Paid sick leave benefits among essential frontline workers serving people experiencing homelessness in Canada during the COVID-19 pandemic.

OBJECTIVES: This study examined the prevalence and factors associated with paid sick leave benefits among direct service providers who work with people experiencing homelessness. STUDY DESIGN: Cross-sectional study using an online survey disseminated during the second wave of the COVID-19 pandemic in Canada. METHODS: Survey data from 572 direct service providers working in the homeless, supportive housing, and harm reduction service sectors were analyzed for this study. Univariate and multivariate logistic regression models were used to examine predictors of paid sick leave benefits. RESULTS: One hundred one (17.7%) participants did not have any paid sick leave benefits. In the univariate models, paid sick leave was associated with older age, greater family income, full-time work, specific employment settings (supportive housing and not emergency shelters or harm reduction programs), having a regular medical doctor, and fewer occupational impacts of the COVID-19 pandemic. Older age, full-time work, and non-receipt of emergency financial benefits remained statistically significant predictors in the multivariate model. CONCLUSIONS: Although the majority of service providers working with people experiencing homelessness have some amount of paid sick leave benefits, there is a precariously employed subset of individuals who are younger and working part-time in the sector. Temporary expansion of paid sick leave and removal of waiting periods for new employees to qualify for benefits are recommended.

Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) - a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14.

AIMS: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. PATIENTS AND METHODS: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. RESULTS: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. CONCLUSIONS: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.

Hospital volume and cesarean delivery among low-risk women in a nationwide sample.

OBJECTIVE: We sought to determine if hospital delivery volume was associated with a patient's risk for cesarean delivery in low-risk women. STUDY DESIGN: This study retrospectively examines a cohort of 1 657 495 deliveries identified in the 2013 Nationwide Readmissions Database. Hospitals were stratified by delivery volume quartiles. Low-risk patients were identified using the Society for Maternal-Fetal Medicine definition (n=845 056). A multivariable logistic regression accounting for hospital-level clustering was constructed to assess the factors affecting a patient's odds for cesarean delivery. RESULTS: The range of cesarean delivery rates was 2.4-51.2% among low-risk patients, and the median was 16.5% (IQR 12.8-20.5%). The cesarean delivery rate was higher in the top two-volume-quartile hospitals (17.4 and 18.2%) compared to the bottom quartiles (16.4 and 16.3%) (P<0.001). Hospital volume was not associated with a patient's odds for cesarean delivery after adjusting for patient and other hospital characteristics (P=0.188). CONCLUSION: Hospital delivery volume is not an independent predictor of cesarean delivery in this population.

Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns.

Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies.

Development of a Postpartum Stressor Measure.

To develop a brief self-report assessment of the type and magnitude of stressors during the postpartum period. A cross-sectional study of a convenience sample of 138 women at Massachusetts General Hospital in Boston, MA completed a measure of postpartum stressors at their 6-week postpartum visit. Item analyses were conducted; items were eliminated based on low relevance, low endorsement, and cross-loadings, resulting in a 9-item measure. Items were summed to create a total postpartum stressors score. To establish concurrent validity with perceived stress, the total postpartum stressors score was correlated with the 4-item Perceived Stress Scale (PSS-4). The stressors score was tested for bivariate associations with depression (Patient Health Questionnaire-2) and with social support (three items adapted from the MOS Social Support Scale). The 9-item measure, which was comprised of three factors (baby care, well-being, and work) demonstrated good reliability (Cronbach's α = .74) and concurrent validity with the PSS-4 (r = .53; p < .001) in the current sample. The stressors total score was negatively associated with social support (p < .001) and was positively associated with depression symptoms (p < .001). The early psychometric results on this measure are promising and associated with postpartum social support and depressive symptoms. With additional research to enhance external validity, this measure could be used and tested in an intervention study at the 6-week postpartum visit to identify women at risk for distress.

Supraretinacular endoscopic carpal tunnel release: surgical technique with prospective case series.

