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Background: Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity. Previous studies have identified associations and predicted the risk of BC using DNAm in blood; however, these studies did not distinguish between genetic and environmental contributions to these DNAm sites. In this study, associations between DNAm and BC are assessed using paired twin models, which control for shared genetic and environmental effects, allowing testing for associations between DNAm and non-shared environmental exposures and behavior. Results: Pre-diagnosis blood samples of 32 monozygotic (MZ) and 76 dizygotic (DZ) female twin pairs discordant for BC were collected at the mean age of 56.0 years, with the mean age at diagnosis 66.8 years and censoring 75.2 years. We identified 212 CpGs (p < 6.4*10–8) and 15 DMRs associated with BC risk across all pairs using paired Cox proportional hazard models. All but one of the BC risks associated with CpGs were hypomethylated, and 198/212 CpGs had their DNAm associated with BC risk independent of genetic effects. According to previous literature, at least five of the top CpGs were related to estrogen signaling. Following a comprehensive two-sample Mendelian randomization analysis, we found evidence supporting a dual causal impact of DNAm at cg20145695 (gene body of NXN, rs480351) with increased risk for estrogen receptor positive BC and decreased risk for estrogen receptor negative BC. Conclusion: While causal effects of DNAm on BC risk are rare, most of the identified CpGs associated with the risk of BC appear to be independent of genetic effects. This suggests that DNAm could serve as a valuable biomarker for environmental risk factors for BC, and may offer potential benefits as a complementary tool to current risk assessment procedures. [ABSTRACT FROM AUTHOR]

We present a case study highlighting prenatal ultrasound findings in monozygotic twins with chromosome 17q12 deletion syndrome. Fetus A exhibited bilateral fetal pyelectasis and talipes equinovarus, while fetus B showed hyperechogenic kidneys. Despite sharing the same de novo variant, the twins displayed distinct clinical phenotypes, suggesting the presence of non‐genetic factors influencing the phenotypic variability of this syndrome. This case represents the first documented instance of prenatally identified identical twins affected by 17q12 deletion syndrome. [ABSTRACT FROM AUTHOR]

BACKGROUND Women with endometriosis may constitute a group at a particularly increased risk of pregnancy-related complications. Furthermore, women selected for assisted reproductive technology (ART) are exposed to additional endocrinological and embryological factors that have been associated with adverse pregnancy outcomes. OBJECTIVE AND RATIONALE This study aimed to investigate the independent effect of endometriosis, adenomyosis, and various ART-related factors on adverse maternal, placental, fetal, and neonatal outcomes. SEARCH METHODS Published randomized controlled trials, cohort studies, and case–control studies were considered eligible. PubMed, MEDLINE, ClinicalTrials.gov, Embase, and Scopus were systematically searched up to 1 March 2024. This systematic review and meta-analysis was performed in line with the PRISMA and the MOOSE reporting guidelines. To thoroughly investigate the association between endometriosis/adenomyosis and adverse pregnancy outcomes, sub-analyses were conducted, whenever possible, according to: the method of conception (i.e. ART and non-ART conception), the endometriosis stage/phenotype, the coexistence of endometriosis and adenomyosis, any pre-pregnancy surgical treatment of endometriosis, and the form of adenomyosis. The odds ratio (OR) with 95% CI was used as effect measure. The quality of evidence was assessed using the GRADE approach. OUTCOMES We showed a higher risk of placenta previa in women with endometriosis compared to controls (34 studies, OR 2.84; 95% CI: 2.47, 3.26; I 2 = 83%, moderate quality). The association was observed regardless of the method of conception and was particularly strong in the most severe forms of endometriosis (i.e. rASRM stage III–IV endometriosis and deep endometriosis (DE)) (OR 6.61; 95% CI: 2.08, 20.98; I 2 = 66% and OR 14.54; 95% CI: 3.67, 57.67; I 2 = 54%, respectively). We also showed an association, regardless of the method of conception, between endometriosis and: (i) preterm birth (PTB) (43 studies, OR 1.43; 95% CI: 1.32, 1.56; I 2 = 89%, low quality) and (ii) cesarean section (29 studies, OR 1.52; 95% CI: 1.41, 1.63; I 2 = 93%, low quality). The most severe forms of endometriosis were strongly associated with PTB. Two outcomes were associated with adenomyosis both in the main analysis and in the sub-analysis that included only ART pregnancies: (i) miscarriage (14 studies, OR 1.83; 95% CI: 1.53, 2.18; I 2 = 72%, low quality) and (ii) pre-eclampsia (7 studies, OR 1.70; 95% CI: 1.16, 2.48; I 2 = 77%, low quality). Regarding ART-related factors, the following associations were observed in the main analysis and confirmed in all sub-analyses conducted by pooling only risk estimates adjusted for covariates: (i) blastocyst stage embryo transfer (ET) and monozygotic twinning (28 studies, OR 2.05; 95% CI, 1.72, 2.45; I 2 = 72%, low quality), (ii) frozen embryo transfer (FET) and (reduced risk of) small for gestational age (21 studies, OR 0.59; 95% CI, 0.57, 0.61; P  < 0.00001; I 2 = 17%, very low quality) and (increased risk of) large for gestational age (16 studies, OR 1.70; 95% CI, 1.60, 1.80; P  < 0.00001; I 2 = 55%, very low quality), (iii) artificial cycle (AC)-FET and pre-eclampsia (12 studies, OR 2.14; 95% CI: 1.91–2.39; I 2 = 9%, low quality), PTB (21 studies, OR 1.24; 95% CI 1.15, 1.34; P  < 0.0001; I 2 = 50%, low quality), cesarean section (15 studies, OR 1.59; 95% CI 1.49, 1.70; P  < 0.00001; I 2 = 67%, very low quality) and post-partum hemorrhage (6 studies, OR 2.43; 95% CI 2.11, 2.81; P  < 0.00001; I 2 = 15%, very low quality). WIDER IMPLICATIONS Severe endometriosis (i.e. rASRM stage III–IV endometriosis, DE) constitutes a considerable risk factor for placenta previa and PTB. Herein, we recommend against superimposing on this condition other exposure factors that have a strong association with the same obstetric adverse outcome or with different outcomes which, if coexisting, could determine the onset of an ominous obstetric syndrome. Specifically, we strongly discourage the use of AC regimens for FET in ovulatory women with rASRM stage III–IV endometriosis or DE. We also recommend single ET at the blastocyst stage in this high-risk population. REGISTRATION NUMBER CRD42023401428. [ABSTRACT FROM AUTHOR]

