Non-healthy Individuals Research Articles

Gut Microbiome Wellness Index 2 enhances health status prediction from gut microbiome taxonomic profiles

Recent advancements in translational gut microbiome research have revealed its crucial role in shaping predictive healthcare applications. Herein, we introduce the Gut Microbiome Wellness Index 2 (GMWI2), an enhanced version of our original GMWI prototype, designed as a standardized disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involves pooling existing 8069 stool shotgun metagenomes from 54 published studies across a global demographic landscape (spanning 26 countries and six continents) to identify gut taxonomic signals linked to disease presence or absence. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the “reject option”). This performance exceeds that of the original GMWI model and traditional species-level α-diversity indices, indicating a more robust gut microbiome signature for differentiating between healthy and non-healthy phenotypes across multiple diseases. When assessed through inter-study validation and external validation cohorts, GMWI2 maintains an average accuracy of nearly 75%. Furthermore, by reevaluating previously published datasets, GMWI2 offers new insights into the effects of diet, antibiotic exposure, and fecal microbiota transplantation on gut health. Available as an open-source command-line tool, GMWI2 represents a timely, pivotal resource for evaluating health using an individual’s unique gut microbial composition.

Blood metabolites–based MCTarg for multi-cancer screening and clinical diagnosis.

e15028 Background: Multi-cancer early detection (MCED) tests have emerged as promising tools for reducing cancer-related healthcare costs and mortality. As metabolome is closely linked to the phenotype of bio-individual, metabolomics analysis enables the high throughput investigating of the pathophysiological conditions. Based on metabolomics and machine learning, we developed the Multiple Cancer Target (MCTarg) analysis for multiple cancer screening and diagnosis by a single blood draw. Methods: A total of 1153 individuals (172 healthy participants, 623 patients with lung cancer, gastric cancer, and colorectal cancer, and 358 these organ-related benign disease patients) were enrolled from three independent clinical sites in China. Plasma samples were collected and measured by mass spectrometry (MS)-based platforms (LC-MS polar and lipid). MCTarg was developed with three machine learning modules for three scenarios (community screening for non-healthy individuals, clinical diagnosis for classifying malignant and benign diseases, and tracing tumor of origin). Results: MCTarg exhibited an Area Under the Curve (AUC) of 0.96 with 92.82% sensitivity at 80% specificity to differentiate the non-healthy individuals from healthy controls, and an AUC of 0.86 with 75.41% sensitivity at 79.66% specificity in discriminating multi-cancer from benign diseases. Notably, the classification accuracy for distinguishing between malignant and benign conditions in the colorectal organ was reached 90.74%, with a sensitivity of 83.87% and a specificity of 100%. Furthermore, the overall accuracy for detecting the cancer origin reached 84.78% with an average sensitivity and specificity of 78.08% and 90.7%, respectively. Conclusions: The outstanding results indicated that blood-metabolites-based MCTarg is poised to be a cost-effective, precise, and versatile tool for diagnosing multi-cancer and discriminating tumor of origin. Its potential applications encompass health checkups and supplementary diagnostic scenarios. More deadly cancer types will be extended and the performance of MCTarg will be validated by prospective and population-scale cohorts with longitudinal follow-up.

Left atrial function in middle-aged men and women with and without paroxysmal atrial fibrillation: Data from the Akershus Cardiac Examination (ACE) 1950 study.

To assess left atrial (LA) function in individuals with known paroxysmal atrial fibrillation (AF) compared with healthy and nonhealthy individuals without atrial fibrillation. The Akershus Cardiac Examination 1950 Study included 3,706 individuals all born in 1950. LA strain assessment of reservoir (LASr), conduit (LAScd) and contractile (LASct) functions were performed in all participants by investigators blinded to clinical data. Participants with cardiovascular disease, obesity, diabetes, pulmonary or renal disease were defined as nonhealthy, and those without as healthy. Patients with paroxysmal AF were identified through medical history and ECG documentation. LA strain assessment was feasible in 3,229 (87%) of the participants (50% women). The healthy group (n=758) had significantly higher LASr and LAScd than the nonhealthy (n=2,376), but LASct was similar between the groups. Participants with paroxysmal AF had significantly lower values of all strain parameters than the other groups. Multivariable logistic regression showed a significantly reduced probability of having AF per standard deviation increase in LASr and LASct. A nonlinear restricted cubic spline model fitted better with the association of LASr with paroxysmal AF than the linear model, and LA strain values below the population mean associated with an increased probability of having AF, but for values above the population mean no such association was present. Compared to participants without AF, those with known paroxysmal AF had significantly lower values of all LA strain parameters during sinus rhythm. Lower values of LA strain were associated with a significantly increased probability of having AF.

