Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Examining the validity of the Mini-Mental State Examination (MMSE) and its domains using network analysis.

BACKGROUND: The Mini-Mental State Examination (MMSE) is the most widely used standardised screener for impairments across a range of cognitive domains. However, the degree to which its domains (orientation, registration, attention, recall, language, and visuospatial) capture cognitive functioning measured using standardised neuropsychological tests is unclear. METHOD: A longitudinal research design with four biannual assessments over a 6-year period was used with an initial sample of 1037 older adults (aged above 70 years). Participants completed MMSE and neuropsychological tests at each assessment. Network analysis was utilised to investigate unique associations among the MMSE and its domains and neuropsychological test performance at each time point. RESULTS: The total MMSE and two of its domains, language and recall, were associated with neuropsychological memory performance. The MMSE orientation, registration and visuospatial domains did not have any unique associations with neuropsychological performance. No stable internal interconnections between MMSE domains were found over time. The association of total MMSE as well as its recall domain with neuropsychological memory performance remained very similar over the 6-year period. CONCLUSIONS: The present study adds evidence to the validity of the MMSE and supports the clinical usage of the MMSE, whereby the total score is used for screening patients with or without cognitive impairments, with repeated administration to monitor cognitive changes over time, to inform intervention. However, the tool is not able to diagnose the cases for changes in specific cognitive domains and as such, should not replace a complete neuropsychological assessment.

Which fatigue scale should I use? A Rasch analysis of two fatigue scales in inflammatory conditions.

OBJECTIVES: This study aimed to assess the psychometric properties of two widely used fatigue scales in a sample of patients with inflammatory conditions. METHODS: Rasch analysis was used to examine scale reliability, item bias, unidimensionality and overall fit to the Rasch model. Sub-test methodology was utilised to attempt to improve model fit for the CFQ and BRAF-MDQ. RESULTS: Initial analysis displayed strong reliability (PSI=0.89 0.96), alongside a lack of item bias in both scales. However, evidence for unidimensionality was not found for either scale. Overall fit to the Rasch model was marginal for the CFQ, and misfitting for the BRAF-MDQ. Local dependency was observed, as well as significant item misfit for both scales. Sub-test modifications resulted in the best model fit for the BRAF-MDQ (χ2(16)=15.77, p=0.469) and the CFQ (χ2(25)=15.49, p=0.929). Modifications resulted in improved fit, reductions in measurement error, and the production of ordinal-to-interval conversion tables for both scales. Conversion tables apply the benefits of enhanced measurement accuracy, valid comparison of BRAF-MDQ and CFQ scores to other interval-level data, appropriate use in parametric statistics, and enhanced precision in clinical cut-off scores-without the need to change administration format. CONCLUSION: The BRAF-MDQ and CFQ are valid, reliable tools for fatigue assessment. Psychometric indices and content factors suggest the CFQ is suited to measuring general fatigue, particularly when response burden is a concern, while the BRAF-MDQ should be used in clinical presentations where other symptoms are severe and the impact of fatigue on daily living, emotional, and social well-being is of interest.

Using network analysis to validate domains of the modified telephone interview for cognitive status.

BACKGROUND: The modified Telephone Interview for Cognitive Status (TICS-M) is a widely used tool for assessing global cognitive functions and screening for cognitive impairments. The tool was conceptualised to capture various cognitive domains, but the validity of such domains has not been investigated against comprehensive neuropsychological assessments tools. Therefore, this study aimed to explore the associations between the TICS-M domains and neuropsychological domains to evaluate the validity of the TICS-M domains using network analysis. MATERIALS AND METHODS: A longitudinal research design was used with a large sample of older adults (aged above 70 years; n = 1037 at the baseline assessment) who completed the TICS-M and comprehensive neuropsychological assessments biennially. We applied network analysis to identify unique links between the TICS-M domains and neuropsychological test scores. RESULTS: At baseline, there were weak internal links between the TICS-M domains. The TICS-M memory and language domains were significantly related to their corresponding neuropsychological domains. The TICS-M attention domain had significant associations with executive function and visuospatial abilities. The TICS-M orientation domain was not significantly associated with any of the five neuropsychological domains. Despite an attrition of almost 50% at wave four, weak internal links between the TICS-M domains and most associations between TICS-M and neuropsychological domains that were found initially, remained stable at least over two waves within the 6-year period. CONCLUSIONS: This study supports the overall structural validity of the TICS-M screener in assessing enduring global cognitive function. However, separate TICS-M cognitive domains should not be considered equivalent to the analogous neuropsychological domains.

