Familial Clustering Research Articles

Observation of SARS-CoV-2 genome characteristics and clinical manifestations within eight family clusters from GH and GK clades in Jakarta, Indonesia

Background: SARS-CoV-2 rapid mutation generates many concerning new strains. Although lockdown had been applied to contain the disease, the household remains a critical place for its transmission. This study aimed to assess the variation of SARS-CoV-2 strains and their clinical manifestations within family clusters in Jakarta, Indonesia. Method: Naso-oropharyngeal swab specimens from family clusters positive for SARS-CoV-2 were collected for whole-genome sequencing. Their baseline data, symptoms, and source of infection were recorded. The whole-genome data was then analyzed with the bioinformatics program to evaluate the SARS-CoV-2 genome characteristic and submitted to GISAID for strain identification. The phylogenetic tree was built to observe the relationship between virus strain within the family cluster and its clinical manifestation. Result: This study obtained eight family clusters from twenty-two patients. Half of the cluster’s source of infection was a family member who had to work at the office. The infection rate ranged from 37.5% to 100%. The phylogenetic tree showed that the same virus within a cluster could generate various clinical outcomes. Five clusters had one family member with pneumonia, while others had mild to no symptoms. Four breakthrough cases were detected in this study, which were infected by the virus from GH and GK clade. Conclusion: Our study observed the SARS-CoV-2 transmission to the household setting through the workplace, which might become a common pathway if the pandemic status is removed. Although vaccination is expected to reduce the burden of COVID-19, adequate control measures remain essential, given that breakthrough infections are evident.

Heterogeneity in familial clustering of metabolic syndrome components in the multiethnic GENNID study.

Metabolic syndrome (MetS) is defined by clustering of cardiometabolic components, which may be present in different combinations. The authors evaluated clustering in individuals and extended families within and across ancestry groups. The prevalence of different combinations of MetS components (high fasting glucose, low high-density lipoprotein cholesterol, high triglycerides, high blood pressure, and abdominal obesity) was estimated in 1651 individuals (340 families) self-reporting as European American (EA), Hispanic/Mexican American (MA), African American (AA), and Japanese American (JA). Odds ratios were estimated using logistic regression with generalized estimating equations comparing individual MetS components, number, and combinations of components for each ancestry group versus EA. Clustering of all five components (Combination #16) was more prevalent in EA (29.9%) and MA (25.2%) individuals than in AA (18.7%) and JA (15.5%) individuals. Compared with EA individuals, AA individuals were 64% and 66% less likely to have high triglycerides and low high-density lipoprotein cholesterol, whereas JA individuals were 85% and 56% less likely to have abdominal obesity and high blood pressure, respectively. Compared with EA individuals, the odds of having two, four, or five components were at least 77% lower in JA individuals, whereas the odds of having three, four, or five components were at least 3.79 times greater in MA individuals. Understanding heterogeneity in MetS clustering may identify factors important in reducing health disparities.

Familial clustering of nonalcoholic fatty liver disease in first-degree relatives of adults with lean nonalcoholic fatty liver disease.

The heritability of nonalcoholic fatty liver disease (NAFLD) in lean individuals is undetermined. This familial aggregation study aimed to evaluate familial linkage for NAFLD and the risk of NAFLD among first-degree relatives of probands with lean NAFLD. This study prospectively recruited cohorts of probands with lean NAFLD, probands with obese NAFLD, and lean probands with non-NAFLD and their respective first-degree relatives. A total of 257 participants were evaluated for liver steatosis, defined by the controlled attenuation parameter ≥288 dB/m2 , metabolic characteristics, and the PNPLA3, TM6SF2, and MBOAT7 polymorphisms. The prevalence of NAFLD in first-degree relatives of lean NAFLD probands (39.9%) was similar to that in the obese NAFLD group (36.9%) and was significantly higher than in lean persons without NAFLD (19.1%). First-degree relatives of probands with NAFLD who were male, and had central obesity, hypertriglyceridaemia, insulin resistance, and the PNPLA3 rs738409C>G allele had a significantly higher prevalence of NAFLD. After multivariable adjustment for gender, metabolic characteristics, and the PNPLA3 rs738409C>G allele, first-degree relatives of probands with lean NAFLD (odds ratio [OR], 5.13; 95% CI, 1.77-14.86) and obese NAFLD (OR, 3.20; 95% CI, 1.14-8.99) exhibited an increased risk of NAFLD compared with those of lean controls without NAFLD. Our well-phenotype cohorts revealed familial clustering of NAFLD and higher risks of NAFLD in first-degree relatives of probands with lean or obese NAFLD. The findings encourage clinicians caring for NAFLD patients to be more vigilant for NAFLD in their family members.

