Regional and developmental characteristics of human embryo mosaicism revealed by single cell sequencing.

Chromosomal mosaicism is common throughout human pre- and post-implantation development. However, the incidence and characteristics of mosaicism in human blastocyst remain unclear. Concerns and confusions still exist regarding the interpretation of chromosomal mosaicism on preimplantation genetic testing for aneuploidy (PGT-A) results and embryo development. Here, we aimed to estimate the genetic concordance between trophectoderm (TE), inner cell mass (ICM) and the corresponding human embryonic stem cells (hESCs), and to explore the characteristics of mosaicism in human blastocyst and hESCs on a single cell level. The single cell sequencing results of TE cells indicated that 65.71% of the blastocysts were mosaic (23 in 35 embryos), while the ICM sequencing results suggested that 60.00% of the blastocysts were mosaic (9 in 15 embryos). The incidence of mosaicism for the corresponding hESCs was 33.33% (2 in 6 embryos). No significant difference was observed between the mosaic rate of TE and that of ICM. However, the mosaic rate of the corresponding hESCs was significantly lower than that of TE and ICM cells, suggesting that the incidence of mosaicism may decline during embryonic development. Upon single cell sequencing, we found several "complementary" copy number variations (CNVs) that were usually not revealed in clinical PGT-A which used multi-cell DNA sequencing (or array analysis). This indicates the potential diagnostic risk of PGT-A based multi-cell analysis routinely in clinical practice. This study provided new insights into the characteristics, and considerable influences, of mosaicism on human embryo development, as well as the clinical risks of PGT-A based on multi-cell biopsies and bulk DNA assays.

Efficacy of a stannous fluoride dentifrice for relieving dentinal hypersensitivity in Chinese population: an 8-week randomized clinical trial.

OBJECTIVES: To compare the effectiveness of using a 0.454% stannous fluoride-containing dentifrice twice daily in relieving dentinal hypersensitivity (DH) in a Chinese population. MATERIALS AND METHODS: This was a single-centre, randomized, controlled, examiner-blind, three-treatment-arm, parallel-group study in participants with clinically diagnosed DH. Subjects who met inclusion criteria (n = 197) were randomly allocated into 3 groups: test group (n = 66)-using a 0.454% stannous fluoride-containing dentifrice twice daily; positive control group (n = 64)-using a 5.0% calcium sodium phosphosilicate-containing dentifrice twice daily; negative control group (n = 67)-using a 1150 ppm of NaF dentifrice twice daily. Status of DH was assessed at week 4 and week 8 by the same independent examiner. Changes from baseline in Schiff sensitivity score, tactile threshold and Dentine Hypersensitivity Experience Questionnaire (DHEQ) score were analysed using analysis of covariance models. The DHEQ evaluated subject-perceived oral health-related quality of life (OHRQoL). RESULTS: Statistically significant improvements in mean Schiff scores (p < 0.0001 for all products at Weeks 4 and 8), tactile threshold (p < 0.0001 for test and negative control at Weeks 4 and 8: Week 4 p = 0.0040 and Week 8 p < 0.0001 for positive control) and all DHEQ scores (p < 0.01 for all groups) were observed. No statistically significant differences were observed in the adjusted mean between all dentifrices at both timepoints, potentially driven by a placebo effect. Forty-two treatment-emergent adverse events (TEAEs) were reported (n = 32 subjects), with 2 serious AEs (n = 1) in the test group. TEAEs were not considered treatment-related. CONCLUSIONS: All groups demonstrated statistically significant improvements in Schiff score, tactile threshold and OHRQoL. However, due to a possible placebo effect in the negative control, there were no statistically significant differences between the dentifrices. CLINICAL RELEVANCE: This study adds to the growing research exploring why the placebo effect is a common phenomenon in DH studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04950465.

Does the urinary microbiome profile change after treatment of bladder cancer?

