Heart Failure Knowledge Assessment and Perceived Patient Satisfaction in Heart Failure Units: A Multicenter Observational Survey.

Background: Self-care and empowerment promotion in patients with heart failure (HF) is essential for improving their prognosis, but there is limited information concerning the patients' depth of knowledge about this pathology as well as patient satisfaction within heart failure units (HFUs). Our objective was to assess both aspects in a cohort of patients regularly followed-up HFUs. Methods: A multicenter, observational study was conducted with consecutive patients followed in 14 HFUs between June and November 2023. It was based on a cross-sectional survey comprising 23 questions related to demographics, knowledge/self-care, and the subjective assessment of perceived quality and satisfaction in HFUs. Results: 281 patients were included (36.7% women, 74.7% aged over 65 years). 48% had hospitalizations for HF or sought emergency department services within the preceding year. The mean correct responses related to knowledge were 9.7 ± 2.3 (80.7% of the total), and 53 patients (18.9%) answered all knowledge questions correctly. 211 (79.6%) could identify potential HF decompensation with abrupt weight gain, and 196 (74.2%) recognized at least three additional signs of worsening HF. 266 patients (98.2%) were likely or very likely to recommend HFUs, and 194 (89.8%) positively appreciated the experience at the day hospital. Conclusions: Patients followed up in HFUs showed adequate but improvable knowledge and capacity for self-care, with a high level of satisfaction.

Therapeutic Targets in Innate Immunity to Tackle Alzheimer's Disease.

There is an urgent need for effective disease-modifying therapeutic interventions for Alzheimer's disease (AD)-the most prevalent cause of dementia with a profound socioeconomic burden. Most clinical trials targeting the classical hallmarks of this disease-ß-amyloid plaques and neurofibrillary tangles-failed, showed discrete clinical effects, or were accompanied by concerning side effects. There has been an ongoing search for novel therapeutic targets. Neuroinflammation, now widely recognized as a hallmark of all neurodegenerative diseases, has been proven to be a major contributor to AD pathology. Here, we summarize the role of neuroinflammation in the pathogenesis and progression of AD and discuss potential targets such as microglia, TREM2, the complement system, inflammasomes, and cytosolic DNA sensors. We also present an overview of ongoing studies targeting specific innate immune system components, highlighting the progress in this field of drug research while bringing attention to the delicate nature of innate immune modulations in AD.

Genetic variants in triglyceride metabolism genes among individuals with hypertriglyceridemia in Colombia.

BACKGROUND: The genetic substrate of severe hypertriglyceridemia (sHTG) in Latin America is insufficiently understood. OBJECTIVE: To identify genetic variants in genes related to triglyceride (TG) metabolism among adults with sHTG from Colombia. METHODS: In individuals with plasma TG≥880 mg/dL at least once in their lifetime, we amplified and sequenced all exons and intron/exon boundaries of the genes LPL, APOC2, APOA5, GPIHBP1 and LMF1. For each variant we ascertained its location, zygosity, allelic frequency and pathogenicity classification according to American College of Medical Genetics (ACMG) criteria. RESULTS: The study included 166 participants (62 % male, mean age 50), peak TG levels ranged between 894 and 11,000 mg/dL. We identified 92 variants: 19 in LPL, 7 in APOC2, 11 in GPIHBP1, 38 in LMF1, and 17 in APOA5. Eighteen of these variants had not been reported. We identified a new pathogenic variant in LMF1 (c.41C>A; p.Ser14*), a new likely pathogenic variant in LMF1 (c.1527 C > T; p.Pro509=, also expressed as c.1447C>T; p.Gln483*), and a known pathogenic variant in LMF1 (c.779G>A; p.Trp260*). Four participants were heterozygous for variant c.953A>G; p.Asn318Ser in LPL, a known risk factor for hypertriglyceridemia. Participants with variants of unknown significance (VUS) in LMF1 had significantly higher peak TG than those with VUS in other genes. Peak TG were 4317 mg/dL in participants with a history of pancreatitis, and 1769 mg/dL in those without it (p = 0.001). CONCLUSION: Our study identified variants associated with sHTG among Latinos, and showed that genetic variation in LMF1 may be frequently associated with sHTG in this population.