Current techniques for endoscopic carpal tunnel release use an infraretinacular approach, inserting the endoscope deep to the flexor retinaculum. We present a supraretinacular endoscopic carpal tunnel release technique in which a dissecting endoscope is inserted superficial to the flexor retinaculum, which improves vision and the ability to dissect and manipulate the median nerve and tendons during surgery. The motor branch of the median nerve and connections between the median and ulnar nerve can be identified and dissected. Because the endoscope is inserted superficial to the flexor retinaculum, the median nerve is not compressed before division of the retinaculum and, as a result, we have observed no cases of the transient median nerve deficits that have been reported using infraretinacular endoscopic techniques.

Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study.

OBJECTIVE: To determine whether outpatient exposure to calcium-channel blockers (CCBs) at the time of delivery is associated with an increased risk for postpartum haemorrhage (PPH). DESIGN: Cohort study. SETTING: United States of America. POPULATION OR SAMPLE: Medicaid beneficiaries. METHODS: We identified a cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or labetalol for pre-existing or gestational hypertension whose days of supply overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity score matching and stratification were used to address potential confounding. MAIN OUTCOME MEASURES: The occurrence of PPH during the delivery hospitalisation. RESULTS: There were 27 patients exposed to CCBs (2.2%) and 232 patients exposed to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for confounders, there was no meaningful association between CCB exposure and PPH in the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained across multiple sensitivity analyses. CONCLUSIONS: The outpatient use of CCBs in late pregnancy for the treatment of hypertension does not increase the risk of PPH.

Epiallelic variation in Arabidopsis thaliana.

Genotype is the primary determinate of phenotype. During the past two decades, however, there has been an emergent recognition of the epigenotype, a separate layer of heredity distinct from the primary DNA sequence that can have profound effects on phenotype. The epigenotype is a collection of chemical modifications to the DNA and nucleosomes in conjunction with noncoding RNA transcripts, and together these epigenetic marks act as a potent and expansive regulatory system for controlling gene expression. In this review, we discuss our current understanding of variation in epigenotype in the model plant Arabidopsis and how allelic differences attributable to epigenetic changes, or epialleles, can affect phenotype. We discuss examples of epialleles that have been created in the laboratory and others that have been identified in natural populations, because these two models provide complementary information regarding the genetic pathways, mechanisms of transmission, and biological and evolutionary context for the role of the epigenotype in phenotypic variation.

Management of a parturient with high-grade osteosarcoma of the proximal femur: a multidisciplinary approach.

Osteosarcoma is the most common primary malignant bone tumor, yet it is exceedingly rare in pregnancy. We present a case of a 33-year-old multiparous woman diagnosed with high-grade osteosarcoma during the third trimester of pregnancy. A plan was formulated to perform cesarean delivery at 33 weeks of gestation under spinal anesthesia, and, in subsequent surgery, radical femoral neck resection with limb salvage and adjuvant chemotherapy. The outcome was a healthy newborn baby boy and a disease-free mother. This case highlights the benefits of multidisciplinary planning: balancing the needs of the developing fetus with those of the mother, mitigating the risk of pathologic fracture and ensuring timely oncologic therapy.

The biceps brachii muscle and its distal insertion: observations of surgical and evolutionary relevance.

BACKGROUND: A sound understanding of the anatomy of the biceps brachii and possible anatomical variants is necessary to manage distal biceps injury. The present study was performed to define the anatomy of the biceps brachii with particular focus on the conformation of the distal biceps tendon, and its relationship of the two heads of the biceps brachii. METHODS: Twenty cadaver specimens were dissected and both qualitative and quantitative observations were made of a series of features relating to the biceps muscle and its tendon. RESULTS AND CONCLUSION: The investigation revealed anatomical variations including supernumerary heads (20%) and 'fusion' of the muscle proximal to tendon formation and a spiralling arrangement of the tendon in its approach to the radial tuberosity. The data from the present study was reviewed in the context of previous studies on the anatomy of this muscle and speculation on the evolutionary basis of the variations and their clinical implications are discussed.

