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Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are genetically distinct disorders typically associated with pathogenic variants in TSC1 and TSC2 for the former and PKD1 and PKD2 for the latter. TSC2 and PKD1 lie adjacent to each other, and large deletions comprising both genes lead to TSC2/PKD1 contiguous gene deletion syndrome (CGS). In this study, we describe a young female patient exhibiting symptoms of TSC2/PKD1 CGS in which genetic analysis disclosed two noncontiguous partial gene deletions in TSC2 and PKD1 that putatively are responsible for the manifestations of the syndrome. Further analysis revealed that both deletions appear to be de novo on the maternal chromosome, presumably with a germline origin. Despite extensive analysis, no maternal chromosomal rearrangement triggering these pathogenic variants was detected. This case elucidates a unique pathogenesis for TSC2/PKD1 CGS, diverging from the common contiguous deletions typically observed, marking the first reported instance of TSC2/PKD1 CGS caused by independent, functionally significant partial gene deletions., (© 2024 Wiley Periodicals LLC.)

Introduction: Emerging research has provided tentative support for the use of heart rate variability biofeedback (HRVB) as a treatment for several psychological disorders, with meta-analyses providing compelling evidence for HRVB as a promising treatment for anxiety, depression, and PTSD. Given the prevalence of PTSD in military veterans and the comparatively lower benefit and higher attrition rate of traditional psychological treatment for PTSD relative to civilian counterparts, it is important to examine complementary and alternative treatment approaches such as HRVB in this population. Although studies of HRVB for PTSD have been conducted with military veterans, they have involved relatively small sample sizes, limiting interpretation. To address this, the current article presents a comprehensive meta-analysis, consolidating existing literature to more accurately evaluate the efficacy of HRVB in reducing PTSD symptoms within military populations., Materials and Methods: This meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and our protocol was registered with PROSPERO to increase review transparency. A literature search of HRVB interventions was conducted using PubMed, PsycINFO, Military Database, PTSDPubs, and EBSCO's Psychological and Behavioral Sciences Collection., Results: Five studies met eligibility criteria, providing a combined sample size of 95 military services members. For all studies, effect sizes were negative, indicating a reduction in PTSD symptoms. Effect sizes ranged from -1.614 to -0.414, resulting in an overall moderate to large mean effect for HRVB (Hedges's g = -0.557; 95% confidence interval = -0.818 to -0.296; P < .001). Additionally, cumulative attrition was 5.8%, significantly lower than commonly reported rates for evidence-based treatments (16%-36%)., Conclusions: The present study is the first meta-analysis to examine HRVB as a treatment for military service members with PTSD. Results indicate that HRVB may be a viable treatment approach to reduce PTSD symptomatology. Low attrition rates, ease of accessibility, and favorable participant outlook serve as additional benefits for the use of HRVB., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objective: Current antibullying programs can reduce overall rates of victimization but appear to overlook processes that give rise to persistent peer victimization. Needed are studies that delineate the interplay between social contextual and individual difference variables that contribute to persistent peer victimization. We examined the extent to which two individual-difference variables - internalizing symptoms (IS) and anxiety sensitivity (AS) - moderated the link between children's average social preference score across the school year and their status as persistent victims., Method: Participants included 659 4 th -grade students (M age  = 9.31 years, SD = 0.50, 51.8% girls; 42.3% Latinx, 28.9% non-Hispanic White, 10.2% Pacific Islander, 7.7% Bi/Multiracial, 1.9% Black, 1.7% Asian, 1.7% Native American, and 3.4% unreported) from 10 public elementary schools in the U.S., Results: As expected, higher social preference scores predicted a decreased likelihood of being persistently victimized. Conversely, IS and AS were positively linked to persistent victim status. AS significantly moderated the link between social preference and persistent victim status such that for children with high AS, compared to those with AS scores at or below the mean, the negative association between social preference and persistent victim status was attenuated., Conclusions: Findings provide evidence that children who experience high levels of IS and AS are at risk for being persistently victimized by peers and that high AS could signal increased risk for persistent victimization even when children are generally liked by peers. We discuss the implications of these findings for efforts to develop focused interventions for chronically bullied children.

Background: The COVID-19 pandemic brought an increased incidence of disease and mortality in the world at large, making it a particularly salient and stressful life event. For those individuals residing in Latin America, the pandemic was met with fragmented healthcare systems, economic downturn, and sociopolitical crisis which puts autistic individuals at risk for more detrimental outcomes. Behavioral and emotional challenges experienced by autistic individuals at the beginning of the pandemic could later develop into more severe symptomatology as the pandemic progresses. The present study aimed to explore changes in dysregulated (overt and internalizing) behaviors and preoccupation with getting sick during the COVID-19 pandemic among autistic children in 7 Latin American countries., Method: Sample consisted of 1,743 caregivers, residing in: Argentina ( n  = 677, 38.8%) Brazil ( n = 156, 9%), Chile ( n = 251, 14.4%), Dominican Republic ( n  = 171, 9.8%), Mexico ( n = 126, 7.2%), Uruguay ( n = 259, 14.9%) and Venezuela ( n  = 103, 5.9%). The majority of caregivers who completed the questionnaire were mothers (85.1%), and most had a male autistic child (81.6%). A series of independent sample t -tests were conducted to assess country differences in dysregulated behaviors and preoccupation with getting sick. Linear regressions were conducted to identify which demographic characteristics and micro-level contextual factors predicted dysregulated overt behaviors and psychological changes., Results: Contextual factors, such as country of residence, were related to preoccupation with getting sick and dysregulated behavior. Particularly, residing in Mexico and Brazil were related to changes in preoccupation with getting sick and mental health concerns. Coexistence predicted dysregulated internalizing behaviors, while being older significantly predicted preoccupation with getting sick. Increased screen time only predicted anxiety., Conclusion: Our findings highlight differences and predictions of behavioral challenges and psychological changes based on certain contextual factors and individual characteristics while experiencing severe life stressors such as a worldwide pandemic. This knowledge could help inform policies and decrees aimed at protecting those most vulnerable due to their increased difficulty adapting to change., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Montenegro, Ramírez, Hernandez Rodriguez, Villalobos, Garrido, Amigo, Valdez, Barrios, Cukier, Rattazzi, Rosoli, García, Paula, Liz and Montiel-Nava.)

