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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).

Background: Numerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population., Results: Associations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival., Conclusion: This study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival., (© 2021. The Author(s).)

Background: Selective IgE deficiency (SIgED) has been previously evaluated in selected patients from allergy units. This study investigates the effects of SIgED on the entire population in a hospital setting and sought to delineate in detail the clinical aspects of SIgED., Methods: A retrospective study of the data obtained from electronic medical records of 52 adult patients (56% female) with a mean age of 43 years and IgE levels of <2.0 kU/L with normal immunoglobulin (Ig) IgG, IgA, and IgM levels, seen at our hospital, without selection bias, from 2010 to 2019., Results: Recurrent upper respiratory infections were recorded in 18 (34.6%) patients, pneumonia was recorded in 16 (30.7%) patients, bronchiectasis was recorded in 16 (30.7%) patients, and asthma was recorded in 10 (19.2%) patients. Eighteen patients (34.6%) suffered autoimmune clinical manifestations either isolated (19%) or combining two or more diseases (15%), Hashimoto's thyroiditis being the most frequent (19%), which was followed by arthritis (10%) and thrombocytopenia and/or neutropenia (5.7%). Other less frequent associations were Graves' disease, primary sclerosing cholangitis, Sjögren's syndrome, and autoimmune hepatitis. Eczematous dermatitis (15.3%), chronic spontaneous urticaria (17.3%), and symptoms of enteropathy (21%) were also highly prevalent. Thirty percent of patients developed malignancies, with non-Hodgkin lymphomas (13.4%) being the most prevalent., Conclusions: The clinical manifestations of SIgED encompass a variety of infectious, non-infectious complications, and malignancy. Since it cannot be ruled out that some type of selection bias occurred in the routine assessment of IgE serum Ievels, prospective studies are required to better characterize SIgED and to determine whether it should be added to the list of antibody deficiencies.

We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (n = 4), genotyping by genome-wide SNP array (n = 34) and whole-genome sequencing (n = 12). We performed genome-wide linkage analysis, family-based association analysis and polygenic risk score estimates. Significant linkage was obtained at chromosome 9 (9q33.1-33.2, LOD score = 4.11), a suggestive region that contains five candidate genes ASTN2, BRINP1, C5, TLR4 and TRIM32, previously associated with MMDs. Comprehensive analysis associated the MMD phenotype with genes of the immune system with dual brain functions. Moreover, the psychotic phenotype was enriched for genes involved in synapsis. These results should be considered once studying the genetics of psychiatric disorders in other families, especially the ones from the same region, since founder effects may be related to the high prevalence., (© 2021. The Author(s).)

In industrialized countries, the use of Cadmium (Cd) produces a form of anthropogenic pollution. Hence, exposure by human populations is becoming a public health problem. With a half-life of up to 40 years, cadmium is now a topic of great interest due to its role as an endocrine disruptor and its effects on male reproduction. Cd's diverse toxic mechanisms are based on its capacity to mimic divalent ions -calcium, zinc, iron- that participate in physiological processes. It alters the mitochondrial function and generates the production of free radicals that can induce apoptosis. In male reproduction, Cd alters the precise coordination of the hypothalamic-hypophysis-testis axis (HHT), resulting in the loss of testicular functions like steroidogenesis, spermatogenesis and the onset of puberty, sexual maturity, sexual behavior and fertility. Exposure to Cd may even cause changes in the immune system that are associated with the reproductive system. This review analyses the state of the question regarding Cd's cellular and physiological mechanisms and the effects of this heavy metal on the neuroendocrine regulation of male reproduction.

