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American Journal of Epidemiology Jun 2024To estimate the effect of geographic variation in historic slavery on perinatal outcomes [chronic hypertension, hypertensive disorders of pregnancy (HDP), very preterm...
OBJECTIVE
To estimate the effect of geographic variation in historic slavery on perinatal outcomes [chronic hypertension, hypertensive disorders of pregnancy (HDP), very preterm birth (VPTB), or very low birth weight birth (VLBW)] among Black people living in states where slavery was legal in 1860 and test mediation by Black homeownership.
METHODS
We linked data from the 1860 census (the proportion of enslaved residents) to natality data on outcomes (2013-2021) using resident county. The percent of Black residents in a county who owned their home was a potential mediator. We fit log binomial models to estimate risk ratios (RRs) representing total and controlled direct effects (accounting for Black homeownership) of proportion enslaved on outcomes, accounting for potential confounding using marginal structural models.
RESULTS
Among 2,443,198 included births, 8.8% (213,829) experienced HDP, 4.1% (100,549) chronic hypertension, 3.3% (81,072) VPTB, and 2.6% (62,538) VLBW. There was an increase in chronic hypertension and VPTB risk, but not HDP or VLBW, in counties with a 10% greater proportion enslaved in 1860 [adjusted RR: 1.06, 95% CI: (1.02, 1.1); 1.02 (1.00, 1.05); 1.00 (0.98, 1.02); 1.01 (1.00, 1.03)]. There was not evidence of mediation by Black homeownership.
CONCLUSIONS
Historic slavery remains relevant for perinatal health.
PubMed: 38944756
DOI: 10.1093/aje/kwae138 -
Journal of Pediatric Urology Jun 2024Many pediatric urology conditions affect putatively normal tissues or appear too commonly to be based solely on specific DNA mutations. Understanding epigenetic...
INTRODUCTION
Many pediatric urology conditions affect putatively normal tissues or appear too commonly to be based solely on specific DNA mutations. Understanding epigenetic mechanisms in pediatric urology, therefore, has many implications that can impact cell and tissue responses to settings, such as environmental and hormonal influences on urethral development, uropathogenic infections, obstructive stimuli, all of which originate externally or extracellularly. Indeed, the cell's response to external stimuli is often mediated epigenetically. In this commentary, we highlight work on the critical role that epigenetic machinery, such as DNA methyltransferases (DNMTs), Enhancer of Zeste Polycomb Repressive Complex 2 Subunit (EZH2), and others play in regulating gene expression and cellular functions in three urological contexts.
DESIGN
Animal and cellular constructs were used to model clinical pediatric uropathology. The hypertrophy, trabeculation, and fibrosis of the chronically obstructed bladder was explored using smooth muscle cell models employing disorganised vs. normal extracellular matrix (ECM), as well as a new animal model of chronic obstructive bladder disease (COBD) which retains its pathologic features even after bladder de-obstruction. Cell models from human and murine hypospadias or genital tubercles (GT) were used to illustrate developmental responses and epigenetic dependency of key developmental genes. Finally, using bladder urothelial and organoid culture systems, we examined activity of epigenetic machinery in response to non uropathogenic vs. uropathogenic E.coli (UPEC). DNMT and EZH2 expression and function were interrogated in these model systems.
RESULTS
Disordered ECM exerted a principal mitogenic and epigenetic role for on bladder smooth muscle both in vitro and in CODB in vivo. Key genes, e.g., BDNF and KCNB2 were under epigenetic regulation in actively evolving obstruction and COBD, though each condition showed distinct epigenetic responses. In models of hypospadias, estrogen strongly dysregulated WNT and Hox expression, which was normalized by epigenetic inhibition. Finally, DNA methylation machinery in the urothelium showed specific activation when challenged by uropathogenic E.coli. Similarly, UPEC induces hypermethylation and downregulation of the growth suppressor p16INK4A. Moreover, host cells exposed to UPEC produced secreted factors inducing epigenetic responses transmissible from one affected cell to another without ongoing bacterial presence.
DISCUSSION
Microenvironmental influences altered epigenetic activity in the three described urologic contexts. Considering that many obstructed bladders continue to display abnormal architecture and dysfunction despite relief of obstruction similar to after resection of posterior valves or BPH, the epigenetic mechanisms described highlight novel approaches for understanding the underlying smooth muscle myopathy of this crucial clinical problem. Similarly, there is evidence for an epigenetic basis of xenoestrogen on development of hypospadias, and UTI-induced pan-urothelial alteration of epigenetic marks and propensity for subsequent (recurrent) UTI. The impact of mechanical, hormonal, infectious triggers on genitourinary epigenetic machinery activity invite novel avenues for targeting epigenetic modifications associated with these non-cancer diseases in urology. This includes the use of deactivated CRISPR-based technologies for precise epigenome targeting and editing. Overall, we underscore the importance of understanding epigenetic regulation in pediatric urology for the development of innovative therapeutic and management strategies.