BACKGROUND Monozygotic (MZ) twins are believed to arise from the fission of a single fertilized embryo at different stages. Monochorionic MZ twins, who share one chorion, originate from the splitting of the inner cell mass (ICM) within a single blastocyst. In the classic model for dichorionic MZ twins, the embryo splits before compaction, developing into two blastocysts. However, there are a growing number of ART cases where a single blastocyst transfer results in dichorionic MZ twins, indicating that embryo splitting may occur even after blastocyst formation. OBJECTIVE AND RATIONALE For monochorionic MZ twins, we conducted a comprehensive analysis of the cellular mechanisms involved in ICM splitting, drawing from both ART cases and animal experiments. In addition, we critically re-examine the classic early splitting model for dichorionic MZ twins. We explore cellular mechanisms leading to two separated blastocysts in ART, potentially causing dichorionic MZ twins. SEARCH METHODS Relevant studies including research articles, reviews, and conference papers were searched in the PubMed database. Cases of MZ twins from IVF clinics were found by using combinations of terms including 'monozygotic twins' with 'IVF case report', 'ART', 'single embryo transfer', or 'dichorionic'. The papers retrieved were categorized based on the implicated mechanisms or as those with unexplained mechanisms. Animal experiments relating to MZ twins were found using 'mouse embryo monozygotic twins', 'mouse 8-shaped hatching', 'zebrafish janus mutant', and 'nine-banded armadillo embryo', along with literature collected through day-to-day reading. The search was limited to articles in English, with no restrictions on publication date or species. OUTCOMES For monochorionic MZ twins, ART cases and mouse experiments demonstrate evidence that a looser ICM in blastocysts has an increased chance of ICM separation. Physical forces facilitated by blastocoel formation or 8-shaped hatching are exerted on the ICM, resulting in monochorionic MZ twins. For dichorionic MZ twins, the classic model resembles artificial cloning of mouse embryos in vitro , requiring strictly controlled splitting forces, re-joining prevention, and proper aggregation, which allows the formation of two separate human blastocysts under physiological circumstances. In contrast, ART procedures involving the transfer of a single blastocysts after atypical hatching or vitrified-warmed cycles might lead to blastocyst separation. Differences in morphology, molecular mechanisms, and timing across various animal model systems for MZ twinning can impede this research field. As discussed in future directions, recent developments of innovative in vitro models of human embryos may offer promising avenues for providing fundamental novel insights into the cellular mechanisms of MZ twinning during human embryogenesis. WIDER IMPLICATIONS Twin pregnancies pose high risks to both the fetuses and the mother. While single embryo transfer is commonly employed to prevent dizygotic twin pregnancies in ART, it cannot prevent the occurrence of MZ twins. Drawing from our understanding of the cellular mechanisms underlying monochorionic and dichorionic MZ twinning, along with insights into the genetic mechanisms, could enable improved prediction, prevention, and even intervention strategies during ART procedures. REGISTRAITON NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background: This study investigates the relationship between MB-COMT DNA methylation (DNAm) and the personality traits outlined in the NEO-PI-Rmodel through an epigenetic study of monozygotic twins. DNAm, a critical epigenetic mechanism, regulates gene expression and has been linked to various biological processes and disorders. By leveraging the genetic similarities of monozygotic twins, this research explores how epigenetic variations influenced by environmental factors correlate with personality differences. Methods: The study utilized the Five-Factor Model (FFM) to categorize personality traits into five domains: Neuroticism, Extraversion, Conscientiousness, Agreeableness, and Openness to Experience. Each domain comprises six facets, providing a granular view of personality. The research centered on the catechol-O-methyltransferase (COMT) gene, focusing on its role in dopamine metabolism, which is hypothesized to influence personality traits through the dopaminergic system. DNAm status in the MBCOMT promoter region was examined to determine its association with personality facets. Results: Preliminary findings suggest a complex interaction between MBCOMT DNAm patterns and personality traits. Specific methylation patterns at different CpG sites were linked to varying expressions of traits such as impulsivity and aggression, highlighting the nuanced impact of epigenetics on personality. Conclusion: This study underscores the potential of integrating genetic, epigenetic, and environmental data to enhance our understanding of personality formation. The results contribute to a broader understanding of how genetic predispositions shaped by environmental factors manifest in complex trait differences, paving the way for future research in genetic psychiatry and personalized medicine. [ABSTRACT FROM AUTHOR]

Introduction: Twin–twin transfusion syndrome (TTTS) complicates approximately 10%–15% of all monochorionic twin pregnancies. The aim of this review was to evaluate the placental architectural characteristics within TTTS twins following laser and elucidate their impact on fetal outcomes and operative success. Material and Methods: Five databases were searched from inception to August 2023. Studies detailing post‐delivery placental analysis within TTTS twins post‐laser were included. Studies were categorized into two main groups: (1) residual anastomoses following laser and (2) abnormal cord insertion: either velamentous and/or marginal or proximate. The primary outcome was to determine the proportion of TTTS placentas with residual anastomoses and abnormal cord insertions post‐laser. Secondary outcomes included assessing residual anastomoses on post‐laser fetal outcomes and assessing the relationship between abnormal cord insertion and TTTS development. Study bias was critiqued using the Joanna Briggs Institute checklists and Cochrane risk of bias tool. Random‐effects meta‐analysis was used, and results were reported as pooled proportions or odds ratio (OR) with 95% confidence interval (CI). PROSPERO registration: CRD42023476875. Results: Twenty‐six studies, comprising 4013 monochorionic twins, were included for analysis. The proportion of TTTS placentas with residual anastomoses following laser was 24% (95% CI, 0.12–0.41), with a mean and standard deviation of 4.03 ± 2.95 anastomoses per placenta. Post‐laser residual anastomoses were significantly associated with intrauterine fetal death (OR, 2.38 [95% CI, 1.33–4.26]), neonatal death (OR, 3.37 [95% CI, 1.65–6.88]), recurrent TTTS (OR, 24.33 [95% CI, 6.64–89.12]), and twin anemia polycythemia sequence (OR, 13.54 [95% CI, 6.36–28.85]). Combined abnormal cord (velamentous and marginal), velamentous cord, and marginal cord insertions within one or both twins following laser were reported at rates of 49% (95% CI, 0.39–0.59), 27% (95% CI, 0.18–0.38), and 28% (95% CI, 0.21–0.36), respectively. Combined, velamentous and marginal cord insertions were not significantly associated with TTTS twins requiring laser (p = 0.72, p = 0.38, and p = 0.71, respectively) vs non‐TTTS monochorionic twins. Conclusions: To the best of our knowledge, this is the first review to conjointly explore outcomes of residual anastomoses and abnormal cord insertions within TTTS twins following laser. A large prospective study is necessitated to assess the relationship between abnormal cord insertion and residual anastomoses development post‐laser. [ABSTRACT FROM AUTHOR]

