Aligned grains and scattered light found in gaps of planet-forming disk.

Polarized (sub)millimetre emission from dust grains in circumstellar disks was initially thought to be because of grains aligned with the magnetic field1,2. However, higher-resolution multi-wavelength observations3-5 and improved models6-10 found that this polarization is dominated by self-scattering at shorter wavelengths (for example, 870 µm) and by grains aligned with something other than magnetic fields at longer wavelengths (for example, 3 mm). Nevertheless, the polarization signal is expected to depend on the underlying substructure11-13, and observations until now have been unable to resolve polarization in multiple rings and gaps. HL Tau, a protoplanetary disk located 147.3 ± 0.5 pc away14, is the brightest class I or class II disk at millimetre-submillimetre wavelengths. Here we show deep, high-resolution polarization observations of HL Tau at 870 µm, resolving polarization in both the rings and the gaps. We find that the gaps have polarization angles with a notable azimuthal component and a higher polarization fraction than the rings. Our models show that the disk polarization is due to both scattering and emission from the aligned effectively prolate grains. The intrinsic polarization of aligned dust grains is probably more than 10%, which is much higher than that expected in low-resolution observations (about 1%). Asymmetries and dust features that are not seen in non-polarimetric observations are seen in the polarization observations.

The association of obesity with post-cesarean inpatient opioid consumption.

BACKGROUND: Obesity and prescription opioid misuse are important public health concerns in the United States. A common intersection occurs when women with obesity undergo cesarean birth and receive narcotic medications for postpartum pain. OBJECTIVE: To examine the association between obesity and inpatient opioid use after cesarean birth. METHODS: A retrospective cohort study of patients that underwent cesarean birth in 2015-2018. Primary outcome was post-cesarean delivery opioid consumption starting 24 h after delivery measured as morphine milliequivalents per hour (MME/h). Secondary outcome was MME/h consumption in the highest quartile of all subjects. Opioid consumption was compared between three BMI groups: non-obese BMI 18.5-29.9 kg/m2; obese BMI 30.0-39.9 kg/m2; and morbidly obese BMI ≥ 40.0 kg/m2 using univariable and multivariable analyses. RESULTS: Of 1620 patients meeting inclusion criteria, 496 (30.6%) were in the non-obese group, 753 (46.5%) were in the obese group, and 371 (22.9%) were in the morbidly obese group. In the univariate analysis, patients with obesity and morbid obesity required higher MME/h than patients in the non-obese group [1.3 MME/h (IQR 0.1, 2.4) vs. 1.6 MME/h (IQR 0.5, 2.8) vs. 1.8 MME/h (IQR 0.8, 2.9), for non-obese, obese, and morbidly obese groups respectively, p < 0.001]. In the multivariable analysis, this association did not persist. In contrast, subjects in the obese and morbidly obese groups were more likely to be in the highest quartile of MME/h opioid consumption compared with those in the non-obese group (23.5% vs. 48.1% vs. 28.4%, p < 0.001, respectively); with aOR 1.42 (95% CI 1.07-1.89, p = 0.016) and aOR 1.60 (95% CI 1.16-2.22, p = 0.005) for patients with obesity and morbid obesity, respectively. CONCLUSION: Maternal obesity was not associated with higher hourly MME consumption during inpatient stay after cesarean birth. However, patients with obesity and morbid obesity were significantly more likely to be in the top quartile of MME hourly consumption.

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.

BACKGROUND: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. OBJECTIVES: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. METHODS: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. RESULTS: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. CONCLUSIONS: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Preterm preeclampsia as an independent risk factor for thromboembolism in a large national cohort.

