iPSC-Based Modeling of Variable Clinical Presentation in Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a frequent cause of heart failure and sudden cardiac death. Our understanding of the genetic bases and pathogenic mechanisms underlying HCM has improved significantly in the recent past, but the combined effect of various pathogenic gene variants and the influence of genetic modifiers in disease manifestation are very poorly understood. Here, we set out to investigate genotype-phenotype relationships in 2 siblings with an extensive family history of HCM, both carrying a pathogenic truncating variant in the MYBPC3 gene (p.Lys600Asnfs*2), but who exhibited highly divergent clinical manifestations. METHODS: We used a combination of induced pluripotent stem cell (iPSC)-based disease modeling and CRISPR (clustered regularly interspersed short palindromic repeats)/Cas9 (CRISPR-associated protein 9)-mediated genome editing to generate patient-specific cardiomyocytes (iPSC-CMs) and isogenic controls lacking the pathogenic MYBPC3 variant. RESULTS: Mutant iPSC-CMs developed impaired mitochondrial bioenergetics, which was dependent on the presence of the mutation. Moreover, we could detect altered excitation-contraction coupling in iPSC-CMs from the severely affected individual. The pathogenic MYBPC3 variant was found to be necessary, but not sufficient, to induce iPSC-CM hyperexcitability, suggesting the presence of additional genetic modifiers. Whole-exome sequencing of the mutant carriers identified a variant of unknown significance in the MYH7 gene (p.Ile1927Phe) uniquely present in the individual with severe HCM. We finally assessed the pathogenicity of this variant of unknown significance by functionally evaluating iPSC-CMs after editing the variant. CONCLUSIONS: Our results indicate that the p.Ile1927Phe variant of unknown significance in MYH7 can be considered as a modifier of HCM expressivity when found in combination with truncating variants in MYBPC3. Overall, our studies show that iPSC-based modeling of clinically discordant subjects provides a unique platform to functionally assess the effect of genetic modifiers.

Haematopoietic stem cell transplantation in children with sickle cell disease: Still to do?

Sickle cell disease affects the whole body through acute and chronic organ damage and results in significant physical and neurological constraints. The report by Cseh et al. demonstrates in a retrospective multinational study that allogeneic haematopoietic stem cell transplantation from HLA-identical siblings using a contemporary conditioning regimen is safe and effective in more than 96% of patients. Commentary on: Cseh et al. Busulfan-fludarabine- or treosulfan-fludarabine-based conditioning before allogeneic HSCT from matched sibling donors in paediatric patients with sickle cell disease: A study on behalf of the EBMT Paediatric Diseases and Inborn Errors Working Parties. Br J Haematol 2024;204:e1-e5. [Correction added on 23 November 2023, after first online publication: In the preceding sentence, the article title and doi have been updated in this version.].

Extra Nestlings That Are Condemned to Die Increase Reproductive Success in Hoopoes.

AbstractThe adaptive value of routinely laying more eggs than can be successfully fledged has intrigued evolutionary biologists for decades. Extra eggs could, for instance, be adaptive as insurance against hatching failures. Moreover, because recent literature demonstrates that sibling cannibalism is frequent in the Eurasian hoopoe (Upupa epops), producing extra offspring that may be cannibalized by older siblings might also be adaptive in birds. Here, directed to explore this possibility in hoopoes, we performed a food supplementation experiment during the laying period and a clutch size manipulation during the hatching stage. We found that females with the food supplement laid on average one more egg than control females and that the addition of a close-to-hatch egg at the end of the hatching period increased the intensity of sibling cannibalism and enhanced fledging success in hoopoe nests. Because none of the extra nestlings from the experimental extra eggs survived until fledging, these results strongly suggest that hoopoes obtain fitness advantages by using temporarily abundant resources to produce additional nestlings that will be cannibalized. These results therefore suppose the first experimental demonstration of the nutritive adaptive function of laying extra eggs in vertebrates with parental care.

Allogeneic transplantation of bone marrow versus peripheral blood stem cells from HLA-identical sibling donors for hematological malignancies in 6064 adults from 2003 to 2020: different impacts on survival according to time period.