Monozygotic (MZ) twins cannot be distinguished using conventional forensic STR typing because they present identical STR genotypings. However, MZ twins do not always live in the same environment and often have different dietary and other lifestyle habits. Metabolic profiles are deyermined by individual characteristics and are also influenced by the environment in which they live. Therefore, they are potential markers capable of identifying MZ twins. Moreover, the production of proteins varies from organism to organism and is influenced by both the physiological state of the body and the external environment. Hence, we used metabolomics and proteomics to identify metabolites and proteins in peripheral blood to discriminate MZ twins. We identified 1749 known metabolites and 622 proteins in proteomic analysis. The metabolic profiles of four pairs of MZ twins revealed minor differences in intra-MZ twins and major differences in inter-MZ twins. Each pair of MZ twins exhibited distinct characteristics, and four metabolites—methyl picolinate, acesulfame, paraxanthine, and phenylbenzimidazole sulfonic acid—were observed in all four MZ twin pairs. These four differential exogenous metabolites conincidently show that the different external environments and life styles can be well distinguished by metabolites, considering that twins do not all have the same eating habits and living environments. Moreover, MZ twins showed different protein profiles in serum but not in whole blood. Thus, our results indicate that differential metabolites provide potential biomarkers for the personal identification of MZ twins in forensic medicine. [ABSTRACT FROM AUTHOR]

Background and Aims: Studies on adolescent alcohol use and cognition are often unable to separate the potential causal effects of alcohol use on cognition from shared etiological influences, including genetic influences or other substance use comorbidities also known to be associated with cognition, such as nicotine use. The present study aimed to fill this gap and clarify the relationship between adolescent alcohol use and young adult cognition by accounting for both measured and unmeasured confounders. Design: A random effects model accounting for nesting in families was used to control for measured confounders. Next, co‐twin comparisons were conducted within the full sample and in monozygotic twin pairs (MZ) to control for unmeasured genetic and environmental confounders shared by co‐twins. Participants/Setting: Participants were 812 individuals (58.6% female, 361 complete pairs, 146 MZ pairs) from the longitudinal FinnTwin12 study in Finland. Measurements Adolescent alcohol use was indexed with measures of frequency of use and intoxication averaged across ages 14 and 17. Cognitive outcomes were measured at average age 22 and included Trail Making Test, California Stroop test, Wechsler Adult Intelligence subtests (Vocabulary, Block Design, Digit Symbol), Digit Span subtest of Wechsler Memory Scale, Mental Rotation Test and Object Location Memory test. Covariates included sex, parental education, general cognitive ability, current alcohol use and nicotine use. Findings Greater frequency of alcohol use and frequency of intoxication across adolescence was associated with decreased vocabulary scores in the co‐twin control [freq: stnd beta = −0.12, 95% confidence interval (CI) = −0.234, −0.013] and MZ only co‐twin control models (freq: stnd beta = −0.305, 95% CI = –0.523, −0.087; intox: stnd beta = −0.301, 95% CI = ‐0.528, −0.074). Conclusions: In Finland, there appears to be little evidence that adolescent alcohol use causes cognitive deficits in young adulthood, except modest evidence for association of higher adolescent alcohol use with lower young adult vocabulary scores. [ABSTRACT FROM AUTHOR]

The article "Serotonin and schizophrenia: what influences what?" explores the relationship between serotonin and schizophrenia, highlighting the role of the serotonergic system in the pathogenesis of schizophrenia. The text discusses the complex nature of schizophrenia, its symptoms, and the impact of genetic and environmental factors on its development. It also delves into the molecular mechanisms linking serotonin to schizophrenia and the bidirectional influence between the two. The article emphasizes the importance of understanding early molecular events to unravel the etiology of schizophrenia and develop interventions to modulate these processes. [Extracted from the article]

This brief report revisits the earliest known hyperscanning study published in 1965, which examined simultaneous EEG recordings of identical twins separated by six meters. The original study's findings suggested that eye closure in one twin elicited alpha activity in the other, despite physical separation. Leveraging contemporary signal processing techniques, we reanalyzed the digitized data to validate their findings. Spectral analysis confirmed alpha activity in the twins' EEG signals, aligning with the original observations. Multitapering along with background noise subtraction also revealed the alpha activity in the unrelated subject, which could not be observed by visual inspection alone. Coherence analysis revealed significant alpha band synchrony between a twin and an unrelated subject, differing from the initial study's conclusions. Our findings indicate that even historical data can yield new insights when revisited with contemporary data analysis tools and highlight the potential for future large-scale studies using advanced techniques to explore nonlocal brain interactions. [ABSTRACT FROM AUTHOR]

Listeriosis is a rare but severe foodborne disease caused by Listeria Monocytogenes (LM), a small facultative intracellular bacillus. When occurring in pregnant women, it can be vertically transmitted to the fetus and the newborn. Infected women usually display aspecific and mild symptoms, and rarely develop the severe forms of the disease (such as neurolisteriosis). On the contrary, fetal and neonatal listeriosis can lead to complications such as fetal loss, preterm birth, neonatal sepsis, and respiratory distress syndrome (RDS). Prompt diagnosis is one of the main challenges because of the aspecific presentation of the disease; therapy relies on antibiotics that reach high intracellular concentration and can penetrate and pass the placenta reaching the fetus. Herein we report an infrequent case of LM infection involving a woman with monochorionic diamniotic twin pregnancy, followed by a comprehensive review of the available literature on listeriosis in pregnancy. [ABSTRACT FROM AUTHOR]

Background: Fabry disease is an X-linked lysosomal storage disease caused by the impairment of α-galactosidase A. The complex intronic haplotype (CIH) variants, located in promoter and intronic regulatory lesions, has been found in patients with classical forms of Fabry disease. We present a case of Fabry disease in female monozygotic twins exhibiting the CIH mutation and classical manifestations. Case presentation: A 61-year-old woman with a history of stroke, carotid artery occlusion, hypertrophic cardiomyopathy, and chronic kidney disease was referred to the nephrology clinic for management of her chronic kidney disease. Her monozygotic twin sister also presented with hypertrophic cardiomyopathy, atrial flutter, carotid stenosis, and proteinuria. Clinical symptoms and a comprehensive family history strongly suggested the presence of Fabry disease. Genetic analysis revealed the presence of 5 variants within a complex intronic haplotype (CIH): c.−10 C > T, c.369 + 990 C > A, c.370 − 81_370–77delCAGCC, c.640–16 A > G, and c.1000–22 C > T. We conducted a review of the patient's previous kidney biopsy findings, which demonstrated the presence of lamellated inclusion bodies in electron microscopy. Remarkably, both the monozygotic twin sister and her son exhibited the same genetic mutation. Enzyme replacement therapy was initiated for the patient. Her kidney function decreased throughout a thorough 2-year follow-up period, while there was a slight decrease in the left ventricular mass index. Conclusions: This is the first reported case of female monozygotic twins with the CIH variants representing cardiac, cerebrovascular, and renal manifestations suggestive of Fabry disease. [ABSTRACT FROM AUTHOR]

