Healthy Control Subjects Research Articles

Methylome-wide association study of adolescent depressive episode with psychotic symptoms and childhood trauma

BackgroundEmerging evidence suggests that DNA methylation is crucial in the mental disorder pathophysiology. The current study attempted to identify the dysregulation of DNA methylation patterns in adolescent patients suffering from depressive episodes (DE) while considering the impact of various subtypes, including psychotic symptoms and a history of childhood trauma. MethodsThe study included 67 patients with DE and 30 healthy controls (HCs) subjects. Severe depressive episode (SDE) patients were grouped according to psychotic symptoms, such as SDE with vs. SDE without psychotic symptoms (cases 29 vs. 21). The Childhood Trauma Questionnaire-Short Form helped assess childhood trauma among all patients. Thus, all the patients were divided into adolescent DE experiencing ≥ two trauma types vs. experiencing ≤ one trauma type (cases, 50 vs. 17). Methylome-wide analysis was conducted on peripheral blood to identify methylation differences in CpG sites for three comparisons: DE vs. HCs, SDE patients with vs. without psychotic symptoms, and DE patients having 0–1 type of childhood trauma vs. those having ≥two types of childhood trauma. ResultsAdolescent DE patients demonstrated a predominant trend of lower methylation levels than HCs, with 259 hypermethylated and 3956 hypomethylated sites. Differentially hypomethylated sites involve related genes such as FKBP5, BDNF, NR3C1, GABRB3, SHANK1, SLC38A1, SLC6A18, CHRNB1, CTNNA2, CTTNBP2, etc. All these genes could be involved in DE pathogenesis. Significant DNA methylation changes could be observed in SDE subgroups with and without psychotic symptoms (e.g., genes like DTNB, CNTN1, CTNNA2), along with those DE patients having 0–1 type of childhood trauma compared to those with ≥2 types (e.g., VWA3B, SYT10, SDK2, CAMSAP3). Many significant methylated sites were associated with genes involved in brain development, highlighting the potential pathophysiological mechanisms linked with DE and its subtypes, such as psychotic symptoms and childhood trauma. ConclusionOur findings suggest that differential DNA methylation is associated with the pathophysiology of DE, as well as the presence of psychotic symptoms and a history of childhood trauma. These blood-based methylation patterns may serve as biomarkers for DE and shed light on underlying mechanisms across these subtypes.

Association of hyperventilation-induced heart rate variability and sudden unexpected death in epilepsy in drug-resistant epilepsy.

Within the general epilepsy population, the incidence of Sudden Unexpected Death in Epilepsy (SUDEP) ranges from approximately 0.35 to 2.3 per 1,000 individuals per year. We aimed to evaluate the relationship between SUDEP risk factors and heart rate variability (HRV) parameters as a potential biomarker of SUDEP in patients with drug-resistant epilepsy (DRE). There were 52 patients diagnosed with DRE and under follow-up, and controls including 45 healthy subjects, included in the study. Hyperventilation-induced HRV (HRVHV) parameters, including the standard deviation of all RR intervals (SDRR), mean heart rate (HR), root mean squares of successive differences (RMSSD), SD of mean NN intervals recordings (SDANN), and HRV triangular index, were assessed during resting. To predict the risk of SUDEP, the relationship between HRV parameters and SUDEP risks was evaluated using the Risk Assessment for Sudden Death in Epilepsy (SUDEP-7) Risk Inventory. No statistically significant difference was found in sympathetic skin response (SSR) latency and amplitudes between the patient and control groups. In comparing healthy control subjects with patients experiencing DRE, we observed significant decreases in SDRRHV and hyperventilation-induced RMSSD (RMSSDHV) values, specifically within HRVHV. Notably, a significant correlation emerged concerning the RMSSDHV values (p < 0.01), when examining the correlation between the SUDEP-7 inventory and HRVHV parameters. This correlation between RMSSDHV and the SUDEP-7 Risk Inventory in patients with DRE represents a novel and consequential finding, suggesting its potential as an indicator of SUDEP risk.

Neuronal current imaging of epileptic activity: An MRI study in patients with a first unprovoked epileptic seizure.

