The Association between Meteorological Parameters and Aneurysmal Subarachnoid Hemorrhage: A Nationwide Analysis

Prior research has suggested that regional weather patterns impact the risk of rupture of cerebral aneurysms, but the findings in the literature have been inconsistent. Furthermore, no nationwide analysis to date has examined the association between meteorological factors and the post-procedural outcomes of patients after the treatment for ruptured cerebral aneurysms. The purpose of this study was to use a nationwide sample to analyze the association between specific meteorological parameters—temperature, precipitation, sunlight, and humidity—and hospital admission rate for and outcome after aneurysmal subarachnoid hemorrhage. Patients were identified using the Nationwide Inpatient Sample (2001–2010): Those with an ICD-9 diagnosis code for subarachnoid hemorrhage and a procedural code for aneurysm repair were included. Climate data were obtained from the State of the Climate Report 2010 released by the National Climatic Data Center. Multivariate regression models were constructed to analyze the association between average state monthly temperature, precipitation, and percent possible sunlight, as well as relative morning humidity and both monthly hospital admission rate, adjusted for annual state population in millions, and in-hospital mortality. 16,970 admissions were included from 723 hospitals across 41 states. Decreased daily sunlight and lower relative humidity were associated with an increased rate of admission for ruptured cerebral aneurysms (p<0.001), but had no association with differential inpatient mortality. No significant changes in these observed associations were seen when multivariate analyses were constructed. This is the first nationwide study to suggest that decreased sunlight and lower relative humidity are associated with admission for ruptured cerebral aneurysms. While it has been postulated that external atmospheric factors may cause hormonal and homeostatic changes that impact the risk of rupture of cerebral aneurysms, additional research is needed to confirm and further understand these relationships

The Impact of Insurance Status on the Outcomes after Aneurysmal Subarachnoid Hemorrhage

Investigation into the association of insurance status with the outcomes of patients undergoing neurosurgical intervention has been limited: this is the first nationwide study to analyze the impact of primary payer on the outcomes of patients with aneurysmal subarachnoid hemorrhage who underwent endovascular coiling or microsurgical clipping. The Nationwide Inpatient Sample (2001–2010) was utilized to identify patients; those with both an ICD-9 diagnosis codes for subarachnoid hemorrhage and a procedure code for aneurysm repair (either via an endovascular or surgical approach) were included. Hierarchical multivariate regression analyses were utilized to evaluate the impact of primary payer on in-hospital mortality, hospital discharge disposition, and length of hospital stay with hospital as the random effects variable. Models were adjusted for patient age, sex, race, comorbidities, socioeconomic status, hospital region, location (urban versus rural), and teaching status, procedural volume, year of admission, and the proportion of patients who underwent ventriculostomy. Subsequent models were also adjusted for time to aneurysm repair and time to ventriculostomy; subgroup analyses evaluated for those who underwent endovascular and surgical procedures separately. 15,557 hospitalizations were included. In the initial model, the adjusted odds of in-hospital mortality were higher for Medicare (OR 1.23, p<0.001), Medicaid (OR 1.23, p<0.001), and uninsured patients (OR 1.49, p<0.001) compared to those with private insurance. After also adjusting for timing of intervention, Medicaid and uninsured patients had a reduced odds of non-routine discharge (OR 0.75, p<0.001 and OR 0.42, p<0.001) despite longer hospital stays (by 8.35 days, p<0.001 and 2.45 days, p = 0.005). Variations in outcomes by primary payer–including in-hospital post-procedural mortality–were more pronounced for patients of all insurance types who underwent microsurgical clipping. The observed differences by primary payer are likely multifactorial, attributable to varied socioeconomic factors and the complexities of the American healthcare delivery system

The Performance and Diversification Potential of Non-Listed Value-Add Real Estate Funds in Japan

Acknowledgments: The authors acknowledge the generous support of ANREV, MSCI and Real Capital Analytics in providing the necessary data for analysis. They are also grateful for the constructive comments by four reviewers.Peer reviewedPublisher PD

International Centre for Guidance Studies (iCeGS) Annual Review 2023 - 25th Anniversary

