Spawning in a natural population of the mummichog, Fundulus heteroclitus, occurs cyclically throughout its reproductive season. Gonadal maturity and spawning readiness of males and females are ...greatest for several days coincident with new or full moon. The spawning rhythm is apparent in size distributions of fry collected during the spawning season. A diurnal cycle in both spawning readiness and gonadal maturity was super-imposed on the lunar spawning rhythm. Although mature eggs were found in the ovaries of fish examined during the day at spawning peaks, these eggs were usually dispersed throughout the stroma of the ovary. Fish sampled at the night high tide usually contained ovulated eggs grouped posteriorly in the lumen of the ovary, at the opening of the ovipositor. This rhythmicity synchronizes spawning with the highest tides of the lunar cycle, and makes possible the deposition of eggs in locations which insure their incubation away from strong tidal currents. The observed spawning rhythm is an important component of a reproductive sequence that appears to be of adaptive significance in the tide marsh environment.
Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We ...investigated whether the African ancestry–specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval CI = 2.13–7.22) and 33.41 (95% CI = 10.86–102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17–25%) for TA heterozygotes and 38% (95% CI = 13–65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants.
We found that rs72725854, an African ancestry–specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.
The African ancestry–specific prostate cancer risk variant at 8q24, rs72725854, is enriched in men diagnosed at younger ages and men with a prostate cancer family history. Carriers of this risk allele would benefit from regular and earlier prostate cancer screening.
Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, ...and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio OR = 1.55, 95% confidence interval CI = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.
Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. ...We used a cross‐validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10‐fold cross‐validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross‐validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47‐4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65‐0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.
What's new?
Polygenic models can provide personalized estimates of cancer risk. However, Africans are a population generally under‐served in genome‐wide studies. In this report, the authors used machine learning to identify three SNPs that significantly improved the performance of an established polygenic‐hazard model of prostate‐cancer risk vs age at diagnosis, specifically tailored to men of African genetic ancestry. Inclusion of these SNPs improved the performance of this novel 'PHS46+African' score by as much as 79% compared to the original model, to levels comparable with Europeans.
To describe a UK-wide re-audit of the 2019 Royal College of Radiologists (RCR) audit evaluating patient-related data and organisational infrastructure in the radiological reporting of vertebral ...fragility fractures (VFFs) on computed tomography (CT) studies and to assess the impact of a series of RCR interventions, initiated to raise VFF awareness, on reporting practice and outcomes.
Patient specific and organisational questionnaires largely replicated those utilised in 2019. The patient questionnaire involved retrospective analysis of between 50 and 100 consecutive, non-traumatic CT studies which included the thoracolumbar spine. All RCR radiology audit leads were invited to participate. Data collection commenced from 1 April 2022.
Data were supplied by 129/194 (67%) departments. One thousand five hundred and eighty-six of 7,316 patients (21.7%) had a VFF on auditor review. Overall improvements were demonstrated in key initial/provisional reporting results; comment on spine/bone (93.2%, 14.4% improvement, p<0.0002); fracture severity assessment (34.7%, 8.5% improvement, p=0.0007); use of recommended terminology (67.8%, 7.5% improvement, p=0.0034); recommendations for further management (11.7%, 9.1% improvement, p<0.0002).
The 2022 national re-audit confirms improvements in diagnostic performance and practice in VFF reporting. Continuing work is required to build on this improvement and to further embed best practice.
•Early and opportunistic diagnosis of VFFs reduces patient morbidity and mortality.•After an audit RCR-led interventions were initiated to improve awareness of VFFs.•A re-audit in 2022 confirms improvements in patient and organisation VFF reporting.•Continued work is required to sustain and build upon demonstrated improvements.•AI will likely gain importance but radiological involvement will remain essential.
Seasonal influenza A infection affects a significant cohort of the global population annually, resulting in considerable morbidity and mortality. Therapeutic strategies are of limited efficacy, and ...during a pandemic outbreak would only be available to a minority of the global population. Over-the-counter medicines are routinely taken by individuals suffering from influenza, but few studies have been conducted to determine their effectiveness in reducing pulmonary immunopathology or the influence they exert upon the generation of protective immunity.
