Tomato pomace-derived nitrated fatty acids: Synthesis and antiplatelet activity.

This study investigates the antiplatelet properties of tomato pulp to combat cardiovascular diseases. Notably, it examines the formation of nitrated fatty acids (NO2-FA) in tomato pomace, renowned for its potential antiplatelet effects. Through diverse assays, including tandem mass spectrometry, microplate-based platelet aggregation, and flow cytometry, the research identifies NO2-OA, NO2-LA, and NO2-LnA as pivotal antiplatelet compounds. It demonstrates the concentration-dependent antiplatelet effects of nitrated tomato pomace against thrombin receptor activator peptide 6 (TRAP-6) and collagen-induced platelet activation, alongside the modulation of platelet activation markers. Additionally, synergistic effects were observed with nitrated tomato pomace extracts. The findings suggest therapeutic potential for NO2-FA derived from tomato pomace in preventing blood clot formation, with nitrated extracts exhibiting superior efficacy compared to non-nitrated ones. This research highlights the promising role of natural products, such as tomato pomace, in mitigating cardiovascular risks and proposes novel strategies for population health enhancement and cardiovascular disease management.

From Rhetoric to Action: Justice, Equity, Diversity, and Inclusion in Coordinated Specialty Care for Early Psychosis.

Attention to inclusivity and equity in health research and clinical practice has grown in recent years; however, coordinated specialty care (CSC) for early psychosis lags in efforts to improve equity despite evidence of ongoing disparities and inequities in CSC care. This Open Forum argues that marginalization and disparities in early psychosis research and clinical care are interrelated, and the authors provide suggestions for paths forward. Commitment to equity and justice demands recentering the perspectives of those most affected by early psychosis services and investing in the integration of historically excluded perspectives across all aspects of practice, policy, and research.

Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial.

BACKGROUND: Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota. METHODS AND FINDINGS: A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n2p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of Phascolarctobacterium faecium (p = 0.019) in the CR group and Ruminococcus bromii (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study. CONCLUSIONS: We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05200468).

Sociodemographic and obstetric factors may affect breastfeeding attitudes, self-efficacy, and knowledge in women with rheumatic diseases: a retrospective analysis of self-reported surveys.

Women with autoimmune rheumatic disease (ARDs) experience difficulties with BF in addition to those concerning their own disease. The aim of this study is to identify the impact factors as infant feeding attitude, the level of BF knowledge, BF self-efficacy, and the sociodemographic have in the intention to BF in women with ARDs. We performed an observational, retrospective, and analytical study. Reproductive-age women (18-50 years old) with ARDs with prior pregnancy history and who filled out self-reported BF surveys as part of the Rheumatology Integral Care Program were included. Sociodemographic and clinical characteristics were retrieved from medical charts. We analyzed three validated BF questionnaires. Sixty-five participants with a mean age of 41.32 ± 7.48 were evaluated. Of these, 63 (97%) women agreed with BF in the first 6 months. The most prevalent infant feeding attitude was neutral with 42 (64.6%) women. The most common level of BF knowledge was poor with 45 (69.2%) patients. There were significant correlations of BF knowledge with education years (p = < 0.001, r = 0.464) and age (p = 0.049, r=-0.245). A significant correlation was found between BF self-efficacy and age (p = 0.039, r = 0.257). Attitude toward BF was significantly associated with education level > 9 years (OR = 3.400; 95% CI = 1.091-10.593) and a history of miscarriage (OR = 3.670; 95% CI = 1.051-12.813). Although most women with ARDs agreed with BF, we identified a poor level of BF knowledge and a neutral infant feeding attitude as the most predominant. By identifying this data in women with ARDs, BF practices may be improved.

Field experience with the 8-HPV-type oncoprotein test for cervical cancer screening among HPV-positive women living with and without HIV in LMICs.

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.

Cardiovascular testing recovery in Latin America one year into the COVID-19 pandemic: An analysis of data from an international longitudinal survey.