Neck Computed Tomography Measurements Associated With Cardiovascular Risk Factors.

Introduction Neck adiposity has been related to cardiovascular risk in healthy and nonhealthy individuals. Our objective was to evaluate the utility of anatomic neck measurements extracted from computed tomography (CT) examinations as a predictor of cardiovascular disease and its risk factors. Methods We investigated patients who had a CT neck examination with intravenous contrast performed at two hospitals between 2013 and 2020. Patients with a neck malignancy, prior neck surgery, age <18 years, incomplete demographic information, and inadequate image quality were excluded. We performed 18 separate measurements of neck anatomy which were correlated with cardiovascular risk factors and disease, as well as relevant lab values and medications. All multivariable linear regressions were controlled for gender and BMI. Associations with p<0.05 were considered statistically significant. The measurements were then used to predict hypertension using random forest, a non-linear prediction algorithm. Results Approximately 20,000 neck CT examinations with contrast were performed between 2013-2020. After applying the inclusion criteria, 458 patients remained in the study population. Eight measurements (all of which include a component of neck adiposity) showed a statistically significant association between anatomic measurements and cardiovascular risk factors. The risk factor most often associated with increases in CT measurements was type 2 diabetes. Accordingly, patients on insulin treatment had a significantly higher average for all eight measurements. Significant measurement increases were also found in those previously diagnosed with hyperlipidemia and in those being treated with hypertension medications. The area under the receiver operating characteristic (AUROC) value of the random forest prediction algorithm was 0.68, meaning our measurements were a good predictor of hypertensive disease status. Conclusion Adipose tissue measurements extracted from CT examinations of the neck are associated with cardiovascular risk factors including hypertension, diabetes, and hyperlipidemia. Machine learning models of anatomic neck measurements can potentially identify patients at risk for cardiovascular disease.

Clinical and genetic definition of serum bilirubin levels for the diagnosis of Gilbert syndrome and hypobilirubinemia.

Gilbert syndrome (GS) is genotypically predetermined by UGT1A1*28 homozygosity in Europeans and is phenotypically defined by hyperbilirubinemia using total bilirubin (TB) cutoff ≥1mg/dL (17μmol/L). The prevalence of illnesses associated with GS and hypobilirubinemia has never been studied prospectively. As TB varies with UGT1A1*28 genotyping, sex, and age, we propose stratified definitions of TB reference intervals and report the prevalence of illnesses and adjusted 15 years survival. UK Biobank with apparently healthy liver participants (middle-aged, n=138,125) were analyzed after the exclusion of of nonhealthy individuals. The stratified TB was classified as GS when TB >90th centile; <10th centile indicated hypobilirubinemia, and between the 10th and 90th centile was normobilirubinemia. We compared the prevalence and survival rates of 54 illnesses using odds ratio (OR), logistic regression, and Cox models adjusted for confounders, and causality by Mendelian randomizations. In women, we identified 10% (7,741/76,809) of GS versus 3.7% (2,819/76,809) using the historical cutoff of ≥1mg/dL (P<0.0001). When GS and hypobilirubinemia participants were compared with normobilirubinemia, after adjustment and Mendelian randomizations, only cholelithiasis prevalence was significantly higher (OR=1.50; 95% CI [1.3-1.7], P=0.001) in men with GS compared with normobilirubinemia and in causal association with bilirubin (P=0.04). No adjusted survival was significantly associated with GS or hypobilirubinemia. In middle-aged Europeans, the stratified TB demonstrates a careless GS underestimation in women when using the standard unisex 1mg/dL cutoff. The prevalence of illnesses is different in GS and hypobilirubinemia as well as survivals before adjusting for confounding factors. With the exception of cholelithiasis in men, these differences were no more significant after adjustment and Mendelian randomization.

