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Abstract Living in isolation is associated with a lack of stimulating experiences, which negatively impacts quality of life and increases risk of advancing cognitive decline for older adults. We examined how engaging in unique events would enhance memory and improve well-being during the COVID-19 pandemic lockdowns, a period characterized by social isolation and monotonous daily experiences lacking diversity. Over 8-weeks during lockdowns, 18 healthy older adults used a smartphone-based application called “HippoCamera”, capturing a total of 670 unique and routine events with short audio-video cues that were later replayed to prompt memory. As expected, unique events were recalled in greater episodic detail relative to routine events. Importantly, unique events were related to increased positive affect, decreased boredom, and the perception of time moving faster. These findings highlight the benefit of unique experiences for both memory and well-being, as well as suggest future interventions to benefit older adults who tend to experience higher levels of social isolation.

IntroductionVibrio alginolyticus is a Gram-negative, rod-shaped bacterium belonging to the family of Vibrionaceae, a common pathogen in aquaculture animals, However, studies on its impact on Scylla serrata (mud crabs) are limited. In this study, we isolated V. alginolyticus SWS from dead mud crab during a disease outbreak in a Hong Kong aquaculture farm, which caused up to 70% mortality during summer.MethodsExperimental infection and histopathology were used to investigate the pathogenicity of V. alginolyticus SWS in S. serrata and validate Koch’s postulates. Comprehensive whole-genome analysis and phylogenetic analysis antimicrobial susceptibility testing, and biochemical characterization were also performed. ResultsOur findings showed that V. alginolyticus SWS caused high mortality (75%) in S. serrata with infected individuals exhibiting inactivity, loss of appetite, decolored and darkened hepatopancreas, gills, and opaque muscle in the claw. Histopathological analysis revealed tissue damage and degeneration in the hepatopancreas, gills, and claw muscle suggesting direct and indirect impacts of V. alginolyticus SWS infection.ConclusionsThis study provides a comprehensive characterization of V. alginolyticus SWS as an emerging pathogen in S. serrata aquaculture. Our findings underscore the importance of ongoing surveillance, early detection, and the development of targeted disease management strategies to mitigate the economic impact of vibriosis outbreaks in mud crab aquaculture.

Abstract We consider the complete set of observables for collider searches for indirect effects of new heavy physics. They consist of SU(3)C × U(1)EM invariant interaction terms/operators that parameterize deviations from the Standard Model. We show that, under very general assumptions, the leading deviations from the Standard Model are given by a finite number of ‘primary’ operators, with the remaining operators given by ‘Mandelstam descendants’ whose effects are suppressed by powers of Mandelstam variables divided by the mass scale M of the heavy physics. We explicitly determine all 3 and 4-point primary operators relevant for Higgs signals at colliders by using the correspondence between on-shell amplitudes and independent operators. We give a detailed discussion of the methods used to obtain this result, including a new analytical method for determining the independent operators. The results are checked using the Hilbert series that counts independent operators. We also give a rough sketch of the phenomenology, including unitarity bounds on the interaction strengths and rough estimates of their importance for Higgs decays at the HL-LHC. These results motivate further exploration of Higgs decays to Z f ¯ f $$ Z\overline{f}f $$ , W f ¯ f ′ $$ W\overline{f}{f}^{\prime } $$ , γ f ¯ f $$ \gamma \overline{f}f $$ , and Zγγ.

Abstract Background Sufficient, safe and nutritious food is unattainable for many people experiencing severe food insecurity, putting them at dietary risk. Food banks, a growing part of the charitable food system (CFS), are the main source of food relief in developed countries. Donations of surplus, unsalable food from supermarkets, producers and manufacturers is the main source of the food supply, and this can be unpredictable, insufficient and inappropriate. The universal performance indicator of food-banking success is a weight-based measure, complemented by various initiatives to track the nutritional quality of food provided. There is currently no method that assesses the dietary risk of donated food related to nutrition and food safety. This protocol describes a method developed to identify and assess the dietary risk of donated food at an Australian food bank including the type, amount, nutrition quality, and food safety. Methods An audit of all food donated to a food bank servicing one Australian state was conducted over five consecutive days in May 2022. The audit process used a mobile device to take photographs of all incoming deliveries to the food bank. The images were manually annotated to document the type of food, product information (brand and product name, variety), the donor’s name, weight (kilograms), and date-marking details. Data was extracted from the photographs and assessed against pre-determined dietary risk criterion for food safety (date marking, damaged packaging, visible food spoilage) and nutrition quality according to the principles of the Australian Guide to Healthy Eating, and the NOVA classification of level of processing. Discussion Fifteen hundred images were required to assess the dietary risk of 86,050 kg of donated food. There were 72 separate donations, largely from supermarkets and food manufacturers. Data analysis will enable identification of dietary risk, particularly for nutrition quality and food safety. This is important given the absence of food regulation for CFS donations, and the vulnerability of the client group. This protocol highlights the need for more transparency and accountability from food donors, about the food they donate.

Objective: This study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time. Methods: In 2022, a total of 4684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes was determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements. Results: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5, 47) = 18.233, p < 0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5, 47) = 2.037, p = 0.091). Conclusion: This study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants.