Background: The COVID-19 pandemic disproportionately impacted Latin America (LATAM), significantly disrupting cardiovascular testing. This study evaluated cardiac procedure recovery in LATAM one year after the outbreak. Methods: The International Atomic Energy Agency (IAEA) surveyed 669 centers in 107 countries worldwide, including 135 facilities in 19 LATAM countries, to assess cardiovascular procedure volumes in March 2019, April 2020, and April 2021, and changes in center practices and staffing conditions one year into the COVID-19 pandemic. Findings: LATAM centers reported a 21 % decrease in procedure volumes in April 2021 from pre-pandemic-baseline, vs. a 0 % change in the rest of the world (RoW), and greater volume reductions for almost all procedure types. Centers in Central America and Mexico reported the largest procedure reductions (47 % reduction) compared to the Caribbean (15 %), and South America (14 %, p = 0.01), and this LATAM region was a significant predictor of lower procedure recovery in multivariable regression. More LATAM centers reported reduced salaries and increased layoffs of clinical staff compared to RoW, and LATAM respondents estimated that half of physician and non-physician staff experienced excess psychological stress related to the pandemic, compared to 25 % and 30 % in RoW (p < 0.001). Conclusions: Cardiovascular testing recovery in LATAM trailed behind RoW for most procedure types, with centers in Central America and Mexico reporting the greatest volume reductions. This study found lasting impacts of COVID-19 on cardiovascular care in LATAM and the need for mental health support for LATAM healthcare workers in current and future pandemics.

Physico-chemical characterization of the tumour microenvironment of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy that accounts for more than 90% of pancreatic cancer diagnoses. Our research is focused on the physico-chemical properties of the tumour microenvironment (TME), including its tumoural extracellular matrix (tECM), as they may have an important impact on the success of cancer therapies. PDAC xenografts and their decellularized tECM offer a great material source for research in terms of biomimicry with the original human tumour. Our aim was to evaluate and quantify the physico-chemical properties of the PDAC TME. Both cellularized (native TME) and decellularized (tECM) patient-derived PDAC xenografts were analyzed. A factorial design of experiments identified an optimal combination of factors for effective xenograft decellularization. Our results provide a complete advance in our understanding of the PDAC TME and its corresponding stroma, showing that it presents an interconnected porous architecture with very low permeability and small pores due to the contractility of the cellular components. This fact provides a potential therapeutic strategy based on the therapeutic agent size.

Effects of Implementing a Standardized Surveillance Program on Cardiac Neurodevelopmental Program Referral Completion.

Differences in surveillance methods have resulted in significant variability in referral volumes and referral completion rates across cardiac neurodevelopmental programs, with frequent barriers to referral completion including high no-show rates, lack of education, and inaccessibility for underrepresented populations. The purpose of this study was to describe implementation of a standardized surveillance program and investigate impact on referral volume and completion over a two-year period. Between fiscal years 2021 and 2022, a surveillance program was implemented which standardized assessment of neurodevelopmental risk via a checklist as well as family education and referral procedures. All patients referred to the cardiac neurodevelopmental program during these two fiscal years were included in the analysis, and patient referrals were categorized as complete or incomplete (due to physician-related or patient-related factors). Referral completion rates between fiscal years were compared using two sample Z test of proportions, while associations between referral completion and demographic/anatomical variables were completed using chi-square tests of independence. Implementation of the formal surveillance program resulted in a 66.7% increase in referral volume. Proportions of both incomplete referrals (z = 2.00, p < 0.05) and incomplete referrals due to physician-related factors (z = 4.34, p < 0.01) were significantly lower after implementation. A significant association was found after implementation between referral completion and race/ethnicity (x2 = 14.08, p < 0.01) due to a significantly high proportion of completed referrals for patients identifying as Hispanic/Latino within the overall distribution of patients. This study describes the successful implementation of a standardized surveillance program, including improvements to referral volume and completion rate. Findings also support implementation of methods that emphasize physician surveillance methods and improve accessibility for historically marginalized groups at greatest risk for disparities in access and quality of care.

Non-haematopoietic Sca-1+ Cells in the Retina of Adult Mice Express Functional TLR2.

The mammal retina does not have the capacity to regenerate throughout life, although some stem and progenitor cells persist in the adult retina and might retain multipotentiality, as previously described in many tissues. In this work we demonstrate the presence of a small lineage- Sca-1+ cell population in the adult mouse retina which expresses functional TLR2 receptors as in vitro challenge with the pure TLR2 agonist Pam3CSK4 increases cell number and upregulates TLR2. Therefore, this population could be of interest in neuroregeneration studies to elucidate its role in these processes.