This publication offers a brief insight into the wide range of activities the iCeGS team has been involved with over the year and the last 25 years. It explores our contribution to policy, research and practice within the career development sector both in the UK and wider afield. iCeGS Annual Review also allows the team to reflect on our many achievements over the last year. Like other years, we feel particularly proud of several activities this year

Adverse childhood experiences, support, and the perception of ability to work in adults with disability

Objective To examine the impact of adverse childhood experiences (ACEs) and support on self-reported work inability of adults reporting disability. Participants Adults (ages 18–64) who participated in the Behavioral Risk Factor Surveillance System in 2009 or 2010 and who reported having a disability (n = 13,009). Design and Main Outcome Measures The study used a retrospective cohort design with work inability as the main outcome. ACE categories included abuse (sexual, physical, emotional) and family dysfunction (domestic violence, incarceration, mental illness, substance abuse, divorce). Support included functional (perceived emotional/social support) and structural (living with another adult) support. Logistic regression was used to adjust for potential confounders (age, sex and race) and to evaluate whether there was an independent effect of ACEs on work inability after adding other important predictors (support, education, health) to the model. Results ACEs were highly prevalent with almost 75% of the sample reporting at least one ACE category and over 25% having a high ACE burden (4 or more categories). ACEs were strongly associated with functional support. Participants experiencing a high ACE burden had a higher adjusted odds ratio (OR) [95% confidence interval] of 1.9 [1.5–2.4] of work inability (reference: zero ACEs). Good functional support (adjusted OR 0.52 [0.42–0.63]) and structural support (adjusted OR 0.48 [0.41–0.56]) were protective against work inability. After adding education and health to the model, ACEs no longer appeared to have an independent effect. Structural support remained highly protective, but functional support only appeared to be protective in those with good physical health. Conclusions ACEs are highly prevalent in working-age US adults with a disability, particularly young adults. ACEs are associated with decreased support, lower educational attainment and worse adult health. Health care providers are encouraged to screen for ACEs. Addressing the effects of ACEs on health and support, in addition to education and retraining, may increase ability to work in those with a disability

Genome-wide search identifies Ccnd2 as a direct transcriptional target of Elf5 in mouse mammary gland

<p>Abstract</p> <p>Background</p> <p>The ETS transcription factor Elf5 (also known as ESE-2) is highly expressed in the mammary gland and plays an important role in its development and differentiation. Indeed studies in mice have illustrated an essential role for Elf5 in directing alveologenesis during pregnancy. Although the molecular mechanisms that underlie the developmental block in Elf5 null mammary glands are beginning to be unraveled, this investigation has been hampered by limited information about the identity of Elf5-target genes. To address this shortcoming, in this study we have performed ChIP-cloning experiments to identify the specific genomic segments that are occupied by Elf5 in pregnant mouse mammary glands.</p> <p>Results</p> <p>Sequencing and genomic localization of <it>cis</it>-regulatory regions bound by Elf5 <it>in vivo </it>has identified several potential target genes covering broad functional categories. A subset of these target genes demonstrates higher expression levels in Elf5-null mammary glands suggesting a repressive functional role for this transcription factor. Here we focus on one putative target of Elf5, the <it>Ccnd2 </it>gene that appeared in our screen. We identify a novel Elf5-binding segment upstream of the <it>Ccnd2 </it>gene and demonstrate that Elf5 can transcriptionally repress Ccnd2 by directly binding to the proximal promoter region. Finally, using Elf5-null mammary epithelial cells and mammary glands, we show that loss of Elf5 <it>in vivo </it>leads to up regulation of Ccnd2 and an altered expression pattern in luminal cells.</p> <p>Conclusions</p> <p>Identification of Elf5-targets is an essential first step in elucidating the transcriptional landscape that is shaped by this important regulator. Our studies offer new toolbox in examining the biological role of Elf5 in mammary gland development and differentiation.</p

