Parental sensitivity and child behavioral problems: A meta-analytic review.

Meta-analytic associations between observed parental sensitivity and child behavioral problems were examined (children aged 0-17 years). Studies (k = 108, N = 28,114) contained sociodemographically diverse samples, primarily from North America and Europe, reporting on parent-child dyads (95% mothers; 54% boys). Sensitivity significantly related to internalizing (k = 69 studies; N = 14,729; r = -.08, 95% CI [-.12, -.05]) and externalizing (k = 94; N = 25,418; r = -.14, 95% CI [-.17, -.11]) problems, with stronger associations found for externalizing. For internalizing problems, associations were significantly stronger among samples with low socioeconomic status (SES) versus mid-high SES, in peer-reviewed versus unpublished dissertations, and in studies using composite versus single scale sensitivity measures. No other moderators emerged as significant.

When the Bough Breaks: A systematic review and meta-analysis of mental health symptoms in mothers of young children during the COVID-19 pandemic.

Parents have experienced considerable challenges and stress during the COVID-19 pandemic, which may impact their well-being. This meta-analysis sought to identify: (1) the prevalence of depression and anxiety in parents of young children (

Los padres han experimentado retos considerables y estrés durante la pandemia del COVID-19, lo cual puede tener un impacto en su bienestar. Este metaanálisis busca identificar: 1) la prevalencia de la depresión y ansiedad en los padres de niños pequeños (

Les parents ont fait l'expérience de défis considérables et d'un stress considérable durant la pandémie du COVID-19, ce qui peut impacter leur bien-être. Cette méta-analyse s'est donné pour but d'identifier: 1) la prévalence de la dépression et de l'anxiété chez les parents de jeunes enfants (<âge 5) durant la pandémie du COVID-18, et 2) les facteurs de modération sociodémographique (par exemple, l'âge du parent, le fait d'être d'une minorité raciale) et méthodologique (par exemple, la qualité de l'étude) qui expliquent l'hétérogénéité dans les étudies. Une recherche systématique a été faite au travers de quatre banques de données du premier janvier 2020 au 3 mars 2021. Un total de 18 études ne se recoupant pas (8981 participants), toutes focalisées sur la santé mentale maternelle, ont rempli les critères d'inclusion. Des méta-analyses à effet aléatoire approprié ont été faites. Les estimations de prévalences regroupées pour une dépression cliniquement importante et des symptômes d'anxiété pour les mères de jeunes enfants durant la pandémie de COVID-19 étaient respectivement de 26,9% (95% CI: 21,3-33,4) et de 41,9% (95% CI: 26,7-58,8). La prévalence d'une dépression cliniquement élevée et de symptômes d'anxiété était plus élevée en Europe et en Amérique du Nord et chez les mères plus âgées. Les symptômes dépressifs cliniquement élevés étaient plus bas dans les études avec un pourcentage plus élevé d'individus de minorités raciales. Par comparaison les symptômes d'anxiété cliniquement élevés étaient plus haut dans les études de moindre qualité d'étude et dans les échantillons avec des mères très éduquées. Les politiques et les ressources visant des améliorations dans la santé mentale maternelle sont essentielles.

Adverse childhood experiences and maternal anxiety and depression: a meta-analysis.

BACKGROUND: It has been proposed that adverse childhood experiences (ACEs) can put women at risk for mental illness in the pregnancy and postpartum periods. While some studies have found strong support for this proposition, others have found weak or no support. This study is a meta-analysis of the association between ACEs and maternal mental health to resolve between-study discrepancies, and to examine potential moderators of associations. METHODS: Three electronic databases (i.e., MEDLINE, Embase, and PsycINFO) were searched up to November 2018 by a health sciences librarian. A hand search was conducted in January 2020 and relevant studies were added. Included studies reported on associations between ACEs and maternal depression and/or anxiety in the perinatal period (pregnancy to 1-year postpartum). Pregnancy and postpartum outcomes were examined separately for both depression and anxiety. Random-effect meta-analyses were conducted. Moderator analyses were conducted using meta-regression. Study quality was evaluated using a 15-point scale. RESULTS: The initial search yielded 4646 non-duplicate records and full text review occurred for 196 articles. A total of 15 studies (N = 7788) were included in the meta-analyses, of which 2 were also described narratively. Publication year ranged from 1998 to 2019. Mothers were approximately 28.93 years of age when they retrospectively reported on their ACEs. All studies had maternal self-report questionnaires for the mental health outcomes. Study quality ranged from 7 to 12. The pooled effect sizes between ACEs and prenatal (N = 12; r = .19; 95% CI= .13, .24) and postpartum (N = 7; r = .23; 95% CI = .06 to .39) depressive symptoms were significant. The pooled effect size between ACEs and prenatal anxiety was also significant (N = 5; r = .14; 95% CI= .07, .21). Moderator analyses indicated that timing of depressive and anxiety symptoms may be important for understanding associations. CONCLUSIONS: ACEs confer risk to maternal mental health, albeit effect sizes are small to moderate in magnitude. Trauma-informed approaches, as well as increased mental health support during and after pregnancy, may help to offset the relative risk of ACEs on maternal mental health.

