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Objective: To evaluate whether there is a differential benefit of planned Cesarean delivery (CD) over planned vaginal delivery (VD) in women with a twin pregnancy and the first twin in cephalic presentation, depending on prespecified baseline maternal and pregnancy characteristics, and/or gestational age (GA) at delivery. Methods: This was a secondary analysis of the Twin Birth Study, which included 2804 women with a twin pregnancy and the first twin (Twin A) in cephalic presentation between 32 + 0 and 38 + 6 weeks' gestation at 106 centers in 25 countries. Women were assigned randomly to either planned CD or planned VD. The main outcome measure was composite adverse perinatal outcome, defined as the occurrence of perinatal mortality or serious neonatal morbidity in at least one twin. The baseline maternal and pregnancy characteristics (markers) considered were maternal age, parity, history of CD, use of antenatal corticosteroids, estimated fetal weight (EFW) of Twin A, EFW of Twin B, > 25% difference in EFW between the twins, presentation of Twin B, chorionicity on ultrasound, method of conception, complications of pregnancy, ruptured membranes at randomization and GA at randomization. Separate logistic regression models were developed for each marker in order to model composite adverse perinatal outcome as a function of the specific marker, planned delivery mode and the interaction between these two terms. In addition, multivariable logistic regression analysis with backward variable elimination was performed separately in each arm of the trial. The association between planned mode of delivery and composite adverse perinatal outcome, according to GA at delivery, was assessed using logistic regression analysis. Results: Of the 2804 women initially randomized, 1391 were included in each study arm. None of the studied baseline markers was associated with a differential benefit of planned CD over planned VD in the rate of composite adverse perinatal outcome. GA at delivery was associated differentially with composite adverse perinatal outcome in the treatment arms (P for interaction < 0.001). Among pregnancies delivered at 32 + 0 to 36 + 6 weeks, there was a trend towards a lower rate of composite adverse perinatal outcome in those in the planned‐VD group compared with those in planned‐CD group (29 (2.2%) vs 48 (3.6%) cases; odds ratio (OR) 0.62 (95% CI, 0.37–1.03)). In pregnancies delivered at or after 37 + 0 weeks, planned VD was associated with a significantly higher rate of composite adverse perinatal outcome, as compared with planned CD (23 (1.5%) vs 10 (0.7%) cases; OR, 2.25 (95% CI, 1.06–4.77)). Conclusion: The perinatal outcome of twin pregnancies with the first twin in cephalic presentation may differ depending on GA at delivery and planned mode of delivery. At 32–37 weeks, planned VD seems to be favorable, while, from around 37 weeks onwards, planned CD might be safer. The absolute risks of adverse perinatal outcomes at term are low and must be weighed against the increased maternal risks associated with planned CD. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Does planned caesarean compared with planned vaginal birth lower the risk of problematic urinary stress, faecal, or flatal incontinence?Design: Women between 320/7 and 386/7 weeks of gestation with a twin pregnancy were randomised to planned caesarean or planned vaginal birth.Setting: The trial took place at 106 centres in 25 countries.Population: A total of 2305 of the 2804 women enrolled in the study completed questionnaires at 2 years (82.2% follow-up): 1155 in the planned caesarean group and 1150 in the planned vaginal birth group.Methods: A structured self-administered questionnaire completed at 2 years postpartum.Main Outcome Measures: The primary maternal outcome of the Twin Birth Study was problematic urinary stress, or fecal, or flatal incontinence at 2 years RESULTS: Women in the planned caesarean group had lower problematic urinary stress incontinence rates compared with women in the planned vaginal birth group [93/1147 (8.11%) versus 140/1143 (12.25%); odds ratio, 0.63; 95% confidence interval, 0.47-0.83; P = 0.001]. Among those with problematic urinary stress incontinence, quality of life (measured using the Incontinence Impact Questionnaire, IIQ-7) was not different for planned caesarean versus planned vaginal birth groups [mean (SD): 18.4 (21.0) versus 19.1 (21.5); P = 0.82]. There were no differences in problematic faecal or flatal incontinence, or in other maternal outcomes.Conclusions: Among women with a twin pregnancy and no prior history of urinary stress incontinence, a management strategy of planned caesarean compared with planned vaginal birth reduces the risk of problematic urinary stress incontinence at 2 years postpartum. Our findings show that the prevalence but not the severity of urinary stress incontinence was associated with mode of birth.Funding: Canadian Institutes of Health Research (CIHR) (grant no. MCT-63164).Tweetable Abstract: For women with twins, planned caesarean compared with planned vaginal birth is associated with decreased prevalence but not severity of urinary stress incontinence at 2 years. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes at 3 months post partum for women randomised to give birth by planned caesarean section (CS) or by planned vaginal birth (VB) in the Twin Birth Study (TBS).Design: We invited women in the TBS to complete a 3-month follow-up questionnaire.Setting: Two thousand and eight hundred and four women from 25 countries.Population: Two thousand and five hundred and seventy women (92% response rate).Methods: Women randomised between 13 December 2003 and 4 April 2011 in the TBS completed a questionnaire and outcomes were compared using an intention-to-treat approach.Main Outcome and Measures: Breastfeeding, quality of life, depression, fatigue and urinary incontinence.Results: We found no clinically important differences between groups in any outcome. In the planned CS versus planned VB groups, breastfeeding at any time after birth was reported by 84.4% versus 86.4% (P = 0.13); the mean physical and mental Short Form (36) Health Survey (SF-36) quality of life scores were 51.8 versus 51.6 (P = 0.65) and 46.7 versus 46.0 (P = 0.09), respectively; the mean Multidimensional Assessment of Fatigue score was 20.3 versus 20.8 (P = 0.14); the frequency of probable depression on the Edinburgh Postnatal Depression Scale was 14.0% versus 14.8% (P = 0.57); the rate of problematic urinary incontinence was 5.5% versus 6.4% (P = 0.31); and the mean Incontinence Impact Questionnaire-7 score was 20.5 versus 20.4 (P = 0.99). Partner relationships, including painful intercourse, were similar between the groups.Conclusion: For women with twin pregnancies randomised to planned CS compared with planned VB, outcomes at 3 months post partum did not differ. The mode of birth was not associated with problematic urinary incontinence or urinary incontinence that affected the quality of life. Contrary to previous studies, breastfeeding at 3 months was not increased with planned VB.Tweetable Abstract: Planned mode of birth for twins doesn't affect maternal depression, wellbeing, incontinence or breastfeeding. [ABSTRACT FROM AUTHOR]

Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks' gestation in the United States (1995-2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999-2002 vs. 1995-1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards. [ABSTRACT FROM AUTHOR]

This study examined the effects of indoor gardening on socialization, activities of daily living (ADLs), and perceptions of loneliness in elderly nursing home residents. A total of 66 residents from two nursing homes participated in this two-phase study. In phase one, experimental group 1 participated once a week for 5 weeks in gardening activities while a control group received a 20-minute visit. While no significant differences were found between groups in socialization or perceptions of loneliness, there were significant pretest-posttest differences within groups on loneliness and guidance, reassurance of worth, social integration, and reliable alliance. The results also demonstrated gardening interventions had a significant effect on three ADLs (transfer, eating, and toileting). Phase two examined differences in the effects of a 5-week versus a 2-week intervention program. Although no significant within-group differences were noted in socialization, loneliness, or ADLs, the 5-week program was more effective in increasing socialization and physical functioning. [ABSTRACT FROM AUTHOR]

Background. Mesangial IgA1 deposition is characteristic of IgA nephropathy (IgAN). Structural abnormalities of the IgA1 glycoprotein may play a key role in its mesangial deposition, particularly the recently described abnormalities of O-glycosylation of the IgA1 hinge region. The mechanism of abnormal O-glycosylation has not yet been elucidated; it is not clear whether there is an alteration in the amino acid sequence of the hinge region, modifying the number of O-glycosylation sites available, or whether there is a post-translational defect in the glycosylation processes. [ABSTRACT FROM PUBLISHER]

Background: Glomerular deposition of IgA1 is a common feature of Henoch-Schonlein purpura, and is indistinguishable from that seen in IgA nephropathy. Serum IgA1 is abnormally O-glycosylated in IgA nephropathy, and this may contribute to mesangial IgA1 deposition and the development of glomerular injury. This altered O-glycosylation of IgA1 can be detected by its increased binding to the lectin Vicia villosa. [ABSTRACT FROM PUBLISHER]

Examines the impact of prenatal diagnosis and pregnancy termination on overall infant mortality in Canada. Implications of selective pregnancy termination for reducing infant deaths; Relative risk percentage of pregnancy terminations; Decrease in congenital anomaly related infant mortality.

OBJECTIVES: It is unclear whether declines in neonatal and infant mortality have led to changes in the occurrence of cerebral palsy. We conducted a study to examine and investigate recent temporal changes in the prevalence of cerebral palsy in a population-based cohort of very preterm infants who were 24 to 30 weeks of gestational age. METHODS: A population-based cohort of very preterm infants who were born between January 1, 1993, and December 31, 2002, was evaluated by the Perinatal Follow-up Program of Nova Scotia. Follow-up extended to age 2 years to ascertain the presence or absence of cerebral palsy and for overall survival. Infant survival and cerebral palsy rates were compared by year and also in two 5-year periods, 1993-1997 and 1998-2002. Logistic regression analyses were used to identify factors that potentially were responsible for temporal changes in cerebral palsy rates. RESULTS: A total of 672 liveborn very preterm infants were born to mothers who resided in Nova Scotia between 1993 and 2002. Infant mortality among very preterm infants decreased from 256 per 1000 live births in 1993 to 114 per 1000 live births in 2002, whereas the cerebral palsy rates increased from 44.4 per 1000 live births in 1993 to 100.0 per 1000 live births in 2002. Low gestational age, postnatal dexamethasone use, patent ductus arteriosus, severe hyaline membrane disease, resuscitation in the delivery room, and intraventricular hemorrhage were associated with higher rates of cerebral palsy, whereas antenatal corticosteroid use was associated with a lower rate. CONCLUSION: Cerebral palsy has increased substantially among very preterm infants in association with and possibly as a consequence of large declines in infant mortality. [ABSTRACT FROM AUTHOR]

Investigates illnesses associated with triplet births in Canada. Determination of fetal mortality; Decrease of infant death due to respiratory distress syndrome; Impact of short gestation and low birth weight.

Investigates changes in fetal and infant mortality due to increases in preterm birth among twins in Canada. Decline of overall fetal mortality; Causes of fetal deaths; Impact of increased obstetric intervention.

Inhibitors of the interaction of menin (MEN1) with lysine methyltransferase 2A (KMT2A) have emerged as novel therapeutic options in the treatment of genetically defined acute leukemias. Herein, we describe the structure-based design, synthesis, and biological evaluation of novel inhibitors of the menin-KMT2A interaction. Our structure-activity relationship campaign focused on achieving high antiproliferative cellular activity while mitigating risks associated with CYP3A4-dependent metabolism and hERG inhibition, which were characterized in some early clinical candidates. Our efforts resulted in the discovery of a triazine-based compound series that inhibited MV4-11 leukemia cell line proliferation with IC 50 as low as 13 nM, and selected compounds demonstrated improved in vitro ADME properties, de-risked CYP3A4 dependency, and lower hERG inhibition., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Introduction: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in trauma patients, despite chemoprophylaxis. Statins have been shown capable of acting upon the endothelium. We hypothesized that statin therapy in the pre- or in-hospital settings leads to a decreased incidence of VTE., Methods: We conducted a retrospective cohort study of injured patients who received statin therapy pre- or in-hospital. Adult, highest-level trauma activation patients admitted from January 2018 to June 2022 were included. Patients on prehospital anticoagulants, had history of inherited bleeding disorder, and who died within the first 24 hours were excluded. Statin users were matched to nonusers by statin use indications including age, current heart and cardiovascular conditions and history, hyperlipidemia, injury severity, and body mass index. Time to in-hospital statin initiation and occurrence of VTE and other complications within 60 days were collected. Differences between groups were determined by univariate, multivariable logistic regression, and Cox proportional hazard analyses., Results: Of 3,062 eligible patients, 79 were statin users, who were matched to 79 nonusers. There were no differences in admission demographics, vital signs, injury pattern, transfusion volumes, lengths of stay, or mortality between groups. The overall VTE incidence was 10.8% (17 of 158). Incidence of VTE in statin users was significantly lower (3%) than nonusers (19%; p = 0.003). Differences between statin users and nonusers were observed for rates of deep vein thrombosis (0% vs. 9%), pulmonary embolism (3% vs. 15%), and sepsis (0% vs. 5%). Exposure to statins was associated with an 82% decreased risk of developing VTE (hazard ratio, 0.18; 95% confidence interval, 0.04-0.86; p = 0.033)., Conclusion: Statin exposure was associated with decline in VTE and lower individual rates of deep vein thrombosis, pulmonary embolism, and sepsis. Our findings indicate that statins should be evaluated further as a possible adjunctive therapy for VTE chemoprophylaxis after traumatic injury., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The fabrication of complex assemblies with interesting collective properties from plasmonic nanoparticles (NPs) is often challenging. While DNA-directed self-assembly has emerged as one of the most promising approaches to forming such complex assemblies, the resulting structures tend to have large variability in gap sizes and shapes, as the DNA strands used to organize these particles are flexible, and the polydispersity of the NPs leads to variability in these critical structural features. Here, we use a new strategy termed docking to DNA origami cages (D-DOC) to organize spherical NPs into a linear heterotrimer with a precisely defined geometrical arrangement. Instead of binding NPs to the exterior of the DNA templates, D-DOC binds the NPs to either the interior or the opening of a 3D cage, which significantly reduces the variability of critical structural features by incorporating multiple diametrically arranged capture strands to tether NPs. Additionally, such a spatial arrangement of the capture strand can work synergistically with shape complementarity to achieve tighter confinement. To assemble NPs via D-DOC, we developed a multistep assembly process that first encapsulates an NP inside a cage and then binds two other NPs to the openings. Microscopic characterization shows low variability in the bond angles and gap sizes. Both UV-vis absorption and surface-enhanced Raman scattering (SERS) measurements showed strong plasmonic coupling that aligned with predictions by electrodynamic simulations, further confirming the precision of the assembly. These results suggest D-DOC could open new opportunities in biomolecular sensing, SERS and fluorescence spectroscopies, and energy harvesting through the self-assembly of NPs into more complex 3D assemblies., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

We conducted a narrative literature review to examine contributing factors of disparities in tobacco usage and outcomes affecting Black Americans. We propose potential solutions that can be used to effectively address these disparities. We identified historical factors; socioeconomic factors; targeted marketing/advertising; the influence of racism/discrimination; neighborhood socioeconomic disadvantage; and mass incarceration. We call for more thorough examinations of these factors as a key element of tobacco-focused research and interventions to eliminate the disproportionate burdens faced by Black Americans. We advocate for greater emphases on the impacts of personal and structural racism on tobacco usage and outcomes affecting Black Americans.