Thirty percent of spontaneously occurring twins are monozygotic, of which two-thirds are monochorionic, possessing a single placenta. A common placental mass with shared intertwin placental circulation is key to the development and management of complications unique to monochorionic gestations. In this Consult, we review general considerations and a contemporary approach to twin-twin transfusion syndrome and twin anemia-polycythemia sequence, providing management recommendations based on the available evidence. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend routine first-trimester sonographic determination of chorionicity and amnionicity (GRADE 1B); (2) we recommend that ultrasound surveillance for twin-twin transfusion syndrome begin at 16 weeks of gestation for all monochorionic-diamniotic twin pregnancies and continue at least every 2 weeks until delivery, with more frequent monitoring indicated with clinical concern (GRADE 1C); (3) we recommend that routine sonographic surveillance for twin-twin transfusion syndrome minimally include assessment of amniotic fluid volumes on both sides of the intertwin membrane and evaluation for the presence or absence of urine-filled fetal bladders, and ideally incorporate Doppler study of the umbilical arteries (GRADE 1C); (4) we recommend fetoscopic laser surgery as the standard treatment for stage II through stage IV twin-twin transfusion syndrome presenting between 16 and 26 weeks of gestation (GRADE 1A); (5) we recommend expectant management with at least weekly fetal surveillance for asymptomatic patients continuing pregnancies complicated by stage I twin-twin transfusion syndrome, and consideration for fetoscopic laser surgery for stage I twin-twin transfusion syndrome presentations between 16 and 26 weeks of gestation complicated by additional factors such as maternal polyhydramnios-associated symptomatology (GRADE 1B); (6) we recommend an individualized approach to laser surgery for early- and late-presenting twin-twin transfusion syndrome (GRADE 1C); (7) we recommend that all patients with twin-twin transfusion syndrome qualifying for laser therapy be referred to a fetal intervention center for further evaluation, consultation, and care (Best Practice); (8) after laser therapy, we suggest weekly surveillance for 6 weeks followed by resumption of every-other-week surveillance thereafter, unless concern exists for post-laser twin-twin transfusion syndrome, post-laser twin anemia-polycythemia sequence, or fetal growth restriction (GRADE 2C); (9) following the resolution of twin-twin transfusion syndrome after fetoscopic laser surgery, and without other indications for earlier delivery, we recommend delivery of dual-surviving monochorionic-diamniotic twins at 34 to 36 weeks of gestation (GRADE 1C); (10) in twin-twin transfusion syndrome pregnancies complicated by posttreatment single fetal demise, we recommend full-term delivery (39 weeks) of the surviving co-twin to avoid complications of prematurity unless indications for earlier delivery exist (GRADE 1C); (11) we recommend that fetoscopic laser surgery not influence the mode of delivery (Best Practice); (12) we recommend that prenatal diagnosis of twin anemia-polycythemia sequence minimally require either middle cerebral artery Doppler peak systolic velocity values >1.5 and <1.0 multiples of the median in donor and recipient twins, respectively, or an intertwin Δ middle cerebral artery peak systolic velocity >0.5 multiples of the median (GRADE 1C); (13) we recommend that providers consider incorporating middle cerebral artery Doppler peak systolic velocity determinations into all monochorionic twin ultrasound surveillance beginning at 16 weeks of gestation (GRADE 1C); and (14) consultation with a specialized fetal care center is recommended when twin anemia-polycythemia sequence progresses to a more advanced disease stage (stage ≥II) before 32 weeks of gestation or when concern arises for coexisting complications such as twin-twin transfusion syndrome (Best Practice). [ABSTRACT FROM AUTHOR]

Purpose: To explore patterns of disease expression in Alagille syndrome (ALGS). Methods: Patients underwent ophthalmic examination, optical coherence tomography (OCT) imaging, fundus intravenous fluorescein angiography (IVFA), perimetry and full-field electroretinograms (ffERGs). An adult ALGS patient had multimodal imaging and specialized perimetry. Results: The proband (P1) had a heterozygous pathogenic variant in JAG1; (p.Gln410Ter) and was incidentally diagnosed at age 7 with a superficial retinal hemorrhage, vascular tortuosity, and midperipheral pigmentary changes. The hemorrhage recurred 15 months later. Her monozygotic twin sister (P2) had a retinal hemorrhage at the same location at age 11. Visual acuities for both patients were 20/30 in each eye. IVFA was normal. OCT showed thinning of the outer nuclear in the peripapillary retina. A ffERG showed normal cone-mediated responses in P1 (rod-mediated ERGs not documented), normal ffERGs in P2. Coagulation and liver function were normal. An unrelated 42-year-old woman with a de-novo pathogenic variant (p. Gly386Arg) in JAG1 showed a similar pigmentary retinopathy and hepatic vascular anomalies; rod and cone function was normal across large expanses of structurally normal retina that sharply transitioned to a blind atrophic peripheral retina. Conclusion: Nearly identical recurrent intraretinal hemorrhages in monozygotic twins with ALGS suggest a shared subclinical microvascular abnormality. We hypothesize that the presence of large areas of functionally and structurally intact retina surrounded by severe chorioretinal degeneration, is against a predominant involvement of JAG1 in the function of the neurosensory retina, and that instead, primary abnormalities of chorioretinal vascular development and/or homeostasis may drive the peculiar phenotypes. [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]

Background: Amniotic Band Syndrome (ABS) is a rare congenital condition characterized by the formation of fibrous bands within the amniotic sac that can entangle and restrict fetal development, leading to various deformities. In this report, we present an unprecedented case of fetal amniotic band ingestion in a monochorionic diamniotic (MCDA) twin pregnancy. Reporting this case is essential for expanding the understanding of the diverse presentations of amniotic bands, considering this rare entity in the differential diagnosis of prenatal ultrasound findings, and emphasizing the importance of vigilant prenatal monitoring and individualized management strategies. Case Presentation: A 35-year-old gravida 2, para 1 woman with an MCDA twin pregnancy experienced an uneventful pregnancy until the 33rd week, when routine ultrasonography revealed mild intrauterine growth restriction in both twins. At 35 weeks and 5 days gestation, the patient presented with mild abdominal pain. An emergency ultrasound revealed that Twin A ingested an amniotic band. Despite the absence of overt fetal distress, a comprehensive risk assessment was conducted, taking into account potential complications, such as airway obstruction and gastrointestinal issues due to prolonged amniotic band ingestion. Considering the risks versus the benefits of continued gestation and the near-term status, an emergency cesarean section was performed. The procedure resulted in the successful delivery of both twins with satisfactory Apgar scores. A 9-cm fibrous strand was promptly extracted from Twin A's oral cavity after delivery, confirming prenatal diagnosis. Both neonates underwent thorough examinations, revealing no additional anomalies, and demonstrated normal development during the nine-month follow-up. Conclusion: This case highlights the inherent challenges in diagnosing and managing the rare presentations of amniotic band-related complications, particularly in MCDA twin pregnancies. The instance of fetal amniotic band ingestion underscores the vital role of comprehensive prenatal imaging in ensuring accurate diagnosis and tailoring individualized risk assessments throughout the pregnancy in such rare and complex situations. [ABSTRACT FROM AUTHOR]