Feasibility of training service providers on the AMBIANCE-Brief measure for use in community settings.

The Atypical Maternal Behavior Instrument for Assessment and Classification-Brief (AMBIANCE-Brief) was developed to provide a clinically useful and psychometrically sound assessment of disrupted parenting behavior for community practitioners. With prior evidence of this tool's reliability and validity in laboratory settings, this study aimed to determine whether providers from family service agencies could become reliable in the use of the level of disrupted communication following a brief training. Providers (N = 46) from three agency sites participated in a 2-day AMBIANCE-Brief training and, at the end of the training, coded eight videotaped mother-child interactions. Novice participant coding was compared to expert consensus ratings using intraclass correlations. On average, participants' interrater agreement was good (ICCmean  = .84, SD = 0.10), with 89% meeting the reliability standards of ICC ≥ .70. In response to queries, 100% of participants indicated that they would recommend the AMBIANCE-Brief training to their colleagues, 85% reported that the AMBIANCE-Brief measure would be useful or very useful for their clinical practice, and 56% of participant clinicians believed that parents would find the measure acceptable or very acceptable for integration into intervention or support planning. Altogether, these findings speak to the feasibility of using the AMBIANCE-Brief in community settings. Future studies are needed in diverse clinical and community contexts to evaluate whether use of this assessment tool can inform more targeted interventions tailored to the specific needs of families.

El Instrumento Abreviado para Evaluación y Clasificación de la Conducta Materna Atípica (AMBIANCE-Abreviado; Madigan, Bronfman, Haltigan y Lyons-Ruth, 2018) se desarrolló para ofrecer a quienes practican en la comunidad una evaluación clínicamente útil y sicométricamente acertada de la conducta de crianza trastornada. Con la anterior evidencia de la confiabilidad y validez de esta herramienta en el marco de los laboratorios (Cooke, Eirich, Racine, Lyons-Ruth y Madigan, 2020), este estudio se propuso determinar si se podría confiar en quienes proveen el servicio como parte de las agencias de servicio a las familias después de un breve entrenamiento. Los proveedores (N = 46) de tres lugares de agencias participaron en un entrenamiento de dos días sobre AMBAIANCE-Abreviado y, al final del entrenamiento, codificaron ocho interacciones madre-niño grabadas en video. Se comparó la forma de codificar de los novatos con el puntaje consenso de los expertos usando correlaciones dentro de clases. El acuerdo entre los evaluadores fue bueno (ICC media = .84, SD = 0.10), con un 89% de los participantes que lograron el estándar de confiabilidad de ICC > .70. En respuesta a preguntas, el 100% de los participantes indicó que ellos recomendarían el entrenamiento de AMBIANCE-Abreviado a sus colegas, 85% reportó que la medida AMBIANCE-Abreviado sería útil o muy útil en su práctica clínica, y 56% creían que los progenitores encontrarían la medida aceptable o muy aceptable para ser integrada en la intervención o el planeamiento de apoyo. En conjunto, estos resultados hablan de la factibilidad de usar AMBIANCE-Abreviado en el marco comunitario.