INTRODUCTION: We sought to investigate the change in the urinary microbiome profile after transurethral resection of bladder tumor (TURBT). METHODS: Urine specimens were collected from consecutive patients with bladder cancer. Patients were divided into those with bladder tumors ("Tumor group": de novo tumors or recurrent/progressed after TURBT ± intravesical therapy) versus those without evidence of recurrence after treatment "No Recurrent Tumor group". Samples were analyzed using 16S rRNA sequencing. Alteration in the urinary microbiome was described in terms of alpha (diversity within a sample measured by Observed, Chao, Shannon, and Simpson indices), beta diversities (diversity among different samples measured by Brady Curtis Diversity index), and differential abundance of bacteria at the genus level. Analyses were adjusted for gender, method of preservation (frozen vs preservative), and method of collection (mid-stream vs. catheter). RESULTS: Sixty-eight samples were analyzed (42 in "Tumor" vs 26 in "No Recurrent Tumor" groups). The median age was 70 years (IQR 64-74) and 85% were males. All patients in the "No Recurrent Tumor" group had non-muscle invasive bladder cancer and 85% received BCG compared to 69% and 43% for the "Tumor" group, respectively. There was no significant difference in alpha diversity (p > 0.05). Beta diversity was significantly different (p = 0.04). Veillonella and Bifidobacterium were more abundant in the "Tumor" group (> 2FC, p = 0.0002), while Escherichia-Shigella (> 2FC, p = 0.0002) and Helococcus (> 2FC, p = 0.0008) were more abundant in the "No Recurrent Tumor" group. CONCLUSION: Bladder cancer patients with no recurrence and/or progression exhibited a different urinary microbiome profile compared to those with tumors.

Pediatric Dance-Related Injuries Treated in Emergency Departments in the United States, 2000-2020.

OBJECTIVE: This study investigated the characteristics and trends of children aged 3 to 19 years treated in US emergency departments for dance-related injuries. METHODS: Retrospective analysis of data from the National Electronic Injury Surveillance System from 2000 through 2020 was conducted. RESULTS: An estimated 489,119 children received emergency treatment for a dance-related injury, averaging 23,291 children annually, and the rate of injury increased 68.1% during the 21-year study period. Girls accounted for 80.3% and children aged 15 to 19 years accounted for 46.5% of cases. Sprains/strains were the most frequent diagnosis (44.4%), and lower extremities were the most commonly injured body region (56.4%). Compared with other body regions, patients aged 3 to 10 years were more likely to sustain head/neck injuries (odds ratio, 3.94, 95% confidence interval, 3.42-4.52) than 11- to 19-year-olds. Falls and noncontact mechanisms of injury accounted for 35.6% and 32.1% of injuries, respectively. Unstructured dance activity was associated with 30.8% of dance-related injuries overall and 67.0% among children aged 3 to 5 years. Ballet/pointe dancers frequently sustained lower extremity sprains/strains (39.2%). Compared with other dance types, break dancing was more commonly associated with injuries to an upper extremity than other body regions (odds ratio, 4.76, 95% confidence interval, 3.66-6.19). CONCLUSIONS: The rate of pediatric dance-related injuries treated in US emergency departments is increasing. Unstructured dance activity was an important source of dance-related injury, especially among children aged 3 to 5 years. The injury diagnosis and body region injured varied by child age and type of dance. Additional targeted prevention efforts should be implemented that address the injury characteristics of dancer subgroups.

Non-invasive oocyte quality assessment.