Evaluating depression anxiety and stress assessment before and during the COVID-19 pandemic using generalisability theory.

The current study investigated the assessment of depression, anxiety, and stress during normal and COVID-19 pandemic conditions. Generalisability theory (G-theory) was applied to examine stable and dynamic aspects of psychological distress and the overall reliability of the Depression, Anxiety and Stress Scales (DASS-21), using data from two independent samples collected on three occasions with 2- to 4-week intervals. The US data (n = 115) was collected before the COVID-19 pandemic, and the New Zealand (NZ) data (n = 114) was obtained during the pandemic. The total DASS-21 demonstrated excellent reliability in measuring enduring symptoms of psychological distress (G = .94-.96) across both samples. While all DASS-21 subscales demonstrated good reliability with the pre-pandemic US sample, the subscales' reliability was below an acceptable level for the NZ sample. Findings from this study indicate that the overall psychological distress is enduring and can be reliably measured by the DASS-21 across different conditions and populations, while shifts across depression, anxiety and stress levels are likely during emergency and uncertainty, as seen in the COVID-19 pandemic.

Establishing conversion of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly scores into interval-level data across multiple samples using Rasch methodology.

BACKGROUND: The 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) is a well-validated and widely-used measure of cognitive changes (CCs) among older adults. This study aimed to use Rasch methodology to establish psychometric properties of the IQCODE-16 and validate the existing ordinal-to-interval transformation algorithms across multiple large samples. METHODS: A Partial Credit Rasch model was employed to examine psychometric properties of the IQCODE-16 using data (n = 918) from two longitudinal studies of participants aged 57-99 years: the Older Australian Twins Study (n = 450) and the Canberra Longitudinal Study (n = 468), and reusing the Sydney Memory and Ageing Study (MAS) sample (n = 400). RESULTS: Initial analyses indicated good reliability for the IQCODE-16 (Person Separation Index range: 0.82-0.90). However, local dependency was identified between items, with several items showing misfit to the model. Replicating the existing Rasch solution could not reproduce the best Rasch model fit for all samples. Combining locally dependent items into three testlets resolved all misfit and local dependency issues and resulted in the best Rasch model fit for all samples with evidence of unidimensionality, strong reliability, and invariance across person factors. Accordingly, new ordinal-to-interval transformation algorithms were produced to convert the IQCODE-16 ordinal scores into interval data to improve the accuracy of its scores. CONCLUSIONS: The findings of this study support the reliability and validity of the IQCODE-16 in measuring CCs among older adults. New ordinal-to-interval conversion tables generated using samples from multiple independent datasets are more generalizable and can be used to enhance the precision of the IQCODE-16 without changing its original format. An easy-to-use converter has been made available for clinical and research use.

Clinical investigation of dynamic and enduring aspects of global cognition in aged population.