Superoxide radical derived metal-free spiro-OMeTAD for highly stable perovskite solar cells.

Lithium salt-doped spiro-OMeTAD is widely used as a hole-transport layer (HTL) for high-efficiency n-i-p perovskite solar cells (PSCs), but unfortunately facing awkward instability for commercialization arising from the intrinsic Li+ migration and hygroscopicity. We herein demonstrate a superoxide radicals (•O2-) derived HTL of metal-free spiro-OMeTAD with remarkable capability of avoiding the conventional tedious oxidation treatment in air for highly stable PSCs. Present work explores the employing of variant-valence Eu(TFSI)2 salts that could generate •O2- for facile and adequate pre-oxidation of spiro-OMeTAD, resulting in the HTL with dramatically increased conductivity and work function. Comparing to devices adopting HTL with LiTFSI doping, the •O2--derived spiro-OMeTAD increases the PSCs efficiency up to 25.45% and 20.76% for 0.05 cm2 active area and 6 × 6 cm2 module, respectively. State-of-art PSCs employing such metal-free HTLs are also demonstrated to show much-improved environmental stability even under harsh conditions, e.g., maintaining over 90% of their initial efficiency after 1000 h of operation at the maximum power point and after 80 light-thermal cycles under simulated low earth orbit conditions, respectively, indicating the potentials of developing metal-free spiro-OMeTAD for low-cost and shortened processing of perovskite photovoltaics.

Evaluation and Future Challenges in a Self-Guided Web-Based Intervention With and Without Chat Support for Depression and Anxiety Symptoms During the COVID-19 Pandemic: Randomized Controlled Trial.

BACKGROUND: The COVID-19 pandemic has had an impact on mental health worldwide. Low- and middle-income countries were largely affected by it. Mexico was one of the most affected countries. Extended periods of lockdowns, isolation, and social distancing, among other factors, highlighted the need to introduce web-based psychological interventions to the Mexican population. In this context, Mental Health COVID-19 emerged as a self-guided web-based intervention (SGWI) aimed at adults to improve mental health during the COVID-19 pandemic. OBJECTIVE: This study aims to assess the efficacy of 2 modalities of a self-guided intervention (with and without chat support) in reducing depression symptoms, generalized anxiety, community posttraumatic stress, widespread fear, anxiety, sleep quality, physiological and affective coping, and suicide ideation. In addition, it aimed to compare the moderating role of coping strategies, acceptance, and satisfaction in participants' symptom reduction. We hypothesize that the self-guided, chat-supported modality will show higher efficacy than the modality without chat support in achieving clinical change and better performance as a moderator of depression symptoms, generalized anxiety, community posttraumatic stress, widespread fear, anxiety, sleep quality, physiological and affective coping, and suicide ideation, as well as an increase in participants' satisfaction and acceptability. METHODS: A randomized controlled trial was conducted. Data were collected from May 2020 to June 2022. We performed intrasubject measures at 4 evaluation periods: pretest, posttest, and follow-up measurements at 3 and 6 months. Differences between intervention groups were assessed through the Mann-Whitney U test for continuous variables and the chi-square test for categorical variables. Changes due to intervention were analyzed using Wilcoxon W test. Moderated regression analysis was performed to test the hypothesized moderating role of coping strategies, usability, and opinion about treatment on clinical change. RESULTS: A total of 36 participants completed the intervention; of these, 5 (14%) were part of the SGWI group, and 31 (86%) were on the SGWI plus chat support (SGWI+C) group, which included a chat service with therapists. The perceived high complexity of the system for the SGWI group had a moderating effect associated with a lack of efficacy of the intervention regarding depression, but not when controlled for sociodemographic variables. A perception of lower helpfulness of the intervention was associated with poorer outcomes. Coping strategies did not show moderating effects. CONCLUSIONS: Enhancing the utility of web-based interventions for reducing clinical symptoms by incorporating a support chat to boost treatment adherence seemed to improve the perception of the intervention's usefulness. Web-based interventions face several challenges, such as eliminating complexities in platform use and increasing the users' perceived utility of the intervention, among other issues identified in the study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04468893; https://clinicaltrials.gov/study/NCT04468893?tab=results. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/23117.