Objective: Hoarding disorder is a complex condition that significantly impacts individuals' lives, characterized by excessive acquiring, difficulty discarding, clutter, distress, and impairment. This study aimed to examine the extent to which genetics and environment influence difficulty discarding, excessive acquisition, and clutter through the implementation of a classical twin study. Method: This classical twin study, conducted between April and September 2021, enrolled 194 twins (97 pairs) from Isfahan, recruited through the Isfahan Twins Registry (ITR). A total of 194 twins, consisting of 100 monozygotic (MZ) and 94 dizygotic (DZ) twins, participated in this study. Participants aged 16-50 were invited electronically and completed an online consent form and questionnaire. Hoarding symptoms were assessed using the saving inventory-revised. Zygosity was determined using a self-report method based on Song et al.'s questionnaire. To estimate the heritability of hoarding symptoms, the classical univariate twin model was employed. Results: Based on the univariate analysis, the heritability estimates for difficulty discarding and excessive acquisition were found to be 0.43 and 0.52, respectively. However, the results did not provide support for the role of genetics in clutter. Instead, it was indicated that the common environment accounted for 0.54 of the variance in clutter, while the specific environment contributed 0.46 to this symptom. Conclusion: The difficulty discarding and excessive acquisition were found to be moderately heritable. On the other hand, considering the contribution of genetics and environment to clutter, the results raise doubts about the association of clutter with hoarding. The relatively low genetic influence suggests that this trait may overlap with other behaviors rather than hoarding. [ABSTRACT FROM AUTHOR]

Objective: Pediatric loss‐of‐control (LOC) eating is associated with high BMI and predicts binge‐eating disorder and obesity onset with age. Research on the etiology of this common comorbidity has not explored the potential for shared genetic risk. This study examined genetic and environmental influences on LOC eating and its shared influence with BMI. Method: Participants were 499 monozygotic and 398 same‐sex dizygotic twins (age = 17.38 years ± 0.67, BMIz = 0.03 ± 1.03, 54% female) from the Colorado Center for Antisocial Drug Dependence Study. LOC eating was assessed dichotomously. Self‐reported height and weight were converted to BMIz. Univariate and bivariate twin models estimated genetic and environmental influences on LOC eating and BMIz. Results: More girls (21%) than boys (9%, p < 0.001) reported LOC eating. The phenotypic correlation with BMIz was 0.03 in girls and 0.18 in boys. Due to the nonsignificant phenotypic correlation in girls, bivariate twin models were fit in boys only. Across all models, the best‐fitting model included genetic and unique environmental effects. Genetic factors accounted for 0.51 (95% CI: 0.23, 0.73) of the variance of LOC eating in girls and 0.54 (0.18, 0.90) in boys. The genetic correlation between LOC eating and BMIz in boys was 0.45 (0.15, 0.75). Discussion: Findings indicate moderate heritability of LOC eating in adolescence, while emphasizing the role of unique environmental factors. In boys, LOC eating and BMIz share a proportion of their genetic influences. [ABSTRACT FROM AUTHOR]

Background: Monochorionic (MC) twins are at risk for severe twin-to-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). In the case of preterm delivery, cesarean section (CS) with immediate umbilical cord clamping (ICC) of both twins is usually performed. While the recipient is at risk for polycythemia and may benefit from ICC, this procedure may result in aggravation of anemia with increased morbidity in the anemic donor. The purpose of this study was to demonstrate that the novel approach of selective extrauterine placental perfusion (EPP) with delayed umbilical cord clamping (DCC) in the donor infant is feasible in neonatal resuscitation of MC twins and may prevent severe anemia in donor and polycythemia in the recipient. Methods: Preterm MC twins with antenatal suspected severe anemia of the donor as measured by Doppler ultrasound, born with birthweights < 1500 g by CS, were transferred to the neonatal resuscitation unit with placenta and intact umbilical cords. In the donor, the umbilical cord was left intact to provide DCC with parallel respiratory support (EPP approach), while the cord of the recipient was clamped immediately after identification. Results: Selective EPP was performed in three cases of MC twins with TAPS and acute peripartum TTTS. All donor twins had initial hemoglobin levels ≥ 13.0 g/dL, and none of them required red blood cell transfusion on the first day after birth. Conclusions: Selective EPP may be a feasible strategy for neonatal resuscitation of MC preterm twins with high stage TAPS and TTTS to prevent anemia-related morbidities and may improve infant outcome. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of ductus venosus agenesis (ADV) in singleton pregnancies ranges from 0.04% to 0.15%, while its prevalence in twins remains largely unknown. To our knowledge, in the literature, there is only a single case report of a monochorionic diamniotic (MCDA) pregnancy complicated by ADV. Fetuses with ADV are at increased risk for congenital cardiac disease, heart failure, and fetal growth restriction (FGR). Consequently, these pregnancies have a heightened risk of experiencing an adverse outcome, like stillbirth and neonatal or infant death. Closer antenatal monitoring is warranted when ADV is suspected. Currently, there are no guidelines regarding the standard of care in cases of ADV and no recommendations for the timing of delivery in either singleton or twin pregnancies. Cases: This study aims to provide a comprehensive overview of the management of twin pregnancies complicated by ADV, featuring two cases of MC twins with concurrent sFGR and ADV in one twin. Discussion: These pregnancies experienced completely different outcomes, underscoring the necessity for personalized management tailored to the specific risk factors present in each pregnancy. Typically, in MCDA pregnancies with severe sFGR (type II and III), delivery represents the most reasonable option when venous Doppler abnormalities are identified. However, the absence of the DV complicates the management and the process of decision-making regarding the timing of delivery in cases of sFGR and ADV. We emphasize that effective decision-making should be guided by the presence of additional risk factors, including velamentous insertion, significant estimated fetal weight discordance, and progressive deterioration of the Doppler over time. Conclusions: Our experience suggests that these factors are strongly correlated with poorer outcomes. Given this context, could it be acceptable, in the case of MC pregnancy complicated by severe sFGR and ADV, with worsening findings and additional risk factors (e.g., velamentous insertion, severe birth weight discrepancy), to anticipate the time of delivery starting from 30 weeks of gestational age? [ABSTRACT FROM AUTHOR]