Clinical psychological science has developed many efficacious treatments for diverse emotional and behavioral difficulties encountered by children and adolescents, although randomized trials investigating these treatments have disproportionally been conducted by American, university-based research labs. The subsection of the world population involved in these studies, however, represents very few people among those in need of psychological services whose voices, perspectives, and orientations to therapy have not generally been reflected in well-funded research trials. Dissemination and implementation of evidence-based services designed to meet the needs of this broader global population, therefore, may require cultural and contextual adaptation to be successful. The current article describes the implementation of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) in 3 separate low-resourced settings (rural South Carolina, Puerto Rico, and El Salvador) utilizing the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework and guided by a community-based participatory research framework. Emphasis is placed on description of program development, building collaborative and responsive partnerships, and the use of implementation strategies to guide continuous quality improvement. Program evaluation data comparing baseline to posttreatment trauma symptoms and treatment completion rates for all sites are also presented, which suggests that treatment was associated with a large reduction in symptoms, exceeding that noted in many TF-CBT randomized trials. The implications of attention to context, adaptation, and methods of building partnerships with global communities are discussed, with a particular focus on propelling more refined models and controlled studies in the future. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Primary care providers are the biggest prescribers of psychopharmacological medications. In this non-randomized retrospective examination, we asked whether primary care patients receiving behavioral health interventions with and without concurrent pharmacological treatments showed differential symptom improvement. Participants (79.4% women, 61.5% Hispanic, M age = 41.68, SD = 13.50) were 431 primary care patients referred to behavioral health with a primary concern of depression at one of three federally qualified health centers. Thirty-three percent of patients initiated or had an increase in pharmacotherapy concurrently with behavioral therapy; 26.9% had no change in medication during the episode of care, and 39.7% had no concurrent psychotropic medication prescribed during the episode of care. One-way analyses of variance revealed patients in the no medication group had higher global functioning, as measured by Global Assessment of Functioning (GAF) scores, than patients who were taking medication, or who initated or had an increase in medication. There was a significant main effect of time, where patients had significantly higher GAF scores during their last session in comparison to the first session. All three patient groups experienced comparable improvements in GAF scores, but patients in the initiated/increased medication group were significantly more likely to terminate behavioral health treatment prematurely. Results suggest primary care patients experience improvements in functioning across an episode of behavioral health care, even without concurrent psychotropic medication use.

Populations of the common chimpanzee (Pan troglodytes) are in an impending risk of going extinct in the wild as a consequence of damaging anthropogenic impact on their natural habitat and illegal pet and bushmeat trade. Conservation management programmes for the chimpanzee have been established outside their natural range (ex situ), and chimpanzees from these programmes could potentially be used to supplement future conservation initiatives in the wild (in situ). However, these programmes have often suffered from inadequate information about the geographical origin and subspecies ancestry of the founders. Here, we present a newly designed capture array with ~60,000 ancestry informative markers used to infer ancestry of individual chimpanzees in ex situ populations and determine geographical origin of confiscated sanctuary individuals. From a test panel of 167 chimpanzees with unknown origins or subspecies labels, we identify 90 suitable non-admixed individuals in the European Association of Zoos and Aquaria (EAZA) Ex situ Programme (EEP). Equally important, another 46 individuals have been identified with admixed subspecies ancestries, which therefore over time, should be naturally phased out of the breeding populations. With potential for future re-introduction to the wild, we determine the geographical origin of 31 individuals that were confiscated from the illegal trade and demonstrate the promises of using non-invasive sampling in future conservation action plans. Collectively, our genomic approach provides an exemplar for ex situ management of endangered species and offers an efficient tool in future in situ efforts to combat the illegal wildlife trade.

In this study, we examined the degree to which children's level of anxiety sensitivity (AS) was a precursor to both internalizing problems and peer victimization experiences. Participants were 581 fourth-grade children (M age = 9.31; 51.8% girls; 42.3% Hispanic/Latinx) and their teachers. Measures of AS, internalizing problems, and peer victimization were collected across a single academic year (Fall, Spring). Structural equation modeling and logistic regression analyses indicated AS predicted future internalizing symptoms as well as self- and teacher-reports of peer victimization. Also, children with heightened AS were 2.70 times more likely to reach elevated levels of self-rated peer victimization and 11.53 times more likely to have clinically elevated internalizing problems. This is the first study to examine prospectively the link between AS and children's peer victimization experiences. We discuss implications of the findings for developing preventative interventions for children at risk for peer victimization and internalizing difficulties.