FRI269 Two Cases Of Familial Polyglandular Autoimmune Syndrome Type II Presenting With Adrenal Insufficiency Precipitated By SARS-CoV-2 Infection

Abstract Disclosure: J. Sassic: None. N. Hosein: None. G. Jackson: None. Introduction: Polyglandular autoimmune syndrome (PGA) type II is characterized primarily by autoimmune adrenal disease and thyroid disease. Additionally, about 50% of patients will experience autoimmune diabetes mellitus. The incidence of PGA type II is around 1:20,000 but shows strong familial clustering, and predominantly affects women in a 3:1 ratio. Here we report a case of two patients, a woman and her son, who were diagnosed 6 months apart with type II PGA who presented with adrenal insufficiency acutely affected by SARS-CoV-2 infection. Clinical Case: Patient 1 is a 59 year-old female with history significant for previously-diagnosed autoimmune thyroiditis who presented with complaint of generalized fatigue and weight loss for months following a SARS-CoV-2 infection, who was found to have severe hyponatremia with serum sodium of 106 mmol/L (137-145 mmol/L) and was admitted to the intensive care unit. There, she received cosyntropin testing which revealed severe adrenal insufficiency, with post-cosyntropin cortisol level at 1.2 mcg/dL (>14 mcg/dL). Anti-21-hydroxylase antibodies were positive. Her A1c was found to be 5.8% (<5.7%), indicating prediabetes in a patient with BMI of 18.5 kg/m2. Glutamic acid decarboxylase antibodies were tested and were also positive. Patient’s sodium was repleted and she was tapered from stress-dose to physiologic steroid dosing and was discharged on hydrocortisone and fludrocortisone. About 6 months later, Patient 2, a 25-year-old male and the son of Patient 1 presented to the emergency department with complaint of a week of nausea and vomiting, and three months of generalized fatigue. He was found to be SARS-CoV-2 positive and was also hyponatremic with serum sodium of 122 mmol/L. He also received cosyntropin testing which was revealed undetectably low cortisol levels both pre- and post-cosyntropin administration. Anti-21-hydroxylase antibodies and anti-thyroid peroxidase antibodies were positive, the latter at 243.3 IU/mL (<5.61 IU/mL). Patient responded well to stress-dose steroids and normal saline to normalize his sodium levels. Due to his mother’s positive antibodies, glutamic acid decarboxylase, anti-islet, and anti-insulin antibodies were also tested, which were negative. Patient was discharged on physiologic hydrocortisone and fludrocortisone. Conclusion: Polyglandular autoimmune syndrome is a relatively uncommon disease but with strong polygenic inheritance. This case was an interesting presentation where SARS-CoV-2 infection likely precipitated the symptoms and acute effects of adrenal insufficiency. Additionally, knowledge of the patient’s family history resulted in rapid diagnosis and management of the patient’s underlying pathophysiology. Presentation: Friday, June 16, 2023

FAKTOR-FAKTOR YANG BERHUBUNGAN DENGAN PERILAKU PENCEGAHAN PENULARAN COVID-19 PADA KLASTER KELUARGA BERDASARKAN THEORY OF PLANNED BEHAVIOR