The prolonged incubation period of traditional culture methods leads to a delay in diagnosing invasive infections. Nanopore 16S rRNA gene sequencing (Nanopore 16S) offers a potential rapid diagnostic approach for directly identifying bacteria in infected body fluids. To evaluate the clinical utility of Nanopore 16S, we conducted a study involving the collection and sequencing of 128 monomicrobial samples, 65 polymicrobial samples, and 20 culture-negative body fluids. To minimize classification bias, taxonomic classification was performed using 3 analysis pipelines: Epi2me, Emu, and NanoCLUST. The result was compared to the culture references. The limit of detection of Nanopore 16S was also determined using simulated bacteremic blood samples. Among the three classifiers, Emu demonstrated the highest concordance with the culture results. It correctly identified the taxon of 125 (97.7%) of the 128 monomicrobial samples, compared to 109 (85.2%) for Epi2me and 102 (79.7%) for NanoCLUST. For the 230 cultured species in the 65 polymicrobial samples, Emu correctly identified 188 (81.7%) cultured species, compared to 174 (75.7%) for Epi2me and 125 (54.3%) for NanoCLUST. Through ROC analysis on the monomicrobial samples, we determined a threshold of relative abundance at 0.058 for distinguishing potential pathogens from background in Nanopore 16S. Applying this threshold resulted in the identification of 107 (83.6%), 117 (91.4%), and 114 (91.2%) correctly detected samples for Epi2me, Emu, and NanoCLUST, respectively, in the monomicrobial samples. Nanopore 16S coupled with Epi2me could provide preliminary results within 6 h. However, the ROC analysis of polymicrobial samples exhibited a random-like performance, making it difficult to establish a threshold. The overall limit of detection for Nanopore 16S was found to be about 90 CFU/ml.

Abstract Background Personalized diet counselling, as part of lifestyle change programs for cardiometabolic risk conditions (combinations of prediabetes or type 2 diabetes, hypertension, dyslipidemia and high waist circumference) has been shown to reduce progression to type 2 diabetes overall. To identify key process of care measures that could be linked to changes in diet, we undertook a secondary analysis of a Canadian pre-post study of lifestyle treatment of metabolic syndrome (MetS). Diet counselling process measures were documented and association with diet quality changes after 3 months were assessed. Results of the primary study showed 19% reversal of MetS after 1 year. Methods Registered dietitians (RDs) reported on contact time, specific food behaviour goals (FBG), behaviour change techniques (BCT; adapted from the Michie CALO-RE taxonomy) and teaching resources at each contact. Diet quality was measured by 2005 Canadian Healthy Eating Index (HEI-C) and assessed for possible associations with individual BCT and FBG. Results Food behaviour goals associated with improved HEI-C at 3 months were: poultry more than red meat, increased plant protein, increased fish, increased olive oil, increased fruits and vegetables, eating breakfast, increased milk and alternatives, healthier fats, healthier snacks and increased nuts, with an adverse association noted for more use (> 2 times/ 3 months) of the balanced meal concept (F test; p 3 times/3 months) was associated with poorer HEI-C at 3 months (F test; p = 0.007). Only self-monitoring, feedback on performance and focus on past success were associated with improved HEI-C. Conclusions These results identify key aspects of process that impact diet quality. Documentation of both FBG and BCT is highly relevant in diet counselling and a summary diet quality score is a promising target for assessing short-term counselling success.

Introduction Fear of cancer recurrence (FCR) is a prevalent and frequently debilitating response to a cancer diagnosis, affecting a substantial proportion of cancer survivors. Approximately 30% of local Hong Kong Chinese cancer survivors in a recent survey reportedly experienced persistent high FCR over the first-year post-surgery. This was associated with lower levels of psychological well-being and quality of life. A manualised intervention (ConquerFear) developed primarily based on the Self-Regulatory Executive Function Model and the Rational Frame Theory, has been found to reduce FCR effectively among Caucasian cancer survivors. The intervention now has been adapted to a Chinese context; ConquerFear-HK. The primary aim of this study is to evaluate its efficacy vs a standard-survivorship-care control (BasicCancerCare) in FCR improvement in a randomised control trial (RCT).Methods and analysis In this RCT, using the sealed envelope method, 174 eligible Chinese cancer survivors will be randomised to either the ConquerFear-HK or BasicCancerCare intervention. Both interventions include six sessions over 10 weeks, which will be delivered via face to face or online by trained therapists. The ConquerFear-HK intervention incorporates value classification, metacognitive therapy, attentional training, detached mindfulness and psychoeducation; BasicCancerCare includes relaxation training, dietary and physical activity consultations. Participants will be assessed at prior randomisation (baseline; T0), immediately postintervention (T1), 3 months (T2) and 6 months postintervention (T3) on the measures of FCR (Fear of Cancer Recurrence Inventory) as a primary outcome; metacognition (30-item Metacognitions Quesionnaire) and cognitive attentional syndrome (Cognitive-attentional Syndrome Questionnaire) as process outcomes; psychological distress (Hospital Anxiety and Depression Scale), cancer-related distress (Chinese Impact of Events Scale), quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire) and treatment satisfaction are secondary outcomes.Ethics and dissemination Ethics approval has been obtained from HKU/HA HKW Institutional Review Board (ref: UW19-183). The patients/participants provide their written informed consent to participate in this study. The study results will be disseminated through international peer-review publications and conference presentations.Trial registration number NCT04568226.

