Inherited CSNK2A1 variants in families with Okur-Chung neurodevelopmental syndrome.

Pedigree showing the autosomal dominant inheritance pattern of CSNK21 variants in families presenting with OCNDS. (A) Maternal inheritance to two daughters in Family 1, (B) Paternal inheritance to a daughter in Family 2, and (C) Maternal inheritance to two sons in Family 3.

Patient organization perspective: a research roadmap for Okur-Chung Neurodevelopmental Syndrome.

Okur-Chung neurodevelopmental syndrome (OCNDS) is an ultra-rare disorder caused by variants in the CSNK2A1 gene. CSNK2A1 encodes for the alpha subunit of casein kinase 2 (CK2), a serine/threonine kinase critical in neural development. CK2 is implicated in many human pathologies, including viral infections, cancer, inflammation, cardiovascular, neurodegenerative, and psychiatric diseases. However, the mechanism of action for the CSNK2A1 variants observed in OCNDS is not fully understood, although studies suggest a loss of function or altered substrate specificity. There are no approved treatments for OCNDS, and current treatments focus on symptom management. The CSNK2A1 Foundation was established in 2018 and aims to find a cure for OCNDS and provide support to affected individuals. OCNDS presents with symptoms at varying severity, including developmental delay/intellectual disabilities, autism, disrupted sleep, speech delays/inability to speak, short stature, and, in ~25% of cases, epilepsy. The foundation has developed a research toolbox that is readily available to researchers worldwide and has awarded ~$1 million in grant funding. These efforts have provided valuable insights into CK2 biology and the natural history of OCNDS. However, additional efforts are needed to fully characterize the disease mechanism and investigate potential treatment interventions. Continued investigation into CK2 and its role in neural development holds promise for a better understanding of OCNDS and related disorders in the future. To accelerate research, we have developed a research roadmap highlighting key focus areas of landscape analysis/toolbox expansion, biomarker development, and therapeutic testing through a series of steps that are nonlinear; we expect these efforts to guide decision-making for therapeutic exploration whether that be drug repurposing, gene therapy, novel drug discovery, or a combination. In this perspective article, we describe OCNDS and the CSNK2A1 gene, highlight gaps in OCNDS research, discuss the research roadmap, and offer the founder's perspective on our growth and future opportunities.

Patient organization perspective: a research roadmap for Okur-Chung Neurodevelopmental Syndrome Okur-Chung Neurodevelopmental Syndrome (OCNDS) is an ultra-rare disorder caused by variants in the CSNK2A1 gene.CSNK2A1 creates a subunit of CK2, a critical protein in brain development among other biological processes.There are no approved treatments for OCNDS, and current suggested treatments focus on symptom management.Individuals with OCNDS exhibit many symptoms at varying severity levels, including developmental delay/intellectual disabilities, autism, disrupted sleep, speech delays/inability to speak, short stature, and in approximately 25% of cases, epilepsy. We think that seizure prevalence may be underreported due to lack of extended EEG recordings for OCNDS patients and that seizures may preferentially occur at night as has been observed in other autism spectrum disorders.The CSNK2A1 Foundation was established in 2018 and aims to find a cure for OCNDS and provide support to affected individuals. The CSNK2A1 Foundation's research tools and efforts have provided valuable insights into the biology of OCNDS and the natural history of the disorder. However, additional efforts are needed to fully understand how OCNDS affects the body and investigate potential treatment approaches.To accelerate OCNDS research, the foundation has developed a research roadmap that is presented in this perspective article. We describe OCNDS and the CSNK2A1 gene, highlight gaps in OCNDS research, discuss the research roadmap, and offer the founder's perspective on our growth and future opportunities.

Gendered norms, sexual exploitation and adolescent pregnancy in rural Tanzania.