Oocyte quality is perhaps the most important limiting factor in female fertility; however, the current methods of determining oocyte competence are only marginally capable of predicting a successful pregnancy. We aim to review the predictive value of non-invasive techniques for the assessment of human oocytes and their related cells and biofluids that pertain to their developmental competence. Investigation of the proteome, transcriptome, and hormonal makeup of follicular fluid, as well as cumulus-oocyte complexes are currently underway; however, prospective randomized non-selection-controlled trials of the future are needed before determining their prognostic value. The biological significance of polar body morphology and genetics are still unknown and the subject of debate. The predictive utility of zygotic viscoelasticity for embryo development has been demonstrated, but similar studies performed on oocytes have yet to be conducted. Metabolic profiling of culture media using human oocytes are also limited and may require integration of automated, high-throughput targeted metabolomic assessments in real time with microfluidic platforms. Light exposure to oocytes can be detrimental to subsequent development and utilization of time-lapse imaging and morphometrics of oocytes is wanting. Polarized light, Raman microspectroscopy, and coherent anti-Stokes Raman scattering are a few novel imaging tools that may play a more important role in future oocyte assessment. Ultimately, the integration of chemistry, genomics, microfluidics, microscopy, physics, and other biomedical engineering technologies into the basic studies of oocyte biology, and in testing and perfecting practical solutions of oocyte evaluation, are the future for non-invasive assessment of oocytes.

Lessons from the implementation of the Health Care Homes program.

Australia's primary health care system works well for most Australians, but 20% of people live with multimorbidity, often receiving fragmented care in a complex system. Australia's 10-year plan for primary health care recognises that person-centred care is essential to securing universal health coverage, improving health outcomes and achieving an integrated sustainable health system. The Health Care Homes trial tested a new model of person-centred care for people with chronic and complex health conditions. This model demonstrated that change can be achieved with dedicated transformational support and highlighted the importance of enablers and reform streams that are now established in the 10-year plan.

Antidepressant exposures associated with exploratory behavior among young children reported to United States poison control centers, 2000-2020.

PURPOSE: This study investigates characteristics and trends of antidepressant exposures among children <6 years old related to exploratory behavior reported to US poison control centers. METHODS: Using data from the National Poison Data System for 2000-2020, population-based annual exposure rates by sex, antidepressant category, serious medical outcome, and health care facility admission were analyzed and odds ratios to assess associations of exposure type and antidepressant category with medical outcome and admission were calculated. RESULTS: There were 215 909 first-ranked unintentional exploratory exposures involving antidepressants among children <6 years old during the study period, averaging 10 281 annually. Most cases were <3 years old (77.8%), involved a single substance (86.9%), and did not receive treatment at a health care facility (57.6%); however, 7.9% were admitted and 3.4% had serious medical outcomes, including 13 deaths. SSRIs were involved in 56.9% of all cases. Compared with SSRIs, bupropion (OR: 5.22, 95% CI: 4.68-5.82), TCAs (OR: 3.74, 95% CI: 3.44-4.07), SNRIs (OR: 2.39, 95% CI: 2.11-2.71), and lithium salts (OR: 2.00, 95% CI: 1.63-2.46) were more likely to be associated with a serious medical outcome. TCAs were the first-ranked substance in 7 of the 13 deaths. CONCLUSIONS: Although most unintentional antidepressant exposures related to pediatric exploratory behavior were inconsequential, an important minority of cases required admission to a HCF or had a serious medical outcome, including 13 deaths. Therefore, increased efforts to prevent these exposures among young children are needed, including public education and improved medication packaging.

Motor vehicle-related electric scooter injuries in the US: A descriptive analysis of NEISS data.

