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The coronavirus disease 2019 (COVID-19) pandemic is a historic event impacting children around the globe. Prior research on the educational experiences of children during the COVID-19 pandemic focused almost exclusively on spring 2020. This article extends this literature past the initial shock of spring 2020, capturing the first full school year (2020-2021) during the COVID-19 pandemic. This registered report study utilized a national sample of 1,666 United States twins in kindergarten through 12th grade from 43 states to provide the current descriptive report of children's educational experiences during this time, as reported by their parents. Specifically, we reported on school format, parents' role in education, parent-teacher interactions, schoolwork struggles, technology access, and school services. About half of children attended in-person schooling, with many children switching from online to in-person throughout the school year. Parents saw the pandemic as a risk to their children's education. During the 2020-2021 school year of the pandemic, parents felt they had a larger role in their children's education and were less satisfied in their interactions with teachers than what they experienced during the prepandemic part of the 2019-2020 school year. Children experienced more schoolwork struggles than they had in previous years, and this was similar across age groups. For most constructs, results were equivalent across age group, but parents of younger children tended to provide more schoolwork help. Overall, this article highlights the disruptions in their educational environments that children continued to experience through the first full school year (2020-2021) of the COVID-19 pandemic.

Parenting behaviors have long been recognized as crucial to children's healthy development. However, examinations of the etiology of these behaviors are less prevalent. The current study investigated the driving forces behind parental warmth and discipline, particularly whether they are related more to traits within the parent or reactions to characteristics of the child. To explore this question, three robust factors of child temperament--effortful control, negative affectivity, and surgency/extraversion--and five parent personality traits were examined in association with parent behaviors through differential parenting within 185 four-year-old twin pairs (370 children; 56% girls; 90% White; predominantly middle class). Genetic analyses showed that parents tend to treat both children similarly in terms of parental warmth, but they treat children less similarly in terms of discipline, regardless of child zygosity. Multilevel linear regressions showed that within twin pairs, the child with higher effortful control received less discipline from parents than their cotwin. Analyses also showed that parent agreeableness was significantly related to parent warmth above and beyond other personality traits and child temperament. This study clarified the direction of effects and genetic contributions to parenting behaviors, supporting previous literature that discipline acts in reaction to the child, whereas warmth is more driven by parent personality. This research suggests the importance of focusing on child temperament and parent personality as they relate to parenting behaviors, allowing clinicians and parents to more effectively correct maladaptive parenting behaviors and encourage healthy and adaptive parenting behaviors, thus promoting positive outcomes for children.

The aim of the study was to examine associations between life events and self-assessed loneliness in adolescence. We used data from a Norwegian population-based twin sample including seven birth cohorts (N = 2,879, 56% females). The participants completed self-report questionnaires three times throughout adolescence, with 2 years in between (i.e., 12-18 years old at Wave 1). By using a random intercept cross-lagged panel model (RI-CLPM), we were able to separate stable influences in the measured constructs from the within-person changes at each measurement occasion. In addition, using data from twins allowed us to examine to what degree the associations between life events and loneliness were genetic and/or environmental in nature. The results showed moderate stability of both loneliness and aggregation scores of life events throughout adolescence. The life events were assigned to clusters based on their independence (i.e., events considered dependent or independent on a person's behavior) and desirability (i.e., positive or negative). The time-stable between-person variance in all three measures, loneliness and person-dependent positive and negative life events, could almost exclusively be accounted for by genetic factors. However, as expected, also shared environmental factors influenced person-independent life events. The associations between time-stable between-person variance in loneliness and life events were small, and nearly exclusively due to shared genetic influences. Furthermore, life events do not seem to predict changes in loneliness or vice versa. In conclusion, the self-reported levels of loneliness throughout adolescence seems to be independent of life events.

Prior theoretical and empirical research has highlighted links between positive parenting and the socioeconomic characteristics of the family's neighborhood, but has yet to illuminate the etiologic origins of this association. One possibility is that the various predictors of parenting outlined by Belsky (1984; e.g., characteristics of the child, characteristics of the parent, and contextual influences) may matter more in some neighborhood contexts than in others. To examine this possibility, we conducted etiologic moderation analyses in a sample of 1,030 families of twins (average age 8 years; 51% male, 49% female; racial composition: 82% White, 10% Black, 1% Asian, 1% Indigenous, and 6% multiracial) from the Twin Study of Behavioral and Emotional Development in Children in the Michigan State University Twin Registry. Neighborhood and parenting were assessed using multiple informants and assessment strategies (neighborhood and family informants, administrative data, and videotaped parent-child interactions). Results pointed to strong evidence of etiologic moderation, such that child effects on positive mothering were prominent in neighborhoods with little opportunity and near zero in neighborhoods with ample opportunity. Such findings not only reframe the magnitude of child effects on the parenting they receive as context-dependent, but also indicate that mothers in impoverished neighborhoods may be more responsive to their children's characteristics than mothers in neighborhoods with ample opportunity.

Purpose: The aim of this study is to establish which specific cognitive abilities are phenotypically related to reading skill in adolescence and determine whether this phenotypic correlation is explained by polygenetic overlap. Method: In an Australian population sample of twins and non-twin siblings of European ancestry (734 [less than or equal to] N [less than or equal to] 1542 [50.7% < F < 66%], mean age = 16.7, range = 11-28 years) from the Brisbane Adolescent Twin Study, mixed-effects models were used to test the association between a dyslexia polygenic score (based on genome-wide association results from a study of 51,800 dyslexics versus >1 million controls) and quantitative cognitive measures. The variance in the cognitive measure explained by the polygenic score was compared to that explained by a reading difficulties phenotype (scores that were lower than 1.5 SD below the mean reading skill) to derive the proportion of the association due to genetic influences. Results: The strongest phenotypic correlations were between poor reading and verbal tests R[superscript 2] up to 6.2%); visuo-spatial working memory was the only measure that did not show association with poor reading. Dyslexia polygenic scores could completely explain the phenotypic covariance between poor reading and most working memory tasks and were most predictive of performance on a test of arithmetic (R[superscript 2] = 2.9%). Conclusion: Shared genetic pathways are thus highlighted for the commonly found association between reading and mathematics abilities, and for the verbal short-term/working memory deficits often observed in dyslexia.

This study describes the case of a student with congenital intestinal perforations and her experience with inclusive education in the Czech Republic. She is also a sister of an identical twin with cerebral palsy. The data were gained from semi-structured interviews and bio-graphical narratives of the student during her studies at the grammar school and from her parents. Van Manen's analyses of lived experiences was used to identify important themes for each participant. The overarching themes present in their narratives concerned Lucy's future and the choice of the most appropriate educational environment. The parents' narratives focused more on barriers to inclusive education, benefits of inclusive environments, medical and educational care and family support based on close cooperation with school. For Lucy, the dominant theme was being a sister with a less severe disability and caretaking of her sister. In addition to enhancing the understanding of different needs of a student with congenital malformations and her parents' experiences with inclusive education, it helped us to explore how the specific sibling's constellation within her family and school contexts impacts her personal perspective on life, driven strongly by a wish for independence.

We compared dyad-focused maternal speech (protoconversations and maternal speech describing the dyad) in interactions of mothers with their twin and singleton infants. Nine twins and nine singletons, coming from urban areas of Crete (Greece), were video-recorded at home in spontaneous face-to-face interactions with their mothers, from the 2nd to the 6th month at 30-day intervals. Continuous micro-analysis revealed that the following: (a) variations in proto-conversations favoured singleton compared to twin infants; (b) twin and singleton mothers addressed different, but possibly of equivalent communicative significance, verbal comments to their infants within protoconversations; (c) both twin and singleton mothers showed age-variant efforts for conversation with their young infants. Though we showed quantitative variations of maternal dyad-focused speech between mother-singleton infant and mother-twin infant dyads, both singleton and twin mothers used devices of equivalent communicative significance and age-variant attempts to respond sensitively to their infants' expressive behaviours according to the latter's age-related motives for communication.