BACKGROUND: Mobilized peripheral blood stem cells (PBSC) have been widely used instead of bone marrow (BM) as the graft source for allogeneic hematopoietic cell transplantation (HCT). Although early studies demonstrated no significant differences in survival between PBSC transplantation (PBSCT) and BM transplantation (BMT) from human leukocyte antigen (HLA)-identical sibling donors to adults with hematological malignancies, recent results have been unclear. OBJECTIVE: The objective of this retrospective study was to compare overall survival (OS), relapse, non-relapse mortality (NRM), hematopoietic recovery and graft-versus-host disease (GVHD) between PBSCT and BMT according to the time period of HCT (2003-2008, 2009-2014, or 2015-2020). STUDY DESIGN: We retrospectively compared the outcomes after PBSCT versus BMT in 6064 adults with hematological malignancies using a Japanese registry database between 2003 and 2020. RESULTS: The adjusted probability of OS was significantly higher in BMT recipients compared to PBSCT recipients during the early period of 2003-2008 (adjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.70-0.91; P < 0.001) and the middle period of 2009-2014 (adjusted HR, 0.80; 95% CI, 0.70-0.91; P < 0.001). However, during the late period of 2015-2020, the adjusted probability of OS was comparable between BMT and PBSCT recipients (adjusted HR, 0.94; 95% CI, 0.79-1.13; P = 0.564), which were mainly due to the reduction of NRM. There was no significant difference in the relapse rate between the groups, irrespective of the time period. Compared to BMT, PBSCT led to faster neutrophil and platelet recovery and the cumulative incidences of grades II-IV and grades III-IV acute and overall and extensive chronic GVHD were significantly higher in PBSCT recipients, irrespective of the time period. CONCLUSIONS: PBSCT and BMT had similar survival outcomes and relapse rates in adult patients with hematological malignancies during the late time period of 2015-2020 despite the hematopoietic recovery and acute and chronic GVHD being higher in PBSCT recipients in all time periods.

OPN, BSP, and Bone Quality-Structural, Biochemical, and Biomechanical Assessment in OPN-/-, BSP-/-, and DKO Mice.

Osteopontin (OPN) and Bone Sialoprotein (BSP), abundantly expressed by osteoblasts and osteoclasts, appear to have important, partly overlapping functions in bone. In gene-knockout (KO, -/-) models of either protein and their double (D)KO in the same CD1/129sv genetic background, we analyzed the morphology, matrix characteristics, and biomechanical properties of femur bone in 2 and 4 month old, male and female mice. OPN-/- mice display inconsistent, perhaps localized hypermineralization, while the BSP-/- are hypomineralized throughout ages and sexes, and the low mineralization of young DKO mice recovers with age. The higher contribution of primary bone remnants in OPN-/- shafts suggests a slow turnover, while their lower percentage in BSP-/- indicates rapid remodeling, despite FTIR-based evidence in this genotype of a high maturity of the mineralized matrix. In 3-point bending assays, OPN-/- bones consistently display higher Maximal Load, Work to Max. Load and in young mice Ultimate Stress, an intrinsic characteristic of the matrix. Young male and old female BSP-/- also display high Work to Max. Load along with low Ultimate Stress. Principal Component Analysis confirms the major role of morphological traits in mechanical competence, and evidences a grouping of the WT phenotype with the OPN-/- and of BSP-/- with DKO, driven by both structural and matrix parameters, suggesting that the presence or absence of BSP has the most profound effects on skeletal properties. Single or double gene KO of OPN and BSP thus have multiple distinct effects on skeletal phenotypes, confirming their importance in bone biology and their interplay in its regulation.

Single-unit unrelated cord blood transplantation versus HLA-matched sibling transplantation in adults with advanced myelodysplastic syndrome: A registry-based study from the adult MDS working group of the Japanese society for transplantation and cellular therapy.

Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)-1 and RAEB-2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (n = 331) or single-unit unrelated cord blood (UCB) (n = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90-1.34; P = 0.347), disease-free survival (HR, 1.01; 95% CI, 0.84-1.23; P = 0.845), relapse (HR, 0.88; 95% CI, 0.68-1.15; P = 0.370), or non-relapse mortality (HR, 1.15; 95% CI, 0.87-1.50; P = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24-0.33; P < 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23-0.36; P < 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft-versus-host disease (GVHD) (HR, 0.57; 95% CI, 0.44-0.75; P < 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32-0.67; P < 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.