Gene fusion occurs when two or more individual genes with independent open reading frames becoming juxtaposed under the same open reading frame creating a new fused gene. A small number of gene fusions described in detail have been associated with novel functions, for example, the hominid-specific PIPSL gene, TNFSF12, and the TWE-PRIL gene family. We use Sequence Similarity Networks and species level comparisons of great ape genomes to identify 45 new genes that have emerged by transcriptional readthrough, that is, transcription-derived gene fusion. For 35 of these putative gene fusions, we have been able to assess available RNAseq data to determine whether there are reads that map to each breakpoint. A total of 29 of the putative gene fusions had annotated transcripts (9/29 of which are human-specific). We carried out RT-qPCR in a range of human tissues (placenta, lung, liver, brain, and testes) and found that 23 of the putative gene fusion events were expressed in at least one tissue. Examining the available ribosome foot-printing data, we find evidence for translation of three of the fused genes in human. Finally, we find enrichment for transcription-derived gene fusions in regions of known segmental duplication in human. Together, our results implicate chromosomal structural variation brought about by segmental duplication with the emergence of novel transcripts and translated protein products., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Teen dating violence is a pervasive issue in adolescence and has been linked to maladjustment (Temple, Shorey, Fite et al., 2013). Physical dating violence is a particularly significant problem with one in five adolescents reporting experiencing physical teen dating violence (TDV; Wincentak et al., 2017). Acceptance of violence has been suggested to increase the risk of TDV; however, most studies to date have been cross-sectional. The purpose of the current study is to examine patterns of acceptance of dating violence and TDV victimization across time. Participants were ethnically diverse teenagers (N = 1042; ages 13-18) who were followed over a four-year period. Multivariate latent growth curve modeling techniques were used to determine trajectories of physical TDV victimization and attitudes accepting of dating violence. Results showed two trajectories for physical TDV victimization, linear and quadratic, and two trajectories for acceptance of dating violence, non-linear and quadratic. Parallel models investigating the interplay between TDV victimization and acceptance demonstrated two possible trends; however, we did not find any evidence for a longitudinal relationship between the two variables, suggesting that change in acceptance was not related to change in physical TDV victimization. Instead, our results suggest a significant amount of heterogeneity in these trajectories. These findings suggest studies are still needed to further explore longitudinal patterns of TDV to better understand how to reduce the risk of teen dating violence., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency characterized by recurrent infections, hypogammaglobulinemia and poor response to vaccines. Its diagnosis is made based on clinical and immunological criteria, after exclusion of other diseases that can cause similar phenotypes. Currently, less than 20% of cases of CVID have a known underlying genetic cause. We have analyzed whole-exome sequencing and copy number variants data of 36 children and adolescents diagnosed with CVID and healthy relatives to estimate the proportion of monogenic cases. We have replicated an association of CVID to p.C104R in TNFRSF13B and reported the second case of homozygous patient to date. Our results also identify five causative genetic variants in LRBA, CTLA4, NFKB1 , and PIK3R1 , as well as other very likely causative variants in PRKCD, MAPK8 , or DOCK8 among others. We experimentally validate the effect of the LRBA stop-gain mutation which abolishes protein production and downregulates the expression of CTLA4, and of the frameshift indel in CTLA4 producing expression downregulation of the protein. Our results indicate a monogenic origin of at least 15-24% of the CVID cases included in the study. The proportion of monogenic patients seems to be lower in CVID than in other PID that have also been analyzed by whole exome or targeted gene panels sequencing. Regardless of the exact proportion of CVID monogenic cases, other genetic models have to be considered for CVID. We propose that because of its prevalence and other features as intermediate penetrancies and phenotypic variation within families, CVID could fit with other more complex genetic scenarios. In particular, in this work, we explore the possibility of CVID being originated by an oligogenic model with the presence of heterozygous mutations in interacting proteins or by the accumulation of detrimental variants in particular immunological pathways, as well as perform association tests to detect association with rare genetic functional variation in the CVID cohort compared to healthy controls.