Neighborhood is a key context where children learn to process social information; however, the field has largely overlooked the ways children's individual characteristics might be moderated by neighborhood effects. We examined 1,030 six- to 11-year-olds (48.7% female; 82% White) twin pairs oversampled for neighborhood disadvantage from the Twin Study of Behavioral and Emotional Development in Children. We evaluated neighbor reports (N = 1,880) of neighborhood structural and social characteristics as moderators of genetic and environmental influences on children's social processing. Although there was no evidence of moderation for children's hostile attributions, there was robust evidence that the social and structural characteristics of the neighborhood moderated the genetic and environmental origins of children's positive expectations of aggressive behavior. Specifically, we found that genetic influences on aggressive expectations increased in the presence of neighborhood deprivation and decreased in the presence of protective social processes and availability of resources. Such findings suggest that protective neighborhood social processes may buffer against the development of aggressive expectations during middle childhood by suppressing the expression of genetic influences on those outcomes. In doing so, they suggest that neighborhood social processes may be able to promote youth resilience to neighborhood deprivation "under the skin."

Emerging literature links neighborhood disadvantage to altered neural function in regions supporting socioemotional and threat processing. Few studies, however, have examined the proximal mechanisms through which neighborhood disadvantage is associated with neural functioning. In a sample of 7- to 19-year-old twins recruited from disadvantaged neighborhoods (354 families, 708 twins; 54.5% boys; 78.5% White, 13.0% Black, 8.5% other racial/ethnic group membership), we found that exposure to community violence was related to increased amygdala reactivity during socioemotional processing and may be one mechanism linking neighborhood disadvantage to amygdala functioning. Importantly, parenting behavior appeared to modulate these effects, such that high parental nurturance buffered the effect of exposure to community violence on amygdala reactivity. These findings elucidate the potential impact of exposure to community violence on brain function and highlight the role parents can play in protecting youth from the neural effects of exposure to adversity.

Mollusk shells protect the animals that form and inhabit them. They are composites of minerals and organics, with diverse mesostructures, including nacre, prismatic calcite, crossed-lamellar aragonite, and foliated calcite. Twins, that is, crystals mirror symmetric with respect to their coherent interface, occurring as formation or deformation twins, are observed in all mollusk shell mesostructures but never within calcite prisms. Here, nanotwins and microwins within single calcite prisms are observed in different shells. Using Polarization-dependent Imaging Contrast (PIC) mapping with 20–60 nm resolution, twins are observed to be 0.2–3 µm thick layers of differently oriented and colored crystals with respect to the main prism crystal. Multiple twins are interspersed with the prism crystal, parallel to one another, and similarly oriented. When comparing images of calcite prisms and twins obtained by PIC mapping and by Electron Back-Scattered Diffraction (EBSD), the images correspond precisely. All twins are e-twin types, with 127° angular distance between c-axes. E-twins are the most common deformation twins in geologic calcite, as also observed here in Carrara marble. Location of all twins near the outer surface of all shells and e-twin type both suggest that twins within calcite prisms in mollusk shells result from deformation twinning.

Background Methods Results Conclusions Food fussiness (FF) describes the tendency to eat a small range of foods, due to pickiness and/or reluctance to try new foods. A common behaviour during childhood, and a considerable cause of caregiver concern; its causes are poorly understood. This is the first twin study of genetic and environmental contributions to the developmental trajectory of FF from toddlerhood to early adolescence, and stability and change over time.Participants were from Gemini, a population‐based British cohort of n = 4,804 twins born in 2007. Parents reported on FF using the Child Eating Behaviour Questionnaire ‘FF’ scale when children were 16 months (n = 3,854), 3 (n = 2,666), 5 (n = 2,098), 7 (n = 703), and 13 years old (n = 970). A mixed linear model examined the trajectory of FF, and a correlated factors twin model quantified genetic and environmental contributions to variation in and covariation between trajectory parameters. A longitudinal Cholesky twin model examined genetic and environmental influences on FF at each discrete age.We modelled a single FF trajectory for all children, which was characterised by increases from 16 months to 7 years, followed by a slight decline from 7 to 13 years. All trajectory parameters were under strong genetic influence (>70%) that was largely shared, indicated by high genetic correlations. Discrete age analyses showed that genetic influence on FF increased significantly after toddlerhood (16 months: 60%, 95% CI: 53%–67%; 3 years: 83%; 81%–86%), with continuing genetic influence as indicated by significant genetic overlap across every age. Shared environmental influences were only significant during toddlerhood. Unique environmental influences explained 15%–26% of the variance over time, with some enduring influence from 5 years onwards.Individual differences in FF were largely explained by genetic factors at all ages. Fussy eating also shows a significant proportion of environmental influence, especially in toddlerhood, and may, therefore, benefit from early interventions throughout childhood. Future work needs to refine the FF trajectory and explore specific trajectory classes. [ABSTRACT FROM AUTHOR]

Objective Background Method Results Conclusion Implication The current study examined the roles of parental differentiation, self‐differentiation, and attachment style and history in parenting twins.Raising twins is a complex parental experience. One of the major roles of parenting twins is to ensure their parallel development, as well as their psychological differentiation and self‐individuation.The study included 91 Israeli adult participants (41 same‐sex fraternal twins; 50 same‐sex nontwin siblings), sampled through social media, who answered a series of questionnaires.Results indicated that twins reported less self‐differentiation, a poorer attachment history with their parents, and less secure attachment than nontwin siblings. Moderation analysis established that the positive link between parental differentiation and self‐differentiation was significantly stronger for twins than nontwin siblings. In contrast, sibling status had no moderating effect on the link between attachment history and style.These findings emphasize the significance of parental differentiation in twins' personal development and the importance of recognizing the unique bond between them.Implications for practitioners focusing on nurturing healthy development, strong sibling relationships, and individual well‐being are discussed. [ABSTRACT FROM AUTHOR]

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic). We additionally tested whether similarity in one domain translated into greater similarity in another. Results suggest that a lower degree of similarity in co-twins' exposome profiles was associated with greater differences in their behavior and substance use. The strongest association was identified between excessive drinking behavior and the external exposome. Overall, our study demonstrates how social behavior and especially substance use are connected to the internal and external exposomes, while controlling for familial confounders. [ABSTRACT FROM AUTHOR]

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent infections with Candida spp., often linked to primary immunodeficiencies. We report a case of two 8‐year‐old monozygotic twin brothers presenting with extensive dermatophytosis, later diagnosed with autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) syndrome due to a homozygous p.M1V mutation in the AIRE gene. The twins exhibited widespread skin and nail infection, along with malabsorption, dental caries, and other autoimmune manifestations. This case highlights the novel presentation of extensive dermatophytosis in APECED, underscoring the variability in clinical expression even within a single family. [ABSTRACT FROM AUTHOR]

