Background & Aims Irritable bowel syndrome (IBS) has been associated with disruptions to the intestinal microbiota, but studies have had limited power, coverage, and depth of analysis. We aimed to ...define microbial populations that can be used discriminate the fecal microbiota of patients with IBS from that of healthy subjects and correlate these with IBS intestinal symptom scores. Methods The microbiota composition was assessed by global and deep molecular analysis of fecal samples from 62 patients with IBS patients and 46 healthy individuals (controls). We used a comprehensive and highly reproducible phylogenetic microarray in combination with quantitative polymerase chain reaction. Results The intestinal microbiota of IBS patients differed significantly ( P = .0005) from that of controls. The microbiota of patients, compared with controls, had a 2-fold increased ratio of the Firmicutes to Bacteroidetes ( P = .0002). This resulted from an approximately 1.5-fold increase in numbers of Dorea, Ruminococcus , and Clostridium spp ( P < .005); a 2-fold decrease in the number of Bacteroidetes ( P < .0001); a 1.5-fold decrease in numbers of Bifidobacterium and Faecalibacterium spp ( P < .05); and, when present, a 4-fold lower average number of methanogens (3.50 × 107 vs 8.74 × 106 cells/g feces; P = .003). Correlation analysis of the microbial groups and IBS symptom scores indicated the involvement of several groups of Firmicutes and Proteobacteria in the pathogenesis of IBS. Conclusions Global and deep molecular analysis of fecal samples indicates that patients with IBS have a different composition of microbiota. This information might be used to develop better diagnostics and ultimately treatments for IBS.
The brain works as an organised, network-like structure of functionally interconnected regions. Disruptions to interconnectivity in certain networks have been linked to symptoms of depression and ...impairments in cognition. Electroencephalography (EEG) is a low-burden tool by which differences in functional connectivity (FC) can be assessed. This systematic review aims to provide a synthesis of evidence relating to EEG FC in depression. A comprehensive electronic literature search for terms relating to depression, EEG, and FC was conducted on studies published before the end of November 2021, according to PRISMA guidelines. Studies comparing EEG measures of FC of individuals with depression to that of healthy control groups were included. Data was extracted by two independent reviewers, and the quality of EEG FC methods was assessed. Fifty-two studies assessing EEG FC in depression were identified: 36 assessed resting-state FC, and 16 assessed task-related or other (i.e., sleep) FC. Somewhat consistent findings in resting-state studies suggest for no differences between depression and control groups in EEG FC in the delta and gamma frequencies. However, while most resting-state studies noted a difference in alpha, theta, and beta, no clear conclusions could be drawn about the direction of the difference, due to considerable inconsistencies between study design and methodology. This was also true for task-related and other EEG FC. More robust research is needed to understand the true differences in EEG FC in depression. Given that the FC between brain regions drives behaviour, cognition, and emotion, characterising how FC differs in depression is essential for understanding the aetiology of depression.
•Functional brain connectivity (FC) drives behaviour, cognition, and emotion•FC can be assessed via scalp electroencephalography (EEG)•Individuals with depression display higher frontal alpha FC and lower posterior theta FC in comparison to healthy controls•EEG FC methodologies used to date are suboptimal and more robust research methodologies are required
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
Acute gastroenteritis (AGE) is a common reason for children to receive medical care. However, the viral etiology of AGE illness is not well described in the post–rotavirus vaccine ...era, particularly in the outpatient (OP) setting.
Methods
Between 2012 and 2015, children 15 days through 17 years old presenting to Vanderbilt Children’s Hospital, Nashville, Tennessee, with AGE were enrolled prospectively from the inpatient, emergency department, and OP settings, and stool specimens were collected. Healthy controls (HCs) were enrolled and frequency matched for period, age group, race, and ethnicity. Stool specimens were tested by means of reverse-transcription real-time quantitative polymerase chain reaction for norovirus, sapovirus, and astrovirus RNA and by Rotaclone enzyme immunoassay for rotavirus antigen, followed by polymerase chain reaction verification of antigen detection.
Results
A total of 3705 AGE case patients and 1563 HCs were enrolled, among whom 2885 case patients (78%) and 1110 HCs (71%) provided stool specimens that were tested. All 4 viruses were more frequently detected in AGE case patients than in HCs (norovirus, 22% vs 8%, respectively; rotavirus, 10% vs 1%; sapovirus, 10% vs 5%; and astrovirus, 5% vs 2%; P < .001 for each virus). In the OP setting, rates of AGE due to norovirus were higher than rate for the other 3 viruses. Children <5 years old had higher OP AGE rates than older children for all viruses.
Conclusions
Norovirus remains the most common virus detected in all settings, occurring nearly twice as frequently as the next most common pathogens, sapovirus and rotavirus. Combined, norovirus, sapovirus, rotavirus, and astrovirus were associated with almost half of all AGE visits and therefore are an important reason for children to receive medical care.