Comparison of microbiological profile of enterotoxigenic Bacteroides fragilis (ETBF) isolates from subjects with colorectal cancer (CRC) or intestinal pre-cancerous lesions versus healthy individuals and evaluation of environmental factors involved in intestinal dysbiosis

ObjectiveThe aim of this study was to analyze enterotoxigenic Bacteroides fragilis (ETBF) isolates from colorectal biopsies of subjects with a histological analysis positive for colorectal cancer (CRC), pre-cancerous lesions (pre-CRC) or with a healthy intestinal tissue and to evaluate the environmental factors that may not only concur to CRC development but may also affect gut microbiota composition. MethodsETBF isolates were typed using the ERIC-PCR method, while PCR assays were performed to investigate the bft alleles, the B. fragilis pathogenicity island (BFPAI) region and the cepA, cfiA and cfxA genes. Susceptibility to antibiotics was tested using the agar dilution method. Environmental factors that could play a role in promoting intestinal dysbiosis were evaluated throughout a questionnaire administered to the subjects enrolled. ResultsSix different ERIC-PCR types were identified. The type denominated C in this study was the most prevalent, in particular among the biopsies of subjects with pre-CRC, while an isolate belonging to a different type, denominated F, was detected in a biopsy from a subject with CRC. All the ETBF isolates from pre-CRC or CRC subjects had a B. fragilis pathogenicity island (BFPAI) region pattern I, while those from healthy individuals showed also different patterns. Furthermore, 71% of isolates from subjects with pre-CRC or CRC were resistant to two or more classes of antibiotics vs 43% of isolates from healthy individuals. The B. fragilis toxin BFT1 was the most frequently detected in this study, confirming the constant circulation of this isoform strains in Italy. Interestingly, BFT1 was found in 86% of the ETBF isolates from patients with CRC or pre-CRC, while the BFT2 was prevalent among the ETBF isolates from healthy subjects. No substantial differences based on sex, age, tobacco and alcohol consumption were observed between healthy and non-healthy individuals included in this study, while most of the subjects with CRC or pre-CRC lesions were subjected to pharmacological therapy (71%) and showed a body mass index (BMI) that falls within the overweight range (86%). ConclusionsOur data suggest that some types of ETBF seem to better adapt and colonize the human gut and that the selective pressure exerted by factors related to lifestyle, such as pharmacological therapy and weight, could facilitate their persistence in the gut and their possible involvement in CRC development.

Normal values of left atrial strain in 62–65 year old men and women from the general population

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority Background Left atrial (LA) function is divided in a reservoir, a conduit and a contractile phase. LA reservoir and contractile function can be quantified through echocardiographic speckle tracking strain analysis and provide prognostic information in cardiovascular disease. Normal values are still not fully established for all age groups. Purpose To provide normal values of LA reservoir (LASr) and contractile (LASct) strain in men and women in their sixties. Methods We included 3,706 men and women, all born in 1950, from the general population in a prospective observational study. Study inclusion and baseline examination including echocardiorgraphy took place between 2012 and 2015. The echocardiographic images were assessed for LA strain analysis, and only participants with sinus rhythm during echocardiography, good image quality without LA foreshortening, and frame rates &amp;gt; 40/second were included. We further defined a healthy group without cardiovascular, cerebrovascular, pulmonary or renal disease. Values of LASr and LASct are presented as median and interquartile range (IQR), and the lower limits of normality (LLN) for LASr and LASct were defined as the 2,5th percentile value in the healthy group. We used Mann Whitney U-test to compare groups. Results Of 3,229 participants with available LA strain analyses, median age was 63.9 years and 50.0% were women. Healthy individuals (n=758) had a median LASr of 35.5% (IQR 29.6%-42.2%), which was significantly higher than the LASr of 33.1% (IQR 27.9%-39.4%) in non-healthy individuals (p&amp;lt;0.001). LASct was similar between the healthy and non-healthy individuals. Men and women of the healthy group had similar measures of LASr and LASct. The LLN of LASr was 21.9%, whereas LASct had a LLN of 9.0%, both similar for males and females. Conclusion We present normal values and limits of normality of LASr and LASct, similar between men and women, in 758 healthy individuals aged 62–65. We found LASr to be significantly higher in healthy compared to non-healthy individuals, whereas LASct was similar between the groups.