Purpose: Multifetal gestation (MFG) is much more common in pregnancies that utilize assisted reproductive technologies (ART). We assessed how these rates have changed over the previous decade and the impact on live birth rates (LBR). Methods: This retrospective cohort study uses the National Summary Reports of the Society for Assisted Reproductive Technology (SART) from 2014 to 2020. Data points included only autologous cycles. The data were divided into five age groups as reported in the database: < 35, 35–37, 38–40, 41–42, and > 42 years old. Descriptive statistics and a two-tailed T-test were used to determine the trends and statistical significance (p < 0.05). Results: Rates of twin births decreased substantially from 2014 to 2020 for autologous embryo transfers across all age groups and diagnoses. Surprisingly, the overall LBR for autologous IVF cycles decreased at similar rates from 2014 to 2020 in all age groups. The mean number of embryos transferred has dramatically reduced, especially across age groups < 42. Conclusion: Rates of twin and higher-level gestations have decreased substantially over the past decade; the effect correlates with the increased utilization of eSET and PGT. The cause of infertility did not significantly impact the rate of MFG. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Do the mothers of twins and singletons differ regarding post-partum and old-age mortality? SUMMARY ANSWER Twin deliveries were associated with higher post-partum maternal mortality than singleton deliveries, but the lifetime post-partum mortality risk was similar for mothers of twins and singletons; survival of twinners was higher than survival of the mothers of singletons after the 67th lifespan percentile. WHAT IS KNOWN ALREADY Twinning is typically associated with higher post-partum maternal mortality. The evidence about whether twinning incurs long-term survival costs of reproduction or is a trait pertinent to long-lived women is scarce and contradictory. STUDY DESIGN, SIZE, DURATION The study is based on the data of the Estonian Family Register (operating from 1926 to 1943) and involves 5565 mothers of twins and 119 613 mothers of singletons born between 1850 and 1899. The subset for comparing maternal lifespans included 1703–1884 mothers of twins and 19 747–36 690 mothers of singletons. PARTICIPANTS/MATERIALS, SETTING, METHODS Post-partum maternal mortality was analyzed in the whole sample (including mothers of a single child) by logistic regression. Most of the analyses were performed in samples where each mother of twins was matched against mothers of singletons based on parity (or number of deliveries), urban versus rural and inland versus coastal origin, whether their lifespan was known, date of birth and age at first birth. Lifespans were compared in linear mixed models. Quantile regression was used to analyze age-dependent variations in maternal mortality rates. All models were adjusted for relevant biodemographic covariates. MAIN RESULTS AND THE ROLE OF CHANCE The twinning rate in the whole sample was 4.4%. During the year after giving birth, maternal mortality for twin deliveries was 0.75% (17/2273) and 0.37% (449/122 750) for singleton deliveries (OR = 2.05, 95% CI = 1.21–3.23). However, the lifetime post-partum mortality risk for mothers of twins (0.51%; 28/5557) and singletons (0.37%; 438/119 466) did not differ significantly (OR = 1.38, 95% CI = 0.91–1.98). The life spans of the mothers of twins and singletons did not differ in matched samples. Past the 67th lifespan percentile, the odds of survival were significantly higher for mothers of twins than mothers of singletons, as indicated by non-overlapping 95% confidence intervals. LIMITATIONS, REASONS FOR CAUTION Relatively low number of individuals (22 802–28 335) with known age at death in matched datasets due to discontinuation of the register after 1943. WIDER IMPLICATIONS OF THE FINDINGS The finding that mothers of twins had higher odds of old-age survival than mothers of singletons is consistent with the contention that twinners represent a non-random subset of women whose robust phenotypic quality allows them to outlive the mothers of singletons in old age. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Estonian Research Council grants PRG1137, PRG2248, and PSG669. The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a childhood-onset complex neurodevelopmental disorder characterized by problems with communication and social interaction and restricted, repetitive, stereotyped behavior. The prevalence of ASD is one in 36 children. The genetic architecture of ASD is complex in spite of its high heritability. To identify the potential candidate genes of ASD, we carried out a comprehensive genetic study of monozygotic (MZ) twins concordant or discordant for ASD. Five MZ twins and their parents were recruited for the study. Four of the twins were concordant, whereas one was discordant for ASD. Whole exome sequencing was conducted for the twins and their parents. The exome DNA was enriched using Twist Human Customized Core Exome Kit, and paired-end sequencing was performed on HiSeq system. We identified several rare and pathogenic variants (homozygous recessive, compound heterozygous, de novo) in ASD-affected individuals. We report novel variants in individuals diagnosed with ASD. Several of these genes are involved in brain-related functions and not previously reported in ASD. Intriguingly, some of the variants were observed in the genes involved in sensory perception (auditory [ MYO15A , PLEC , CDH23 , UBR3 , GPSM2 ], olfactory [ OR9K2 ], gustatory [ TAS2R31 ], and visual [ CDH23 , UBR3 ]). This is the first comprehensive genetic study of MZ twins in an Indian population. Further validation is required to determine whether these variants are associated with ASD. [ABSTRACT FROM AUTHOR]

Objective: This scoping review aimed to summarize current knowledge from twin studies on migraine. Migraine heritability, genetic correlations with migraine comorbid disorders, and the use of discordant twin pairs in migraine research are described. Further, the review considers the unused potential of twin studies in migraine research and reflects on future directions. Background: Twin studies can be used to understand how heritable and environmental factors influence human traits and disorders. The classical twin design compares the resemblance of a trait in monozygotic twins to that in dizygotic twins. The classical twin design can be extended to estimate the genetic correlation between disorders, model causality, and describe differences within discordant twin pairs. Methods: Studies focusing on migraine and using a twin study design were included. The search was performed on the PubMed‐MEDLINE database using the search terms "migraine" AND "twin" OR "twins." It was done in May 2023, rerun in November 2023, and managed with the Covidence software. Results: The search identified 52 twin studies on migraine. In 24 papers, the heritability of migraine was estimated with a classical twin design. Heritability estimates ranged from 0.36 to 0.48 for studies with adults, both men and women, and unspecified migraine. Migraine heritability was predominantly estimated with twin cohorts of North European ancestry, and only two studies examined migraine subtypes. A multilevel classical twin design was used in 11 studies to examine the co‐occurrence between migraine and comorbid disorders. The differences within migraine discordant twin pairs were examined in nine studies. Conclusion: The heritability of migraine was estimated with a classical twin design in twin cohorts from seven different countries, with remarkably similar results across studies. Future studies should include migraine subtypes and twin cohorts of non‐North European ancestry to better reflect the global population. Beyond heritability estimations, the twin method is a valuable tool for understanding causality and describing differences within discordant twin pairs. Despite more than 80 years of twin studies in migraine research, the twin design has a large unused potential to advance our understanding of migraine. Plain Language Summary: This review summarizes what has been learned about the inheritance of migraine from studies with twins. Studies with adults, both men and women, estimated the inheritance of migraine at about 36%–48%. However, most of these studies included twins with North European ancestry, and future studies should include twins from different parts of the world to understand how migraine affects people globally. [ABSTRACT FROM AUTHOR]

Premature infants may be at risk for lower effortful control, and subsequent lower academic achievement, peer competence, and emotional and physical wellness throughout the lifespan. However, because prematurity is related to obstetrical and neonatal complications, it is unclear what may drive the effect. Effortful control also has a strong heritable component; therefore, environmental factors during pregnancy and the neonatal period may interact with genetic factors to predict effortful control development. In this study, we aimed to dissect the influences of genetics, prematurity, and neonatal and obstetrical complications on the development of effortful control from 12 months to 10 years using a twin cohort. This study used data from the Arizona Twin Project, an ongoing longitudinal study of approximately 350 pairs of twins. Twins were primarily Hispanic/Latinx (23.8%–27.1%) and non-Hispanic/Latinx White (53.2%–57.8%), and families ranged in socioeconomic status with around one third falling below or near the poverty line. Of the twins, 62.6% were born prematurely. Effortful control was assessed via parent report at six waves. There was not a significant relationship between gestational age and effortful control regardless of whether obstetrical and neonatal complications were controlled for. Biometric twin modeling revealed that the attentional focusing subdomain of effortful control was highly heritable. Gestational age did not moderate genetic and environmental estimates. Our findings help inform the risk assessment of prematurity and provide evidence for the differing etiology of each subdomain of effortful control and the strong role of genetics in effortful control development. Public Significance Statement: This study advances the current understanding of the development of effortful control. There was no compelling evidence that premature birth was a risk factor for lower effortful control. Further, although effortful control is heritable, particularly the attentional focusing subdomain of effortful control, the genetic and environmental estimates for effortful control were not influenced by obstetrical and neonatal complications. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). Materials and Methods: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. Results: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%. In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. Conclusions: This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role. [ABSTRACT FROM AUTHOR]

Gene therapy using recombinant adeno‐associated virus (rAAV) as delivery vehicles has garnered much interest in recent years. There are still significant gaps in our fundamental understanding of the manufacturing processes to deliver sufficient products. Manufacturing efforts of rAAV using HEK293 cells have commonly relied on fixed bed falling film bioreactors like the iCELLis®. We used computational fluid dynamics (CFD) to validate the operating conditions required for a predictive iCELLis® 500 scale‐down model. The small‐scale and at‐scale systems have different flow paths causing validation of the corresponding agitation rates required to achieve the same linear flow through the fixed bed across scales to be non‐trivial. Therefore, we used CFD to predict the theoretical scaling relationship. In addition, CFD could predict kLa differences between the two systems and the operating conditions required to match kLa between scales. We also confirmed that the location of DO control must be the same in both systems to achieve proper scaling. Experimental runs confirming the validity of the novel scale‐down model showed that based on the modifications to the iCELLis® Nano system, we achieved similar DO, key metabolite, pH, and GC titer trends in both systems. [ABSTRACT FROM AUTHOR]

