Adult Controls Research Articles

Cerebral blood flow and arterial transit time responses to exercise training in older adults

Brain vascular health worsens with age, as is made evident by resting grey matter cerebral blood flow (CBFGM) reductions and lengthening arterial transit time (ATTGM). Exercise training can improve aspects of brain health in older adults, yet its effects on CBFGM and ATTGM remain unclear. This randomised controlled trial assessed responses of CBFGM and ATTGM to a 26 week exercise intervention in 65 healthy older adults (control: n = 33, exercise: n = 32, aged 60–81 years), including whether changes in CBFGM or ATTGM were associated with cognitive function changes. Multiple-delay pseudo-continuous arterial spin labelling data were used to estimate resting global and regional CBFGM and ATTGM. Results showed no between-group differences in CBFGM or ATTGM following the intervention. However, exercise participants with the greatest cardiorespiratory gains (n = 17; ∆V̇O2peak >2 mL/kg/min) experienced global CBFGM reductions (-4.0 [-7.3, -0.8] mL/100 g/min). Cognitive functions did not change in either group and changes were not associated with changes in CBFGM or ATTGM. Our findings indicate that exercise training in older adults may induce global CBFGM reductions when high cardiorespiratory fitness gains are induced, but this does not appear to affect cognitive functions.

Ruta angustifolia Essential oil: Behavioral and Insecticidal Effects against Larvae and Adults of Tribolium castaneum.

The study aims to evaluate the behavioraland insecticidal effects ofRutaangustifoliaEO (RAEO) against larvae and adults of a major pest insectTribolium castaneum.RAEO exhibited a strong repellency against both adults and larvae where percentages as high as 74 and 72% of PR (Percentage of Repellency) were recorded respectively, at 0.47 µL/cm2 after 2h. Regarding the antifeedant bioassay, no feeding deterrence was recorded in adults while an increase in appetite was registered in larvae exhibiting -80% of FDI recorded at 0.2 µL/pellet. In terms of feeding preference, the response significantly depended on thedevelopmental stage(F=97.19, P<0.05) and larvae were attracted to treated pellets recording percentages of 84 and 73% of PI (Preference index) after 5 and 30 min at 0.05 µL/pellet; on the other hand, adults expressed a repulsive behavior at 0.2 µL/pellet with a PI of -81.1 (20min),and -69.2% (30 min). Regarding topical application toxicity, asignificant difference wasobserved between larvae and adults (p<0.05 F=174.56). The study promotes the use ofRAEO as a repellent andbioinsecticide for the control of larvae and adults of T. castaneum.

Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children.

Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines. We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay. Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups. We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.

Deep learning-based detection of affected body parts in Parkinson’s disease and freezing of gait using time-series imaging

We proposed a deep learning method using a convolutional neural network on time-series (TS) images to detect and differentiate affected body parts in people with Parkinson’s disease (PD) and freezing of gait (FOG) during 360° turning tasks. The 360° turning task was performed by 90 participants (60 people with PD [30 freezers and 30 nonfreezers] and 30 age-matched older adults (controls) at their preferred speed. The position and acceleration underwent preprocessing. The analysis was expanded from temporal to visual data using TS imaging methods. According to the PD vs. controls classification, the right lower third of the lateral shank (RTIB) on the least affected side (LAS) and the right calcaneus (RHEE) on the LAS were the most relevant body segments in the position and acceleration TS images. The RHEE marker exhibited the highest accuracy in the acceleration TS images. The identified markers for the classification of freezers vs. nonfreezers vs. controls were the left lateral humeral epicondyle (LELB) on the more affected side and the left posterior superior iliac spine (LPSI). The LPSI marker in the acceleration TS images displayed the highest accuracy. This approach could be a useful supplementary tool for determining PD severity and FOG.