L'Instrument d'Evaluation et de Classification-Brève du Comportement Maternel Atypique (AMBIANCE-Bref; Madigan, Bronfman, Haltigan, & Lyons-Ruth, 2018) a été développé afin d'offrir une évaluation du comportement de parentage perturbé, cliniquement utile et saine du point de vue psychométrique, pour les acteurs communautaires. Avec des preuves préalables de la fiabilité et de la validité de cet outil en laboratoire (Cooke, Eirich, Racine, Lyons-Ruth, & Madigan, 2020), cette étude s'est donné pour but de déterminer si les prestataires des agences de service à la famille pouvaient devenir fiables pour son utilisation après une formation courte. Des prestataires (N = 46) de trois sites d'agence ont participé à une formation AMBIANCE-Bref de deux jours et à la fin de la formation ont codé huit interactions mère-enfant filmées. Le codage du participant débutant a été comparé aux évaluations par consensus d'expertes en utilisant des corrélations intraclasses. Le coefficient d'objectivité était bon (moyenne des coefficient de corrélation intraclasse [ICC] = 84, SD = 0,10), avec 89% des participants remplissant les standards de fiabilité d'ICC ICC ³,70. En répondant aux questions, 100% des participants ont indiqué qu'ils ou elles recommanderaient la formation AMBIANCE-bref à leurs collègues, 85% ont indiqué que la mesure AMBIANCE-bref serait utile ou très utile pour leur pratique clinique, et 56% ont déclaré qu'ils ou elles croyaient que les parents trouveraient cette mesure acceptable ou très acceptable pour une intégration à une intervention ou le plan de soutien. Au total, ces résultats parlent de la viabilité de l'utilisation de l'AMBIANCE-bref dans des contextes communautaires.

Label-free microfluidic enrichment of photoreceptor cells.

Inherited retinal degenerative disorders such as retinitis pigmentosa and Usher syndrome are characterized by progressive death of photoreceptor cells. To restore vision to patients blinded by these diseases, a stem cell-based photoreceptor cell replacement strategy will likely be required. Although retinal stem cell differentiation protocols suitable for generating photoreceptor cells exist, they often yield a rather heterogenous mixture of cell types. To enrich the donor cell population for one or a few cell types, scientists have traditionally relied upon the use of antibody-based selection approaches. However, these strategies are quite labor intensive and require animal derived reagents and equipment that are not well suited to current good manufacturing practices (cGMP). The purpose of this study was to develop and evaluate a microfluidic cell sorting device capable of exploiting the physical and mechanical differences between retinal cell types to enrich specific donor cell populations such as Retinal Pigment Epithelial (RPE) cells and photoreceptor cells. Using this device, we were able to separate a mixture of RPE and iPSC-derived photoreceptor precursor cell lines into two substantially enriched fractions. The enrichment factor of the RPE fraction was 2 and that of the photoreceptor precursor cell fraction was 2.7. Similarly, when human retina, obtained from 3 independent donors, was dissociated and passed through the sorting device, the heterogeneous mixture could be reliably sorted into RPE and photoreceptor cell rich fractions. In summary, microfluidic cell sorting is a promising approach for antibody free enrichment of retinal cell populations.

The Prevalence of Sexting Behaviors Among Emerging Adults: A Meta-Analysis.

Sexting is the sharing of sexually explicit images, videos, and/or messages via electronic devices. Prevalence estimates of sexting have varied substantially, potentially due to broad age ranges being examined. The current study sought to synthesize relevant findings examining the prevalence of consensual and non-consensual sexting in a specific developmental period, emerging adulthood (≥ 18-< 29), to try to explain discrepancies in the literature. Searches were conducted in electronic databases for articles published up to April 2018. Relevant data from 50 studies with 18,122 emerging adults were extracted. The prevalence of sexting behaviors were: sending 38.3% (k = 41; CI 32.0-44.6), receiving 41.5% (k = 19; CI 31.9-51.2), and reciprocal sexting 47.7% (k = 16; CI 37.6-57.8). Thus, sexting is a common behavior among emerging adults. The prevalence of non-consensual forwarding of sexts was also frequent in emerging adults at 15.0% (k = 7; CI 6.9-23.2). Educational awareness initiatives on digital citizenship and psychological consequences of the non-consensual forwarding of sexts should be targeted to youth and emerging adults with the hopes of mitigating this potentially damaging and illegal behavior.

End of life in acute hospital setting-A systematic review of families' experience of spiritual care.