Cilacap Regency had 29,219 confirmed cases of COVID in September 2021. The household or family cluster is considered to be one of the most prominent transmitters of COVID-19 in Cilacap Regency, Central Java. Based on secondary data obtained, confirmed cases of COVID-19 in the work area of the UPTD Puskesmas Kroya I reached 860 cases with cases per cluster, namely the religious activities cluster 16 cases, the market cluster 23 cases, the boarding school cluster 86 cases, and the highest was the family cluster 85% (735 cases). This study aims to analyze the factors associated with COVID-19 transmission prevention behavior in the family cluster based on the Theory of Planned Behavior. This type of research is quantitative research with an observational analytic study design using a cross-sectional approach. The sample in the study was wives / housewives of adult age (20-60) years, sampling using cluster sampling technique with a total sample of 296 people. Data were collected using an instrument in the form of a questionnaire, data analysis was carried out, namely univariate analysis, bivariate using chi square test, and multivariate using regression test, data were analyzed using SPSS. The results showed that there was a relationship between attitude (p=0,024), subjective norm (p=0,003), perceived behavioral control (p=0,015) with intention. A relationship between attitude (p=0,008), subjective norm (p=0,000), perceived behavioral control (p=0,024), intention (p=0,000) with COVID-19 transmission prevention behavior. It is necessary to provide information related to COVID-19 to the family cluster in order to improve COVID-19 prevention behavior properly.

Epidemiological and molecular evidence of intrafamilial transmission through sexual and vertical routes in Bahia, the state with the highest prevalence of HTLV-1 in Brazil.

Familial clustering of HTLV-1 and related diseases has been reported in Brazil. However, intrafamilial transmission of HTLV-1 based on molecular analysis has been studied only in a few communities of Japanese immigrants and African-Brazilians. To investigate the familial clustering of HTLV-1 infection and to determine the likely routes of transmission through epidemiological and genetic analyzes. Medical records of 1,759 HTLV-1+ patients from de the Center for HTLV in Salvador, Brazil, were evaluated to identify first-degree relatives previously tested for HTLV-1. Familial clustering was assumed if more than one member of the same family was HTLV-1+. LTR regions of HTLV-1 sequences were analyzed for the presence of intrafamilial polymorphisms. Family pedigrees were constructed and analyzed to infer the likely transmission routes of HTLV-1. In 154 patients at least one other family member had tested positive for HTLV-1 (a total of 182 first-degree relatives). Of the 91 couples (182 individuals), 51.6% were breastfed, and 67.4% reported never using a condom. Of the 42 mother-child pairs, 23.8% had a child aged 13 years or younger; all mothers reported breastfeeding their babies. Pedigrees of families with 4 or more members suggests that vertical transmission is a likely mode of transmission in three families. Three families may have had both vertical and sexual transmission routes for HTLV-1. The genetic signatures of the LTR region of 8 families revealed 3 families with evidence of vertical transmission, another 3 families (spouses) with sexual transmission, and one family with both transmission routes. HTLV-1 sequences belonged to Cosmopolitan subtype HTLV-1a Transcontinental subgroup A. Sexual and vertical transmission routes contribute to the intrafamilial spread of HTLV-1 in the state of Bahia.

Human leukocyte antigen association in systemic sclerosis patients: our experience at a tertiary care center in North India.

Systemic sclerosis (SSc) is a chronic multisystem autoimmune rheumatic disease of unknown etiology. Several studies have established that SSc is triggered by a dynamic interplay between genetic factors and environmental stimuli. In the present study, we aimed to study the association of human leukocyte antigen (HLA) with familial and non-familial SSc patients [limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc)] from North India. The HLA-A, B, DRB1, and DQB1 genotyping of 150 (70 lcSSc and 80 dcSSc) adult-onset SSc patients and 150 age-gender-matched healthy controls were performed with sequence-specific oligonucleotide (SSO) typing kits using the luminex platform. HLA typing for HLA class I (A, B, and C) and II (DRB1, DQB1, and DPB1) in five North Indian families consisting of parent-child/sibling pairs affected with SSc or overlap syndrome was performed by Next Generation Sequencing (NGS) with Illumina MiniSeq. Among the non-familial SSc patients, HLA- DRB1*11 (P = 0.001, OR: 2.38, P c = 0.01) was identified as a risk allele, and DRB1*12 (P = .0001, OR: 0.00, P c = 0.001) as a protective allele. There was no statistical association found with HLA-DQB1*. Also, no significant association was observed between HLA antigens and different clinical subsets (lcSSc and dcSSc) of SSc. Two cases of familial SSc patients had the DRB1*11 allele. The DRB1*12 allele was absent in all the familial SSc patients. HLA DRB1*11 (risk allele) and DRB1*12 (protective allele) were found to be strongly associated with non-familial SSc patients and partially explain the disease's familial clustering, supporting the susceptible genetic background theory for SSc development. The study also indicates the HLA allele as a common genetic risk factor in distinct autoimmune diseases contributing to overlap syndrome or polyautoimmunity.

Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown. This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality. Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36-2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07-4.27; PHeterogeneity= 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36-1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67-2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01-1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15-3.23), but not of HCC (aHR 1.43, 95% CI 0.87-2.35). There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low. Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.

Inheritance-Specific Dysregulation of Th1- and Th17-Associated Cytokines in Alopecia Areata.

Autoimmune diseases tend to cluster in families, suggesting genetic predisposition to autoimmunity associated with familial background. We have previously reported similarities in gene expression patterns and PTPN22 polymorphisms between alopecia areata (AA) patients and their healthy relatives, but not unrelated healthy controls. However, the spectrum of disease promoting (or preventing) pathways that may be activated in blood relatives of AA patients remains to be defined. Here, we investigated the extent to which cytokines associated with the Th1 and Th17 pathway are differentially expressed in the blood of patients with AA and its clinical subtypes in comparison to both healthy relatives as well as unrelated healthy controls. A comprehensive set of Th1- and Th17-related cytokines were evaluated by ELISA. We found a significant elevation of the Th17 inducer IL-23, the Th17 product IL-17A, the Th1 hallmark cytokine IFNγ, and TNFα, a Th1 cytokine with relevance to the Th17 pathway in AA patients, regardless of disease subtype, compared to healthy individuals. On further examination, we found that healthy family members grouped together with patients in terms of elevated Th1- and Th17-pathway cytokines in an inheritance-specific manner, distinct from unrelated controls. The elevation of Th17-associated cytokines in healthy controls related to AA patients indicates that Th1 and Th17 dysregulation in AA may be genetically based. Of note, one unrelated control displayed elevated levels of IL-17A and IL-23 similar to those detected in patients. One year after initial blood draw, areas of beard hair loss consistent with the diagnosis of AA were reported by this individual, indicating that the elevation in Th17-related cytokines may have predictive value.

Na1.5Cs0.5[Al{BO3}{B9O15(OH)3}1/3]: An Acentric Layered Aluminoborate with Nonlinear-Optical Properties.

An acentric aluminoborate (ABO), Na1.5Cs0.5[Al{BO3}{B9O15(OH)3}1/3] (1), has been made under solvothermal conditions. The alternations of AlO4 tetrahedra and BO3 triangles first build up the 2D ABO layer with 6-MR (membered-ring) windows. The fanlike B9O15(OH)3 cluster adorns the layer through Al-O-B linkages, producing a pair of unclosed channels with 7-MR aperture on the lateral side of the layers. The novel B9O15(OH)3 cluster represents the largest oxoboron cluster in the acentric ABO family. 1 not only shows a moderate second-harmonic-generation response of 1.2 times that of potassium dihydrogen phosphate but also has a short cutoff edge below 200 nm, indicating its potential applications in deep-UV regions.

A Proposed Artificial Intelligence Model for Android-Malware Detection

There are a variety of reasons why smartphones have grown so pervasive in our daily lives. While their benefits are undeniable, Android users must be vigilant against malicious apps. The goal of this study was to develop a broad framework for detecting Android malware using multiple deep learning classifiers; this framework was given the name DroidMDetection. To provide precise, dynamic, Android malware detection and clustering of different families of malware, the framework makes use of unique methodologies built based on deep learning and natural language processing (NLP) techniques. When compared to other similar works, DroidMDetection (1) uses API calls and intents in addition to the common permissions to accomplish broad malware analysis, (2) uses digests of features in which a deep auto-encoder generates to cluster the detected malware samples into malware family groups, and (3) benefits from both methods of feature extraction and selection. Numerous reference datasets were used to conduct in-depth analyses of the framework. DroidMDetection’s detection rate was high, and the created clusters were relatively consistent, no matter the evaluation parameters. DroidMDetection surpasses state-of-the-art solutions MaMaDroid, DroidMalwareDetector, MalDozer, and DroidAPIMiner across all metrics we used to measure their effectiveness.