This study evaluates the performance of the novel MRI sequence stimulus-induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin-lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin-lock MR pulses in comparison with scalp-EEG in first seizure patients. We employed a novel method for measurements of neuronal activity through the detection of a resonant oscillating field, stimulus-induced rotary saturation contrast (SIRS) at spin-lock frequencies of 120 and 240 Hz acquired at a single 3T MRI system. Within a prospective observational study, we conducted SIRS experiments in 55 patients within 7 days after a suspected first unprovoked epileptic seizure and 61 healthy control subjects. In this study, we report on the analysis of data from a single 3T MRI system, encompassing 35 first seizure patients and 31 controls. The SIRS method was applicable in all patients and healthy controls at frequencies of 120 and 240 Hz. We did not observe any significant age- or sex-related differences. Specificity of SIRS at 120 Hz was 90.3% and 93.5% at 240 Hz. Sensitivity was 17.1% at 120 Hz and 40.0% at 240 Hz. SIRS targets neuronal oscillating magnetic fields in patients with epilepsy. The coupling of presaturated spins to epilepsy-related magnetic field perturbations may serve as a-at this stage experimental-diagnostic test in first seizure patients to complement EEG findings as a standard screening test. Routine diagnostic tests carry several limitations when applied after a suspected first seizure. SIRS is a noninvasive MRI method to enable time-sensitive diagnosis of image correlates of epileptic activity with increased sensitivity compared to routine EEG.

Irregularity of visual motion perception and negative symptoms in schizophrenia.

Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.

Reduced pineal gland volume in patients with obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) can have hyperactivity of the hypothalamic-pituitary-adrenal axis and may have increased secretion of adrenocorticotropic hormone and cortisol and reduced secretion of melatonin. Examination of pineal gland volumes in patients with OCD compared to healthy controls, thus, is an important consideration and the focus of this study. A total of 20 patients with OCD and 20 healthy controls were enrolled. Demographic and clinical characteristics of participants were assessed, and structural magnetic resonance imaging was performed. Patients with OCD had a statistically significant smaller pineal gland volumes compared to healthy controls. In this initial small study, patients with OCD exhibited smaller pineal gland volumes compared to healthy control subjects. While this finding suggests a potential link between the pineal gland and OCD pathophysiology, further research with larger sample sizes and measurement of hormonal changes are necessary.

Aphasia outcome: the role of diffusion tensor tractography in patients with acute ischemic stroke

BackgroundsRecovery for poststroke aphasia has a decelerating trajectory, with the greatest improvement is within weeks and the slope of change decreasing over time. Therefore, it is essential to predict the prognosis of aphasia at an early stage as it could provide useful data in specific plans for management strategies. The aim of this work was to assess the arcuate fasciculus in stroke patients with aphasia and its impact on predicting the outcome. A prospective study was performed including 25 patients with acute ischemic stroke and aphasia and 10 healthy control subjects with no history of neurologic or psychiatric disease. All patients underwent language assessment using an Arabic version of the Comprehensive Aphasia Test (Arabic CAT), with the resultant mean T-score aphasia quotient (AQ). Early assessment of stroke and delayed assessment at three months. All patients had diffusion-weighted magnetic resonance imaging (DWI-MRI) of the brain to localize the lesion and 3D diffusion tensor imaging (DTI) of the arcuate fasciculus (AF) within 30 days of stroke.ResultsPatients in whom the AF could not be reconstructed had a poor score in early and late AQ and a poor prognosis compared to those in whom the AF could be reconstructed. Preservation of the left AF on DTI could mean the potential recovery of aphasia after stroke.ConclusionThe prognosis of aphasia in patients whose left AF could be reconstructed was better than those whose left AF could not be reconstructed, irrespective of the AF's integrity. That is why, we can assume that evaluation of the DTI of the left AF at early stages of stroke can help in predicting outcome of aphasia.