AIMS AND OBJECTIVES: To systematically review qualitative studies exploring families' experiences of spiritual care at the end of life in acute hospital settings. BACKGROUND: Although there is a widespread belief that the consideration of spiritual and religious needs is outdated in the context of secularism, from a practical perspective patients and families appear to benefit from spiritual support at the end of life. METHODS: Six key databases, CINAHL, MEDLINE, EMBASE, Global Health Library, Web of Science and Applied Social Sciences Index and Abstracts (ASSIA), were searched, and three reviewers independently extracted the data and coded them into themes and subthemes. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used as a reporting framework. RESULTS: Five main themes emerged: anticipating needs; honouring the family by honouring the patient; personal connection; lack of sensitivity; and making space for religious and spiritual practices. CONCLUSIONS: Families experiencing end-of-life care in acute hospital settings may benefit from spiritual care. While this can also be considered as fundamental care, understanding this through the lenses of spiritual care allows for incorporation of religious and spiritual practices that many seek at this time, irrespective of their faith perspectives. RELEVANCE TO CLINICAL PRACTICE: Although hospice care is well established internationally, many families experience end-of-life care in acute hospital settings. Nurses usually get to know families well during this time; however, the demands of the clinical environment place restrictions on family care and perceptions of lack of communication, limited support and/or limited sensitivity can compound families' suffering. Consideration of families' spiritual needs can help to support families during this time. Nurses are ideally placed for this and can anticipate and plan for patient and family needs in this regard, or refer to a specialist, such as the Healthcare Chaplain.

Validation of the AMBIANCE-brief: An observational screening instrument for disrupted caregiving.

Resulting from a community-identified need for a well-validated indicator of caregiving difficulties for use in practice settings, a brief form of the Atypical Maternal Behavior Instrument for Assessment and Classification System (AMBIANCE) was developed for use as a screening instrument. Prior to its dissemination, this study aimed to assess the feasibility, reliability, and validity of the AMBIANCE-Brief. Adolescent mother-infant dyads (N = 69) participated in the Strange Situation Procedure, as well as play sessions with and without toys. Maternal disrupted caregiving was coded from the play sessions using the AMBIANCE and AMBIANCE-Brief. The AMBIANCE-Brief demonstrated convergent validity with the AMBIANCE in the play session with toys (r = .65, p < .001) and without toys (r = .61, p < .001). Concurrent validity of the AMBIANCE-Brief was also demonstrated in relation to infant attachment disorganization in the play session with toys (r = .36, p < .05) and without toys (r = .32, p < .01). These findings suggest a shorter protocol for assessing disrupted caregiving may be feasible and valid for use in community settings. Future studies are in progress to train community practitioners in the use of the AMBIANCE-Brief and to evaluate their reliability.

Como resultado de una necesidad identificada por la comunidad para un indicador bien validado de dificultades en la prestación de cuidado para uso en escenarios prácticos, se desarrolló una forma breve del Sistema del Instrumento de Conducta Materna Atípica para la Evaluación y Clasificación (AMBIANCE) para ser usado como instrumento de detección. Antes de ser diseminado, la meta de este estudio fue de evaluar la posibilidad, confiabilidad y validez de AMBIANCE-Abreviado. Las díadas de madres adolescentes e infantes (N = 69) participaron en el Procedimiento de la Situación Extraña, así como en sesiones de juego con y sin juguetes. La interrumpida prestación de cuidado materna fue codificada a partir de las sesiones de juego usando AMBIANCE y AMBIANCE-Abreviado. El AMBIANCE-Abreviado demostró una validez convergente con AMBIANCE en la sesión de juego con juguetes (r = .65, p < .001) y sin juguetes (r = .61, p < .001). También se demostró la validez concurrente de AMBIANCE-Abreviado en relación con la desorganización de la afectividad del infante en la sesión de juegos con juguetes (r = .36, p < .05) y sin juguetes (r = .32, p <.01). Estos resultados sugieren que un protocolo más corto para evaluar la interrumpida prestación de cuidado pudiera ser posible y válido para uso en escenarios comunitarios. Hay estudios futuros en progreso para entrenar al personal de la práctica comunitaria en el uso de AMBIANCE-Abreviado y para evaluar su confiabilidad.