Abstract A primary goal of present and future colliders is measuring the Higgs couplings to Standard Model (SM) particles. Any observed deviation from the SM predictions for these couplings is a sign of new physics whose energy scale can be bounded from above by requiring tree-level unitarity. In this paper, we extend previous work on unitarity bounds from the Higgs cubic coupling to Higgs couplings to vector bosons and top quarks. We find that HL-LHC measurements of these couplings compatible with current experimental bounds may point to a scale that can be explored at the HL-LHC or a next-generation collider. Our approach is completely model-independent: we assume only that there are no light degrees of freedom below the scale of new physics, and allow arbitrary values for the infinitely many couplings beyond the SM as long as they are in agreement with current measurements. We also extend and clarify the methodology of this analysis, and show that if the scale of new physics is above the TeV scale, then the deviations can be described by the leading higher-dimension gauge invariant operator, as in the SM effective field theory.

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10−3 substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.

Abstract Schizophrenia (SZ) is a devastating brain disease that affects about 1% of world population. Among the top genetic associations, zinc finger protein 804A (ZNF804A) gene encodes a zinc finger protein, associated with SZ and biolar disorder (BD). Copy number variants (CNVs) of ZNF804A have been observed in patients with autism spectrum disorders (ASDs), anxiety disorder, and BD, suggesting that ZNF804A is a dosage sensitive gene for brain development. However, its molecular functions have not been fully determined. Our previous interactomic study revealed that ZNF804A interacts with multiple proteins to control protein translation and neural development. ZNF804A is localized in the cytoplasm and neurites in the human cortex and is expressed in various types of neurons, including pyramidal, dopaminergic, GABAergic, and Purkinje neurons in mouse brain. To further examine the effect of gene dosage of ZNF804A on neurite morphology, both knockdown and overexpression of ZNF804A in primary neuronal cells significantly attenuate dendritic complex and spine formation. To determine the factors mediating these phenotypes, interestingly, three binding proteins of ZNF804A, galectin 1 (LGALS1), fasciculation and elongation protein zeta 1 (FEZ1) and ribosomal protein SA (RPSA), show different effects on reversing the deficits. LGALS1 and FEZ1 stimulate neurite outgrowth at basal level but RPSA shows no effect. Intriguingly, LGALS1 but not FEZ1, reverses the neurite outgrowth deficits induced by ZNF804A knockdown. However, FEZ1 and RPSA but not LGALS1, can ameliorate ZNF804A overexpression-mediated dendritic abnormalities. Thus, our results uncover a critical post-mitotic role of ZNF804A in neurite and synaptic development relevant to neurodevelopmental pathologies.

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare form of non-Hodgkin’s lymphoma, characterized by an aggressive disease course. While CNS relapse is common, systemic relapse is rare with no consensus on optimal treatment. This paper presents an unusual case of advanced PCNS-DLBCL with systemic relapse, including adrenal gland involvement. A review of the existing literature and a discussion on the management of systemic relapse in PCNS-DLBCL is also provided.

Hemostatic management is essential for ensuring the safety of patients with hemophilia during surgery. This phase 3, prospective, uncontrolled trial, evaluated hemostatic efficacy, consumption, and safety of a recombinant factor IX concentrate, nonacog gamma (BAX 326, Rixubis ® [Baxalta US Inc., a Takeda company, Lexington, MA, USA]), in intraoperative and postoperative settings in previously treated patients (PTPs) with severe or moderately severe hemophilia B undergoing elective surgery (N = 38 surgeries; 21 major, 17 minor). Predefined preoperative hemostatic factor IX levels (80-100% of normal for major and 30-60% for minor surgeries) were maintained for each patient. Intraoperative efficacy was rated as “excellent” or “good” for all surgeries. Postoperative hemostatic efficacy on day of discharge was rated as “excellent,” “good,” and “fair,” respectively, for 29 (76.3%), 7 (18.4%), and 2 (5.3%) surgical procedures. All adverse events were considered unrelated to study drug; most frequently reported was mild procedural pain (9 patients). No thrombotic events, severe allergic reactions, or inhibitor formation were observed. Nonacog gamma was well tolerated and effective for intraoperative and postoperative hemostatic management of PTPs with hemophilia B. NCT01507896, EudraCT: 2011-000413-39

Invasive pneumococcal disease (IPD) is the most severe clinical presentation of infection by Streptococcus pneumoniae. Peru since 2008 includes pneumococcal vaccine in the national immunization schedule. We report a case of a 10 year old girl who goes by emergency showing meningeal signs; in addition, abdominal pain, infiltrated right basal hilum on chest radiography, presence of peritoneal fluid and peritoneal adenopathy in diagnostic imaging support. It is isolated in blood and CSF cultures Streptococcus pneumoniae serotype 11A, no vaccine-strain, being sensitive to ceftriaxone and vancomycin. We recommend the need to know more about the presence of not vaccine pneumococcal serotypes in the clinical and epidemiological context and its pathogenic role in Peruvian population.