The inhibitory control deficit of internet gaming disorder: An Event-Related Potentials(ERPs) study

IntroductionThe primary difficulty and challenge encountered by individuals with Internet Gaming Disorder (IGD) is inhibitory control deficit. Given that different types of inhibitory control have different effects on IGD patients, it is critical to investigate the neurological cognitive processes underlying various inhibitory control problems. MethodsThe IGD-20 questionnaire was used to identify Internet game disorder and healthy control group, and finally Internet game disorder in (n=25) and healthy control group (n=28) in Flanker task, Internet game disorder (n=29) and health control group (n=24) in GO/NOGO task. The Flanker task was employed to investigate distractor interference inhibition control in those with IGD, while the Go/NoGo task was used to measure their prepotent response inhibitory control. Event-related potentials (ERPs) were used to evaluate the brain mechanisms difference of both IGD and healthy participants during these different inhibitory control tasks. ResultsFindings indicate that compared to healthy control subjects, individuals with Internet Gaming Disorder (IGD) have deficits in inhibitory control tasks during both distraction inhibition and prepotent response inhibition tasks, and distraction inhibition occurs earlier than prepotent response inhibition. In distraction inhibition tasks, the IGD group's N2 amplitude is significantly lower than the healthy control groups. In prepotent response inhibition, the N2 amplitude provoked in the IGD group is not only significantly lower than in the healthy control group, but the P3 amplitude is also significantly larger in the IGD group. The main brain activity areas of interference inhibitory control are the frontal lobe and prefrontal lobe, while the main brain activity areas of prepotent response inhibitory control are the frontal lobe and occipital lobe. ConclusionThe present study concentrates on the differential neurophysiological characteristics observed in individuals with Internet gaming problems, notably the ability to avoid distractions and prepotent reactions. The current research provides foundations for the assessment and development of tailored therapy and treatment methods to address the wide variety of cognitive problems reported in individuals with Internet Gaming Disorder (IGD).

A novel mouse model reproducing frontal alterations related to the prodromal stage of dementia with LEWY bodies

BackgroundDementia with Lewy bodies (DLB) is the second most common age-related neurocognitive pathology after Alzheimer's disease. Animal models characterizing this disease are lacking and their development would ameliorate both the understanding of neuropathological mechanisms underlying DLB as well as the efficacy of pre-clinical studies tackling this disease. MethodsWe performed extensive phenotypic characterization of a transgenic mouse model overexpressing, most prominently in the dorsal hippocampus (DH) and frontal cortex (FC), wild-type form of the human α-synuclein gene (mThy1-hSNCA, 12 to 14-month-old males). Moreover, we drew a comparison of our mouse model results to DH- and FC- dependent neuropsychological and neuropathological deficits observed in a cohort of patients including 34 healthy control subjects and 55 prodromal-DLB patients (males and females). ResultsOur study revealed an increase of pathological form of soluble α-synuclein, mainly in the FC and DH of the mThy1-hSNCA model. However, functional impairment as well as increase in transcripts of inflammatory markers and decrease in plasticity-relevant protein level were exclusive to the FC. Furthermore, we did not observe pathophysiological or Tyrosine Hydroxylase alterations in the striatum or substantia nigra, nor motor deficits in our model. Interestingly, the results stemming from the cohort of prodromal DLB patients also demonstrated functional deficits emanating from FC alterations, along with preservation of those usually related to DH dysfunctions. ConclusionsThis study demonstrates that pathophysiological impairment of the FC with concomitant DH preservation is observed at an early stage of DLB, and that the mThy1-hSNCA mouse model parallels some markers of this pathology.

Corneal Epithelial Wavefront Error as a Novel Diagnostic Marker for Epithelial Basement Membrane Dystrophy.