PubMed: 38944627
DOI: 10.1016/j.jpurol.2024.06.008 -
Journal of Pediatric Surgery Jun 2024Gunshot injuries are the leading cause of death among children in the United States. The goal of this study was to better understand if certain age groups, mechanisms of...
BACKGROUND
Gunshot injuries are the leading cause of death among children in the United States. The goal of this study was to better understand if certain age groups, mechanisms of injury, and type of firearms were associated with the increasing rates of pediatric gun-related trauma. We hypothesized that the extremities were disproportionately targeted when compared with the random likelihood of striking specific body-surface areas.
METHODS
This study includes pediatric firearm-related injury (FRI) patients who presented to a single free-standing level 1 pediatric hospital or died at the scene from 2010 to 2021. The hospital data was collected prospectively as part of a level 1 trauma system electronic database. Death data was collected from the local coroner's office.
RESULTS
Between 2010 and 2021, 1,126 pediatric FRI occurred in the geographic region studied. Demographic information available for 1,118 patients showed that 897 (80.23%) were male, and that black individuals had a statistically significant increased rate of FRI compared with white or Hispanic individuals. Mean age was 13.69 years. Most injuries were caused by handguns.
CONCLUSIONS
This data could help leaders design strategies to combat the violence, such as legislation that limits handgun access to all, especially children, and mandates safe storage of handguns. Gun-lock programs, universal background checks, and firearm-ownership education also might help stem this tide of violence.
LEVEL OF EVIDENCE
Level II Prognosis study.
PubMed: 38944592
DOI: 10.1016/j.jpedsurg.2024.06.003 -
Comparative Biochemistry and... Jun 2024The daily variations of temperature are one of the main synchronizers of the circadian rhythms. In addition, water temperature influences the embryonic and larval...
Ontogeny of daily rhythms in the expression of metabolic factors in Nile tilapia (Oreochromis niloticus) kept at two different temperature regimes: Thermocycle and constant temperature.
The daily variations of temperature are one of the main synchronizers of the circadian rhythms. In addition, water temperature influences the embryonic and larval development of fish and directly affects their metabolic processes. The application of thermocycles to fish larvae has been reported to improve growth and the maturation of the digestive system, but their effects on metabolism are poorly understood. The aim of the present study was to evaluate the effect of two different temperature regimes, cycling versus constant, on the daily rhythms of metabolic factors of Nile tilapia (Oreochromis niloticus) larvae. For this purpose, fertilized eggs were divided into two groups: one reared in a 31 °C:25 °C day:night thermocycle (TCY) and another group maintained in a constant 28 °C temperature (CTE). The photoperiod was set to a 12:12 h light/dark cycle. Samples were collected every 4 h during a 24-h cycle on days 4, 8 and 13 post fertilization (dpf). The expression levels of alanine aminotransferase (alt), aspartate aminotransferase (ast), malic enzyme, glucose-6-phosphate dehydrogenase (g6pd), phosphofructokinase (pfk) and pyruvate kinase (pk) were analyzed by qPCR. Results showed that, in 13 dpf animals, most of the genes analyzed (alt, ast, malic, g6pd and pfk) showed daily rhythms in TCY, but not in the group kept at constant temperature, with most acrophases detected during the feeding period. An increase in nutrient metabolism around feeding time can improve food utilization and thus increase larval performance. Therefore, the use of thermocycles is recommended for tilapia larviculture.
PubMed: 38944269
DOI: 10.1016/j.cbpa.2024.111687 -
The Journal of Arthroplasty Jun 2024Ceramic-on-ceramic (CoC) bearings have been increasingly used in total hip arthroplasty (THA) because of their superior wear resistance and biocompatibility. However,...
INTRODUCTION
Ceramic-on-ceramic (CoC) bearings have been increasingly used in total hip arthroplasty (THA) because of their superior wear resistance and biocompatibility. However, there is a scarcity of reports on the computed tomography (CT) evaluation of CoC bearings with more than 10 years. The aim of this study was to evaluate the long-term CT results of THA using CoC bearings for more than 20 years of follow-up. We hypothesized that there would be no wear, osteolysis, or ceramic fracture.