Objetives: To describe the clinical and epidemiological characteristics, evolution and to identify mortality factors associated in patients with SNP. Material and methods: Descriptive study of a serie of cases of the Intensive Care Unit (ICU) of a General Hospital. Medical records of patients which received medical attention and who meet the selection criteria were reviewed.Results: Forty-one clinical records were evaluated. The average age was 69 old, predominantly male (68,3%). SNP was the reason of admission in 60.9% and 95.1% required mechanical ventilation. Hospital stay prior to diagnosis was 10 days, 65% of patients had some risk factor for multi resistence organisms, CPIS of entry was 9.3, cultures were positive in 39% of the cases and of these, 48.8% received proper antibiotic according to culture results. The days of stay in ICU were 20.6 days and 20 of the 41 medical records were for death patients. The clinical and epidemiological characteristics were similar between death and alive patients. An analysis of factors that could be associated with mortality SNP was made and it was found that for an age ≥ 70 years, the presence of any risk factor for multidrug resistence organism and control CPIS ≥ 6 were associated with higher mortality; while acquisition of the ICU was associated to lower mortality.Conclusions: The clinical, epidemiological characteristics and evolution of patients with SNP in our ICU were similar to those describe in the literature. Three factors associated with mortality in the ICU were identified.

We present a case of rapid onset severe psychosis followed by suicide attempt in a United States Navy sailor. Investigation revealed a left temporal lobe brain mass suspicious for low-grade glioma. After hospitalization and medical management with olanzapine and lurasidone the patient’s psychosis improved. The purpose of this paper is to add to the existing case reports that suggest a relationship between temporal lobe lesions and psychiatric illness, specifically psychosis. In addition, this case adds insight into the effectiveness of medical therapy for brain tumor patients that are not immediate candidates for neurosurgical intervention.

This study evaluated the effectiveness of the essential oil of Pimenta pseudocaryophyllus in inhibiting the growth of the main bacteria responsible for bad perspiration odor (Staphylococcus epidermidis, Proteus hauseri, Micrococcus yunnanensis and Corynebacterium xerosis). The chemical profile of the essential oil was evaluated by high-resolution gas chromatography (HR-GC) and four constituents were identified, eugenol being the major component (88.6 %). The antimicrobial activity was evaluated by means of the turbidimetric method, using the microdilution assay. The minimum inhibitory concentration (MIC) values of the essential oil ranged from 500 to 1,000 μg mL-1. Scanning electron microscope (SEM) observations confirmed the physical damage and morphological alteration of the test bacteria treated with the essential oil, reference drugs and eugenol. The findings of the study demonstrated that this essential oil can be used in the formulation of personal care products.

“I don’t forget and I struggle” is a phrase that decorates all Greek Cypriot classrooms. Since 1974 the phrase has become the symbol of an educational system that has fostered the collective memory of new generations of Greek Cypriots who were born in conditions of semi-occupation, under the weight of an unresolved political problem. In this paper we review the Greek Cypriot educational context in the period since the 1974 Turkish invasion and we argue that the kind of collective memory it has fostered contradicts the declared curricular goals of citizenship for a pluralistic and democratic society. We argue that European citizenship education, with its emphasis on overcoming past conflicts through shared political values, could be the key for a new citizenship ideal both for Greek Cypriots and Turkish Cypriots.El lema “Yo no olvido y lucho” decora todas las aulas greco-chipriotas. Desde 1974 se ha convertido en el símbolo de la preservación de la memoria colectiva en la escuela, donde es transmitida a las nuevas generaciones que nacieron bajo un régimen de semi-ocupación y crecieron bajo el peso de un problema político sin resolver. Este trabajo somete a examen la contradicción entre el principio de ciudadanía para una sociedad pluralista y democrática como objetivo curricular y el tipo de memoria colectiva promovida en el contexto educativo greco-chipriota durante el período posterior a la invasión turca de 1974. Se sostiene, así mismo, que la educación para la ciudadanía europea, que enfatiza el papel de los valores comunes en la resolución de conflictos, podría ser la clave de un nuevo ideal de ciudadanía, tanto para la comunidad greco-chipriota como para la turco-chipriota.

This article outlines the basic principles of educational inclusion, focusingspecifically on the inclusion of disabled students in mainstream classrooms, and arguesthat inclusive education should be understood as a process of transforming traditionalschools into spaces of learning for all students. The article uses the lens of critical pedagogyto argue that exclusionary educational practices have been developed through themedicalization of learning disabilities which focused on the disability rather than theabilities of disabled students. Following the same line of thinking, the article providesscientific evidence to debunk myths related to the education of disabled students; especiallymyths that contributed to their exclusion from mainstream classrooms. Finally,based on the Learning Communities model, we provide some concrete strategies fortransforming mainstream classrooms into fully inclusive environments.