Target-capture approach has improved over the past years, proving to be very efficient tool for selectively sequencing genetic regions of interest. These methods have also allowed the use of noninvasive samples such as faeces (characterized by their low quantity and quality of endogenous DNA) to be used in conservation genomic, evolution and population genetic studies. Here we aim to test different protocols and strategies for exome capture using the Roche SeqCap EZ Developer kit (57.5 Mb). First, we captured a complex pool of DNA libraries. Second, we assessed the influence of using more than one faecal sample, extract and/or library from the same individual, to evaluate its effect on the molecular complexity of the experiment. We validated our experiments with 18 chimpanzee faecal samples collected from two field sites as a part of the Pan African Programme: The Cultured Chimpanzee. Those two field sites are in Kibale National Park, Uganda (N = 9) and Loango National Park, Gabon (N = 9). We demonstrate that at least 16 libraries can be pooled, target enriched through hybridization, and sequenced allowing for the genotyping of 951,949 exome markers for population genetic analyses. Further, we observe that molecule richness, and thus, data acquisition, increase when using multiple libraries from the same extract or multiple extracts from the same sample. Finally, repeated captures significantly decrease the proportion of off-target reads from 34.15% after one capture round to 7.83% after two capture rounds, supporting our conclusion that two rounds of target enrichment are advisable when using complex faecal samples., (© 2017 The Authors. Molecular Ecology Resources Published by John Wiley & Sons Ltd.)

Background: Whole genome re-sequencing data from dogs and wolves are now commonly used to study how natural and artificial selection have shaped the patterns of genetic diversity. Single nucleotide polymorphisms, microsatellites and variants in mitochondrial DNA have been interrogated for links to specific phenotypes or signals of domestication. However, copy number variation (CNV), despite its increasingly recognized importance as a contributor to phenotypic diversity, has not been extensively explored in canids., Results: Here, we develop a new accurate probabilistic framework to create fine-scale genomic maps of segmental duplications (SDs), compare patterns of CNV across groups and investigate their role in the evolution of the domestic dog by using information from 34 canine genomes. Our analyses show that duplicated regions are enriched in genes and hence likely possess functional importance. We identify 86 loci with large CNV differences between dogs and wolves, enriched in genes responsible for sensory perception, immune response, metabolic processes, etc. In striking contrast to the observed loss of nucleotide diversity in domestic dogs following the population bottlenecks that occurred during domestication and breed creation, we find a similar proportion of CNV loci in dogs and wolves, suggesting that other dynamics are acting to particularly select for CNVs with potentially functional impacts., Conclusions: This work is the first comparison of genome wide CNV patterns in domestic and wild canids using whole-genome sequencing data and our findings contribute to study the impact of novel kinds of genetic changes on the evolution of the domestic dog.

The genus Pan is the closest related to humans (Homo sapiens) and it includes two species: Pan troglodytes (chimpanzees) and Pan paniscus (bonobos). Different characteristics, some of biomedical aspect, separate them from us. For instance, some common human medical conditions are rare in chimpanzees (menopause, Alzheimer disease) although it is unclear to which extent longevity plays an active role in these differences. However, both humans and chimpanzees present similar pathologies, thus, understanding traits in chimpanzees can help unravel the molecular basis of human conditions. Here, we sequenced the genome of Nico, a central chimpanzee diagnosed with a particular biomedical condition, the Chiari malformation. We performed a variant calling analysis comparing his genome to 25 whole genomes from healthy individuals (bonobos and chimpanzees), and after predicting the effects of the genetic variants, we looked for genes within the OMIM database. We found a novel, private, predicted as damaging mutation in Nico in LRP5, a gene related to bone density alteration pathologies, and we suggest a link between this mutation and his Chiari malformation as previously shown in humans. Our results reinforce the idea that a comparison between humans and chimpanzees can be established in this genetic frame of common diseases.