Estimating the prevalence of chronic kidney disease while accounting for nonrandom testing with inverse probability weighting

Chronic kidney disease (CKD) prevalence estimation is central to guiding the medical community and policymakers on where to focus prevention and disease management strategies. Population sources make the estimation of CKD prevalence challenging. In screening cohort studies, healthy individuals are more likely to participate than nonhealthy individuals, which may lead to the underestimation of CKD prevalence. In routine care cohorts, persons undergoing testing for creatinine to estimate glomerular filtration rate (eGFR) and albuminuria may be sicker and with indication for the testing (i.e., with diabetes or hypertension), which may lead to the overestimation of CKD prevalence.

References Values of Soluble α-Klotho Serum Levels Using an Enzyme-Linked Immunosorbent Assay in Healthy Adults Aged 18-85 Years.

α-Klotho protein is a powerful predictor of the aging process and lifespan. Although lowered circulating soluble α-Klotho levels have been observed in aged non-healthy individuals, no specific reference values across a wide range of ages and sex using an enzyme-linked immunosorbent assay (ELISA) are available for larger cohorts of healthy individuals. The present analytical cross-sectional study was aimed to establish the reference values of soluble α-Klotho serum levels in healthy adults by age and sex groups. A total of 346 (59% women) healthy individuals aged from 18 to 85 years were recruited. Subjects were divided by sex and age as: (i) young (18–34.9 years), (ii) middle-aged (35–54.9 years), and (iii) senior (55–85 years) individuals. The soluble α-Klotho levels were measured in serum using ELISA. Senior adults were the age-group that presented the lowest soluble α-Klotho serum levels (p < 0.01), with age showing a negative association with soluble α-Klotho serum levels (p < 0.001). No differences between sexes were observed. Therefore, soluble α-Klotho levels were especially decreased—regardless of sex—in our cohort of healthy individuals because of the physiological decline derived from the aging process. We recommend routine assessments of soluble α-Klotho levels using ELISA as a simple and cheap detectable marker of aging that improves quality of life in the elderly.

Proposal of a health gut microbiome index based on a meta-analysis of Korean and global population datasets.

The disruption of the human gut microbiota has been linked to host health conditions, including various diseases. However, no reliable index for measuring and predicting a healthy microbiome is currently available. Here, the sequencing data of 1,663 Koreans were obtained from three independent studies. Furthermore, we pooled 3,490 samples from public databases and analyzed a total of 5,153 fecal samples. First, we analyzed Korean gut microbiome covariates to determine the influence of lifestyle on variation in the gut microbiota. Next, patterns of microbiota variations across geographical locations and disease statuses were confirmed using a global cohort and di-sease data. Based on comprehensive comparative analysis, we were able to define three enterotypes among Korean cohorts, namely, Prevotella type, Bacteroides type, and outlier type. By a thorough categorization of dysbiosis and the evaluation of microbial characteristics using multiple datasets, we identified a wide spectrum of accuracy levels in classifying health and disease states. Using the observed microbiome patterns, we devised an index named the gut microbiome index (GMI) that could consistently predict health conditions from human gut microbiome data. Compared to ecological metrics, the microbial marker index, and machine learning approaches, GMI distinguished between healthy and non-healthy individuals with a higher accuracy across various datasets. Thus, this study proposes a potential index to measure health status of gut microbiome that is verified from multiethnic data of various diseases, and we expect this model to facilitate further clinical application of gut microbiota data in future.

