Early Course Research Articles

Early Childhood Behavior Patterns in Merpati Hamlet, Naru Village

Education is a place to form a good image in humans so that they develop their full potential. SISDIKNAS Law No. 20 of 2003 education is a conscious and planned effort to create a learning atmosphere and learning process so that students actively develop their potential to have religious spiritual strength, self-control, personality, intelligence, noble character, and the skills needed by themselves and society. Formal education is education that can be obtained by participating in activities or educational programs that are structured and planned by government agencies, for example through schools or universities, while non-formal education is education that can be obtained through activities of daily life that are not bound by institutions formed by the government, for example learning through experience, self-study through books and learning through others. The purpose of this writing is to find out the problems of early childhood in Merpati Hamlet, Naru Village and as an assignment for the Early Childhood Cognitive Development course.

예비유아교사의 놀이에 대한 인식 탐색

The purpose of this study is to examine early childhood preservice teacher’s perception on play using the concept mapping analysis. Multidimentional scale analysis and hierarchical cluster analysis were performed. The results of this study can be summarized as follows. 47 final statements were finally generated based on the perception on play, and were classified into two dimensions of “the essence of play-play support” and “the educational significance of play-the developmental importance of play”. In addition, the statements were classified into five clusters: ‘diversity of play’, ‘aspects of play’, ‘role of teacher’, ‘necessity of play in young children’, and ‘value of play’. This study provides implication for support necessary for early childhood preservice teachers or the direction of early childhood teacher education course to form the desirable perception on play.

P293 Correlation between clinical measures to capture disease burden and prediction of the initial course of Crohn’s disease - findings from a Copenhagen IBD Inception Cohort Study (IBD Prognosis Study)

Abstract Background The initial disease burden of Crohn’s disease (CD) is dissimilar across patients; however, the ability to capture and predict the disease burden at diagnosis is scarcely investigated. The aim of the current study was to describe the initial disease burden of Crohn’s disease. Methods IBD Prognosis Study is an ongoing prospective population-based inception cohort of newly diagnosed patients with CD between May 1st, 2021, and November 1st, 2022, according to the Copenhagen IBD Criteria.1 We defined an indolent disease presentation as no need for CD-related surgery, hospitalization, nor initiation of steroid, immunomodulatory, or biologic therapies within the first 30 days after diagnosis, while a complicated course was defined as the opposite. Results The study included 134 patients with adult-onset CD, of whom approximately one-third (44/134, 33%) had an early indolent course, with 26 patients (19%) not requiring any medication (Tables 1-2). In demographic factor adjusted analyses, a colonic phenotype (adjusted odds ratio (aOR) =4.5 (95% confidence interval (CI) 1.6-15) and a low symptom load measured with Harvey-Bradshaw Index (HBI) <5 (aOR = 3.1 (CI 1.0-10) were independently associated with an indolent course. In contrast, a C-reactive protein (CRP) level higher than 10 mg/L was the only parameter associated with a complicated onset of CD (aOR = 4.7 (CI 2.1-12)). Pearson’s correlation analyses demonstrated a significant, moderate correlation between fecal (F-) calprotectin, CRP, and endoscopic lesions, measured with Simple Endoscopic Score for CD (SES-CD) (Table 3). HBI and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) exhibited a significant but weak correlation with CRP. In a sensitivity analysis allowing exposure to anti-inflammatory therapy for only up to seven days, the platelet count, F-calprotectin, and bowel wall thickness measured in IBUS-SAS demonstrated a significant and moderate correlation with SES-CD. The total IBUS-SAS and CRP showed a significant but weak correlation, and other measures included in the IBUS-SAS did not yield significant correlations. Conclusion Preliminary data from the ongoing population-based cohort indicate that one-third of patients with newly diagnosed CD have an early indolent course. This study identified colonic disease location and CRP levels to be associated with the early course, while platelet count, bowel wall thickness, and CRP were correlated with endoscopic lesions at the onset of CD.

Role of GeneXpert in diagnosis of rifampicin resistant tuberculosis in patients with cervical lymphadenopathy

Tuberculosis is one of the most common causes for cervical lymphadenopathy apart from distant metastasis and lymphoma. Early diagnosis of this disease reduces the patient’s morbidity by initiating early course of Antitubercular treatment with complete resolution of disease. Hence, for diagnosis of this condition we are searching for a modality which can give results in shorter period of time, which is more sensitive, specific and most important easier to perform. Gene Xpert is one such modality which fits into these criteria. In our case series, we are aiming to study the role of Gene Xpert in diagnosis of rifampicin resistant tuberculosis in patients with cervical lymphadenopathy. In our study, excisional biopsy from cervical region was done in 30 cases and were sent for acid fast bacilli culture, Ziehl Neelsen staining and GeneXpert studies, histopathological examination and results were analyzed.

