The impact of water-induced degradation on the mechanical properties of the chosen two PTFE-coated, glass threads woven fabrics is investigated in this paper. The paper begins with a survey of literature concerning the investigation and determination of coated woven fabric properties. The authors carried out the uniaxial tensile tests with an application of flat and curved grips to establish the proper values of the ultimate tensile strength and the longitudinal stiffness of groups of specimens treated with different moisture conditions. Despite the water resistance of the main materials used for fabrics manufacturing, the change of the mechanical properties caused by the influence of water immersion has been noticed. The reduction in the tensile strength resulting under waterlogged is observed in the range from 5% to 16% depending on the type of investigated coated woven fabric and direction of weft or warp. The glass threads, polytetrafluoroethylene (PTFE)-coated woven fabrics are one of the most popular types of architectural fabrics applied in membrane structures see  and are The coated woven fabrics called architectural fabrics spark a vital interest in the community of engineers, designers, and scientists to take into consideration, as the subject of different investigations to describe their complex mechanical behavior and influence on thermal and environmental conditions. In the beginning, the authors decided to perform a survey of literature concerning the investigation carried out on coated woven fabrics with topical grouping to show how the widespread research and development area of coated woven fabrics is.Due to discrete microstructure, non-linear, and inelastic strain-stress relationships of the coated woven fabrics, a large number of the constitutive models are proposed and developed . Hass 55 and PieThe different types of laboratory tests  are performed to a proper description of the behavior of the coated woven fabrics. Reinhardt  comparedBesides uniaxial and biaxial tensile tests a cyclic, creep, tearing, etc. tests are carried out to show and measure additional complex behaviors of coated woven fabrics. Ansell et al.  investigGenerally, the final product used directly in the tensile structures is tested. Nevertheless, some works investigated also uncoated fabric. Chen et al.  investigInvestigations on a description of material and mechanical properties for different coated woven fabrics are widely conducted also. Bassett et al.  reviewedA large number of investigations are also performed on assessment changes of coated woven fabric properties influences by temperature, aging processes, or other factors. Zhang et al.  determinThe literature concerning coated woven fabrics is very extensive, nevertheless, the authors pay attention to chosen studies concerning the wide and comprehensive studies on the coated woven fabrics. The literature review indicates research concerning constitutive models, different types of laboratory tests, determination of material and mechanical properties, assessment of coated woven fabric mechanical properties changes under different factors, etc. The studies concerning water-induced degradation on coated woven fabrics are limited. Therefore, there is a necessity for carrying out detailed and extended research in this area. Continuous development in textile and membrane materials provides an impulse to conduct new investigations on coated woven fabrics. It can be mentioned that coated fabrics are still developed, tested, and investigated by engineers, researchers, and scientists.The fabrics producers usually provide the designer with strength parameters for dry material. But when the final construction is exposed to changing weather conditions, especially during the rain or winter season, when rain or wet snow can remain for a long time on the roof surface, the tensile strength can be reduced. There are many factors, which can affect the mechanical properties and final behavior of the coated woven fabrics. Environmental conditions that occur during coated woven fabric exploitation  seem to be a prominent factor. One of that factors is rain and high moisture. The present study is aimed at the determination of the influence of water-induced degradation on mechanical parameters of chosen PTFE-coated woven fabrics on changing of mechanical properties under uniaxial tensile tests with an application of two types of grips (flat and curved). This paper provides scientists, engineers, and designers with experimental assessments of the influence of water-induced degradation on mechanical parameters (tensile strength) of investigated two types of PTFE-coated woven fabrics.Two woven fabrics having glass threads coated by PTFE were chosen for laboratory tests. According to manufacturers’  declarations given in The uniaxial tensile tests were conducted on the Zwick 020 mechanical testing machine , under the video extensometer control based on the digital image correlation method with the base of the optical extensometer of about 50 mm. The results from the video extensometer were used to identify the fabric stiffness functions. The specimens had 50 ± 1 mm width, and the active length equal to 200 ± 1 mm for application of flat grips see a, and thThree main groups of coated fabric specimens were tested. All specimens were cut out from the bales of fabric stored for a long time in the laboratory in room conditions. For the first group, the fabric specimens were cut in the warp and weft direction from the base material (virgin fabric). Then they were, measured, weighed, and then immediately tested. Results for this group are denoted S or B regarding S type or B type coated fabrics. The two remaining groups of specimens fabric were immersed into room temperature water for two weeks. The immersion period was twice longer than taken by Asadi et al. . After tα = 0.05.To recognize the importance of mechanical parameters changes according to moisture conditions and history of water impact on the coated fabric, the one-way ANOVA statistical analysis  was After weighing (with an accuracy of ±0.01 g) and dimension measuring (with an accuracy of ±1 mm) for each sample dry, after soaking, and after air-drying were determined the total mass per unit area for chosen types of PTFE coated woven fabrics. The results of measurements of surface weight determining are collected in p < 0.05 and not the important difference between dry and air-dried groups for the S type (p = 0.218). That means that the S type of fabric has almost the same density before soaking and after the air-drying process from the statistical point of view.The comparison of the surface weight of investigated groups of fabrics showed the statistically important differences for all three groups for the B type of fabric The uniaxial tensile tests were performed to evaluate the tensile strength and the related elongation at break, as well as the fabric stiffness in the specified ranges of deformation. The results  have been recorded by a computer and recalculated to the stress-strain functions presented in Based on the performed uniaxial tensile tests the elongation at break and the tensile strength are specified for fabrics investigated under different conditions: dry, wet, and air-dray. For evaluation of the tensile strength, the type of used grips may play an important role. The ISO 1421 standard  does notThe large differences between tensile strength  are connected with exhibited of breaks of fabrics specimens near the grips thus the flat grips results sometimes cannot be treated as proper value of the tensile strength of coated fabrics. Nevertheless, in this investigation, for the flat grips results for the B-type fabric in the warp direction, the tensile strength is greater than for curved grips.The specified mean values of tensile strength of the dry S-type fabric (base specimens) for weft and warp directions is 185 ± 2 kN/m and 173.1 ± 2 kN/m see  and theyp < 0.05 (for dry/wet p = 0.377). For warp direction the important difference has been obtained for dry/wet comparison only . For the B-type of fabric, the relevant differences have been obtained for all compared groups.The importance of the influence of water-induced degradation mechanisms on the tensile strength has been verified by the ANOVA one-way statistical analysis. The change of the tensile strength should be analyzed for curved grips as an application of flat grips usually generates the jaws breaks and cause a reduction of the tensile strength, see . For theiF (kN/m) and the intersection points iF (kN/m) were determined from the linear approximation of the stress-strain relationship using the piecewise linear model.Analyzing the stress-strain curves for the S and B types of PTFE-coated fabrics see , the chaThe application of the video extensometer made it possible to unify the results of tests for flat and curved grips into one group. The video extensometer measures strain in the middle part of the specimen without a touch of the specimen, far from the grips, see FB and FC it may be concluded that the difference of stiffnesses between the dry and wet fabrics ranges from 2% (for weft) to 5% (for warp) for the S-type fabric, see FA of the wet S-type fabric is vary by about 2% for weft and 9% for warp in comparison with dry properties, while for the wet B-type fabric differs by about 10% (for weft and warp), see Taking into account the mean stiffnesses of The reduction in the tensile strength resulting under waterlogged was observed in the range from 5% (for weft) to 14% (for warp) for S-type fabric and from 16% (for weft) to 10% (for warp) for B-type fabric, respectively. A similar conclusion came from the authors of , where tThe mechanical properties of investigated PTFE coated fabric under water-induced are degraded not only via in-plane watering at unsealed cut edges but also via out-of-plane watering through the coating.The influence of moisture is not the same for different physical parameters. The most sensitive is the tensile strength.Even small moisture changes as it has been reported between the base fabric and air-dried material cause statistically important changes in the tensile strength. The changes in fabric stiffness are much less sensitive and from the statistical point of view, they can be neglected.Changes in the stress-strain curve characteristic under different moisture conditions of PTFE coated fabrics cannot be indicated due to the significant scatter of obtained results, see The ANOVA analysis indicated that the longitudinal stiffnesses differences among the investigated groups  are not statistically significant. Future investigations should take into account a more large number of specimens to confirm differences.Types of grips used in tensile tests influenced the determined values of the tensile strength. The type of grips is not important during the stiffness of fabric determination. Determination of the tensile strength should be rather performed by using the curved grips to avoid the close-to-grip breaks in coated fabric specimens that are often observed when the flat grips are used. Such close-to-grip breaks reduce the tensile strength value.In the present paper, two chosen architectural fabrics constructed from glass threads and have the PTFE coating  are investigated. The main materials used to produce the fabrics are water-resistant. Nevertheless, the final product is sensitive to the level of moisture. Based on performed investigation the following conclusions may be drawn:The paper provides scientists, civil engineers, and designers with knowledge of water-induced degradation of chosen PTFE-coated woven fabrics’ mechanical properties and requirements to applying curved grips during the process of determination of tensile strengths. Determination of the proper values of tensile strengths of coated woven fabrics under environmental conditions requires assessment of the dry and wet conditions. The coated woven fabrics producers should provide the designer with strength parameters for dry and wet material. The obtained results encourage the authors to continue the research directed towards understanding mechanisms of water-induced degradation of coated woven fabrics’ mechanical properties, based on an extension of uniaxial tensile tests and biaxial tensile tests for waterlogged fabrics.