Frequency and Prognostic Value of ABO Blood Groups in Patients with Hypertension, Obesity, Diabetes Mellitus, and Anemia in Local Population of Al-Najaf City/ Iraq

This study was designed to investigate the distribution of ABO blood types and the possible association of hypertension, diabetes mellitus, obesity, and anemia diseases with ABO types. A total of 535 individuals 277 (51.77% males and 258 (48.22% females) were participating in the present study. Among them, 389 healthy subjects (187 (48.07% males and 202 (51.92% females) as well as 146 patients 90 (61.60%) males and 56 (38.40% females), 67 (37.85 % had hypertension, 51 (28.81%) had DM, 29 (16.38% had obesity and 30 (16.94%) subjects had anemia, the participants were attending hospitals, clinics, and laboratories. The demographic and clinical details, including ABO blood groups, blood glucose, blood pressure, blood hemoglobin as well as height and weight were obtained for both groups. Data analysis was done using the Chi-square test for comparing data. Based on the results, O blood type was the most common group with a percentage of (43.18% and 47.26%) followed by A type (25.44% and 26.02%) then B (22.87% and 13.01%), and AB (8.48% and 13.69%) respectively for healthy and non-healthy individuals. Hypertension and diabetes mellitus diseases were the greatest percentage (37.85% and 28.81%) respectively comparing with obesity (16.38%) and anemia (16.94%). The present study indicated that individuals of blood group O and A (52.48% and 23.75%, respectively) were more susceptible to diseases as compared with patients of blood group B (12.70%) and AB (11.04%). Our results suggested that the relative risk for hypertensive and diabetic patients was found to be higher in blood group AB (45% and 35% respectively) and lower in blood group O (36.84% and 25.26% respectively); high incidence of obesity was found in type O blood (24.21%) compared to other ABO types, while anemia was prone for patients with A blood group (20.93%). The results showed no association between ABO blood groups with hypertension, diabetes mellitus, obesity, and anemia diseases.

Референсные интервалы параметров ротационной тромбоэластометрии у беременных и родильниц: одноцентровое рандомизированное исследование

Введение: В последнее время стали востребованы интегральные тесты оценки системы гемостаза у женщин во время беременности, а также во время акушерских операций, связанных с кровотечением. В нашей стране отсутствуют работы по определению популяционных норм ротационной тромбоэластометрии (РОТЕМ) у беременных, рожениц и родильниц. Цель исследования: определить пределы референсных интервалов показателей РОТЕМ во время физиологически протекающей беременности и в раннем послеродовом периоде и провести корреляционный анализ со стандартными показателями коагулограммы. Материалы и методы: Обследовано 229 женщин Красноярского края, которые были поделены на 5 групп: небеременные (контроль), беременные II и III триместров, женщины раннего послеродового периода после операции кесарева сечения и естественных родов. Все женщины были сопоставимы по возрасту, индексу массы тела, сопутствующей патологии. Референсные интервалы рассчитывали либо через среднее и стандартное отклонение (для нормального распределения), либо через медиану и 2,5 и 97,5% перцентили (для ненормального распределения). Результаты: В процессе исследования подтвердилось, что во время беременности и в раннем послеродовом периоде происходят изменения в системе гемостаза в сторону гиперкоагуляции. Показатели ROTЕM у женщин в III триместре беременности и раннем послеродовом периоде существенно отличаются от показателей небеременных в популяции. У женщин после родов вне зависимости от способа родоразрешения различий между параметрами ROTЕM не установлено. Корреляция между параметрами ROTЕM и традиционными лабораторными тестами коагуляции выявила взаимосвязь между амплитудой плотности сгустка в тесте FIBTEM и уровнем фибриногена по Клаусу. Заключение: Представлены референсные интервалы параметров РОТЕМ у женщин Красноярского края. Найдена корреляция между параметрами РОТЭМ и уровнем фибриногена. Background: Recently, integral tests for hemostasis assessment in pregnant women as well as during obstetric surgery associated with bleeding have become popular. In our country, there are no studies of population norms for rotational thromboelastometry (ROTEM) in pregnant women, parturients and puerperants. Objectives: to identify reference intervals limits for ROTEM parameters during physiological pregnancy and in early postpartum period and to carry out correlation analysis with standard coagulogram parameters. Patients/Methods: We examined 229 women in Krasnoyarsk region; they were divided into 5 groups: nonpregnant (control), pregnant women in II and III trimesters, women in early postpartum period after cesarean section and after vaginal delivery. All women were comparable in age, body mass index, and concomitant pathology. Reference intervals were calculated either as the mean and standard deviation (for normal distribution), or as the median and 2.5 and 97.5% percentiles (for abnormal distribution). Results: The study confirmed hemostasis hypercoagulation changes during pregnancy and in early postpartum period. ROTEM parameters in women in III trimester of pregnancy and in early postpartum period differ significantly from those in non-pregnant women. Differences between ROTEM parameters in puerperants, regardless of the delivery method, not found. The correlation between ROTEM parameters and traditional laboratory coagulation tests revealed a relationship between clot density amplitude in FIBTEM test and Klaus fi brinogen level. Conclusions: Reference intervals of ROTEM parameters in women of Krasnoyarsk region are presented. A correlation was found between ROTEM parameters and fibrinogen level