Mollusk shells protect the animals that form and inhabit them. They are composites of minerals and organics, with diverse mesostructures, including nacre, prismatic calcite, crossed‐lamellar aragonite, and foliated calcite. Twins, that is, crystals mirror symmetric with respect to their coherent interface, occurring as formation or deformation twins, are observed in all mollusk shell mesostructures but never within calcite prisms. Here, nanotwins and microwins within single calcite prisms are observed in different shells. Using Polarization‐dependent Imaging Contrast (PIC) mapping with 20–60 nm resolution, twins are observed to be 0.2–3 µm thick layers of differently oriented and colored crystals with respect to the main prism crystal. Multiple twins are interspersed with the prism crystal, parallel to one another, and similarly oriented. When comparing images of calcite prisms and twins obtained by PIC mapping and by Electron Back‐Scattered Diffraction (EBSD), the images correspond precisely. All twins are e‐twin types, with 127° angular distance between c‐axes. E‐twins are the most common deformation twins in geologic calcite, as also observed here in Carrara marble. Location of all twins near the outer surface of all shells and e‐twin type both suggest that twins within calcite prisms in mollusk shells result from deformation twinning. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVDs) are major causes of mortality and morbidity worldwide; yet the understanding of their molecular basis is incomplete. Multi-omics studies have significant potential to uncover these mechanisms, but such studies are challenged by genetic and environmental confounding—a problem that can be effectively reduced by investigating intrapair differences in twins. Here, we linked data on all diagnoses of the circulatory system from the nationwide Danish Patient Registry (spanning 1977–2022) to a study population of 835 twins holding genome-wide DNA methylation and gene expression data. CVD diagnoses were divided into prevalent or incident cases (i.e., occurring before or after blood sample collection (2007–2011)). The diagnoses were classified into four groups: cerebrovascular diseases, coronary artery disease (CAD), arterial and other cardiovascular diseases (AOCDs), and diseases of the veins and lymphatic system. Statistical analyses were performed by linear (prevalent cases) or cox (incident cases) regression analyses at both the individual-level and twin pair-level. Significant genes (p < 0.05) in both types of biological data and at both levels were inspected by bioinformatic analyses, including gene set enrichment analysis and interaction network analysis. Results: In general, more genes were found for prevalent than for incident cases, and bioinformatic analyses primarily found pathways of the immune system, signal transduction and diseases for prevalent cases, and pathways of cell–cell communication, metabolisms of proteins and RNA, gene expression, and chromatin organization groups for incident cases. This potentially reflects biology related to response to CVD (prevalent cases) and mechanisms related to regulation and development of disease (incident cases). Of specific genes, Myosin 1E was found to be central for CAD, and DEAD-Box Helicase 5 for AOCD. These genes were observed in both the prevalent and the incident analyses, potentially reflecting that their DNA methylation and gene transcription levels change both because of disease (prevalent cases) and prior disease (incident cases). Conclusion: We present novel biomarkers for CVD by performing multi-omics analysis in twins, hereby lowering the confounding due to shared genetics and early life environment—a study design that is surprisingly rare in the field of CVD, and where additional studies are highly needed. [ABSTRACT FROM AUTHOR]

Background: Separating with close siblings and leaving the parental home at an early age represents a major life event for an adolescent (reflected by age at separation in a twin pair) and may predispose them to poor mental health. This study aims to examine the association of age at separation and residential mobility on depressive symptoms in late adolescence and young adulthood and to explore possible underlying genetic effects. Methods: Residential mobility consisted of the number and total distance of moves before age 17. Based on 3071 twins from the FinnTwin12 cohort, we used linear regression to assess the association of age at separation and residential mobility with General Behavior Inventory (GBI) scores at age 17 and in young adulthood. A higher GBI score indicated more depressive symptoms occurred. Then, the mixed model for repeated measures (MMRM) was used to visualize the scores' trajectory and test the associations, controlling for "baseline" state. Twin analyses with a bivariate cross-lagged path model were performed between the difference in GBI scores, between cotwins, and separation status for the potential genetic influence. Results: Compared to twins separated before age 17, twins who separated later had significantly lower GBI scores at age 17 and in young adulthood. In MMRM, separation at a later age and a higher number of moves were associated with a higher GBI score in young adulthood. A small genetic effect was detected wherein GBI within-pair differences at age 17 were associated with separation status before age 22 (coefficient: 0.01). Conclusion: The study provides valid evidence about the influence of siblings and family on depressive symptoms in later adolescence and young adulthood while finding some evidence for a reverse direction effect. This suggests more caution in the interpretation of results. A strong association between residential mobility and depressive symptoms was affirmed, although further detailed research is needed. [ABSTRACT FROM AUTHOR]

It has been shown that vertical transmission of the SARS-CoV-2 strain is relatively rare, and there is still limited information on the specific impact of maternal SARS-CoV-2 infection on vertical transmission. The current study focuses on a transcriptomics analysis aimed at examining differences in gene expression between placentas from mother–newborn pairs affected by COVID-19 and those from unaffected controls. Additionally, it investigates the in situ expression of molecules involved in placental inflammation. The Papa Giovanni XXIII Hospital in Bergamo, Italy, has recorded three instances of intrauterine transmission of SARS-CoV-2. The first two cases occurred early in the pandemic and involved pregnant women in their third trimester who were diagnosed with SARS-CoV-2. The third case involved an asymptomatic woman in her second trimester with a twin pregnancy, who unfortunately delivered two stillborn fetuses due to the premature rupture of membranes. Transcriptomic analysis revealed significant differences in gene expression between the placentae of COVID-19-affected mother/newborn pairs and two matched controls. The infected and control placentae were matched for gestational age. According to the Benjamani–Hochberg method, 305 genes met the criterion of an adjusted p-value of less than 0.05, and 219 genes met the criterion of less than 0.01. Up-regulated genes involved in cell signaling (e.g., CCL20, C3, MARCO) and immune response (e.g., LILRA3, CXCL10, CD48, CD86, IL1RN, IL-18R1) suggest their potential role in the inflammatory response to SARS-CoV-2. RNAscope® technology, coupled with image analysis, was utilized to quantify the surface area covered by SARS-CoV-2, ACE2, IL-1β, IL-6, IL-8, IL-10, and TNF-α on both the maternal and fetal sides of the placenta. A non-statistically significant gradient for SARS-CoV-2 was observed, with a higher surface coverage on the fetal side (2.42 ± 3.71%) compared to the maternal side (0.74 ± 1.19%) of the placenta. Although not statistically significant, the surface area covered by ACE2 mRNA was higher on the maternal side (0.02 ± 0.04%) compared to the fetal side (0.01 ± 0.01%) of the placenta. IL-6 and IL-8 were more prevalent on the fetal side (0.03 ± 0.04% and 0.06 ± 0.08%, respectively) compared to the maternal side (0.02 ± 0.01% and 0.02 ± 0.02%, respectively). The mean surface areas of IL-1β and IL-10 were found to be equal on both the fetal (0.04 ± 0.04% and 0.01 ± 0.01%, respectively) and maternal sides of the placenta (0.04 ± 0.05% and 0.01 ± 0.01%, respectively). The mean surface area of TNF-α was found to be equal on both the fetal and maternal sides of the placenta (0.02 ± 0.02% and 0.02 ± 0.02%, respectively). On the maternal side, ACE-2 and all examined interleukins, but not TNF-α, exhibited an inverse mRNA amount compared to SARS-CoV-2. On the fetal side, ACE-2, IL-6 and IL-8 were inversely correlated with SARS-CoV-2 (r = −0.3, r = −0.1 and r = −0.4, respectively), while IL-1β and IL-10 showed positive correlations (r = 0.9, p = 0.005 and r = 0.5, respectively). TNF-α exhibited a positive correlation with SARS-CoV-2 on both maternal (r = 0.4) and fetal sides (r = 0.9) of the placenta. Further research is needed to evaluate the correlation between cell signaling and immune response genes in the placenta and the vertical transmission of SARS-CoV-2. Nonetheless, the current study extends our comprehension of the molecular and immunological factors involved in SARS-CoV-2 placental infection underlying maternal–fetal transmission. [ABSTRACT FROM AUTHOR]