Increasing number of long-lived ancestors marks a decade of healthspan extension and healthier metabolomics profiles

Globally, the lifespan of populations increases but the healthspan is lagging behind. Previous research showed that survival into extreme ages (longevity) clusters in families as illustrated by the increasing lifespan of study participants with each additional long-lived family member. Here we investigate whether the healthspan in such families follows a similar quantitative pattern using three-generational data from two databases, LLS (Netherlands), and SEDD (Sweden). We study healthspan in 2143 families containing index persons with 26 follow-up years and two ancestral generations, comprising 17,539 persons. Our results provide strong evidence that an increasing number of long-lived ancestors associates with up to a decade of healthspan extension. Further evidence indicates that members of long-lived families have a delayed onset of medication use, multimorbidity and, in mid-life, healthier metabolomic profiles than their partners. We conclude that both lifespan and healthspan are quantitatively linked to ancestral longevity, making family data invaluable to identify protective mechanisms of multimorbidity.

Comparative transcriptome and gene co-expression network analysis identifies key candidate genes associated with resistance to summer mortality in the Pacific oyster (Crassostrea gigas)

The global oyster industry is severely hampered by frequent outbreaks of summer massive mortalities. Selective breeding of disease-resistant broodstock is considered as a key strategy to address this problem, and marker-assisted selection programs would help develop oyster lines that are resistance to summer mortality. However, there is currently a need to identify candidate genes associated with disease resistance and to develop molecular markers based on these genes. To identify candidate genes associated with summer mortality resistance, we selected three most resistant and three most susceptible oyster families and compared their basal transcriptomes. A total of 59 families were tested in two sites, and there were significant differences in summer survival among families of different genetic backgrounds. Principal component analysis showed that there was significant clustering of different resistant families, suggesting that the molecular mechanisms underlying the development of resistance characteristics in different resistant families may be similar. Interestingly, transcriptome results showed that the highly expressed genes in resistant families were mainly associated with innate immunity, especially some pattern recognition receptors, including C-type lectins, fibrinogen-related proteins and scavenger receptors. Some transient receptor potential family genes showed differential expression in the both resistant and susceptible families, which may be related to the thermal tolerance of oysters. Notably, some genes related to antioxidant responses and detoxification were highly expressed in resistant families, such as glutathione S-transferase and Cytochrome P450, suggesting that oysters with summer mortality resistance may have greater antioxidant and detoxification capacities. In addition, weighted gene co-expression network analysis (WGCNA) identified three modules that were significantly positively associated with summer survival. The network map of key modules allows us to identify a series of hub genes, such as PEAR1, MCT12, RPL23, TRPM2, MFAP4, TLN1, SCARF1, GAL9 and ACOD. Overall, our study provides new insight into summer mortality resistance by employing comparative transcriptome and WGCNA, and the genes identified in this study should be further investigated for use in marker-assisted selection breeding programs.

Heredity of pregnancy-related pelvic girdle pain in Sweden.

Pelvic girdle pain during and after pregnancy is a major public health problem with significant daily problems for affected women and their families. There is now accumulating evidence that pregnancy-related pelvic girdle pain originates from the sacroiliac joints and the pubic symphysis as well as their extra-articular ligaments. However, the heritability of the disease remains to be determined. We hypothesized that there is an increased familial risk of pregnancy-related pelvic girdle pain. A population-based national database linkage registry study of approximately 9.3 million individuals within 4.2 million families in Sweden with a recruitment period from 1997 to 2018. The Swedish Multi-generation register was used to find female pairs of twins, full siblings, half-siblings and first cousins where both in the pairs had a completed pregnancy. The outcome measure was diagnosis of pregnancy-related pelvic girdle pain (International Classification of Diseases-10 O26.7 [1997-2018]) in the first pregnancy. Data was obtained from the Swedish Hospital Discharge Register, the Swedish Outpatient Care Register, the Swedish Medical Birth Register, the Primary Healthcare Register, and Medical Treatment Register. Cox regression analysis was used to calculate adjusted estimated effect of the exposure variable familial history of pregnancy-related pelvic girdle pain on the outcome variable pregnancy-related pelvic girdle pain at first birth. From the registers, 1 010 064 women pregnant with their first child within 795 654 families were collected. In total, 109 147 women were diagnosed with pregnancy-related pelvic girdle pain. The adjusted hazard ratio for a familial risk of pregnancy-related pelvic girdle pain was 2.09 (95% CI 1.85-2.37) among twins (monozygotic and dizygotic), 1.78 (95% CI 1.74-1.82) in full siblings, 1.16 (95% CI 1.06-1.28) in half-siblings from the mother, 1.09 (95% CI 1.024-1.16) in half-siblings from the father and 1.09 (95% CI 1.07-1.12) in first cousins. This nationwide observational study showed a familial clustering of pregnancy-related pelvic girdle pain. The hazard ratio for the condition was associated with the degree of relatedness, suggesting that heredity factors contribute to the development of pregnancy-related pelvic girdle pain. There is no causal treatment available for pregnancy-related pelvic girdle pain and further studies are now encouraged to clarify the specific genetic factors that contribute to the disease and for future targeted interventions.