Determination of the Role of Fusobacterium Nucleatum in the Pathogenesis in and Out the Mouth.

One of the most important types of microorganisms in the oral cavity in both healthy and non-healthy individuals is Fusobacterium nucleatum. Although present as a normal resident in the oral cavity, this Gram-negative pathogen is dominant in periodontal disease and it is involved in many invasive infections in the population, acute and chronic inflammatory conditions, as well as many adverse events with a fatal outcome. To determine the role of F. nucleatum in the development of polymicrobial biofilms thus pathogenic changes in and out of the oral media. A systematic review of the literature concerning the determination and role of F. nucleatum through available clinical trials, literature reviews, original research and articles published electronically at Pub Med and Google Scholar. The presence of Fusobacterium nucleatum is commonly associated with the health status of individuals. These anaerobic bacteria plays a key role in oral pathological conditions and has been detected in many systemic disorders causing complex pathogenethic changes probably due to binding ability to various cells thus several virulence mechanisms. Most common diseases and conditions in the oral cavity associated with F.nucleatum are gingivitis (G), chronic periodontitis (CH), aggressive periodontitis (AgP), endo-periodental infections (E-P), chronic apical periodontitis (PCHA). The bacterium has been identified and detected in many systemic disorders such as coronary heart disease (CVD) pathological pregnancy (P); polycystic ovary syndrome (PCOS), high-risk pregnancy (HRP), colorectal cancer (CRC); pre-eclampsia (PE); rheumatoid arthritis (RA); osteoarthritis (OA).

Dissecting the Heterogeneous Population Genetic Structure of Candida albicans: Limitations and Constraints of the Multilocus Sequence Typing Scheme

Candida albicans is a fungal opportunistic pathogen of significant public health importance mainly due to the recent emergence of strains with increased aggressiveness and antifungal resistance. Here, we aimed to describe the epidemiological profiles and approximate the population structure of C. albicans by analyzing the C. albicans multilocus sequence typing (MLST) database (Calb-MLST-DB), which contains the largest publically available dataset for this species. Based on 4,318 database isolates, we confirmed the ubiquitous nature of C. albicans including a group of diploid sequence types (DSTs) obtained from Healthy individuals exclusively (taken as an indicator of lack of association with illnesses in its host), until isolates established from Non-Healthy individuals (potentially associated with pathogenic processes) and other DSTs reported in both types (Healthy and Non-Healthy). The highest number of reported DSTs was related to blood, oral and vaginal swabs (32.4, 20.5, and 13.8%, respectively). High genetic diversity was observed in the seven housekeeping genes included in the MLST scheme, with a diverse population structure (154 clonal complexes, CCs; and a high number of singletons, n = 1,074). Phylogenetic reconstruction on the concatenated alignment of these housekeeping genes for all the reported DSTs (n = 3,483) was partially concordant with the CC assignment, however, an absence of bootstrap threshold supported nodes or p-distance, and the lack of association with the other epidemiological variables, evidenced the limitations of the MLST scheme. Marked genetic admixture signals were identified by STRUCTURE, with the majority being attributable to recombination events according to the RDP program results, although another type of exchange event cannot be ruled out. Our results reaffirm the genetic diversity inherent in the genes used for the MLST scheme, which are associated with the chromosomal remodeling already proposed for C. albicans. This was also corroborated with an internal validation at a micro geographical scale. Despite these results are biased due to the unavailability of considering the broad global spectrum of C. albicans isolates around the world. This suggests that the strategy used to population type this pathogen should be reevaluated to improve epidemiological monitoring of its health impact.

