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IntroductionThe etiology of substance-induced psychotic disorder (SIPD) is an important research area to study.ObjectivesIt is aimed to investigate clinical risk status for psychosis, schizotypal features and neurocognitive functions in siblings of the patients who have been diagnosed as SIPD and who have no family history of psychotic spectrum disorder.MethodsThis study included 41 healthy siblings of patients who have been diagnosed as SIPD according to DSM-V and 41 healthy controls without family history of psychiatric disorders (matched on age, gender, and years of education). The data collected with sociodemographic and clinical data form, Digid Span Test, Trail Making Test A, Trail Making Test B, Verbal Fluency Test and Stroop Test, Comprehensive Assesment of At-Risk Mental States (CAARMS) and Structured Interview for Schizotypy-Revised.ResultsIt is determined that %41.5 of siblings and %7.3 of healthy controls are in one of the clinical high risk groups for psychosis according to CAARMS. There is significant difference in Trail Making Test A error and Trail Making Test B error and correction, verbal fluency test- lexical fluency-perseveration mean scores between siblings of patients and healthy controls.ConclusionsSiblings of patients with SIPD have more schizotypal features than healthy control group and they take part more frequent in one of high risk group for psychosis. Schizotypal features are known as trait factor and show genetic predisposition. Siblings who are in high risk groups have more schizotypal features and it may point that predisposition to psychosis is more related to underlying genetic predisposition than environmental factors and social stressors.DisclosureNo significant relationships.

Purpose Mesothelioma is the primary tumor of the mesothelial cell membrane. The most important etiology is asbestos exposure. The development of malignant mesothelioma in very few of the population exposed to asbestos and its frequent occurrence in some families may be significant in terms of genetic predisposition. Again, the presence of relatives with mesothelioma who did not have asbestos contact strengthens this argument. This disease, which has limited treatment options and has a poor prognosis, revealing a genetic predisposition, if any, may prolong survival with early diagnosis and effective treatment. Methods Based on the genetic predisposition idea, we diagnosed and followed a total of ten individuals of relatives with mesothelioma. DNA was isolated from peripheral blood and whole genome sequencing analysis was done. Common gene mutations in ten individuals were filtered using bioinformatics. After this filter, from the remaining variants, very rare in the population and damaging mutations are selected. Results Eight thousand six hundred and twenty-two common variants have been identified in ten individuals with this analysis. In total, 120 variants were found on 37 genes in 15 chromosomes. These genes are PIK3R4, SLC25A5, ITGB6, PLK2, RAD17, HLA-B, HLA-DRB1, HLA-DQB1, GRM, IL20RA, MAP3K7, RIPK2, and MUC16. Conclusion Our finding, PIK3R4 gene, is directly associated with mesothelioma development. Twelve genes, which are associated with cancer, were detected in literature. Additional studies, which scan first-degree relatives of individual, are needed to find the specific gene region.

Introduction Parental predisposition and age of onset may be independently associated with 1-year total weight loss (TWL) failure (< 20%) after metabolic–bariatric surgery (MBS). Methods This cohort study includes all cases of the German StuDoQ|MBE register (2015–2019) with data on parental predisposition, obesity onset, and at least 1-year follow up after primary MBS procedures ( n  = 14,404). We provide descriptive statistics of the cohort in terms of the main outcome and 1-year TWL failure, and provide characteristics of surgery type subgroups. Finally, we provide a multivariate logistic regression model of 1-year TWL failure. Results 58.8% and 45.7% of patients reported maternal and paternal predisposition for obesity, respectively. Average onset of obesity was 15.5 years and duration of disease 28.3 years prior to MBS. SG is the most frequently performed procedure (47.2%) followed by RYGB (39.7%) and OAGB (13.1%). Mean 1-year TWL is 32.7 ± 9.3%, and 7.8% ( n  = 1,119) of patients show TWL failure (< 20%). Multivariate analysis shows independent association of early onset of obesity (< 18 years), male sex, age at operation, pre-operative BMI, pre-operative weight loss, sleeve gastrectomy (SG), and type 2 diabetes (T2D) with 1-year TWL failure ( p  < 0.001). Conclusion The proportions of MBS patients that report on paternal and maternal predisposition for obesity are 45.7% and 58.8% respectively, and average age at onset is 15.5 years. 7.8% of patients do not meet current target criteria of successful response to surgery at 1 year. Early onset, male sex, age at operation, pre-operative BMI, pre-operative weight loss, SG, and T2D are independently associated with weight loss failure. Graphical abstract