En este artículo presentamos los principios básicos de la inclusión educativa,centrándonos especialmente en la inclusión del alumnado con discapacidad, y sostenemosque la educación inclusiva debería ser entendida como un proceso de transformaciónde las escuelas tradicionales en espacios de aprendizaje para todo el alumnado. Elartículo se basa en la pedagogía crítica para argumentar que las prácticas educativasexcluyentes se han desarrollado centrándose en la discapacidad más que en las capacidadesde este alumnado. En esta misma línea, el artículo proporciona evidencias científicaspara desacreditar mitos relacionados con la educación del alumnado con discapacidad,especialmente mitos que han contribuido a su exclusión de las aulas ordinarias.Finalmente, basándonos en el modelo de las Comunidades de Aprendizaje, proporcionamosalgunas estrategias concretas para la transformación de las aulas ordinarias enambientes plenamente inclusivos.This article outlines the basic principles of educational inclusion, focusingspecifically on the inclusion of disabled students in mainstream classrooms, and arguesthat inclusive education should be understood as a process of transforming traditionalschools into spaces of learning for all students. The article uses the lens of critical pedagogyto argue that exclusionary educational practices have been developed through themedicalization of learning disabilities which focused on the disability rather than theabilities of disabled students. Following the same line of thinking, the article providesscientific evidence to debunk myths related to the education of disabled students; especiallymyths that contributed to their exclusion from mainstream classrooms. Finally,based on the Learning Communities model, we provide some concrete strategies fortransforming mainstream classrooms into fully inclusive environments.

Dengue viruses are major contributors to illness and death globally. Here we analyze the extrinsic and intrinsic incubation periods (EIP and IIP), in the mosquito and human, respectively. We identified 146 EIP observations from 8 studies and 204 IIP observations from 35 studies. These data were fitted with censored Bayesian time-to-event models. The best-fitting temperature-dependent EIP model estimated that 95% of EIPs are between 5 and 33 days at 25°C, and 2 and 15 days at 30°C, with means of 15 and 6.5 days, respectively. The mean IIP estimate was 5.9 days, with 95% expected between days 3 and 10. Differences between serotypes were not identified for either incubation period. These incubation period models should be useful in clinical diagnosis, outbreak investigation, prevention and control efforts, and mathematical modeling of dengue virus transmission.

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Objective: Acute Pulmonary Embolism (APE) is a disease with increasing incidence worldwide. Antithrombotics are the cornerstone of the treatment. Bleeding is an adverse event related to this therapy. The objective was to evaluate the prevalence of bleeding in a sample of Brazilian patients hospitalized with APE and the impact of this complication on mortality. Additionally, the performance of some bleeding predictive scores was evaluated in this sample., Methods: A retrospective cohort study was carried out on patients hospitalized with APE from January 2009 through August 2017. The medical records of these patients were reviewed, and the bleeding recorded during hospital stay was classified according to the "Thrombolysis in Myocardial Infarction (TIMI) bleeding risk." Five different predictive scores for bleeding after APE (RIETE, PE-SARD, VTE-BLEED, Kuijer, and ATRIA) were applied. Overall mortality at 30 days and one year were assessed., Results: One hundred fifty-nine patients were included. The prevalence of any bleeding was 36/159 (23 %), major bleeding was 10/159 (06 %), minor bleeding was 11/159 (07 %), and bleeding requiring attention was 15/159 (10 %). Only major bleeding was associated with higher mortality at one-year follow-up with a Relative Risk (RR) of 2.00 (95 % CI 1.16-3.57; p = 0.044). All bleeding predictive scores evaluated showed low accuracy in identifying patients at higher risk of bleeding., Conclusion: Patients hospitalized with APE in Brazil had a high prevalence of bleeding. The major bleeding increased the one-year mortality. The bleeding predictive scores assessed showed limited accuracy in identifying patients at high risk of bleeding., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Among flowering plants, self-compatibility, longer lifespan, and generalized pollination syndrome are each thought to increase the lifetime odds of finding a mate, particularly in isolated locales. An accumulated body of evidence supports the role of breeding system in island colonization, but less is known about the impact of other traits and their interactions during establishment. We employ a global dataset of 3222 flowering plant species from 169 families to estimate the effects of traits on the probability of island occurrence. Our analyses additionally account for taxonomic group membership and assess the role of island arrival opportunity. Self-compatibility is strongly associated with island colonization. A longer lifespan and generalized pollination syndrome are also associated with increased island colonization, although this is influenced by their interaction with breeding system. The probability of island colonization is highly dependent on taxonomically conserved unmeasured traits and arrival opportunity. As expected, mate limitation appears to increase with dispersal distance, although many other factors are at play. We find that arrival opportunity and breeding system are the primary drivers of island colonization relative to other life-history traits we account for here, lending additional support for the positive role of uniparental reproduction in establishment following long-distance dispersal., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Background: Reported results of clinical trials assessing higher-dose anticoagulation in patients hospitalized for COVID-19 have been inconsistent., Purpose: To estimate the association of higher- versus lower-dose anticoagulation with clinical outcomes., Data Sources: Randomized trials were identified from the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov with no restriction by trial status or language., Study Selection: Eligible randomized trials assigned patients hospitalized for COVID-19 to higher- versus lower-dose anticoagulation., Data Extraction: 20 eligible trials provided data in a prospectively agreed format. Two further studies were included based on published data. The primary outcome was all-cause mortality 28 days after randomization. Secondary outcomes were progression to invasive mechanical ventilation or death, thromboembolic events, and major bleeding., Data Synthesis: Therapeutic- compared with prophylactic-dose anticoagulation with heparins reduced 28-day mortality (OR, 0.77 [95% CI, 0.64 to 0.93]; I 2  = 29%; 11 trials, 6297 patients, of whom 5456 required low or no oxygen at randomization). The ORs for 28-day mortality were 1.21 (CI, 0.93 to 1.58; I 2  = 0%) for therapeutic-dose compared with intermediate-dose anticoagulation (6 trials, 1803 patients, 843 receiving noninvasive ventilation at randomization) and 0.95 (CI, 0.76 to 1.19; I 2  = 0%; 10 trials, 3897 patients, 2935 receiving no or low oxygen at randomization) for intermediate- versus prophylactic-dose anticoagulation. Treatment effects appeared broadly consistent across predefined patient subgroups, although some analyses were limited in power. Higher- compared with lower-dose anticoagulation was associated with fewer thromboembolic events, but a greater risk for major bleeding., Conclusion: Therapeutic-dose compared with prophylactic-dose anticoagulation reduced 28-day mortality. Mortality was similar for intermediate-dose compared with prophylactic-dose anticoagulation and higher for therapeutic-dose compared with intermediate-dose anticoagulation, although this comparison was not estimated precisely., Primary Funding Source: No direct funding. (PROSPERO: CRD42020213461)., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Background: Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients., Methods: This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function., Results: The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 μm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS)., Conclusion: SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose The number of B-lines on lung ultrasound at hospital discharge in patients admitted with acute heart failure (AHF) is associated with poor outcomes. Assessing B-lines can be challenging to execute and replicate, depending on the clinical context. This study aims to determine whether the lung ultrasound score (LUS) at discharge predicts hospital readmission or emergency department (ED) visits in the 30 days after an AHF hospital admission. Methods  We conducted an observational study at the medical ward of the emergency unit of the Clinics Hospital of the Ribeirao Preto Medical School, University of Sao Paulo, a tertiary university hospital in Ribeirao Preto, Sao Paulo, Brazil, where consecutive adults admitted with AHF were included. On the day of hospital discharge, we measured the LUS and tracked these patients for up to 30 days to monitor emergency department visits, hospital readmission, and the number of days free from hospital stay. Results  A total of 46 patients were included in the study. A composite outcome of ED visits or hospital readmission in the 30 days after hospital discharge was achieved for 22 (47.8%) patients. The LUS at hospital discharge had a receiver operating characteristic (ROC) area of 0.93 (95% CI, 0.82-0.99) to predict the composite outcome, against 0.67 (95% CI, 0.52-0.81) for the clinical congestion score (CCS). A LUS ≥ 7 at discharge had a sensitivity of 95.5% and a specificity of 87.5% to predict the composite outcome. The average exam duration was 176±65 (sd) seconds. Conclusions The LUS at hospital discharge following admission for AHF proves to be an accurate tool for predicting the likelihood of return to the ED and/or hospital readmission within 30 days post discharge., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ferreira et al.)

Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the "backbone" of this structure. Several studies have shown eGC shedding in sepsis and its involvement in organ dysfunction. Matrix metalloproteinases (MMP) contribute to eGC shedding through their ability for syndecan-1 cleavage. This study aimed to investigate if doxycycline, a potent MMP inhibitor, could protect against eGC shedding in lipopolysaccharide (LPS)-induced sepsis and if it could interrupt the vascular hyperpermeability, neutrophil transmigration, and microvascular impairment. Rats that received pretreatment with doxycycline before LPS displayed ultrastructural preservation of the eGC observed using transmission electronic microscopy of the lung and heart. In addition, these animals exhibited lower serum syndecan-1 levels, a biomarker of eGC injury, and lower perfused boundary region (PBR) in the mesenteric video capillaroscopy, which is inversely related to the eGC thickness compared with rats that only received LPS. Furthermore, this study revealed that doxycycline decreased sepsis-related vascular hyperpermeability in the lung and heart, reduced neutrophil transmigration in the peritoneal lavage and inside the lungs, and improved some microvascular parameters. These findings suggest that doxycycline protects against LPS-induced eGC shedding, and it could reduce vascular hyperpermeability, neutrophils transmigration, and microvascular impairment., (© 2024. The Author(s).)

Objective: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19., Methods: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1β, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days., Results: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1β., Conclusion: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19., Trial Registration Numbers: RBR-8jyhxh., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In clinical practice, we need to develop new tools to identify the residual cardiovascular risk after acute coronary syndrome (ACS). This study aimed to evaluate whether the monocyte to high-density lipoprotein cholesterol ratio (MHR) variation (ΔMHR) obtained during hospital admission (MHR1) and repeated in the first outpatient evaluation (MHR2) is a predictor of major adverse cardiovascular events (MACE) after ACS. One hundred ninety-one patients admitted for ACS were prospectively included. The ΔMHR was calculated by subtracting MHR1 from MHR2. Patients were followed for 166±38 days in which the occurrence of MACE was observed. The best cutoff for ΔMHR was zero (0), and individuals were divided into two groups: ΔMHR<0 (n=113) and ΔMHR≥0 (n=78). The presence of MACE was higher in the ΔMHR≥0 (22%) than in the ΔMHR<0 (7%), with a hazard ratio (HR) of 3.96 (95% confidence interval [CI]: 1.74-8.99; P=0.0004). After adjusting for confounders, ΔMHR≥0 remained an independent MACE predictor with an adjusted HR of 3.13 (95%CI: 1.35-7.26, P=0.008). In conclusion, our study showed that ΔMHR was an independent MACE predictor after ACS. Thus, ΔMHR is a potential marker of residual cardiovascular risk after ACS.