Symptom contributors to quality of life in schizophrenia: Exploratory factor and network analyses.

Individuals with schizophrenia and other associated disorders experience significant disturbance to their quality of life (QoL) due to a multitude of co-occurring symptoms. Popular evidence-based practices (EBPs) devote significant effort to reduce positive symptomatology in order to prevent relapse, while emerging research posits that other symptoms (cognitive deficits, negative and affective symptoms) are more indicative of QoL disturbance. This study sought to examine the impact of symptom constructs on QoL and attempt to infer directionality of influence via network analysis. A total of 102 recovery phase adult outpatients with schizophrenia spectrum disorders were assessed on positive, negative, and affective symptomatology, in addition to QoL and cognitive abilities. Exploratory factor analysis and network analysis were performed to identify associations and infer directed influence between symptom constructs, and a directed acyclic graph was constructed to observe associations between symptom domains and QoL. Factor analysis results indicated that individual measures align with their respective symptom constructs. Strong factor correlations were found between QoL and the negative and affective symptom constructs, with weaker associations found between positive symptoms and cognition. Visualization of the network structure illustrated QoL as the central cluster of the network, and examination of the weighted edges found the strongest connectivity between QoL, negative symptomatology, and affective symptoms. More severe negative and affective symptoms were most directly linked with poorer QoL and may prove to be integral in attaining positive outcomes in schizophrenia treatment. Incorporation of psychosocial treatments in addition to pharmacotherapy may prove effective in targeting negative and affective symptoms.

Expert Revision of Key Elements for Clinical-Grade Production and Qualification of Perinatal Derivatives.

Perinatal derivatives have been proposed as adjunct therapeutic strategies or innovative treatments. Undoubtedly, perinatal derivatives can offer the opportunity and source material to isolate multipotent stem cells, but both maternal- and fetal-derived tissues can be processed and transformed into engineered tissues or advanced biomedical devices, whose potential remains to be fully elucidated. Promising preclinical and clinical results collected so far clearly foresee an escalation of such novel treatments. Market forecasts predict exponential growth in such advanced medicinal products during the next decade, with a pragmatic innovation for medicine into a more advanced biomedical version, enlarging the portfolio for treating a wide range of congenital and acute conditions. However, all these promising and fascinating therapeutic possibilities cannot gain a solid and recognized role in established medical practice without rigid and harmonized manufacturing strategies. The implementation of strategies according to guidelines and directives compiled by Regulatory Agencies, in conformity to (European) Pharmacopoeia and for Good Manufacturing Practice -conforming production of such products, represent critical steps required to translate perinatal technologies into effective therapeutic approaches. During the past 5 years, a panel of European experts and developers, gathered under the umbrella of the COST Sprint Action, supported by the European Cooperation in Science and Technology action, had the opportunity to revise and summarize experience and recommendations for a fruitful and proficient generation of perinatal biomedical products. In order to facilitate the creation and potential commercialization of perinatal bioengineered and advanced pharmaceutical products and technologies, such a collection of data and recommendations is described and discussed here.

Influence of socioeconomic factors on liver transplant survival outcomes in patients with autoimmune liver disease in the United States.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILDs): autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) have different survival outcomes after liver transplant (LT). Outcomes are influenced by factors including disease burden, medical comorbidities, and socioeconomic variables. MATERIALS AND METHODS: Using the United Network for Organ Sharing database (UNOS), we identified 13,702 patients with AILDs listed for LT between 2002 and 2021. Outcomes of interest were waitlist removal, post-LT patient survival, and post- LT graft survival. A stepwise multivariate analysis was performed adjusting for transplant recipient gender, race, diabetes mellitus, model for end-stage liver disease (MELD) score, and additional social determinants including the presence of education, reliance on public insurance, working for income, and U.S. citizenship status. RESULTS: Lack of college education and having public insurance increased the risk of waitlist removal (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.09; 95 % CI, 1.00-1.18; respectively), and negatively influenced post-LT patient survival (HR, 1.16; 95 % CI, 1.06-1.26, and HR, 1.15; 95 % CI, 1.06-1.25; respectively) and graft survival (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.15; 95 % CI, 1.06-1.25; respectively). Not working for income proved to have the greatest detrimental impact on both patient survival (HR, 1.41; 95 % CI, 1.24-1.6) and graft survival (HR, 1.21; 95 % CI, 1.09-1.35). CONCLUSIONS: Our study highlights that lack of college education and public insurance have a detrimental impact on waitlist mortality, patient survival, and graft survival. Not working for income negatively affects post-LT survival outcomes. Not having U.S. citizenship does not affect survival outcomes in AILDs patients.