BACKGROUND: Preterm preeclampsia, a product of vascular dysfunction, is associated with prolonged hospital admission and proteinuria, significant risk factors for thromboembolism in pregnancy. The risk of thromboembolism in preterm preeclampsia warrants further investigation. OBJECTIVE: To determine the relationship between preterm preeclampsia and thromboembolic risk. We hypothesize that preterm preeclampsia is an independent risk factor for thromboembolism in pregnancy. STUDY DESIGN: This is a retrospective cohort study using the National Inpatient Sample database via Healthcare Cost and Utilization Project-Agency for Healthcare Cost and Utilization Project from 2017-2019. All subjects with an International Classification of Diseases, Tenth Revision code for pregnancy or peripartum encounter were included. Subjects were excluded if the gestational age at delivery was <20 weeks or if they had a history of thromboembolism, inherited thrombophilia, or antiphospholipid syndrome. Patients with preterm (delivered <37 weeks) preeclampsia and term (delivered ≥37 weeks) preeclampsia were compared with those without preeclampsia. The primary outcome was a composite of any thromboembolic event, including pulmonary embolism, deep vein thrombosis, cerebral thrombosis or transient ischemic attack, or other thromboses. The secondary outcomes were rates of each type of thromboembolic event. The groups were compared via variance analysis, chi-square, and logistic regression analyses. The logistic regression included those variables that differed between groups with P<.05. RESULTS: Of individuals in the database, >2.2 million met the inclusion criteria. A total of 56,446 (2.7%) had preterm preeclampsia, and 86,152 (6.7%) had term preeclampsia. Those with preterm preeclampsia were more likely to be older, identify as non-Hispanic black, have obesity, have chronic hypertension among other chronic diseases, and be in the lowest quartile of income (P<.001). Among patients with preterm preeclampsia, 0.32% experienced thromboembolism, whereas those with term preeclampsia and without preeclampsia experienced thromboembolism at 0.10% and 0.09%, respectively. After controlling for confounders that differed between groups with P<.05, preterm preeclampsia remained independently associated with any thromboembolic event (adjusted odds ratio, 2.21 [95% confidence interval, 1.84-2.65]), and each type of thromboembolism. Term preeclampsia was not associated with an increased risk of thromboembolism (adjusted odds ratio, 1.18 [95% confidence interval, 0.94-1.48]). CONCLUSION: Preterm preeclampsia is independently associated with an increased risk of thromboembolic events.

Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: a systematic review and meta-analysis.

OBJECTIVE: Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder. Recently, uterine-sparing techniques have been introduced in conservative management of placenta accreta spectrum disorder to preserve fertility and potentially reduce surgical complications. However, despite patients often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcomes after conservative management of placenta accreta spectrum disorder. Thus, we aimed to perform a systematic review and meta-analysis to assess these outcomes. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a history of placenta accreta spectrum disorder who underwent any type of conservative management. METHODS: The R programming language with the "meta" package was used. The random-effects model and inverse variance method were used to pool the proportion of pregnancy outcomes. RESULTS: We identified 5 studies involving 1458 participants that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1) and resection surgery (n=1), and was not reported in 3 studies. The rate of placenta accreta spectrum disorder recurrence in the subsequent pregnancy was 11.8% (95% confidence interval, 1.1-60.3; I2=86.4%), and 1.9% (95% confidence interval, 0.0-34.1; I2=82.4%) of participants underwent cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% confidence interval, 0.3-81.4; I2=96.7%). A composite adverse maternal outcome was reported in 22.7% of participants (95% confidence interval, 0.0-99.4; I2=56.3%). CONCLUSION: Favorable pregnancy outcome is possible following successful conservation of the uterus in a placenta accreta spectrum disorder pregnancy. Approximately 1 out of 4 subsequent pregnancies following conservative management of placenta accreta spectrum disorder had considerable adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population.

Lab cognition going wild: Implementing a new portable touchscreen system in vervet monkeys.

Touchscreen technology has provided researchers with opportunities to conduct well-controlled cognitive tests with captive animals, allowing researchers to isolate individuals, select participants based on specific traits, and control aspects of the environment. In this study, we aimed to investigate the potential utility of touchscreen technology for the study of cognition in wild vervet monkeys. We assessed the viability of touchscreen testing by comparing rates of participation between wild and sanctuary-housed vervets. Additionally, we compared performance on a simple associative learning task in order to verify that wild participants are able to engage meaningfully with a touchscreen task presented in their natural environment. We presented eight groups of vervet monkeys (four wild and four sanctuary groups, totalling 240 individuals) with a portable touchscreen device. The touchscreen displayed tasks in which food rewards could be gained by touching a stimulus displayed on the screen. We assessed individuals' likelihood of interacting with the touchscreen, their frequency of participation, and their performance on a simple associative learning task. We found that sanctuary-housed monkeys were more likely to interact with the touchscreen. Participation in wild vervet monkeys was influenced by sex and age. However, monkeys in the two contexts (sanctuary vs. wild) did not differ in their performance on a simple associative learning task. This study demonstrates that touchscreen technology can be successfully deployed in a population of wild primates. This gives us a starting point to test animal cognition under natural conditions that include varying group composition, environmental challenges and ongoing activities such as foraging, which are challenging to recreate in captivity. While rates of participation were lower than those found in captivity, reasonable sample sizes can be achieved, and wild primates can successfully learn touchscreen tasks in a manner comparable to their captive counterparts.