Comparable outcomes of allogeneic peripheral blood versus bone marrow hematopoietic stem cell transplantation from a sibling donor for pediatric patients.

Traditionally, bone marrow (BM) has been preferred as a source of stem cells (SCs) in pediatric hematopoietic SC transplantation (HSCT); however, the use of peripheral blood SCs (PBSC) has recently increased. With advancing graft-versus-host disease (GVHD) prophylaxis, whether the BM is still a better SC source than PB in sibling donor HSCT remains controversial. Here, we compared the results of BM transplantation (BMT) and PBSC transplantation (PBSCT) in pediatric patients with malignant or non-malignant diseases receiving sibling HSCT using a total of 7.5 mg/kg of anti-thymocyte globulin (ATG). We retrospectively reviewed children who received HSCT from a sibling donor between 2005 and 2020 at Seoul National University Children's Hospital. Of the 86 patients, 40 underwent BMT, and 46 underwent PBSCT. Fifty- six patients had malignant diseases, whereas thirty patients had non-malignant diseases. All conditioning regimens comprised ATG. Busulfan-based myeloablative conditioning regimens were administered to patients with malignant diseases and approximately half of those with non-malignant diseases. The remaining half of the patients with non-malignant diseases were administered cyclophosphamide-based reduced- intensity conditioning regimens. According to studies conducted at our center, all BM donors received G-CSF before harvest to achieve early engraftment. In all 86 patients (47 males and 39 females), the median age at the time of HSCT was 11.4 (range, 0.7 - 24.6) years. The median follow-up period was 57.9 (range, 0.9-228.6) months, and the corresponding values for those with BM and PBSC were 77 (range, 2.4-228.6) months and 48.7 (range, 0.9-213.2) months, respectively. Engraftment failure occurred in one patient with BM and no patient with PBSC. The cumulative incidence of acute GVHD with grades II-IV was higher in PBSC (BM 2.5%, PBSC 26.1%, p = 0.002), but there was no significant difference in those with grades III-IV acute GVHD (BM 0%, PBSC 6.5%, p = 0.3703) and extensive chronic GVHD (BM 2.5%, PBSC 11.6%, p = 0.1004). There were no significant differences in treatment-related mortality (TRM) (BM 14.2%, PBSC 6.8%, p = 0.453), 5-year event-free survival (EFS) (BM 71.5%, PBSC 76.2%, p = 0.874), and overall survival (OS) rates (BM 80.8%, PBSC 80.3%, p = 0.867) between BM and PBSC in the univariate analysis. In the multivariate analysis, which included all factors with p < 0.50 in the univariate analysis, there was no significant prognostic factor for EFS or OS. There was no significant difference in the relapse incidence between BM and PBSC among patients with malignant diseases (BM 14.2%, PBSC 6.8%, p = 0.453). Additionally, there were no significant differences in the TRM, 5-year EFS, and OS rates between malignant and non-malignant diseases nor between the busulfan-based myeloablative regimen and reduced-intensity chemotherapy using cyclophosphamide. In this study, we showed no significant differences in EFS, OS, TRM, and GVHD, except for acute GVHD grades II-IV, between BMT and PBSCT from sibling donors, using ATG (a total of 7.5 mg/kg). Therefore, PB collection, which is less invasive for donors and less labor-intensive for doctors, could also be considered an acceptable SC source for sibling donor HSCT in children.

Genetic influences on sibling bullying and mental health difficulties.

BACKGROUND: Sibling bullying is associated with mental health difficulties; both in the short and long term. It is commonly assumed that sibling bullying leads to mental health difficulties but additional explanations for the relationship between the two are seldom investigated. METHODS: To address this gap in knowledge, we used a genetically sensitive design with data from the Avon Longitudinal Study of Parents and Children (maximum N = 3,959, 53% female). At ages 11-13 years, individuals self-reported their involvement in sibling bullying, as a victim and perpetrator, and parents reported on their child's mental health difficulties. Polygenic scores, indices of genetic risk for psychiatric disorders (major depressive disorder and attention deficit hyperactivity disorder) were computed using children's genetic data. Regression and structural equation models were fitted to the data. RESULTS: Sibling bullying, victimisation and perpetration, and polygenic scores both predicted mental health difficulties in an additive manner but there was no interaction between them. Polygenic scores for mental health difficulties were also associated with sibling bullying. CONCLUSIONS: These findings suggest that sibling bullying, victimisation and perpetration, is associated with mental health difficulties, even after accounting for some genetic effects. Additionally, the relationship between sibling bullying and mental health difficulties may be, at least partly, due to shared genetic aetiology. One possibility is that genetic risk for mental health difficulties influences the onset of mental health difficulties which in turn make children more susceptible to sibling bullying.