METHODS
Between November 1997 and June 2003, 956 hips underwent THA using alumina-on-alumina bearings at a tertiary referral hospital. Among them, 107 hips were assessed, all of which underwent a CT examination more than 20 years after the index surgery. The mean age at the time of surgery was 41 years, and a CT scan was performed at an average of 22.0 years postoperatively (range, 20.0 to 25.1). The CT scans were thoroughly assessed for osteolysis, stem notching, and ceramic component fracture.
RESULTS
No loosening was observed in the acetabular cup or femoral stem. Stem notching was observed in 3 hips (2.8%). In the CT scan taken after a minimum of 20 years of follow-up, one case (0.9%) of osteolysis around the cup and two cases (1.9%) of osteolysis around the femoral stem were noted. Suspected chip fractures of the ceramic insert were discovered in four cases (3.7%). Despite these findings, the patients remained asymptomatic, and no subsequent surgical intervention was needed after close follow-up.
CONCLUSION
Routine CT examinations for patients who underwent THA using CoC bearings over 20 years ago revealed unexpected findings, such as osteolysis and suspected chip fractures of the ceramic liner. However, routine CT scans may not be universally necessary. The CT evaluation in this cohort should be selectively performed for patients who have relevant clinical symptoms.
PubMed: 38944063
DOI: 10.1016/j.arth.2024.06.058 -
BMC Medical Education Jun 2024Patient care ownership (PCO) among medical students is a growing area in the field of medical education. While PCO has received increasing attention, there are no...
BACKGROUND
Patient care ownership (PCO) among medical students is a growing area in the field of medical education. While PCO has received increasing attention, there are no instruments to assess PCO in the context of Japanese undergraduate medical education. This study aimed to translate, culturally adapt, and validate the PCO Scale - Medical students (PCOS-S) in the Japanese context.
METHODS
We collected survey data from fifth- and sixth-grade medical students from five different universities varying in location and type. Structural validity, convergent validity, and internal consistency reliability were examined.
RESULTS
Data from 122 respondents were analyzed. Factor analysis of the Japanese PCOS-S revealed three factors with Cronbach's alpha values exceeding the satisfactory criterion (0.70). A positive correlation was observed between the total Japanese PCOS-S scores and the global rating scores for the clinical department as a learning environment (Pearson's correlation coefficient = 0.61).
CONCLUSIONS
We conducted the translation of the PCOS-S into Japanese and assessed its psychometric properties. The Japanese version has good reliability and validity. This instrument has potential value in assessing the development of medical students' PCO.
Topics: Humans; Students, Medical; Japan; Reproducibility of Results; Psychometrics; Female; Male; Surveys and Questionnaires; Translations; Education, Medical, Undergraduate; Ownership; Patient Care; Translating; Factor Analysis, Statistical
PubMed: 38943114
DOI: 10.1186/s12909-024-05704-8 -
BMC Oral Health Jun 2024Early childhood caries (ECC) is a multifactorial disease in which environmental factors could play a role. The purpose of this scoping review was to map the published... (Review)
Review
BACKGROUND
Early childhood caries (ECC) is a multifactorial disease in which environmental factors could play a role. The purpose of this scoping review was to map the published literature that assessed the association between the Sustainable Development Goal (SDG) 11, which tried to make cities and human settlements safe, inclusive, resilient and sustainable, and ECC.
METHODS
This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. In July 2023, a search was conducted in PubMed, Web of Science, and Scopus using tailored search terms related to housing, urbanization, waste management practices, and ECC. Studies that solely examined ECC prevalence without reference to SDG11 goals were excluded. Of those that met the inclusion criteria, a summary highlighting the countries and regions where the studies were conducted, the study designs employed, and the findings were done. In addition, the studies were also linked to relevant SDG11 targets.
RESULTS
Ten studies met the inclusion criteria with none from the African Region. Six studies assessed the association between housing and ECC, with findings suggesting that children whose parents owned a house had lower ECC prevalence and severity. Other house related parameters explored were size, number of rooms, cost and building materials used. The only study on the relationship between the prevalence of ECC and waste management modalities at the household showed no statistically significant association. Five studies identified a relationship between urbanization and ECC (urbanization, size, and remoteness of the residential) with results suggesting that there was no significant link between ECC and urbanization in high-income countries contrary to observations in low and middle-income countries. No study assessed the relationship between living in slums, natural disasters and ECC. We identified links between ECC and SDG11.1 and SDG 11.3. The analysis of the findings suggests a plausible link between ECC and SDG11C (Supporting least developed countries to build resilient buildings).