The calcifying epithelial odontogenic tumor is a rare benign neoplasm that accounts for approximately 1% of all odontogenic tumors. Most of the cases occur in the posterior mandible, and a few involve the maxilla. Despite their relatively indolent biological behavior, tumors in the maxilla tend to grow fast. We report the case of a 33-year-old female patient exhibiting swelling in the right maxilla. An isodense area associated with an impacted supernumerary tooth was found on imaging examination. The histopathologic diagnosis was a calcifying epithelial odontogenic tumor. The treatment of choice was surgical removal of the lesion and associated dental elements. The patient has been followed up for 11 months and shows no signs of recurrence. Besides describing this case, we reviewed the literature on the association of calcifying epithelial odontogenic tumors with supernumerary teeth and found two case reports addressing this subject. According to the last classification of WHO 2017), these tumors are categorized based on their biological behavior and whether they derive from the epithelium or mesenchyme. The calcifying epithelial odontogenic tumor (CEOT) is classified as a benign neoplasm of epithelial origin, accounting for only 0.6% to 1.7% of all odontogenic tumors.7, these ,The etiopathogenesis of CEOT is still controversial, but the tumor is believed to arise from dental lamina remnants, from the reduced epithelium or intermediate layer of the enamel organ, or even from the oral epithelium.The diagnosis of COET is made by histopathological analysis of a fragment obtained preferentially through an incisional biopsy. Microscopically, the tumor appears as a benign neoplastic process of odontogenic epithelial origin characterized by the proliferation of polyhedral cells in an arrangement of sheets, islands, or nests amidst a stroma of fibrous connective tissue. Typically, the tumor contains amyloid-like material and basophilic concentric calcifications (Liesegang rings).Reports of cases of COET are scarce in the literature. The study of these rare tumors is important since it provides information that assists in the diagnosis, thus allowing better treatment planning and minimizing the risk of recurrence. This study aims to report an uncommon case of CEOT in the posterior maxilla associated with a supernumerary tooth.A 33-year-old female patient sought a referral center for oral-maxillofacial surgery, reporting a 15-year history of an asymptomatic swelling in the right maxilla, which started to exhibit ulceration about 8 months earlier. An extraoral physical examination revealed no alterations.On intraoral physical examination, a normochromic, hardened, sessile mass of exophytic growth was observed in the right maxillary region, with bulging along the bottom of the vestibule. The lesion was associated with ulcerations and paresthesia .Panoramic radiography revealed a unilocular lesion surrounding a mineralized structure that resembled a denticle between the roots of the first and second right upper premolars A. Cone-bHistopathological analysis of the specimen showed the presence of sheets, islands, and sometimes nests of polyhedral odontogenic epithelial cells with well-defined contours amidst a stroma of fibrous connective tissue. The cells exhibited cellular and nuclear pleomorphism. The tumor also contained areas of amyloid-like eosinophilic amorphous material, as well as small irregular foci of concentric calcifications (Liesegang rings) A-B.The treatment of choice was enucleation followed by curettage and extraction of right upper premolars and first molar associated with the lesion. The maxillary defect was reconstructed using titanium meshes and autogenous corticomedullary bone grafts removed from the mandibular symphysis and right ramus A-D. A suAfter 12 months postoperatively, the superficial titanium mesh was removed due to its intraoral exposure A-B. The ,In 2017, the World Health Organization (WHO) classified CEOT as a benign epithelial odontogenic tumor.-,Approximately 90% of CEOT cases are intraosseous, and the mandible is the most affected site in these patients. Maxillary tumors are observed in 25% to 41% of cases and generally occur in the posterior region.,,,,,There is no sex predilection for CEOT, and the tumor usually causes a painless, slow-growing swelling.,,,The clinical characteristics of CEOT are nonspecific. The radiographic features of CEOT vary according to the evolution time of the tumor, usually appearing as a radiolucent, uni- or multilocular lesion.,,The typical microscopic features of CEOT were identified in the present case: a proliferation of polyhedral cells of epithelial odontogenic origin arranged in sheets, islands, or nests amidst a stroma of fibrous connective tissue; extensive deposition of amyloid-like material; deposition of mineral material forming oval and concentric structures (Liesegang rings).,CEOT can infiltrate bone trabeculae even in the radiographic absence of involvement of this region or can cause cortical bone perforation or erosion.,Although CEOT is considered a benign tumor, rare cases of metastasis have been reported, especially to the cervical lymph nodes and lungs.The present patient had a CEOT at an uncommon anatomical site associated with a supernumerary tooth, representing a rare case given the findings described in the literature. The clinical-radiographic features of the tumor were similar to other odontogenic lesions. Thus, histopathological analysis is essential for establishing of the final diagnosis, which together with the clinical and imaging findings, will indicate the most appropriate therapeutic protocol for these tumors. Since CEOT associated with supernumerary teeth is rare, this case report adds to the literature and assists in establishing the epidemiological profile, biological behavior, and better therapeutic approaches for this tumor.


The Portfolio Diet has demonstrated its cardiovascular benefit from interventions, but the association between Portfolio Diet adherence and the risk of all-cause and cause-specific mortality has not been examined in Chinese population. The present study has collected Portfolio Diet adherence (assessed by food frequency questionnaire), lifestyle factors and mortality status of 3991 participants in the Mr. Osteoporosis (OS) and Ms. OS Study. Cox regression models were used to examine the association between the Portfolio Diet adherence and mortality risk . The highest quartile of the Portfolio Diet score was associated with a 28% lower risk of all-cause  and cancer (HR: 0.72) mortality, respectively. The association between Portfolio Diet adherence and cardiovascular disease mortality did not reach statistical significance . Among male participants, the highest adherence to the Portfolio Diet was also associated with a lower risk of all-cause (HR: 0.63) and cancer mortality (HR: 0.59), and there was an inverse association between food sources of plant protein and the risk of cardiovascular mortality (HR: 0.50). However, most associations between the Portfolio Diet and mortality were not significant among females. The protection for cancer mortality risk might reach the plateau at the highest adherence to the Portfolio Diet for females. To conclude, greater adherence to the Portfolio Diet was significantly associated with a lower risk of mortality in Hong Kong older adults, and the associations appeared stronger among males. Maintaining a healthy diet is a major lifestyle factor to prevent diabetes and cardiovascular diseases (CVD), two chronic diseases that have resulted in a huge public health burden worldwide. Although multiple studies have evaluated the relationship between individual nutrients and health, emerging evidence has suggested how dietary patterns may explain the interactions between different foods and food components and their associations with health outcomes . Some weAmongst dietary patterns that may improve cardiovascular health, the Dietary Portfolio, or the Portfolio Diet, is a plant-based dietary pattern developed in the early 2000s to lower low-density lipoprotein cholesterol (LDL-C) ,5. The PIn addition to clinical trials for patients with dyslipidemia, the health benefits of the Portfolio Diet were also examined among cohort studies. A Portfolio Diet score (PDS) has been developed and validated to assess the adherence to the Portfolio Diet using food frequency questionnaires (FFQ) , and to Despite groundwork being established, the PDS needs to be assessed in other cohorts and ethnic groups to compare with previous findings and verify its applicability internationally. In addition, the previous work using WHI data only included postmenopausal women. The present study has evaluated how the adherence to the Portfolio Diet may have sex-specific associations with the risk of all-cause, CVD and cancer mortality among a prospective cohort of Hong Kong older adults, an ageing Chinese population with high life expectancy . When anTo measure the Portfolio Diet adherence in the Hong Kong Chinese context, we have used data from the Mr. Osteoporosis and Ms. Osteoporosis Study . Since 2001–2003, the OS Study has been a long-term cohort study that recruited 4000 community-living Hong Kong Chinese men and women aged at least 65 years. The target was to recruit a stratified sample that equally assigned them into each of these age groups, namely 65–69, 70–74, and ≥75. Compared with the general population in this age group, participants had higher educational level (9.8% vs. 3.8% with tertiary education), higher proportion of being married (70.7% vs. 59.9%) and slightly lower proportion of living alone (10.8% vs. 11.3%) . The stuDietary assessment was conducted using a validated FFQ  with 280 food items validated against 24 dietary recalls ,14. EachFood items recommended in the Portfolio Diet were extracted from the OS FFQ and were categorized into the six components of the Portfolio Diet. For most components, servings per day were summed over all consumed food items in each component for every participant. More points were given to participants with higher intakes of food recommended in the Portfolio Diet, whereas fewer points were given to participants with higher intakes of food not recommended in the Portfolio Diet. These points were given for each of the six dietary components , saturated fat/cholesterol sources) by splitting the components into quintiles (according to the sex-specific data distribution in the OS Study). Those in the highest quintile of foods recommended  received 5 points and those in the lowest quintile received 1 point. Reverse scoring was done for those with foods not recommended , meaning those with the highest intake (quintile 5) received 1 point, and those