Glycaemic variability-based classification of impaired glucose tolerance vs. type 2 diabetes using continuous glucose monitoring data

Many glycaemic variability (GV) indices extracted from continuous glucose monitoring systems data have been proposed for the characterisation of various aspects of glucose concentration profile dynamics in both healthy and non-healthy individuals. However, the inter-index correlations have made it difficult to reach a consensus regarding the best applications or a subset of indices for clinical scenarios, such as distinguishing subjects according to diabetes progression stage. Recently, a logistic regression-based method was used to address the basic problem of differentiating between healthy subjects and those affected by impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in a pool of 25 GV-based indices. Whereas healthy subjects were classified accurately, the distinction between patients with IGT and T2D remained critical. In the present work, by using a dataset of CGM time-series collected in 62 subjects, we developed a polynomial-kernel support vector machine-based approach and demonstrated the ability to distinguish between subjects affected by IGT and T2D based on a pool of 37 GV indices complemented by four basic parameters—age, sex, BMI, and waist circumference—with an accuracy of 87.1%.

Desenvolvimento de um protótipo de degrau para avaliação da capacidade física de indivíduos saudáveis e portadores de doenças respiratórias e cardíacas

Step tests are tests representing the daily physical activities that can classify different degrees of physical capacity of healthy and non-healthy individuals evaluating the causes that limit stress and exercise tolerance. Despite being widely employed in clinical practice, currently there are several variations in the implementation, testing standards, and step sizes which contribute to greater difficulty in assessment and interpretation of the examiner. Thus, the objective of this study was to produce a step with an integrated software system to facilitate the evaluation and interpretation of the data obtained during the test from the incremental step clocked externally. This exploratory study has developed a prototype step to assist physiotherapists in monitoring real-time test, sending the results to a computer program. The results may be stored and processed by the program in order that the events are reconhecid error. The step was built with an MDF wooden board; Rubber tube; Aluminum plate; Copper wiring with insulation coating; Screws; Angles; Wing nuts and rubber flooring. In addition, for communication with the computer, the integrated circuit needs to be manufactured and connected to a microcontroller, as well as a USB serial cable. The development of a single, standardized instrument, with the ability to identify errors and track the progress of the test, can be a first step towards a consensus and standardization of the test.

HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.

To determine whether serum levels of high mobility group box protein 1 (HMGB1) could differentiate malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Hyperacetylated and nonacetylated HMGB1 (together referred to as total HMGB1) were blindly measured in blood collected from malignant mesothelioma patients (n = 22), individuals with verified chronic asbestos exposure (n = 20), patients with benign pleural effusions (n = 13) or malignant pleural effusions not due to malignant mesothelioma (n = 25), and healthy controls (n = 20). Blood levels of previously proposed malignant mesothelioma biomarkers fibulin-3, mesothelin, and osteopontin were also measured in nonhealthy individuals. HMGB1 serum levels reliably distinguished malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Total HMGB1 was significantly higher in malignant mesothelioma patients and asbestos-exposed individuals compared with healthy controls. Hyperacetylated HMGB1 was significantly higher in malignant mesothelioma patients compared with asbestos-exposed individuals and healthy controls, and did not vary with tumor stage. At the cut-off value of 2.00 ng/mL, the sensitivity and specificity of serum hyperacetylated HMGB1 in differentiating malignant mesothelioma patients from asbestos-exposed individuals and healthy controls was 100%, outperforming other previously proposed biomarkers. Combining HMGB1 and fibulin-3 provided increased sensitivity and specificity in differentiating malignant mesothelioma patients from patients with cytologically benign or malignant non-mesothelioma pleural effusion. Our results are significant and clinically relevant as they provide the first biomarker of asbestos exposure and indicate that hyperacetylated HMGB1 is an accurate biomarker to differentiate malignant mesothelioma patients from individuals occupationally exposed to asbestos and unexposed controls. A trial to independently validate these findings will start soon. Clin Cancer Res; 22(12); 3087-96. ©2016 AACR.