Context Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. Objective We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. Methods We treated 2 monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, vital signs, anthropometric measurements, and neurocognitive functions. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P321L mutation. The effects of GPB were compared to the effects of DITPA and TRIAC, thyromimetic medications that the patients had received in the past. Results NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment reduced high T3 and increased low T4 levels. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neurocognitive improvement was observed, in hyperreflexia score and in cognitive functions. Serum metabolites did not exceed the toxic range, but elevated liver transaminases were observed. Conclusion In the first report of GPB treatment in MCT8 deficiency we found an improvement in TH profile and body mass index, with minor neurodevelopmental changes. [ABSTRACT FROM AUTHOR]

Cognitive, behavioral, and disease traits are influenced by both genetic and environmental factors. Individual differences in these traits have been associated with graph theoretical properties of resting-state networks, indicating that variations in connectome topology may be driven by genetics. In this study, we establish the heritability of global and local graph properties of resting-state networks derived from functional MRI (fMRI) and magnetoencephalography (MEG) using a large sample of twins and non-twin siblings from the Human Connectome Project. We examine the heritability of MEG in the source space, providing a more accurate estimate of genetic influences on electrophysiological networks. Our findings show that most graph measures are more heritable for MEG compared to fMRI and the heritability for MEG is greater for amplitude compared to phase synchrony in the delta, high beta, and gamma frequency bands. This suggests that the fast neuronal dynamics in MEG offer unique insights into the genetic basis of brain network organization. Furthermore, we demonstrate that brain network features can serve as genetic fingerprints to accurately identify pairs of identical twins within a cohort. These results highlight novel opportunities to relate individual connectome signatures to genetic mechanisms underlying brain function. Graph theoretical properties of resting-state networks are more heritable for source-level MEG compared to fMRI, and brain network features can serve as genetic fingerprints to accurately identify identical twins in a cohort. [ABSTRACT FROM AUTHOR]

Research into the risk of anorexia nervosa (AN) has examined twin pairs to further the understanding of the contributions of genetics, trait inheritance, and environmental factors to eating disorder (ED) development. Investigations of twin experiences of EDs have been biologically-based and have not considered the qualitative, phenomenological aspects of twin experiences. A gap in the literature exists regarding understanding of discordant twins with EDs. This research was developed in response, with the aim to deepen understanding of AN in discordant twins and to create novel ideas for further research and testing. The case studies presented in this article provide lived experience insights of two identical discordant twin pairs: one twin pair discordant for longstanding AN and one twin pair discordant for 'atypical' AN (the twin with AN has recovered). The perspectives and experiences of each co-twin (one with AN and one without) explore a number of factors that may have contributed to twin discordance in these cases, and how each twin has responded to the impact of AN in their lives. Through use of first-person accounts in case study presentation, this article centres social justice values of lived experience leadership and involvement in research. This article aims to extend current knowledge and understanding of EDs in discordant twins, particularly regarding risk for ED development, ED duration, diagnosis and treatment, and recovery processes. [ABSTRACT FROM AUTHOR]

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We aimed to provide a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe setup. Procedural characteristics and outcomes as well as the accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9–6.0]). One pET was stopped due to fetal deceleration. The patients were delivered at 33.0 weeks [IQR 31.9–33.3] with two survivors and no neonatal transfusion requirements. The IUT volume was 48 mL [IQR 39–63 mL] and the pET volume was 32 mL [IQR 20–50], utilizing aliquots of 5–20 mL for the latter (p = 0.021). For the IUTs, the assumption of a fetal blood volume below 150 mL/kg underestimated the required transfusion volume. For the pETs, all formulas required adjustment of the dilution volume based on bedside testing (p < 0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin. [ABSTRACT FROM AUTHOR]

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training. We studied the effects of regular exercise training on LFC, PFC, and metabolism in monozygotic twin pairs discordant for BMI. We recruited 12 BMI-discordant monozygotic twin pairs (age 40.4, SD 4.5 years; BMI 32.9, SD 7.6, 8 female pairs). Ten pairs completed six months of training intervention. We measured hepatic insulin-stimulated glucose uptake using [18F]FDG-PET and fat content using magnetic resonance spectroscopy before and after the intervention. At baseline LFC, PFC, gamma-glutamyl transferase (GT), and hepatic glucose uptake were significantly higher in the heavier twins compared to the leaner co-twins (p = 0.018, p = 0.02 and p = 0.01, respectively). Response to training in liver glucose uptake and GT differed between the twins (Time*group p = 0.04 and p = 0.004, respectively). Liver glucose uptake tended to decrease, and GT decreased only in the heavier twins (p = 0.032). In BMI-discordant twins, heavier twins showed higher LFC and PFC, which may underlie the observed increase in liver glucose uptake and GT. These alterations were mitigated by exercise. The small number of participants makes the results preliminary, and future research with a larger pool of participants is warranted. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the short- and long-term outcome of selective reduction by fetoscopy-guided bipolar cord coagulation in monochronic twin pregnancies. Methods: Retrospective analysis was conducted of a consecutive cohort of all monochorionic twin pregnancies treated with fetoscopy-guided bipolar cord coagulation between December 2015 and December 2022 in a single center in China. Results: A total of 43 monochronic twin pregnancies undergoing fetoscopy-guided bipolar cord coagulation were analyzed. There were 5 intrauterine deaths with an 88.4% (38/43) survival rate overall. The preterm premature rupture of the membranes rate was 13.2%, and the preterm birth before 37 and 32 weeks was 42.1% and 13.1%, respectively. An uptrend in the survival rate (78.9 vs. 95.8%, p = 0.086) and a downtrend of procedure time (30 vs. 16.5 min, p = 0.036) were observed over time (period 1 from December 2015 to December 2019 verses period 2 from January 2020 to December 2022). Long-term outcome was assessed in 94.6% (35/37) of survivors, and 91.4% (32/35) had normal neurodevelopmental outcome. Conclusion: Fetoscopy-guided bipolar cord coagulation for fetal reduction in complicated monochorionic twin pregnancies could achieve a favorable short- and long-term outcome, especially in experienced hands. [ABSTRACT FROM AUTHOR]

Background: The STAG1 gene encodes a component of the cohesin complex, involved in chromosome segregation and DNA repair. Variants in genes of the cohesin complex determine clinical conditions characterized by facial dysmorphisms, upper limb anomalies, intellectual disability, and other neurological deficits. However, to date, the STAG1-related clinical phenotype has been poorly investigated (around 20 cases reported). Methods and Results: We report, for the first time, two twins affected by a syndromic neurodevelopmental disorder associated with a de novo variant in the STAG1 gene. Although both the twins showed a neurodevelopmental delay, one of them showed a more severe phenotype with greater behavioral problems, speech defects and limb apraxia. CGH array showed a 15q13.3 microduplication, inherited from an unaffected mother. Conclusions: We found different degrees of behavioral, speech and cognitive impairment in two twins affected by a neurodevelopmental disorder associated with a STAG1 variant. These findings highlight the variability of the STAG1-associated phenotype or a probable role of associated variants (like the discovered 15q13.3 microduplication) in modulating the clinical features. [ABSTRACT FROM AUTHOR]