with the lowest intake (quintile 1) received 5 points. The total points were then added for each respondent, resulting in a score range between 6 and 30, with higher scores indicating higher adherence to the Portfolio Diet. The adherence score of Portfolio Diet has been validated in 652 participants in the Toronto Healthy Diet Study, which has shown inverse association with lower LDL-C, and showed reasonable agreement between the score from the FFQ and 7-day dietary record .Plant sterols were the only score component based on mg per day, while all other components are food-based in servings per day. Since the OS FFQ compositional database does not have plant sterols available as a nutrient variable for their FFQ, we have established a plant sterol database (mg per day) based on literature values. Data sources in European countries or the United States were used, including the Finnish Food Composition Database , the datData on mortality were obtained from the Death Registry of the Department of Health of Hong Kong and collected through March 2014 with a median follow-up of 11.1 years. Apart from all-cause mortality, cardiovascular or cancer causes of death were identified by the cause of death reported on the death certificate and classified according to the International Classification of Disease version 10 codes. Participants were followed up until death or loss to follow-up, whichever occurred first .Demographic, lifestyle and health information was collected from each participant including education level (secondary school or below vs. post-secondary education), smoking habit , alcohol consumption , physical activity, dietary intake and self-reported history of chronic diseases . Physical activity level was evaluated using the Physical Activity Scale for the Elderly (PASE) . Body wep < 0.05 would suggest a better fit regression model by including the quadratic term, hence a non-linear relationship between the PDS and all-cause, CVD or cancer mortality.Baseline characteristics were stratified by sex  and the quartiles of the PDS using means with standard deviations for continuous variables and frequencies with percentages for categorical variables. To compare baseline characteristics, chi-square tests were used for categorical variables and analysis of variance for continuous variables. Participants were categorized into quartiles of the Portfolio Diet score, with the lowest quartile serving as the reference group. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between the PDS quartiles and mortality outcomes. The Cox regression model was adjusted for sex , age, dietary energy, body mass index, physical activity, systolic blood pressure , medical history , smoking habit , alcohol drinking  and education level (post-secondary education vs. secondary school or below). We also applied subgroup analyses according to sex . Trend analysis was performed by assigning median values of each PDS quartile and treating it as a continuous variable in the regression model. To examine the potential non-linear relationship between the PDS and the risk of mortality, we compared the fit of continuous models with or without cubic spline terms of PDS. A likelihood test with p < 0.05 was considered statistically significant. Most statistical analyses were conducted with IBM SPSS Statistics 23  and we have used R 4.1.1  for examining the non-linear relationship between the PDS and the risk of mortality, and the competing risk analysis [Additional analyses included evaluating associations between the six individual components of the Portfolio Diet and risk of the mortality outcomes. We conducted subgroup analysis on the Portfolio Diet components using the same covariates as listed in the regression analysis. Sensitivity analyses on the association between the PDS and the risk of mortality were conducted by excluding people who had ever smoked or with individual comorbidity at baseline  as they may have different diets than those without smoking nor comorbidities. Since the influence of the PDS on blood pressure could be the causal pathway on the risk of mortality, we also removed systolic blood pressure from the regression model in a sensitivity analysis. Another sensitivity analysis comprised using the age at death as the survival time in the Cox regression model, instead of the observation period from enrolment to the end of the study or the subject’s death, because the exposure (Portfolio Diet adherence) for each subject began before the period of enrolment. With regard to the competing nature of cardiovascular disease and cancer in mortality risk, we have also computed the cumulative sub-distribution hazards (SHR) for the Fine–Gray models , and comanalysis .After excluding 9 people with missing information on dietary intake or covariates, a total of 3991 participants were included in the analyses. The baseline characteristics of participants in the OS Study are presented by sex in p > 0.05).The baseline characteristics of participants in the OS Study by PDS quartiles are presented in p-values for the trend were significant for the association between PDS and all-cause mortality among all participants and males only, as well as the association between PDS and cancer mortality among overall participants. The p-values for non-linearity were significant for the association between PDS and all-cause mortality among males, and the association between PDS and cancer mortality among males and females. We then checked the assumption by testing the proportionality of the risks according to outcomes  and sex . As revealed by the Schoenfeld test in p = 0.0199).The association between the Portfolio Diet adherence in quartiles and the risk of mortality are presented in When looking into individual components of the Portfolio Diet , higher After excluding participants who smoked or with comorbidities at baseline, excluding SBP from the regression model, or using the age at death as survival time, the association between the highest quartile of PDS and the risk of mortality remained significant among male participants . Among fThis examination of approximately 4000 older adults in Hong Kong is the first prospective cohort study to examine the association between the Portfolio Diet and mortality in the Asian region. A higher Portfolio Diet score was associated with a 28% lower risk of all-cause and cancer mortality, respectively. Among male participants, the highest adherence to the Portfolio Diet was also associated with a lower risk of all-cause and cancer mortality, and there was an inverse association between food sources of plant protein and the risk of cardiovascular mortality. Since most associations were not significant among female participants, the findings from the present study are likely driven by male participants. Sex differences in the consumption of food sources rich in plant protein, viscous fiber and nuts, as well as smoking rate, may explain the relationship between the Portfolio Diet and mortality risk reduction. Despite some non-linearity in the shape of the relationships, the general results from the present study have suggested protective associations of the Portfolio Diet in decreasing the risk of mortality. The protection for all-cause and cancer mortality risk may be significant at the highest quartile of PDS for males, while the protection for cancer mortality risk might reach the plateau at the highest quartile of PDS for females.To the best of our knowledge, this study is the first to demonstrate the potential role of the Portfolio Diet in preventing all-cause mortality; therefore, comparison with other literature is challenging. An analysis of postmenopausal women that participated in the WHI showed that the adherence to the Portfolio Diet was associated with lower risk of total CVD , coronary heart disease , and heart failure , comparing the highest to lowest quartile of adherence , which iAlthough the present study has not demonstrated the long-term benefit of the Portfolio Diet in reducing mortality risk due to CVD, further recent analyses revealed the prospective benefit of the adherence to the Portfolio Diet on cardiometabolic health. Higher adherence to the PDS was associated with lower LDL-C in the Toronto Healthy Diet Study , as wellWhen looking into the individual components of the Portfolio Diet, plant protein, nuts and viscous fiber was associated with lower mortality risk, whereas plant protein consumption was associated with lower risk of CVD death in our analysis. In the present analysis, the magnitude of association between the Portfolio Diet and all-cause mortality  was comparable to plant protein sources , viscous fiber sources  and nuts . Moreover, plant protein sources had an inverse association with CVD mortality among male  participants. The findings of our present analyses are in line with related studies on the association between plant-based foods, CVD and cancer mortality. For example, evidence from meta-analyses have suggested the consumption of legumes , viscousOur subgroup analyses showed that greater adherence to the Portfolio Diet was associated with a lower risk of all-cause and cancer mortality among men only. Similarly, an analysis of the Adventist Health Study 2 found that vegetarian dietary patterns  were associated with a reduced risk of mortality due to ischemic heart disease or CVD in men but the associations were insignificant in women . AlthougThe strengths of our study include the prospective cohort design and over 10 years of follow-up for mortality outcomes. Nevertheless, there are some limitations. First, participants in the OS Study had a higher educational level compared with the general Hong Kong population and, therefore, they may have better dietary habits and improved dietary profile. Second, although the FFQ is considered a common method to collect data of usual dietary intake in large epidemiological studies, the data are self-reported. In addition, the smaller number of CVD mortality events than all-cause and cancer deaths may explain the null association between Portfolio Diet adherence and the risk of CVD mortality. Moreover, diet and lifestyle factors might change over time, and the relevant information was only available at baseline in this current study. Lastly, causation cannot be established because of the observational design, and residual confounding cannot be ruled out.Greater adherence to a Portfolio Diet was significantly associated with lower risk of mortality in Hong Kong older adults. These findings have supported the benefits of a Portfolio Diet in reducing the risk of cancer mortality. However, our findings have to be verified in additional populations, including in cohort studies that measured repeated dietary habits over time.