BACKGROUND: A major issue in evaluating the cognitive status of ageing populations is a clear distinction between enduring and dynamic aspects of global cognition necessary for evaluating risks of dementia and effectiveness of preventive interventions. MATERIALS AND METHODS: Generalizability Theory was applied to investigate dynamic and enduring aspects of global cognition using longitudinal data over 10 years of follow-up. Measures included the Mini-Mental Status Examination (MMSE) and the Telephone Interview for Cognitive Status-modified (TICS-M). The sample (N = 238) included 154 females, mean age = 76.54 years, SD = 3.94 from the Sydney Memory and Ageing Study. RESULTS: The MMSE measured dynamic and enduring aspects of cognition to a comparable degree with 56% of variance explained by enduring aspects and 44% by dynamic aspects and showed low sensitivity/high specificity in detecting dementia. A shortened version of the MMSE (MMSE-D8) better captured dynamic aspects of cognition after removing three items less sensitive to change. The TICS-M predominantly measured enduring aspects of cognition (72%) with the remaining 28% due to dynamic aspects and displayed high sensitivity/high specificity for dementia screening. CONCLUSIONS: The MMSE measures both dynamic and enduring cognitive aspects and is suitable for general clinical assessments, while the MMSE-D8 can be used to monitor transitory changes of global cognition over time. The TICS-M is more useful for measuring enduring features of cognition and screening for dementia. Our findings highlight the value of generalizability theory to distinguish dynamic and enduring features of cognition, which may contribute to preventive interventions and monitoring cognitive ability over time.

Networks of inflammation, depression, and cognition in aging males and females.

BACKGROUND: Prioritizing the maintenance of healthy cognitive aging and personalizing preventive interventions to enhance their effectiveness is crucial as the global population ages. Systemic inflammation and depression in older people have been associated with decreased levels of cognition but results have been inconsistent. AIMS: To explore the interactive network of inflammation, depression and cognition by sex in older people. METHODS: We used novel network analysis to explore the unique associations between inflammatory biomarkers, depression, cognition, and somatic, genetic, and lifestyle risk factors in an older (aged 70-90 years), non-demented, community-dwelling sample from the longitudinal Sydney Memory and Aging Study (N = 916) at baseline and at a two-year follow-up. RESULTS: The networks of biomarkers, depression, cognition, and relevant covariates were significantly different between males and females. A stable negative link between depression and cognition was found in females only; a stable positive association between biomarker interleukin-6 and depression was found in females only; and a stable positive association between biomarker interleukin-8 and alcohol was found in females only. For both males and females, a stable, positive relationship was found between the presence of APOE-ε4 gene and biomarker C-reactive protein; between education and cognition; and between biomarker interleukin-6 and all other biomarkers. CONCLUSIONS: These findings suggest different psychophysiological mechanisms underlie the interactive network of biomarkers, depression and cognition in males and females that should be considered when designing personalized preventive interventions to maintain cognitively healthy aging.

A novel way to quantify schizophrenia symptoms in clinical trials.

BACKGROUND: A major problem in quantifying symptoms of schizophrenia is establishing a reliable distinction between enduring and dynamic aspects of psychopathology. This is critical for accurate diagnosis, monitoring and evaluating treatment effects in both clinical practice and trials. MATERIALS AND METHODS: We applied Generalizability Theory, a robust novel method to distinguish between dynamic and stable aspects of schizophrenia symptoms in the widely used Positive and Negative Symptom Scale (PANSS) using a longitudinal measurement design. The sample included 107 patients with chronic schizophrenia assessed using the PANSS at five time points over a 24-week period during a multi-site clinical trial of N-Acetylcysteine as an add-on to maintenance medication for the treatment of chronic schizophrenia. RESULTS: The original PANSS and its three subscales demonstrated good reliability and generalizability of scores (G = 0.77-0.93) across sample population and occasions making them suitable for assessment of psychosis risks and long-lasting change following a treatment, while subscales of the five-factor models appeared less reliable. The most enduring symptoms represented by the PANSS were poor attention, delusions, blunted affect and poor rapport. More dynamic symptoms with 40%-50% of variance explained by patient transient state including grandiosity, preoccupation, somatic concerns, guilt feeling and hallucinatory behaviour. CONCLUSIONS: Identified dynamic symptoms are more amendable to change and should be the primary target of interventions aiming at effectively treating schizophrenia. Separating out the dynamic symptoms would increase assay sensitivity in trials, reduce the signal to noise ratio and increase the potential to detect the effects of novel therapies in clinical trials.

Enhancing precision of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) using Rasch methodology.