This study provides a systematic comparison of the norms of 3 Spanish-language Wechsler Adult Intelligence Scales (WAIS-III) batteries from Mexico, Spain, and Puerto Rico, and the U.S. English-language WAIS-III battery. Specifically, we examined the performance of the 4 normative samples on 2 identical subtests (Digit Span and Digit Symbol-Coding) and 1 nearly identical subtest (Block Design). We found that across most age groups the means associated with the Spanish-language versions of the 3 subtests were lower than the means of the U.S. English-language version. In addition, we found that for most age ranges the Mexican subsamples scored lower than the Spanish subsamples. Lower educational levels of Mexicans and Spaniards compared to U.S. residents are consistent with the general pattern of findings. These results suggest that because of the different norms, applying any of the 3 Spanish-language versions of the WAIS-III generally risks underestimating deficits, and that applying the English-language WAIS-III norms risks overestimating deficits of Spanish-speaking adults. There were a few exceptions to these general patterns. For example, the Mexican subsample ages 70 years and above performed significantly better on the Digit Symbol and Block Design than did the U.S. and Spanish subsamples. Implications for the clinical assessment of U.S. Spanish-speaking Latinos and test adaptation are discussed with an eye toward improving the clinical care for this community. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Introduction: Type 2 diabetes is often comorbid with internalizing mental health disorders and associated with greater psychiatric treatment resistance. Integrating psychotherapy into primary care can help treat internalizing disorders generally. We explored whether such treatment had comparable effectiveness in patients with and without Type 2 diabetes., Method: Participants were 468 consecutive adults (23% male; 62% Hispanic, Mage = 41.46 years) referred by medical staff for psychotherapy appointments to address internalizing symptoms (e.g., depression). After each visit, patients completed a self-report measure and clinicians assessed patient symptom severity. These data and demographics extracted from electronic medical records were analyzed using descriptive and multilevel modeling analyses., Results: Patients with and without diabetes were similar in types of internalizing disorders experienced and baseline clinician- and self-reported symptomology. Multilevel modeling suggested improvements in self-reported symptomology was comparable across patient groups; however, only patients without diabetes significantly improved according to clinician reports., Discussion: Although findings suggested integrated psychotherapy resulted in comparable patient-reported reductions of internalizing symptoms, these effects were not evident in clinician reports of diabetic patients. Possible reasons for this discrepancy (e.g., reporting biases) are discussed. Integrated psychotherapy for internalizing disorders may be effective for Type 2 diabetic patients, though caution is warranted. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

The genus Pan is the closest genus to our own and it includes two species, Pan paniscus (bonobos) and Pan troglodytes (chimpanzees). The later is constituted by four subspecies, all highly endangered. The study of the Pan genera has been incessantly complicated by the intricate relationship among subspecies and the statistical limitations imposed by the reduced number of samples or genomic markers analyzed. Here, we present a new method to reconstruct complete mitochondrial genomes (mitogenomes) from whole genome shotgun (WGS) datasets, mtArchitect, showing that its reconstructions are highly accurate and consistent with long-range PCR mitogenomes. We used this approach to build the mitochondrial genomes of 20 newly sequenced samples which, together with available genomes, allowed us to analyze the hitherto most complete Pan mitochondrial genome dataset including 156 chimpanzee and 44 bonobo individuals, with a proportional contribution from all chimpanzee subspecies. We estimated the separation time between chimpanzees and bonobos around 1.15 million years ago (Mya) [0.81-1.49]. Further, we found that under the most probable genealogical model the two clades of chimpanzees, Western + Nigeria-Cameroon and Central + Eastern, separated at 0.59 Mya [0.41-0.78] with further internal separations at 0.32 Mya [0.22-0.43] and 0.16 Mya [0.17-0.34], respectively. Finally, for a subset of our samples, we compared nuclear versus mitochondrial genomes and we found that chimpanzee subspecies have different patterns of nuclear and mitochondrial diversity, which could be a result of either processes affecting the mitochondrial genome, such as hitchhiking or background selection, or a result of population dynamics., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

We examined change processes associated with the school-based, lunchtime mentoring of bullied children. We used data from a one-semester open trial of Lunch Buddy (LB) mentoring (N = 24) to examine changes in bullied children's lunchtime peer relationships. We also tested whether these changes predicted key outcomes (i.e., peer victimization, social preference) post-mentoring. Results provided partial support that bullied children paired with LB mentors experienced improved lunchtime peer relationships and that gains in lunchtime relationships predicted post-mentoring levels of social preference and peer victimization. Neither child nor mentors' ratings of the mentoring relationship predicted post-mentoring outcomes; however, child-rated mentor support and conflict predicted improvements in lunchtime peer relationships. We discuss implications for future research on school-based mentoring as a form of selective intervention for bullied children.