Objective: To identify feature immune-related genes (IRGs) in patients with hypertrophic cardiomyopathy (HCM) and verify their ability to diagnose HCM.Methods: The GSE160997 dataset on cardiac tissue from 18 HCM patients and 5 controls was downloaded from the Gene Expression Omnibus database. A false discovery rate <0.05 and |log2 fold change| >1 were the filters applied to identify the differentially expressed genes (DEGs). The differentially expressed IRGs were the intersection results between the DEGs and an IRG dataset from the IMMPORT database. The protein-protein interaction network of differentially expressed IRGs was constructed, and the top 20 hub genes with the most adjacent nodes in the network were selected. The least absolute shrinkage and selection operator regression algorithm and a random forest algorithm were used to identify the feature IRGs as biomarkers that were then verified against GSE36961.Results: A total of 1079 DEGs were identified in GSE160997. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that immune-related mechanisms play an important role in the pathogenesis of HCM. A total of 121 differentially expressed IRGs were identified, and 5 feature IRGs were selected, 4 of which were confirmed as potential biomarkers of HCM by external verification with excellent discrimination ability. A diagnosis model of HCM based on the four feature IRGs was developed and visualized as a nomogram with a C-index of 0.925 .Conclusion: Our study identified four feature IRGs as biomarkers for the diagnosis of HCM, offering an innovative perspective of the underlying immune-related pathological molecular mechanisms. Hypertrophic cardiomyopathy (HCM) is a hereditary heart disease that is defined as unexplained, isolated, progressive myocardial hypertrophy, usually accompanied by heart failure or arrhythmia. It is considered the primary underlying condition in sudden cardiac death in young adults and athletes. Mutations in the genes encoding proteins of the cardiomyocytic contractile apparatus are considered the main cause of HCM. However, the relationship between sarcomere mutations and clinical outcomes remains unpredictable in patients with HCM, largely because of genetic and phenotypic heterogeneity , 2. DuriSarcomere protein gene  mutations have become targets in the genetic testing of HCM. Unfortunately, in the genetic testing of different HCM cohorts, up to 50–68% of patients were negative for sarcomere protein gene mutations  network of differentially expressed IRGs was constructed using the STRING database [ that had been confirmed in previous studies as being involved in the natural immune process was downloaded from the IMMPORT database [; https:/The least absolute shrinkage and selection operator (LASSO) regression arithmetic and Boruta arithmetic  were useThe selected feature IRGs were further verified using the independent dataset GSE36961 with 106 HCM patients and 39 healthy controls. The gene expression values were displayed by boxplots, and receiver-operating characteristic (ROC) curves were used to assess the discrimination ability of the feature IRGs. A five-fold cross-validation was conducted 500 times on the GSE36961 cohort to conform the reliability of the area under the ROC curves (AUC) of the selected biomarkers. Moreover, an online webtool NetworkAnalyst  was usedAfter the normalization of GSE160997 dataset , a totalA total of 121 differentially expressed IRGs between the DEGs and an IRG dataset from the IMMPORT database were identified . These 1The LASSO arithmetic selected 6 feature IRGs  and the The gene expression values of the five selected IRGs in GSE36961 are illustrated in The miRNA—feature IRG regulatory network and transcription factor (TF)—feature IRG regulatory network were listed as HCM is a common inherited cardiovascular disease that occurs in one of 500 people in the general population and leads to heart failure, fatal arrhythmia, and stroke. Mutations in genes encoding proteins of the cardiomyocytic contractile apparatus are considered the main cause of HCM. Genetic tests focusing on sarcomere protein genes have been recommended in current guidelines and experience widespread adoption. However, with the accumulation of experimental data –26, apprAccording to bioinformatics analysis, the GO annotation and KEGG enrichment analysis of the DEGs in GSE160997 were dominated by immune and inflammatory response mechanisms, such as neutrophil and macrophage activation, neutrophil degranulation, regulation of leukocyte-mediated immunity, and immune effector processes. Currently, inflammation and immunity attract substantial interest with regard to their role in the pathophysiology of cardiovascular diseases. Some previous studies –31 suggeThe preliminary results of bioinformatics analysis enabled further exploration of IRGs as biomarkers of HCM. A dataset with 1,793 unique IRGs was downloaded from the IMMPORT database and used to identify the IRGs among the DEGs in GSE160997. A total of 121 IGRs were selected from the 1,079 DEGs, and 5 feature IRGs were identified as candidate biomarkers by both the LASSO and Boruta arithmetic. Finally, four feature IRGs were confirmed as biomarkers with an excellent AUC score using the GSE36961 dataset of HCM patients and 39 healthy controls. Our novel diagnosis model of HCM constructed based on these four feature IRGs showed high discrimination ability (C-index = 0.925) and favorable calibration. This pioneering research offers a new perspective on the identification of potential biomarkers that might aid in the diagnosis of HCM.Angiotensin II receptor type 1 (AGTR1) is a significant effector of the renin-angiotensin-aldosterone system, which is associated with cardiovascular diseases, especially cardiac remodeling. The system consists of two regulatory pathways: a pathological pro-inflammatory pathway and a protective anti-inflammatory pathway. AGTR1, involved in the former, can promote vasoconstriction, cell proliferation, inflammation, oxidative stress, hypertrophy, and fibrosis, and angiotensin II–type 1 receptor blockers are widely used to prevent cardiac remodeling after acute myocardial infarction and heart failure , 33.Atypical chemokine receptor 3 (ACKR3) , previouCCR1 gene encodes a protein that acts as a chemokine receptor. This protein and its ligands macrophage inflammatory protein 1  and regulated on activation normal T expressed and secreted protein  can be expressed in monocytes/macrophages/T lymphocytes, whose signaling is the key to recruit effector immune cells to inflammatory sites. Liehn et al. proved that in model mice with myocardial infarction, the deletion of CCR1 can reduce tissue inflammatory injury and protect the myocardium . Data frThe protein encoded by cytochrome b-245 beta chain (CYBB) gene, also named NOX-2, is a component of cytochrome b-245, which plays an important role in the development of phagocytic microbicidal oxidase system. A consensus has been reached that the deficiency of CYBB leads to decreased NADPH oxidase activity in phagocytes, and neutrophils phagocytize bacteria but do not effectively kill bacteria, and that this might be the potential pathogenesis of chronic granulomatous disease . In addiThe strengths of this study are (a) the innovative perspective that immune and inflammation may underlie the molecular mechanism of HCM and (b) the identification of IRGs as diagnostic biomarkers using bioinformatics analysis of transcriptome datasets of HCM patients and healthy controls. Nonetheless, some limitations of this study need to be recognized. First, the study was a retrospective data analysis and lacked detailed clinical or prognostic information, such as the thickness of the ventricular septum and the occurrence of major adverse cardiovascular events in patients with HCM. This limited the further exploration of the relevant genes determining these clinical features or outcomes. Second, although the four feature biomarkers were verified by an independent dataset of sufficient size and achieved excellent discrimination, a larger dataset is essential for verification in the future. Third, the different transcriptome datasets were detected by different sequencing platforms. The baselines of the different transcriptome datasets were inconsistent, indicating that they may only determine whether the expression of characteristic genes is abnormal without the ability to identify a generally applicable reference range.The systematic analysis of the transcriptional profiles of HCM and exploration of the potential underlying molecular mechanisms led to the identification of four feature IRGs as biomarkers of HCM. Based on these, a diagnosis model of HCM was developed that brings a novel aspect to the current understanding of the pathological processes and required genetic testing in HCM.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/XZ and GL were involved in the conception and design of the study. XZ was responsible for visualization and article writing. RH provided scientific supervision. All authors reviewed and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


During the start of the first wave of the coronavirus disease 2019 (COVID-19) pandemic, two family physicians in Tshwane, South Africa, reviewed the people at high-risk within their Health Catchment Area. The largest residential mental health care facility in Gauteng fell under their care, and they were responsible for providing care and support to this facility. Family physicians have to lead the primary care team and simultaneously take care of the well-being of their team members. This report discusses how these family physicians used digital platforms and virtual care to successfully coordinate and manage the response to an outbreak of COVID-19 at this mental healthcare facility. The family physician takes responsibility for all primary care facilities, old age homes, special needs facilities and health related activities in this area. The family physician previously fulfilled all their different roles through being physically present and moving around the HCA. As a result of the coronavirus disease 2019 (COVID-19) pandemic, the key roles of the Family Physician  had to be applied in a new context.This report describes the virtual support provided by two family physicians to Paul Jungnickel Home (PJH), a mental healthcare institution in their HCA in Tshwane, during the first wave of the pandemic in 2020. Paul Jungnickel Home is a residential care facility that offers medical and residential care to 160 severe and profoundly disabled adults. The Department of Family Medicine at UP has given clinical support and coordinated care for the home since 2010 and provided on-site support during two Shigella outbreaks. The COVID-19 pandemic presented the healthcare team at PJH with some very specific challenges. Patients with severe intellectual impairments struggled to adhere to general COVID-19 prevention measures such as wearing mask, social distancing and using hand sanitizer. Many of these patients had comorbidities, limited mobility and obesity. Because of these factors, the team expected rapid spread of the virus and a high mortality rate. In addition, these patients would not be prioritised for intensive care or ventilation, particularly in this resource limited setting.An on-site facility readiness assessment and disaster management plan were completed in April 2020, after the facility went into a strict lockdown. Everyone realised that it would not be business as usual, and that technology would play a big role in providing support.2 Telemedicine assisted in providing early interventions in the context of the restriction of movement during lockdown. It minimised infection risk to non-infected individuals, contributed to the effective use of doctors’ time and assisted in optimising the workload.3 The use of WhatsApp has been promoted as a tool to provide clinical assistance and screen potential urgent cases.4 Informed by existing literature on the topic, a virtual coordination of care plan was devised to support the patients of PJH in their home-based care setting.Telemedicine and the use of digital health technologies have long been discussed as a potential solution to many challenges, including primary care. The COVID-19 pandemic dramatically catalysed the uptake of these technologies in a matter of weeks.The first COVID-19 case in PJH, diagnosed on 28 June 2020, was a staff member and three days later the first resident tested positive. A WhatsApp group with the nursing sisters and the family physicians was formed to facilitate real-time communication. Additionally, daily meetings were arranged via Zoom. Each of these two communication platforms provided unique features and opportunities. The WhatsApp group facilitated real-time communication where questions, results and clinical images could be shared and responded to. Zoom provided the opportunity to do daily ‘virtual ward rounds’ where patients could be discussed and advice given. Directions on the use of blood tests, oxygen concentrators, antibiotics and steroids were given daily. The information gained by making use of these platforms made it simple for the family physicians to refer patients to hospital if they could not be managed at the PJH.Between June 2020 and August 2020, only 13 patients out of a total of 160 patients tested positive. The effective and timeous quarantine and isolation procedures contributed to the containment of the disease within PJH. Of the infected patients, two were referred to hospital, four needed oxygen therapy at PJH and only one patient passed away.Through the support of PJH by the Department of Family Medicine, valuable lessons were learnt on being responsive to challenges and thinking outside the box. Without being physically present, it was still possible to fulfil all the key roles of a family physician in the HCA. The use of technology to provide virtual care was a timesaving measure and allowed for real time support that was quicker than the traditional face-to-face interactions. Team building and strengthening of networks in the HCA specifically benefited from the use of virtual platforms and WhatsApp groups. The nursing manager of PJH summarised the impact of this support during the COVID-19 pandemic well:Paul Jungnickel Home] died from COVID-19 [coronavirus disease 2019] is truly remarkable. It would not have been possible without the support of the two family physicians during this crisis time. They empowered us as nurses and assisted in procuring the necessary tools to provide treatment to very special and complex patients in their own safe, home environment. Their moral support was invaluable.’ ‘The fact that only one patient at PJH [The support to the PJH represents one of the many contributions that family physicians in primary care made during the first wave of the COVID-19 pandemic in Tshwane District. Assistance with planning, co-ordinating clinical care and responsiveness led to an excellent outcome during the COVID-19 outbreak and affirms the importance of the different roles that family physicians play in the South African health context. It also shows the advantages of using innovative strategies and technology to fulfil these different roles.