A mouse model of influenza infection was utilised to assess the efficacy of paracetamol (acetaminophen) in reducing influenza-induced pathology and to examine whether paracetamol affects generation of protective immunity.
Administration (intraperitoneal) of paracetamol significantly decreased the infiltration of inflammatory cells into the airway spaces, reduced pulmonary immunopathology associated with acute infection and improved the overall lung function of mice, without adversely affecting the induction of virus-specific adaptive responses. Mice treated with paracetamol exhibited an ability to resist a second infection with heterologous virus comparable with that of untreated mice.
Our results demonstrate that paracetamol dramatically reduces the morbidity associated with influenza but does not compromise the development of adaptive immune responses. Overall, these data support the utility of paracetamol for reducing the clinical symptoms associated with influenza virus infection.
BACKGROUND: The suggestion that body mass index (BMI) cutoffs to define obesity should differ in persons of Polynesian descent compared with Europeans is based principally on the observation that ...persons of Polynesian descent have a relatively higher proportion of lean body mass for a given BMI. OBJECTIVES: The objectives were to determine whether the relation between BMI, waist circumference, and metabolic comorbidity differs in the 2 major ethnic groups in New Zealand and to ascertain whether ethnicity-specific BMI and waist circumference cutoffs for obesity are justified for Māori (indigenous New Zealanders). DESIGN: Subjects included a convenience sample of 1539 men and women aged 17-82 y (47% Māori, 53% white) with measures of BMI, waist circumference, blood pressure, fasting insulin, glucose, and lipids. The sensitivity and specificity of BMI (in kg/m²; 30 and 32), waist circumference (80 and 88 cm in women, 94 and 102 cm in men), and waist-to-height ratio (WHtR; ≥0.6) in relation to insulin sensitivity, insulin resistance, and the metabolic syndrome were determined. Receiver operating characteristic curves and areas under the curve (AUCs) were also calculated. RESULTS: No ethnic or sex differences between AUCs were observed for BMI, waist circumference, or WHtR, which showed that these anthropometric measures perform similarly in Māori and European men and women and correctly discriminate between those with and without insulin resistance or the metabolic syndrome 79-87% of the time. Any increase in specificity from a higher BMI cutoff of 32 in Māori was offset by appreciable reductions in sensitivity. CONCLUSION: These findings argue against having different BMI or waist circumference cutoffs for people of Polynesian descent.
This study aimed to determine the well-being outcomes and quality of work environment among emergency nurses compared with inpatient nurses working in Magnet hospitals and identify recommendations in ...emergency department work environments that hold promise for enhancing emergency nurses' well-being.
This is a cross-sectional analysis of multicenter survey data collected in 2021 from 11,743 nurses practicing in 60 United States Magnet hospitals. Nurses report on burnout, job dissatisfaction, intent to leave, work environment, and recommendations to improve well-being.
Emergency nurses are significantly more likely to report high burnout (P = .04), job dissatisfaction (P < .001), and intent to leave (P < .001) than inpatient nurses working in the same Magnet hospitals. Emergency nurses are significantly more likely to report insufficient staffing (P = .001), an unfavorable work environment (P < .001), and lack confidence that management will act to resolve problems in patient care (P < .001) but did report significantly better working relationships with physicians (P < .001) than their inpatient counterparts. The 2 greatest recommendations to improve well-being included improving nurse staffing (91.4%) and the ability to take uninterrupted breaks (86.7%); the lowest-ranked recommendations were employing more advanced practice providers (25.9%) and appointing a wellness champion (21.2%).
High burnout and other adverse nurse outcomes are common among emergency nurses in Magnet hospitals. Modifiable features of ED work environments including inadequate nurse staffing, inability of nurses to take uninterrupted breaks, and lack of responsiveness of management to persistent problems in patient care warrant high priority attention by Magnet hospital leaders.
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