Our study documented a decline in rotavirus post–rotavirus vaccine implementation and noted that norovirus has emerged to be the leading cause of pediatric acute gastroenteritis. Enteric viruses accounted for nearly half of the cases.
Cognitive impairments are common in patients with schizophrenia. Changes in total cholesterol (TC) may be involved in the development of schizophrenia and associated with cognitive function. This ...study aimed to investigate differences in serum TC level and cognitive function between schizophrenia patients and healthy controls and explore the relationship between serum TC level and cognitive function in patients with schizophrenia. A total of 105 schizophrenia patients and 105 healthy controls were recruited. Results showed that patients with schizophrenia had significantly lower scores on the overall RBANS scale and subscales (i.e., immediate memory, language, attention, and delayed memory) than those of healthy controls. Pearson's correlation analyses showed that in patients with schizophrenia, serum TC levels were positively associated with RBANS subscale scores of immediate memory and language. Furthermore, multivariate regression analyses showed that serum TC level was positively associated with the immediate memory index in patients with schizophrenia. However, no significant association was found between serum TC level and RBANS score in the healthy control group. Our results suggest that elevated serum TC level may be related to improved cognitive function in patients with schizophrenia, especially that of immediate memory.
•Patients had lower cognitive function scores compared with healthy controls.•Cholesterol level was positively associated with cognitive function in patients.•Cholesterol level was not associated with cognitive function in healthy controls.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lipidomics has become a pivotal tool in biomarker discovery for the diagnosis of psychiatric illnesses. However, the composition and quantitative analysis of peripheral lipids in female patients with ...bipolar disorder (BD) have been poorly addressed. In this study, plasma samples from 24 female patients with BD and 30 healthy controls (HCs) were analyzed by comprehensive lipid profiling and quantitative validation based on liquid chromatography-mass spectrometry. Clinical characteristics and a correlation between the level of lipid molecules and clinical symptoms were also observed. We found that the quantitative alterations in several lipid classes, including acylcarnitine, lysophosphatidylethanolamine, GM2, sphingomyelin, GD2, triglyceride, monogalactosyldiacylglycerol, phosphatidylinositol phosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylethanolamine, phosphatidylserine, and lysophosphatidylinositol, were remarkably upregulated or downregulated in patients with BD and were positively or negatively correlated with the severity of psychotic, affective, or mania symptoms. Meanwhile, the composition of different carbon chain lengths and degrees of fatty acid saturation for these lipid classes in BD were also different from those of HCs. Moreover, 55 lipid molecules with significant differences and correlations with the clinical parameters were observed. Finally, a plasma biomarker set comprising nine lipids was identified, and an area under the curve of 0.994 was obtained between patients with BD and the HCs. In conclusion, this study provides a further understanding of abnormal lipid metabolism in the plasma and suggests that specific lipid species can be used as complementary biomarkers for the diagnosis of BD in women.
Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains sNfL) or astroglia activation (serum glial fibrillary acidic protein ...sGFAP) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
When the brain is not engaged in goal-directed activities and at rest, there are still measureable patterns of activity. One resting-state network, the default mode network (DMN) is responsible for a ...self-referential introspective state. There are many factors that influence normal changes in brain activity. The purpose of this review is to summarize differences in DMN functional connectivity in healthy individuals by age, sex, cognitive function, and analysis type to characterize what is "normal." Studies were systematically selected up to August 2016. Two reviewers independently used predetermined inclusion and exclusion criteria to identify relevant studies. Studies that provided sufficient information were included in a subsequent voxel-wise meta-analysis. Strength of DMN functional connectivity follows an inverse U-shape, where it is strongest in adulthood and lowest in children and elderly. Cognitive function is positively correlated with DMN functional connectivity. Females exhibit stronger intranetwork connectivity compared with males. Effects of analysis type were inconclusive and more studies need to incorporate complementing techniques. The voxel-wise meta-analysis was only conducted for the age factor. Findings supported an immature network in children compared with adults and a stronger network in adults compared with elderly. This is the first study to review differences of DMN functional connectivity in healthy individuals by age, sex, cognitive function, and analysis type. Findings add to the understanding of normal variance. Furthermore, defining a normal comparative base may allow for the identification of DMN change into pathology. This is important since it may allow for the detection of an intermediate risk phenotype and could serve as a biomarker for treatment response.
•Patients with severe mental illness and healthy controls were included.•CMV antibody positivity associated with smaller dentate gyrus in male patients.•Higher CMV antibody titers associated with ...smaller dentate gyrus in male patients.•No CMV-dentate gyrus association in female patients.•No CMV-dentate gyrus associations in male or female healthy controls.