Multiple photoreceptors contribute to nonimage-forming visual functions predominantly through melanopsin-containing retinal ganglion cells.

In the absence of functional rod and cone photoreceptors, mammals retain the ability to detect light for a variety of physiological functions such as circadian photoentrainment and pupillary light reflex. This is attributed to a third class of photoreceptors, the intrinsically photosensitive retinal ganglion cells that express the photopigment melanopsin. Even though in the absence of rods and cones, mammals retain the ability to detect light for various nonimage-forming visual functions, rods and cones can compensate for the absence of the melanopsin protein in nonvisual light-dependent physiological behaviors. Several studies have addressed the relative contribution of each photoreceptor type to nonimage-forming visual functions; however, a comprehensive model for these interactions is far from complete. Under conditions where melanopsin-containing retinal ganglion cells were genetically ablated, image formation is maintained, whereas circadian photoentrainment and pupillary light reflex are severely impaired. The findings indicate that multiple photoreceptors contribute to nonimage-forming visual functions through signaling via melanopsin-containing retinal ganglion cells. Future studies will aim to determine more quantitatively the relative contributions of each retinal photoreceptor in signaling light for nonimage-forming visual functions.

Genome-wide analysis of chromosomal features repressing human immunodeficiency virus transcription.

We have investigated regulatory sequences in noncoding human DNA that are associated with repression of an integrated human immunodeficiency virus type 1 (HIV-1) promoter. HIV-1 integration results in the formation of precise and homogeneous junctions between viral and host DNA, but integration takes place at many locations. Thus, the variation in HIV-1 gene expression at different integration sites reports the activity of regulatory sequences at nearby chromosomal positions. Negative regulation of HIV transcription is of particular interest because of its association with maintaining HIV in a latent state in cells from infected patients. To identify chromosomal regulators of HIV transcription, we infected Jurkat T cells with an HIV-based vector transducing green fluorescent protein (GFP) and separated cells into populations containing well-expressed (GFP-positive) or poorly expressed (GFP-negative) proviruses. We then determined the chromosomal locations of the two classes by sequencing 971 junctions between viral and cellular DNA. Possible effects of endogenous cellular transcription were characterized by transcriptional profiling. Low-level GFP expression correlated with integration in (i) gene deserts, (ii) centromeric heterochromatin, and (iii) very highly expressed cellular genes. These data provide a genome-wide picture of chromosomal features that repress transcription and suggest models for transcriptional latency in cells from HIV-infected patients.

[Diabetes Infobus 1999. Blood pressure]. / Diabetes-Infobus. Blutdruck.

In comparison to non-diabetic normotensive control subjects, hypertensive diabetic patients have a four-fold increased risk for cardiovascular morbidity and mortality. Additional to WHO/IHS definition, the terminus "high-normal blood pressure" (systolic 130-140 mm Hg and diastolic 85 - < 90 mm Hg) was used for data analysis. The mean blood pressure was elevated among diabetic subjects (157/85 mmHg) when compared to the non-diabetic group (141/82 mm Hg). The analysis of visitors with an already known diabetes yielded only 14% of probands having normal blood pressure, whereby 63% of diabetic subjects were definitely in the hypertensive range. In overweight (BMI > 28 kg/m2) subjects, whose percentage in our population were 32%, blood pressure was elevated (RR > 150/90) in 51%. In subclasses with high blood pressure, an increased cholesterol level was often seen; 64% of these subjects had a cholesterol level of greater 200 mg/dl.

The ethylene pathway: a paradigm for plant hormone signaling and interaction.

To dissect the web of signals that control plant growth, it is important to understand how the individual components of the pathway are modulated. Ethylene is a plant hormone involved in a large number of developmental processes. Biochemical and genetic approaches have provided a detailed view of the biosynthetic and signal transduction pathways of this hormone in the reference plant Arabidopsis thaliana. The effects of several hormones and of developmental changes on the regulation of the key enzymes of ethylene biosynthesis, ACC synthase and ACC oxidase, serve as a clear example of interaction between signals in the generation of complex responses. We now have a picture of how ethylene is sensed by the ethylene receptors and how the signal is further transduced to the nucleus. Although some of the ethylene receptors show a tissue-specific pattern of expression, little is known about the regulation of the components of the ethylene transduction cascade by other hormones or developmental factors. Once the ethylene signal reaches the nucleus, it activates a transcriptional cascade that results in changes in the expression of a number of genes. We describe some of the results that suggest an interaction at the transcriptional level between ethylene, other hormones, and stress signals.