Introduction: The current study documented levels of anxiety, depression, posttraumatic stress, and COVID-19 fears and impacts among Latinxs living near the U.S.-Mexico border during the COVID-19 pandemic., Methods: Participants of this cross-sectional study were 305 Latinx adults living in the Rio Grande Valley (RGV) who completed an online survey between June and November 2020., Results: About half of participants scored above the cut-off for anxiety (50.2%; GAD-7 scores ≥10) and depression (48.8%; PHQ-9 scores ≥10), and more than a quarter of participants showed clinical levels of posttraumatic stress (27.3%; PCL-5 scores ≥31). Latinxs reported on average 22 types of negative pandemic life impacts on the Epidemic-Pandemic Impacts Inventory. Endorsement of mental health symptoms, severity of COVID-19 fears, and COVID-related life impacts varied based on several demographic characteristics including gender, marital status, educational attainment, employment, income, insurance coverage, vulnerability to COVID-19, and essential worker status., Discussion: Overall, the cross-sectional results of this study revealed that RGV Latinx residents experienced high levels of psychological distress during the pandemic. Results suggest that Latinx women were most affected by the psychological consequences of the pandemic. More research is needed with communities living near the U.S.-Mexico border as they may be particularly vulnerable to mental health problems during the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Villalobos and Hernandez Rodriguez.)

Cancer arises from the complex interplay of various factors. Traditionally, the identification of driver genes focuses primarily on the analysis of somatic mutations. We describe a new method for the detection of driver gene pairs based on an epistasis analysis that considers both germline and somatic variations. Specifically, the identification of significantly mutated gene pairs entails the calculation of a contingency table, wherein one of the co-mutated genes can exhibit a germline variant. By adopting this approach, it is possible to select gene pairs in which the individual genes do not exhibit significant associations with cancer. Finally, a survival analysis is used to select clinically relevant gene pairs. To test the efficacy of the new algorithm, we analyzed the colon adenocarcinoma (COAD) and lung adenocarcinoma (LUAD) samples available at The Cancer Genome Atlas (TCGA). In the analysis of the COAD and LUAD samples, we identify epistatic gene pairs significantly mutated in tumor tissue with respect to normal tissue. We believe that further analysis of the gene pairs detected by our method will unveil new biological insights, enhancing a better description of the cancer mechanism.

The blood-brain barrier (BBB) is an essential gatekeeper for the central nervous system and incidence of neurodevelopmental disorders (NDDs) is higher in infants with a history of intracerebral hemorrhage (ICH). We discovered a rare disease trait in thirteen individuals, including four fetuses, from eight unrelated families associated with homozygous loss-of-function variant alleles of ESAM which encodes an endothelial cell adhesion molecule. The c.115del (p.Arg39Glyfs ∗ 33) variant, identified in six individuals from four independent families of Southeastern Anatolia, severely impaired the in vitro tubulogenic process of endothelial colony-forming cells, recapitulating previous evidence in null mice, and caused lack of ESAM expression in the capillary endothelial cells of damaged brain. Affected individuals with bi-allelic ESAM variants showed profound global developmental delay/unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/cerebral calcifications, the latter being also observed in the fetuses. Phenotypic traits observed in individuals with bi-allelic ESAM variants overlap very closely with other known conditions characterized by endothelial dysfunction due to mutation of genes encoding tight junction molecules. Our findings emphasize the role of brain endothelial dysfunction in NDDs and contribute to the expansion of an emerging group of diseases that we propose to rename as "tightjunctionopathies.", Competing Interests: Declaration of interests J.R.L. has stock ownership in 23andMe and is a paid consultant for the Regeneron Genetics Center., (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Comments on an article by Nomi S. Weiss-Laxer et al. (see record 2022-71815-001). Providing virtual services takes time for many providers and families to get familiar with and many prefer in-person contact over telehealth; however, many of the challenges of doing telehealth can be overcome with creativity and flexibility. As clinicians, they agree with the authors that using the features of the technology to our advantage was helpful and that confirming with each person that they had privacy was vital to effective communication. Problem-solving was often needed, and most times parents had the best ideas for working around the limitations of their home environment. The article highlighted the possibility of hybrid models of care considering the needs and wants of both patients and providers. Such a hybrid approach can increase connection to clinics through in-person visits which can jump-start the establishment of therapeutic relationships and build trust (confianza) with clinicians and clinic staff. As the pandemic becomes more controlled, giving parents a choice and flexibility to change modalities can help them stay engaged and reduce drop out. Clinics will need to assess the language preferences of the families they serve to ensure they have enough staff and providers who are bilingual or multilingual to deliver such programs or use trained interpreters. These concerns would need to be addressed if implementation were increased on a large scale. (PsycInfo Database Record (c) 2022 APA, all rights reserved).