Association of SARS-CoV-2 immunoserology and vaccination status with myocardial infarction severity and outcome.

BACKGROUND: The COVID-19 pandemic adversely affected the severity and prognosis of patients with acute myocardial infarction (MI) caused by atherothrombosis (type 1 MI). The effect, if any, of COVID-19 vaccination and natural SARS-CoV2 serologic immunity in these patients is unclear. Our aim was to analyze the association between the severity and outcome of patients with type 1 MI and their previous SARS-CoV2 vaccination and serostatus. METHODS: A single-center retrospective cohort study conducted between March 1, 2020 and March 1, 2023. Clinical and follow-up information was collected from medical records and patients. Total antibodies (IgM, IgA, IgG) to nucleocapsid (N) antigens were measured by ECLIA (electrochemiluminescence-based immunoassay) to test the immune response to natural infection. If positive, IgM and IgG antibodies to spike (S) surface antigens were measured by CLIA to test the immune response to vaccine or natural infection. Multivariable logistic regression analysis was performed, adjusting for age, sex, hypertension, diabetes, and dyslipidemia. RESULTS: Total sample of 949 patients, 656 with ST-segment elevation MI (STEMI) and 293 with non-ST-segment elevation MI (NSTEMI). Mean age was 64 (SD 13) years, 80 % men. Pre-admission vaccination status was: ≥ 1 dose, 53 % of patients; complete vaccination, 49 %; first booster dose, 25 %. The majority (84 %) of vaccines administered were mRNA-based. Six months after MI, 92 (9.7 %) patients had a major adverse cardiac event (MACE) and 50 died; 11 % of patients had severe heart failure or cardiogenic shock (Killip III-IV) after STEMI. Vaccinated patients with STEMI and positive serology (Pos/Vax group) had a higher risk of Killip III-IV on admission: OR 2.63 (1.27-5.44), p = 0.010. SARS-CoV-2 S-specific IgG titers were highest in this group (median > 2080 AU/mL, [IQR 1560- >2080] vs 91 [32-198] in the unvaccinated group). In the overall sample, a higher incidence of 6-month MACE was not demonstrated (OR 1.89 [0.98-3.61], p = 0.055). CONCLUSIONS: The combination of vaccination and natural SARS-CoV2 infection was associated with the development of severe heart failure and cardiogenic shock in patients with STEMI, possibly related to an increased serological response.

Optimising the indications for biliary stent placement during endoscopic retrograde cholangiopancreatography: a quality improvement initiative to enhance patient care and reduce healthcare resource utilisation.

BACKGROUND: A retrospective chart audit was performed to review biliary stent utilisation from January 2020 to January 2021. Non-guideline-based stent insertion was identified in 16% of patients with common bile duct (CBD) stones presenting for endoscopic retrograde cholangiopancreatography (ERCP). To improve this knowledge-practice gap, a quality improvement (QI) intervention was devised and trialled. AIM: To synchronise clinical indications for biliary stent insertion in patients with CBD stones in accordance with published guidelines. METHODS: Using a QI pre-post study design, chart audits were completed and shared with the ERCP team (n=6). Indication for biliary stent insertion was compared to published guidelines assessed by two reviewers independently (kappa statistic calculated). The QI intervention included an education session and quarterly practice audits. An interrupted time series with segmented regression was completed. RESULTS: A total of 661 patients (337 F), mean age 59±19 years (range 12-98 years), underwent 885 ERCPs during this postintervention period. Of 661 patients, 384 (58%) were referred for CBD stones. A total of 192 biliary stents (105 plastic, 85 metal) were placed during the first ERCP (192/661, 29%), as compared with the preintervention year (223/598, 37%, p=0.2). Furthermore, 13/192 stents (7%) were placed not in accordance with published guidelines (kappa=0.53), compared with 63/223 (28%) in the preintervention year (p<0.0001). A 75% reduction in overall avoidable stent placement was achieved with a direct cost avoidance of $C97 500. For the CBD stone subgroup, there was an 88% reduction in avoidable biliary stent placement compared with the preintervention year (8/384, 2% vs 61/375, 16%, p<0.0001). CONCLUSIONS: Education with audit and feedback supported the closing of a knowledge-to-practice gap for biliary stent insertion during ERCP, especially in patients with CBD stones. This has resulted in a notable reduction of avoidable stent placements and additional follow-up ERCPs and an overall saving of healthcare resources.

Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase.

Actin dynamics control early T-cell receptor (TCR) signalling during T-cell activation. However, the precise regulation of initial actin rearrangements is not completely understood. Here, we have investigated the regulatory role of the phosphatase Slingshot-1 (SSH1) in this process. Our data show that SSH1 rapidly polarises to nascent cognate synaptic contacts and later relocalises to peripheral F-actin networks organised at the mature immunological synapse. Knockdown of SSH1 expression by CRISPR/Cas9-mediated genome editing or small interfering RNA reveal a regulatory role for SSH1 in CD3ε conformational change, allowing Nck binding and proper downstream signalling and immunological synapse organisation. TCR triggering induces SSH1-mediated activation of actin dynamics through a mechanism mediated by Limk-1 inactivation. These data suggest that during early TCR activation, SSH1 is required for rapid F-actin rearrangements that mediate initial conformational changes of the TCR, integrin organisation and proximal signalling events for proper synapse organisation. Therefore, the SSH1 and Limk-1 axis is a key regulatory element for full T cell activation.

Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes.

Microglia are crucial for maintaining brain health and neuron function. Here, we report that microglia establish connections with neurons using tunneling nanotubes (TNTs) in both physiological and pathological conditions. These TNTs facilitate the rapid exchange of organelles, vesicles, and proteins. In neurodegenerative diseases like Parkinson's and Alzheimer's disease, toxic aggregates of alpha-synuclein (α-syn) and tau accumulate within neurons. Our research demonstrates that microglia use TNTs to extract neurons from these aggregates, restoring neuronal health. Additionally, microglia share their healthy mitochondria with burdened neurons, reducing oxidative stress and normalizing gene expression. Disrupting mitochondrial function with antimycin A before TNT formation eliminates this neuroprotection. Moreover, co-culturing neurons with microglia and promoting TNT formation rescues suppressed neuronal activity caused by α-syn or tau aggregates. Notably, TNT-mediated aggregate transfer is compromised in microglia carrying Lrrk22(Gly2019Ser) or Trem2(T66M) and (R47H) mutations, suggesting a role in the pathology of these gene variants in neurodegenerative diseases.

Tracing the Scientific Legacy: Bibliometric Analysis of LATAM Research in Bariatric Surgery for 33 Years.

INTRODUCTION: Metabolic and bariatric surgery (MBS) has experienced considerable growth, addressing the challenges of obesity and its complications. The lack of a comprehensive bibliometric analysis in Latin America motivates this study, highlighting the need to understand the evolution of research in this area and its impact on clinical decision-making and health policies. METHODOLOGY: A cross-sectional bibliometric study was carried out using the Scopus database. A structured search strategy was designed to identify articles related to bariatric surgery with authors affiliated with Latin American countries. Inclusion and exclusion criteria were applied, followed by a descriptive and bibliometric analysis of the scientific production found. RESULTS: A total of 3553 documents published between 1991 and 2024 were included. There was an annual growth of 11%, with an average age of documents of 7.5 years. A concentration was observed in some countries, notably Brazil, Mexico, and Chile. Although scientific output increased, the average number of citations per article showed a downward trend since 2003. DISCUSSION: Despite the growth in scientific production, the quality and relevance of research is questioned, especially given the decrease in the impact received. It highlights the lack of meaningful regional collaboration, which could limit the sharing of knowledge and resources. Questions are raised about gaps in research capacity and the economic and development implications are discussed. CONCLUSIONS: This study provides valuable information to strengthen future research in bariatric surgery in Latin America. It highlights the importance of promoting regional and international collaboration and improving research training in countries with less participation. Clinical intervention strategies can benefit from better understanding research trends and adopting evidence-based practices in a more informed manner.