Exercise Predicts a Good Night's Sleep: Preliminary Findings from a UCLA Study of First-Episode Schizophrenia.

Physical exercise can improve sleep quality in the general population. Understanding the negative impact of poor sleep quality on multiple domains of functioning among persons with schizophrenia is a new frontier of exploration. It is also imperative to investigate non-pharmacologic methods to improve sleep quality as these approaches may not carry the side effect burdens associated with medication. We examined the relationship between regular physical exercise and sleep quality among participants in an intervention consisting of both cognitive training and exercise. Participants (N = 48) were schizophrenia patients who had a first psychotic episode within two years of study entry. Participants received 4 h/week of internet-based cognitive training and an aerobic exercise program over a 6-month period. Sleep was assessed with the Pittsburgh Sleep Quality Index at baseline and six months later. During the 3 months prior to the 6-month follow-up sleep assessment, participants completed an average of 12.6 group exercise sessions and an average of 12.9 individual at-home exercise sessions. A significant relationship between the number of exercise sessions and global sleep quality was seen at month six, r = -0.44, df = 39, p < 0.01. Group exercise frequency was also associated with improvement in global sleep quality over the six-month intervention, t(34) = -2.84, p = 0.008. We demonstrated that a group of young adults with schizophrenia can be engaged in a regular exercise program, even during the tumultuous early course of the disorder. The number of exercise sessions in which they participated was associated with better sleep quality at six months and pre-postintervention improvement in sleep quality. Improved sleep quality appears to be a benefit of regular exercise among individuals with serious mental illness.

Remdesivir Alone or in Combination with Monoclonal Antibodies as an Early Treatment to Prevent Severe COVID-19 in Patients with Mild/Moderate Disease at High Risk of Progression: A Single Centre, Real-Life Study.

Early treatment with antivirals against SARS-CoV-2 infection can prevent the onset of severe COVID-19 in fragile and immunocompromised patients. In this real-life, prospective, observational study, we evaluated efficacy and safety of a 3-day early treatment with remdesivir in adult and fragile patients with a diagnosis of SARS-CoV-2 infection who referred to the COVID-19 early treatment service of Infectious Diseases Unit of University of Naples Federico from 10 January 2022 to 31 March 2022. The included patients could be treated with either remdesivir alone or with remdesivir plus a monoclonal antibody with activity against SARS-CoV-2. Among the 62 included patients, we showed low rates of hospitalization (8%), increase in oxygen supplementation (3.2%), ICU admission (1.6%) and death (1.6%). The rate of disease progression was 8% and it was similar in patients treated with remdesivir alone or in combination with monoclonal antibodies (6.7% and 9.4%, respectively; p = 0.531). The rate of adverse drug reaction was low and similar in the two groups (13.3% in patients treated with remdesivir, 15.6% in patients treated with the combination; p = 0.543). Most common adverse events were headache and fever. In conclusion, in our cohort of patients at a high risk of worse COVID-19 outcomes, an early course of remdesivir showed low rates of disease progression and adverse drug reactions.

Age at Onset Influences Progression of Motor and Non-Motor Symptoms during the Early Stage of Parkinson's Disease: A Monocentric Retrospective Study.

The interactions between the age at onset with other pathogenic mechanisms and the interplays between the disease progression and the aging processes in Parkinson's disease (PD) remain undefined, particularly during the first years of illness. Here, we retrospectively investigated the clinical presentation and evolution of the motor and non-motor symptoms and treatment-related complications during the first 5 years of illness in subjects categorized according to age at onset. A total of 131 subjects were divided into "Early-Onset-PD" (EOPD; onset ≤49 years), "Middle-Onset-PD" (MOPD; onset 50-69 years) and "Late-Onset-PD" (LOPD; onset ≥70 years). The T0 visit was set at the time of the clinical diagnosis; the T1 visit was 5 years (±5 months) later. At T0, there were no significant differences in the motor features among the groups. At T1, the LOPD patients displayed a significantly higher frequency of gait disturbances and a higher frequency of postural instability. Moreover, at T1, the LOPD subjects reported a significantly higher frequency of non-motor symptoms; in particular, cardiovascular, cognitive and neuropsychiatric domains. The presented results showed a significantly different progression of motor and non-motor symptoms in the early course of PD according to the age at onset. These findings contribute to the definition of the role of age at onset on disease progression and may be useful for the pharmacological and non-pharmacological management of PD.

Features of Cerebral Small Vessel Disease Contributes to the Differential Diagnosis of Alzheimer's Disease.

Cerebral small vessel disease (CSVD), which comprises the typical features of white matter hyperintensity (WMH) and Vichor-Robin spaces (VRSs) in the brain, is one of the leading causes of aging-related cognitive decline and, ultimately, contributes to the occurrence of dementia, including Alzheimer's disease (AD). To investigate whether CSVD imaging markers modify the pathological processes of AD and whether these markers improve AD diagnosis. 208 participants were enrolled in the China Aging and Neurodegenerative Initiative (CANDI). Fluid AD biomarkers were detected using a single-molecule array, and cerebral small vessel dysfunction was determined using magnetic resonance imaging. WMH contributed to AD pathology only within the NC and MCI groups (CDR ≤0.5), whereas VRSs had no effect on AD pathology. The associations between AD biomarkers and cognitive mental status were consistent with the presence of CSVD pathology. That is, within individuals without CSVD pathology, the MMSE scores were correlated with AD fluid biomarkers, except for plasma Aβ42 and Aβ40. Increased plasma p-Tau levels were associated with worse cognitive performance in individuals with WMH (β= -0.465, p = 0.0016) or VRSs (β= -0.352, p = 0.0257) pathology. Plasma AD biomarkers combined with CSVD markers showed high accuracy in diagnosing dementia. Findings from this cross-sectional cohort study support the notion that CSVD is a risk factor for dementia and highlights that vascular pathology can promote AD biomarker levels, especially in the early course of the disease. Moreover, our results suggest that adding a vascular category to the ATN framework improves the diagnostic accuracy of AD.

Study of the accuracy of a radial arterial pressure waveform cardiac output measurement device after cardiac surgery

BackgroundLess invasive monitoring, such as radial arterial pulse contour analysis (ProAQT® sensor), represents an alternative when hemodynamic monitoring is necessary to guide postoperative management and invasive monitoring is not technically feasible. The aim of the study is to evaluate the accuracy of the ProAQT® sensor cardiac output measurements in comparison with Pulmonary Artery Catheter (PAC) during the postoperative course of patients who underwent cardiac surgery with cardiopulmonary bypass.Case presentationProspective observational study in a Surgical Intensive Care Unit of a tertiary university hospital. Ten patients with a mean age of 73.5 years were included. The main comorbidities were hypertension, diabetes, dyslipidemia and the preoperative left ejection fraction was 43.8 ± 14.5%. Regarding the type of surgery, six patients underwent valve surgery, two underwent coronary artery bypass grafting and two underwent aortic surgery. The cardiac index measured simultaneously by the ProAQT® sensor was compared with the PAC. The parameters were evaluated at predefined time points during the early postoperative courses (6 h, 12 h, 24 h, 48 h and 72 h). The degree of agreement with the cardiac index between the PAC and the ProAQT® sensor along the time points was measured using the concordance correlation coefficient, Bland–Altman analysis, and four-quadrant plot. Sixty-three pairs of measurements were analyzed. We showed that measurements of cardiac index were slightly higher with PAC (β ̂ = − 0.146, p-value = 0.094). The concordance correlation coefficient for the additive model of cardiac index was 0.64 (95% Confidence Interval: 0.36, 0.82), indicating a high concordance between both sensors. Bland-Altmann analysis showed a mean bias of 0.45 L·min−1·m−2, limits of agreement from − 1.65 to 2.3 L·min−1·m−2, and percentage of error was 82.5%. Four-quadrant plot of changes in cardiac index showed a good concordance rate (75%), which increases after applying the exclusion zone (87%).ConclusionsIn patients undergoing cardiac surgery, the ProAQT® sensor may be useful to monitor cardiac index during the postoperative period, especially when more invasive monitoring is not possible.

Systemic inflammatory markers and EEG features of children with FIRES receiving anakinra.

In a retrospective case series of 10 children with cryptogenic FIRES, we sought to describe the early clinical course and potential biomarkers following anakinra initiation. Six children achieved anesthetic withdrawal within 3 weeks of therapy and one in week four. Of the available cEEG (six children), CRP (10 children), and serum cytokine (six children) studies, there were temporal changes in highly epileptiform bursts (observed in three children), CRP, IL-6, and IL-10 levels that might parallel clinical progression. These observations may represent candidate biomarkers for monitoring clinical progression and therapeutic interventions including anakinra, which merits further investigation in future studies.

Health, Suicidal Thoughts, and the Life Course: How Worsening Health Emerges as a Determinant of Suicide Ideation in Early Adulthood.

Poor physical health places adults at greater risk for suicide ideation. However, the linkage between health and suicidal thoughts may emerge and become established during early adulthood, concomitant with other social processes underlying suicidality. Using nationally representative survey data from Waves III through V of the National Longitudinal Study of Adolescent to Adult Health (n = 8,331), we examine the emergence of health as a predictor of suicide ideation across the early adult life course (ages 18-43). We find that worsening health does not significantly predict suicide ideation until young adults approach the transition into midlife. Our findings suggest this may be due to the increasing severity of health problems, reduced social network engagement, and disruption of social responsibilities later in early adulthood. Our findings underscore the need for social science research to examine the relationship between mental and physical health from a life course perspective.

In Situ and Quantitatively Monitoring the Dynamic Process of Ferroptosis in Single Cancer Cells by Scanning Electrochemical Microscopy.

Ferroptosis, as a promising therapeutic strategy for cancers, has aroused great interest. Quantifying the quick dynamic changes in key parameters during the early course of ferroptosis can provide insights for understanding the underlying mechanisms of ferroptosis and help the development of therapies targeting ferroptosis. However, in situ and quantitatively monitoring the quick responses of living cancer cells to ferroptosis at the single-cell level remains technically challenging. In this work, we selected HuH7 cells (hepatocellular carcinoma (HCC) cells) as a cell model and Erastin as a typical ferroptosis inducer. We utilized scanning electrochemical microscopy (SECM) to quantitatively and in situ monitor the early course of ferroptosis in HuH7 cells by characterizing the three key parameters of cell ferroptosis (i.e., cell membrane permeability, respiratory activity, and the redox state). The SECM results show that the membrane permeability of ferroptotic HuH7 cells continuously increased from 0 to 8.1 × 10-5 m s-1, the cellular oxygen consumption was continuously reduced by half, and H2O2 released from the cells exhibited periodic bursts during the early course of ferroptosis, indicating the gradually destroyed cell membrane structure and intensified oxidative stress. Our work realizes, for the first time, the in situ and quantitative monitoring of the cell membrane permeability, respiratory activity, and H2O2 level of the early ferroptosis process of a single living cancer cell with SECM, which can contribute to the understanding of the physiological process and underlying mechanisms of ferroptosis.

Emerging drugs for the treatment of type 1 diabetes mellitus: a review of phase 2 clinical trials

ABSTRACT Introduction Despite therapeutic advances in the field of diabetes management since the discovery of insulin 100 years ago, there are still unmet clinical needs for people with type 1 diabetes mellitus (T1DM). Areas covered Genetic testing and islet autoantibodies testing allow researchers to design prevention studies. This review discusses the emerging therapy for prevention of T1DM, disease modification therapy in early course of T1DM, and therapies and technologies for established T1DM. We focus on phase 2 clinical trials with promising results, thus avoiding the exhausted list of every new therapy for T1DM. Expert opinion Teplizumab has demonstrated potential as a preventative agent for individuals at risk prior to the onset of overt dysglycemia. However, these agents are not without side effects, and there are uncertainties on long-term safety. Technological advances have led a substantial influence on quality of life of people suffering from T1DM. There remains variation in uptake of new technologies across the globe. Novel insulins (ultra-long acting), oral insulin, and inhaled insulin attempt to narrow the gap of unmet needs. Islet cell transplant is another exciting field, and stem cell therapy might have potential to provide unlimited supply of islet cells.

Difference in the early clinical course between children with type 1 diabetes having a single antibody and those having multiple antibodies against pancreatic β-cells.

Islet-cell associated antibodies are predictive and diagnostic markers for type 1 diabetes. We studied the differences in the early clinical course of children with type 1 diabetes with a single antibody and those with multiple antibodies against pancreatic β-cells. Sixty-seven children with type 1 diabetes aged less than 15 years diagnosed between 2010 and 2021 were included in the study and subdivided into two subgroups: children who were single positive for either glutamic acid decarboxylase (GAD) antibodies (n = 16) or insulinoma-associated antigen-2 (IA-2) antibodies (n = 13) and those positive for both antibodies (n = 38) at diagnosis. We compared the patients' clinical characteristics, pancreatic β-cell function, and glycemic control during the 5 years after diagnosis. All clinical characteristics at diagnosis were similar between the two groups. One and two years after diagnosis, children who tested positive for both antibodies showed significantly lower postprandial serum C-peptide (CPR) levels than those who tested positive for either GAD or IA-2 antibodies (p < 0.05). In other periods, there was no significant difference in CPR levels between the two groups. There was a significant improvement in glycosylated hemoglobin (HbA1c) levels after starting insulin treatment in both groups (p < 0.05), but no significant difference in HbA1c levels between the groups. Residual endogenous insulin secretion may be predicted based on the number of positive islet-cell associated antibodies at diagnosis. Although there are differences in serum CPR levels, optimal glycemic control can be achieved by individualized appropriate insulin treatment, even in children with type 1 diabetes.

ЭФФЕКТИВНОСТЬ ПРИМЕНЕНИЯ ИСКУССТВЕННОГО ПНЕВМОПЕРИТОНЕУМА ДО И ПОСЛЕ ПНЕВМОНЭКТОМИИ У БОЛЬНЫХ РАСПРОСТРАНЕННЫМ ДЕСТРУКТИВНЫМ ТУБЕРКУЛЕЗОМ ЛЕГКИХ

Aim: to evaluate the effectiveness of artificial pneumoperitoneum (APP) in the pre-operative and post-operative period in patients, who underwent pneumonectomy due to advanced destructive pulmonary TB. Materials and methods. We studied 104 patients, who underwent pneumonectomy with anterior mediastinal plasty (AMP) due to advanceddestructive pulmonary TB. The patients were divided into two groups. The main group consisted of 34 patients enrolled prospectively, who underwent APP before and after pneumonectomy with AMP. The comparison group consisted of 70 patients enrolled retrospectively, who did not undergo APP before and after pneumonectomy with AMP. Treatment effectiveness was estimated based on the parameters of the early course and late course (after 2 months) of post-operative period and dynamic chest X-ray signs. We also performed morphological and bacteriological studies of resection samples to estimate TB activity and bacterioexcretion massivity. Results. The effectiveness of APP for prevention of mediastinal lung hernias (MLH) was 93.3%. The studies of resection samples from the main group patients revealed decreased incidence of lymphohematogenic or bronchogenic dissemination, as well as more pronounced organization of granulomas and small foci as compared to resection samples from the controls. The comparison of key spirometry parameters in the groups did not reveal significant differences. Conclusion. The use of APP before and after pneumonectomy with AMP is a safe and highly effective method for prevention of MLH. It also contributes to stabilization of TB process in the remaining lung.

A Cross Sectional Study on the Correlation between Waist Circumference and Fatty Liver on Ultrasonography among Non-Alcoholic Filipino Adults

Objectives: This study aimed to determine the correlation between waist circumference and fatty liver on ultrasonography among non-alcoholic Filipino adults. This will aid in detecting non-alcoholic fatty liver disease in its early course, hence improving our current therapeutic recommendations in preventing and managing the adverse health outcomes of NAFLD. Methods and Materials: A cross-sectional study with a total of 65 recruited participants. The data collected were age, sex, waist-circumference, co-morbidities with maintenance medications, history of alcohol intake with emphasis on the quantity and duration, and history of drug intake. Waist circumference was measured and recorded. The presence of NAFLD was determined through a review of the ultrasonography results of all subjects. The demographic profile and waist circumference of all subjects were described using descriptive statistics. The chi-square test was utilized to test the independence of the NAFLD and WC in the quartile. Pearson correlation was used to determine the linear relationship between the variables. Pearson correlation coefficient was statistically significant at p 0.05. Results: Among the subjects, 26 (42%) presented with fatty liver based on ultrasonography, 15 (58%) and 11 (42%), males and females, respectively. The mean waist circumference of 97.5 ± 12.43 was significantly related to the fatty liver with a p-value of 0.0001. Waist circumference showed a positive correlation with the frequency of fatty liver on ultrasonography with p-values of 0.000755 (r = 0.590083) and 3.04366E—05 (r = 0.659143523), in males and females, correspondingly. The overall correlation between waist circumference and fatty liver on ultrasonography is statistically significant with a p-value of 4.10503E—08 (r = 0.634737127). Conclusion: One measure used to assess central obesity is waist circumference. In addition, it can also be utilized to assess risk for NAFLD since they are strongly correlated as reported in this study. Waist circumference cut-off values for the Filipinos proposed in this study are the following: >88 cm and >95 cm, in males and females, respectively.

Autoimmune Mechanisms in Focal Epilepsy of Unknown Cause

ABSTRACT The manifestation of immunological findings in diverse disorders presenting with seizures points to autoimmunity and inflammation in the etiology of epilepsy. Typical examples of autoimmunity-associated epilepsy are autoimmune encephalitis, Rasmussen encephalitis, and glutamic acid decarboxylase (GAD) antibody-positive temporal lobe epilepsy (TLE). The last entity is a typical example of antibody-positive focal epilepsy of unknown cause (FEUC). One of the most prominent findings emphasizing the coexistence of epilepsy and autoimmunity is the detection of anti-neuronal antibodies in patients manifesting with seizures. Emergence of antibody-producing plasma cells in the early course of GAD-antibody-positive TLE and induction of seizures in rodents upon intracerebral administration of N-methyl-D-aspartate receptor antibodies indicate that anti-neuronal antibodies may play a causal (rather than bystander) role in the induction of seizures. By contrast, innate immunity of the central nervous system (CNS) and infiltrating cytotoxic T-cells appear to participate in Rasmussen encephalitis and autoimmune encephalitis with antibodies to intracellular antigens. In addition, repetitive seizures may activate glial cells through the release of damage-associate molecular pattern mediators and activation of toll-like receptors, which in turn leads to disrupted blood–brain barrier and increased cerebral infiltration of peripheral blood immune cells. In conclusion, complex interactions of humoral and cellular immunity in the CNS appear to cause or at least contribute to seizure induction in FEUC. The nature of these interactions has recently started to be understood. Investigation of these mechanisms is substantial for the discovery of new treatment strategies and biomarkers in epilepsy.

Diabetic post-covid mucormycosis: A dermatoglyphic prediction.

To identify the characteristic pattern/parameter among diabetic post-covid mucormycosis patients which may further help in identifying such susceptible patients in a much earlier course of the disease. The study was done with 30 diabetic patients (21 males and 9 females) admitted in RIMS Ranchi during the second wave of Covid-19 for post-covid complications. Palm and fingerprint pattern was taken by ink and pad method to measure the qualitative and quantitative parameters. Diabetic post-covid mucormycosis patients were found to have predominantly whorl pattern in males, loop in females, and C-line pattern absent in 36.6%. Proximal axial triradii with ulnar deviation was 76.6%. All the ridge counts (except ab ridge count of right hand) when compared with hypothesized value were found to be significant with P value (<0.005). None of the three angles measured were found to be significant. All the ridge counts (except ab ridge count of right hand) were found to be a reliable parameter for the diagnosis of diabetic post-covid mucormycosis. ATD angle known to be the most reliable parameter for diagnosis of diabetes mellitus in dermatoglyphics is found to be nonreliable with respect to diabetes post-covid mucormycosis.

DNA Methylation Analysis in Monozygotic Twins Discordant for ALS in Blood Cells.

ALS is a fatal motor neuron disease that displays a broad variety of phenotypes ranging from early fatal courses to slowly progressing and rather benign courses. Such divergence can also be seen in genetic ALS cases with varying phenotypes bearing specific mutations, suggesting epigenetic mechanisms like DNA methylation act as disease modifiers. However, the epigenotype dictated by, in addition to other mechanisms, DNA methylation is also strongly influenced by the individual's genotype. Hence, we performed a DNA methylation study using EPIC arrays on 7 monozygotic (MZ) twin pairs discordant for ALS in whole blood, which serves as an ideal model for eliminating the effects of the genetic-epigenetic interplay to a large extent. We found one CpG site showing intra-pair hypermethylation in the affected co-twins, which maps to the Glutamate Ionotropic Receptor Kainate Type Subunit 1 gene (GRIK1). Additionally, we found 4 DMPs which were subsequently confirmed using 2 different statistical approaches. Differentially methylated regions or blocks could not be detected within the scope of this work. In conclusion, we revealed that despite a low sample size, monozygotic twin studies discordant for the disease can bring new insights into epigenetic processes in ALS, pointing to new target loci for further investigations.

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.