INSECTICIDE SUSCEPTIBILITY IN TWO POPULATIONS OF Aedes aegypti L. (Diptera: Culicidae) FROM GUERRERO, MEXICO, AND RECOMMENDATIONS FOR THEIR MANAGEMENT

The Aedes aegypti L. mosquito is a vector of diseases such as classic and hemorrhagic dengue (DENV), chikungunya (CHIKV), Zika (ZIKV), yellow fever (YFV), and Mayaro (MAYV). In 2019 alone, in Latin America, there were 2.7 million cases and 1206 deaths. In Mexico, government programs for managing this pest include the elimination of larval habitats and chemical control of larvae and adults. The objective of this study was to evaluate the response of two larvae and adult populations of A. aegypti from the state of Guerrero, Mexico, under laboratory conditions, to insecticides with different modes of action and to make considerations for their management. In the bioassays, larvae showed susceptibility to permethrin, malathion, deltamethrin, and Bacillus thuringiensis var. israelensis; low resistance to Temephos and propoxur; as well as moderate resistance to Spinosad. Both adult populations showed resistance to permethrin and susceptibility to deltamethrin, while the Acapulco population showed resistance to alpha-cypermethrin. For larvae, Spinosad is suggested to be used in times of high incidence of dengue. During drought, it is advisable to include rotations of B. thuringiensis var. israelensis with organophosphates. For adults, the use of imidacloprid in combination with botanical insecticides is considered a rational alternative to rotations with organophosphates and pyrethroids.

Social Support for Thai Adults with Type 2 Diabetes: A Case-Control Study.

Non-communicable diseases, including type 2 diabetes (T2DM), are the number one cause of death in Thailand. With its well-known social networking and strong kinship, evidence of social support may be a potential of low-cost approach for T2DM self- management. Social support is quite important for T2DM prevention and control but such evidence in Thai setting is still limited. Therefore, we aimed to study social support and associated determinants for T2DM patients compared to non-diabetes people. An observational study with a case-control study design was conducted in Chiang Mai, Thailand, in 2019-2020. Using inclusion and exclusion criteria, a total of 300 participants: 150 cases, 150 controls were recruited. Participants were selected based on outcome status of having "T2DM". Cases were defined as newly diagnosed (diagnosis of T2DM within 6 months) adult Thai residents and community controls were non-diabetes participants from the same residential area of cases. Data were analyzed by STATA 17. Descriptive analysis compared the characteristics between case and control group. The relation between social support and T2DM was investigated using multivariable Robust regression analysis. About 96.7% of T2DM patients had good social support. T2DM had a significant association with social support in all models defined by potential confounders. Social support was significantly positively associated with having family mealtimes in model 2 and model 3 and increasing age in model 2. BMI and T2DM family history had significant negative association in model 2 and model 3. Social support of Thai T2DM patients is higher than control group. It can either be originated from a newly acquired peer groups network or from the positive social support by family. Future research should focus on behavioral intervention including family and peers to help them understand their role in life-style modification and management of such a prevalent chronic disease.

Caudate nucleus volume in medicated and unmedicated patients with early- and adult-onset schizophrenia

The caudate nucleus is a part of the striatum, and striatal hyperdopaminergia is considered central to the pathophysiology of schizophrenia. How caudate volume is affected in schizophrenia and what role antipsychotics play remains unclear. In early-onset schizophrenia (EOS), where psychosis emerges during a neurodevelopmentally critical phase, the caudate may exhibit a heightened vulnerability to the effects of antipsychotic medications. We hypothesized effects of both antipsychotic medication use and age of onset on caudate in schizophrenia. We included adult patients with EOS (n = 83) and adult-onset schizophrenia (AOS) (n = 246), adult healthy controls (HC, n = 774), adolescent patients with non-affective psychosis (n = 56) and adolescent HC (n = 97). We obtained T1-weighted MRI scans using a 1.5T Siemens scanner and General Electric 3T scanners. In our main analysis, we tested for main and interaction effects of diagnosis and current antipsychotic medication use on caudate volume. Adult patients with EOS (p < 0.001) and AOS (p = 0.002) had both larger caudate than HC. Age of onset (EOS/AOS) interacted with antipsychotic use (p = 0.004) which was associated with larger caudate in EOS (p < 0.001) but not in AOS (p = 0.654). Conversely, among medicated patients only, EOS had larger caudate than AOS (p < 0.001). No other subcortical structures showed differences between medicated EOS and AOS. Medicated adolescent patients with non-affective psychosis and medicated adult patients with EOS showed similar caudate volumes. The results may indicate a schizophrenia-related and a medication-induced caudate increase, the latter restricted to patients with EOS and possibly occurring already in adolescence shortly after disease onset.

