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Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants., Methods: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies., Results: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities., Conclusion: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: In sub-Saharan Africa many children live in extreme poverty and experience a burden of illness and disease that is disproportionately high. The emergence of HIV and AIDS has only exacerbated long-standing challenges to improving children's health in the region, with recent cohorts experiencing pediatric AIDS and high levels of orphan status, situations which are monitored globally and receive much policy and research attention. Children's health, however, can be affected also by living with HIV-infected adults, through associated exposure to infectious diseases and the diversion of household resources away from them. While long recognized, far less research has focused on characterizing this distinct and vulnerable population of HIV-affected children., Methods: Using Demographic and Health Survey data from 23 countries collected between 2003 and 2011, we estimate the percentage of children living in a household with at least one HIV-infected adult. We assess overlaps with orphan status and investigate the relationship between children and the adults who are infected in their households., Results: The population of children living in a household with at least one HIV-infected adult is substantial where HIV prevalence is high; in Southern Africa, the percentage exceeded 10% in all countries and reached as high as 36%. This population is largely distinct from the orphan population. Among children living in households with tested, HIV-infected adults, most live with parents, often mothers, who are infected; nonetheless, in most countries over 20% live in households with at least one infected adult who is not a parent., Conclusion: Until new infections contract significantly, improvements in HIV/AIDS treatment suggest that the population of children living with HIV-infected adults will remain substantial. It is vital to on-going efforts to reduce childhood morbidity and mortality to consider whether current care and outreach sufficiently address the distinct vulnerabilities of these children.

Rural-to urban migration is increasingly common among youth and could affect sexual activities. We use life history calendar data collected in Kisumu, Kenya, to investigate how the timing and number of rural-to-urban moves are associated with premarital pregnancy. Among sexually experienced young women aged 18-24 (N=226), 39 percent have experienced a premarital pregnancy and 60 percent experienced a move in the last 10 years. Results of the event history analysis show that those who experienced one or two moves or whose most recent move occurred in the last seven to 12 months are at increased risk of premarital pregnancy compared to nonmovers. Those whose last move occurred at age 13 or younger were also at an elevated risk. Migration brings about specific needs for youth, including the need for sexual and reproductive health education and services, which should be made available and accessible to new urban residents.

Social, political, epidemiological, and economic forces have produced family instability during childhood for many young people transitioning to adulthood in South Africa. This study identifies pathways to adulthood for youth in Cape Town that capture the timing and sequencing of role transitions across the life domains of school, work, and family formation. It then uses these pathways to investigate the relationship between childhood family instability and the way young people's lives unfold during the transition to adulthood. Results indicate that changes in co-residence with parents are associated with following less advantageous pathways into adulthood, independent of particular family structure or orphan status. Overall, the findings suggest that family instability influences not only single transitions for youth, but also combinations of transitions. They also indicate the value of a multi-dimensional conceptualization of the transition to adulthood in empirical work.

Epidemiological, economic, and social forces have produced high levels of volatility in family and household structure for young people growing up in sub-Saharan Africa in recent decades. However, scholarship on the family to date has not examined the influence of this family instability on young people's well-being. The current study employs unique life history calendar data from Western Kenya to investigate the relationship between instability in caregiving and early initiation of sexual activity. It draws on a body of work on parental union instability in the United States, and examines new dimensions of family change. Analyses reveal a positive association between transitions in primary caregiver and the likelihood of early sexual debut that is rapidly manifested following caregiver change and persists for a short period. The association is strongest at early ages, and there is a cumulative effect of multiple caregiver changes. The results highlight the importance of studying family stability in sub-Saharan Africa, as distinct from family structure, and for attention to dimensions such as age and recency.