Impact of dexamethasone on transplant-related mortality in pediatric patients: a multi-site, propensity score-weighted, retrospective assessment.

Dexamethasone use during hematopoietic cell transplant (HCT) conditioning varies between pediatric centers. This study aimed to estimate the difference in 1-year treatment-related mortality (TRM) between patients who did or did not receive dexamethasone during HCT conditioning. Secondary objectives were to estimate the difference between dexamethasone-exposed and dexamethasone-unexposed groups in 1-year event-free survival (EFS), time to neutrophil engraftment, acute graft-versus-host disease (aGVHD), and invasive fungal disease (IFD) at day + 100. This was a seven-site, international, retrospective cohort study. Patients < 18 years old undergoing their first allogeneic or autologous myeloablative HCT for hematologic malignancy or aplastic anemia between January 1, 2012, and July 31, 2017, were included. To control for potential confounders, propensity score weighting was used to calculate the standardized mean difference for all endpoints. Among 242 patients, 140 received dexamethasone during HCT conditioning and 102 did not. TRM was unaffected by dexamethasone exposure (1.7%; 95% CI - 7.4, 10.2%). Between-group differences in secondary outcomes were small. However, dexamethasone exposure significantly increased possible, probable, and proven IFD incidence (9.0%, 95% CI 0.8, 17.3%). TRM is not increased in pediatric patients who receive dexamethasone during HCT conditioning. Clinicians should consider potential IFD risk when selecting chemotherapy-induced vomiting prophylaxis for pediatric HCT patients.

Phylogeny and species delimitation of ciliates in the genus Spirostomum (Class, Heterotrichea) using single-cell transcriptomes.

Ciliates are single-celled microbial eukaryotes that diverged from other eukaryotic lineages over a billion years ago. The extensive evolutionary timespan of ciliate has led to enormous genetic and phenotypic changes, contributing significantly to their high level of diversity. Recent analyses based on molecular data have revealed numerous cases of cryptic species complexes in different ciliate lineages, demonstrating the need for a robust approach to delimit species boundaries and elucidate phylogenetic relationships. Heterotrich ciliate species of the genus Spirostomum are abundant in freshwater and brackish environments and are commonly used as biological indicators for assessing water quality. However, some Spirostomum species are difficult to identify due to a lack of distinguishable morphological characteristics, and the existence of cryptic species in this genus remains largely unexplored. Previous phylogenetic studies have focused on only a few loci, namely the ribosomal RNA genes, alpha-tubulin, and mitochondrial CO1. In this study, we obtained single-cell transcriptome of 25 Spirostomum species populations (representing six morphospecies) sampled from South Korea and the USA, and used concatenation- and coalescent-based methods for species tree inference and delimitation. Phylogenomic analysis of 37 Spirostomum populations and 265 protein-coding genes provided a robustious insight into the evolutionary relationships among Spirostomum species and confirmed that species with moniliform and compact macronucleus each form a distinct monophyletic lineage. Furthermore, the multispecies coalescent (MSC) model suggests that there are at least nine cryptic species in the Spirostomum genus, three in S. minus, two in S. ambiguum, S. subtilis, and S. teres each. Overall, our fine sampling of closely related Spirostomum populations and wide scRNA-seq allowed us to demonstrate the hidden crypticity of species within the genus Spirostomum, and to resolve and provide much stronger support than hitherto to the phylogeny of this important ciliate genus.

Cumulative lifetime stressor exposure impairs stimulus-response but not contextual learning.

Greater exposure to stressors over the life course is believed to promote striatum-dependent over hippocampus-dependent learning and memory processes under stressful conditions. However, little research in this context has actually assessed lifetime stressor exposure and, moreover, it remains unknown whether greater cumulative lifetime stressor exposure exerts comparable effects on striatum-dependent learning and hippocampus-dependent learning in non-stressful contexts. To investigate this issue, we used the Stress and Adversity Inventory for Adults (Adult STRAIN) and Multicued Search Task to investigate the relation between cumulative lifetime stressor exposure and striatum-dependent stimulus-response learning and hippocampus-dependent contextual learning under non-stressful conditions among healthcare professionals (N = 205; 157 females, 48 males; Age: M = 34.23, SD 9.3, range 20-59 years). Individuals with moderate, but not low, cumulative lifetime stressor exposure exhibited impaired learning for stimulus-response associations. In contrast, learning for context associations was unrelated to participants' lifetime stressor exposure profiles. These results thus provide first evidence that cumulative lifetime stressor exposure may have negative consequences on human striatum-dependent stimulus-response learning under non-stressful environmental conditions.