Codeployment of Passive Samplers and Mussels Reveals Major Source of Ongoing PCB Inputs to the Anacostia River in Washington, DC.

Remedial investigations of sites contaminated with legacy pollutants like polychlorinated biphenyls (PCBs) have traditionally focused on mapping sediment contamination to develop a site conceptual model and select remedy options. Ignoring dissolved concentrations that drive transport and bioaccumulation often leads to an incomplete assessment of ongoing inputs to the water column and overestimation of potential effectiveness of sediment remediation. Here, we demonstrate the utility of codeployment of passive equilibrium samplers and freshwater mussels as dual lines of evidence to identify ongoing sources of PCBs from eight main tributaries of the Anacostia River in Washington, DC, that has been historically polluted from industrial and other human activities. The freely dissolved PCB concentrations measured using passive samplers tracked well with the accumulation in mussels and allowed predictions of biouptake within a factor of 2 for total PCBs and a factor of 4 for most congeners. One tributary was identified as the primary source of PCBs to the water column and became a focus of additional ongoing investigations. Codeployment of passive samplers and mussels provides strong lines of evidence to refine site conceptual models and identify ongoing sources critical to control to achieve river water quality standards and reduce bioaccumulation in the aquatic food web.

Evaluation of tumour surveillance protocols and outcomes in von Hippel-Lindau disease in a national health service.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis and surveillance. However, there is limited information on the "real world" management of VHL disease. METHODS: A national audit of VHL disease in the United Kingdom. RESULTS: VHL disease was managed mostly via specialist clinics coordinated through regional clinical genetics services (but frequently involving additional specialties). Over the study period, 19 genetic centres saw 842 individuals (393 males, 449 females) with a clinical and/or molecular diagnosis of VHL disease and 74 individuals (35 male, 39 female) with a prior risk of 50% (affected parent). All centres offered retinal, central nervous system and abdominal surveillance to affected individuals and at-risk relatives though surveillance details differed between centres (but complied with international recommendations). Renal lesions detected on the first surveillance scan were, on average, larger than those detected during subsequent scans and the larger the diameter at detection the greater the likelihood of early intervention. CONCLUSIONS: In a state-funded health care system individuals with a rare inherited cancer predisposition syndrome are generally able to access appropriate surveillance and patient management is improved compared to historical data. The "real world" data from this study will inform the future development of VHL management protocols.

SDHC phaeochromocytoma and paraganglioma: A UK-wide case series.

OBJECTIVE: Phaeochromocytomas and paragangliomas (PPGL) are rare, but strongly heritable tumours. Variants in succinate dehydrogenase (SDH) subunits are identified in approximately 25% of cases. However, clinical and genetic information of patients with SDHC variants are underreported. DESIGN: This retrospective case series collated data from 18 UK Genetics and Endocrinology departments. PATIENTS: Both asymptomatic and disease-affected patients with confirmed SDHC germline variants are included. MEASUREMENTS: Clinical data including tumour type and location, surveillance outcomes and interventions, SDHC genetic variant assessment, interpretation, and tumour risk calculation. RESULTS: We report 91 SDHC cases, 46 probands and 45 non-probands. Fifty-one cases were disease-affected. Median age at genetic diagnosis was 43 years (range: 11-79). Twenty-four SDHC germline variants were identified including six novel variants. Head and neck paraganglioma (HNPGL, n = 30, 65.2%), extra-adrenal paraganglioma (EAPGL, n = 13, 28.2%) and phaeochromocytomas (PCC) (n = 3, 6.5%) were present. One case had multiple PPGLs. Malignant disease was reported in 19.6% (9/46). Eight cases had non-PPGL SDHC-associated tumours, six gastrointestinal stromal tumours (GIST) and two renal cell cancers (RCC). Cumulative tumour risk (95% CI) at age 60 years was 0.94 (CI: 0.79-0.99) in probands, and 0.16 (CI: 0-0.31) in non-probands, respectively. CONCLUSIONS: This study describes the largest cohort of 91 SDHC patients worldwide. We confirm disease-affected SDHC variant cases develop isolated HNPGL disease in nearly 2/3 of patients, EAPGL and PCC in 1/3, with an increased risk of GIST and RCC. One fifth developed malignant disease, requiring comprehensive lifelong tumour screening and surveillance.

Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.

Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development.

Correlates of Insulin Selection as a First-Line Pharmacological Treatment for Gestational Diabetes.

OBJECTIVE: The aim of this study was to investigate prenatal factors associated with insulin prescription as a first-line pharmacotherapy for gestational diabetes mellitus (GDM; compared with oral antidiabetic medication) after failed medical nutrition therapy. STUDY DESIGN: This is a retrospective cohort study of 437 women with a singleton pregnancy and diagnosis of A2GDM (GDM requiring pharmacotherapy), delivering in a university hospital between 2015 and 2019. Maternal sociodemographic and clinical characteristics, as well as GDM-related factors, including provider type that manages GDM, were compared between women who received insulin versus oral antidiabetic medication (metformin or glyburide) as the first-line pharmacotherapy using univariable and multivariable analyses. RESULTS: In univariable analysis, maternal age, race and ethnicity, insurance, chronic hypertension, gestational age at GDM diagnosis, glucose level after 50-g glucose loading test, and provider type were associated with insulin prescription. In multivariable analysis, after adjusting for sociodemographic and clinical maternal factors, GDM characteristics and provider type, Hispanic ethnicity (0.26, 95% confidence interval [CI]: 0.09-0.73), and lack of insurance (0.34, 95% CI: 0.13-0.89) remained associated with lower odds of insulin prescription, whereas endocrinology management of GDM (compared with obstetrics and gynecology [OBGYN]) (8.07, 95% CI: 3.27-19.90) remained associated with higher odds of insulin prescription. CONCLUSION: Women of Hispanic ethnicity and women with no insurance were less likely to receive insulin and more likely to receive oral antidiabetic medication for GDM pharmacotherapy, while management by endocrinology was associated with higher odds of insulin prescription.This finding deserves more investigation to understand if differences are due to patient choice or a health disparity in the choice of pharmacologic agent for A2GDM. KEY POINTS: · Insulin is recommended as a first-line pharmacotherapy for gestational diabetes.. · Women of Hispanic ethnicity were less likely to receive insulin as first line.. · Lack of insurance was also associated with lower odds of insulin prescription..

Dissection of contiguous gene effects for deletions around ERF on chromosome 19.

Heterozygous intragenic loss-of-function mutations of ERF, encoding an ETS transcription factor, were previously reported to cause a novel craniosynostosis syndrome, suggesting that ERF is haploinsufficient. We describe six families harboring heterozygous deletions including, or near to, ERF, of which four were characterized by whole-genome sequencing and two by chromosomal microarray. Based on the severity of associated intellectual disability (ID), we identify three categories of ERF-associated deletions. The smallest (32 kb) and only inherited deletion included two additional centromeric genes and was not associated with ID. Three larger deletions (264-314 kb) that included at least five further centromeric genes were associated with moderate ID, suggesting that deletion of one or more of these five genes causes ID. The individual with the most severe ID had a more telomerically extending deletion, including CIC, a known ID gene. Children found to harbor ERF deletions should be referred for craniofacial assessment, to exclude occult raised intracranial pressure.

Expanding the phenotype of ASXL3-related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic variants in ASXL3.

The study aimed at widening the clinical and genetic spectrum of ASXL3-related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3-related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3-related syndrome, we define its natural history and clinical evolution occurring with age. We report familial ASXL3 pathogenic variants, characterize the phenotype in mildly affected individuals and discuss nonpenetrance. We also discuss the role of missense variants in ASXL3. We delineate a variable but consistent phenotype. The most characteristic features are neurodevelopmental delay with consistently limited speech, significant neuro-behavioral issues, hypotonia, and feeding difficulties. Distinctive features include downslanting palpebral fissures, hypertelorism, tubular nose with a prominent nasal bridge, and low-hanging columella. The presented data will inform clinical management of individuals with ASXL3-related syndrome and improve interpretation of new ASXL3 sequence variants.

Should commercial sex workers have unrestricted healthcare access across the world?

We argue commercial sex workers have rights to healthcare and psychosocial support. While decriminalization is not legally enacted in most countries, we would suggest these workers rights include freedom from harassment and opportunities to lead healthy lives. The need for healthcare access for all is heightened in the COVID-19 pandemic where some people flout rules on lockdown by engaging with commercial sex workers and may unwittingly spread SARS-CoV-2 in so doing. Unrestricted healthcare access without stigma for commercial sex workers protects them, and has a beneficial societal effect on those who engage with them and on their contacts.