Synopsis: Corneal epithelial wavefront error and epithelial thickness variance qualify as highly sensitive and specific biomarkers for epithelial basement membrane dystrophy (EBMD). The biomarkers show a normalization after treatment of EBMD with phototherapeutic keratectomy. Purpose: To gauge the diagnostic value of epithelial basement membrane dystrophy (EBMD), a novel spectral-domain optical coherence tomography (SD-OCT)-based imaging modality for simultaneous morphological (thickness profile) and refractive (optical wavefront) assessment of the corneal epithelial layer in one of the most common but often underdiagnosed corneal dystrophies. Methods: In this prospective observational study, a total of 32 eyes of 32 patients diagnosed with EBMD and 32 eyes of 32 healthy control subjects were examined with high-resolution anterior segment SD-OCT (MS-39; CSO, Florence, Italy). Various epithelial thickness and epithelial wavefront-derived terms were compared between groups and receiver operating characteristic (ROC) curves were computed to analyze the diagnostic capacity of the respective parameters. A total of 17 of 32 EBMD patients underwent treatment with phototherapeutic keratectomy (PTK) and were followed up for 3 months. Results: Epithelial thickness variance (60.4 ± 56.7 µm versus 7.6 ± 6.1 µm) and interquartile range (11.0 ± 6.9 versus 3.3 ± 1.9 µm) were markedly elevated in EBMD patients as compared with healthy controls (both with p < 0.001). Epithelial wavefront analysis showed a highly statistically significant excess in all examined aberration terms in EBMD patients (all with p < 0.001). Significantly greater areas under the curve (AUCs) were yielded by the epithelial wavefront-derived parameters (e.g., total epithelial wavefront error: AUC = 0.966; 95% confidence interval (CI) 0.932-1) than by the epithelial thickness-derived parameters (e.g., variance: AUC = 0.919; 95% CI 0.848-0.990). Conclusions: Corneal epithelial wavefront aberrometry proved valuable as an objective biomarker for EBMD, with high sensitivity and specificity. PTK resulted in a reduction of morphological and refractive epithelial irregularities in EBMD.

MIND Diet Impact on Multiple Sclerosis Patients: Biochemical Changes after Nutritional Intervention.

There is substantial evidence supporting the neuroprotective effects of the MIND diet in neurodegenerative diseases like Parkinson's and Alzheimer's. Our aim was to evaluate the impact of a nutritional intervention (NI) with this diet on multiple sclerosis (MS) patients. The study was conducted in two stages. In the first stage, two groups were included: MS patients before the NI (group A) and healthy control subjects (group B). In this stage, groups (A) and (B) were compared (case-control study). In the second stage, group (A) was assessed after the NI, with comparisons made between baseline and final measurements (before-and-after study). In the case-control stage (baseline evaluation), we found significant differences in fatigue scores (p < 0.001), adherence to the MIND diet (p < 0.001), the serum levels of brain-derived neurotrophic factor (BDNF) (p < 0.001), and higher oxidative status in the MS group, with lower levels of reduced glutathione (p < 0.001), reduced/oxidised glutathione ratio (p < 0.001), and elevated levels of lipoperoxidation (p < 0.002) and 8-hydroxy-2'-deoxyguanosine (p < 0.025). The before-and-after intervention stage showed improvements in fatigue scores (p < 0.001) and physical quality-of-life scores (MSQOL-54) (p < 0.022), along with decreases in the serum levels of glial-derived neurotrophic factor (GDNF) (p < 0.041), lipoperoxidation (p < 0.046), and 8-hydroxy-2'-deoxyguanosine (p < 0.05). Consumption of the MIND diet is linked to clinical and biochemical improvement in MS patients.

Associations between quantitative susceptibility mapping with male obstructive sleep apnea clinical and imaging markers

PurposeTo quantitatively measure and compare whole-brain iron deposition between OSA patients and a healthy control group, we initially utilized QSM and evaluated its correlation with PSG results and cognitive function. Materials and methodsA total of 28 OSA patients and 22 healthy control subjects matched in age, education level, and BMI were enrolled in our study. Each participant underwent scanning with 3D T1 and multi-echo GRE sequences. Additionally, PSG results were collected from OSA patients, and they underwent simple cognitive assessments. Finally, we analyzed the relationship between iron content in different brain regions, PSG results, and cognitive ability. ResultsIn OSA patients, iron content increased in the left temporal-pole-sup and right putamen, while it decreased in the left fusiform gyrus, left middle temporal gyrus, right inferior occipital gyrus, and right superior temporal gyrus. The correlation analysis between brain iron content and PSG results/cognitive scales is as follows: left fusiform gyrus and MMSE (r = −0.416, p = 0.028); right superior temporal gyrus and MMSE (r = 0.422, p = 0.025); left middle temporal gyrus and average oxygen saturation (r = −0.418, p = 0.027); left temporal-pole-sup and REM stage (rs = 0.466, p = 0.012); the right putamen and N1 stage (rs = 0.393. p = 0.039). Moreover, both MoCA (r = 0.598, p = 0.001) and MMSE (r = 0.456, p = 0.015) show a positive correlation with average oxygen saturation. ConclusionThis study is the first to use QSM technology to show abnormal brain iron levels in OSA. Correlations between brain iron content, PSG, and cognition in OSA may reveal neuropathological mechanisms, aiding OSA diagnosis.