A systematic review: is Anopheles vagus a species complex?

BACKGROUND: Anopheles vagus (subgenus Cellia) has been identified as a vector for malaria, filariasis, and Japanese encephalitis in Asia. Sporozoites of Plasmodium falciparum and Plasmodium vivax have been found in this zoophilic mosquito in Asia and Indonesia. This study systematically reviews publications regarding An. vagus species, variation, bio-ecology, and malaria transmission in various localities in Asia, especially Indonesia, to determine whether the current data support An. vagus as a species complex. METHODS: The databases Pubmed, Scopus, Europe PMC, and Proquest were searched to identify information regarding the morphology, karyotypes, polytene chromosome, cross-mating, ecology, and molecular identification of An. vagus was then evaluated to determine whether there were possible species complexes. RESULTS: Of the 1326 articles identified, 15 studies were considered for synthesis. The Anopheles spp. samples for this study came from Asia. Eleven studies used morphology to identify An. vagus, with singular studies using each of karyotype identification, chromosomal polytene identification, and cross-breeding experiments. Ten studies used molecular techniques to identify Anopheles spp., including An. vagus. Most studies discovered morphological variations of An. vagus either in the same or different areas and ecological settings. In this review, the members of An. vagus sensu lato grouped based on morphology (An. vagus, An. vagus vagus, An. vagus limosus, and An. limosus), karyotyping (form A and B), and molecular (An. vagus genotype A and B, An. vagus AN4 and AN5). Genetic analysis revealed a high conservation of the ITS2 fragment among members except for the An. vagus genotype B, which was, in fact, Anopheles sundaicus. This review also identified that An. vagus limosus and An. vagus vagus were nearly identical to the ITS2 sequence. CONCLUSION: Literature review studies revealed that An. vagus is conspecific despite the distinct morphological characteristic of An. vagus and An. limosus. Further information using another barcoding tool, such as mitochondrial COI and ND6 and experimental cross-mating between the An. vagus and An. limosus may provide additional evidence for the status of An. vagus as a species complex.

Combining Mendelian randomization with the sibling comparison design.

Mendelian randomization (MR) is a popular epidemiologic study design that uses genetic variants as instrumental variables (IVs) to estimate causal effects, while accounting for unmeasured confounding. The validity of the MR design hinges on certain IV assumptions, which may sometimes be violated due to dynastic effects, population stratification, or assortative mating. Since these mechanisms act through parental factors it was recently suggested that the bias resulting from violations of the IV assumptions can be reduced by combing the MR design with the sibling comparison design, which implicitly controls for all factors that are constant within families. In this article, we provide a formal discussion of this combined MR-sibling design. We derive conditions under which the MR-sibling design is unbiased, and we relate these to the corresponding conditions for the standard MR and sibling comparison designs. We proceed by considering scenarios where all three designs are biased to some extent, and discuss under which conditions the MR-sibling design can be expected to have less bias than the other two designs. We finally illustrate the theoretical results and conclusions with an application to real data, in a study of low-density lipoprotein and diastolic blood pressure using data from the Swedish Twin Registry.

Development of a blueprint for sibling psychosocial services: A nationwide study.

