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MedRxiv : the Preprint Server For... May 2024Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal...
BACKGROUND
Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Discordant outcomes among dizygotic twins could be explained by genetic susceptibly or protection. Among several well-recognized threats to the developing brain, Zika is a mosquito-borne, positive-stranded RNA virus that was originally isolated in Uganda and spread to cause epidemics in Africa, Asia, and the Americas. In the Americas, the virus caused congenital Zika syndrome and a multitude of neurodevelopmental disorders. As of now, there is no preventative treatment or cure for the adverse outcomes caused by prenatal Zika infection. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium was initiated in 2016 to identify factors modulating prenatal brain injury and postnatal neurodevelopmental outcomes for Zika and other prenatal viral infections.
METHODS
The Consortium has pooled information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic data repository. This repository is being mined to search for modifiers of virally induced brain injury and developmental outcomes. Multilateral partnerships include commitments with Children's National Hospital (USA), (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), and Zika (Brazil), in addition to the Centers for Disease Control and Prevention and the National Institutes of Health.
DISCUSSION
Our goal in bringing together these sets of patient data was to test the hypothesis that personal and populational genetic differences affect the severity of brain injury after a prenatal viral infection and modify neurodevelopmental outcomes. We have enrolled 4,102 mothers and 3,877 infants with 3,063 biological samples and clinical data covering over 80 phenotypic fields and 5,000 variables. There were several notable challenges in bringing together cohorts enrolled in different studies, including variability in the timepoints evaluated and the collected clinical data and biospecimens. Thus far, we have performed whole exome sequencing on 1,226 participants. Here, we present the Consortium's formation and the overarching study design. We began our investigation with prenatal Zika infection with the goal of applying this knowledge to other prenatal infections and exposures that can affect brain development.
PubMed: 38826415
DOI: 10.1101/2024.05.24.24307899 -
Children (Basel, Switzerland) Apr 2024Enteroviruses (EVs) are the most common causes of viral myocarditis in neonates. Neonatal enterovirus myocarditis manifestations range from nonspecific febrile illness...
Enteroviruses (EVs) are the most common causes of viral myocarditis in neonates. Neonatal enterovirus myocarditis manifestations range from nonspecific febrile illness to congestive heart failure and cardiogenic shock with high risk of in-hospital mortality and long-term cardiac sequelae. Early recognition is essential to undertake appropriate therapy and predict outcomes. Echocardiography and echo-derived left ventricular strain measures seem promising for these purposes. We herein report two cases of neonatal enterovirus-associated myocarditis in dichorionic diamniotic twins, with different presentation, clinical course, and intensity of treatments.
PubMed: 38790501
DOI: 10.3390/children11050506 -
HGG Advances May 2024While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in...
While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.
PubMed: 38773773
DOI: 10.1016/j.xhgg.2024.100301 -
BMC Pregnancy and Childbirth May 2024To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived... (Comparative Study)
Comparative Study
Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison.
OBJECTIVE
To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally.
METHODS
We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally.
RESULT
MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05).
CONCLUSION
Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.
Topics: Humans; Female; Pregnancy; Pregnancy, Twin; Reproductive Techniques, Assisted; Pregnancy Outcome; Retrospective Studies; Adult; Twins, Monozygotic; Chorion; Premature Birth; Twins, Dizygotic; Infant, Newborn; Placenta Previa
PubMed: 38698326
DOI: 10.1186/s12884-024-06521-z -
Genes Apr 2024The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of...
The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ twins, 69.91% females; mean age-75.79 ± 5.44) were studied. Peripheral blood gene expression was assessed using Illumina microarrays. A heritability analysis was performed using structural equation modelling. There were 5269 probes (19.9%) from 4603 unique genes (23.9%) (total 26,537 probes from 19,256 genes) that were significantly heritable (mean h = 0.40). A pathway analysis of the top 10% of significant genes showed enrichment for the immune response and ageing-associated genes. In a comparison with two other gene expression twin heritability studies using adults from across the lifespan, there were 38 out of 9479 overlapping genes that were significantly heritable. In conclusion, our study found ~24% of the available genes for analysis were heritable in older adults, with only a small number common across studies that used samples from across adulthood, indicating the importance of examining gene expression in older age groups.
Topics: Humans; Female; Aged; Male; Aged, 80 and over; Aging; Twins, Dizygotic; Twins, Monozygotic; Gene Expression
PubMed: 38674429
DOI: 10.3390/genes15040495 -
JAMA Psychiatry Jun 2024
Topics: Humans; Obsessive-Compulsive Disorder; Male; Female; Diseases in Twins; Adult; Twins, Monozygotic; Twins, Dizygotic; Genetic Predisposition to Disease
PubMed: 38568562
DOI: 10.1001/jamapsychiatry.2024.0299 -
NeuroImage. Clinical 2024Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus,...
OBJECTIVE
Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS.
METHODS
FSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV.
RESULTS
54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003).
CONCLUSION
We offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.