Cardiac troponin T as a serum biomarker of respiratory impairment in amyotrophic lateral sclerosis.

OBJECTIVE: Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis. METHODS: In this retrospective observation, we analyzed two independent hospital-based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (nd = 298; nv = 49), serum neurofilament light chain (nd = 117; nv = 17), and respiratory tests (nd = 93; nv = 49). RESULTS: Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = -0.45, p = 0.001) and slow vital capacity % (r = -0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62-0.84) and <50% (AUC 0.80, 95% CI 0.68-0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61-0.83) and <50% (AUC 0.79, 95% CI 0.67-0.91). INTERPRETATION: Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function.

A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial contact site and cristae organizing system (MICOS) complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae-shaping factors, has not been fully determined. Here, we examine the MICOS complex in Schizosaccharomyces pombe, a minimal model whose genome only encodes for four core subunits. Using an unbiased proteomics approach, we identify a poorly characterized inner mitochondrial membrane protein that interacts with MICOS and is required to maintain cristae morphology, which we name Mmc1. We demonstrate that Mmc1 works in concert with MICOS to promote normal mitochondrial morphology and respiratory function. Mmc1 is a distant relative of the dynamin superfamily of proteins (DSPs), GTPases, which are well established to shape and remodel membranes. Similar to DSPs, Mmc1 self-associates and forms high-molecular-weight assemblies. Interestingly, however, Mmc1 is a pseudoenzyme that lacks key residues required for GTP binding and hydrolysis, suggesting that it does not dynamically remodel membranes. These data are consistent with the model that Mmc1 stabilizes cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane. Our study reveals a new class of proteins that evolved early in fungal phylogeny and is required for the maintenance of cristae architecture. This highlights the possibility that functionally analogous proteins work with MICOS to establish cristae morphology in metazoans.

Impulsivity in fatal suicide behaviour: A systematic review and meta-analysis of psychological autopsy studies.

Our aim is to review and perform a meta-analysis on the role of impulsivity in fatal suicide behaviour. We included papers who used psychological autopsy methodology, assessed adult death by suicide, and included assessment of impulsivity. We excluded papers about assisted suicide, terrorist suicide, or other cause of death other than suicide or postmortem diagnosis made only from medical records or database. 97 articles were identified. 33 were included in the systematic review and nine in the meta-analysis. We found that people who die by suicide with high impulsivity are associated with younger age, substance abuse, and low intention to die, whereas those with low impulsivity were associated with older age, depression, schizophrenia, high intention to die and low social support. In the meta-analysis, suicide cases had higher impulsivity scores than living controls (Hedges' g = 0.59, 95 % CI [0.28, 0.89], p=.002). However, studies showed heterogeneity (Q = 90.86, p<.001, I2=89.0 %). Impulsivity-aggressiveness interaction was assessed through meta-regression (ß=0.447, p=.045). Individuals with high impulsivity would be exposed to a higher risk of fatal suicide behaviour, aggressiveness would play a mediating role. People who die by suicide with high and low impulsivity display distinct characteristics, which may reflect different endophenotypes leading to suicide by different pathways.

Innate immune activation in neurodegenerative diseases.

Activation of the innate immune system following pattern recognition receptor binding has emerged as one of the major pathogenic mechanisms in neurodegenerative disease. Experimental, epidemiological, pathological, and genetic evidence underscores the meaning of innate immune activation during the prodromal as well as clinical phases of several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Importantly, innate immune activation and the subsequent release of inflammatory mediators contribute mechanistically to other hallmarks of neurodegenerative diseases such as aberrant proteostatis, pathological protein aggregation, cytoskeleton abnormalities, altered energy homeostasis, RNA and DNA defects, and synaptic and network disbalance and ultimately to the induction of neuronal cell death. In this review, we discuss common mechanisms of innate immune activation in neurodegeneration, with particular emphasis on the pattern recognition receptors (PRRs) and other receptors involved in the detection of damage-associated molecular patterns (DAMPs).