Antimicrobial Efficacy of the Use of Mouthwash with Cetylpiridinium Chloride for Aerosol Producing Procedures. A Systematic Review / Eficacia antimicrobiana del uso del enjuague bucal con cloruro de cetilpiridinio en procedimientos que generan aerosoles. Revisión sistemática

Abstract The present research aims to determine the antimicrobial efficacy of the mouthwashes based on cetylpyridinium chloride (CPC), before aerosol producing dental procedures. A data search was performed during August 2021 in five databases MEDLINE (PubMed), SCOPUS, SCIELO, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar. Randomized clinical trials (RCTs) were included based on the PICO question, comparing the efficacy of the mouthwashes based on cetylpyridinium chloride (CPC), versus other mouthwashes and water, before aerosol producing dental procedures, papers in English, Spanish and Portuguese were included without time limits. The risk of the included studies was evaluated with the tool RoB 2.0. Number of registration PROSPERO N° CRD42021275982. 120 papers were obtained in the preliminary search, discarding those that didn't comply with the selection criteria, leaving only 3 studies. These papers reported the use of cetylpyridinium chloride (CPC) was effective for the reduction of bacteria during the ultrasonic prophylactic procedure. The use of CPC mouthwashes previous to the dental treatment with ultrasonic prophylaxis showed only antibacterial capacity.

Resumen El presente trabajo de investigación tiene como objetivo determinar la eficacia antimicrobiana de los colutorios a base de cloruro de Cetilpiridinio (CPC), previo a tratamientos dentales que generen aerosol. Se realizó una búsqueda bibliográfica hasta agosto del 2021 en cinco bases de datos: MEDLINE (vía PubMed), SCOPUS, SCIELO, Cochrane Central Register of Controlled Trials (CENTRAL) y Google Scholar. Se incluyeron ensayos clínicos aleatorizados (ECAs), basándose en la pregunta PICOS, que compare la eficacia del colutorio a base de cloruro de Cetilpiridinio (CPC) con otro colutorio, placebo o agua, previo a un tratamiento dental que genere aerosol, en los idiomas español, inglés o portugués y sin límite de tiempo. El riesgo de los estudios incluidos se evaluó con la herramienta RoB 2.0. Número de registro PROSPERO N° CRD42021275982. Se obtuvo un total de 120 artículos en la búsqueda preliminar, descartando aquellos que no cumplían con los criterios de selección, quedando sólo 3articulos. Estos artículos informaron que el uso de CPC es efectivo para la reducción de bacterias durante el procedimiento de profilaxis con ultrasonido. El uso de los enjuagues bucales a base de CPC previo al tratamiento dental de profilaxis con ultrasonido sólo tiene eficacia antibacteriana.

The Detection of Resilience in Families Grieving Over a Suicide.

The study, conducted in 2021, describes the relationship between resilience development factors and dimensions and the grief processes of persons affected by the suicide of a family member. The objective was to analyze whether the loved ones of suicide victims had developed resilient behaviors and how these were manifested during the mourning process. To achieve this, two instruments were used: the Brief Resilience Coping Scale (BRCS), and in-depth interviews, in both cases applied to a sample of 21 individuals from whom narratives of their experiences were obtained as elements for analysis. These narratives were operationalized, coded and analyzed according to the theoretical framework advanced by the authors Edith Grotberg and Cecily Knight. The behaviors detected took the form, among others, of artistic expression and/or the provisioning of support services to people affected by suicide, generally through participation in associations and self-help groups dedicated to the care and facilitation of emotional expression resulting from the traumatic event.