Purpose: To examine age‐related macular degeneration (AMD) and retinal pigment epithelium (RPE)–Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs. Methods: In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35‐degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age‐Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE‐BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis. Results: Twenty‐nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2–4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3–4) versus the other being unaffected (AREDS 1). The within‐pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418–0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE‐BrM complex volume. RPE‐BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172–0.688, p < 0.01). Conclusion: A substantial proportion of monozygotic twin pairs are discordant with regard to age‐related macular degeneration phenotype. RPE‐BrM complex volume associated with age and intermediate and late AMD. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8+ T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8+ T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8+ T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8+ T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease. Editor's summary: Multiple sclerosis (MS) is an inflammatory disease of the nervous system in which CD8 T cells are present in MS lesions, but their role in disease progression remains unclear. Kavaka et al. analyzed CD8 T cells from the blood and cerebrospinal fluid of monozygotic twins, where one twin had MS and the other showed no signs or subclinical signs of neuroinflammation (SCNI). CD8 T cells from individuals with MS and cotwins with SCNI exhibited proinflammatory immunological and metabolic features consistent with enhanced activation and migration. These findings were validated in a separate cohort of individuals with MS, providing insights into the role of CD8 T cells in MS progression. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Twin anemia–polycythemia sequence (TAPS) in monochorionic twin pregnancies is a potentially serious complication caused by unidirectional vascular anastomoses in the placenta, resulting in one anemic donor twin and one polycythemic recipient twin. Diagnosis of this condition is achieved through Doppler ultrasound assessment of the difference between the MoM of the peak systolic velocity of the middle cerebral artery between the twins, establishing the diagnosis with a delta value >0.5 MoM. Management of this situation is individualized and may include intrauterine transfusions, intrauterine laser treatment, and expectant management through ultrasound monitoring of both fetuses to prevent complications. In severe cases, pregnancy termination may be necessary. It is essential that these pregnancies are managed by a multidisciplinary team of professionals, including obstetricians specialized in fetal medicine and neonatologists, to ensure the best possible outcome for both the mother and the fetuses. Early detection and treatment are crucial in the management of pregnancies complicated by twin anemia–polycythemia sequence. The main objective of this article is to conduct a review of the existing literature on the anemia–polycythemia sequence in monochorionic pregnancies, emphasizing the exceptional nature of the presented case due to its spontaneous occurrence, which has a very low prevalence compared to post-laser TAPS cases. It also discusses the different treatment options, highlighting the importance of expectant management and individualization in each case. [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]

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]

Unvaccinated identical twins developed bilateral anterior uveitis soon after the onset of coronavirus disease 2019 symptoms. During follow-up, both patients developed choroiditis, and one twine developed posterior scleritis and serous retinal detachment. Prompt treatment with oral prednisone ameliorated the lesions, and no recurrence was observed at the 18-month follow-up. Choroiditis may rarely be associated with severe acute respiratory syndrome coronavirus 2 infection, and it responds well to corticosteroid therapy. Although the exact mechanism is unknown, we hypothesize that the virus may act as an immunological trigger for choroiditis. [ABSTRACT FROM AUTHOR]

Trichotillomania is a clinical psychiatric manifestation involving significant hair loss in association with recurrent hair-pulling behavior, the etiology of which is still unknown. The aim of this study was to investigate the genetic and environmental and behavioral contribution to trichotillomania (hair-pulling disorder) and to relate the findings to contemporary theories about the etiology. This was a descriptive correlational and twins study design. 672 twins (MZ=474; DZ=202) were selected from Iranian twins associations in 2018. The Massachusetts General Hospital Hair-pulling Scale(1995) and the Self-Report of Zygosity were used as research instrument. Twin modeling methods were employed to decompose the variance in the liability trichotillomania (hair-pulling disorder) into additive genetic and shared and non-shared environmental factors. The data was analyzed by SPSS, STATA and M-plus. Univariate model-fitting analyses showed that genetic factors accounted for approximately 64% of the variance in TTM. The best extracted model for TTM was the DE model. The correlation coefficient results indicated that the correlation rate was 0/61 and 0/31 in MZ and DZ group respectively. It can be concluded that TTM phenotype is the results of a polygenetic. There is no intermediate despite of the dominance effect and it results from a gene-gene interaction or a dominant gene.

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Summary: Multiple sclerosis (MS) affects more than 2.8 million people worldwide but the distribution is not even. Although over 200 gene variants have been associated with susceptibility, studies of genetically identical monozygotic twin pairs suggest that the genetic make‐up is responsible for only about 20%–30% of the risk to develop disease, while the rest is contributed by milieu factors. Recently, a new, unexpected player has entered the ranks of MS‐triggering or facilitating elements: the human gut microbiota. In this review, we summarize the present knowledge of microbial effects on formation of a pathogenic autoreactive immune response targeting the distant central nervous system and delineate the approaches, both in people with MS and in MS animal models, which have led to this concept. Finally, we propose that a tight combination of investigations of human patients with studies of suitable animal models is the best strategy to functionally characterize disease‐associated microbiota and thereby contribute to deciphering pathogenesis of a complex human disease. [ABSTRACT FROM AUTHOR]

Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in sFGR using molecular biology experiments and gain- or loss-of-function assays. We found that the levels of MALAT1, ERRγ, and HSD17B1 were downregulated and that of miR-424 was upregulated in the placental shares of the smaller twins. Moreover, angiogenesis was impaired in the placental share of the smaller fetus and MALAT1 could regulate the paracrine effects of trophoblasts on endothelium angiogenesis and proliferation by regulating miR-424. In trophoblasts, MALAT1 could competitively bind to miR-424 to regulate the expression of ERRγ and HSD17B1, thus regulating trophoblast invasion and migration. MALAT1 overexpression could decrease apoptosis and promote proliferation, alleviating cell damage induced by hypoxia. Taken together, the downregulation of MALAT1 can reduce the expression of ERRγ and HSD17B1 by competitively binding to miR-424, impairing the proangiogenic effect of trophoblasts, trophoblast invasion and migration, and the ability of trophoblasts to compensate for hypoxia, which may be involved in the pathogenesis of sFGR through various aspects. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to investigate the association between the presence of placental anastomoses and intertwin differences in renin‐angiotensin‐aldosterone activation in monochorionic twins using amniotic fluid aldosterone (AF‐ALD) levels. In addition, this study also examined the association between AF‐ALD and the ALD levels in the umbilical cord blood (UCB‐ALD) in monochorionic twins. Material and Methods: This prospective study included monochorionic diamniotic (MD) twin pregnancies that were not complicated by twin‐to‐twin transfusion syndrome (TTTS) at delivery. Amniotic fluid and umbilical cord vein blood samples were collected from each twin at delivery, and the ALD levels were measured subsequently. The MD twins were divided into two groups: those with placental anastomoses and those without anastomoses owing to fetoscopic laser surgery. The differences in the AF‐ALD levels between the larger and smaller twins were analyzed. Results: The AF‐ALD levels showed a strong and significant positive correlation with UCB‐ALD levels in 131 MD twins (r = 0.804, p < 0.001). Intertwin differences were examined in 41 and 28 pairs of MD twins with and without placental anastomoses, respectively. The AF‐ALD levels in the smaller twins were significantly higher than those in the larger twins among the pairs of MD twins with placental anastomoses (p = 0.003); however, no statistically significant intertwin differences were observed among the twins without placental anastomoses (p > 0.05). Conclusions: The AF‐ALD levels reflect the UCB‐ALD levels in MD twins. The presence of placental anastomoses led to intertwin discordance in the ALD levels in MD twins even uncomplicated with TTTS. It was considered that monochorionic twins have this clinical background, and it leads to the development of TTTS. [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]