Performance evaluation of the FastIC readout ASIC with emphasis on Cherenkov emission in TOF-PET.

Objective.The efficient usage of prompt photons like Cherenkov emission is of great interest for the design of the next generation, cost-effective, and ultra-high-sensitivity time-of-flight positron emission tomography (TOF-PET) scanners. With custom, high power consuming, readout electronics and fast digitization the prospect of sub-300 ps FWHM with PET-sized BGO crystals have been shown. However, these results are not scalable to a full system consisting of thousands of detector elements.Approach.To pave the way toward a full TOF-PET scanner, we examine the performance of the FastIC ASIC with Cherenkov-emitting scintillators (BGO), together with one of the most recent SiPM detector developments based on metal trenching from FBK. The FastIC is a highly configurable ASIC with 8 input channels, a power consumption of 12 mW ch-1and excellent linearity on the energy measurement. To put the timing performance of the FastIC into perspective, comparison measurements with high-power consuming readout electronics are performed.Main results.We achieve a best CTR FWHM of 330 ps for 2 × 2 × 3 mm3and 490 ps for 2 × 2 × 20 mm3BGO crystals with the FastIC. In addition, using 20 mm long LSO:Ce:Ca crystals, CTR values of 129 ps FWHM have been measured with the FastIC, only slightly worse to the state-of-the-art of 95 ps obtained with discrete HF electronics.Significance.For the first time, the timing capability of BGO with a scalable ASIC has been evaluated. The findings underscore the potential of the FastIC ASIC in the development of cost-effective TOF-PET scanners with excellent timing characteristics.

Stricture dilation via balloon-assisted endoscopy in Crohn's disease: approach and intraprocedural outcomes with the single-balloon and double-balloon systems.

Background: Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures via balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature. Objectives: This study assesses the intra-procedural success and safety of EBD via BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes. Design: Retrospective consecutive patient cohort analysis. Methods: We retrospectively assessed a consecutive small bowel CD patient cohort undergoing BAE at the University of Alberta Hospital endoscopy unit from 2013 to 2020. The primary endpoint discerned the safety and immediate success rate of EBD during endoscopy, and comparisons of the dilation parameters and efficacy of SBE versus DBE were assessed as secondary outcomes. Results: During the study period, 87 patients (44 male) with a mean age of 56 ± 14.7 years underwent 179 endoscopic procedures (92 DBE and 87 SBE). Of 358 strictures encountered, 320 (89.4%) were successfully dilated and traversed. The mean maximum dilation diameter was 15.76 ± 2.10 mm. There were no perforations or major adverse events. Conclusion: EBD via BAE is a safe procedure in small bowel CD with a high intraprocedural success rate. Overall, SBE had a higher success rate in traversing strictures before and after dilation using our technique. This analysis is limited by the retrospective nature of our study and must be balanced against the inherent benefits of the DBE system.

Outcome and approach of small-bowel stricture dilation using balloon-assisted endoscopy in patients with Crohn's disease This study investigated the safety and success of using balloon-assisted endoscopy as a method to dilate small bowel strictures in patients with Crohn's disease. As a secondary outcome, we compared the overall safety and success between two different types of endoscopic systems: the single- and double-balloon systems.

Triadic Approximation Reveals the Role of Interaction Overlap on the Spread of Complex Contagions on Higher-Order Networks.

Contagion processes relying on the exposure to multiple sources are prevalent in social systems, and are effectively represented by hypergraphs. In this Letter, we derive a mean-field model that goes beyond node- and pair-based approximations. We reveal how the stability of the contagion-free state is decided by either two- or three-body interactions, and how this is strictly related to the degree of overlap between these interactions. Our findings demonstrate the dual effect of increased overlap: it lowers the invasion threshold, yet produces smaller outbreaks. Corroborated by numerical simulations, our results emphasize the significance of the chosen representation in describing a higher-order process.