Background: Regional myocardial sympathetic denervation is a conspicuous and early disorder in patients with chronic Chagas' cardiomyopathy (CCC), potentially associated to the progression of myocardial dysfunction OBJECTIVE: To evaluate in a longitudinal study the association between the presence and the progression of regional myocardial sympathetic denervation with the deterioration of global and segmental left ventricular dysfunction in CCC., Methods: 18 patients with CCC were submitted at initial evaluation and after 5.5 years to rest myocardial scintigraphy with 123 Iodo-metaiodobenzylguanidine and 99m Tc-sestamibi and to two-dimensional echocardiography to assess myocardial sympathetic denervation, extent of fibrosis, and the left ventricular ejection fraction (LVEF) and wall motion abnormalities., Results: In the follow-up evaluation, compared to the initial one, we observed a significant decrease in LVEF (56 ± 11 to 49% ± 12; P = .01) and increased summed defects scores in the myocardial innervation scintigraphy (15 ± 10 to 20 ± 9; P < .01). The presence of regional myocardial sympathetic denervation in ventricular regions of viable non-fibrotic myocardium presented an odds ratio of 4.25 for the development of new wall motion abnormalities (P = .001)., Conclusion: Regional and global myocardial sympathetic denervation is a progressive derangement in CCC. In addition, the regional denervation is topographically associated with areas of future development of regional systolic dysfunction in patients with CCC., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: We aimed to evaluate the impact of providing dental care to critically ill patients on their risk of death and ventilator-associated pneumonia (VAP)., Methods: A quasi-experimental study was conducted in 2 intensive care units (ICU) from 2016 to 2019. The intervention consisted of implementing routine dental care, focusing on oral hygiene and periodontal treatment, at least 3 times a week, for patients admitted to the study units. In the pre-intervention period, routine oral hygiene was provided by the ICU nursing staff. The primary and secondary study outcomes were mortality, evaluated at the end of the ICU stay, and VAP incidence density, respectively. Data were analyzed using the ARIMA (autoregressive integrated moving average) time series model in R software., Results: During the intervention period, 5,147 dental procedures were performed among 355 patients. The time series showed that ICU mortality was 36.11%, 32.71%, and 32.30% within the 3 years before the intervention, and 28.71% during the intervention period (P = .015). VAP incidence density did not significantly change during the study period (P = .716)., Conclusion: A dental care intervention focused on oral hygiene and periodontal treatment regularly provided by dentists to critically ill patients may decrease their risk of dying in the ICU. Randomized clinical trials should be performed to confirm these findings., Trial Registration: WHO-affiliated Brazilian Clinical Trials Registry. RBR-4jmz36. Registered 7 October 2018, before first patient enrollment., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe the process of implementing a palliative care team (PCT) in a Brazilian public tertiary university hospital and compare this intervention as an active in-hospital search (strategy I) with the Emergency Department (strategy II)., Methods: We described the development of a complex Palliative Care Team (PCT). We evaluated the following primary outcomes: hospital discharge, death (in-hospital and follow-up mortality) or transfer, and performance outcomes-Perception Index (difference in days between hospitalization and the evaluation by the PTC), follow-up index (difference in days between the PTC evaluation and the primary outcome), and the in-hospital stay., Results: We included 1203 patients-strategy I (587; 48.8%) and strategy II (616; 51.2%). In both strategies, male and elderly patients were prevalent. Most came from internal medicine I (39.3%) and II (57.9%), p <  0.01. General clinical conditions (40%) and Oncology I (27.7%) and II (32.4%) represented the majority of the population. Over 70% of all patients had PPS 10 and ECOG 4 above 85%. There was a reduction of patients identified in ICU from I (20.9%) to II (9.2%), p <  0.01, reduction in the ward from I (60.8%) to II (42.5%), p <  0.01 and a significant increase from I (18.2%) to II (48.2%) in the emergency department, p <  0.01. Regarding in-hospital mortality, 50% of patients remained alive within 35 days of hospitalization (strategy I), while for strategy II, 50% were alive within 20 days of hospitalization (p <  0.01). As for post-discharge mortality, in strategy II, 50% of patients died 10 days after hospital discharge, while in strategy I, this number was 40 days (p <  0.01). In the Cox multivariate regression model, adjusting for possible confounding factors, strategy II increased 30% the chance of death. The perception index decreased from 10.9 days to 9.1 days, there was no change in follow-up (12 days), and the duration of in-hospital stay dropped from 24.3 to 20.7 days, p <  0.01. The primary demand was the definition of prognosis (56.7%)., Conclusion: The present work showed that early intervention by an elaborate and complex PCT in the ED was associated with a faster perception of the need for palliative care and influenced a reduction in the length of hospital stay in a very dependent and compromised old population., (© 2022. The Author(s).)