OBJECTIVE: This study aimed to investigate psychometric properties and enhance precision of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) up to interval-level scale using Rasch methodology. DESIGN: Partial Credit Rasch model was applied to the IQCODE-16 scores using longitudinal data spanning 10 years of biennial follow-up. SETTING: Community-dwelling older adults aged 70-90 years and their informants, living in Sydney, Australia, participated in the longitudinal Sydney Memory and Ageing Study (MAS). PARTICIPANTS: The sample included 400 participants of the MAS aged 70 years and older, 109 out of those were diagnosed with dementia 10 years after the baseline assessment. MEASUREMENTS: The IQCODE-16. RESULTS: Initial analysis indicated excellent reliability of the IQCODE-16, Person Separation Index (PSI) = 0.92, but there were four misfitting items and local dependency issues. Combining locally dependent items into four super-items resulted in the best Rasch model fit with no misfitting or locally dependent items, strict unidimensionality, strong reliability, and invariance across person factors such as participants' diagnosis and relationship to their informants, as well as informants' age and sex. This permitted the generation of conversion algorithms to transform ordinal scores into interval data to enhance precision of measurement. CONCLUSIONS: The IQCODE-16 demonstrated strong reliability and satisfied expectations of the unidimensional Rasch model after minor modifications. Ordinal-to-interval transformation tables published here can be used to increase accuracy of the IQCODE-16 without altering its current format. These findings could contribute to enhancement of precision in assessing clinical conditions such as cognitive decline in older people.

Enhanced stability of the optical responses from all-inorganic perovskite nanocrystals embedded in a synthetic opal matrix.

Nanostructured luminescent materials based on perovskite nanocrystals (p-NCs) are attractive since their optical properties can be tuned in a wide spectral range with high luminescence quantum yields and lifetimes, however, they lack stability. In this work, the optical properties of highly luminescent colloidal p-NCs (CsPbX3, where X = Cl/Br, Br, I) embedded in porous opal matrices are presented. It is shown that the photoluminescence of the p-NCs embedded into opal matrices possess increased longtime stability of its spectral and kinetic parameters under ambient conditions. LEDs based on the developed materials show pure color p-NC emission with stability of its parameters. The results of this work may expand the knowledge of interactions between luminescent nanoparticles within multicomponent nanostructured materials for further photonic applications.

Development of a mental health recovery module for the WHOQOL.

PURPOSE: The WHOQOL tools are widely used, multi-faceted, patient-rated, quality of life (QoL) measures, developed by the World Health Organization. The WHOQOL questionnaires are used to assess generic quality of life issues affected by all health problems. This study developed a module to use with the WHOQOL tools to improve their sensitivity to Health Related QoL issues relevant to mental health recovery. METHODS: Using a sequential mixed-methods approach, two research stages occurred. A qualitative stage invited 88 participants with experience of mental health recovery, into focus groups and importance rating activities, to identify candidate items for the new module. Following this, a quantitative stage involved 667 participants with, and without, mental health/addiction issues completing online or paper-based questionnaires to analyze which candidate items differentiated between those with and without mental health/addiction issues. Classical test theory and iterative Partial Credit Rasch Analysis were used to identify the most suitable candidate items for a reliable and valid mental health recovery module to be used with the WHOQOL tools. RESULTS: Seventeen candidate items captured important HRQoL facets relevant to mental health recovery. Rasch analysis removed 10 misfitting items. The final 7-item module, which demonstrated the best Rasch model fit, enquires about recovery beliefs, identifying strengths, self-awareness, acceptance, capacity to relate, feeling understood, and recovery progress. Ordinal-to-interval conversion tables have been developed to optimize measurement precision when using the module. CONCLUSIONS: Important HRQoL issues central to mental health recovery can be reliably evaluated by using the recovery module with the WHOQOL tools.

Validation of the WHOQOL-BREF and Shorter Versions Using Rasch Analysis in Traumatic Brain Injury and Orthopedic Populations.