DISCRIMINATION OF DENGUE DISEASE FROM HEALTHY BASED ON THE CHEMOMETRY OF 1H NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

Dengue is the most important human viral disease transmitted by arthropod vectors and over half of the world's populations live in areas at risk of infection. The severity of the infection depends on the form of the disease, which can be symptomatic or asymptomatic. Currently there is neither specific treatment nor vaccine to tackle this emerging disease. Metabolomics applied in this study, aimed to provide a global snapshot of all small-molecule metabolites in urine as biological sample of choice to more focused studies of metabolism to distinguish between healthy and dengue infected subjects. Fifty-two patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were recruited in this study. 1H-nuclear magnetic resonance (NMR) spectroscopy combined with multivariate analysis (MVA) methods such as principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA) were employed for statistical data exploration. The model score plot results showed that all three MVAs showed very good spatial distributions with clear clusters/grouping between healthy individuals and dengue infected individuals. Also, statistically, the PLS-DA and OPLS-DA models had high reproducibility and predictivity values, &gt; 0.5. In conclusion, this study established the potential of using a combination of 1H NMR spectroscopy and multivariate data analyses in differentiating healthy and non-healthy individuals, based on obtained score plots reflecting the metabolites pertubation, where spectral features contributing most to variation or separation are identified for further analysis.

Using a Multi-Locus Microsatellite Typing method improved phylogenetic distribution of Candida albicans isolates but failed to demonstrate association of some genotype with the commensal or clinical origin of the isolates

The dimorphic yeast Candida albicans is a component of the normal microflora at the mucosal surfaces of healthy individuals. It possesses an array of phenotypic properties considered as virulence traits that contribute to pathogenicity of the yeast in immuno-compromised patients. We addressed the question of the pathogenicity of lineages of C. albicans with regard to their genotype in three series of C. albicans isolates (a series of commensal isolates collected in healthy individuals, a group of bloodstream isolates and a group of non-bloodstream clinical isolates) using a Multi-Locus Microsatellite Typing (MLMT) approach based on the analysis of the polymorphism of 11 microsatellite loci. The MLMT analysis of the three series, corresponding to 174 C. albicans isolates, gave a 100% typability to the method, with a DP index of 0.999. The UPGMA analysis showed that the isolates segregated in eight phylogenetic groups. Interestingly, the clustering was comparable when using NJ and MS-tree algorithms and a good concordance index of the clustering was observed with MLST. All in all our data strongly indicated MLMT as a reliable tool for DNA-typing studies in C. albicans. Isolates from healthy and non-healthy individuals segregated at the same proportions into the eight phylogenetic groups, suggesting that isolates of different origin share the same overall pathogenicity. Surprisingly allelic frequencies at the HIS3 microsatellite differed significantly in commensal isolates (group A) from pooled groups B and C (clinical isolates), raising the possibility that some individual alleles at the HIS3 microsatellite may be associated with distinct pathogenic profiles in C. albicans.

STATISTICS OF EXTREME VARIATIONS OF RR HEARTBEAT INTERVALS

We performed an extreme value analysis of the heart beat fluctuations. We analyzed 24 h Holter ECG signals of 90 healthy individuals and 90 unhealthy individuals suffering of congestive heart failure (chf). Precisely, we studied separately the increment time series ΔRR corresponding to sleeping and daily activities. We found strong differences in the median return times of positive high threshold values of the increments for healthy and nonhealthy individuals, during both daily and sleeping activities. Our results suggest that healthy individuals have more often than chf patients the tendency to suddenly slow their heartbeat rate.