Cognitive control is a critical feature in adapting our behavior to environmental and internal demands with two types of inhibition having been identified, namely the proactive and the reactive. Aiming to shed light on their respective neural correlates, we decided to focus on the cerebral activity before or after presentation of the target demanding a subject’s stop as a way to separate the proactive from the reactive components associated with the tasks. Accordingly, we performed three Activation Likelihood Estimation (ALE) meta-analyses of fMRI studies exploring proactive and reactive inhibitory phases of cognitive control. For this purpose, we searched for fMRI studies investigating brain activity preceding or following target stimuli. Eight studies  were identified for the proactive analysis. Five of these studies and those previously analyzed by others  were meta-analyzed to explore the neural correlates of reactive inhibition. Overall, our results showed different networks for the two inhibitory components. Notably, we observed a contiguity between areas in the right inferior frontal gyrus pertaining to proactive inhibition and in the right middle frontal gyrus regarding reactive inhibition. These neural correlates allow proposal of a new comprehensive model of cognitive control. High order processes such as decision making involve adaptive and flexible cognitive control. This adaptability provides the resources to modify planned responses and to appropriately react to ever-changing information from external stimuli and internal goals . Admittedly, the double nature of these tasks does not help separate involvement of the two components from each other. However, by focusing exclusively on the timing of the cerebral activity (acquired volumes), i.e. before or following presentation of the target demanding the subject’s stop, separation of the proactive from the reactive components associated with the tasks would be possible. For the sake of completeness, we also included data originally collected by Simmonds et al.  to accouPubMed (https://www.ncbi.nlm.nih.gov/pubmed/) and Web of Science (https://webofknowledge.com). The selected keywords were combined using the Boolean operator AND and OR. The PubMed search input was: ((((proactive control) OR proactive inhibition) OR alerting) OR readiness) AND fMRI. The Web of Science search input was: TS =  AND fMRI). Additional studies were searched from the references of all identified publications. Eligibility was determined by a two-step procedure performed by three of the authors . First, the titles and abstracts of all identified articles were screened. In the second step, the full texts of studies, according to predefined eligibility criteria, were independently examined and agreement was reached after discussion. Our study was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines  whole-brain analysis performed on fMRI data ; 2) availability of coordinates of activation foci clearly provided either in Montreal Neurological Institute (MNI) or Talairach reference space; 3) availability of data related to the brain activity preceding a target stimulus ; 4) availability of studies conducted on healthy participants reporting contrasts against rest or baseline. We excluded studies that used the go trials or other contrast conditions as baseline in the proactive phase. The selection of these strict criteria allowed us to select homogeneous studies in order to obtain theoretically more robust measures . Neuroanatomical coordinates reported in MNI space were transformed to Talairach space  meta-analysis  and the size of the resulting supra-threshold clusters was compared (applying a threshold of P < 0.05) to a null distribution of cluster sizes determined by 1000 permutations of the data.ALE is a coordinate-based meta-analysis technique that uses peak coordinates reported in functional studies as input. The description of the exact procedure of ALE meta-analyses can be found in several methodological papers . The second one included the activation foci generated in the contrasts associated to the volume following the stimulus against the baseline (Reactive Process: Nogo-Baseline) of our studies cumulated with those reported by Simmonds et al. . The oveIn the last analysis we rerun the data collected by Simmonds et al.  dealing http://rii.uthscsa.edu/mango/) which is an anatomical image overlay program, and superimposed onto a standardized anatomical template in Talairach space.Whole-brain maps of the thresholded ALE images were visualized in Mango V.4.0.1  and the Go/No-go task acquired during fMRI. The ALE meta-analysis of foci associated with the proactive inhibition phase showed significant convergence of activation in bilateral ACC and insulae, the rIFG and right thalamus.As previously reported in studies on proactive inhibition  were included in the list of brain regions reported by Simmonds et al. , althougSecond, r-MFG was the only region related to the reactive process to consistently emerge among the meta-analyses conducted in the present study, in particular considering the contrast between the reactive and the proactive inhibition Fig. . DiffereOverall, our analyses make it possible to spatially differentiate areas involved in proactive and reactive components of inhibition which formerly were assigned to a single network  of the inhibitory control is in line with the distributed nature of the brain systems associated with the higher functions in mammals Fig. . This diThe right inferior cortices and pre-SMA are traditionally considered key structures in the inhibitory component of cognitive control  and reactive (r-MFG) phases in order to evaluate when, and if, to inhibit an action. Consistently with other works (Swann et al. By meta-analyzing neural correlates reported in task-based fMRI studies we propose a new model of cognitive control. Since all studies selected were based on fMRI protocols, we are aware that the accuracy of our results might be influenced by the low temporal resolution of this instrument. This is the main limitation of the present work. In particular, we recognize that the hypothesized role of switch we attributed to the ACC being temporally brief and spread between the proactive and reactive phases needs to be evaluated by further investigations. Different techniques with improved temporal resolution as compared to fMRI, like MEG and/or the combination of EEG-fMRI, might be used for this purpose with an exploration at higher temporal resolution by means of additional parameters of the BOLD contrast and beyond. With these methods one may verify the model proposed here as well as validate and potentially detail the mechanism of the ACC.Moreover, on clinical grounds, a separate analysis of the proactive and reactive components in future fMRI studies might increase our understanding of addictive behaviors in psychiatric conditions and of the physiopathological mechanisms underlying loss of cognitive control in neurodegenerative or infective diseases predominantly affecting the frontal and cingulate cortices. These include, on the one hand, fronto-temporal dementia, Huntington chorea, and Progressive Supranuclear Palsy and, on the other hand, Herpes Encephalitis. The same approach might be pursued in vascular or inflammatory diseases involving the subcortical white matter as in small vessel diseases or multiple sclerosis. Finally, useful information could be gathered in cases of infarct in the territory of the anterior cerebral arteries which typically includes the ACC.We designed and performed meta-analyses on proactive and reactive inhibition by mirroring and replicating the study on reactive inhibition conducted a decade ago by Simmonds et al. . We anal


The Healthcare sector has been at the forefront of the adoption of artificial intelligence (AI) technologies. Owing to the nature of the services and the vulnerability of a large section of end-users, the topic of responsible AI has become the subject of widespread study and discussion. We conduct a mixed-method study to identify the constituents of responsible AI in the healthcare sector and investigate its role in value formation and market performance. The study context is India, where AI technologies are in the developing phase. The results from 12 in-depth interviews enrich the more nuanced understanding of how different facets of responsible AI guide healthcare firms in evidence-based medicine and improved patient centered care. PLS-SEM analysis of 290 survey responses validates the theoretical framework and establishes responsible AI as a third-order factor. The 174 dyadic data findings also confirm the mediation mechanism of the patient’s cognitive engagement with responsible AI-solutions and perceived value, which leads to market performance. In recent years, there has been an enhanced focus on artificial intelligence (AI) in various domains, to resolve complex issues Chen, . In healUtilization of recent AI technologies in healthcare, coupled with patient’s growing adoption of AI-enabled devices, allows collection and storage of and access to large scale data, both by healthcare providers and technology vendors  to explain the relevance of the constructs under study and identify additional measurement parameters. In the second stage, a quantitative survey (N = 290) was conducted among healthcare professionals, which established responsible AI as a third-order factor. Finally, we collected dyadic data (N = 174) utilizing a survey of healthcare professionals and patients. We used PLS-SEM to test the proposed relationships. The findings highlight the complex factors of responsible AI. This study is a first step to establish the constituents of responsible AI as a third-order factor. The results of this study enrich the more nuanced understanding of how responsible AI influences the patient’s instrumental and terminal values, which in turn affect market performance. The findings of the study bridge the gap between theory and practice by clarifying how ethical concerns, technical skills, and risk mitigation factors should be implemented to design responsible AI systems. Our study confirms the mediating mechanism of cognitive engagement with responsible AI and instrumental and terminal values. The implications for researchers and practitioners are discussed, emphasizing that healthcare service providers need to design responsible AI to develop value propositions and improve market performance.In recent years, AI