Optimal seatbelt practices for pregnant women with twins at different gestational ages remain uncertain. To offer recommendations for a comfortable seatbelt system, this cross-sectional observational study explored seatbelt usage and driving habits among women with twins across various pregnancy stages through an online survey that explored driving conditions and comfortable seatbelts at different stages of pregnancy. Women who drove daily before their pregnancy with twins decreased their driving frequency as the pregnancy progressed. Correct seatbelt usage was lower and no seatbelt usage was higher among pregnant women with twins than those with singleton pregnancies. They adapted their seatbelt-wearing techniques to minimise pressure on the chest in the first and third trimesters and the abdomen from the second trimester onwards. The comfortable seatbelts were those that could alleviate belt pressure, featuring waist belts to reduce pressure, wider belts to avoid localised pressure, and shoulder belts resembling a backpack type. When wearing a seatbelt, avoiding pressure on the thorax and abdomen is key for pregnant women with twins. This study suggests that the suitability of driving for pregnant women with twins in their last trimester and the reliability of seatbelts designed for such women should be further examined and validated. [ABSTRACT FROM AUTHOR]

To assess the hemodynamics of twin-to-twin transfusion syndrome (TTTS), we measured the intraventricular pressure difference (IVPD), a sensitive marker of myocardial diastolic function, using fetal echocardiography.We included 28 monochorionic diamniotic (MD) twins diagnosed with TTTS who underwent fetoscopic laser photocoagulation (FLP) between 2018 and 2022. Color M-mode Doppler images of both cardiac ventricles were obtained before and after FLP. According to this evaluation, the IVPDs were divided into three groups; those with total, basal, and mid-apical IVPD.Of the 28 twins, 21 were available for analysis (including eight, eight, three, and two cases in stages Quintero Ⅰ, Ⅱ, Ⅲd, and Ⅲr, respectively). Comparing the pre and postFLP results, significant increases in total and mid-apical IVPD in the left ventricle (LV) of recipient twins were noted (total and mid-apical IVPD: p=0.026 and 0.013, respectively). In the LV of the donor twins, all IVPDs were significantly increased after FLP (total, basal, and mid-apical IVPD: p=0.003, 0.001, and 0.022, respectively). In addition, comparisons between the donor and recipient groups did not show significant differences in either ventricle before FLP.IVPD detected subtle hemodynamics changes, such as volume overload and diastolic dysfunction in TTTS before and after FLP. Therefore, IVPD may be a useful marker for monitoring myocardial diastolic function in TTTS. [ABSTRACT FROM AUTHOR]

Purpose: To document risk factors for combined delivery, defined as unplanned cesarean section for the second twin after vaginal delivery of the first twin, particularly focusing on delivery interval between twins. Methods: A multi-center cross-sectional study among a cohort of 5411 women with twin pregnancy experiencing vaginal delivery of the first twin in 2007–2016 at 191 tertiary referral hospitals in Japan was conducted. Primary outcome was the occurrence of combined delivery, and data were collected through the Japan Society of Obstetrics and Gynecology perinatal database. Risk factors for combined delivery were investigated using Poisson regression analysis. Results: Combined delivery occurred in 235 women (5.1%) and was significantly associated with delivery interval (P < 0.001). Multivariate analysis showed women with ≥ 25 kg/m2 pre-pregnancy body mass index (BMI) and with birthweight < 1500 g of the second twin had significantly higher risk for combined delivery than women with 18.5–25 kg/m2 pre-pregnancy BMI and with birthweight ≥ 2500 g of the second twin (adjusted risk ratio (aRR) 1.72, 95% confidence interval (CI) 1.15–2.57, and aRR 2.06, 95% CI 1.14–3.72, respectively). Breech and transverse presentation of the second twin were also risk factors for combined delivery compared with cephalic presentation (aRR 3.60, 95% CI 2.67–4.85, and aRR 9.94, 95% CI 6.50–15.0, respectively). Although association of combined delivery with pre-pregnancy BMI was attenuated after adjustment by delivery interval, association with birthweight of the second twin was strengthened. Conclusion: Delivery interval was significantly associated with combined delivery and mediated the association between combined delivery and some other risk factors. [ABSTRACT FROM AUTHOR]

It is often argued that certain metaphysical complications surrounding the phenomenon of monozygotic twinning force us to conclude that, prior to the point at which twinning is no longer possible, the zygote or early embryo cannot be considered an individual human organism. In this essay, I argue, on the contrary, that there are in fact several ways of making sense of monozygotic twinning that uphold the humanity of the original zygote, but also that there is no easy answer to what happens when the human zygote twins. All of the options available carry with them one or more surprising, alarming, or otherwise counterintuitive implications. All things considered, I conclude that the "budding option," according to which the original human organism present before twinning carries on as one of the resulting embryos but not the other, is the most plausible explanation of what happens when a human zygote twins. [ABSTRACT FROM AUTHOR]

Background: West syndrome (WS), also known as infantile spasm, is a rare form of severe epilepsy that begins during early infancy. This case series aimed to describe the early motor repertoire and examine the developmental function outcomes of infants with WS. Case Descriptions: Three infants (one female) with WS were assessed for early motor repertoire using the General Movement Assessment (GMA) which determined General Movement Optimality Scores (GMOS) at 4 post-term weeks of age, and Motor Optimality Scores (MOS) at 12 post-term weeks of age. Cognitive, language, and motor development were evaluated with the Bayley Scales of Infant and Toddler Development – Third Edition (Bayley-III) at 3, 6, 12, and 24 months of age. Outcomes: At 4-weeks post-term, one infant showed poor repertoire movements, while the other two showed cramped-synchronized movements with their GMOS ranging from 6 to 16 (out of 42). All infants showed sporadic/absent fidgety movements at 12 weeks post-term with their MOS ranging from 5 to 9 (out of 28). All sub-domain scores of Bayley-III were <2 SD at all follow-up assessments, that is <70, indicating severe developmental delay. Conclusion: These infants with WS had less than optimal scores of early motor repertoire, and developmental delay at a later age. Early motor repertoire might be an early sign for developmental function outcome at a later age in this population suggesting the need for additional research. [ABSTRACT FROM AUTHOR]

Summary: We report a case of monozygotic twin sisters with hereditary spastic paraplegia type 4 (SPG4) and epilepsy, only one of whom had a diagnosis of narcolepsy type 1 (NT1). The older sister with NT1 exhibited excessive daytime sleepiness, cataplexy, sleep‐onset rapid eye movement period in the multiple sleep latency test, and decreased orexin levels in cerebrospinal fluid. Both sisters had HLA‐DRB1*15:01‐DQB1*06:02 and were further identified to have a novel missense mutation (c.1156A > C, p.Asn386His) in the coding exon of the spastin (SPAST) gene. The novel missense mutation might be involved in the development of epilepsy. This case is characterised by a combined diagnosis of SPG4 and epilepsy, and it is the first report of NT1 combined with epilepsy and genetically confirmed SPG4. The fact that only one of the twins has NT1 suggests that acquired and environmental factors are important in the pathogenesis of NT1. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy with respiratory distress type 1 (SMARD1; OMIM #604320, ORPHA:98920) is a rare autosomal recessive congenital motor neuron disease. It is caused by variants in the IGHMBP2 gene. Clinically, it presents with respiratory failure due to diaphragmatic paralysis, progressive muscle weakness starting in the distal parts of the limbs, dysphagia, and damage to sensory and autonomic nerves. Unlike spinal muscular atrophy (SMA), SMARD1 has a distinct genetic etiology and is not detected in the population newborn screening programs. Most children with SMARD1 do not survive beyond the first year of life due to progressive respiratory failure. Artificial ventilation can prolong survival, but no specific treatment is available. Therapy focuses on mechanical ventilation and improving the patient's quality of life. Research into gene therapy is ongoing. We report three female patients with SMARD1, including twins from a triplet pregnancy. In twin sisters (patient no. 1 and patient no. 2), two heterozygous variants in the IGHMBP2 gene were identified: c.595G>C/p.Ala199Pro and c.1615_1623del/p.Ser539_Tyr541del. In patient no. 3, a variant c.1478C>T/p.Thr493Ile and a variant c.439C>T/p.Arg147* in the IGHMBP2 gene were detected. Our findings underscore the variability of clinical presentations, even among patients sharing the same pathogenic variants in the IGHMBP2 gene, and emphasize the importance of early genetic diagnosis in patients presenting with respiratory failure, with or without associated diaphragmatic muscle paralysis. [ABSTRACT FROM AUTHOR]