Effect of ethanol leaf extract of Moringa oleifera on D-galactose induced changes in lipid profile of aged Wistar rats

Uncontrolled hyperlipidaemia is linked to some age-related diseases like obesity, diabetes mellitus, and cardiovascular diseases. To examine the blood lipid profile in wistar rats, this study employed D-galactose-induced aging as a model. The lipid profiles were analysed using standard methods. Thirty (30) male albino rats were randomly assigned into five (5) groups of six (6) rats each and fed with basal diets. Group 1 and 5 which served as the young and adult controls respectively received basal diet only while the others were administered D-galactose (150mg/kg) and Moringa oleifera extract (MOLE-200mg/kg and 400mg/kg) respectively for eight (8) weeks. At the end of the study rats were sacrificed and blood samples were collected. At week 0, the results of the total cholesterol concentrations (98.81 ± 6.43), TAG (69.15 ± 1.34), LDL-cholesterol (31.80 ± 4.10), VLDL-cholesterol (13.83 ± 0..27) and HDL-cholesterol (35.64 ± 2.81) in rats administered M. oleifera leaf extract, D-galactose and distilled water respectively showed no significant (P &gt; 0.05) difference across all the groups but at week 8 treatment with high dose of MOLE resulted in a significant (P ≤ 0.05) decrease in total serum cholesterol (112.45 ± 3.05), TAG (114.05 ± 5.47), LDL-cholesterol (19.66 ± 4.06) concentrations relative to the D-galactose only treated group. Conversely, HDL-cholesterol concentration was significantly increased (P ≤ 0.05) following treatment with both low (69.53 ± 1.94) and high dose (69.99 ± 2.64) of MOLE relative to the D-galactose (63.65 ± 2.54) treated group. These results suggest that Moringa oleifera leaf extract exerts an anti-hyperlipidaemic effect against D-galactose-induced toxicity and thus could confer protection against aging.

ANXA3 as a novel biomarker for sepsis diagnosis: Evidence from integrative WGCNA analysis

Sepsis is a dysregulated immune response to infection that comes with multiple organ dysfunction and high mortality. The management of sepsis relies heavily on early recognition and diagnosis, but current diagnostic methods have limitations in timeliness, sensitivity, and discriminability. This study aims to discover novel biomarkers for sepsis diagnosis. Four datasets from different regions were analyzed using weighted gene co-expression network analysis (WGCNA), and genes with high Gene Significance values across these datasets were overlapped. Finally, two genes, CD177 and ANXA3, were identified. ANXA3 was validated as a potential sepsis biomarker by checking multiple datasets and Receiver Operating Characteristic (ROC) Curve Analysis. Of note, ANXA3 could distinguish not only between adult and child sepsis patients and healthy controls, but also between septic shock and cardiogenic shock. Moreover, a murine sepsis model was established and the results showed that the transcription of ANXA3 in peripheral blood of septic mice was significantly higher than that of healthy controls, while Escherichia coli infection alone did not significantly increase the transcription level of this gene. Subsequent studies of sepsis in mice revealed that the predictive effect of Anxa3 on sepsis could be observed as early as 6 h post-modeling. Interestingly, ANXA3 expression was predominantly up-regulated in myeloid cells, up-regulated in spleen, down-regulated in lung, and not detected in liver after sepsis modeling. Taken together, this study provides a way for the discovery of biomarkers and finds that ANXA3 may be a novel diagnostic biomarker for sepsis.

Validation of EncephalApp Stroop Test for Diagnosing Minimal Hepatic Encephalopathy in the Romanian Population.