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]

Objective: Single intrauterine fetal death Background: One of the obstetric complications of twin pregnancy is the intrauterine death of one fetus. A death that occurs in the first trimester usually leads to fewer complications than a death in the second and third trimester. In the second and third trimesters, single fetal death of twin pregnancy was reported to increase the death, preterm birth, and neurological injury of the surviving co-twin. Although rare, it can trigger a coagulation defect in the mother as well. Neurological morbidities were also more common in monochorionic twins than in dichorionic gestation. Thus, a consideration of pregnancy termination might persist. Case Report: We present a case of a primigravida woman with a monochorionic twin pregnancy with intrauterine death of one fetus at 20-21 weeks of gestation. We treated this patient with pregnancy continuation under close monitoring for more than 12 weeks, until she delivered the surviving baby at term. The outcome of the surviving baby was a normal condition and appropriate weight, and no fetal morbidity, and there was no maternal morbidity related to coagulation disorder in the mother. Conclusions: Conservative management under close monitoring until term in monochorionic twin pregnancy with single fetal death could be the best option to obtain a favorable outcome. We recommend conservative management with close surveillance monitoring using non-stress tests after 32 weeks, biweekly ultrasound, and at least one maternal coagulation profile test. [ABSTRACT FROM AUTHOR]

Objective This study investigated the clinical outcome of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). Study Design International Peace Maternal and Child Health Hospital of Shanghai ultrasound database was investigated to identify all MCDA delivered from January 2013 to December 2017. After identifying 43 pairs of MCDA twins with sIUGR and 282 pairs of normal MCDA twins, we compared clinical outcomes between the two groups. Results Compared with normal twins, sIUGR fetuses had significantly shorter gestational age at delivery, smaller average birth weight of both twins, more significant intertwin difference in birth weight, lower Apgar scores, and higher intrauterine fetal demise (IUFD) rate, and smaller placental weight. The rate of abnormal umbilical cord insertions and abnormal blood flow in the ductus venosus (DV) and middle cerebral artery (MCA) is significantly higher in the sIUGR group. In addition, the subtype analysis of sIUGR groups indicated the poorest outcomes in type II with no significant difference between type I and III. Conclusion MCDA twins with sIUGR generally exhibited limited clinical outcomes than normal MCDA twins. These limitations are mainly associated with abnormal umbilical cord insertions and blood flow in the DV and MCA. Clinical outcomes differed among the three types of sIUGR, with type II having the worst prognosis and the highest IUFD rate. Key points sIUGR generally exhibited limited clinical outcomes than normal MCDA twins. These limitations are mainly associated with blood flow of the DV and MCA. sIUGR with type II has the worst prognosis and the highest IUFD rate. [ABSTRACT FROM AUTHOR]

Introduction: The etiology of osteochondrosis dissecans (OCD), a chondropathy associated with detachment of the subchondral bone and the overlaying cartilage, is not yet fully understood. While repetitive physical exercise-related stress is usually assumed to be the main risk factor for the occurrence of OCD, genetic predisposition could have an underestimated influence on the development of the disease. Case report: We report a case of monozygotic twins with almost identical stages of bilateral osteochondrosis dissecans of the knee joint. In both patients, initially, a unilateral lesion occurred; despite restricted physical exercise, in the further course of the disease a lesion also developed on the contralateral side. While the lesion found most recently demonstrated an ongoing healing process at a 6-month follow-up, the other three lesions showed a natural course of healing under conservative treatment with significant clinical as well as radiological improvements after one year and complete consolidation in magnetic resonance imaging (MRI) after 2 years. Conclusion: There could be a genetic component to the development of OCD, although this has not yet been proven. Based on a two-year MRI follow-up, we were able to show the self-limiting characteristics of juvenile osteochondrosis dissecans. [ABSTRACT FROM AUTHOR]

This article discusses the potential of medicinal plants in combating age-related brain decline by mitigating the harmful effects of reactive oxygen species (ROS) on the brain. The oxidative damage theory suggests that ROS are key drivers of aging and contribute to the development of diseases. The article highlights the antioxidant and anti-inflammatory properties of medicinal plants such as Euonymus alatus leaf extract, Curcuma longa, and compounds derived from plants like resveratrol and quercetin. The neuroprotective properties of these phytochemicals are associated with their ability to reduce oxidative stress levels and enhance the production of neurotrophins, which are critical for neuronal survival and function. The article also mentions the potential of nanotechnology in enhancing the antioxidant properties of phytochemicals. Overall, this research edition emphasizes the significance of natural remedies in combating neurodegeneration and offers insights into the future of therapeutic interventions for neurological disorders. [Extracted from the article]

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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]

Introduction: The aim of the study was to explore patients' perspectives on diagnosis and treatment options for complicated monochorionic multiple gestations, and experiences with fetoscopic laser photocoagulation. Methods: This is a prospective cohort study of patients undergoing laser photocoagulation. Participants were interviewed during pregnancy and the postpartum period. Qualitative analysis was performed. Result: Twenty-seven patients who were candidates for laser photocoagulation were included. All elected to have laser photocoagulation. Patients chose surgery with goals of improving survival, decreasing the risk of preterm delivery, and improving the long-term health of their fetuses. They demonstrated accurate knowledge of the risks and benefits of treatment. Most (74%) felt that laser photocoagulation represented their only viable clinical option. Few seriously considered pregnancy termination or selective reduction (7% and 11% respectively). Postpartum, patients expressed no regrets about their decisions for surgery, but many felt unprepared for the challenges of preterm delivery. Conclusion: Participants weighed treatment options similarly to fetal specialists. They acknowledged but did not seriously consider treatments other than fetoscopic laser photocoagulation and were highly motivated to do whatever they could to improve outcomes for their fetuses. [ABSTRACT FROM AUTHOR]