Social networks and people with intellectual disabilities: A systematic review.

BACKGROUND: Despite the importance of social networks for health and well-being, relatively little is known about the ways in which adults with intellectual disabilities in the U.K. experience their social networks. METHOD: A systematic review was completed to identify research focused on the social networks of adults with intellectual disabilities. Studies published from 1990 to 2019 were identified. Studies were thematically analysed. RESULTS: Quantitative, qualitative and mixed methods studies were analysed to identify key factors influencing social networks. Experiences of people with intellectual disabilities identified themes of identity, powerlessness, inclusion, family and support. These themes are discussed with reference to theories of stigma and normalisation. CONCLUSIONS: Stigma and normalisation can be used to better understand the needs, desires and dreams of people with intellectual disabilities for ordinary relationships, from which they are regularly excluded. Implications for policy and practice are discussed in relation to building and repairing often spoiled identities.

The timing of initiation of pharmacotherapy for women with gestational diabetes mellitus.

BACKGROUND: The decision to initiate pharmacotherapy is integral in the care for pregnant women with gestational diabetes mellitus (GDM). We sought to compare pregnancy outcomes between two threshold percentages of elevated glucose values prior to initiation of pharmacotherapy for GDM. We hypothesized that a lower threshold at pharmacotherapy initiation will be associated with lower rates of adverse perinatal outcomes. METHODS: This was a retrospective cohort study of women with GDM delivering in a single tertiary care center. Pregnancy outcomes were compared using bivariable and multivariable analyses between women who started pharmacotherapy (insulin or oral hypoglycemic agent) after a failed trial of dietary modifications at two different ranges of elevated capillary blood glucose (CBG) values: Group 1 when 20-39% CBG values were above goal; Group 2 when ≥40% CBG values were above goal. The primary outcome was a composite GDM-associated neonatal adverse outcome that included: macrosomia, large for gestational age (LGA), shoulder dystocia, hypoglycemia, hyperbilirubinemia requiring phototherapy, respiratory distress syndrome, stillbirth, and neonatal demise. Secondary outcomes included cesarean delivery, preterm birth (< 37 weeks), neonatal intensive care unit (NICU) admission, and small for gestational age (SGA). RESULTS: A total of 417 women were included in the study. In univariable analysis, the composite neonatal outcome was statistically significantly higher in Group 2 compared to Group 1 (47.9% vs. 31.4%, p = 0.001). In addition, rates of preterm birth (15.7% vs 7.4%, p = 0.011), NICU admission (11.7% vs 4.0%, p = 0.006), and LGA (21.2% vs 9.1% p = 0.001) were higher in Group 2. In contrast, higher rates of SGA were noted in Group 1 (8.0% vs. 2.9%, p = 0.019). There was no difference in cesarean section rates. These findings persisted in multivariable analysis after adjusting for confounding factors (composite neonatal outcome aOR = 0.50, 95%CI [0.31-0.78]). CONCLUSIONS: Initiation of pharmacotherapy for GDM when 20-39% of CBG values are above goal, compared to ≥40%, was associated with decreased rates of adverse neonatal outcomes attributable to GDM. This was accompanied by higher rates of SGA among women receiving pharmacotherapy at the lower threshold. Additional studies are required to identify the optimal threshold of abnormal CBG values to initiate pharmacotherapy for GDM.

Maternal pregnancy vitamin D supplementation increases offspring bone formation in response to mechanical loading: Findings from a MAVIDOS Trial sub-study.

The Maternal Vitamin D Osteoporosis (MAVIDOS) trial reported higher total body bone mineral content in winter-born infants of mothers receiving vitamin D supplementation [1000 IU/day cholecalciferol] compared with placebo from 14 weeks gestation until delivery. This sub-study aimed to determine whether antenatal vitamin D supplementation altered postnatal bone formation in response to mechanical stimulation. Thirty-one children born to MAVIDOS participants randomised to either placebo (n=19) or cholecalciferol (n=12) were recruited at age 4-5 years. Children received whole body vibration (WBV) for 10 minutes on 5 consecutive days. Fasting blood samples for bone homeostasis, 25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and bone turnover markers (Pro-collagen Type 1 N-terminal propeptide, P1NP; Cross-linked C-telopeptide of Type I Collagen, CTX) were collected pre-WBV and on day 8 (D8). Mean changes (D) in P1NP (ng/ml) between baseline and D8 in the vitamin-D intervention and placebo groups were 40.6 and -92.6 respectively and mean changes (Δ) in CTX (ng/ml) were 0.034 (intervention) and -0.084 (placebo) respectively. Between-group DP1NP difference was 133.2ng/ml [95% CI 0.4, 266.0; p=0.049] and ΔCTX 0.05ng/ml (95% CI -0.159, 0.26ng/mL; p=0.62). Antenatal vitamin-D supplementation resulted in increased P1NP in response to WBV, suggesting early life vitamin D supplementation increases the anabolic response of bone to mechanical loading in children.