has achieved an accelerated momentum to deliver the best possible outcomes and is increasingly prevalent in business and society , an exploratory qualitative study was conducted with in-depth interviews. A purposive sampling strategy was utilized to recruit the participants. The sampling criteria ensured the likelihood of healthcare professionals  expressing their understanding of the constituents of responsible AI in healthcare. The criteria for the interviewees were experience in and knowledge of responsible AI. The exploratory interviews emphasized the participants’ perception of responsible AI and their views as to the constituents and consequences of responsible AI. The interview guide was prepared from the concepts derived from the extant literature. We utilized a few open-ended questions  in our model to conduct the survey . The sampling frame was the top five performing hospitals in India. The inclusion criteria were bed strength, the volume of patients, and healthcare firms’ market performance. We approached the potential respondents Table  through We first specified the hierarchical model, which represents the relationships between the higher-order constructs, sub-dimensions, and the measurement indicators. We constructed the model indicating the first and second-order constructs as reflective (Mode A), based on the related studies and subsequent conceptualization. The third order was constructed as formative (Mode B). To depict the hierarchical model in PLS-SEM, we first constructed the first-order latent variables and connected them to their corresponding indicators  approach to SEM (PLS-SEM) is used for the estimation of a complex and hierarchical model with the assumptions of soft modeling  values for Technical Skill (Q2 = 0.3299), Ethical Concerns (Q2 = 0.409), Risk Mitigation (Q2 = 0.375), and Resp AI (0.204), thus indicating a satisfactory predictive relevance. Finally, the overall model fit was assessed by using standardized root mean square (SRMR) residuals as an index for model validation  Data  and Algorithm  on ‘Technical Skill’ (2) Individual ethics  and Service-ethics  on ‘Ethical concerns’ and (3) Adaptability , Co-operation , and Transparency , on ‘Risk mitigation’ factors- were significant. Further, the indicator weights of the third-order construct – Technical Skill , Ethical Concerns  and Risk mitigation  were statistically significant  had been using AI-enabled tools or other platforms for the last one to two years . Thus, we further found the respondents’ list, which consisted of the other end of the healthcare provider-patient dyad  and TNV  was significant. Thus, the hypothesis H1 and H2 are supported Table . MediatiIn this study, we specifically examined the design and implementation of responsible AI in the Indian healthcare context. The mixed-method approach provided insight into the critical constituents of responsible AI in healthcare. The findings revealed three significant pillars of responsible AI in the context of healthcare deliveries: technical skills, ethical concerns, and risk mitigation. Identification of the three facets of responsible AI further divulged exciting aspects of their healthcare implementation. For instance, exploratory interviews revealed that healthcare professionals are becoming competent and skilled in areas other than medicine. This was highlighted as an essential concern as continuous medical education remains an essential priority for most healthcare professionals. The learning requirements associated with responsible AI create a divergent learning track that needs balancing and integration.Excessive focus on the collection of data was another primary concern emerging from the qualitative study. Respondents indicated that their decisions are increasingly based on recent data, and the department concerned is involved in a continuous evaluation of a large variety of data. The complexity of socially beneficial AI technology necessitates a collaborative effort with technology vendors  at the center and assess how healthcare companies can be benefitted by the potential healthcare market, as envisaged by the Indian Brand Equity Foundation.AI technologies could enable access to a full continuum of care and create an ecosystem with in-home monitoring, acute functionality, and patient assistance for high-value therapies. However, these rapid developments also require technical skills to handle data and algorithms safely, raise individual and service ethics and emphasize risk management. This study highlights the apparent areas of understanding of how responsible AI may be shaped in the healthcare context. The technical challenges relating to data-set appropriateness and suitability and the explainability of algorithms require expertise and team effort. The results suggest that algorithmic issues need much attention to become executable at the frontline of medical care. The study also suggests legitimate data security and privacy invasion avoidance, which are The study’s findings are also aligned with the need for innovations in data science and artificial intelligence, to support global efforts to combat outbreaks of a pandemic like COVID-19  to provide a robust understanding. A fruitful avenue of future research is the extension of the framework by considering the cultural characteristics and collecting the multi-national samples to assess the strength of the relationships. Second, the study contributes to the constituents of ‘Responsible AI’ in healthcare by considering several psychological and social aspects. However, there may be other contextual variables affecting the formation of Responsible AI, which remain unexplored. Future studies should also be conducted to better understand the antecedents of responsible AI. Third, we believe that the nature of tasks and the degree of involvement with AI-enabled technology may also moderate this relationship. For example, different users may use different tools and platforms as per their requirements. Task-related and rational motives may affect the perceived benefits and value differently. Future researchers should take into account the moderating roles of such variables and explore these issues of personal habits and task characteristics, which the current study has not considered. Finally, theories of psychology suggest that the factors responsible for cognitive engagement are affected by the brands of service products, and may also change over time. Therefore, a longitudinal study considering the brand values of the AI-enabled technologies will provide more useful insights to strengthen the theorizing in this context.The widespread interest in responsible AI shown by scholars and practitioners motivated this research article. Although several industry reports and contributions of practitioners have populated the literature on responsible AI, researchers have only recently begun exploring its underlying dynamics. In essence, this study provides a background to the infrastructure and ecosystem that supports the formation of responsible AI in the healthcare context. This study highlights the dark side that a typical AI project could present and thus addresses an urgent need to develop AI technologies with social and ethical concerns. In doing so, we adopted a mixed methodology, using a sample of both healthcare professionals and customers (patients) in India. Our results first identify the constituents of responsible AI and establish it as a third-order factor with three underlying dimensions: technical skills, ethical concerns, and risk-mitigation. We found that data and algorithmic issues, privacy invasion, adaptability, quick recovery from malfunctions, and collaborative efforts were important in shaping responsible AI in healthcare. The insights of the study can be used for easing the leveraging of responsible AI in India. Our findings guide healthcare firms in designing and implementing responsible AI, while simultaneously clarifying how such technological advancements affect patients’ cognitive engagement. Our findings provide the insight that responsible AI affects the value formation and market performance of a healthcare firm.


The complex mechanism by which kidneys fail and progress to end stage renal disease (ESRD) involves renal hemodynamics, glomerular function, and tubular function. A progressive decline in glomerular filtration (GFR) to ESRD ultimately requires dialysis and kidney transplantation . This wave of new modeling technologies includes glomerulus-on-a-chip, three dimensional microfluidic models, and organoids that can enable better predictions of cell-to-cell interactions in the glomerulus. The continuous development of better modeling of the glomerulus is sure to accelerate discoveries that will lead to better therapeutics for glomerular diseases.The complexity of the glomerulus and glomerular filtration barrier has led to modeling that considers the functions of the different cell types. A review article provides an update on the ever-expanding research efforts to model glomerular function . The findings of this study revealed that low levels of plasma galactose deficient IgA1 (GdlgA1), IgG antiglycan autoantibodies were found in patients with combined IgA nephropathy and minimal change disease . The plasma from these IgA nephropathy and minimal change patients resulted in a weaker inflammatory response when added to mesangial cells than plasma from IgA nephropathy patients . A second study evaluated plasma from IgA nephropathy patients and podocyte injury . Angiopoietin-like protein 4 (Angptl4) levels in IgA nephropathy patients correlated with podocyte injury . The next two studies evaluated traditional Chinese medicines on nephropathy. The ability for modified Huangqi decoction (MHCD) to reduce IgA nephropathy in rats was determined . MHCD reduced proteinuria, decreased mesangial cell hyperplasia and matrix expansion, and increased podocyte number in IgA nephropathy rats . A study in patients with refractory idiopathic membranous nephropathy demonstrated that Shulifenxiao treatment for up to 2 years had a favorable safety profile, increased the remission rate, and improved glomerular function . These studies highlight factors that contribute to damaging glomerular cells in nephropathies and potential therapies that target glomerular cells to combat nephropathies.Four original research articles to the Research Topic tackle IgA and membranous nephropathy. A major complexity to glomerular diseases is that