Recommendations for the Management of Cardiomyopathy Mutation Carriers: Evidence, Doubts, and Intentions.

Cardiomyopathies may be hereditary and associated with a familial predilection. Morbidity and mortality can be caused by heart failure, sudden death, or arrhythmias. Sometimes these events are the first manifestations of cardiovascular disease. Hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy are perhaps most thoroughly studied in that context. Dilated cardiomyopathy, although most frequently of secondary etiology, has a significant familial cluster. Noncompaction of the left ventricle can sometimes be seen in healthy individuals and, in other instances, is associated with severe LV dysfunction. Genetic testing is of utmost importance, since it might allow for the identification of individuals carrying mutations predisposing them to these diseases. In addition, certain variants may benefit from tailored therapeutic regimens, and thus searching for a causal mutation can impact clinical practice and is recommended for all patients with HCM or ACM. Patients with DCM and positive family history should be included as well. Regular follow-ups are advised, even in those with negative phenotypes, because these disorders are often age dependent. During pregnancy and in the case of athletes, special consideration should be made as well. We intend to summarize the most current evidence regarding their management.

Familial Analysis of Nonunion in a Genealogic Population Database Demonstrates No Evidence of Heritable Risk.

To determine whether there is evidence of heritable risk for nonunion using a large, state-wide population database. Database. Level 1 Trauma Center. All Utah residents from 1996 to 2021 who sustained a long bone fracture and their family members were included. The primary outcome was nonunion and the prevalence of nonunion among the patients' first-, second-, and third-degree relatives. The secondary objective was to identify demographic, injury, and socioeconomic risk factors associated with nonunion. In total, 150,263 fractures and 6577 nonunions (4.4%) were identified. This was highly refined to a 1:3 matched cohort of 4667 nonunions of 13,981 fractures for familial clustering analysis. Cox proportional hazards did not demonstrate excessive risk of nonunion among first- ( P = 0.863), second- ( P = 0.509), and third-degree relatives ( P = 0.252). Further analysis of the entire cohort demonstrated that male sex (relative risk [RR] = 1.15; P < 0.001), Medicaid enrollment (RR = 2.64; P < 0.001), open fracture (RR = 2.53; P < 0.001), age group 41-60 years (RR = 1.43; P < 0.001), and a history of obesity (RR = 1.20; P < 0.001) were independent risk factors for nonunion. Our results demonstrate no evidence of heritable risk for nonunion. Independent risk factors for nonunion were male sex, Medicaid enrollment, open fracture, middle age, and a history of obesity. Although it is important to identify modifiable and nonmodifiable risk factors, these results continue to support that the risk of nonunion is multifactorial, relating to injury characteristics, operative techniques, and patient-specific risk factors. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Weighing poor immunometabolic health in relatives for severity of affective symptoms: A study of patients with depressive and anxiety disorders and their siblings

BackgroundAffective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands’ immunometabolic health on siblings’ psychological symptoms and on the association between immunometabolic health and these symptoms in siblings. MethodsThe sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering. ResultsIn siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p < 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings. ConclusionsOur findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health.