Objectives: Evaluate the impact of ABO histo-blood group type on COVID-19 severity., Background: ABO histo-blood type has been associated with different outcomes in infectious diseases. It has also shown a higher proportion of type A patients with SARS-CoV-2. In this observational study, extracted from an ongoing clinical trial on the efficacy of convalescent plasma transfused in COVID-19 patients, we describe the impact of ABO blood type on the risk of developing severe COVID-19., Materials and Methods: Seventy-two consecutive patients (37 type A, 23 type O, 11 type B, 1 type AB) with severe (respiratory failure) COVID-19 were included. Control group was composed of 160 individuals randomly selected from the same populational basis., Results: Blood group A was overrepresented (51.39%) in the patient group in relation to the control group (30%), whereas blood group O was less represented (31.94%) in patient than in control group (48%). Odds ratio (A vs. O) was 2.581 (1.381-4.817), CI 95%; p = 0.004. Also, blood group A patients appeared to have more severe disease, given by the scores of the Sequential Organ Failure Assessment and Simplified Acute Physiologic Score 3 (p = 0.036 and p = 0.058, respectively)., Conclusion: Histo-blood type A is associated with a higher risk of developing severe COVID-19 in relation to blood type O., (© 2021 British Blood Transfusion Society.)

Background: About 40% of patients with ST-segment elevation myocardial infarction (STEMI) in Brazil do not receive reperfusion therapy., Objective: The use of a telemedicine network based on WhatsApp® could increase the percentage of patients receiving reperfusion therapy., Methods: A cross-sectional study analyzed outcomes before and after the organization of a telemedicine network to send the electrocardiogram via WhatsApp® of patients suspected of STEMI from 25 municipalities that are members of the Regional Health Department of Ribeirão Preto (DRS-XIII) to a tertiary hospital, which could authorize immediate patient transfer using the same system. The analyzed outcomes included the percentage of patients who received reperfusion therapy and the in-hospital mortality rate. A p value < 0.05 was considered statistically significant., Results: The study compared 82 patients before (February 1, 2016 to January 31, 2018) with 196 patients after this network implementation (February 1, 2018 to January 31, 2020). After implementing this network, there was a significant increase in the proportion of patients who received reperfusion therapy (60% vs. 92%), relative risk (RR): 1.594 [95% confidence interval (CI) 1.331 - 1.909], p < 0.0001 and decrease in the in-hospital mortality rate (13.4% vs. 5.6%), RR: 0.418 [95%CI 0.189 - 0.927], p = 0.028., Conclusion: The use of WhatsApp®-based telemedicine has led to an increase in the percentage of patients with STEMI who received reperfusion therapy and a decrease in the in-hospital mortality rate.

To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.

Background: Emergency department (ED) crowding is a frequent situation. To decrease this overload, patients without a life-threating condition are transferred to wards that offer ED support. This study aimed to evaluate if implementing a rapid response team (RRT) triggered by the modified early warning score (MEWS) in high-risk wards offering ED support is associated with decreased in-hospital mortality rate., Methods: A before-and-after cross-sectional study compared in-hospital mortality rates before and after implementation of an RRT triggered by the MEWS ≥4 in two wards of a tertiary hospital that offer ED support., Results: We included 6863 patients hospitalized in these wards before RRT implementation from July 2015 through June 2017 and 6944 patients hospitalized in these same wards after RRT implementation from July 2018 through June 2020. We observed a statistically significant decrease in the in-hospital mortality rate after intervention, 449 deaths/6944 hospitalizations [6.47% (95% confidence interval (CI) 5.91%- 7.07%)] compared to 534 deaths/6863 hospitalizations [7.78% (95% CI 7.17-8.44)] before intervention; with an absolute risk reduction of -1.31% (95% CI -2.20 --0.50)., Conclusion: RRT trigged by the MEWS≥4 in high-risk wards that offer ED support was found to be associated with a decreased in-hospital mortality rate. A further cluster-randomized trial should evaluate the impact of this intervention in this setting., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes., Design: We present the results of a randomised, double-blinded, placebo-controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 75 patients allocated 1:1 from 11 April to 30 August 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The primary endpoints were the need for supplemental oxygen, time of hospitalisation, need for admission and length of stay in intensive care unit and death rate., Results: Seventy-two patients (36 for placebo and 36 for colchicine) completed the study. Median (and IQR) time of need for supplemental oxygen was 4.0 (2.0-6.0) days for the colchicine group and 6.5 (4.0-9.0) days for the placebo group (p<0.001). Median (IQR) time of hospitalisation was 7.0 (5.0-9.0) days for the colchicine group and 9.0 (7.0-12.0) days for the placebo group (p=0.003). At day 2, 67% versus 86% of patients maintained the need for supplemental oxygen, while at day 7, the values were 9% versus 42%, in the colchicine and the placebo groups, respectively (log rank; p=0.001). Two patients died, both in placebo group. Diarrhoea was more frequent in the colchicine group (p=0.26)., Conclusion: Colchicine reduced the length of both, supplemental oxygen therapy and hospitalisation. The drug was safe and well tolerated. Once death was an uncommon event, it is not possible to ensure that colchicine reduced mortality of COVID-19., Trial Registration Number: RBR-8jyhxh., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Veras et al.)