Two Decades of Liver Transplants for Primary Biliary Cholangitis: A Comparative Study of Living Donors vs. Deceased Donor Liver Transplantations.

Primary biliary cholangitis (PBC) prompts liver transplantation (LT) due to cholestasis, cirrhosis, and liver failure. Despite lower MELD scores, recent studies highlight higher PBC waitlist mortality, intensifying the need for alternative transplantation strategies. Living donor liver transplant (LDLT) has emerged as a solution to the organ shortage. This study compares LDLT and deceased donor liver transplant (DDLT) outcomes in PBC patients via retrospective analysis of the UNOS database (2002-2021). Patient survival, graft failure, and predictors were evaluated through Kaplan-Meier and Cox-proportional analyses. Among 3482 DDLTs and 468 LDLTs, LDLT showed superior patient survival (92.3%, 89.1%, 87.6%, 85.0%, 77.2% vs. 91.5%, 88.3%, 86.3%, 82.2%, 71.0%; respectively; p = 0.02) with no significant graft survival difference at 1-, 2-, 3-, 5-, and 10-years post-LT (91.0%, 88.0%, 85.7%, 83.0%, 75.4% vs. 90.5%, 87.4%, 85.3%, 81.3%, 70.0%; respectively; p = 0.06). Compared to DCD, LDLT showed superior patient and graft survival (p < 0.05). Younger male PBC recipients with a high BMI, diabetes, and dialysis history were associated with mortality and graft failure (p < 0.05). Our study showed that LDLT had superior patient survival to DDLT. Predictors of poor post-LT outcomes require further validation studies.

Symbiosis between cyanobacteria and plants: from molecular studies to agronomic applications.

Nitrogen-fixing cyanobacteria from the order Nostocales are able to establish symbiotic relationships with diverse plant species. They are promiscuous symbionts, as the same strain of cyanobacterium is able to form symbiotic biological nitrogen-fixing relationships with different plants species. This review will focus on the different types of cyanobacterial-plant associations, both endophytic and epiphytic, and provide insights from a structural viewpoint, as well as our current understanding of the mechanisms involved in the symbiotic crosstalk. In all these symbioses, the benefit for the plant is clear; it obtains from the cyanobacterium fixed nitrogen and other bioactive compounds, such as phytohormones, polysaccharides, siderophores, or vitamins, leading to enhanced plant growth and productivity. Additionally, there is increasing use of different cyanobacterial species as bio-inoculants for biological nitrogen fixation to improve soil fertility and crop production, thus providing an eco-friendly, alternative, and sustainable approach to reduce the over-reliance on synthetic chemical fertilizers.

Comparison among three predictive models for cancer-associated thromboembolism in a hispanic population.

In this study we aimed to evaluate and compare the overall performance of the Khorana, PROTECHT, and CONKO scores as predictive scores for the occurrence of venous thromboembolism (VTE) among ambulatory Hispanic patients with solid tumors. We included all outpatients with newly diagnosed solid tumors receiving systemic chemotherapy in Hospital San Juan Dios, San José, Costa Rica, from January to December 2021. For each patient the Khorana, PROTECHT, and CONKO scores were calculated at the beginning of treatment. The sixth-month cumulative incidence of VTE was estimated using the Fine & Gray competing risk model. The receiver operating characteristic (ROC) curve was used to assess the performance of each predictive tool through the analysis of the c-statistic, sensitivity, and specificity. A total of 708 patients were included in the research. After a median follow-up of 8.13 months, the cumulative VTE incidence at six months was 4.45% (95%CI: 3.25-6.91%) for the overall population. At the conventional positivity threshold of 3 points, these scores classified from 17.7 to 32.5% of all patients as high-risk for VTE. Patients belonging to the high-risk category of the Khorana, PROTECHT, and CONKO scores had significantly higher risk of VTE in comparison to low-risk patients (Khorana score: Hazard Ratio (HR): 2.66; 95%CI:1.20-5.89; p = 0.042; PROTECHT score: HR: 3.44; 95%CI:1.63-7.21; p = 0.001; CONKO score HR: 3.68; 95%CI:1.72-7.85; p = 0.001). The c-statistic of the ROC curve was: 0.62 (95%CI: 0.52-0.72), 0.62 (95%CI: 0.52-0.73), and 0.65 (95%CI: 0.56-0.76) for the Khorana, PROTECHT, and CONKO scores, respectively; with similar sensitivity (range: 67-70%) and specificity (range: 52-62%) among them. For Hispanic patients with solid tumors the Khorana, PROTECHT, and CONKO scores accurately categorize their risk of VTE. However, the overall discriminatory performance of these models remains poor (c-statistic from 0.62 to 0.65) for predicting all patients at risk for thromboembolic events.