BACKGROUND: Siblings of youth with cancer have heightened risk for poor long-term psychosocial outcomes. Although sibling psychosocial care is a standard in pediatric oncology, this standard is among those least likely to be met. To address barriers to providing sibling services, a blueprint for systematic psychosocial screening and support of siblings was developed based on feedback from a national sample of psychosocial providers. PROCEDURE: Semi-structured interviews were conducted with a purposive sample of psychosocial care providers (N = 27) of various disciplines working in US pediatric cancer centers, varied in size, type, and extent of sibling support. Interviews queried providers' suggestions for the future of sibling psychosocial care and impressions of a blueprint for sibling service delivery, which was iteratively refined based on respondents' feedback. Interviews were analyzed using applied thematic analysis. RESULTS: Based on existing literature and refined according to providers' recommendations, the Sibling Services Blueprint was developed to provide a comprehensive guide for systematizing sibling psychosocial care. The blueprint content includes: (i) a timeline for repeated sibling screening and assessment; (ii) a stepped model of psychosocial support; (iii) strategies for circumventing barriers to sibling care; and (iv) recommendations for how centers with varying resources might accomplish sibling-focused care. The blueprint is available online, allowing providers to easily access and individualize the content. Providers indicated enthusiasm and high potential utility and usability of the blueprint. CONCLUSIONS: The Sibling Services Blueprint may be a useful tool for systematizing sibling psychosocial care, promoting wider availability of sibling-focused services, and addressing siblings' unmet needs.

Reviewing the Evidence on Sibling Sexual Behaviour: Impact on Research, Policy and Practice.

PURPOSE OF REVIEW: This paper reviews recent research into sibling sexual behaviour (SSB). This is an emerging professional and community issue that binds together a limited evidence base across research, practice and policy in psychology, criminology, politics, social work and policy studies. The review will demonstrate that a multi-disciplinary, life course, family system approach is the most effective way of starting to develop interventions to prevent and respond to this issue. RECENT FINDINGS: SSB has previously been researched as a form of intrafamilial abuse or sibling incest. As a result of this SSB is poorly and inconsistently defined as a concept, meaning that research, practice and policy are sometimes at odds with each other and need to pull together to develop a cohesive framing of the issue. This means that a lot of older research needs to be contextualised in new emerging frames of thinking and ways of working. Current research emphasises the importance of understanding the role of the family system in creating conditions where SSB can occur and its central role in preventing and stopping it from occurring. The research also stresses the importance of professionals understanding the family context of SSB and has the confidence to identify and work proactively with families in a multi-agency and cross-disciplinary way. The prevention of, and response to, SSB requires a multi-level, multi-disciplinary approach. Successful prevention of and response to SSB are as much about the family system as it is about the attitudes, behaviours and experiences of the siblings impacted by the abuse.

Familial confounding or measurement error? How to interpret findings from sibling and co-twin control studies.

Epidemiological researchers often examine associations between risk factors and health outcomes in non-experimental designs. Observed associations may be causal or confounded by unmeasured factors. Sibling and co-twin control studies account for familial confounding by comparing exposure levels among siblings (or twins). If the exposure-outcome association is causal, the siblings should also differ regarding the outcome. However, such studies may sometimes introduce more bias than they alleviate. Measurement error in the exposure may bias results and lead to erroneous conclusions that truly causal exposure-outcome associations are confounded by familial factors. The current study used Monte Carlo simulations to examine bias due to measurement error in sibling control models when the observed exposure-outcome association is truly causal. The results showed that decreasing exposure reliability and increasing sibling-correlations in the exposure led to deflated exposure-outcome associations and inflated associations between the family mean of the exposure and the outcome. The risk of falsely concluding that causal associations were confounded was high in many situations. For example, when exposure reliability was 0.7 and the observed sibling-correlation was r = 0.4, about 30-90% of the samples (n = 2,000) provided results supporting a false conclusion of confounding, depending on how p-values were interpreted as evidence for a family effect on the outcome. The current results have practical importance for epidemiological researchers conducting or reviewing sibling and co-twin control studies and may improve our understanding of observed associations between risk factors and health outcomes. We have developed an app (SibSim) providing simulations of many situations not presented in this paper.

Comparing between HLA-matched sibling donor allogenic HSCT and non-sibling matched related donor allogenic HSCT outcome in pediatric patients; single center retrospective study.

