BACKGROUND: While ambient air pollution has been associated with fetal growth in singletons, its correlation among twins is not well-established due to limited research in this area.
METHODS: The effects of exposure to PM2.5 particulate matter and its main components during pregnancy on birth weight and the incidence of large for gestational age (LGA) were investigated in 6177 twins born after in vitro fertilization at the Center for Reproductive Medicine of Shanghai Ninth People\'s Hospital (Shanghai, China) between 2007 and 2021. Other birth weight-related outcomes included macrosomia, low birth weight, very low birth weight, and small for gestational age (SGA). The associations of PM2.5 exposure with birth weight outcomes were analyzed using linear mixed-effect models and random-effect logistic regression models. Distributed lag models were incorporated to estimate the time-varying associations.
RESULTS: The findings revealed that an interquartile range (IQR) increase (18 μg/m3) in PM2.5 exposure over the entire pregnancy was associated with a significant increase (57.06 g, 95 % confidence interval [CI]: 30.91, 83.22) in the total birth weight of twins. The effect was more pronounced in larger fetuses (34.93 g, 95 % CI: 21.13, 48.72) compared to smaller fetuses (21.77 g, 95 % CI: 6.94, 36.60) within twin pregnancies. Additionally, an IQR increase in PM2.5 exposure over the entire pregnancy was associated with a 34 % increase in the risk of LGA (95 % CI: 11 %, 63 %). Furthermore, specific chemical components of PM2.5, such as sulfate (SO42-), exhibited effect estimates comparable to the PM2.5 total mass.
CONCLUSIONS: Overall, the findings indicate that exposures to PM2.5 and its specific components are associated with fetal overgrowth in twins.

暂无摘要。

BACKGROUND: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers.
METHODS: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causation between Aβs and t-Tau.
RESULTS: No clear evidence that Aβ40 or Aβ42 directly causes changes in t-Tau was observed; the alternative causal hypotheses also fit the data well. In contrast, exploratory analyses suggested a causal impact of the Aβ biomarkers on NFL. Separately, reciprocal causation was observed between t-Tau and NFL.
CONCLUSIONS: Plasma Aβ40 or Aβ42 do not appear to have a direct causal impact on t-Tau. In contrast, Aβ aggregation may causally impact NFL in cognitively unimpaired men in their late 60s.

This study investigates the association between maternal exposure to particulate matter (PM10) and nitric dioxide (NO2) during the first, second and third trimester and placental weight and birth weight/placental weight (BW/PW) ratio in twins at birth.
Cross-sectional data of 3340 twins from the East Flanders Prospective Twin Survey was used. Air pollutant exposure was estimated via spatial temporal interpolation. Univariable and multivariable mixed model analyses with a random intercept to account for the relatedness of newborns were conducted for twins with separate placentas. Twin pairs with one placental mass were studied with linear and logistic regression.
In the third trimester, for each 10 μm/m3 increase in PM10 or NO2 placental weight decreased -19.7 g (95%-C.I. -35.1; -4.3) and -17.7 g (95%-C.I. -30.4; -0.5) respectively, in moderate to late preterm twins with separate placentas. Consequently, BW/PW ratio increased with higher air pollution exposure. PM10 exposure in the last week of pregnancy was associated with a higher odds ratio (OR) of 1.20 (95%-C.I. 1.00; 1.44) for a \"small for gestational age placenta\" (placental weight <10th percentile). Conversely, first trimester air pollutant exposure was associated with lower ORs of 0.55 (95%-C.I. 0.35; 0.88) and 0.60 (95%-C.I. 0.42; 0.84).
The association of PM10 and NO2 on placental weight is trimester-specific, differs for twins with one versus two placentas and is most pronounced in moderate to late preterm twins. Longitudinal studies are needed to better understand the relationship between air pollutant exposure and placental weight evolution across different trimesters.

BACKGROUND: This retrospective study investigated the hypothesis that maternal hemoglobin (Hb) levels in twin pregnancy fall between the first and second trimesters and that higher falls are associated with higher gestational age at birth and higher birthweight (BW).
METHODS: The study population was defined as pregnant women with twin pregnancies delivering two live, phenotypically normal neonates, after 24+0 weeks of gestation, between October 2009 and September 2021 at an inner London maternity unit. Maternal Hb and mean corpuscular volume (MCV), at ≤14+0 weeks of gestation (Hb1) and again at 20+0-30+0 weeks gestation (Hb2) were recorded from the Hospital\'s perinatal database. MCV was used as a possible indicator of iron deficiency anemia. The association of Hb drop, defined as [Hb1(adjusted for gestational age) - Hb2], and MCV values with gestational age at birth, BW of both twins and delivery of small for gestational age (SGA) neonates, defined as BW <10th percentile for gestation, was evaluated.
RESULTS: 923 pregnant women with twin pregnancies were included. Maternal Hb1 did not correlate with any outcomes measured. However, a lower Hb2 and a larger Hb drop was associated with a higher gestational age at birth (p < 0.001), a larger BW of twin 1 and 2 (p < 0.001 for both) and a reduction in the incidence of delivering one or two SGA neonates (p < 0.001 for both). MCV values did not correlate significantly with these outcomes.
CONCLUSIONS: This study showed that in twin pregnancy, a larger maternal Hb drop from the first to the second trimester is associated with a higher gestational age at birth and a larger BW. This change may represent a larger plasma volume expansion.