Effectiveness of Saccharomyces Boulardii CNCM I-745 probiotic in acute inflammatory viral diarrhoea in adults: results from a single-centre randomized trial.

BACKGROUND: Probiotics are effective for treating acute infectious diarrhoea caused by bacteria, but there are inconsistent results for the effectiveness of probiotics for diarrhoea caused by viruses. In this article we want to determine whether Sb supplementation has an effect on acute inflammatory viral diarrhoea diagnosed with the multiplex panel PCR test. The aim of this study was to evaluate the efficacy of Saccharomyces boulardii (Sb) as a treatment in patients diagnosed with viral acute diarrhoea. METHODS: From February 2021 to December 2021, 46 patients with a confirmed diagnosis of viral acute diarrhoea diagnosed with the polymerase chain reaction multiplex assay were enrolled in a double-blind, randomized placebo-controlled trial. Patients received paracetamol 500 mg as a standard analgesic and 200 mg of Trimebutine as an antispasmodic treatment plus 600 mg of Sb (n = 23, 1 × 109/100 mL Colony forming unit) or a placebo (n = 23) orally once daily for eight days. The improvement in and severity of symptoms were measured using a symptom diary, the Patient Global Impression and the Patient Global Impression of Change scales (days 4 and 8), both answered and recorded by the patient. RESULTS: Of the 46 patients who completed treatment, 24 (52%) were men and 22 (48%) were women. The average age was 35.6 ± 12.28 years (range 18 to 61 years). The average duration of the evolution of illness at the time of diagnosis was 0.85 ± 0.73 days (maximum 2 days). On day 4 after the diagnosis, 20% reported pain and 2% reported fever, but on day 8, no patient reported pain or fever. On day 4, 70% of patients in the Sb group and 26% in the placebo group reported improvement (P = 0.03), based on the Patients' Global Impression of Change scale, which assesses patient's rating of overall improvement. These findings suggest that 3 to 4 days of treatment with Sb helped to improve symptoms of diarrhoea caused by a virus. CONCLUSION: Treatment with Sb on acute inflammatory diarrhoea of viral aetiology shows no changes regarding the severity of the symptoms; nevertheless, it seems to impact improvement positively. TRIAL REGISTRATION: 22CEI00320171130 dated on 16/12/2020, NCT05226052 dated on 07/02/2022.

Molecular Dynamics Simulations of HPr Proteins from a Thermophilic and a Mesophilic Organism: A Comparative Thermal Study.

The histidine-containing phosphocarrier (HPr) is a monomeric protein conserved in Gram-positive bacteria, which may be of mesophilic or thermophilic nature. In particular, the HPr protein from the thermophilic organism B. stearothermophilus is a good model system for thermostability studies, since experimental data, such as crystal structure and thermal stability curves, are available. However, its unfolding mechanism at higher temperatures is yet unclear at a molecular level. Therefore, in this work, we researched the thermal stability of this protein using molecular dynamics simulations, subjecting it to five different temperatures during a time span of 1 µs. The analyses of the structural parameters and molecular interactions were compared with those of the mesophilic homologue HPr protein from B. subtilis. Each simulation was run in triplicate using identical conditions for both proteins. The results showed that the two proteins lose stability as the temperature increases, but the mesophilic structure is more affected. We found that the salt bridge network formed by the triad of Glu3-Lys62-Glu36 residues and the salt bridge made up of Asp79-Lys83 ion pair are key factors to keep stable the thermophilic protein, maintaining the hydrophobic core protected and the structure packed. In addition, these molecular interactions neutralize the negative surface charge, acting as "natural molecular staples".