BACKGROUND: Extended family donor search other than siblings may yield an HLA matched donor in communities with high rate of consanguinity. The outcome of patients who are transplanted from non-sibling matched related donors (NS-MRD) including engraftment and graft versus host disease (GVHD) are scarce in comparison with matched sibling donor (MSD). METHODS: We retrospectively reviewed the outcome of all our pediatric hematopoietic stem cell transplantation (HSCT) patients who had non-sibling matched related donor and controlled them with matched sibling donor HSCT (based on age, indication of HSCT, conditioning regimen, GVHD prophylaxis, serotherapy, stem cell source and cytomegalovirus status). RESULTS: A total of 76 patients were reviewed during study period. Thirty patients (39.5%) in NS-MRD arm and 46 patients in MSD (60.5%) were identified after matching in age, disease, and conditioning regimens. All patients had similar approach including stem cell source and GVHD prophylaxis (CNI + 2nd agent). Out of the NS-MRD group, 18 patients (59%) had one of their parents as a donor and the rest as second degree relatives. Both groups were equally distributed and were homogeneous. Both groups had no statistically significant difference in outcome including engraftment, GVHD and Chimerism tests results. GVHD was seen in (13%) NS-MRD patients compared to (11%) in MSD patients. All patients remain alive with median follow up of 1249 days (431-3525). CONCLUSIONS: This study showed no significant difference in allogenic HSCT outcomes between matched sibling donors and non-sibling matched related donors and support using the same management approach in terms of conditioning therapy, GVHD prophylaxis, and serotherapy only if indicated.

The brother's penalty: Boy preference and girls' health in rural China.

This paper identifies the health penalty experienced by girls due to having a brother from endogenous sibling gender composition. We propose a girls-to-girls comparison strategy and rule out the confounding effect from the sibship size, birth interval, and birth order. Employing an instrumental variable approach and data from the Chinese Family Panel Studies, we find that girls with a brother are demonstrably shorter and report poorer health. This "brother's penalty" manifests even prenatally. Alternative explanations, such as birth order disadvantages, are carefully addressed and ruled out. The results hold even after excluding gender-neutral ethnic minorities. This observed penalty is likely attributed to unequal resource allocation within families and potential parental neglect. This penalty is amplified in families with lower income and maternal education, implying resource constraints contribute to gender discrimination. Our findings highlight the importance of addressing intrafamily gender bias for ensuring equal opportunities and health outcomes. Clinical trial registration: Not applicable.

Child health and its effect on adult social capital accumulation.

Although studies have demonstrated important effects of poor health in childhood on stocks of human and health capital, little research has tested economic theories to investigate the effect of child health on social capital in adulthood. Studies on the influence of child health on adult social capital are mixed and have not used sibling fixed effects models to account for unmeasured family and genetic characteristics, that are likely to be important. Using the Add-Health sample, health in childhood was assessed as self-rated health, the occurrence of a physical health condition or mental health condition, while social capital in adulthood was measured as volunteering, religious service attendance, team sports participation, number of friends, social isolation, and social support. We used sibling fixed effects models, which attenuated several associations to non-significance. In sibling fixed effects models there was significant positive effects of greater self-rated health on participation in team sports and social support, and negative effect of mental health in childhood on social isolation in adulthood. These results suggest that children with poor health require additional supports to build and maintain their stock of social capital and highlight further potential benefits to efforts that address poor child health.

Healthy siblings' perspectives about paediatric palliative care: A qualitative systematic review and meta-synthesis.

BACKGROUND: Siblings of children requiring palliative care are often forgotten and overlooked, as the focus tends to be on the ill child and their parents. Limited knowledge of non-bereaved siblings' perspectives makes it challenging to provide appropriate support for them. A review of existing literature is thus needed to better understand the experiences of these siblings and to identify research gaps that may require further examination. AIM: To consolidate the available qualitative evidence on the perspectives of non-bereaved healthy siblings regarding paediatric palliative care. DESIGN: A qualitative systematic review using a meta-synthesis approach was conducted. DATA SOURCES: Six electronic databases (PubMed, CINAHL, PsycINFO, Embase, Scopus and ProQuest Dissertations and Theses Global) were searched from each database's inception date until October 2022. The search included qualitative and mixed-method studies that reported the perceptions and associations of siblings of patients receiving paediatric palliative care. Data were synthesised using thematic analysis. RESULTS: Eleven studies were included. The overarching theme of the review would be 'A walking shadow: Living in the darkness shaped by the dying sibling', and three key themes and nine subthemes were identified from the included articles: (1) Changing family dynamics; (2) Impact on school and socialisation and (3) Psychological impact and coping. CONCLUSION: Siblings demonstrated negative psychological impacts and were affected by changing family structure and relationships. However, socialisation with society, and varied coping skills such as cognitive coping and using distraction techniques, were significant for siblings to go through this journey and even led to some positive outcomes for them.