Dysbiosis of pro-inflammatory and anti-inflammatory salivary cytokines during psoriasis providing a therapeutic window and a valuable diagnostic aid in future.

The objective of this article is to evaluate the salivary levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 in patients with active psoriasis and compare them with those in healthy control subjects. This study included 60 subjects who were clinically diagnosed cases with active psoriasis (categorized further into 33 mild to moderate and 27 severe cases based on the Psoriasis Area Severity Index score) and 60 age- and gender-matched healthy control subjects. Levels of TNF-α, IFN-γ, IL-2, and IL-10 in the unstimulated saliva of subjects were determined via enzyme-linked immunosorbent assay (BT Lab). The salivary levels of TNF-α, IFN-γ, and IL-2 were significantly higher, whereas IL-10 concentration was significantly reduced in psoriatic patients in comparison to controls, and the difference increased with the progressing severity of the disease. Assessment of cytokine profiles in psoriasis patients is significant for diagnostic validation and monitoring the disease severity. Saliva offers an alternate, noninvasive, and readily available biological sample for evaluating cytokine levels. Extensive research in this field has been recommended for better scientifically proven conclusions.

Prevalence and risk factors of sleep disorders in inflammatory bowel disease: a cross-sectional study

BackgroundSleep disorders are one of the major public health problems, which can potentially induce inflammation and exacerbate disease activity, resulting in compromised sleep quality. This study aimed to investigate the prevalence and risk factors associated with sleep disorders among patients with inflammatory bowel disease (IBD).MethodsBetween March 2023 and February 2024, the Pittsburgh Sleep Quality Index was employed to assess sleep quality in both IBD patients and healthy control subjects. Univariate and multivariate analysis were performed to identify the risk factors associated with SD in IBD patients.ResultsOverall, 208 IBD patients [150 Crohn’s disease (CD) and 58 ulcerative colitis (UC)] and 199 healthy individuals were included. Sleep disorders were observed in 59.6% of patients with IBD, with a higher prevalence among females (63.5%) compared to males (56.9%) (P = 0.476). The prevalence of sleep disorders in IBD patients was significantly higher than that found in healthy controls (37.7%) (all P < 0.01). The prevalence of sleep disorders among CD and UC patients was 58% and 63.8%, respectively (P = 0.291). The multivariate analysis revealed that older age (OR, 1.070; 95% CI: 1.035–1.105, P = 0.000), smoking (OR, 2.698; 95% CI: 1.089–6.685, P = 0.032), and depression (OR, 4.779; 95% CI: 1.915–11.928, P = 0.001) were risk factors for sleep disorders in IBD patients. However, higher body mass index (OR, 0.879; 95% CI: 0.790–0.977, P = 0.017) was identified as a protective factor.ConclusionSleep disorders are common among IBD patients regardless of activity levels. Smoking and depression are the major risk factors.

Aging-related biomarkers for the diagnosis of Parkinson's disease based on bioinformatics analysis and machine learning.