INTRODUCTION: The introduction of scooter-share programs across the United States has led to an increased incidence of electronic scooter (e-scooter) injuries presenting to emergency departments (EDs). As legislation begins to push scooters from the sidewalk to the street, injuries resulting from collisions between e-scooters and motor vehicles are an important, but poorly characterized consideration. This study leverages data from a national injury surveillance system to characterize e-scooter versus motor vehicle collisions resulting in ED presentation. METHODS: This study utilizes data from the National Electronic Injury Surveillance System (NEISS). NEISS was queried for e-scooter-related injuries from January 1st, 2015 through December 31st, 2019. Injuries were characterized as motor vehicle-related (MV-involved) or non-motor-vehicle-related (MV-uninvolved) based on a manual review by the study investigators. Weighted tabular analyses were used to characterize both types of e-scooter injuries across demographic, diagnostic, and event-related factors. RESULTS: Over the study period an estimated 60,554 (95% CI: 37,525-84,594) injuries were treated in US EDs. Approximately 19% of these injuries involved motor vehicles. Those sustaining MV-involved injuries were significantly younger (p = 0.01), with a higher proportion of males injured (p = 0.01). Additionally, when compared to MV-uninvolved injuries, a significantly higher proportion of those with MV-involved injuries were admitted to the hospital for treatment (8.8% vs. 14.6%, p < 0.01). MV-involved injuries occurred primarily in the street (96.3%), while MV-uninvolved injuries were split across streets (44.0%), at one's home (~20%), and on public property (~20%) (p < 0.01). CONCLUSIONS: Electric scooter injuries involving a motor vehicle differed from those that did not across several key categories. As e-scooters and motor vehicles start to share the road more frequently, greater consideration should be made regarding how these two modes of transportation interact with each other. The promotion of thoughtful e-scooter legislation and infrastructure changes could help promote safer travel.

Active Surveillance in Prostate Cancer: Current and Potentially Emerging Biomarkers for Patient Selection Criteria.

BACKGROUND: Prostate cancer (PCa) represents one of the most frequent malignancies and the fifth leading cause of cancer death in adult men worldwide. PCa mortality rates have been declining in several Western countries; one of the possible reasons may be related to the application of prostate-specific antigen early detection policies. These early detection protocols increase PCa-specific patient survival; however, a high percentage of these cases corresponds to low-risk PCa that grows very slowly and is unlikely to metastasize to threaten survival. Many low-risk PCa patients receive aggressive therapies, such as radical prostatectomy and radiotherapy, that are costly for patients and/or health systems and generate side effects that affect the quality of life. An alternative to surgery and radiotherapy treatments for low-risk PCa is active surveillance (AS), a strategy based on close disease monitoring and intervention only if the disease progresses. However, proper identification of low-risk PCa patients at the time of diagnosis is essential for the effectiveness AS. The selection of AS candidates remains challenging; thus, effective prognostic biomarkers are needed. SUMMARY: This review article addresses the characteristics of the current and emerging PCa prognostic biomarkers, including tests available for tissue, blood, and urine analyses, for the appropriate selection of PCa patients for AS. In addition, and based on published literature, we performed a selection of potential new biomarkers that can distinguish low-risk PCa. KEY MESSAGES: The literature search yielded four tissue-based tests, two blood-based tests, and six urine-based tests that can be used to determine PCa risk classification. However, most available tests are expensive; thus, cost-effective analyses are needed in order to obtain the approval of government agencies and to be financed by the health systems. Available prognostic urine tests have shown great progress over the last years, and they have the advantage of being minimally invasive; therefore, they may become a routine disease progression test for patients under AS. In addition, new research conducted in the last decade has shown promising biomarkers, including mRNA, miRNA, long noncoding RNA, and metabolites, that could improve existing tests or allow the development of new tools for AS patient selection.

Tumor-Suppressor Role of the α1-Na/K-ATPase Signalosome in NASH Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, with an estimate of 0.84 million cases every year. In Western countries, because of the obesity epidemic, non-alcoholic steatohepatitis (NASH) has become the major cause of HCC. Intriguingly, the molecular mechanisms underlying tumorigenesis of HCC from NASH are largely unknown. We hypothesized that the growing uncoupled metabolism during NASH progression to HCC, manifested by lower cell redox status and an apoptotic 'switch' activity, follows a dysregulation of α1-Na/K-ATPase (NKA)/Src signalosome. Our results suggested that in NASH-related malignancy, α1-NKA signaling causes upregulation of the anti-apoptotic protein survivin and downregulation of the pro-apoptotic protein Smac/DIABLO via the activation of the PI3K → Akt pro-survival pathway with concomitant inhibition of the FoxO3 circuit, favoring cell division and primary liver carcinogenesis. Signalosome normalization using an inhibitory peptide resets apoptotic activity in malignant cells, with a significant decrease in tumor burden in vivo. Therefore, α1-NKA signalosome exercises in HCC the characteristic of a tumor suppressor, suggesting α1-NKA as a putative target for clinical therapy.

