battery of hippocampal-dependent mnemonic tasks and social behaviors.

Arterial hypertension in patients with atrial fibrillation in Europe: A report from the EURObservational Research Programme pilot survey on atrial fibrillation.

BACKGROUND: Hypertension (HTN) is the most prevalent co-morbidity among atrial fibrillation (AF) patients; the relationship between the two is bidirectional, with an incremental effect on adverse outcomes. PURPOSE: To study clinical features, treatment patterns and 1year outcomes amongst AF patients with HTN in the EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry, a prospective multi-national survey conducted by the European Society of Cardiology in 9 European countries. METHODS: Of 3119 enrolled AF patients, 2194 were diagnosed with HTN (AF-HTN) and 909 were normotensive (AF-NT) (16 patients had unknown HTN status). We compared baseline clinical features, management strategy and 1-year outcomes in terms of all-cause death, cardiovascular (CV) death, and any thrombosis-related event (TE: stroke, transient ischemic attack, acute coronary syndrome, coronary intervention, cardiac arrest, peripheral/pulmonary embolism) in AF-HTN vs AF-NT patients. RESULTS: The AF-HTN patients had more prevalent CV risk factors and comorbidities (median CHA2DS2-VASc score (IQR) 4 (3, 5) in AF-HTN, versus 2 (1, 3) in AF-NT; p<0.01). Crude rate of all-cause death and any TE event was higher in AF-HTN (194 (11.2%) versus 60 (8.2%), p=0.02). Kaplan-Meier analysis curves for death by hypertensive status showed no significant differences between the subgroups (log rank test, p=0.22). On logistic regression analysis, HTN did not emerge as an independent risk factor for outcomes (OR 1.08, 95% CI 0.76-1.54). CONCLUSION: AF-HTN patients have a higher prevalence of comorbidities and this conferred a higher risk for a composite endpoint of all-cause death and thromboembolic events. In this cohort HTN did not independently predict all-cause mortality at 1-year.

Effect of cellobiose supplementation on in vitro fermentation activity and bacterial numbers of porcine inocula.

In this in vitro study, the modified Hohenheim gas test (HGT) was applied to determine fermentation activity and bacterial composition of pig's faecal microbial inoculum using different concentrations of cellobiose. Incubation procedures included normal buffered and osmotic stress conditions (elevated medium salinity). After 24 hr of fermentation, production of gas, ammonia and short-chain fatty acid (SCFA) was measured, and the gene copy numbers of total bacteria, Lactobacillus spp., Bifidobacterium spp., Roseburia spp., Clostridium Cluster IV spp. and Enterobacteriaceae were analysed using real-time polymerase chain reaction. There was a significant reduction in gas production after 24 hr when comparing osmotic stress conditions with normal buffered conditions. Under osmotic stress, increasing cellobiose concentrations linearly increased gas production (p < .001), while ammonia, acetic acid and isobutyric acid concentrations decreased (p < .001, p = .012, p = .035 respectively). Under normal buffered conditions, Roseburia spp. gene copies linearly increased with increasing cellobiose concentrations (p = .048). Lactobacillus spp. and Bifidobacterium spp. numbers were higher under osmotic stress (p < .001) compared to normal conditions. Results might point towards a positive impact of cellobiose supplementation on gut health especially under osmotic stress conditions.

Implementation of buffy-coat-derived pooled platelet concentrates for internal quality control of light transmission aggregometry: a proof of concept study.

Essentials In platelet function testing, standardized internal controls (IQC) are not commercially provided. Platelet function testing was performed daily on aliquoted pooled platelet concentrates. Pooled platelet concentrates showed stability for control purposes from Monday to Friday. Pooled platelet concentrates provide the necessary steadiness to serve as IQC material. SUMMARY: Background Standardized commercially available control material for internal quality control (IQC) of light transmission aggregometry (LTA) is still lacking. Moreover, the availability of normal blood donors to provide fresh platelets is difficult in small laboratories, where 'volunteers' may be in short supply. Objectives To evaluate the implementation of buffy-coat-derived pooled platelet concentrates (PCs) for IQC material for LTA. Methods We used buffy-coat-derived pooled PCs from the blood bank as IQC material for LTA. On each weekend one PC was prepared (> 200 mL) and aliquoted from the original storage bag on a daily basis in four baby bags (40-50 mL), which were delivered from Monday to Friday to our laboratory. The IQC measurements of at least 85 work-weeks (from Monday to Friday) were evaluated with this new IQC material. LTA was performed on a four-channel Chronolog 700 Aggregometer (Chronolog Corporation, Havertown, PA, USA) (agonists: collagen, adenosine diphosphate [ADP], arachidonic acid [AA] and thrombin receptor activator peptide-6 [TRAP-6]). Results The medians of platelet aggregation from IQC measurements with collagen, ADP and AA from Monday to Friday were 68.0-59.5, 3.0-2.0 and 51.0-50.0%, respectively, and the mean of platelet aggregation with TRAP-6 was 71.2-66.4%. Conclusions Buffy-coat-derived pooled PCs serve as a reliable and robust IQC material for LTA measurements and would be beneficial for the whole laboratory procedure and employees' safety.

The PF4/PPBP/CXCL5 Gene Cluster Is Associated with Periodontitis.

Periodontitis is a common dysbiotic inflammatory disease with an estimated heritability of 50%. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWAS) of chronic periodontitis (CP) have been unsuccessful in discovering susceptibility factors. A strategy that combines agnostic GWAS with a well-powered candidate-gene approach has the potential to discover novel loci. We combined RNA-seq data from gingival tissues with quantitative trait loci (QTLs) that were identified in a F2-cross of mice resistant and susceptible to infection with oral bacterial pathogens. Four genes, which were located within the mapped QTLs, showed differential expression. The chromosomal regions across the human orthologous were interrogated for putative periodontitis-associated variants using existing GWAS data from a German case-control sample of aggressive periodontitis (AgP; 651 cases, 4,001 controls), the most severe and early onset form of periodontitis. Two haplotype blocks, one upstream to the coding region of UGT2A1 (rs146712414, P = 9.1 × 10-5; odds ratio [OR], 1.34; 95% confidence interval [CI], 1.16-1.56) and one downstream of the genes PF4/PPBP/CXCL5 (rs1595009, P = 1.3 × 10-4; OR, 1.32; 95% CI, 1.15-1.52), were associated with AgP. The association of rs1595009 was validated in an independent cohort of CP of European Americans (1,961 cases and 1,864 controls; P = 0.03; OR, 1.45; 95% CI, 1.01-1.29). This association was further replicated in another sample of 399 German CP cases (disease onset <60 y of age) and 1,633 controls ( P = 0.03; OR, 1.75; 95% CI, 1.06-2.90). The combined estimates of association from all samples were P = 2.9 × 10-5 (OR, 1.2; 95% CI, 1.1-1.3). This study shows the strength of combining QTL mapping and RNA-Seq data from a mouse model with association studies in human case-control samples to identify genetic risk variants of periodontitis.