Interictal psychosis is a psychotic symptom that is not temporally related to epileptic seizures. Pregnancy delusion is defined as a person's fixed belief that she is pregnant despite objective evidence that she is not pregnant. In this case report, pregnancy delusion was described in a patient with epilepsy. A 31-year-old woman with epilepsy was admitted to a psychiatric ward. The patient, whose pregnancy test results were never positive, believed that she was pregnant. It was learned that her identical twin had experienced reproductive-sexuality-themed psychotic symptoms 10 years ago. The patient was hospitalized for three weeks and discharged in remission with paliperidone 6 mg/day and biperiden 2 mg/day. Caution should be exercised when using antipsychotics because of their epileptogenic effects. Pregnancy delusion in epilepsy is rare. In addition to this rare condition, it is noteworthy that reproductive-sexual delusions were reported in the patient's twin brother who was diagnosed with epilepsy. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To investigate the contribution of longitudinal mean arterial pressure (MAP) measurement during the first, second, and third trimesters of twin pregnancies to the prediction of pre‐eclampsia.A retrospective cohort study was conducted on women with twin pregnancies. Historical data between 2019 and 2021 were analyzed, including maternal characteristics and mean artery pressure measurements were obtained at 11–13, 22–24, and 28–33 weeks of gestation. The outcome measures included pre‐eclampsia with delivery <34 and ≥34 weeks of gestation. Models were developed using logistic regression, and predictive performance was evaluated using the area under the curve, detection rate at a given false‐positive rate of 10%, and calibration plots. Internal validation was conducted via bootstrapping.A total of 943 twin pregnancies, including 36 (3.82%) women who experienced early‐onset pre‐eclampsia and 93 (9.86%) who developed late‐onset pre‐eclampsia, were included in this study. To forecast pre‐eclampsia during the third trimester, the most accurate prediction for early‐onset pre‐eclampsia resulted from a combination of maternal factors and MAP measured during this trimester. The optimal predictive model for late‐onset pre‐eclampsia includes maternal factors and MAP data collected during the second and third trimesters. The areas under the curve were 0.937 (95% confidence interval [CI] 0.894–0.981) and 0.887 (95% CI 0.852–0.921), respectively. The corresponding detection rates were 83.33% (95% CI 66.53%–93.04%) for early‐onset pre‐eclampsia and 68.82% (95% CI 58.26%–77.80%) for late‐onset pre‐eclampsia.Repeated measurements of MAP during pregnancy significantly improved the accuracy of late‐onset pre‐eclampsia prediction in twin pregnancies. The integration of longitudinal data into pre‐eclampsia screening may be an effective and valuable strategy. [ABSTRACT FROM AUTHOR]

Background: The experiences and challenges associated with breastfeeding multiple births can be considerably more complex than those of singletons. Multiple births refer to the delivery of more than one offspring in a single birth event. Emphasizing the needs and experiences of mothers with multiple births during breastfeeding can enable healthcare providers to design targeted interventions that enhance breastfeeding rates. However, existing breastfeeding and health education resources and practices do not fully meet the needs of women who breastfeed multiples. This review aimed to review and synthesize qualitative studies on the breastfeeding experiences of women with multiple births. Methods: A systematic search was conducted in 10 electronic databases for papers published from the inception of the database to March 2024. The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research was utilized to evaluate the methodological quality of the studies included. The thematic synthesis method of Thomas and Harden was employed to integrate and analyze the included literature to derive new categories and conclusions. Findings: Eight studies met the inclusion criteria and quality assessment criteria for this study. Through the integration of their results, four themes were identified: the choice and willingness to breastfeed multiple births; the challenges of breastfeeding multiple births; stage management and individualised adaptation of breastfeeding; and the experience of support. Conclusion: Throughout the feeding process from pregnancy to the postpartum period, mothers with multiple births often have predominantly negative experiences with breastfeeding. Consequently, hospitals should create a multidisciplinary follow-up team comprising obstetrics, neonatology, psychology, and community services to offer specialized and personalized support to these women at various stages. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [PROSPERO 2024 CRD42024520348]. [ABSTRACT FROM AUTHOR]

Objective Despite an increase in twin pregnancies in recent decades, the Institute of Medicine twin weight gain recommendations remain provisional and provide no guidance for the pattern or timing of weight change. We sought to characterize gestational weight change trajectory patterns and examine associations with birth outcomes in a cohort of twin pregnancies. Study Design Prenatal and delivery records were examined for 320 twin pregnancies from a maternal–fetal medicine practice in Austin, TX 2011-2019. Prenatal weights for those with >1 measured weight in the first trimester and ≥3 prenatal weights were included in analyses. Trajectories were estimated to 32 weeks (mean delivery: 33.7 ± 3.3 weeks) using flexible latent class mixed models with low-rank thin-plate splines. Associations between trajectory classes and infant outcomes were analyzed using multivariable Poisson or linear regression. Results Weight change from prepregnancy to delivery was 15.4 ± 6.3 kg for people with an underweight body mass index, 15.4 ± 5.8 kg for healthy weight, 14.7 ± 6.9 kg for overweight, and 12.5 ± 6.4 kg for obesity. Three trajectory classes were identified: low (Class 1), moderate (Class 2), or high gain (Class 3). Class 1 (24.7%) maintained weight for 15 weeks and then gained an estimated 6.6 kg at 32 weeks. Class 2 (60.9%) exhibited steady gain with 13.5 kg predicted total gain, and Class 3 (14.4%) showed rapid gain across pregnancy with 21.3 kg predicted gain. Compared to Class 1, Class 3 was associated with higher birth weight z -score (β = 0.63, 95% confidence interval [CI]: 0.31,0.96), increased risk for large for gestational age (IRR = 5.60, 95% CI: 1.59, 19.67), and birth <32 weeks (IRR = 2.44, 95% CI: 1.10, 5.4) that was attenuated in sensitivity analyses. Class 2 was associated with moderately elevated birth weight z -score (β = 0.24, 95% CI: 0.00, 0.48, p = 0.050). Conclusion Gestational weight change followed a low, moderate, or high trajectory; both moderate and high gain patterns were associated with increased infant size outcomes. Optimal patterns of weight change that balance risk during the prenatal, perinatal, and neonatal periods require further investigation, particularly in high-risk twin pregnancies. Key Points A majority gained weight below IOM twin recommendations. Three patterns of GWC across pregnancy were identified. Moderate or high GWC was associated with infant size. [ABSTRACT FROM AUTHOR]

Background: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks. Methods: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs. Results: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks. Conclusions: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusion To develop and test an Objective Structured Assessment of Technical Skills (OSATS) score for the internal version and total breech extraction of the second twin if in a non‐engaged cephalic position.This prospective interventional study took place in a tertiary obstetrics department in France. An objective scoring system was developed, and a standardized simulation scenario was set up. Score evaluation was blinded and analyzed according to group and number of past successful vaginal twin deliveries in real life. A satisfaction evaluation was performed, based on the “Student Design Scale” questionnaire.Simulation was performed on 33 participants in three groups: novice group (15 first‐ and second‐year residents), intermediate group (11 third‐ to sixth‐year residents), and expert group (seven senior obstetricians). The total score obtained by experts was higher than that of the intermediate group (P = 0.001), which was higher than that of the novice group (P < 0.001). In the intermediate group, no correlation was found between OSATS score and number of past successful vaginal twin deliveries. Participants' satisfaction was excellent.The OSATS score developed was reliable and valid to evaluate an internal version and a total breech extraction of the second twin, and to differentiate novice, intermediate, and expert practitioners. [ABSTRACT FROM AUTHOR]