Résultat d'un besoin identifié au niveau communautaire d'un indicateur bien validé de difficultés dans les soins pour une utilisation dans des contextes de pratique, une forme écourtée ("brève", ci-dessous) de l'Instrument d'Evaluation et du Système de Classification du Comportement Maternel Atypique (abrégé AMBIANCE en anglais, nous gardons ici l'abréviation anglaise) a été développée pour une utilisation à des fins d'outil de dépistage. Avant sa dissémination, cette étude s'était donnée pour but d'évaluer la faisabilité, la fiabilité et la validité de l'AMBIANCE-Brève. Des dyades adolescentes mères-nourrissons (N = 69) ont participé à la Procédure de Situation Etrange, ainsi qu'à des séances de jeu avec et sans jouets. Les soins maternels perturbés ont été codés à partir des séances de jeu en utilisant l'AMBIANCE et l'AMBIANCE-Brève. L'AMBIENCE-Brève a fait preuve de validité de convergence avec l'AMBIENCE dans les séances de jeu avec des jouets (r = ,65, p <,001) et sans jouets (r = ,61, p <,001). La validité concurrente de l'AMBIENCE-Brève a aussi été démontrée pour ce qui concerne la désorganisation de l'attachement du bébé dans la séance avec les jouets (r = ,36, p <,05) et sans jouets (r = ,32, p <,01). Ces résultats suggèrent qu'un protocole écourté pour l'évaluation de soin perturbé peut s'avérer plus fiable et valide pour l'utilisation en contexte communautaire. Des études supplémentaires sont en cours afin de former les praticiens communautaires à l'utilisation de l'AMBIENCE-Brève et afin d'évaluer leur fiabilité.

Differential effects of MYH9 and APOL1 risk variants on FRMD3 Association with Diabetic ESRD in African Americans.

Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed using the Affymetrix SNP Array 6.0 in 966 AA with T2DN and 1,032 non-diabetic, non-nephropathy (NDNN) controls, with and without adjustment for c22 nephropathy risk variants. No associations were seen between FRMD3 SNPs and T2DN before adjusting for c22 variants. However, logistic regression analysis revealed seven FRMD3 SNPs significantly interacting with MYH9-a finding replicated in 640 additional AA T2DN cases and 683 NDNN controls. Contrasting all 1,592 T2DN cases with all 1,671 NDNN controls, FRMD3 SNPs appeared to interact with the MYH9 E1 haplotype (e.g., rs942280 interaction p-value = 9.3E⁻7 additive; odds ratio [OR] 0.67). FRMD3 alleles were associated with increased risk of T2DN only in subjects lacking two MYH9 E1 risk haplotypes (rs942280 OR = 1.28), not in MYH9 E1 risk allele homozygotes (rs942280 OR = 0.80; homogeneity p-value = 4.3E⁻4). Effects were weaker stratifying on APOL1. FRMD3 SNPS were associated with T2DN, not type 2 diabetes per se, comparing AAs with T2DN to those with diabetes lacking nephropathy. T2DN-associated FRMD3 SNPs were detectable in AAs only after accounting for MYH9, with differential effects for APOL1. These analyses reveal a role for FRMD3 in AA T2DN susceptibility and accounting for c22 nephropathy risk variants can assist in detecting DN susceptibility genes.

A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes.

It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4x10(-6), odds ratio = 1.61, 95% confidence interval [CI]: 1.33-1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35 x 10(-8), odds ratio = 1.61, 95% Cl: 1.35-1.91). Rs2268388 was also associated with type 2 diabetes-associated end-stage renal disease (ESRD) in European Americans (p = 6 x 10(-4), odds ratio = 1.61, 95% Cl: 1.22-2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes.

Intergenerational transmission of parent adverse childhood experiences to child outcomes: A systematic review and meta-analysis.

OBJECTIVE: The current meta-analytic review provides a comprehensive synthesis of studies examining parent exposure to ACEs and the developmental and mental health outcomes of their children. PARTICIPANTS AND SETTING: Eligible studies up to August 2021 were identified through comprehensive database searches in PsycINFO, MEDLINE, and Embase. Studies that were included examined the intergenerational effects of parent ACEs on child development (i.e., cognitive, language, motor, social difficulties, and early social-emotional development) or mental health (i.e., internalizing problems, externalizing problems) outcomes. METHODS: Data were extracted by two coders using a standardized extraction protocol. A multi-level meta-analytic approach was used to derive pooled effect sizes and test for moderators. RESULTS: A total of 52 studies were included in the meta-analysis. Parent ACEs were positively associated with child mental health problems (r=0.17, 95% CI [0.12, 0.21], p<.001), child externalizing difficulties (r=0.20, 95% CI [0.15, 0.26], p<.001), and child internalizing difficulties (r=0.17, 95% CI [0.11, 0.22], p<.001). There were no significant sociodemographic (i.e., child age, parent age, income level, child sex, or racial/ethnic minority status) or methodological (i.e., study type or quality) moderators of these associations. Preliminary evidence suggests that parent ACEs were not associated with offspring developmental outcomes, such as cognitive or language skills. CONCLUSIONS: Results suggest that parent ACEs are associated with some, but not all child outcomes. Additional research focused on the mechanisms of transmission are needed to inform policies and practices related to the intergenerational transmission of ACEs.