Adolescent pregnancy places girls at increased risk for poor health and educational outcomes that limit livelihood options, economic independence, and empowerment in adulthood. In Tanzania, adolescent pregnancy remains a significant concern, with over half of all first births occurring before women reach the age of 20. A participatory research and action project (Vitu Newala) conducted formative research in a rural district on the dynamics of sexual risk and agency among 82 girls aged 12-17. Four major risk factors undermined girls' ability to protect their own health and well-being: poverty that pushed them into having sex to meet basic needs, sexual expectations on the part of older men and boys their age, rape and coercive sex (including sexual abuse from an early age), and unintended pregnancy. Transactional sex with older men was one of the few available sources of income that allowed adolescent girls to meet their basic needs, making this a common choice for many girls, even though it increased the risk of unintended (early) pregnancy. Yet parents and adult community members blamed the girls alone for putting themselves at risk. These findings were used to inform a pilot project aimed to engage and empower adolescent girls and boys as agents of change to influence powerful gender norms that perpetuate girls' risk.

A systematic review and meta-analysis of intimate partner violence during pregnancy and selected birth outcomes.

BACKGROUND: Intimate partner violence (IPV) has a detrimental impact on the lives of women worldwide. Several studies have examined the effect IPV has on adverse birth outcomes when it occurs during pregnancy. OBJECTIVES: To explore the association between IPV and selected adverse birth outcomes. SEARCH STRATEGY: Multiple databases were searched to identify studies investigating the association between IPV and low birth weight (LBW), preterm birth, and/or intrauterine growth restriction (IUGR). SELECTION CRITERIA: Included studies defined the perpetrator of violence as an intimate partner, the type of violence as physical and/or sexual, and the study outcomes as LBW, preterm birth, or IUGR, with violence preceding delivery. DATA COLLECTION AND ANALYSIS: Random-effects meta-analysis was used to calculate adjusted/unadjusted odds ratios (ORs). Subanalyses explored the effect of emotional/psychological violence on birth outcomes. MAIN RESULTS: Nineteen studies met the inclusion criteria (15 LBW, 12 preterm birth, 4 IUGR). IPV was associated with LBW (OR 1.18, 95% confidence interval 1.05-1.31; I(2)=0.70, P<0.001) and preterm birth (OR 1.42, 95% confidence interval 1.21-1.63; I(2)=0.20, P<0.001). No statistically significant association was found for IUGR. CONCLUSIONS: There are associations between IPV and LBW and preterm birth that could be causal.

Stigma, shame and women's limited agency in help-seeking for intimate partner violence.

In Tanzania, 44% of women experience intimate partner violence (IPV) in their lifetime, but the majority never seeks help, and many never tell anyone about their experience. Even among the minority of women who seek support, only 10% access formal services. Our research explored the social and structural barriers that render Tanzanian women unable to exercise agency in this critical domain of their lives. We collected qualitative data in three regions of Tanzania through 104 key informant interviews with duty bearers and participatory focus groups with 96 male and female community members. The findings revealed numerous sociocultural barriers to help-seeking, including gendered social norms that accept IPV and impose stigma and shame upon survivors. Because IPV is highly normalised, survivors are silenced by their fear of social consequences, a fear reinforced by the belief that it is women's reporting of IPV that brings shame, rather than the perpetration of violence itself. Barriers to help-seeking curtail women's agency. Even women who reject IPV as a 'normal' practice are blocked from action by powerful social norms. These constraints deny survivors the support, services and justice they deserve and also perpetuate low reporting and inaccurate estimates of IPV prevalence.

Immigration policies increase south Asian immigrant women's vulnerability to intimate partner violence.

OBJECTIVE: To explore forms of immigration-related partner abuse and examine the association of such abuse and immigration status with physical and sexual intimate partner violence (IPV) among South Asian women residing in greater Boston. METHOD: Cross-sectional survey data on demographics,immigration status, immigration-related partner abuse, IPV, and health were collected from immigrant South Asian women currently in relationships with men (n=189). In-depth interviews were conducted with immigrant South Asian women with histories of IPV (n=23). The majority of women in both the quantitative and qualitative studies were Indian (96% and 65%), not US citizens (69% and 83%), and highly educated (48% and 39% reported postgraduate training). Logistic regression analyses adjusted for related demographics and 95% confidence intervals were used to assess quantitative data. Qualitative data were assessed via a grounded theory approach. RESULTS: The odds of reporting IPV (23% of the sample)were higher for women who reported that their partners refused to change their immigration status (OR 7.8; CI 1.4, 44.6) or threatened them with deportation (OR 23.0; CI 4.5, 118.8) and for those on spousal dependent visas (OR 2.8; CI 1.1, 7.4) than they were for other women. Abused women interviewed also described how their partners used immigration laws prohibiting them from working or petitioning for status change to limit their autonomy. CONCLUSION: Immigration policies that prevent women on spousal visas from working and petitioning to change their status increase women's vulnerability to partner abuse. Such legal barriers may constitute human rights violations and should be reformed to protect immigrant battered women and their children.