Obesity and preeclampsia: the potential role of inflammation.

OBJECTIVE: Systemic inflammation might contribute to the pathogenesis of preeclampsia. In addition, the association between obesity and inflammation in preeclampsia has not been examined in detail. We determined whether first-trimester elevation of serum C-reactive protein, an index of systemic inflammation, was associated with preeclampsia. METHODS: We conducted a prospective, nested case-control study among women enrolled in the Massachusetts General Hospital Obstetrical Maternal Study cohort. High-resolution C-reactive protein assays were performed on first-trimester (11 +/- 2 weeks' gestation) serum samples in 40 women in whom preeclampsia developed (blood pressure [BP] greater than 140/90 mmHg, and proteinuria, either 2+ or more by dipstick or greater than 300 mg per 24 hours), and in 80 matched controls. This sample size had greater than 80% power to detect a difference in C-reactive protein levels between cases and controls. We used nonparametric tests to compare C-reactive protein levels and conditional logistic regression to control for confounding variables. RESULTS: First-trimester C-reactive protein levels were significantly higher among women in whom preeclampsia subsequently developed compared with controls (4.6 compared with 2.3 mg/L, P =.04). When women were subdivided into C-reactive protein quartiles, the odds ratio (OR) of being in the highest quartile of C-reactive protein was 3.2 (95% confidence interval [CI] 1.1, 9.3, P =.02) among cases of preeclampsia compared with controls. When body mass index (BMI) was added to the multivariable model, the highest quartile of C-reactive protein was no longer associated with increased risk of preeclampsia (OR 1.1, 95% CI.3, 4.3, P =.94). In the same model without BMI, the highest quartile of C-reactive protein was associated with increased risk of preeclampsia (OR 3.5, 95% CI 1.3, 9.5, P =.01). CONCLUSION: In women with preeclampsia, there was evidence of increased systemic inflammation in the first trimester. Inflammation might be part of a causal pathway through which obesity predisposes to preeclampsia.

Increased risk of cesarean delivery with advancing maternal age: indications and associated factors in nulliparous women.

OBJECTIVE: To investigate factors that contribute to the increased risk of cesarean delivery with advancing maternal age. STUDY DESIGN: We reviewed demographic and ante- and intrapartum variables from a data set of term, nulliparous women who delivered at Brigham and Women's Hospital in 1998 (n = 3715). RESULTS: Cesarean delivery rates increased with advancing maternal age (< 25 years, 11.6%; > or = 40 years, 43.1%). Older women were more likely to have cesarean delivery without labor (< 25 years, 3.6%; > or = 40 years, 21.1%). Malpresentation and prior myomectomy were the indications for cesarean delivery without labor that were more prevalent in our older population as compared to our younger population. Even among women with spontaneous or induced labor, cesarean delivery rates increased with maternal age (< 25 years, 8.3%; > or = 40 years, 30.6%). Cesarean delivery rates were higher with induced labor, and rates of induction rose directly and continuously with maternal age, especially the rate of elective induction. Cesarean delivery for failure to progress or fetal distress was more common among older parturients, regardless of whether labor was spontaneous or induced. Among women who underwent cesarean delivery because of failure to progress, use of oxytocin and length of labor did not vary with age. CONCLUSIONS: Older women are at higher risk for cesarean delivery in part because they are more likely to have cesarean delivery without labor. However, even among those women who labor, older women are more likely to undergo cesarean delivery, regardless of whether labor is spontaneous or induced. Part of the higher rate among older women who labor is explained by a higher rate of induction, particularly elective induction. Among women in both spontaneous and induced labor, cesarean delivery for the diagnoses of failure to progress and fetal distress was more frequent in older patients, although management of labor dystocia for these patients was similar to that for younger patients.