multiple diseases can occur at the same time in patients. The combination of IgA nephropathy and minimal change were the focus of a retrospective patient cohort study . A hypothesis and theory article puts forth evidence that intravitreally administered VEGF inhibitors can cause thrombotic microangiopathy and acute kidney injury . This supports the concept that glomerular disease needs to be monitored in patients receiving in intravitreally administered VEGF inhibitors . Next, the ability for a dual soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) inhibitor, PTUPB to combat hypertension and glomerular injury during systemic administration of the VEGF and multikinase inhibitor sorafenib is demonstrated . PTUPB was able to decrease glomerular permeability and improve podocyte and mesangial cell function in rats administered sorafenib . Taken together, the glomerular damage induced by VEGF inhibitors needs to be monitored; however, novel therapies to mitigate the glomerular damage are on the horizon.Vascular endothelial growth factor (VEGF) inhibition on glomerular function is the topic in two articles that are published in this Research Topic. VEGF inhibitors are given systemically to treat cancers and intravitreally for age-related macular degeneration and diabetic retinopathy . Urate transporters in the kidney provide a mechanism for therapies to lower urate levels in hyperuricaemia . Glomerular nephropathy can be induced by environmental factors falling under the responsibility of occupational safety and health. Trichloroethylene is solvent widely used for degreasing metal, parts cleaning and exposure to this chemical exceeds 20,000 industry and warehouse workers every year in China. Wang and colleagues report signs of renal insufficiency in six patients with occupational medicamentosa-like dermatitis due to TCE. To study mechanisms of renal toxicity of TCE, the authors administer trichloroethylene in Freund's complete adjuvant to Balb/c mice . The sensitized animals exhibit ultrastructural damage and loss of podocytes, plus increased plasma BUN and creatinine. The involvement of mTOR/cathepsin-L hyperactivity in TCE-induced renal damage is demonstrated by a series of rapamycin treatments and histopathological analyses . Nephrology patients develop extrarenal abnormalities due to uremia, vitamin D deficiency, electrolyte imbalance and other complications. Hemodialysis brings additional risks—access complications and use of anticoagulants. As a result, dialysis patients exhibit systemic vascular damage and inflammation which erodes the glycocalyx layer. Kusuzawa et al. present a single-center study featuring whether syndican-1, a polysaccharide component of glycocalyx, can be used as a marker of endothelial injury in patients on dialysis. The authors analyze syndican-1 level in relation to the procedure settings, fluid removal, and use of anticoagulants and conclude that assessment of syndican-1 can be used in the selection of treatment and limiting endothelial injury .Various aspects of kidney and glomerular damage are the focus of a review and two scientific studies published in this Research Topic. Hyperuricaemia which occurs due to alterations in urate production and excretion was the focus of a review article (Interactions between podocytes, mesangial cells, and glomerular endothelial cells in glomerular diseases demonstrates the need for a better understanding of mechanisms that contribute to glomerular function and damage. This collection of ten articles demonstrates that glomerular diseases are diverse and include different glomerular cell types and their interactions. Therefore, there is great need for a better understanding of these glomerular cell types in diseases to allow for the development of effective therapies to combat glomerular diseases.The Research Topic JI conceived the content and drafted the manuscript. JI, XZ, AE, and TP revised and approved the final manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases DK126452 and DK123266.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


However, this method is not in real time or continuous, limits accessibility to the electrogram, and results in missed diagnosis.Postoperative arrhythmias are most often diagnosed through analysis of electrograms displayed on the bedside monitor from surface electrodes. However, rhythm discrimination can be difficult or impossible when interpreting surface electrograms owing to the inability to distinguish the atrial and ventricular signals. In particular, on the surface electrogram, much smaller atrial signals may not be visible. Owing to this diagnostic challenge, American Heart Association (AHA) practice standards recommend using the atrial electrogram for more accurate rhythm identification.Recently, a novel device, the AtriAmp , was developed to improve postoperative rhythm identification by providing continuous real-time display of the atrial electrogram on the bedside monitor. At the same time, if pacing is required, the AtriAmp can connect to a temporary pacemaker to allow atrial monitoring and pacing using a temporary pacemaker.We describe the first-in-human use of the AtriAmp for continuous real-time monitoring of the atrial electrogram for more accurate rhythm identification in a postoperative pediatric patient.The AtriAmp, a single-use device, can provide continuous atrial electrogram monitoring on the bedside monitors. To do this, the AtriAmp A connectIf atrial pacing (or sensing from the pacemaker) is required, the AtriAmp may be connected to a temporary pacemaker using a separately provided cable D. If pacA term female infant was noted to have progressive fussiness and difficulty feeding over the first month of life. As the infant was from the plain clothes community, the first medical evaluation was at 1 month of age by their midwife. A murmur prompted cardiac evaluation, which discovered a large perimembranous ventricular septal defect and hypoplastic arch. Afterload reduction and diuretics were trialed but at 6 weeks of age, with continued weight loss and poor feeding, the infant presented for elective repair.The infant weighed 2.6 kg at ventricular septal defect closure, aortic isthmus resection, and arch augmentation with an end-to-side anastomosis of the descending to ascending aorta. During the procedure, atrial and ventricular temporary epicardial pacing wires  were placed in a bipolar arrangement on the atrial or ventricular myocardium. The infant was transferred to the pediatric intensive care unit (ICU) after the surgery with no complications and with no residual disease.Once in the ICU, the bedside monitor was set to display 2 electrograms, a surface lead and the V lead, to allow display of both the atrial electrogram from the AtriAmp on the V lead and the surface electrogram. The AtriAmp was the attached to patient’s atrial epicardial wires and the V lead from the bedside monitor as shown in During the ICU admission, while the atrial epicardial wires were in place, the AtriAmp displayed the atrial electrogram continuously on the bedside monitor and was visible though the remote telemetry. The accurate assessment of atrial activation assisted with the identification of sinus rhythm, sinus tachycardia, and ventricular arrhythmias in this patient. The rapid confirmation of sinus rhythm through easy and accurate identification of the atrial signals was also frequently helpful.The patient demonstrated occasional premature ventricular complexes and a few short runs of a wide complex rhythm. Overnight, using the surface leads, an episode of wide complex rhythm was tentatively diagnosed as either a supraventricular tachycardia with aberrancy or a ventricular arrhythmia. Review of the atrial electrogram confirmed a 7-beat run of ventricular tachycardia, as demonstrated in Premature ventricular complexes (PVCs) were also noted and could be confidently diagnosed with the simple and accurate identification of the atrial signals b.The identification of the ventricular arrhythmia, including the PVCs, resulted in additional diligence with monitoring, but ultimately required no intervention. The arrhythmias decreased and subsided by discharge. The epicardial wires were removed on postoperative day 2. The patient continued routine postprocedure convalescence, though she continued to have slow weight gain and marginal feeding. She was discharged home on postoperative day 10.We describe the first-in-human use of the AtriAmp, a device that can allow continuous and real-time atrial electrogram monitoring using the bedside monitoring equipment. This device is the first device to provide continuous atrial electrogram monitoring while, if required, at the same time allow for atrial pacing using a temporary pacemaker.,Atrial electrogram monitoring has been used for more accurate rhythm identification for the last 40 years and is even recommended in the American Heart Association Practice Standards for postoperative ECG monitoring.Though this case report describes the first-in-human use of the AtriAmp in a single patient with ventricular arrhythmias, we have noted that the atrial electrogram has been especially useful for the confirmation of sinus tachycardia and the identification of junctional rhythms in subsequent patients. Given this, we expect this to be especially helpful for early identification and more accurate diagnoses of arrhythmias in the pediatric population in particular. At the time of this manuscript, the AtriAmp has not been used in the adult population, though we expect it will be especially helpful for rapid and accurate atrial fibrillation diagnosis.•Postoperative arrhythmias are common after cardiac surgery. These arrhythmias may increase morbidity and mortality and lengthen hospital stay.•Current technology, using surface electrograms, is inadequate for accurate arrhythmia identification and diagnoses.•The atrial electrogram allows for greater accuracy than surface electrograms and is recommended for rhythm identification by the American Heart Association.•This case report describes the first-in-human usage of the AtriAmp, a device to allow continuous real-time display of the atrial electrogram from atrial epicardial wires after heart surgery.We describe the first-in-human use of the AtriAmp, which allows continuous postoperative atrial electrogram monitoring after cardiac surgery. The improved ability to identify the atrial electrogram resulted in more accurate diagnosis in this pediatric patient.