Sibling Availability, Sibling Sorting, and Subjective Health Among Chinese Adults.

Despite rising numbers of only children in China, little is known about their family dynamics and well-being in adulthood-for example, how often they marry other only children and whether those in siblingless families have worse or better health than others. Theoretical expectations produce opposing predictions: siblings might provide social and emotional support and reduce parental caregiving pressures, but only children might receive more support from parents and grandparents. Using the 2010 China Family Panel Study, we examine marital sorting on Chinese adults' number of siblings and test whether sibling availability and sibling sorting are associated with subjective physical and mental health. Despite general perceptions that China has an exceedingly high prevalence of adults with no siblings that might produce very small families, results demonstrate a low prevalence of siblingless couples (i.e., both spouses are only children). Married adults with no siblings or siblings-in-law have better subjective physical health but similar levels of subjective mental health relative to their counterparts with siblings. The health advantages of siblingless marital unions are greater for rural and female adults. Declining sibling prevalence in China will shape future family demographic dynamics but appears less detrimental to population health than sometimes assumed.

Comorbidities in women with polycystic ovary syndrome: a sibling study.

BACKGROUND: Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. PCOS may be influenced by prenatal androgen excess, poor intrauterine or childhood environmental factors, childhood obesity and learned health risk behaviors. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. METHODS: This total-population register-based cohort study included 333,999 full sisters, born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjects´ early-life and social characteristics. In the main analysis, sister fixed effects (FE) models were used to control for all time-invariant factors that are shared among sisters, thereby testing whether the association between PCOS and examined comorbidities is influenced by unobserved familial environmental, social or genetic factors. RESULTS: Three thousand five hundred seventy women in the Sister sample were diagnosed with PCOS, of whom 14% had obesity, 8% had depression, 7% had anxiety and 4% experienced sleeping, sexual and eating disorders (SSE). Having PCOS increased the odds of obesity nearly 6-fold (adjusted OR (aOR): 5.9 [95% CI:5.4-6.5]). This association was attenuated in models accounting for unobserved characteristics shared between full sisters, but remained considerable in size (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). For depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when controlling for factors shared between sisters. Being diagnosed with SSE disorders yielded a 2.4 aOR (95% CI:2.0-2.6) when controlling for a comprehensive set of individual-level confounders, which only decreased slightly when controlling for factors at the family level such as shared genes or parenting style. Accounting for differences between sisters in observed early-life circumstances influenced the estimated associations marginally. CONCLUSION: Having been diagnosed with PCOS is associated with a markedly increased risk of obesity and sleeping, sexual and eating disorders, also after accounting for factors shared between sisters and early-life conditions.

The feeding siblings questionnaire (FSQ): Development of a self-report tool for parents with children aged 2-5 years.

Over the last decade, there have been repeated calls to expand the operationalisation of food parenting practices. The conceptualisation and measurement of these practices has been based primarily on research with parent-child dyads. One unexplored dimension of food parenting pertains to the evaluation of practices specific to feeding siblings. This study describes the development and validation of the Feeding Siblings Questionnaire (FSQ) - a tool designed to measure practices in which siblings are positioned as mediators in parents' attempts to prompt or persuade a child to eat. Item development was guided by a conceptual model derived from mixed-methods research and refined through expert reviews and cognitive interviews. These interviews were conducted in two phases, where parents responded to the questionnaire primarily to test i) the readability and relevance of each item, and ii) its overall feasibility. The instrument was completed by 330 parents (96.1% mothers) in Australia with two children aged 2-5 years, and repeated by 133 parents (40.3%) two weeks later. Exploratory factor analysis was performed on baseline data. Internal consistency and test re-test reliability of the subsequent subscales were examined. Construct validity was assessed through comparisons with existing measures of food parenting practices and child eating behaviours. The final FSQ scale included 22 items, reflecting five food parenting practices: sibling competitiveness, active sibling influence, threatening unequal division of food, sibling role modelling, and vicarious operant conditioning. Internal consistency and test re-test reliability estimates were high, and there was some evidence of convergent construct validity. While its factor structure should be confirmed in a different sample, the FSQ offers a novel tool for assessing, monitoring, and evaluating feeding interactions beyond those confined to the parent-child dyad.