Clinical outcomes of percutaneous debulking of tricuspid valve endocarditis in intravenous drug users.

OBJECTIVES: A retrospective case series of a percutaneous approach to debulk tricuspid valve endocarditis (TVE) using an 8 French mechanical aspiration system in patients with a history of intravenous drug use (IVDU) was reported. IVDU associated TVE is increasing in the United States and is associated with high mortality despite early surgical debridement. Patients with advanced disease, shock, and respiratory failure may not be candidates for surgical debridement or replacement. These patients have recurrent events despite medical therapy METHODS: About 25 patients with IVDU associated TVE with persistent bacteremia confirmed by repeat blood cultures after 72 hr of sensitivity directed antibiotics and presence of pulmonary emboli confirmed by computed tomographic (CT) scan, who had undergone percutaneous aspiration were included. Patients were all deemed high risk for surgical debridement by a CT surgeon and evaluated by an infectious disease consultant. Procedures were performed under moderate sedation with intracardiac echo and a steerable guide with a CAT8 Penumbra aspiration catheter. RESULTS: There were no intraprocedural deaths or complications. About 36% had septic shock on presentation. Survival of index hospitalization was 88%. Repeat blood cultures showed no growth on all surviving patients. Readmission rate was 4% (n = 1) at 1 month. About 40% (n = 2) patients with septic shock survived at 1 month compared with 100% survival (n = 20) in those without shock. Presence of septic shock was associated with reduced survival at 1 month (p < .01). CONCLUSION: Percutaneous mechanical aspiration with an 8 Fr system is a feasible, minimally invasive alternative to surgical debulking. Mortality remains high in those presenting with septic shock. Further studies are needed to evaluate long-term outcomes.

Assessing the Accuracy of a Deep Learning Method to Risk Stratify Indeterminate Pulmonary Nodules.

Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.Objectives: To develop and validate a deep learning method to improve the management of IPNs.Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions.Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4-90.7%) and 91.9% (95% CI, 88.7-94.7%), compared with 78.1% (95% CI, 68.7-86.4%) and 81.9 (95% CI, 76.1-87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts.Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.

A cross-sectional study of characteristics of bicyclist upper and lower extremity injuries in bicycle-vehicle crashes in Ohio, United States, 2013-2017.

BACKGROUND: Extremity injury is one of the most common injury types for bicyclists. Extremity injury can lead to long-term disability and contribute to adverse health-related quality of life and prolonged absence from work. OBJECTIVES: The objectives of our study were to identify crash factors associated with bicyclist upper and lower extremity injury and characterize type of extremity injury by bicyclist age category. METHODS: We linked the 2013-2017 Ohio police accident report and hospital databases. The logistic regression model was used to model the odds of sustaining upper or lower extremity injury among bicyclists involved in bicycle-vehicle crashes. Bicyclist upper and lower extremity injury were further described by the detailed injured body regions (e.g., forearm and elbow or lower leg) and the nature of injury (e.g., superficial or fracture). RESULTS: Bicyclists 65 years or older had higher odds (odds ratio [OR] = 1.46, 95% confidence interval [CI]: 1.03-2.08) of sustaining upper extremity injury, bicyclists aged 3-14 years (OR = 1.34, 95% CI: 1.09-1.66) and 15-24 years (OR = 1.24, 95% CI: 1.03-1.49) had higher odds of sustaining lower extremity injury, compared to bicyclists 25-44 years old. In addition, colder weather, bicyclist sex, and intersection-related crashes were associated with bicyclists' odds of sustaining upper or lower extremity injury. Compared to individuals under 65 years old, bicyclists 65 years or older had a higher percentage of injury to the wrist, hand and finger, or knee. Bicyclists aged 65 years or older also had a higher percentage of fractures. CONCLUSIONS: Our study has identified important factors that were associated with bicyclists' odds of sustaining an extremity injury. Based on these findings, targeted educational efforts and interventions can be implemented to prevent bicyclists from these injuries.

Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48 440 adult patients.

OBJECTIVES: To compare hospitalisation rates, intensive care unit (ICU) admissions and mortality for patients with COVID-19 who were consistently inactive, doing some activity or consistently meeting physical activity guidelines. METHODS: We identified 48 440 adult patients with a COVID-19 diagnosis from 1 January 2020 to 21 October 2020, with at least three exercise vital sign measurements from 19 March 2018 to 18 March 2020. We linked each patient's self-reported physical activity category (consistently inactive=0-10 min/week, some activity=11-149 min/week, consistently meeting guidelines=150+ min/week) to the risk of hospitalisation, ICU admission and death after COVID-19 diagnosis. We conducted multivariable logistic regression controlling for demographics and known risk factors to assess whether inactivity was associated with COVID-19 outcomes. RESULTS: Patients with COVID-19 who were consistently inactive had a greater risk of hospitalisation (OR 2.26; 95% CI 1.81 to 2.83), admission to the ICU (OR 1.73; 95% CI 1.18 to 2.55) and death (OR 2.49; 95% CI 1.33 to 4.67) due to COVID-19 than patients who were consistently meeting physical activity guidelines. Patients who were consistently inactive also had a greater risk of hospitalisation (OR 1.20; 95% CI 1.10 to 1.32), admission to the ICU (OR 1.10; 95% CI 0.93 to 1.29) and death (OR 1.32; 95% CI 1.09 to 1.60) due to COVID-19 than patients who were doing some physical activity. CONCLUSIONS: Consistently meeting physical activity guidelines was strongly associated with a reduced risk for severe COVID-19 outcomes among infected adults. We recommend efforts to promote physical activity be prioritised by public health agencies and incorporated into routine medical care.

Mouse oocyte vitrification with and without dimethyl sulfoxide: influence on cryo-survival, development, and maternal imprinted gene expression.

PURPOSE: Oocytes and embryos can be vitrified with and without dimethyl sulfoxide (DMSO). Objectives were to compare no vitrification (No-Vitr), vitrification with DMSO (Vitr + DMSO), and vitrification without DMSO (Vitr - DMSO) on fresh/warmed oocyte survival, induced parthenogenetic activation, parthenogenetic embryo development, and embryonic maternal imprinted gene expression. METHODS: In this prospective controlled laboratory study, mature B6C3F1 female mouse metaphase II oocytes were treated as: i) No-Vitr, ii) Vitr + DMSO/warmed, and iii) Vitr - DMSO/warmed with subsequent parthenogenetic activation and culture to the blastocyst stage. Oocyte cryo-survival, parthenogenetic activation and embryo development, parthenogenetic embryo maternal imprinted gene expression were outcome measures. RESULTS: Oocyte cryo-survival was significantly improved in Vitr + DMSO versus Vitr - DMSO at initial warming and 2 h after warming. Induced parthenogenetic activation was similar between all three intervention groups. While early preimplantation parthenogenetic embryo development was similar between control, Vitr + DMSO, Vitr - DMSO oocytes, the development to blastocysts was significantly inferior in the Vitr - DMSO oocytes group compared to the control and Vitr + DMSO oocyte groups. Finally, maternal imprinted gene expression was similar between intervention groups at both the 2-cell and blastocyst parthenogenetic embryo stage. CONCLUSION(S): Inclusion of DMSO in oocyte vitrification solutions improved cryo-survival and developmental potential of parthenogenetic embryos to the blastocyst stage without significantly altering maternal imprinted gene expression.

A CD24-p53 axis contributes to African American prostate cancer disparities.