CONCLUSION
There are few studies identifying links between ECC and SDG11, with the findings suggesting the possible differences in the impact of urbanization on ECC by country income-level and home ownership as a protective factor from ECC. Further research is needed to explore measures of sustainable cities and their links with ECC within the context of the SDG11.
Topics: Humans; Sustainable Development; Dental Caries; Child, Preschool; Cities; Housing; Urbanization; Waste Management; Child
PubMed: 38943110
DOI: 10.1186/s12903-024-04521-1 -
The American Journal of the Medical... Jun 2024Idiopathic edema (IE) is a disease that occurs predominantly in women. It is characterized by increasing weight gain of > 1.4 kg from morning to night, increasing edema,... (Review)
Review
Idiopathic edema (IE) is a disease that occurs predominantly in women. It is characterized by increasing weight gain of > 1.4 kg from morning to night, increasing edema, increasing truncal and abdominal girth with bloating when assuming an upright position and nocturia that is unrelated to menses. There is an increase in morbidity but not mortality. Increased capillary membrane leakage appears to be the underlying pathophysiologic abnormality that explains the myriad of clinical presentations. We present 2 cases of life-threatening complications of IE that resulted in seizures related to acute hyponatremia in one and extreme postural dizziness and fainting induced by postural hypotension in the other. The first patient was successfully treated with salt restriction, timely use of furosemide and limitation of water intake; the other was successfully treated by use of support hose. Treatment of these patients required a fundamental understanding of the intricate pathophysiological consequences of a leaky capillary membrane, an understanding of Starling forces and detailing the effectiveness of a low salt diet, use of diuretics and limited water intake in one and why support hose would be beneficial in the other patient. Both patients experienced significant physical and emotional benefits that substantially improved quality of life.
PubMed: 38942171
DOI: 10.1016/j.amjms.2024.06.024 -
The Lancet. Oncology Jun 2024The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate...
Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.
BACKGROUND
The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only.
METHODS
In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or T N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual.
FINDINGS
Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related.
INTERPRETATION
Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma.
FUNDING
US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.
PubMed: 38942046
DOI: 10.1016/S1470-2045(24)00211-0 -
Gynecologic Oncology Jun 2024Mirvetuximab soravtansine may be a potentially effective therapeutic option for ovarian low-grade serous carcinoma (LGSC), but the prevalence of folate receptor alpha...
OBJECTIVE
Mirvetuximab soravtansine may be a potentially effective therapeutic option for ovarian low-grade serous carcinoma (LGSC), but the prevalence of folate receptor alpha (FRα) overexpression in this tumor type is unknown. We sought to characterize FRα expression in LGSC and its association with clinical and molecular features.
METHODS
FRα immunohistochemistry was performed on a tissue microarray comprised of 89 LGSCs and 42 ovarian serous borderline tumors (SBTs). Clinical tumor-normal panel-based sequencing was performed on 78 LGSCs. Associations between FRα-high status and clinicopathologic characteristics and survival outcomes were examined.
RESULTS
Of 89 LGSCs, 36 (40%) were FRα-high (≥75% of viable tumor cells exhibiting moderate-to-strong membranous expression). Of 9 patients with LGSC and samples from different timepoints, 4 (44%) had discordant results, with conversion from FRα-negative to FRα-high in 3 (33%) cases. There was no association between FRα-high status with age, race, or progression-free/overall survival. A MAPK pathway genetic alteration, most commonly involving KRAS (n = 23), was present in 45 (58%) LGSCs. Those lacking MAPK pathway alterations were more likely to be FRα-high compared to MAPK-altered LGSCs (61% vs 20%, p < 0.001). In SBTs, FRα-high expression was associated with high-risk (micropapillary) histology and/or subsequent LGSC recurrence compared to conventional SBTs without malignant recurrence (53% vs 9%, p = 0.008).
CONCLUSIONS
Future studies of FRα-directed therapy in patients with LGSC are warranted. Discordant FRα status at recurrence suggests potential benefit for retesting. A biomarker-driven approach to direct treatment selection in LGSC is recommended. As high FRα expression is more common amongst tumors lacking MAPK pathway genetic alterations, FRα testing to determine eligibility for mirvetuximab soravtansine therapy is particularly recommended for this subgroup.
PubMed: 38941962
DOI: 10.1016/j.ygyno.2024.06.008