Phototropin-related NPL1 controls chloroplast relocation induced by blue light.

In photosynthetic cells, chloroplasts migrate towards illuminated sites to optimize photosynthesis and move away from excessively illuminated areas to protect the photosynthetic machinery. Although this movement of chloroplasts in response to light has been known for over a century, the photoreceptor mediating this process has not been identified. The Arabidopsis gene NPL1 (ref. 2) is a paralogue of the NPH1 gene, which encodes phototropin, a photoreceptor for phototropic bending. Here we show that NPL1 is required for chloroplast relocation induced by blue light. A loss-of-function npl1 mutant showed no chloroplast avoidance response in strong blue light, whereas the accumulation of chloroplasts in weak light was normal. These results indicate that NPL1 may function as a photoreceptor mediating chloroplast relocation.

An Arabidopsis circadian clock component interacts with both CRY1 and phyB.

Most organisms, from cyanobacteria to mammals, use circadian clocks to coordinate their activities with the natural 24-h light/dark cycle. The clock proteins of Drosophila and mammals exhibit striking homology but do not show similarity with clock proteins found so far from either cyanobacteria or Neurospora. Each of these organisms uses a transcriptionally regulated negative feedback loop in which the messenger RNA levels of the clock components cycle over a 24-h period. Proteins containing PAS domains are invariably found in at least one component of the characterized eukaryotic clocks. Here we describe ADAGIO1 (ADO1), a gene of Arabidopsis thaliana that encodes a protein containing a PAS domain. We found that a loss-of-function ado1 mutant is altered in both gene expression and cotyledon movement in circadian rhythmicity. Under constant white or blue light, the ado1 mutant exhibits a longer period than that of wild-type Arabidopsis seedlings, whereas under red light cotyledon movement and stem elongation are arrhythmic. Both yeast two-hybrid and in vitro binding studies show that there is a physical interaction between ADO1 and the photoreceptors CRY1 and phyB. We propose that ADO1 is an important component of the Arabidopsis circadian system.

Pulse pressure and risk of preeclampsia: a prospective study.

OBJECTIVE: To find whether pulse pressure, a measure of arterial compliance, is associated early in pregnancy with increased risk of developing preeclampsia. METHODS: In a prospective cohort of 576 nulliparas, we examined blood pressures throughout pregnancy and at 6-8 weeks postpartum. Measurements during weeks 7-15, 16-24, and 25-38 of gestation were pooled to find averages for each period. Outcomes assessed were gestational hypertension and preeclampsia. Logistic regression analysis was used to develop relative risks and 95% confidence intervals. RESULTS: We confirmed 34 (5.9%) cases of preeclampsia, 32 (5.6%) cases of gestational hypertension, and 510 normotensive women. Mean systolic and diastolic blood pressures and mean arterial pressures were elevated throughout pregnancy in women who developed hypertensive disorders of pregnancy compared with normotensive women. Pulse pressure at 7-15 weeks was significantly higher in women who developed preeclampsia (45 +/- 6 mmHg) than in those who developed gestational hypertension (41 +/- 7 mmHg, P =.03) and normotensive women (41 +/- 8 mmHg, P =.01). Examined in tertiles, increasing pulse pressure was associated with increasing risk of developing preeclampsia (P for trend =.01) but not gestational hypertension (P for trend =.95). After adjustment for potential confounders, a 1-mmHg rise in early pregnancy pulse pressure was associated with a 6% (95% confidence interval: 1, 10) increase in risk for developing preeclampsia but not gestational hypertension (relative risk: 1%; 95% confidence interval: -1, 6). Beyond 15 weeks' gestation, differences between groups diminished, but women with any hypertensive disorder had higher pulse pressures than women with uncomplicated pregnancies. CONCLUSION: Elevated pulse pressure, indicating poor arterial compliance, was evident early in pregnancies of women who subsequently developed preeclampsia.