BACKGROUND: Using a functional analysis of prostate cancer cells, we found a CD24-dependent inactivation of mutant p53, but the clinical significance of this observation remained uncertain. Here, we validated these results with samples of human prostate cancer and explored the role of a CD24-p53 axis in racial disparities of prostate cancer. METHODS: Samples of formalin-fixed, paraffin-embedded prostate cancer from 141 European Americans (EAs) and 147 African Americans (AAs) in two independent sample cohorts were assessed for protein expression of CD24, mutant p53, mouse double minute 2 human homolog (MDM2), and cyclin dependent kinase inhibitor 2A (ARF) using immunohistochemical analyses. All samples were analyzed for TP53R175H and TP53R273H . RESULTS: CD24, mutant p53, MDM2, and ARF proteins were expressed in 55%, 24%, 39%, and 68% of prostate cancer samples, respectively. CD24 and mutant p53 were present more frequently in late-stage and metastatic prostate cancer. The presence of CD24 was associated with a greater than fourfold risk of metastasis, which included lymph node and distant metastases. H score analysis showed positive correlations of CD24 expression with mutant p53 (r = .308, P < .001) and MDM2 (r = .227, P = .004). There was a negative correlation for CD24 with ARF (r = -.280, P < .001). A racial disparity was evident for CD24 (AAs/EAs: 64% vs 47%; P = .004) but not for mutant p53 (AA/EA: 28% vs 21%; P = .152). In 32 CD24+ /mutant p53+ cases, a TP53R273H mutation was found in five cases, but no TP53R175H mutation was found. CONCLUSION: The CD24-p53 axis may contribute to aggressive and metastatic prostate cancers, especially those of AAs. This observation enhances understanding of the pathogenesis of prostate cancer and its associated racial disparities.

Comparison of the effectiveness of female voice, male voice, and hybrid voice-tone smoke alarms for sleeping children.

BACKGROUND: To test whether children awaken from slow wave sleep and perform an escape procedure better in response to a smoke alarm that uses a male voice, female voice, combination of a low-frequency tone plus a female voice (hybrid alarm), or high-frequency tone. METHODS: Using a randomized, non-blinded, repeated-measures design, 188 children aged 5-12 years were exposed during stage 4 slow wave sleep to four smoke alarms. RESULTS: Among study subjects, 84.6%, 87.2%, 88.8%, and 56.4% awakened and 84.0%, 86.7%, 88.8%, and 55.3% successfully performed the escape procedure within 5 min of alarm onset in response to the male voice, female voice, hybrid, and high-frequency tone alarms, respectively, while the median time-to-escape was 12.0, 12.0, 13.0, and 96.5 s for these four alarms, respectively. All pairwise comparisons between the high-frequency tone alarm and each of the other three alarms were statistically significant for the proportions of subjects who awakened or escaped and for time-to-awaken and time-to-escape. There were no significant differences in these outcome measures between the latter three alarms. CONCLUSIONS: Use of the male or female voice or hybrid alarms in children's sleep areas may reduce residential fire-related injuries and deaths among children old enough to perform self-rescue. IMPACT: The male voice, female voice, and hybrid alarms were each significantly more effective than a high-frequency tone alarm in awakening children aged 5-12 years from slow wave sleep and prompting their performance of an escape procedure. There were no significant differences in the effectiveness of the male voice, female voice, and hybrid alarms when compared with each other. Use of these alarms in children's sleep areas may reduce residential fire-related injuries and deaths among children old enough to perform self-rescue.

Suicide-related over-the-counter analgesic exposures reported to United States poison control centers, 2000-2018.