To characterize the distinct clinicopathological patterns and identify independent risk factors in synchronous breast-thyroid dual primary malignancies (DBTMs), a rare yet clinically significant entity. In this retrospective case-control study (2019.03-2021.12), 58 DBTM patients were compared with 89 age-matched solitary breast cancer controls. Comprehensive clinicopathological parameters including hormone receptor status and molecular profiles were analyzed. Multivariable logistic regression identified prognostic determinants with 2-year follow-up for recurrence/metastasis and survival outcomes. Statistically significant differences were observed in age, BMI, menopausal status, ER, PR, and HER-2 status between the study and control groups (P < 0.05). During the 2-year follow-up, the study group had 12 cases of recurrence or metastasis and 5 deaths, while the control group had 9 cases of recurrence or metastasis and 2 deaths (P < 0.05). Univariate analysis indicated that age, breast cancer stage, and ER status were associated with overall survival in patients with synchronous primary breast and thyroid cancer. Additionally, age, breast cancer stage, ER status, menopausal status, and a family history of breast cancer were significantly associated with recurrence or metastasis (P < 0.05). Multivariate logistic regression analysis identified age, ER positivity, and a family history of breast cancer as independent risk factors for synchronous primary breast and thyroid cancer (P < 0.05). This first matched case-control analysis reveals that synchronous DBTMs represent a unique clinical subgroup with aggressive biological behavior. The identified triad of young age, ER positivity, and familial predisposition provides a risk stratification framework for dual-cancer screening and targeted surveillance strategies.

There is sparse literature on parental chronic obstructive pulmonary disease (COPD) as a risk factor for the development of COPD in adult offspring, and the impact on disease severity. We aimed to map the literature reporting on the prevalence of and/or association between parental COPD and COPD in offspring, and to evaluate whether or not the literature reports on the severity of COPD or other health-related outcomes in offspring with parental COPD. A systematic literature search in Embase and Ovid MEDLINE was performed in June 2021. Search terms revolved around COPD and predisposition. Thirteen studies were identified: 10 case-control studies, two cross-sectional studies and one cohort study. Population size varied from 44 to 2668 offspring cases; the distribution of female cases varied from 5% to 80% and mean age ranged from 27 to 65. Nine studies used an antecedents approach and evaluated the prevalence of parental COPD in patients with COPD, which ranged from 19% to 58%. Four studies used a descendants approach, by identifying patients with COPD and subsequently evaluated prevalence of COPD in their offspring, and found a prevalence of 0% to 17%. Apart from one, all the studies found an increased odds ratio for COPD in individuals with parental COPD. Four studies reported on parental smoking history and nine studies reported on smoking history in offspring. Three studies evaluated the association between parental COPD and COPD-related outcomes in patients with COPD. This review indicates that parental COPD is associated with a higher risk of COPD in offspring. The literature is sparse, and we identified a knowledge gap on whether parental COPD is a risk factor for severe COPD and other health conditions in offspring.

Background Endometriosis is a common, chronic disease among fertile-aged women. Disease course may be highly invasive, requiring extensive surgery. The etiology of endometriosis remains elusive, though a high level of heritability is well established. Several low-penetrance predisposing loci have been identified, but high-risk susceptibility remains undetermined. Endometriosis is known to increase the risk of epithelial ovarian cancers, especially of endometrioid and clear cell types. Here, we have analyzed a Finnish family where four women have been diagnosed with surgically verified, severely symptomatic endometriosis and two of the patients also with high-grade serous carcinoma. Results Whole-exome sequencing revealed three rare candidate predisposing variants segregating with endometriosis. The variants were c.1238C>T, p.(Pro413Leu) in FGFR4 , c.5065C>T, p.(Arg1689Trp) in NALCN , and c.2086G>A, p.(Val696Met) in NAV2 . The only variant predicted deleterious by in silico tools was the one in FGFR4 . Further screening of the variants in 92 Finnish endometriosis and in 19 endometriosis–ovarian cancer patients did not reveal additional carriers. Histopathology, positive p53 immunostaining, and genetic analysis supported the high-grade serous subtype of the two tumors in the family. Conclusions Here, we provide FGFR4 , NALCN , and NAV2 as novel high-risk candidate genes for familial endometriosis. Our results also support the association of endometriosis with high-grade serous carcinoma. Further studies are required to validate the findings and to reveal the exact pathogenesis mechanisms of endometriosis. Elucidating the genetic background of endometriosis defines the etiology of the disease and provides opportunities for expedited diagnostics and personalized treatments.