Purpose: In a certain proportion of dichorionic twin pregnancies, the two placentas are fused. The clinical significance of this finding remains unclear. Our objective was to compare outcomes of dichorionic twin pregnancies with fused versus separate placentas as determined on first-trimester ultrasound. Methods: Retrospective study of patients with dichorionic twins followed at a tertiary center between 2014 and 2022. The co-primary outcomes were fetal growth restriction and preeclampsia. Associations between fused placentas and the study outcomes were estimated using multivariable Poisson regression and were reported as adjusted relative risk (aRR) with a 95%-confidence interval (CI). Results: Of the 328 eligible patients, 175 (53.4%) and 153 (46.6%) had fused and separate placentas, respectively. Compared with pregnancies with separate placentas, patients with fused placentas had a lower risk of preeclampsia [aRR 0.48 (95%-CI 0.24–0.97)] but a higher risk of fetal growth restriction [aRR 1.23 (95%-CI 1.02–1.48)] and admission to the neonatal intensive care unit [aRR 1.31 (95%-CI 1.01–1.71)]. In addition, pregnancies with fused placentas were more likely to have a total placental weight below the 10th percentile than those with separate placentas [aRR 1.93 (95%-CI 1.16–3.21)]. Discussion: Dichorionic twin pregnancies with fused placentas have a lower risk of preeclampsia but are more likely to be complicated by fetal growth restriction, observations that may be attributed to the lower total placentas mass in pregnancies with fused compared with separate placentas. Fused placentas can be used as a potential biomarker for the prediction of pregnancy complications in dichorionic twin pregnancies. [ABSTRACT FROM AUTHOR]

Purpose: An ancient description of the competition between twins for first breath is found in the biblical story of Jacob and Esau (Genesis 25:26) when Jacob pulled his older brother's heel in the hope of becoming firstborn but to no avail. In this study, we sought to evaluate the short and long-term outcomes of twin pairs, comparing between the second- and first-born twin. Methods: A population-based cohort study, including dichorionic twin deliveries occurring between the years 1991 and 2021 at Soroka University Medical Center. A General estimation equation (GEE) was applied to adjust for confounders. The incidence of offspring's hospitalizations due to various medical conditions was compared. Kaplan–Meier survival analyses compared cumulative morbidity. Cox proportional hazards models were used to control for confounders. Results: 5507 twin deliveries met the inclusion criteria. Second-born twins had higher rates of cesarean deliveries, statistically significant in the GEE multivariable analysis. More first-twin fetuses were experiencing non-reassuring fetal heart rate patterns, although other obstetrical outcomes as well as mortality rates were comparable between groups. Second twins weighed lower than their older sibling (mean difference 33 g) and were more frequently SGA and low birthweight (1500–2500 g); (p < 0.05). Later during childhood, offspring of twin deliveries experienced notable morbidity due to infectious (23.8–24.1%), respiratory (10.5–10.9%), neurological (7.0–7.8%) and cardiovascular pathologies (1.7–1.9%) during childhood, that was unaffected by birth order. Conclusion: Other than birthweight differences, the birth order of dichorionic twins is not associated with adverse neonatal health indices, nor does it predict excess risk for morbidity during childhood. [ABSTRACT FROM AUTHOR]

Epigenetic clocks based on DNA methylation have been known as biomarkers of aging, including principal component (PC) clocks representing the degree of aging and DunedinPACE representing the pace of aging. Prior studies have shown the associations between epigenetic aging and T2DM, but the results vary by epigenetic age metrics and people. This study explored the associations between epigenetic age metrics and T2DM or glycemic traits, based on 1070 twins (535 twin pairs) from the Chinese National Twin Registry. It also explored the temporal relationships of epigenetic age metrics and glycemic traits in 314 twins (157 twin pairs) who participated in baseline and follow‐up visits after a mean of 4.6 years. DNA methylation data were used to calculate epigenetic age metrics, including PCGrimAge acceleration (PCGrimAA), PCPhenoAge acceleration (PCPhenoAA), DunedinPACE, and the longitudinal change rate of PCGrimAge/PCPhenoAge. Mixed‐effects and cross‐lagged modelling assessed the cross‐sectional and temporal relationships between epigenetic age metrics and T2DM or glycemic traits, respectively. In the cross‐sectional analysis, positive associations were identified between DunedinPACE and glycemic traits, as well as between PCPhenoAA and fasting plasma glucose, which may be not confounded by shared genetic factors. Cross‐lagged models revealed that glycemic traits (fasting plasma glucose, HbA1c, and TyG index) preceded DunedinPACE increases, and TyG index preceded PCGrimAA increases. Glycemic traits are positively associated with epigenetic age metrics, especially DunedinPACE. Glycemic traits preceded the increases in DunedinPACE and PCGrimAA. Lowering the levels of glycemic traits may reduce DunedinPACE and PCGrimAA, thereby mitigating age‐related comorbidities. [ABSTRACT FROM AUTHOR]

This study tested phenotypic and biometric associations between physical and cognitive catch‐up growth in a community sample of twins (n = 1285, 51.8% female, 89.3% White). Height and weight were measured at up to 17 time points between birth and 15 years, and cognitive ability was assessed at up to 16 time points between 3 months and 15 years. Weight and length at birth were positively associated with cognitive abilities in infancy and adolescence (r's =.16–.51). More rapid weight catch‐up growth was associated with slower, steadier cognitive catch‐up growth. Shared and nonshared environmental factors accounted for positive associations between physical size at birth and cognitive outcomes. Findings highlight the role of prenatal environmental experiences in physical and cognitive co‐development. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the mediating role of sleep quality in the relationship between multidimensional perceived social support and fatigue among mothers of twin infants. One hundred and six (106) twin mothers participated in this cross-sectional study, who completed the Descriptive Information Form, Multidimensional Scale of Perceived Social Support, Pittsburgh Sleep Quality Index, and Checklist Individual Strength. The scale score averages of the mothers in the study are as follows: social support, 61.41 ± 23.86; fatigue, 77.64 ± 28.68; and sleep quality, 8.26 ± 2.38. According to the path model, perceived social support has a negative effect on poor sleep quality (p =.001, Beta = −0.411), and poor sleep quality has a positive effect on fatigue (p =.001, Beta = 0.335). Sleep quality also mediates the effect of multidimensional perceived social support on mothers' fatigue levels (p =.001, Beta = −0.138). The study results suggest that the perceived social support and fatigue levels of twin mothers are moderate, while their sleep quality is poor. Therefore, mothers of twin infants may benefit from increased social support to alleviate fatigue and enhance sleep quality. [ABSTRACT FROM AUTHOR]

Objective: To estimate the effect of antenatal corticosteroids on newborn respiratory morbidity in twins. Design: Regression discontinuity applied to population‐based birth registry data. Setting: British Columbia, Canada, 2008–2018. Population: Twin pregnancies admitted for birth between 31+0 and 36+6 weeks of gestation. Methods: During our study period, Canadian clinical practice guidelines recommended antenatal corticosteroid administration for imminent preterm birth up to 33+6 weeks. We used a logistic model to compare the predicted risks of our outcomes among pregnancies admitted for birth immediately before this clinical cut‐point (higher probability of exposure to antenatal corticosteroids) versus immediately after it (lower probability). Main outcome measures: Our primary outcome was a composite of newborn respiratory distress or in‐hospital death. Our secondary outcome was a composite of newborn respiratory intervention or in‐hospital death. Results: Among 2524 pregnancies (5035 liveborn twins), 47% of admissions before 34+0 weeks of gestation were exposed to antenatal corticosteroids but only 4.2% of admissions after this cut‐point were exposed. The risk of newborn respiratory distress or in‐hospital mortality increased abruptly at 34+0 weeks, corresponding to a protective effect of treatment (risk ratio [RR] 0.69, 95% CI 0.53–0.90; risk difference [RD] −12 cases per 100 births, 95% CI −20 to −4.1). There was no clear evidence for or against an effect on newborn respiratory intervention or in‐hospital death (RR 0.89, 95% CI 0.70–1.13; RD −4.2 per 100, 95% CI −13 to +4.2). Conclusions: Our findings provide evidence for the effectiveness of antenatal corticosteroids in preventing adverse newborn respiratory outcomes in twins. [ABSTRACT FROM AUTHOR]