Parkinson's disease (PD) is a multifactorial disease that lacks reliable biomarkers for its diagnosis. It is now clear that aging is the greatest risk factor for developing PD. Therefore, it is necessary to identify novel biomarkers associated with aging in PD. In this study, we downloaded aging-related genes from the Human Ageing Gene Database. To screen and verify biomarkers for PD, we used whole-blood RNA-Seq data from 11 PD patients and 13 healthy control (HC) subjects as a training dataset and three datasets retrieved from the Gene Expression Omnibus (GEO) database as validation datasets. Using the limma package in R, 1435 differentially expressed genes (DEGs) were found in the training dataset. Of these genes, 29 genes were found to occur in both DEGs and 307 aging-related genes. By using machine learning algorithms (LASSO, RF, SVM, and RR), Venn diagrams, and LASSO regression, four of these genes were determined to be potential PD biomarkers; these were further validated in external validation datasets and by qRT-PCR in the peripheral blood mononuclear cells (PBMCs) of 10 PD patients and 10 HC subjects. Based on the biomarkers, a diagnostic model was developed that had reliable predictive ability for PD. Two of the identified biomarkers demonstrated a meaningful correlation with immune cell infiltration status in the PD patients and HC subjects. In conclusion, four aging-related genes were identified as robust diagnostic biomarkers and may serve as potential targets for PD therapeutics.

CACNA1C rs58619945 genotype influences the cortical thickness of attention network among patients with Bipolar Ⅰ disorder

To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. Compared with the HC group, the BD-I patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex. A significant interaction between the CACNA1C genotype and the cortical thickness of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted. Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex predominantly among carriers of the BD-I G allele. The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Abnormal left atrial strain and left atrial stiffness index are associated with adverse outcomes in children with cardiomyopathies: a pilot study

Conventional diastolic dysfunction parameters seem to be imperfect when applied to the pediatric cardiomyopathy population. The aim of this pilot study was to search for novel echocardiographic parameters associated with adverse outcomes in children with the most common cardiomyopathies. Fifty-six patients with pediatric cardiomyopathies (28 with dilated, 21 with hypertrophic, 7 with left ventricular non-compaction cardiomyopathy) and 28 healthy subjects were included in the study. Left atrial reservoir (LASr), conduit (LAScd) and contraction (LASct) strain, left atrial stiffness index (LASI), as well as conventional diastolic dysfunction parameters were measured using echocardiography. Adverse outcomes were defined as heart failure (including heart transplant) and arrhythmic endpoints. Patients with adverse outcomes presented with significantly lower LASr (16.68% ± 8.64% vs. 33.97% ± 9.99%, p-value < 0.001), lower LAScd (− 10.37% ± 5.83% vs. − 25.50% ± 9.24%, p-value < 0.001) and higher values of LASI (0.69 [IQR 0.34; 1.11] vs. 0.21 [IQR 0.16; 0.31], p-value < 0.001). LASr < 20%, LAScd ≥ − 12%, and LASI ≥ 0.26 were all associated with reduced survival. LASr, LAScd and LASI seem to be promising parameters in predicting adverse outcomes in the most common pediatric cardiomyopathies. Left atrial strain parameters and LASI are helpful in differentiating healthy control subjects from children with hypertrophic and dilated cardiomyopathies.

Orientation Regulation of Class-switch Recombination in Human B Cells.

We developed a linear amplification-mediated high-throughput genome-wide translocation sequencing method to profile Ig class-switch recombination (CSR) in human B cells in an unbiased and quantitative manner. This enables us to characterize CSR junctions resulting from either deletional recombination or inversion for each Ig class/subclass. Our data showed that more than 90% of CSR junctions detected in peripheral blood in healthy control subjects were due to deletional recombination. We further identified two major CSR junction signatures/patterns in human B cells. Signature 1 consists of recombination junctions resulting from both IgG and IgA switching, with a dominance of Sµ-Sγ junctions (72%) and deletional recombination (87%). Signature 2 is contributed mainly by Sµ-Sα junctions (96%), and these junctions were almost all due to deletional recombination (99%) and were characterized by longer microhomologies. CSR junctions identified in healthy individuals can be assigned to both signatures but with a dominance of signature 1, whereas almost all CSR junctions found in patients with defects in DNA-PKcs or Artemis, two classical nonhomologous end joining (c-NHEJ) factors, align with signature 2. Thus, signature 1 may represent c-NHEJ activity during CSR, whereas signature 2 is associated with microhomology-mediated alternative end joining in the absence of the studied c-NHEJ factors. Our findings suggest that in human B cells, the efficiency of the c-NHEJ machinery and the features of switch regions are crucial for the regulation of CSR orientation. Finally, our high-throughput method can also be applied to study the mechanism of rare types of recombination, such as switching to IgD and locus suicide switching.