BACKGROUND: This study investigates the relationship between cognitive functioning and 59 modifiable and intrinsic factors at the cusp of midlife.
METHODS: We analyzed data from 1221 participants in the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife; Mage = 33.20, %Female = 52.74). We assessed the impact of 59 factors on cognitive functioning using regularized regression and co-twin control models, controlling for earlier-life cognitive functioning and gray matter volume.
RESULTS: Eight robust factors were identified, including education attainment, cognitive complexity, purpose-in-life, and smoking status. Twins reporting higher levels of cognitive complexity and purpose-in-life showed better cognitive performance than their cotwin, while smoking was negatively associated. Using meta-analytically derived effect size threshold, we additionally identified that twins experiencing more financial difficulty tend to perform less well compared with their cotwin.
CONCLUSIONS: The findings highlight the early midlife link between cognitive functioning and lifestyle/psychological factors, beyond prior cognitive performance, brain status, genetic and familial confounders. Our results further highlight the potential of established adulthood as a crucial window for dementia prevention interventions targeting lifestyle and psychosocial factors.
UNASSIGNED: Cog complexity(+), purpose-in-life(+) were associated with cognition in early midlife.Smoking(-) was also associated with cognition in early midlife.Results were consistent controlling for genetic and environmental confounds.Association between EA and cognition might be mostly genetic and familial confounded.

OBJECTIVE: To evaluate the relative impact of different strategies of medically assisted reproduction (MAR), i.e. first line treatment (ovarian stimulation with or without intrauterine insemination) and in vitro fertilization (IVF) procedures (conventional IVF or intracytoplasmic sperm injection), on the risk of multiple births.
METHODS: We utilized the health care utilization databases of the Lombardy region to identify births resulting from MAR between 2007 and 2022. We gathered data on the total number of multiple births and calculated the prevalence rate by dividing the number of multiples by the total number of births. To examine the temporal trend in the proportion of multiple births after MAR over time, a linear regression model was employed separately for different types of techniques and in strata of maternal age.
RESULTS: A total of 30,900 births after MAR were included; 4485 (14.5 %) first line treatments and 26,415 (85.5 %) IVF techniques. Overall, 4823 (15.6 %) multiple births were identified. The frequency of multiple births over the study period decreased from 22.0 % in 2007 to 8.7 % in 2022 (p < 0.01). Multiple births from first line treatments were stable ranging from 13.5 % in 2007-2008 to 12.0 % in 2021-2022 (p = 0.29). Multiple births from IVF procedures decreased from 23.8 % in 2007-2008 to 8.4 % in 2021-2022 (p < 0.01). Stratifying for maternal age (i.e. < 35 and ≥ 35 years), the trends remained consistent.
CONCLUSIONS: The reduction in multiple births has been influenced by changes in IVF strategy and procedures. The decline has been gradual but steady since 2009, when a law restricting embryo freezing was repealed in Italy. In contrast, the proportion of multiple births resulting from first line treatments has remained constant over time. Despite declining, multiple births from MAR remained about one order of magnitude higher than those from spontaneous pregnancies.

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

Biallelic pathogenic variants in CCN6 cause progressive pseudorheumatoid dysplasia (PPD), a rare skeletal dysplasia. The predominant features include noninflammatory progressive joint stiffness and enlargement, which are not unique to this condition. Nearly 100% of the reported variants are single nucleotide variants or small indels, and missing of a second variant has been reported. Genome sequencing (GS) covers various types of variants and deep phenotyping (DP) provides detailed and precise information facilitating genetic data interpretation. The combination of GS and DP improves diagnostic yield, especially in rare and undiagnosed diseases. We identified a novel compound heterozygote involving a disease-causing copy number variant (g.112057664_112064205del) in trans with a single nucleotide variant (c.624dup(p.Cys209MetfsTer21)) in CCN6 in a pair of monozygotic twins, through the methods of GS and DP. The twins had received three nondiagnostic results before. The g.112057664_112064205del variant was missed by all the tests, and the recorded phenotypes were inaccurate or even misleading. The twins were diagnosed with PPD, ending a 13-year diagnostic odyssey. There may be other patients with PPD experiencing underdiagnosis and misdiagnosis due to inadequate genetic testing or phenotyping methods. This case highlights the critical role of GS and DP in facilitating an accurate and timely diagnosis.

A domain-resolved synchrotron single-crystal X-ray diffraction study of a LaAlO3 pseudo-merohedral twin crystal was successfully carried out in combination with powder diffraction data from the same sample. Multiscale structure information ranging from micro- to nano- to atomic scale was determined from one single crystal. There is almost no change of domain ratios at temperatures of less than 400 K indicating no movement of the domain wall. The changes in domain ratio indicating domain-wall movement were observed in the temperature range of 450 to 700 K, which is consistent with the result of the previous mechanical measurement. It is also found that the ratio of four twin components becomes equal (25%), just below phase transition temperature. These findings are important for domain engineering and theoretical studies related to LaAlO3. The temperature dependence of domain ratio was preserved in the heating and cooling cycle except for the first heating process to 840 K. Therefore, the domain structure after heating to 840 K is intrinsic to the crystal. Accurate structure parameters were determined through unit-cell parameter calibration and domain-resolved structure analysis. The method for calibration of unit-cell parameters from twin crystal data was derived and used to solve the inconsistent unit-cell parameters between single crystal and powder data in the present and previous studies.