Effect of Family-Based Education on Improving Family Health Tasks in Preventing the Transmission of Covid-19

Background: During the 2020 pandemic, West Java established 4 red zones (where the transmission of Covid-19 was considered high), one of the cities was Cimahi. Based on the data, the accumulation cases was dominated by family clusters, so the government established policies to protect family members from Covid-19 transmission, namely modifying behaviours relating to carrying out activities by implementing health protocols. Consistency in implementing health protocols is way to prevent the transmission of Covid-19. Family-based education also has an important role to socialize and teach family members about health protocols that must be adhered to during the Covid-19 pandemic. The existence of Family-based has been found to improve the implementation of health tasks in the family.Objective: This study aims to determine the effect of family-based education on improving family health tasks in preventing the transmission of Covid-19.Methods: The research design used a quasi-experimental pre- and post-test control group design. The research respondents were 31 families for the intervention group and 31 families for the control group. The sampling technique was proportional random sampling. The educational intervention as provided in 3 meetings. Data analysis used Wilcoxon and Mann-Whitney.Results: The results showed that there family-based education had an effect on increasing family health tasks relation to the prevention of the transmission of Covid-19 because the p-value was 0.000.Conclusions: Therefore, it was recommended that the head of the Public Health and Disease Control program implement family-based education in order to prevent the transmission of Covid 19 within the family and community.

Seroprevalence of SARS-CoV-2 and risk factors in Bantul Regency in March-April 2021, Yogyakarta, Indonesia.

COVID-19 case counts in Indonesia inevitably underestimate the true cumulative incidence of infection due to limited diagnostic test availability, barriers to testing accessibility and asymptomatic infections. Therefore, community-based serological data is essential for understanding the true prevalence of infections. This study aims to estimate the seroprevalence of SARS-CoV-2 infection and factors related to the seropositivity in Bantul Regency, Yogyakarta, Indonesia. A cross-sectional study involving 425 individuals in 40 clusters was conducted between March and April 2021. Participants were interviewed using an e-questionnaire developed in the Kobo toolbox to collect information on socio-demographic, COVID-19 suggestive symptoms, history of COVID-19 diagnosis and COVID-19 vaccination status. A venous blood sample was collected from each participant and tested for immunoglobulin G (Ig-G) SARS-CoV-2 antibody titers using the enzyme-linked immunosorbent assay (ELISA). Seroprevalence was 31.1% in the Bantul Regency: 34.2% in semi-urban and 29.9% in urban villages. Participants in the 55-64 age group demonstrated the highest seroprevalence (43.7%; p = 0.00), with a higher risk compared to the other age group (aOR = 3.79; 95% CI, 1.46-9.85, p<0.05). Seroprevalence in the unvaccinated participants was 29.9%. Family clusters accounted for 10.6% of the total seropositive cases. No significant difference was observed between seropositivity status, preventive actions, and mobility. Higher seroprevalence in semi-urban rather than urban areas indicates a gap in health services access. Surveillance improvement through testing, tracing, and treatment, particularly in areas with lower access to health services, and more robust implementation of health protocols are necessary.

Koala retrovirus status and putative koala retrovirus-associated diseases in koalas (Phascolarctos cinereus) in North American zoos. In Proceedings of the Second Koala Retrovirus Workshop, ed. D. E. Alquezar-Planas, D. P. Higgins, C. L. Singleton, and A. D. Greenwood

The living koala population in North America is predominantly descended from koalas imported from a single Australian facility in 1976 and 1981, with several smaller imports from other facilities between 1985 and 2013. Koala retrovirus subtype B (KoRV-B) entered the North American population via imports in 2005, 2008, and 2013. The 2005 and 2008 KoRV-B positive lineages are deceased, but the 2013 KoRV-B positive lineage has seven surviving koalas, including one female of breeding age. Three koalas born to KoRV-B negative dams were documented as being KoRV-B positive at 15 months of age after nursing from a KoRV-B positive female. The prevalence of koala retrovirus subtype A (KoRV-A) detection in North America is 100% but the prevalence of KoRV-B detection is 17%. Lymphoid neoplasia is a common cause of mortality, dating back to founder koalas. Most cases of lymphoid neoplasia have occurred in presumptive KoRV-B negative koalas, and many cases have occurred between the ages of four and nine years. Familial clusters of lymphoid neoplasia are apparent. Additionally, myelodysplasia and fatal peripheral cytopenias are important putative KoRV-associated diseases that cause mortality in koalas in North America, with higher prevalence in koalas younger than two years of age. Since 2013, breeding of known KoRV-B positive koalas has been managed, to maintain separation from the remainder of the KoRV-B negative population.