De novo and biallelic DEAF1 variants cause a phenotypic spectrum.

PURPOSE: To investigate the effect of different DEAF1 variants on the phenotype of patients with autosomal dominant and recessive inheritance patterns and on DEAF1 activity in vitro. METHODS: We assembled a cohort of 23 patients with de novo and biallelic DEAF1 variants, described the genotype-phenotype correlation, and investigated the differential effect of de novo and recessive variants on transcription assays using DEAF1 and Eif4g3 promoter luciferase constructs. RESULTS: The proportion of the most prevalent phenotypic features, including intellectual disability, speech delay, motor delay, autism, sleep disturbances, and a high pain threshold, were not significantly different in patients with biallelic and pathogenic de novo DEAF1 variants. However, microcephaly was exclusively observed in patients with recessive variants (p < 0.0001). CONCLUSION: We propose that different variants in the DEAF1 gene result in a phenotypic spectrum centered around neurodevelopmental delay. While a pathogenic de novo dominant variant would also incapacitate the product of the wild-type allele and result in a dominant-negative effect, a combination of two recessive variants would result in a partial loss of function. Because the clinical picture can be nonspecific, detailed phenotype information, segregation, and functional analysis are fundamental to determine the pathogenicity of novel variants and to improve the care of these patients.

Case report of massive hemoptysis in pregnancy requiring veno-venous extracorporeal membrane oxygenation.

Hemoptysis in pregnancy is rare and can be life-threatening. This case describes management of hemoptysis in pregnancy requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO). The patient presented with massive hemoptysis in respiratory failure at 26 weeks gestation. VV-ECMO was utilized for maternal stability due to severe hypoxia from lung parenchymal damage. An extensive work-up for hemoptysis returned negative except for an elevated Bordetella pertussis IgG antibody. The patient was delivered via cesarean section with a complicated post-partum course. She and the infant were discharged in stable condition after long hospital stays. Prior publications describing VV-ECMO use in pregnancy are limited to treatment of respiratory infections such as influenza or pneumonia. This case is the first in the literature to describe VV-ECMO utilization for hemoptysis in pregnancy, specifically, and demonstrates its significant benefit in cases of respiratory failure due to hemoptysis.

Multitarget transcranial direct current stimulation for freezing of gait in Parkinson's disease.

BACKGROUND: Recent findings suggest that transcranial direct current stimulation of the primary motor cortex may ameliorate freezing of gait. However, the effects of multitarget simultaneous stimulation of motor and cognitive networks are mostly unknown. The objective of this study was to evaluate the effects of multitarget transcranial direct current stimulation of the primary motor cortex and left dorsolateral prefrontal cortex on freezing of gait and related outcomes. METHODS: Twenty patients with Parkinson's disease and freezing of gait received 20 minutes of transcranial direct current stimulation on 3 separate visits. Transcranial direct current stimulation targeted the primary motor cortex and left dorsolateral prefrontal cortex simultaneously, primary motor cortex only, or sham stimulation (order randomized and double-blinded assessments). Participants completed a freezing of gait-provoking test, the Timed Up and Go, and the Stroop test before and after each transcranial direct current stimulation session. RESULTS: Performance on the freezing of gait-provoking test (P = 0.010), Timed Up and Go (P = 0.006), and the Stroop test (P = 0.016) improved after simultaneous stimulation of the primary motor cortex and left dorsolateral prefrontal cortex, but not after primary motor cortex only or sham stimulation. CONCLUSIONS: Transcranial direct current stimulation designed to simultaneously target motor and cognitive regions apparently induces immediate aftereffects in the brain that translate into reduced freezing of gait and improvements in executive function and mobility. © 2018 International Parkinson and Movement Disorder Society.