The composition of microbiota and the gut-brain axis is increasingly considered a factor in the development of various pathological conditions. The etiology of multiple sclerosis (MS), a chronic autoimmune disease affecting the CNS, is complex and interactions within the gut-brain axis may be relevant in the development and the course of MS. In this article, we focus on the relationship between gut microbiota and the pathophysiology of MS. We review the contribution of germ-free mouse studies to our understanding of MS pathology and its implications for treatment strategies to modulate the microbiome in MS. This summary highlights the need for a better understanding of the role of the microbiota in patients’ responses to disease-modifying drugs in MS and disease activity overall. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS). The disease leads to the formation of inflammatory lesions in the CNS, in which myelin sheaths break down and demyelinated axons are damaged. This leads to neurological symptoms such as impairment of motor functions, sensitivity, balance, vision, and sphincters, but also fatigue, depression, and cognitive changes.This disease has a complex etiology with genetic and environmental factors playing a significant role. Studies in identical twins show that the genetic influence on the disease risk is only about 30%  with humOver the past decade, there has been a growing recognition of the role of microbiota in the regulation of the so-called gut-brain axis in the maintenance of homeostasis. The gut-brain axis as a bidirectional signaling communication network is involved in the regulation of neural, hormonal, and immunological pathways and its dysfunction is implicated in various inflammatory, psychiatric, and neurodegenerative disorders (with MS being one of them).Microorganisms that colonize the human gastrointestinal tract (GIT) are symbiotic under steady state conditions and contribute to the homeostasis of the human host. The term microbiome refers to the collective genetic material contained in these microorganisms. Interestingly, even though there is a remarkable variation in the diversity and abundance in the microbiota that occupy different habitats, metabolic pathways remain stable within a healthy population . The composition and diversity of the microbiota vary greatly according to their location in the GIT and also vary in composition according to the age of the individual . SeveralThe microbiota also plays a fundamental role in the functioning of host innate and adaptive immune responses. There is evidence that suggests that the human immune system modulates itself in order to maintain the balance between symbiotic, commensal, and pathological microorganisms. This relationship between the host immune system and microbiota induces protective mechanisms against pathogens and is involved in the regulatory response towards the tolerance of harmless antigens. Alterations of the host microbiota due to changes in diet and lifestyle, antibiotic overuse, and the eradication of helminth nematodes, especially in developed countries, may have predisposed individuals to flawed microbiota in terms of their immune response . This phConclusions of studies of microbiome profiling, using methods such as 16S rRNA and metagenomic shotgun sequencing technologies, suggest that changes in the relative composition of intestinal microbiota, known as intestinal or gut dysbiosis, play a role in several autoimmune diseases. Evidence suggests that intestinal microbiota modulate the immune system and affect the neural and endocrine systems of the gut .Germ-free mice studies confirm the role of gut microbiota in the healthy functioning and development of the immune system . CommensToll-like receptors (TLR) and related microbe associated molecular pattern recognition (MAMP) ligands are important for B-cell regulation. Microbial metabolites such as short-chain fatty acids (SCFAs) and adenosine triphosphate (ATP) have shown to be significant for mucosal antibody production. SCFAs exert an anti-inflammatory effect via the inhibition of histone deacetylases (HDACs) on Treg and microglia. This process is mediated by G-protein-coupled receptors (GPCR) primarily expressed by epithelial cells and some myeloid cells. Moreover, SCFAs are integrated into cellular metabolism following their conversion to acetyl-CoA, and this greatly affects the cellular metabolism in T and B cells .A communication network between intestinal epithelial cells (IECs), the gut microbiota, and immune cells regulates inflammation through effectors from the immune system (TLRs) and microbes [lipopolysaccharide (LPS)] and maintains the intricate balance between them. IECs, with their tight junctions, create a barrier between host immune cells and gut microbiota and are important in distinguishing between beneficial commensal bacteria and pathogenic bacteria. This network maintains homeostasis at the mucosal surface. A breach in this barrier causes increased gut permeability and allows for the systemic dissemination of the bacteria and/or their products. This so-called “leaky gut syndrome” is associated with several autoimmune and inflammatory diseases .Complex interactions within the gut-brain axis may be relevant to the pathophysiology of neurological disorders, autoimmune disorders, and multiple sclerosis specifically. Clinical symptoms of multiple sclerosis (MS) typically appear between the 20th and 30th years of life; however, the disease starts years before as is documented by initial magnetic resonance imaging (MRI) of the brain. The diagnosis of MS is based on a clinical event that leads to a discovery of demyelinating lesions of different ages in the brain and/or spinal cord through MRI (dissemination in time and space) and evidence of immune activation specific to the cerebrospinal fluid (CSF) compartment  .The crucial role of activated myelin antigen-specific T cells in the pathogenesis of MS has been evidenced by experimental autoimmune encephalomyelitis (EAE), the animal model of MS . The cauOur understanding of the pathophysiology and the development of treatment options for MS has long been influenced by the T cell-dependent EAE model. The efficacy of anti-CD20 treatment has demonstrated the definite role of B cells, which are believed to activate T cells, produce pro-inflammatory cytokines, function as antigen-presenting cells, and produce antibodies. Intrathecally produced antibodies detectable as oligoclonal bands have been used since the 1960s to support the diagnosis of MS. The recent work of Bjornevik et al. highlighted a long-suspected connection between EBV and the development of MS . MultiplAcute attacks of MS are treated with high doses of corticosteroids, but the overall prognosis can be changed only by early treatment with disease-modifying drugs that now includes a number of options: interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, fingolimod, cladribine, natalizumab, ocrelizumab, alemtuzumab, ofatumumab, siponimod, and non-specific immunosuppressive drugs. It is currently not known what individual characteristics of patients determine the optimal treatment option and whether the microbiome plays a role in the efficacy of treatment in MS. The influence of the microbiome could explain the unidentified environmental risk factors in the development of MS, and it may be involved in influencing the immune system and the course of the disease. It is now well known that pathological changes in the intestinal microbiota (dysbiosis) can affect inflammation in the CNS . In patients with MS, it was found that the composition of their microbiota was relatively different from that of healthy individuals . Most imThe animal model of MS ) is induced in susceptible animals by the adoptive transfer or active induction of autoreactive myelin-specific lymphocytes . After tThe relapsing-remitting model of spontaneously developing experimental autoimmune EAE has been used to demonstrate the involvement of microbiota in disease development . The immune system of mice that are kept in a germ-free environment behaves differently from that of mice who are exposed to common microbes found in their environment. The transmission of intestinal microbiota from MS patients leads to the induction of spontaneous EAE in mice. The study of microbiota samples from twins, where one is healthy and the other has MS, reveales that the influence of the genetic background and the environmental differences in childhood development is minimal . The colIt has not yet been possible to characterize an accurate description of dysbiosis in MS; as such, the possibility of the therapeutic application of one or more species of bacteria does not look very promising . The difIt is, therefore, necessary to systematically collect a large number of samples from a diverse set of patients , and to establish conclusive evidence of correlations between intestinal dysbiosis and MS.The observation of an increase in allergic and autoimmune diseases in industrialized nations in recent decades has led to the development of a “hygienic hypothesis” that claims that this is the result of an environment that is too clean to properly stimulate, nurture, and regulate the immune system. However, it now seems that some revision of this hypothesis in connection with autoimmune diseases is needed . EnvironAs early as 1996, a prerequisite study of the enabling interactions between the intestinal microbiota and the CNS was published, i.e., increased intestinal permeability . The conThe existing human studies of microbiome composition have limitations and have not yet identified clear patterns of altered gut microbiota in people with MS. Nonetheless, there is sufficient evidence for the role of microbiome changes in the pathophysiology of autoimmune diseases, including MS; so much so that it has been identified as a potential therapeutic target. The immunomodulatory properties of both antibiotics and probiotics and their presumed beneficial effects on autoimmune diseases were studied both in the experimental animal model (EAE) and MS.It was observed that a cocktail of broad-spectrum antibiotics impaired the development of EAE  and modiSome studies report a positive effect of probiotics, whereas recent meta-analysis in EAE is not very encouraging . ProbiotA recent meta-analysis in patients with relapsing-remitting MS found four trials with 213 patients (106 with intervention) and concluded that there was an improvement in disability, depression, and general health in patients using probiotics . This shT. crassiceps, S. mansoni, T. pseudospiralis, T. spiralis, and F. hepatica. All these infections were shown to potently modulate EAE in association with a Th2-type response that is low in TNF-α, IFN-γ, and IL-17A. Some studies used helminth-derived products to mimic the effect of the whole infection with the same result. The potency of this treatment was superior even to that observed for dexamethasone [There exists a negative correlation between the geographical distribution of autoimmune diseases and helminth infections. Helminths may be important environmental regulators for tolerance induction against autoimmunity, in accordance with the original hygiene hypothesis proposed in 1989. Helminths regulate inflammation to their benefit, including strong Th2-biased responses, as well as the induction of many regulatory cells such as alternatively activated macrophages (AAMs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Tregs), B-regulatory (Bregs), and tolerogenic dendritic cells (iDCs) . It is hethasone .T. suis ova every two weeks for three months. MRI enhancing lesion numbers fell around 70% at the end of the treatment but returned to baseline values two months after treatment discontinuation [In MS patients, the observation that autoimmune downregulation occurs secondary to parasite infections (fewer and milder relapses and less MRI activity) has been explained by the induction of regulatory T cells secreting suppressive cytokines IL-10 and TGF-b, as well as CD4þ, CD25þ, and FoxP3þ T cells displaying significant suppressive function . Followiinuation . HoweverA safer and more reliable alternative to live infection would be to identify and use the specific immune-modulatory molecules produced by helminth parasites . This woClostridium difficile infection and inflammatory bowel syndrome due to its ability to restore gut microbiota diversity [Case reports of the miraculous effects of FMT in MS patients can be found in the scientific literature. Fecal microbiota transplantation (FMT) appears to be an effective treatment for the iversity . One stuiversity ,55. RebuIn animal studies, FMT led to a reduced abundance of the Akkermansia genus (in phylum Verrucomicrobia) and an elevated abundance of the Prevotella genus (in phylum Bacteroidetes) in gut microbiota, which recalls the findings of decreased gut Akkermansia after probiotic intervention  and incrA detailed study including metagenomics in a single MS patient after FMT showed not only an improved composition of gut microbiota with a high sustained production of SCFAs, improved gait, and no relapses during a year of follow up but also a sustained increase in the serum levels of brain-derived neurotrophic factor (BDNF), which is known to be low in MS. BDNF levels correlated with the production of SCFA in the gut. One possible mechanism for increased BDNF is an increased abundance of butyrate-producers after FMT, because BDNF-production is inhibited by the immune systemic inflammatory state and butyrate has anti-inflammatory activities . Phase 1The crucial step in understanding the role of microbiota in the course of MS is to understand its role in the onset and the early stages of the disease and its changes throughout the treatment . The effect of corticotherapy commonly used to treat MS relapses on the microbiome has not been investigated in either the short or long term. Though there is some knowledge on the effect of first-line therapies (interferon beta and glatiramer acetate) on the microbiome of MS patients, the role of the microbiome in first-line treatment failure is still unknown. There is a lack of knowledge about the long-term effects of high efficacy therapeutic options  on the gut microbiota during the treatment process and how it correlates with treatment effectiveness; although some studies have been announced . Studies in the field of gut microbiota may bring a new quality to the overall management of MS by either adding recommendations for MS patients in terms of treatment strategies or by influencing their microbiota completely in addition to increasing the armamentarium of drugs being developed to modulate the immune response in MS. Unfortunately, these drugs are not 100% effective in all patients, and research in new areas, such as the modulation of gut microbiota composition, is warranted.