Association of rs8670 Polymorphism in the MSX1 Gene With Non-Syndromic Cleft Lip With or Without Cleft Palate in Malay Population.

This study aimed to investigate the association between variants present in the MSX1 gene and the risk of developing non-syndromic cleft lip with or without cleft palate (NSCL±P) among individuals of Malay ethnicity in Malaysia. This case-control study involved 89 patients with NSCL±P and 100 healthy control subjects. Polymerase chain reaction (PCR) was performed on both exon 1 and exon 2 of the MSX1 gene using four pairs of primers. The amplification products were then subjected to denaturing high-pressure liquid chromatography for initial screening, and the presence of a heteroduplex peak was validated using direct sequencing analysis to detect the single-nucleotide polymorphism. Five previously known variations (c.-36G>A, p.Ala30Ala, p.Ala34Gly, p.Gly110Gly, and rs8670: C>T) were detected within the MSX1 gene in both NSCL±P patients and controls.A significant association was found between the rs8670: C>T variant and NSCL±P (p = 0.017; OR: 0.368; 95% CI: 0.152 - 0.893), with this particular single-nucleotide polymorphism present in 20% (20) among controls and 7.9% (7) of the NSCL±P cases. Our data showed a lower incidence of thers8670: C>Tpolymorphism among NSCL±P cases compared to control in this Malay population. However, since this variant is located in the 3'UTR, it could potentially impact the stability ofMSX1mRNA.

A novel super-resolution microscopy platform for cutaneous alpha-synuclein detection in Parkinson's disease.

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, we imaged total and phosphorylated-aSyn at the single molecule level in sweat glands and nerve bundles of skin biopsies from healthy controls (HCs) and PD patients. We developed a user-friendly analysis platform that offers a comprehensive toolkit for researchers that combines analysis algorithms and applies a series of cluster analysis algorithms (i.e., DBSCAN and FOCAL) onto dSTORM images. Using this platform, we found a significant decrease in the ratio of the numbers of neuronal marker molecules to phosphorylated-aSyn molecules, suggesting the existence of damaged nerve cells in fibers highly enriched with phosphorylated-aSyn molecules. Furthermore, our analysis found a higher number of aSyn aggregates in PD subjects than in HC subjects, with differences in aggregate size, density, and number of molecules per aggregate. On average, aSyn aggregate radii ranged between 40 and 200 nm and presented an average density of 0.001-0.1 molecules/nm2. Our dSTORM analysis thus highlights the potential of our platform for identifying quantitative characteristics of aSyn distribution in skin biopsies not previously described for PD patients while offering valuable insight into PD pathology by elucidating patient aSyn aggregation status.

Changeable factors for diabetes mellitus type II patients and compare it with healthy control

A study has been analysed “Changeable factors for diabetes mellitus type II patients and compare it with healthy control.” A random sample total 150 well-informed, informed consented subjects of either male and female 35-70 years of age group has been selected from Bihar. 100 patients suffering from diabetes mellitus type II were placed in group 1 (serving as cases) and fifty (50) apparently healthy individuals with matched age were place in group 2 (serving as a healthy control). The number of the disease population is believed to be approx. 70-90 per% of apparently healthy Indians have under vitamin D level across all the regions and age groups. In the present, diabetic cases had 19.09±5.34 ng/ml of serum vitamin D level. Healthy control subjects had 26.55±3.61 ng/ml of serum. The results been showed that 53% male and 47% female participants among cases. 40% male and 60% female participants among healthy control. Diabetes mellitus of patients, 17 cases were under good control, 28 were under fair control and 55 were under poor control. Diabetic cases had 19.09±5.34 ng/ml of serum vitamin D level. Healthy control subjects had 26.55±3.61 ng/ml of serum vitamin D.