Migration during the formative adolescent years can affect important life-course transitions, including the initiation of sexual activity. In this study, we use life history calendar data to investigate the relationship between changes in residence and timing of premarital sexual debut among young people in urban Kenya. By age 18, 64 percent of respondents had initiated premarital sex, and 45 percent had moved at least once between the ages of 12 and 18. Results of the event history analysis show that girls and boys who move during early adolescence experience the earliest onset of sexual activity. For adolescent girls, however, other dimensions of migration provide protective effects, with greater numbers of residential changes and residential changes in the last one to three months associated with later sexual initiation. To support young people's ability to navigate the social, economic, and sexual environments that accompany residential change, researchers and policymakers should consider how various dimensions of migration affect sexual activity.

In Southern Africa, high adult HIV prevalence has fueled concern about the welfare of children losing parents to the epidemic. A growing body of evidence indicates that parental, particularly maternal, death is negatively associated with child outcomes. However, a better understanding of the mechanisms is needed. In addition, the way orphan disadvantage and the mechanisms giving rise to it are understood on the ground is essential for the successful translation of research into policies and programs. This study employs data from 89 in-depth interviews with caregivers and key informants in Lesotho, a setting where approximately one-quarter of adults is infected with HIV, to elaborate understandings of orphan disadvantage. Our analysis focuses on two questions: (i) Do local actors perceive orphans to be disadvantaged compared to non-orphans, and if so, in what ways; and (ii) How do they explain orphans' differential disadvantage?Analyses suggest that orphans were widely perceived to be disadvantaged; respondents described this disadvantage in material as well as affective domains. Thematic analyses reveal five broad categories of explanation: poverty, love and kin connection, caregiver character, perceptions of orphans, and community norms related to orphan care. These results underscore the need for research and policy to address (i) multiple types of disadvantage, including deficits in kindness and attention; and (ii) the social embeddedness of disadvantage, recognizing that poverty, kinship, and community interact with individual attributes to shape caregiving relationships and child experiences. The findings suggest limited success for programs and policies that do not address the emotional needs of children, or that focus on child or caregiver support to the exclusion of community outreach.

Transactional sex, or the exchange of money and gifts for sexual activities within nonmarital relationships, has been widely considered a contributing factor to the disproportionate prevalence of HIV/AIDS among young women in sub-Saharan Africa. This study applied social exchange theory to premarital relationships in order to investigate the linkages between a variety of young women's resources-including employment and material transfers from male partners-and sexual behaviors. Data on the first month of premarital relationships (N=551 relationships) were collected from a random sample of young adult women ages 18-24 in Kisumu, Kenya, using a retrospective life history calendar. Consistent with the hypotheses, results showed that young women's income increases the likelihood of safer sexual activities, including delaying sex and using condoms consistently. Material transfers from the male partner displayed the opposite effect, supporting the view that resources obtained from within the relationship decrease young women's negotiating power.

Ischemic optic neuropathy and retinal arterial occlusion are 2 forms of arterial occlusive disease affecting the eye. Reports in the literature suggest platelet hyperactivity in acute arterial occlusive diseases affecting other organ systems. Therefore, 14 patients with ischemic optic neuropathy and 17 patients with central or branch retinal artery occlusion were studied to determine whether platelets have a role in the pathogenesis of these vascular occlusive disorders. The results of the following investigations were no different in these patients compared with those in 18 control patients with non-vascular eye diseases: prothrombin times, partial thromboplastin times, plasma fibrinogen, factor V, factor VIII, platelet counts and threshold concentrations of ADP, epinephrine and collagen resulting in secondary platelet aggregation and serotonin release. In contrast, platelet coagulant activities concerned with the early stages of intrinsic coagulation were significantly increased in patients with retinal artery occlusion without hypertension or type IV hyperlipoproteinemia, but generally normal in patients with ischemic optic neuropathy and in patients with retinal artery occlusion associated with hypertension, type IV hyperlipoproteinemia, diabetes mellitus and generalized atherosclerosis. These results are consistent with a platelet contribution to retinal arterial occlusive disease in patients without other known contributing factors such as hypertension, serum lipid abnormalities, diabetes mellitus and generalized atherosclerosis and may have implications regarding prophylaxis.