Minimal hepatic encephalopathy (MHE) represents the mildest form of hepatic encephalopathy. MHE has been associated with impairment of quality of life and job performance, and is a major cause of premature retiring in cirrhotic patients. However, MHE is usually overlooked by most physicians, due to its asymptomatic nature. We aim to present our experience with the EncephalApp Stroop Test for diagnosing MHE in cirrhotic patients. We also want to establish if Stroop test performance correlates with age, educational level, liver disease severity (as assessed by the MELD and Child-Pugh scores), duration of disease, previous episodes of overt hepatic encephalopathy, and other relevant clinical or laboratory parameters. A cross-sectional observational single-center study, in which 100 adult patients diagnosed with liver cirrhosis were evaluated for the presence of MHE by using the EncephalApp Stroop Test. In parallel, 45 healthy adult controls without liver cirrhosis were recruited and tested under the same conditions as the patients. There were no age-related differences between the two groups (p=0.6). Stroop test performance of the controls (143.1 ± 20.8 seconds) was significantly better than that of the patients (171.9 ± 33.3 seconds) (p<0.0001). Stroop test results correlated with the MELD (R=0.28, p=0.005) and Child-Pugh scores (R=0.2, p=0.04). There was a positive correlation between Stroop test results and age in patients (R=0.45, p<0.0001) and controls (R=0.75, p<0.0001). Stroop test performance was not influenced by the duration of liver disease (p=0.4) or prior episodes of overt hepatic encephalopathy (p=0.25). Gender and level of education did not have an impact on Stroop test results. Alcoholic liver disease, diabetes mellitus, hyperglycemia, anemia and hyponatremia were associated with poorer performances. EncephalApp Stroop Test proved to be a quick and simple method for diagnosing minimal hepatic encephalopathy in the hospital setting. Test performance was influenced primarily by age, but also by liver disease severity, anemia, hyponatremia and hyperglycemia.

Immunometabolic Chaos in Septic Shock.

Septic shock is associated with over 40% mortality. The immune response in septic shock is tightly regulated by cellular metabolism and transitions from early hyper-inflammation to later hypo-inflammation. Patients are susceptible to secondary infections during hypo-inflammation. The magnitude of the metabolic dysregulation and the effect of plasma metabolites on the circulating immune cells in septic shock are not reported. We hypothesized that the accumulated plasma metabolites affect the immune response in septic shock during hypo-inflammation. Our study took a unique approach. Using peripheral blood from adult septic shock patients and healthy controls, we studied: 1. Whole blood stimulation ± E. Coli lipopolysaccharide (LPS: endotoxin) to analyze plasma TNF protein, and 2. Plasma metabolomic profile by Metabolon. Inc. 3. We exposed peripheral blood mononuclear cells (PBMCs) from healthy controls to commercially available carbohydrate, amino acid, and fatty acid metabolites and studied the response to LPS. We report that: 1. The whole blood stimulation of the healthy control group showed a significantly upregulated TNF protein, while the septic shock group remained endotoxin tolerant, a biomarker for hypo-inflammation. 2. A significant accumulation of carbohydrate, amino acid, fatty acid, ceramide, sphingomyelin, and TCA cycle pathway metabolites in septic shock plasma. 3. In vitro exposure to five metabolites repressed while two metabolites upregulated the inflammatory response of PBMCs to LPS. We conclude that the endotoxin-tolerant phenotype of septic shock is associated with a simultaneous accumulation of plasma metabolites from multiple metabolic pathways, and these metabolites fundamentally influence the immune response profile of circulating cells.

Protocol for a clinically annotated biorepository of samples from Australian immune-compromised patients to investigate the host–microbiome interaction

IntroductionThe human gut microbiota has the potential to modulate the outcomes of several human diseases. This effect is likely to be mediated through interaction with the host immune system. This...

Recurrent pericarditis in older adults: Clinical and laboratory features and outcome.

Current guidelines for the diagnosis and treatment of pericarditis refer to the general adult population. Few and fragmentary data regarding recurrent pericarditis in older adults exist. Given the absence of specific data in scientific literature, we hypothesized that there might be clinical, laboratory and outcome differences between young adults and older adults affected by idiopathic recurrent pericarditis. We performed an international multicentric retrospective cohort study analyzing data from patients affected by recurrent pericarditis (idiopathic or post-cardiac injury) and referring to tertiary referral centers. Clinical, laboratory, and outcome data were compared between patients younger than 65 years (controls) and patients aged 65 or older. One hundred and thirty-three older adults and 142 young adult controls were enrolled. Comorbidities, including chronic kidney diseases, atrial fibrillation, and diabetes, were more present in older adults. The presenting symptom was dyspnea in 54.1% of the older adults versus 10.6% in controls (p < 0.001); pain in 32.3% of the older adults versus 80.3% of the controls (p < 0.001). Fever higher than 38°C was present in 33.8% versus 53.5% (p = 0.001). Pleural effusion was more prevalent in the older adults (55.6% vs 34.5%, p < 0.001), as well as severe pericardial effusion (>20 mm) (24.1% vs 12.7%, p = 0.016) and pericardiocentesis (16.5% vs 8.5%, p = 0.042). Blood leukocyte counts were significantly lower in the older adults (mean + SE: 10,227 + 289/mm3 vs 11,208 + 285/mm3, p = 0.016). Concerning therapies, NSAIDS were used in 63.9% of the older adults versus 80.3% in the younger (p = 0.003), colchicine in 76.7% versus 87.3% (p = 0.023), corticosteroids in 49.6% versus 26.8% (p < 0.001), and anakinra in 14.3% versus 23.9% (p = 0.044). Older adults affected by recurrent pericarditis show a different clinical pattern, with more frequent dyspnea, pleural effusion, severe pericardial effusion, and lower fever and lower leukocyte count, making the diagnosis sometimes challenging. They received significantly less NSAIDs and colchicine, likely due to comorbidities; they were also treated less commonly with anti-IL1 agents, and more frequently with corticosteroids.