Propensity of Patient-Derived iPSCs for Retinal Differentiation: Implications for Autologous Cell Replacement.

Prior to use, newly generated induced pluripotent stem cells (iPSC) should be thoroughly validated. While excellent validation and release testing assays designed to evaluate potency, genetic integrity, and sterility exist, they do not have the ability to predict cell type-specific differentiation capacity. Selection of iPSC lines that have limited capacity to produce high-quality transplantable cells, places significant strain on valuable clinical manufacturing resources. The purpose of this study was to determine the degree and root cause of variability in retinal differentiation capacity between cGMP-derived patient iPSC lines. In turn, our goal was to develop a release testing assay that could be used to augment the widely used ScoreCard panel. IPSCs were generated from 15 patients (14-76 years old), differentiated into retinal organoids, and scored based on their retinal differentiation capacity. Despite significant differences in retinal differentiation propensity, RNA-sequencing revealed remarkable similarity between patient-derived iPSC lines prior to differentiation. At 7 days of differentiation, significant differences in gene expression could be detected. Ingenuity pathway analysis revealed perturbations in pathways associated with pluripotency and early cell fate commitment. For example, good and poor producers had noticeably different expressions of OCT4 and SOX2 effector genes. QPCR assays targeting genes identified via RNA sequencing were developed and validated in a masked fashion using iPSCs from 8 independent patients. A subset of 14 genes, which include the retinal cell fate markers RAX, LHX2, VSX2, and SIX6 (all elevated in the good producers), were found to be predictive of retinal differentiation propensity.

Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans.

BACKGROUND: Polymorphisms in the non-muscle myosin IIA gene (MYH9) are associated with focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease (ESRD) in African Americans and FSGS in European Americans. We tested for association of single nucleotide polymorphisms (SNPs) in MYH9 with T2DM-ESRD in European Americans; additionally, three APOL1 gene variants were evaluated. METHODS: Fifteen MYH9 SNPs and two APOL1 SNPs plus a 6-bp deletion were genotyped in 1963 European Americans, 536 cases with T2DM-ESRD and 1427 non-nephropathy controls (467 with T2DM and 960 without diabetes). RESULTS: Comparing T2DM-ESRD cases with the 467 T2DM non-nephropathy controls, single variant associations trending toward significance were detected with SNPs rs4821480, rs2032487 and rs4281481 comprising part of the major MYH9 E1 risk haplotype [P-values 0.053-0.055 recessive, odds ratio (OR) 6.08-6.14]. Comparing T2DM-ESRD cases to all 1427 non-nephropathy controls, we confirmed evidence of association in these three SNPs as well as in the fourth E1 SNP (rs3752462) (P-values 0.017-0.035, OR 1.41-3.72). APOL1 G1/G2 nephropathy risk variants were rare in individuals of European American heritage, present in 0.28% of chromosomes in T2DM-ESRD cases and 0.32% of controls. CONCLUSIONS: MYH9 SNPs rs4821480, rs2032487, rs4281481 and rs3752462 are associated with T2DM-ESRD susceptibility in European Americans. The APOL1 risk variants are not present at appreciable frequency in this cohort with T2DM-ESRD. Therefore, polymorphisms in MYH9 appear to influence nephropathy risk in this sample.

The Impact of Parent-Child Closeness and Romantic Attachment on Dating Violence Perpetration in Adolescence.