OBJECTIVE: To use Rasch analysis to validate the World Health Organization Quality of Life-BREF (WHOQOL-BREF) and existing short versions in individuals with traumatic brain injury and orthopedic injuries, with comparisons to a general population group. DESIGN: The Partial Credit Rasch model was applied to evaluate the WHOQOL-BREF as well as shortened versions using a cross-sectional study design. SETTING: Regional hospital, and national electoral sample in New Zealand. PARTICIPANTS: Individuals with traumatic brain injury (n=74), individuals with orthopedic injuries (n=114), general population (n=140). INTERVENTIONS: None. MAIN OUTCOME MEASURE: WHOQOL-BREF. RESULTS: The WHOQOL-BREF met expectations of the unidimensional Rasch model and demonstrated good reliability (person separation index [PSI] =0.82) when domain items were combined into physical-psychological, social, and environmental superitems. Analysis of shorter versions, the EUROHIS-QOL-8 and World Health Organization Quality of Life-5 (WHOQOL-5), indicated overall acceptable fit to the Rasch model and evidence of unidimensionality. The EUROHIS-QOL-8 showed good reliability (PSI=0.81); however, reliability of the WHOQOL-5 (PSI=0.68) was below acceptable standards for group comparisons, in addition to demonstrating poor person-item targeting. CONCLUSIONS: The WHOQOL-BREF and the 8-item EUROHIS-QOL-8 version are both reliable and valid in the assessment of quality of life in both injury and general populations. Ordinal-interval conversion tables published for these validated scales as well as for the WHOQOL-5 can be used to improve precision of assessment. The transformation of ordinal scale scores into an interval measure of health-related quality of life also permits the calculation of a single summary score for the WHOQOL-BREF, which will be useful in a wide range of clinical and research contexts. Further validation work of the WHOQOL-5 is needed to ascertain its psychometric properties.

Direct laser writing of barriers with controllable permeability in porous glass.

Barriers were produced in porous glass through its local bulk density modification by direct femtosecond writing accompanied by СО2-laser surface thermal densification, to make functional microfluidic elements separated by such physical barriers with different controlled permeability. The separation of multi-component solutions into individual components with different molecule sizes (molecular separation) was performed in this first integrated microfluidic device fabricated in porous glass. Its application in the environmental gas-phase analysis was demonstrated.

Intravenous Treatment With Coenzyme Q10 Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Brain Ischemia in Rats.

Coenzyme Q10 (CoQ10) crosses the blood-brain barrier when administered intravenously and accumulates in the brain. In this study, we investigated whether CoQ10 protects against ischemia-reperfusion injury by measuring neurological function and brain infarct volumes in a rat model of transient focal cerebral ischemia. In male Wistar rats, we performed transient middle cerebral artery occlusion (tMCAO) for 60 minutes, followed by reperfusion for 24 hours or 7 days. Forty-five minutes after the onset of occlusion (or 15 minutes before reperfusion), rats received a single intravenous injection of solubilized CoQ10 (30 mg·mL(-1)·kg(-1)) or saline (2 mL/kg). Sensory and motor function scores and body weights were obtained before the rats were killed by decapitation, and brain infarct volumes were calculated using tetrazolium chloride staining. CoQ10 brain levels were measured by high-performance liquid chromatography with electrochemical detection. CoQ10 significantly improved neurological behavior and reduced weight loss up to 7 days after tMCAO (P < 0.05). Furthermore, CoQ10 reduced cerebral infarct volumes by 67% at 24 hours after tMCAO and 35% at 7 days (P < 0.05). Cerebral ischemia resulted in a significant reduction in endogenous CoQ10 in both hemispheres (P < 0.05). However, intravenous injection of solubilized CoQ10 resulted in its increase in both hemispheres at 24 hours and in the contralateral hemisphere at 7 days (P < 0.05). Our results demonstrate that CoQ10 is a robust neuroprotective agent against ischemia-reperfusion brain injury in rats, improving both functional and morphological indices of brain damage.

Prospects of Intravenous Coenzyme Q10 Administration in Emergency Ischemic Conditions.

