Characteristics associated with quality of life among people with drug-resistant epilepsy

Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants’ mean score was 66, with a wide range (25–99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy

DEAD-Box Protein Ddx46 Is Required for the Development of the Digestive Organs and Brain in Zebrafish

Spatially and temporally controlled gene expression, including transcription, several mRNA processing steps, and the export of mature mRNA to the cytoplasm, is essential for developmental processes. It is well known that RNA helicases of the DExD/H-box protein family are involved in these gene expression processes, including transcription, pre-mRNA splicing, and rRNA biogenesis. Although one DExD/H-box protein, Prp5, a homologue of vertebrate Ddx46, has been shown to play important roles in pre-mRNA splicing in yeast, the in vivo function of Ddx46 remains to be fully elucidated in metazoans. In this study, we isolated zebrafish morendo (mor), a mutant that shows developmental defects in the digestive organs and brain, and found that it encodes Ddx46. The Ddx46 transcript is maternally supplied, and as development proceeds in zebrafish larvae, its ubiquitous expression gradually becomes restricted to those organs. The results of whole-mount in situ hybridization showed that the expression of various molecular markers in these organs is considerably reduced in the Ddx46 mutant. Furthermore, splicing status analysis with RT-PCR revealed unspliced forms of mRNAs in the digestive organ and brain tissues of the Ddx46 mutant, suggesting that Ddx46 may be required for pre-mRNA splicing during zebrafish development. Therefore, our results suggest a model in which zebrafish Ddx46 is required for the development of the digestive organs and brain, possibly through the control of pre-mRNA splicing

Higher occurrence of nausea and vomiting after total hip arthroplasty using general versus spinal anesthesia: an observational study.

BACKGROUND: Under the assumption that postoperative nausea and vomiting (PONV) may occur after total hip arthroplasty (THA) regardless of the anesthetic technique used, it is not clear whether general (GA) or spinal (SA) anesthesia has higher causal effect on this occurrence. Conflicting results have been reported. METHODS: In this observational study, we selected all elective THA interventions performed in adults between 1999 and 2008 in a Swiss orthopedic clinic under general or spinal anesthesia. To assess the effect of anesthesia type on the occurrence of PONV, we used the propensity score and matching methods, which allowed us to emulate the design and results of an RCT. RESULTS: Among 3922 procedures, 1984 (51 %) patients underwent GA, of which 4.1 % experienced PONV, and 1938 underwent SA, of which 3.5 % experienced PONV. We found that the average treatment effect on the treated, i.e. the effect of anesthesia type for a sample of individuals that actually received spinal anesthesia compared to individuals who received GA, was ATET = 2.00 % [95 % CI, 0.78-3.19 %], which translated into an OR = 1.97 [95 % CI 1.35; 2.87]. CONCLUSION: This suggests that the type of anesthesia is not neutral regarding PONV, general anesthesia being more strongly associated with PONV than spinal anesthesia in orthopedic surgery

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

10.1371/journal.pone.0058857PLoS ONE83

Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey

OBJECTIVE: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression. RESULTS: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81). CONCLUSION: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs

Automated control and optimisation of laser driven ion acceleration

The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimisation of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimisation. Here, an automated, HRR-compatible system produced high fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimisation of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually-optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimisation of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources

Automated control and optimisation of laser driven ion acceleration

The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimisation of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimisation. Here, an automated, HRR-compatible system produced high fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimisation of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually-optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimisation of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources

Studying Adolescent Male Sexuality: Where Are We?

This article critically reviews the literature about adolescent males’ sexuality in order to describe the state of the science and to identify promising concepts and research designs that have the potential to guide the next generation of research. A critique was conducted on 94 peer-reviewed studies of sexual behaviors that included a sample of adolescent males; 11 scholarly texts and 2 dissertations. Most studies lacked a theoretical foundation and had cross-sectional designs. For those studies with a theoretical base, 3 perspectives were most often used to guide research: cognitive, biological, or social-environmental. Studies frequently relied on older adolescents or young adult males to report behaviors during early adolescence. Male-only samples were infrequent. Findings include (a) the measurement of sexual activity is frequently limited to coitus and does not explore other forms of “sex”; (b) cognitive factors have been limited to knowledge, attitudes, and intent; (c) little is known about younger males based on their own self-reports; (d) little is known about the normative sexuality development of gay adolescent males; and (e) longitudinal studies did not take into account the complexities of biological, social, and emotional development in interaction with other influences. Research on adolescent sexuality generally is about sexual activity, with little research that includes cognitive competency or young males’ sense of self as a sexual being. The purpose of the paper is to critically review the literature about male sexuality in order to describe the state of the science as well as to identify potential directions to guide the next generation of adolescent male sexual being research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45299/1/10964_2005_Article_5762.pd