Subjective health ratings are associated with dementia risk such that those who rate their health more poorly have increased risk for dementia. The genetic and environmental mechanisms underlying this association are unclear, as prior research cannot rule out whether the association is due to genetic confounds. The current study addresses this gap in two samples of twins, one from Sweden (N = 548) and one from Denmark (N = 4,373). Using genetically-informed, bivariate regression models, we assessed whether additive genetic effects explained the association between subjective health and dementia risk as indexed by a latent variable proxy measure. Age at intake, sex, education, depressive symptomatology, and follow-up time between subjective health and dementia risk assessments were included as covariates. Results indicate that genetic variance and other sources of confounding accounted for the majority of the effect of subjective health ratings on dementia risk. After adjusting for genetic confounding and other covariates, a small correlation was observed between subjective health and latent dementia risk in the Danish sample (rE = −.09, p <.05). The results provide further support for the genetic association between subjective health and dementia risk, and also suggest that subjective ratings of health measures may be useful for predicting dementia risk. [ABSTRACT FROM AUTHOR]

• The association between cognition and hormone therapy (HT) changed after 2002. • The Women's Health Initiative study altered the health profile of those using HT. • The association between HT and cognition is influenced by a selection effect. Mild cognitive impairment may be caused by pathophysiological changes occurring decades prior to symptom development. It has been hypothesised that oestrogen can prevent such changes. We aimed to investigate the association between postmenopausal hormone therapy and cognition in Danish female twins and to examine differences in this association before and after publication of the findings from the Women's Health Initiative study in 2002. This study includes cognitive assessment of 4510 twins aged 50+ years. Information on hormone therapy was obtained through Danish health registries. The association between current hormone therapy use and cognition was analysed in twins aged 50+ using both cross-sectional, intrapair and longitudinal analysis, adjusting for age, education, social class, and unobserved familial confounding. Cross-sectionally, systemic HT users aged 70+ had a significantly lower cognitive function than non-users, whereas systemic HT users aged 50–69 did not differ from non-users before 2002. Longitudinal data in younger twins aged 50–69 showed a significantly lower cognitive function in systemic HT users after 2002 compared to non-users. Systemic HT users aged 70+ showed that the lower cognitive function was most explicit before 2002, whereas after 2002 the cognitive function was closer to non-users. Twins aged 50–69 who changed from systemic HT to local HT after 2002, or dropped it altogether, performed cognitively better. Our findings cautiously indicate a change in the association between cognition and hormone therapy use after 2002, which suggests an alteration in the hormone therapy user profile in the wake of the 2002 WHI publication. [ABSTRACT FROM AUTHOR]

Background: Germline mutations have been identified in a small number of hereditary cancers, but the genetic predisposition for many familial cancers remains to be elucidated. Methods: This study identified a Chinese pedigree that presented different cancers (breast cancer, BRCA; adenocarcinoma of the esophagogastric junction, AEG; and B‐cell acute lymphoblastic leukemia, B‐ALL) in each of the three generations. Whole‐genome sequencing and whole‐exome sequencing were performed on peripheral blood or bone marrow and cancer biopsy samples. Whole‐genome bisulfite sequencing was conducted on the monozygotic twin brothers, one of whom developed B‐ALL. Results: According to the ACMG guidelines, bioinformatic analysis of the genome sequencing revealed 20 germline mutations, particularly mutations in the DNAH11 (c.9463G > A) and CFH (c.2314G > A) genes that were documented in the COSMIC database and validated by Sanger sequencing. Forty‐one common somatic mutated genes were identified in the cancer samples, displaying the same type of single nucleotide substitution Signature 5. Meanwhile, hypomethylation of PLEK2, MRAS, and RXRA as well as hypermethylation of CpG island associated with WT1 was shown in the twin with B‐ALL. Conclusions: These findings reveal genomic alterations in a pedigree with multiple cancers. Mutations found in the DNAH11, CFH genes, and other genes predispose to malignancies in this family. Dysregulated methylation of WT1, PLEK2, MRAS, and RXRA in the twin with B‐ALL increases cancer susceptibility. The similarity of the somatic genetic changes among the three cancers indicates a hereditary impact on the pedigree. These familial cancers with germline and somatic mutations, as well as epigenomic alterations, represent a common molecular basis for many multiple cancer pedigrees. [ABSTRACT FROM AUTHOR]

Twin pregnancy in cattle is undesirable for a number of reasons, including a higher abortion risk compared to pregnancies with a single foetus. Yet, the abortion risk is significantly influenced by the intrauterine location of the foetuses, that is, the abortion risk is several times higher if they are implanted in the same uterine horn (unilateral twin pregnancy) than if they are implanted with one foetus in each uterine horn (bilateral twin pregnancy). The reason for the higher abortion risk in unilateral twin pregnancies is unknown, but it may be related to malnutrition of the outermost foetus due to a limited placental capacity, as is the case for equine twin foetuses. A slaughterhouse study was performed and the foetuses of cattle pregnant with twins were measured. We identified 65 cases of twin pregnancies, of which 35 were unilateral twin pregnancies and 30 were bilateral twin pregnancies. There was no significant difference between the outermost and the more centrally located foetus in unilateral twin pregnancies in terms of body weight and length of the metacarpal diaphysis. Growth retardation of the outermost foetus could therefore not be confirmed as the cause of the higher abortion risk in unilateral bovine twin pregnancies. Four cases of pre‐slaughter foetal mortality were identified. In three of these cases, both twins were dead, of equal size and at a comparable level of degradation. In the fourth case, with approximately 40‐day‐old twin foetuses of equal size, only one of the foetuses showed signs of pre‐slaughter death. [ABSTRACT FROM AUTHOR]

Objectives: To identify the high-risk factors associated with postpartum hemorrhage (PPH) after an elective cesarean delivery of twins. Material and methods: This retrospective cohort study included all women with twin gestations who chose to have an elective cesarean delivery after 28 weeks of gestation at at the Women's Hospital, School of Medicine, Zhejiang University between September 2014 and April 2019. Women with an intrauterine fetal demise of one or both twins were excluded. PPH was defined as an estimated blood loss of = 1,000 mL within 24 h of birth. A total of 532 women were analyzed and classified into the PPH group (n = 70) and the no-PPH group (n = 462). Univariate and multivariate logistic regression analyses were performed to assess the independent risk factors. Results: Among the 532 women pregnant with twins, PPH occurred in 13.2% women (n = 70). There were statistically significant differences in preeclampsia (p = 0.005), premature rupture of membrane (PROM, p < 0.001), placenta previa (p < 0.001), anemia [hemoglobin (Hb) < 100 g/L; p = 0.003], and antenatal magnesium sulfate (MgSO4) use (p < 0.001) between the two groups. However, the following were the independent risk factors for PPH after an elective cesarean delivery for a twin pregnancy: preeclampsia [odds ratio (OR): 2.91; 95% confidence interval (CI): 1.33-6.36], PROM (OR: 8.57; 95% CI: 2.54-28.89), placenta previa (OR: 9.46; 95% CI: 3.59-24.89), antenatal MgSO4 use (OR: 7.64; 95% CI; 3.18-18.41), and anemia (Hb < 100 g/L; OR: 2.68; 95% CI: 1.42-5.06). Conclusions: Preeclampsia, PROM, placenta previa, and antenatal MgSO4 use were the risk factors for PPH after an elective cesarean delivery for twin pregnancies. Risk factor identification and prevention should be a priority. [ABSTRACT FROM AUTHOR]