PURPOSE: To investigate suicide-related over-the-counter (OTC) analgesic medication exposures among individuals ≥6 years old reported to United States (US) poison control centers. METHODS: Data from the National Poison Data System for the years 2000-2018 were retrospectively analyzed. RESULTS: From 2000 to 2018, US poison control centers recorded 549 807 suicide-related cases involving OTC analgesics, including 327 781 cases (59.6%) admitted to the hospital and 1745 deaths (0.3%). Most cases involved a single substance (67.5%) and occurred among females (72.7%) and individuals 6-19 years old (49.7%). Overall, the rate of exposures increased significantly by 33.5% from 2000 to 2018, primarily driven by the increasing exposure rate among 6- to 19-year-old females. From 2000 to 2018, exposure rates for acetaminophen and ibuprofen increased, while that for acetylsalicylic acid decreased. Additionally, the proportion of cases resulting in a serious medical outcome or healthcare facility admission increased for all types of OTC analgesics. Acetaminophen and acetylsalicylic acid accounted for 48.0% and 18.5% of cases, respectively, and 64.5% and 32.6% of deaths, respectively. Both acetaminophen and acetylsalicylic acid had greater odds of healthcare facility admission (ORs 2.56 and 2.63, respectively) and serious medical outcomes (ORs 2.54 and 4.90, respectively) compared with ibuprofen. CONCLUSIONS: The rate of suicide-related OTC analgesic cases is increasing. Acetaminophen and acetylsalicylic acid cases are associated with greater morbidity and mortality. Prevention efforts should include implementing unit-dose packaging requirements and restrictions on package sizes and purchase quantities for acetaminophen and acetylsalicylic acid products to reduce access to large quantities of these analgesics.

Alternative polyadenylation coordinates embryonic development, sexual dimorphism and longitudinal growth in Xenopus tropicalis.

RNA alternative polyadenylation contributes to the complexity of information transfer from genome to phenome, thus amplifying gene function. Here, we report the first X. tropicalis resource with 127,914 alternative polyadenylation (APA) sites derived from embryos and adults. Overall, APA networks play central roles in coordinating the maternal-zygotic transition (MZT) in embryos, sexual dimorphism in adults and longitudinal growth from embryos to adults. APA sites coordinate reprogramming in embryos before the MZT, but developmental events after the MZT due to zygotic genome activation. The APA transcriptomes of young adults are more variable than growing adults and male frog APA transcriptomes are more divergent than females. The APA profiles of young females were similar to embryos before the MZT. Enriched pathways in developing embryos were distinct across the MZT and noticeably segregated from adults. Briefly, our results suggest that the minimal functional units in genomes are alternative transcripts as opposed to genes.

Nonfatal horse-related injuries treated in emergency departments in the United States, 1990-2017.

BACKGROUND: Horse-related injuries can cause severe morbidity and mortality. The objective of this study is to investigate the epidemiological features of horse-related injuries treated in emergency departments (EDs) in the United States. METHODS: A retrospective analysis of horse-related injuries from 1990 through 2017 was conducted utilizing the National Electronic Injury Surveillance System (NEISS). Cases were identified using the NEISS code 1239 (Horseback Riding: Activity, Apparel, or Equipment). Analyses performed included calculation of national injury estimates, relative risks (RRs) with 95% confidence intervals (CIs), and linear regression. RESULTS: From 1990 through 2017, an estimated 1,836,536 (95% CI: 1,494,788-2,178,284) individuals presented to United States EDs with horse-related injuries. The annual injury rate decreased by 30.8% from 1990 to 1996, increased by 33.0% from 1996 to 2000, and then decreased by 46.0% from 2000 to 2017. Among older adults >60 years of age, the annual injury rate increased by 139.6% during the study period. The number of concussion and closed head injury diagnoses increased by 337.2% from 1990 to 2009. The most common mounted mechanism of injury was a fall or being thrown (73.9%), while the most common unmounted mechanism was being kicked (42.1%). Mounted injuries were more likely to lead to hospitalization than unmounted injuries (RR, 2.10, 95% CI: 1.59-2.77). CONCLUSIONS: Despite the recent decline in horse-related injuries, these injuries are still common. Clinicians should be aware of the spectrum of ED presentations of horse-related injuries. Prevention efforts focused on older adults and concussions and closed head injuries warrant special attention.