Coenzyme CoQ10 (CoQ10) is an endogenous lipid-soluble antioxidant that effectively protects lipids, proteins, and DNA from oxidation due to its ability to undergo redox transitions between oxidized and reduced forms. Various oxidative stress-associated infectious and somatic diseases have been observed to disrupt the balance of CoQ10 concentration in tissues. As a high molecular weight polar lipophilic compound, CoQ10 exhibits very limited oral bioavailability, which restrains its therapeutic potential. Nevertheless, numerous studies have confirmed the clinical efficacy of CoQ10 therapy through oral administration of high doses over extended time periods. Experimental studies have demonstrated that in emergency situations, intravenous administration of both oxidized and reduced-form CoQ10 leads to a rapid increase in its concentration in organ tissues, offering protection for organ tissues in ischemic conditions. This suggests that the cardio- and neuroprotective efficacy of intravenously administered CoQ10 forms could present new opportunities in treating acute ischemic conditions. Based on these findings, the review provides reasoning supporting further research and implementation of CoQ10 dosage forms for intravenous administration in emergency situations into clinical practice.

Cross-country assessment of the unique contributions of psychological factors to vaccination: Perspectives on the COVID-19 pandemic.

We have identified the most relevant and significant psychological factors in relation to COVID-19 vaccination attitudes in Ghana, Germany, New Zealand and India. This study recruited 1822 participants from the general populations of India (n = 411), New Zealand (n = 413), Ghana (n = 523) and Germany (n = 475) to participate in a cross-sectional online survey. After controlling for the country of residence, individual psychological factors played a significant role in shaping attitudes towards COVID-19 vaccination. The results also revealed strong direct predictors that explained significant portions of the variance in the COVID-19 vaccination attitudes. Positive affect emerged as the strongest contributor in Ghana (7%), while self-compassion strongly influenced COVID-19 vaccination attitudes in India (66%). Dispositional optimism was the strongest predictor in New Zealand (5%). In Germany, compassion towards others was the strongest positive predictor (2%), while psychological distress had a strong negative impact (3%). Results highlight the importance of promoting emotional well-being to enhance vaccination coverage.

Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis.

BACKGROUND: The gut-liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate. AIM: To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection. METHODS: This study included 48 patients with Child-Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii) for 3 months. RESULTS: Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child-Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child-Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child-Pugh scores (P = 0.046), as well as a higher level of the Child-Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis. CONCLUSION: The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut-liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.

Gut Microbiota and Biomarkers of Intestinal Barrier Damage in Cirrhosis.

Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut microbiota in cirrhosis. The blood levels of DAO were inversely correlated with blood levels of claudin 3, lipopolysaccharide (LPS), presepsin, TNF-α, and the severity of cirrhosis according to Child-Pugh scores. The blood level of I-FABP was directly correlated with the blood level of claudin 3 but not with that of DAO. Patients with small intestinal bacterial overgrowth (SIBO) had lower DAO levels than patients without SIBO. There was no significant difference in claudin 3 levels and I-FABP detection rates between patients with and without SIBO. The DAO level was directly correlated with the abundance of Akkermansiaceae, Akkermansia, Allisonella, Clostridiaceae, Dialister, Lactobacillus, Muribaculaceae, Negativibacillus, Ruminococcus, Thiomicrospiraceae, Verrucomicrobiae, and Verrucomicrobiota; and it was inversely correlated with the abundance of Anaerostipes, Erysipelatoclostridium, and Vibrio. The I-FABP level was directly correlated with Anaerostipes, Bacteroidia, Bacteroidota, Bilophila, Megamonas, and Selenomonadaceae; and it was inversely correlated with the abundance of Brucella, Pseudomonadaceae, Pseudomonas, and Vibrionaceae. The claudin 3 level was directly correlated with Anaerostipes abundance and was inversely correlated with the abundance of Brucella, Coriobacteriia, Eggerthellaceae, and Lactobacillus.

Usability and feasibility of PreventS-MD web app for stroke prevention.

BACKGROUND: Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. METHODS: This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0-50 unacceptable; 51-68 poor; 68-80.3 good; >80.3 excellent) were used to determine usability of PreventS-MD. FINDINGS: Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2; 95% CI [77.0-84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7; 95% CI [79.1-84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations. INTERPRETATION: The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and individuals at risk of stroke/CVD. Individuals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD.