First-degree Relatives Research Articles

Documents to procure gamma irradiation chamber and license for operation in blood center

Abstract: Graft-versus-host disease is a critical posttransplant complication, particularly affecting individuals with compromised immune systems. Patients undergoing bone marrow transplants, neonates receiving intrauterine transfusions, and those recipients of blood from first-degree relatives are vulnerable to this condition. The significance of efficient lymphocyte inactivation has driven the widespread adoption of Gamma Irradiation Chambers (GICs) utilizing radiation sources such as Cesium-137 (Cs-137) or Cobalt-60 (Co-60). However, the effective operation of these chambers is contingent on navigating a complex regulatory landscape (Cs-137 or Co-60 is commonly used as the source of gamma rays. The usual dose is 25 Gray [Gy] to 35 Gy [1 Gy = 100 rads], this dosage inactivates 85%–95% of lymphocytes in the blood components without any adverse effect on other cellular components of the blood). GIC unit mainly houses either Co-60 or Cs-137as radiation sources (model no BI-2000, BI-5000 mfr. by Board of Radiation and Isotope Technology with typical radioactivity ranging from tens to hundreds of terabecquerel. These units are also used in research institutions, hospitals, blood center, etc. A review of legal, regulatory, and policy aspects of the operation of GIC in India regarding its issues, challenges, and opportunities. We aimed to prepare a standard guidance document for GIC for a smooth process of the Atomic Energy Regulatory Board (AERB) licensing and equipment purchasing. The present article was written based on the experience of applying for GIC with AERB and recurrent support extended to colleagues in the fraternity. The documents prepared for licensing and various procedural steps involved in the same are included. Many documents and many days are required from procurement to the receipt of the license for operation GIC. At the same time, with very few user institutes and less number of experienced people in the country, it becomes difficult to find a proper method to approach the national government body. If blood center/radiological safety officer are properly trained as per the guidelines available, this can reduce man-days and facilitate the earliest operations.

Altered Use of Context During Visual Perception in Psychotic Psychopathology: A Neurophysiological Investigation of Tuned and Untuned Suppression During Contrast Perception.

The human visual system streamlines visual processing by suppressing responses to textures that are similar to their surrounding context. Surround suppression is weaker in individuals with schizophrenia (ISZ); this altered use of visuospatial context may relate to the characteristic visual distortions they experience. To understand atypical surround suppression in psychotic psychopathology, we investigated neurophysiological responses in ISZ, healthy controls (HC), individuals with bipolar disorder (IBP), and first-degree relatives (ISZR/IBPR). Participants performed a contrast judgment task on a circular target with annular surrounds, with concurrent electroencephalography. Orientation-independent (untuned) suppression was estimated from responses to central targets with orthogonal surrounds; the orientation-dependence of suppression was estimated by fitting an exponential function to the increase in suppression as surrounds became more aligned with the center. ISZ exhibited weakened untuned suppression coupled with enhanced orientation-dependence of suppression. The N1 visual evoked potential was associated with the orientation-dependence of suppression, with ISZ and ISZR (but not IBP or IBPR) showing enhanced orientation-dependence of the N1. Collapsed across orientation conditions, the N1 for ISZ lacked asymmetry toward the right hemisphere; this reduction in N1 asymmetry was associated with reduced untuned suppression, real-world perceptual anomalies, and psychotic psychopathology. The overall amplitude of the N1 was reduced in ISZ and IBP. Key measures of symptomatology for ISZ are associated with reductions in untuned suppression. Increased sensitivity for ISZ to the relative orientation of suppressive surrounds is reflected in the N1 VEP, which is commonly associated with higher-level visual functions such as allocation of spatial attention or scene segmentation.

Pancreatic beta cell function and insulin resistance profiles in first-degree relatives of patients with prediabetes and type 2 diabetes.

To evaluate insulin secretion and insulin resistance profiles in individuals with family history of prediabetes and type 2 diabetes. This was a cross-sectional study to evaluate clinical and metabolic profiles between individuals with type 2 diabetes, prediabetes and their relatives. There were 911 subjects divided into five groups: (i) normoglycemic (NG), (ii) type 2 diabetes, (iii) prediabetes, (iv) first-degree relatives of patients with type 2 diabetes (famT2D), and (v) first-degree relatives of patients with prediabetes (famPD); anthropometrical, biochemical and nutritional evaluation, as well as insulin resistance and pancreatic beta cell function measurement was performed by oral glucose tolerance to compare between groups. The most prevalent type 2 diabetes risk factors were dyslipidemia (81%), family history of type 2 diabetes (76%), central obesity (73%), male sex (63%), and sedentary lifestyle (60%), and most of them were progressively associated to prediabetes and type 2 diabetes groups. Insulin sensitivity was lower in famT2D groups in comparison to NG group (p < 0.0001). FamPD and famT2D had a 10% lower pancreatic beta cell function (DI) than the NG group (NG group 2.78 ± 1.0, famPD 2.5 ± 0.85, famT2D 2.4 ± 0.75, p˂0.001). FamPD and famT2D patients had lower pancreatic beta cell function than NG patients, highlighting that defects in insulin secretion and insulin sensitivity appear long time before the development of hyperglycemia in patients genetically predisposed.

Risk for progression to type 1 diabetes in first-degree relatives under 50 years of age.

The detection of pancreatic autoantibodies in first-degree relatives of patients with type 1 diabetes (T1D) is considered a risk factor for disease. Novel available immunotherapies to delay T1D progression highlight the importance of identifying individuals at risk who might benefit from emerging treatments. The objective was to assess the autoimmunity in first-degree relatives of patients with T1D, estimate the time from autoimmunity detection to the onset of clinical diabetes, and identify the associated risk factors. Retrospective multicenter study of 3,015 first-degree relatives of patients with T1D recruited between 1992 and 2018. Pancreatic autoantibodies (IAA, GADA, IA2A, and ZnT8A) were determined by radioimmunoassay, starting the analyses at diagnosis of the proband. All those with positive autoimmunity and normal fasting blood glucose without clinical symptoms of diabetes were followed up in the study. The progression rate to T1D was assessed according to sex, relationship with the proband, age at autoimmunity detection, type/number of autoantibodies, and HLA-DRB1 genotype. Cox proportional-hazard models and Kaplan-Meier survival plots were used for statistical analyses. Among the relatives, 21 progenitors [43.7 years (IQR: 38.1-47.7)] and 27 siblings [7.6 years (IQR: 5.8-16.1)] had positive autoantibodies. Of these, 54.2% (95% CI: 39.2%-68.6%) developed T1D (age at autoimmunity detection 11 months to 39 years) in a median of 5 years (IQR: 3.6-8.7; ranged from 0.9 to 22.6 years). Risk factors associated with faster progression to T1D were multiple autoimmunity and <20 years at autoimmunity detection. Younger relatives (<20 years) with multiple autoantibodies had a 5-year cumulative risk of developing diabetes of 52.9% (95% CI: 22.1%-71.6%) and a 20-year risk of 91.2% (95% CI: 50.5%-98.4%). The 20-year risk decreased to 59.9% (95% CI: 21.9%-79.5%) if only one risk factor was met and to 35.7% (95% CI: 0.0%-66.2%) if the relative was older than 20 years with one autoantibody. In first-degree relatives with autoimmunity, the time to progression to T1D is faster in children and adolescents with multiple autoantibodies. Young adults are also at risk, which supports their consideration in screening strategies for people at risk of developing T1D.

Innovative Implementation Strategies for Familial Hypercholesterolemia Cascade Testing: The Impact of Genetic Counseling.

The IMPACT-FH study implemented strategies (packet, chatbot, direct contact) to promote family member cascade testing for familial hypercholesterolemia (FH). We evaluated the impact of genetic counseling (GC) on medical outcomes, strategy selection, and cascade testing. Probands (i.e., patients with FH) were recommended to complete GC and select sharing strategies. Comparisons were performed for both medical outcomes and strategy selection between probands with or without GC. GEE models for Poisson regression were used to examine the relationship between proband GC completion and first-degree relative (FDR) cascade testing. Overall, 46.3% (81/175) of probands completed GC. Probands with GC had a median LDL-C reduction of -13.0 mg/dL (-61.0, 4.0) versus -1.0 mg/dL (-16.0, 17.0) in probands without GC (p = 0.0054). Probands with and without GC selected sharing strategies for 65.3% and 40.3% of FDRs, respectively (p < 0.0001). Similarly, 27.1% of FDRs of probands with GC completed cascade testing, while 12.0% of FDRs of probands without GC completed testing (p = 0.0043). Direct contact was selected for 47 relatives in total and completed for 39, leading to the detection of 18 relatives with FH. Proband GC was associated with improved medical outcomes and increased FDR cascade testing. Direct contact effectively identified FH cases for the subset who participated.

Assessing genetic and environmental components for pterygium: a nationwide study in Taiwan

This study aims to estimate the familial risks of pterygium and assess its relative contributions to environmental and genetic factors using the 2000–2017 Taiwan National Health Insurance Research Database. The marginal Cox's model and the polygenic liability model were made. In Taiwan, the prevalence rate of pterygium in 2017 was 1.64% for individuals with affected first-degree relatives, higher than the general population (1.34%). The adjusted relative risk (RR) for pterygium was highest for twins of the same sex (15.54), followed by siblings of the same sex (4.69), offsprings (3.39), siblings of the different sex (2.88), spouse (2.12), parents (1.86), twins of the different sex (1.57), respectively. The phenotypic variance of pterygium was 21.6% from additive genetic variance, 24.3% from common environmental factors shared by family members, and 54.1% from non-shared environmental factors, respectively. Sensitivity analysis by restricting those with surgical pterygium reveals that aRRs and the three components were similar to those of the overall pterygium. In summary, the prevalence rate of pterygium was higher for individuals with affected first-degree relatives than for the general population. The non-shared environmental factors account for half of the phenotypic variance of pterygium; genetic and shared environmental factors explain the rest.

Developing a Paired Whole Genome Sequencing Service for Children With Cancer

BackgroundThe uniqueness of paired (tumor and germline) whole genome sequencing (PWGS) in cancer diagnosis and management lies in not just its ability to uncover oncogenic drivers and potential treatment targets but also on the identification of underlying cancer predisposition syndromes, which has significant implications for the patient and their family. AimsThis is a descriptive article highlighting the processes taken by our team to incorporate PWGS into routine National Health Service (NHS) clinical care for children with cancer. The main aim of this article is to share our experience with other centers that may wish to set up similar services and set the stage for future quantitative/qualitative research. MethodsThis article is further supported by an audit focusing on children in whom an underlying cancer predisposition was confirmed. ResultsThe audit highlights the success of the program to date, with 100% of families identified as being at risk of a cancer predisposition syndrome being offered referral to clinical genetics and 100% of at-risk first-degree relatives being offered predictive counseling and testing. Areas requiring improvement included discussion of reproductive options as only six out of nine families (67%) had a documented discussion. ConclusionsIncorporation of the audit recommendations will improve our service, and sharing of our experience will hopefully encourage more pediatric oncology services to introduce PWGS into routine clinical care and reduce inequity of access. Further work is required to assess the long-term cancer risk reduction and establish the psychosocial impact of PWGS for the child and family.

An observational study of auditory-evoked potential mismatch negativity response in individuals at high genetic risk for schizophrenia

Objectives: This study presents a novel approach by investigating the abnormal mismatch negativity (MMN) found during response to auditory-evoked potential (ERP) in schizophrenia (SZ) patients. Our unique focus is on the genetic high-risk (GHR) for SZ, comparing it with healthy controls (HC). In addition, we aim to illuminate the interrelationship of MMN with socio-occupational functioning in the GHR group, a novel aspect of our research. Material and Methods: We conducted this study with a rigorous methodology, ensuring the reliability and validity of our findings. Thirty first-degree relatives of SZ patients (GHR) who met the inclusion and exclusion criteria were recruited by purposive sampling and compared with thirty HCs. We collected sociodemographic and clinical data from all study participants, which were assessed by the Family Interview of Genetic Studies. GHR was evaluated for current socio-occupation functioning using the Social and Occupational Functioning Assessment Scale (SOFAS). All the participants underwent 128-channel electroencephalographic recording using an auditory-evoked responses paradigm. The MMN was calculated at the frontal electrode clusters, ensuring accurate and reliable data collection. Results: The study revealed a statistically significant difference in frontal MMN latency between GHR and HC. Moreover, a positive relationship was noted between the SOFAS score and MMN amplitude, and a negative relationship was found between the latencies at the frontal region. Conclusion: Our research has made a significant breakthrough in understanding SZ. Our findings reveal that individuals with a genetic susceptibility to SZ exhibit a unique response in a particular test known as MMN. This test measures the automatic auditory change detection mechanism, which detects minor alterations in the acoustic environment and is referred to as MMN. This newfound insight could prove instrumental in developing more effective diagnoses and treatments for SZ.

Screening for familial disease presence in first-degree relatives of Behçet's disease patients: Is measurement of common femoral vein wall thickness valuable for the diagnosis?

We aimed to assess first degree relatives (FDRs) of BD patients for the presence of clinical symptoms and signs of BD and evaluate common femoral vein (CFV) wall thickness measurement for the diagnosis. Patients with BD(n=129) and FDRs(n=230) of these patients were included. FDRs were questioned in terms of BD symptoms by phone. Pathergy test and CFV wall thickness measurement were performed among 111 FDRs who accepted the clinical assessment. Clinical assessment group were classified according to the criteria sets for BD. FDRs who did not meet the criteria sets and had at least one clinical finding in addition to oral aphthae(OA) were categorized as the "suspected BD". :We observed increased frequency of isolated BD manifestations in FDRs. Ten FDRs were diagnosed with BD during clinical evaluation. Significantly increased CFV wall thickness was observed in FDRs of BD patients fulfilling diagnostic BD criteria (p<0.001 for both sides) and also in those with suspected BD group (p<0.05 for both sides). Presence of OA, genital ulcer, folliculitis or erythema nodosum were associated with increased CFV wall thickness (p<0.05). . Our results suggest that CFV wall thickness measurement can be used in diagnosis of familial BD.

The assessment of public perception towards chronic kidney disease in Jordan: a cross-sectional study

Objectives Kidney diseases are considered silent killers due to the lack of well-defined symptoms. Public knowledge about chronic kidney disease (CKD) management has been shown to decrease the risk of CKD onset and progression to end-stage renal disease and renal failure. The main objective of this study was to assess the knowledge of kidney function, CKD symptoms, etiology, prevention and treatment in the general population. Methods A cross-sectional study using a validated questionnaire was conducted in Jordan to assess public knowledge of CKD. Public knowledge of CKD was assessed using a questionnaire consisting of 32 knowledge questions, including risk factors, symptoms, treatment, protective measures and kidney function. The knowledge level was classified according to the total score: poor (0–50%), intermediate (51–70%) and good/high (71–100%). Multiple regression analysis was performed to compare knowledge scores (KS) and predict associations with the participants’ baseline characteristics. Results The level of knowledge about CKD among the 2181 participants was intermediate. The KS was significantly higher among participants with health issues such as hypertension, diabetes and heart problems, first-degree relatives working in the medical field, majors relevant to health, married, employed, highly educated, high-income and smokers. The main sources of knowledge about CKD were health professionals, TV shows, books and magazines. Multiple regression analysis showed an association between KS and age, sex, functional status, educational level and field, income, smoking status, having a family member/spouse work in the medical field, and knowledge source. Conclusions The public level of knowledge about CKD management is greatly influenced by participants’ health and social factors. Thus, improving public knowledge and perception through education and the media will significantly reduce CKD prevalence and incidence.

Laboratory Testing for Celiac Disease: Clinical and Methodological Considerations.

Celiac disease (CeD) has an estimated prevalence of 1%-3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth.CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations. Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma. Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.

Prevalence of Frank's sign in healthy young individuals, morphological characteristics, and its association with family history of chronic disease.

Frank's sign (FS, earlobe crease) is known to be associated with many chronic diseases i.e. coronary, cerebrovascular, and peripheral vascular diseases. The objective of this study is to investigate the presence and grade of FS in healthy, young-adult individuals aging between 18 and 25. Furthermore, to evaluate the relationship between FS and the chronic disease history of first-degree family members. 853 healthy people with a mean age of 20.09 years were imvolved in the research on a voluntary basis. Of 853 individuals, 85.3% (n:728) had no FS, whereas 14.7% (n:125) had. Of the 125 people observed FS, 41.6% (n:52) were female and 58.4% (n:73) were male. Of the 125 people diagnosed with FS, 32.8% (n:41) had no family history of any chronic disease, and 67.2% (n:84) had at least 1 family history of chronic disease as well. It was determined that there was a statistically significant (p < 0.05) relationship between FS identified in healthy individuals and familial chronic disease history. In this study, while no FS was observed in 85.3% of the participants, grade 1 was detected in 12.4% (n:105), grade 2a in 1.9% (n:16), grade 2b in 0.2% (n:2), and grade 3 in 0.2% (n:2). To the best of our knowledge, this study investigated the relationship between the presence and grade of FS in the healthy, young, Turkish population and the presence/absence of chronic disease in the first-degree relatives of individuals for the very first time. As a result of larger studies, being aware of the presence of FS, especially in young healthy individuals, may help predict some chronic diseases, and caution may be taken to avoid these diseases at an early age in at-risk individuals.

Development and Validation of an Integrative Risk Score for Future Risk of Crohn’s Disease in Healthy First-Degree Relatives: A Multicentre Prospective Cohort Study

Development and Validation of an Integrative Risk Score for Future Risk of Crohn’s Disease in Healthy First-Degree Relatives: A Multicentre Prospective Cohort Study

Prevalence of Multiple Sclerosis in Vitiligo Patients and Their First-Degree Relatives: Two Diseases with Similarities in Pathogenesis and Treatment.

Vitiligo is a common pigmentation disorder manifested by white macules and patches. It is accompanied by some autoimmune and neurological diseases. Recently, it has been suggested that multiple sclerosis (MS) is more common in vitiligo patients and that they have a higher risk of developing MS during their lifetime. In this study, we aimed to determine the prevalence of MS in patients with vitiligo and their first-degree relatives and compare it with the prevalence in the population. In this cross-sectional study, data were consecutively collected from patients referred to Razi Hospital from March 2020 to December 2021. Seven hundred and nine patients with vitiligo participated in this study, and 15 reported a history of MS (2.12%, 95% confidence interval [CI] 1.06%-3.17%). This rate was significantly higher than the prevalence of MS in the average population of Tehran (P < 0.001). Of the 2886 first-degree relatives of the patients, 10 had MS (0.35%, 95%CI 0.13&-0.56%), which was higher than the prevalence of MS, yet not statistically significant. A significant association between vitiligo and MS was observed, which should be of clinical and therapeutic importance. However, the prevalence of MS in first-degree relatives of vitiligo patients was higher than the average rate, yet not statistically significant.

Anti-CCP Antibodies in Unaffected First-Degree Relatives of Rheumatoid Arthritis Patient

Introduction: Rheumatoid arthritis (RA) is perhaps the most common inflammatory arthritis, affecting 0.5% to 1% of the general population worldwide. Environmental and genetic influences are important risk factors for pathogenesis of RA. First-degree relatives (FDRs) of RA patients sharing genetic and environmental risk factors for RA may represent as pre-RA state. Since anti-CCP antibody appears years before the onset of RA, it can be used to estimate risk-potential for future development of RA in unaffected FDRs of RA patient. Objective: To see the serum anti-CCP antibody in unaffected FDRs of RA patients. Materials and Methods: This cross-sectional study was conducted from July 2019 to June 2020 in Department of Biochemistry, Dhaka Medical College, Dhaka. A total number of 50 subjects were selected among which 25 were unaffected FDRs of RA patients and the other 25 were age &amp; gender matched healthy subjects. The related RA patients were selected from Rheumatology outdoor, Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and the healthy subjects were taken from the attendants came to the same institute who did not have RA patient in their family. The key variables (age and gender) were recorded and outcome variable (anti-CCP antibody in study subjects) was estimated. Statistical analysis was done by SPSS 26.0 and the significance was defined as p &lt; 0.05. Results: Mean age of the FDRs of RA patient was 31.36 ± 10.51 years and that of healthy subjects was 31.56 ± 8.89 years. Most of the participants were in age group 20-29 years followed by 30-39 years. 4% of FDRs of RA patient were anti-CCP antibody positive and no positive case was recorded in healthy subjects. The median level of anti-CCP antibody in FDRs of RA patient was 0.50 U/mL and that in healthy subjects was 0.09 U/mL. The level of significance (p = 0.002) showed that serum anti-CCP antibody level was significantly higher (within normal range) in FDRs of RA patient than in healthy subjects, which was even more significant in FDRs of seropositive RA patients. Conclusion: This study revealed that serum anti-CCP antibody level was significantly higher (within normal range) in FDRs of RA patient than in healthy subjects and the proportion of positive anti-CCP antibody was more in FDRs of RA patient than in healthy subjects. Medicine Today 2024, Vol.36 (2): 76-81

Shared aetiology underlying multiple sclerosis and other immune mediated inflammatory diseases: Swedish familial co-aggregation and large-scale genetic correlation analyses

BackgroundWhile multiple sclerosis (MS) affects less than 1 % of the general population, immune mediated inflammatory diseases (IMIDs) collectively influence 5–10 % of the population. Understanding familial co-aggregation of MS and other IMIDs carries important clinical and public health implications that will enable early detection and personalized treatment. ObjectiveTo estimate the familial association between MS and other IMIDs and to quantify their shared genetic basis. DesignRegister-based multi-generational nested case-control familial co-aggregation study and genetic correlation study. SettingSweden. Participants24,995 individuals with MS matched with 253,870 controls and 1,283,502 first-degree relatives (mothers, fathers, full siblings, and offspring) for familial co-aggregation analysis; population of European ancestry for genetic correlation analysis. MeasurementsLogistic regressions with adjustment for covariates were used to estimate the odds ratios (ORs) of developing MS in individuals with first-degree relatives diagnosed with IMIDs compared to those without such family history. Pairwise genome-wide genetic correlations were estimated with linkage-disequilibrium score regression. ResultsWe observed an OR for familial co-aggregation of MS of 1.09 (95 % confidence interval (95%CI) = 1.07−1.11) in families with IMIDs history compared to families without. The association remained broadly consistent after stratification by sex concordance of relative pairs and by kinships. 18 IMID subtypes showed a familial association with MS, 7 of which including other acute widespread myelin destruction, encephalitis or myelitis or encephalomyelitis, inflammatory bowel disease, autoimmune thyroid diseases, systemic lupus erythematosus, other inflammatory system diseases, and sarcoidosis withstood multiple correction. Genetic correlations further revealed a shared genetic basis between 7 IMID subtypes with MS. ConclusionWe demonstrated a modest familial co-aggregation of MS with several IMIDs, and such association is likely due to shared genetic factors.

Comparing cognition in parents with schizophrenia or bipolar disorder and their 7-year-old offspring

Individuals with schizophrenia (SZ) or bipolar disorder (BP) display cognitive impairments, while their first-degree relatives perform at an intermediate level between the patient groups and controls. However, the environmental impact of having an ill relative likely varies with the type of kinship and some studies suggest that offspring may be particularly disadvantaged. The present study aimed to investigate the relationship between parent and child cognition in parents with SZ or BD and their 7-year-old offspring. A population-based cohort of 522 children (parental SZ, n = 202; parental BP, n = 120; controls, n = 200) and their parents underwent the same assessment battery covering a wide range of cognitive functions. We used Bayesian statistics to model performance. We found that performance on non-verbal tests was better in offspring than parents with SZ or BP, using the controls as reference. However, for verbal tests, there was little to no evidence for this pattern or even some evidence for the opposite in the BP group: relatively better performance in parents than offspring. The findings suggest that the offspring of parents with SZ or BP may be particularly disadvantaged in verbal abilities. Future studies will show whether this pattern persists throughout development.

Clinical characteristics of pediatric noninfectious uveitis and risk factors for severe disease: a single-center study

ObjectivesWe aimed to present the demographic, clinical, laboratory, and treatment data of children with non-infectious uveitis and to evaluate the risk factors for the development of complications and the need for biological treatment.MethodPatients diagnosed with non-infectious uveitis in childhood and followed up for at least 1 year were included in the study. Demographic data, including age, gender, age at diagnosis, uveitis in first-degree relatives, and rheumatologic diseases, were obtained retrospectively from medical records. The presence of complications or the need for biologic therapy was considered a composite outcome suggesting severe disease.ResultsThe study included 123 patients (female: n = 59, 48%). The mean age at diagnosis was 14.89 ± 4.86 years. Uveitis was symptomatic in 104 patients (84.6%). Approximately one-quarter of the patients had at least one rheumatic disease (n = 35, 28.5%), the most common being juvenile idiopathic arthritis. Thirty-three patients (26.8%) had anti-nuclear antibody positivity. Biologic agents were needed in 60 patients (48.8%). Complications developed in 14 patients (11.4%). Early age at disease onset (aOR, 0.875; 95% C.I. 0.795–0.965, p = 0.007) and female gender (aOR, 2.99; 95% C.I. 1.439–6.248, p = 0.003) were significantly associated with the need for biologic treatment, while Behçet’s disease (BD) was strongly associated with uveitis-related complications (aOR, 14.133; 95% C.I. 2.765–72.231, p = 0.001).ConclusionWe suggest that among pediatric patients with non-infectious uveitis, females, those with an early age of disease onset, and those with BD need to be closely monitored due to a significantly increased risk of severe disease.Key Points• Limited data exist on the clinical course of non-infectious uveitis in children and the associated risk factors for severe disease.• Our study reveals that nearly a quarter of pediatric patients with non-infectious uveitis also have a rheumatic disease.• Among pediatric patients diagnosed with non-infectious uveitis, we observed an increased risk of severe disease in those with an earlier onset age, in female patients, and in those diagnosed with Behçet’s disease.

Narrative Ability in Autism and First-Degree Relatives.

Narrative is an important communication skill for sharing personal experiences and connecting with others. Narrative skills are often impacted in autism spectrum disorder (ASD) and have important consequences for social interactions and relationships. Subtle differences in narrative have also been reported among first-degree relatives of autistic individuals, suggesting that narrative may also be an etiologically important language-related skill that is influenced by genes associated with ASD. This study examined narrative ability and related visual attention during narration in ASD and first-degree relatives of individuals with ASD (siblings and parents) to understand how narrative and related attentional styles may be variably impacted across the spectrum of ASD genetic influence. Participants included 56 autistic individuals, 42 siblings of autistic individuals, 49 controls, 161 parents of autistic individuals, and 61 parent controls. Narratives were elicited using a wordless picture book presented on an eye tracker to record concurrent gaze. Findings revealed parallel patterns of narrative differences among ASD and sibling groups in the use of causal language to connect story elements and the use of cognitive and affective language. More subtle differences within the domain of causal language were evident in ASD parents. Parallel patterns in the ASD and sibling groups were also found for gaze during narration. Findings implicate causal language as a critical narrative skill that is impacted in ASD and may be reflective of ASD genetic influence in relatives. Gaze patterns during narration suggest similar attentional mechanisms associated with narrative among ASD families.

From the First Case Reports to KDM1A Identification: 35 Years of Food (GIP)-Dependent Cushing's Syndrome.

Food-dependent Cushing's syndrome (FDCS) is a rare presentation of hypercortisolism from adrenal origin, mostly observed in primary bilateral macronodular adrenal hyperplasia (PBMAH) but also in some cases of unilateral adrenocortical adenoma. FDCS is mediated by the aberrant expression of glucose-dependent insulinotropic peptide (GIP) receptor (GIPR) in adrenocortical cells. GIP, secreted by duodenal K cells after food intake, binds to its ectopic adrenal receptor, and stimulates cortisol synthesis following meals. FDCS was first described more than 35 years ago, and its genetic cause in PBMAH has been recently elucidated: KDM1A inactivation by germline heterozygous pathogenic variants is constantly associated with a loss-of-heterozygosity of the short arm of chromosome 1, containing the KDM1A locus. This causes biallelic inactivation of KDM1A, resulting in the GIPR overexpression in the adrenal cortex. These new insights allow us to propose the KDM1A genetic screening to all PBMAH patients with signs of FDCS (low fasting cortisol that increases after a mixed meal or oral glucose load) and to all first-degree relatives of KDM1A variant carriers. Given that KDM1A is a tumor suppressor gene that has also been associated with monoclonal gammopathy of uncertain significance and multiple myeloma, the investigation of FDCS in the diagnostic management of patients with PBMAH and further genetic testing and screening for malignancies should be encouraged.