Background: Several studies have examined the anterior cruciate ligament (ACL) injury history among relatives of patients undergoing ACL reconstruction (ACLR), but they have primarily analyzed adults with variable results. Hypothesis: We hypothesized that he rate of familial ACL injuries among pediatric patients with ACL tears would be greater than that among pediatric patients with uninjured knees. Study Design: Cohort study; Level of evidence, 3. Methods: Pediatric patients (≤18 years of age) who underwent ACLR between January 2009 and May 2016 were contacted to complete a questionnaire on subsequent complications and family history of ACL tears. A control cohort was recruited from children with uninjured knees seen in the concussion clinic of our institution. Binary logistic regression was used to determine the factors predictive of having a familial ACL tear history or complications. Results: Overall, 450 pediatric patients with primary ACL tears were included. Age at the time of surgery was 14.9 ± 2.2 years with a follow-up of 4.3 ± 2.1 years. When compared with 267 control patients, those with an ACL tear reported a higher rate of first-degree relatives with an ACL injury history (25.1% vs 12.0%; P < .001). In multivariate analysis, children with ACL injury had nearly 3 times (odds ratio [OR], 2.7) higher odds of having a first-degree relative with an ACL tear (95% CI, 1.7-4.2; P < .001). Patients were stratified by the number of first-degree relatives with ACL tears: no relatives, 1 relative, or ≥2 relatives. Children with ≥2 first-degree relatives were more likely to sustain a postoperative graft failure (OR, 5.1; 95% CI 1.7-15.2; P = .003) or a complication requiring surgical intervention (OR, 7.5; 95% CI, 2.6-22.0; P < .001). Conclusion: A family history of ACL injury is more likely in pediatric patients with ACL tears than in uninjured children. Further, patients undergoing primary ACLR as well as a strong family history of ACL tears are more likely to sustain a postoperative graft rupture or complication requiring surgery.

Advanced paternal age is associated with increased risk of schizophrenia. This study aimed to explore whether older paternal age is associated with earlier onset among co-affected schizophrenia sib-pairs with the same familial predisposition. A total of 1297 patients with schizophrenia from 630 families, which were ascertained to have at least two siblings affected, throughout Taiwan were interviewed using the Diagnostic Interview for Genetic Studies. Both inter-family comparisons, a hierarchical regression model allowing for familial dependence and adjusting for confounders, and within-family comparisons, examining the consistency between onset order and birth order, were performed. An inverted U shape was observed between paternal age and onset of schizophrenia. Affected offspring with paternal age of 20-24 years had the oldest onset. As paternal age increased over 25 years, older paternal age exhibited a linear decrease in the onset of schizophrenia. On average, the onset was lowered by 1.5 years for paternal age of 25-29 years and by 5.5 years for paternal age ⩾50 years (p = 0.04; trend test). The proportion of younger siblings with earlier onset (58%) was larger than that of older siblings with earlier onset (42%) (p = 0.0002). These findings indicate that paternal age older than 25 years and younger than 20 years were both associated with earlier onset among familial schizophrenia cases. The associations of advanced paternal age with both increased susceptibility to schizophrenia and earlier onset of schizophrenia are consistent with the rate of increases in spontaneous mutations in sperm as men age.

This retrospective cohort study evaluated pregnancy outcomes and similarities between pairs of nulliparous sisters with a singleton fetus who delivered between 2013 and 2020. The “Sister-1 group” was defined as the sibling who delivered first, while the “Sister-2 group” included the siblings who gave birth after Sister-1. Obstetrical complications and delivery outcomes were compared. The relative risk for recurrence of a complication in Sister-2 was calculated. The study included 743 sister pairs. There were no between-group differences in maternal BMI, gestational age at delivery, gravidity, smoking, or epidural rates. The Sister-2 group was older than the Sister-1 group (26.4 ± 5 vs. 25.8 ± 4.7 years, respectively, p = 0.05). Higher birthweights and more large-for-gestational-age infants characterized the Sister-2 group compared with the Sister-1 group (3241 ± 485 g vs. 3148 ± 536 g, p < 0.001 and 7.7% vs. 4.8%, p = 0.025, respectively). There were no between-group differences in the rate of small-for-gestational-age, gestational diabetes, hypertensive disorders, pre-term births, vacuum extraction, or cesarean deliveries. Logistic regression analysis found that if Sister-1 underwent vacuum extraction, her sibling had an increased risk for vacuum delivery (adjusted RR 3.03, 95% CI 1.4–6.7; p = 0.003) compared with those whose sibling (Sister-1) did not. There was a three-fold risk of vacuum extraction delivery between sisters. This finding could be related to biological inheritance, environmental factors, and/or psychological issues that may affect similarities between siblings’ delivery outcomes.

Spheroidal corneal degeneration is predominantly seen in advanced age and hereditary predisposition to this disorder is very rare. This report describes the occurrence of bilateral band-shaped spheroidal corneal degeneration in two siblings. Keywords: Spheroidal degeneration of the cornea and conjunctiva, band-shaped amber-colored spherules, familial predisposition, in vivo confocal microscopy