Topics: Humans; Adult; Female; Male; Twins, Monozygotic; Magnetic Resonance Imaging; Multiple Sclerosis; Middle Aged; Brain; Young Adult; Age of Onset; Organ Size
PubMed: 38522363
DOI: 10.1016/j.nicl.2024.103597 -
Clinical Case Reports Mar 2024To raise awareness about the increasing incidence of superfetation and heterotopic pregnancy in patients with ovarian induction, their insidious symptoms of abdominal...
KEY CLINICAL MESSAGE
To raise awareness about the increasing incidence of superfetation and heterotopic pregnancy in patients with ovarian induction, their insidious symptoms of abdominal pain, anemia, and hemodynamic instability in early pregnancy, and the usefulness of transvaginal ultrasound (TVUS) and quantitative beta human chorionic gonadotrophin (b-hCG) for diagnosis.
ABSTRACT
Superfetation, occurrence of ovulation, fertilization, and implantation during an ongoing pregnancy and heterotopic pregnancy (HP) simultaneous presence of intrauterine and extrauterine pregnancies are infrequent phenomena. We report a case where both coexisted, challenges in diagnosis and management and association with the widespread use of assisted reproductive technologies (ARTs). A 32-year-old woman, who previously underwent ovulation induction therapy, presented with abdominal pain at 8 weeks pregnancy according to her last menstrual period. The patient had high quantitative serum beta-human chorionic gonadotropin (b-hCG) (30,883 mIU/mL). She was vitally stable and not anemic. Transvaginal ultrasound (TVUS) revealed two pregnancies at different gestational ages: an intrauterine pregnancy at 5 weeks and 3 days, and a right intact tubal ectopic pregnancy at 10 weeks and 5 days. Superfetation resulting in HP was then diagnosed. Subsequently, the patient underwent right laparoscopic salpingectomy. The intrauterine pregnancy progressed normally, resulting in delivery of a healthy full-term neonate via Cesarean section at 38 weeks. Superfetation is typically rare from suppression of follicular development and ovulation during pregnancy. Various theories have been proposed to explain its etiology, including polyovulation, delayed blastocyst implantation, and abnormal estrogen and b-hCG surges. In superfetation, an embryo resulting from a previous conception coexists with another embryo, either intrauterine, resulting in diamniotic dizygotic twins with significantly different gestational ages, or extrauterine resulting in HP. Despite being particularly challenging to diagnose because its presenting symptoms can overlap with those of other more common clinical conditions in early pregnancy, HP is increasingly seen with ARTs. In addition, the treatment of HP is versatile, ranging from expectant management to laparoscopic surgery. High level of suspicion for HP and superfetation is crucial in patients who, after ART, present with abdominal pain, hemodynamic instability, or anemia. Additionally, patients planning to undergo subsequent ART cycles should be thoroughly screened with b-hCG and TVUS to exclude an ongoing intrauterine or extrauterine pregnancy.
PubMed: 38505479
DOI: 10.1002/ccr3.8571 -
Translational Psychiatry Mar 2024Flow is a phenomenon where one experiences optimal challenge, marked by an intense, effortless, and rewarding concentration on a task. Past research shows that flow...
Flow is a phenomenon where one experiences optimal challenge, marked by an intense, effortless, and rewarding concentration on a task. Past research shows that flow proneness is associated with good mental and cardiovascular health. However, this research has been primarily cross-sectional, based on self-report data, and has not controlled for potential confounding effects of neuroticism. In a large, longitudinal twin sample (N = 9361), we used nationwide patient registry data to test whether flow proneness predicted registry-based diagnoses of depression, anxiety, schizophrenia, bipolar disorder, stress-related disorders, or cardiovascular diseases. We used survival analyses taking time to diagnosis into account to test if (a) there is a relationship between flow proneness and health diagnoses over time, (b) neuroticism confounds this relationship, and (c) the relationship remains present within discordant monozygotic twin pairs (N = 952), thereby controlling for genetic and shared environmental confounding. Individuals with higher flow proneness had a decreased risk of receiving diagnoses for depression (16%; CI [14%, 18%]), anxiety (16%; CI [13%, 18%]), schizophrenia (15%; CI [4%, 25%]), bipolar (12%; CI [6%, 18%]), stress-related (9%; CI [9%, 12%]), and cardiovascular disorders (4%; CI [1%, 8%]). When controlling for neuroticism, higher flow proneness still decreased the risk of depression (6%; CI [3%, 9%]) and anxiety diagnoses (5%; CI [1%, 8%]). Monozygotic twins who experienced more flow than their co-twin had a lower risk for depression (16%; CI [5%, 26%]) and anxiety (13%; CI [1%, 24%]), though only the association with depression remained significant when also controlling for neuroticism (13%; CI [1%, 24%]). Findings are in line with a causal protective role of flow experiences on depression and potentially anxiety and highlight that neuroticism and familial factors are notable confounding factors in observed associations between flow proneness and health outcomes.
Topics: Humans; Cross-Sectional Studies; Prospective Studies; Twins, Dizygotic; Anxiety; Anxiety Disorders; Twins, Monozygotic
PubMed: 38480692
DOI: 10.1038/s41398-024-02855-6