Past research has demonstrated that romantic attachment insecurity is a risk factor for dating violence in adolescence. However, few studies to date have longitudinally examined whether earlier relational experience, such as perceived closeness with parents, may serve as an antecedent of this relationship. To examine longitudinal associations among youths' perceived closeness with parents, romantic attachment insecurity, and perpetration of dating violence in adolescence. Adolescents (N = 1016) were recruited from seven public high schools in south Texas and reported on their perceived closeness with parents, romantic attachment styles, and perpetration of physical and psychological dating violence at three assessments between 2010 and 2014. Data were analyzed using structural equation modeling. Adolescents' romantic attachment anxiety, but not attachment avoidance, significantly mediated the relationship between low perceived closeness with parents and the perpetration of physical and psychological dating violence in late adolescence. Multi-group analyses showed the mediation model only held for females but not males, and for Hispanic youth but not for Non-Hispanic White, African American, and youth of other races and ethnicities. Through its link to romantic attachment anxiety, perceived closeness with parents could play an important role in the perpetration of dating violence in adolescence, especially for girls and Hispanic youth. Findings suggest that dating violence interventions may benefit from targeting aspects of parent-child relationships.

A genome-wide association study for diabetic nephropathy genes in African Americans.

A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD.

Maternal Adverse Childhood Experiences and Child Behavior Problems: A Systematic Review.

CONTEXT: A growing body of research has examined the role of maternal adverse childhood experiences (ACEs) on child behavior problems. OBJECTIVE: To summarize the literature examining the association between maternal ACEs and child behavior problems via a systematic review. DATA SOURCES: Electronic searches were conducted in Medline, PsycINFO, and Embase (1998-June 2020). Reference lists were reviewed. In total, 3048 records were screened. STUDY SELECTION: Studies were included if an association between maternal ACEs and child externalizing (eg, aggression) and/or internalizing (eg, anxiety) problems was reported. In total, 139 full-text articles were reviewed for inclusion. DATA EXTRACTION: Data from 16 studies met full inclusion criteria. Studies were synthesized by child externalizing and internalizing outcomes. RESULTS: Maternal ACEs were significantly associated with child externalizing problems across all studies (number of studies synthesized per outcome [k] = 11). Significant associations were also found for inattention, hyperactivity, and impulsivity (k = 4), and aggression (k = 2). For internalizing problems (k = 11), significant associations were identified across 8 studies and nonsignificant associations were reported for 3 studies. Maternal ACEs were consistently associated with child anxiety and depression (k = 5). However, inconsistent findings were reported for somatization (k = 2). LIMITATIONS: Results are limited to mother-child dyads and questionnaire measures of behavior problems in primarily North American countries. CONCLUSIONS: Mothers' ACEs demonstrated largely consistent associations with children's behavior problems. Future research is needed to determine if specific types of maternal ACEs (eg, household dysfunction) are more strongly associated with child behavior problems.

Global Prevalence of Depressive and Anxiety Symptoms in Children and Adolescents During COVID-19: A Meta-analysis.

Importance: Emerging research suggests that the global prevalence of child and adolescent mental illness has increased considerably during COVID-19. However, substantial variability in prevalence rates have been reported across the literature. Objective: To ascertain more precise estimates of the global prevalence of child and adolescent clinically elevated depression and anxiety symptoms during COVID-19; to compare these rates with prepandemic estimates; and to examine whether demographic (eg, age, sex), geographical (ie, global region), or methodological (eg, pandemic data collection time point, informant of mental illness, study quality) factors explained variation in prevalence rates across studies. Data Sources: Four databases were searched (PsycInfo, Embase, MEDLINE, and Cochrane Central Register of Controlled Trials) from January 1, 2020, to February 16, 2021, and unpublished studies were searched in PsycArXiv on March 8, 2021, for studies reporting on child/adolescent depression and anxiety symptoms. The search strategy combined search terms from 3 themes: (1) mental illness (including depression and anxiety), (2) COVID-19, and (3) children and adolescents (age ≤18 years). For PsycArXiv, the key terms COVID-19, mental health, and child/adolescent were used. Study Selection: Studies were included if they were published in English, had quantitative data, and reported prevalence of clinically elevated depression or anxiety in youth (age ≤18 years). Data Extraction and Synthesis: A total of 3094 nonduplicate titles/abstracts were retrieved, and 136 full-text articles were reviewed. Data were analyzed from March 8 to 22, 2021. Main Outcomes and Measures: Prevalence rates of clinically elevated depression and anxiety symptoms in youth. Results: Random-effect meta-analyses were conducted. Twenty-nine studies including 80 879 participants met full inclusion criteria. Pooled prevalence estimates of clinically elevated depression and anxiety symptoms were 25.2% (95% CI, 21.2%-29.7%) and 20.5% (95% CI, 17.2%-24.4%), respectively. Moderator analyses revealed that the prevalence of clinically elevated depression and anxiety symptoms were higher in studies collected later in the pandemic and in girls. Depression symptoms were higher in older children. Conclusions and Relevance: Pooled estimates obtained in the first year of the COVID-19 pandemic suggest that 1 in 4 youth globally are experiencing clinically elevated depression symptoms, while 1 in 5 youth are experiencing clinically elevated anxiety symptoms. These pooled estimates, which increased over time, are double of prepandemic estimates. An influx of mental health care utilization is expected, and allocation of resources to address child and adolescent mental health concerns are essential.