Cytomegalovirus (CMV) infection is usually inapparent in healthy adults but persists for life. Neural progenitor/stem cells are main CMV targets, and dentate gyrus (DG) a major neurogenic niche. Smaller DG volume has been repeatedly reported in severe mental illness (SMI). Considering the suggested immune system, blood–brain barrier and DG disturbances in SMI, we hypothesized that CMV exposure is associated with smaller DG volume in patients, but not healthy controls (HC). Due to the differential male and female immune response to CMV, we hypothesized sex-dependent associations. 381 adult patients with SMI (schizophrenia spectrum or bipolar spectrum disorders) and 396 HC were included. MRI scans were obtained with 1.5T Siemens MAGNETOM Sonata scanner or 3T General Electric Signa HDxt scanner, and processed with FreeSurfer v6.0. CMV immunoglobulin G antibody concentrations were measured by solid phase immunoassay. We investigated main and interaction effects of CMV status (antibody positivity/CMV + vs. negativity/CMV-) and sex on DG in patients and HC. Among patients, there was a significant CMV-by-sex interaction on DG (p = 0.009); CMV + male patients had significantly smaller DG volume than CMV- male patients (p = 0.001, 39 mm3 volume difference) whereas no CMV-DG association was found in female patients. Post-hoc analysis among male patients showed that the CMV-DG association was present in both hemispheres and in both patients with schizophrenia spectrum and bipolar spectrum disorders, and further, that higher CMV antibody titers were associated with smaller DG. No CMV-DG association was found in HC. The results indicate a DG vulnerability to CMV infection in men with SMI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Colonic contractility normally shows circadian variability regulated by sleep and especially food intake. However, individuals with type 1 diabetes have a reduced or even absent gastrocolic response ...to a meal, indicating that colonic contractility may be affected by the disease. We hypothesized that individuals with type 1 diabetes and distal symmetric polyneuropathy (DSPN) have decreased motility (expressed as the motility index) and contractility of the colon and a reduced increase in motility index from night to morning compared to healthy controls and individuals with type 1 diabetes without DSPN. Cohorts of 35 individuals with type 1 diabetes and DSPN, 40 individuals with type 1 diabetes without DSPN, and 28 healthy controls were included in this post-hoc, cross-sectional analysis. We investigated, using a wireless motility capsule that measures pH, temperature, and pressure throughout the gastrointestinal tract, whether individuals with type 1 diabetes with and without DSPN, compared to healthy controls, exhibit altered colonic contractility in the evening, night, and morning. Max amplitude, mean peak amplitude, mean contraction, and motility index of the colon were calculated at the afore-designated times. Motility index of the colon tended to be higher in individuals with type 1 diabetes and DSPN compared to controls in the evening (
= .064), but the effect size was small (1.74%). There was no difference in motility index between the groups in the morning or evening. Furthermore, there was no difference in max amplitude, mean peak amplitude, or mean contraction between groups in the morning, evening, and night. As expected, overall contractility increased from night to morning in all groups, but there was no difference between groups in the increase in contractility from night to morning. Colonic contractility generally peaked in the morning, decreased in the evening, and was almost absent at night. Type 1 diabetes and/or DSPN did not impair contractility of the colon at any time point. Contractility and motility increased from morning to night unaffected by type 1 diabetes and/or DSPN.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Objectives:
The pathophysiology of a frozen shoulder (FS) is thought to be related to chronic inflammation. Chronic inflammation may disturb the immune system and consequently the nervous system as ...part of an overarching system. The aim of this study was to determine the presence of disturbed autonomic nervous system function and altered central pain processing (CPP) in patients with FS. Secondarily, the presence of psychological variables (catastrophizing and hypervigilance) and self-reported associated symptoms of altered CPP in patients with FS were investigated.
Methods:
Patients with FS and healthy controls completed the Composite Autonomic Symptom Score (autonomic function) and underwent quantitative sensory testing to assess tactile sensitivity (ie, allodynia), pressure pain thresholds (PPTs, ie, hyperalgesia), temporal summation of pain, and Conditioned Pain Modulation (CPM). Psychological issues were explored with the Pain Catastrophizing Scale and the Pain Vigilance and Awareness Questionnaire, and self-reported symptoms associated with altered CPP were determined with the Central Sensitization Inventory.
Results:
Thirty-two patients with FS and 35 healthy controls were analyzed in the study. Patients with FS showed more self-reported autonomic symptoms and symptoms of altered CPP, higher levels of pain catastrophizing and hypervigilance, and are more sensitive to tactile touches and mechanical pressure compared with controls.
Discussion:
On the basis of the effect sizes, between-group differences in allodynia, hyperalgesia, catastrophizing, and hypervigilance were clinically relevant, but only local allodynia, hyperalgesia, catastrophizing, and hypervigilance were statistically different. Therefore, obvious altered CPP was not present at the group level in patients with FS compared with controls.
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