Risk factors for men's lifetime perpetration of physical violence against intimate partners: results from the international men and gender equality survey (IMAGES) in eight countries.

This paper examines men's lifetime physical intimate partner violence (IPV) perpetration across eight low- and middle-income countries to better understand key risk factors that interventions can target in order to promote gender equality and reduce IPV. We use data from men (n = 7806) that were collected as part of the International Men and Gender Equality Survey (IMAGES) in Bosnia and Herzegovina, Brazil, Chile, Croatia, Democratic Republic of Congo (DRC), India, Mexico, and Rwanda. Results show that there is wide variation across countries for lifetime self-reported physical violence perpetration (range: 17% in Mexico to 45% in DRC), men's support for equal roles for men and women, and acceptability of violence against women. Across the sample, 31% of men report having perpetrated physical violence against a partner in their lifetime. In multivariate analyses examining risk factors for men ever perpetrating physical violence against a partner, witnessing parental violence was the strongest risk factor, reinforcing previous research suggesting the inter-generational transmission of violence. Additionally, having been involved in fights not specifically with an intimate partner, permissive attitudes towards violence against women, having inequitable gender attitudes, and older age were associated with a higher likelihood of ever perpetrating physical IPV. In separate analyses for each country, we found different patterns of risk factors in countries with high perpetration compared to countries with low perpetration. Findings are interpreted to identify key knowledge gaps and directions for future research, public policies, evaluation, and programming.

Influences on tobacco use among urban Hispanic young adults in Baltimore: findings from a qualitative study.

BACKGROUND: Among Hispanics, lung cancer is the leading cause of cancer-related death for men and the second leading cause of cancer death for women in the United States. Despite recent growth in Baltimore City's Hispanic population, few data exist on tobacco use behaviors in this group. OBJECTIVES: The present research sought to explore the social and environmental influences and norms that encourage or discourage tobacco use among Hispanic young adults in Baltimore. METHODS: In collaboration with several community stakeholders, we conducted focus groups with Hispanic young adults 18 to 24 years old. Participants were recruited from a community-based service organization and invited to take part in one of four focus groups segregated by gender. RESULTS: A total of 13 young men and 11 young women participated. Data from these focus groups indicate that cultural identity and gender norms leverage substantial influence in young adults' decision about whether, where, and with whom to smoke. The data also suggest multiple social and familial influences on their smoking and nonsmoking behaviors. Participants identified smoking practices and clear brand preferences that they feel distinguish Hispanics from other racial and ethnic groups. Despite acknowledging the high price of cigarettes, cost was not mentioned as a factor influential in their smoking decisions. CONCLUSION: These results provide essential guidance for the development of appropriate tobacco prevention and cessation intervention strategies and policy recommendations to eliminate tobacco use among Hispanic young adults in Baltimore.

South Asian victims of intimate partner violence more likely than non-victims to report sexual health concerns.

To assess relationships between intimate partner violence (IPV) and sexual health among South Asian women in Boston. Surveys assessed demographics, IPV and sexual and reproductive health outcomes of women in relationships with men (N=208). In-depth interviews explored these issues with women with a history of IPV (N=23). Subjects were majority Indian, non-U.S. citizens, and highly educated. Quantitative data were assessed by logistic regression, qualitative data by a grounded theory approach. About 21.2% of the survey sample reported IPV in the current relationship. These women are 2.6 times as likely to report discolored vaginal discharge in the past year (95% CI=1.27-6.50), 3.1 times as likely to report burning during urination in the past year (95% CI=1.52-6.31) and 3.4 times as likely to report unwanted pregnancy in the current relationship (95% CI=1.33-8.66). Interviewed women described how abuse reduces sexual autonomy, increasing risk for unwanted pregnancy and multiple abortions. Study findings demonstrate the need for increased gynecologic health outreach to abused South Asian women in the U.S.