Patient derived stem cells for discovery and validation of novel pathogenic variants in inherited retinal disease.

Our understanding of inherited retinal disease has benefited immensely from molecular genetic analysis over the past several decades. New technologies that allow for increasingly detailed examination of a patient's DNA have expanded the catalog of genes and specific variants that cause retinal disease. In turn, the identification of pathogenic variants has allowed the development of gene therapies and low-cost, clinically focused genetic testing. Despite this progress, a relatively large fraction (at least 20%) of patients with clinical features suggestive of an inherited retinal disease still do not have a molecular diagnosis today. Variants that are not obviously disruptive to the codon sequence of exons can be difficult to distinguish from the background of benign human genetic variations. Some of these variants exert their pathogenic effect not by altering the primary amino acid sequence, but by modulating gene expression, isoform splicing, or other transcript-level mechanisms. While not discoverable by DNA sequencing methods alone, these variants are excellent targets for studies of the retinal transcriptome. In this review, we present an overview of the current state of pathogenic variant discovery in retinal disease and identify some of the remaining barriers. We also explore the utility of new technologies, specifically patient-derived induced pluripotent stem cell (iPSC)-based modeling, in further expanding the catalog of disease-causing variants using transcriptome-focused methods. Finally, we outline bioinformatic analysis techniques that will allow this new method of variant discovery in retinal disease. As the knowledge gleaned from previous technologies is informing targets for therapies today, we believe that integrating new technologies, such as iPSC-based modeling, into the molecular diagnosis pipeline will enable a new wave of variant discovery and expanded treatment of inherited retinal disease.

Prevalence of posttraumatic and general psychological stress during COVID-19: A rapid review and meta-analysis.

Emerging evidence suggests rates of posttraumatic stress and psychological stress in the general population are elevated due to COVID-19. However, a meta-analysis is needed to attain more precise prevalence estimates due to between-study variability. Thus, we performed a rapid review and meta-analysis of posttraumatic stress and general psychological stress symptoms during COVID-19. Electronic searches were conducted up to May 26th, 2020 using key terms: mental illness and COVID-19. A total of k = 14 non-overlapping studies were identified for inclusion. Random effects meta-analyses indicated that the pooled prevalence of posttraumatic stress symptoms and psychological stress in the general population was 23.88% and 24.84%, respectively. In both meta-analyses, the prevalence of stress symptoms was higher in unpublished compared to peer-reviewed studies. Overall, nearly one-in-four adults experienced significant stress due to the COVID-19 pandemic. Psychological resources and services must be allocated to help address the mental health burden of COVID-19. High quality, longitudinal research on the long-term mental health effects of the pandemic is greatly needed.

Identifying neural progenitor cells in the adult brain.

There is incontrovertible evidence that neural progenitor cells (NPC) are found in the adult brain. The ability to identify and track NPC in the adult brain is of considerable importance if the properties of these cells are to be harnessed as potential therapies for degenerative brain disorders. The most commonly used approach of identifying these NPC in experimental studies, bromodeoxyuridine (BrdU) labelling, is outlined in this chapter. Immunohistochemical protocols for detecting endogenous and exogenous (introduced via transplantation) NPC in fresh-frozen and paraffin wax embedded brain tissue are described. Advice on how to label these NPC is also offered and multi-label fluorescence immunochemical staining approaches to determine the differentiation fate of NPC are described.