Metabolic loss of deuterium from isotopically labeled glucose

The isotopically substituted molecule (6- 13 C, 1, 6, 6- 2 H 3 )glucose was evaluated to determine whether metabolic 2 H loss would prevent its use in quantitating pentose phosphate pathway (PPP) activity. PPP activity causes the C1 of glucose to be lost as CO 2 , while C6 can appear in lactate. 2 H NMR analysis of the lactate produced from this glucose can distinguish (3- 2 H)-lactate (from C1 of glucose) from (3- 13 C, 3, 3- 2 H Z )lactate (from C6 of glucose). 2 H NMR spectroscopic analysis of medium containing (4- 13 C, 1,6,6 −2 H 3 ) glucose after incubation with cultured rat 9L glioma cells suggested a 30.8 ± 2.1% PPP activity as compared with 6.0 ± 0.8% from separate, parallel incubations with (1- 13 C)glucose and (6- 13 C)glucose. Subsequent experiments with other isotopically labeled glucose molecules suggest that this discrepancy is due to selective loss of 2 H from the C1 position of glucose, catalyzed by phosphoman-nose isomerase. Failure to consider 2 H exchange from the C1 and C6 positions of glucose can lead to incorrect conclusions in metabolic studies utilizing this and other deuterated or tritiated glucose molecules.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38491/1/1910320317_ftp.pd

MSR1 repeats modulate gene expression and affect risk of breast and prostate cancer

[Background] MSR1 repeats are a 36–38 bp minisatellite element that have recently been implicated in the regulation of gene expression, through copy number variation (CNV).[Patients and methods] Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer.[Results] MSR1s are predominately located at chromosome 19 and are functionally enriched in regulatory regions of the genome, particularly regions implicated in short-range regulatory activities (H3K27ac, H3K4me1 and H3K4me3). MSR1-regulated genes were found to have specific molecular roles, such as serine-protease activity (P = 4.80 × 10−7) and ion channel activity (P = 2.7 × 10−4). The kallikrein locus was found to contain a large number of MSR1 clusters, and at least six of these showed CNV. An MSR1 cluster was identified within KLK14, with 9 and 11 copies being normal variants. A significant association with the 9-copy allele and non-familial breast cancer was found in two independent populations (P = 0.004; P = 0.03). In the white British population, the minor allele conferred an increased risk of 1.21–3.51 times for all non-familial disease, or 1.7–5.3 times in early-onset disease. The 9-copy allele was also found to be associated with increased risk of prostate cancer in an independent population (odds ratio = 1.27–1.56; P =0.009).[Conclusions] MSR1 repeats act as molecular switches that modulate gene expression. It is likely that CNV of MSR1 will affect risk of development of various forms of cancer, including that of breast and prostate. The MSR1 cluster at KLK14 represents the strongest risk factor identified to date in non-familial breast cancer and a significant risk factor for prostate cancer. Analysis of MSR1 genotype will allow development of precise stratification of disease risk and provide a novel target for therapeutic agents.Prostate cancer study is supported by an National Health and Medical Research Council (NHMRC) grant and Career Development Fellowship APP1090505 to JB. The Australian Prostate Cancer BioResource is supported by the NHMRC Enabling Grant APP614296 and by a grant from the Prostate Cancer Foundation, Australia.Peer reviewe

A functional variant on 20q13.33 related to glioma risk alters enhancer activity and modulates expression of multiple genes.

Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with glioma risk on 20q13.33, but the biological mechanisms underlying this association are unknown. We tested the hypothesis that a functional SNP on 20q13.33 impacted the activity of an enhancer, leading to an altered expression of nearby genes. To identify candidate functional SNPs, we identified all SNPs in linkage disequilibrium with the risk-associated SNP rs2297440 that mapped to putative enhancers. Putative enhancers containing candidate functional SNPs were tested for allele-specific effects in luciferase enhancer activity assays against glioblastoma multiforme (GBM) cell lines. An enhancer containing SNP rs3761124 exhibited allele-specific effects on activity. Deletion of this enhancer by CRISPR-Cas9 editing in GBM cell lines correlated with an altered expression of multiple genes, including STMN3, RTEL1, RTEL1-TNFRSF6B, GMEB2, and SRMS. Expression quantitative trait loci (eQTL) analyses using nondiseased brain samples, isocitrate dehydrogenase 1 (IDH1) wild-type glioma, and neurodevelopmental tissues showed STMN3 to be a consistent significant eQTL with rs3761124. RTEL1 and GMEB2 were also significant eQTLs in the context of early CNS development and/or in IDH1 wild-type glioma. We provide evidence that rs3761124 is a functional variant on 20q13.33 related to glioma/GBM risk that modulates the expression of STMN3 and potentially other genes across diverse cellular contexts