Tai Chi Practice Buffers Aging Effects in Functional Brain Connectivity.

Tai Chi (TC) practice has been shown to improve both cognitive and physical function in older adults. However, the neural mechanisms underlying the benefits of TC remain unclear. Our primary aims are to explore whether distinct age-related and TC-practice-related relationships can be identified with respect to either temporal or spatial (within/between-network connectivity) differences. This cross-sectional study examined recurrent neural network dynamics, employing an adaptive, data-driven thresholding approach to source-localized resting-state EEG data in order to identify meaningful connections across time-varying graphs, using both temporal and spatial features derived from a hidden Markov model (HMM). Mann-Whitney U tests assessed between-group differences in temporal and spatial features by age and TC practice using either healthy younger adult controls (YACs, n = 15), healthy older adult controls (OACs, n = 15), or Tai Chi older adult practitioners (TCOAs, n = 15). Our results showed that aging is associated with decreased within-network and between-network functional connectivity (FC) across most brain networks. Conversely, TC practice appears to mitigate these age-related declines, showing increased FC within and between networks in older adults who practice TC compared to non-practicing older adults. These findings suggest that TC practice may abate age-related declines in neural network efficiency and stability, highlighting its potential as a non-pharmacological intervention for promoting healthy brain aging. This study furthers the triple-network model, showing that a balancing and reorientation of attention might be engaged not only through higher-order and top-down mechanisms (i.e., FPN/DAN) but also via the coupling of bottom-up, sensory-motor (i.e., SMN/VIN) networks.

Altered muscle synergy structure in patients with poststroke stiff knee gait

Stiff knee gait (SKG) occurrence after a stroke is associated with various abnormal muscle activities; however, the interactions among these muscles are unclear. This study aimed to elucidate the muscle synergy characteristics during walking in patients with SKG after a stroke. This cross-sectional study included 20 patients with poststroke SKG (SKG group), 16 patients without poststroke SKG (non-SKG group), and 15 healthy adults (control group). Participants walked a 10-m distance at a comfortable speed, and electromyographic data were recorded from six lower-limb muscles. Non-negative matrix factorization was employed to derive time-varying activity (C), muscle weights (W), and the percentage of total variance accounted for (tVAF) for muscle synergies. The SKG group showed a higher tVAF than the control group. The initial stance module (including knee extensors) showed increased activity during the swing phase. The initial swing module (including hip flexors and ankle dorsiflexors) exhibited a higher activity during the single-support phase but a lower activity during the swing phase. The synergy structure in patients with SKG after stroke was simplified, with specific abnormalities in synergy activities. SKG may arise from several synergy alterations involving multiple muscles, indicating that approaches focused on controlling individual muscle activities are unsuitable.

Genetic association of antinuclear antibodies with HLA in JIA patients: a Swedish cohort study

BackgroundJuvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition.MethodsWe analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm.ResultsCase–control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to HLA-DQA1 and HLA-DRB1. HLA-DRB1*08:01, HLA-DQA1*04:01, and HLA-DQB1*04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the HLA-DRB1-DQA1-DQB1 haplotype, our analysis suggests that HLA-DRB1*08 might be the primary allele linked to JIA susceptibility. The HLA-DRB1*11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the HLA-DRB1-DQA1-DQB1 haplotype, HLA-DRB1*11, and HLA-DPB1*02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity.ConclusionsThis study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.

Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

Aquatic high-intensity interval training improves cardiometabolic profile and physical fitness in active middle-age and older adults: quasi-randomized clinical trial study

Introduction: aquatic exercises have been increasingly suggested to the population. Despite evidence on the benefits of high-intensity interval training in aquatic environments, scientific production still needs to be improved. Research involving middle-aged and older individuals usually seeks physiological responses from the assumption that they are sedentary. Objective: to assess the physical fitness, lipid profile, and glycemic control of active middle-aged and older adults undergoing aquatic high-intensity interval training associated or not with intense water walking. Methods: it is a quasi-randomized clinical trial composed of 45 active middle-aged and older adults subdivided into two groups with aquatic high-intensity interval training in the absence (AHIIT) or presence (AHIITW) of intense water walking. Participants were dosed with biochemical parameters, bioimpedance analysis, and physical and cardiopulmonary tests at the intervention’s beginning and end. Results: both groups showed increased HDL, reduced LDL, and hemoglobin glycated, with increased endurance and strength of upper and lower limbs. The AHIIT group showed a lean mass gain and fat mass decline compared to the AHIITW. The intense walking promoted an increase in oxygen ventilatory equivalent, maximum oxygen consumption, and the task metabolic equivalent at values like the AHIIT. Conclusion: our findings indicate that high-intensity aquatic training holds the potential to enhance the lipid profile of individuals. However, the incorporation of pool walking into the training regimen did not lead to any notable differences in this regard. Conversely, the inclusion of pool aquatic exercises did result in improved functional capacity among participants. Brazilian Registry of Clinical Trials (ReBEC): #RBR-99b6jr6

Gastrointestinal manifestations in Williams syndrome: A prospective analysis of an adult and pediatric cohort.

Williams syndrome (WS) is a multi-system condition caused by the deletion of 25-27 coding genes on human chromosome 7. Irritability, gastrointestinal (GI) reflux and slow growth are commonly reported in infants with WS, but less data exist regarding GI concerns in older children and adults with the condition. This study evaluates 62 individuals with WS (31 children aged 3-17, and 31 adults aged 18-62) as well as 36 pediatric and adult controls to assess current and historical rates of common GI symptoms. Data were evaluated using a regression model including age, sex, self-reported race, and diagnosis. Symptoms including food intolerance, reflux, dysphagia, choking/gagging, vomiting, constipation, bloating, diarrhea, hematochezia, rectal prolapse, abdominal pain, and weight loss are more common in those with WS relative to controls. In addition, people with WS utilize more GI medications, specialty care, procedures, and supplemental feeds. Among those with WS, symptoms were present at similar rates in children and adults, except for diverticular disease, which was not noted until adulthood. GI symptoms are frequent in people with WS and serve as a significant source of morbidity.

Increased frequency of infections and autoimmune disease in adults with PTEN Hamartoma Tumour Syndrome

There are indications for immune dysregulation in PTEN Hamartoma Tumour Syndrome (PHTS), however information on the clinical immune phenotype is lacking. We aimed to assess the frequency of infections and autoimmune disease in PHTS patients. A retrospective cohort study including 81 paediatric and 109 adult PHTS patients and 73 female adult controls and self-reported data from yearly surveillance visits. Differences between adult patients and controls were assessed with odds ratios (OR). Of paediatric patients, 1% reported fungal infections, 23% tonsillectomy/adenoidectomy, 36% bacterial infections requiring antibiotics, and 2% autoimmune disease. Of adult patients, up to 67% repeatedly reported fungal infections, and 73% was ever affected which was similar to controls. Compared to controls, adult patients more often reported (signs of) viral infections: tonsillectomy/adenoidectomy (78%; OR = 7.4 (95%CI: 3.7–15.8)), frequent infections during childhood (43%; OR = 2.5 (95%CI: 1.3–5.2)), and flu or cold infections more often than others (49%; OR = 3.9 (95%CI: 2.0–8.0)). Autoimmune disease was also more frequent (24%, OR = 2.7 (95%CI: 1.1–7.3)) in adult patients, and antibiotics use (38%, OR = 4.7 (95%CI: 1.3–23.0)) in female adult patients. PHTS patients experience a broad clinical phenotype of immune dysregulation. At adult age, this consists of more often viral and bacterial infections and autoimmune disease, and repetitive fungal infections.