Early Life and Childhood Environmental Exposures, More Than Genetic Predisposition, Influence Age of Diagnosis in a Diverse Cohort of 2952 Patients With IBD.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) develops from a combination of genetic and environmental factors. The aim of this study was to determine the contribution of established environmental risk factors and genetic risk on age of IBD diagnosis in a diverse cohort. METHODS: IBD patients in clinic completed detailed questionnaires. Blood was drawn for genetic analysis. Environmental risk factors and age of diagnosis were analyzed by ethnicity (Hispanic/Latinx or non-Hispanic White [NHW] individuals) and IBD subtype (ulcerative colitis or Crohn's disease [CD]). Weighted genetic risk scores and environmental risk scores were developed. We examined the relationship between environmental risk scores, genetic risk scores, and age of diagnosis. RESULTS: A total of 2952 patients were included: 58.9% had CD. A total of 46.83% were of Hispanic background. Early life exposures like cesarean delivery and being born in a developed country were associated with a younger age of IBD diagnosis. Childhood exposures such as frequent plastic water bottle use and having more than 1 bathroom at home were associated with a younger age of IBD. Hispanic and NHW individuals shared similar susceptibilities to environmental exposures. Environmental factors explained 21% of the variance in age of CD diagnosis and 39% in ulcerative colitis. In models incorporating genetic risk score and environmental risk score, the environment was the only significant factor associated with younger age of IBD diagnosis in all groups. CONCLUSIONS: Early life and childhood exposures impact IBD diagnosis and influence Hispanic and NHW individuals similarly. A cumulative environmental risk score contributes more to age of IBD diagnosis than genetic risk.

[A new norsesquiterpenoid from Arctium lappa leaves].

Chemical constituents were isolated and purified from ethyl acetate fraction of Arctium lappa leaves by silica gel, ODS, MCI, and Sephadex LH-20 column chromatography. Their structures were identified with multiple spectroscopical methods including NMR, MS, IR, UV, and X-ray diffraction combined with literature data. Twenty compounds(1-20) were identified and their structures were determined as arctanol(1), citroside A(2), melitensin 15-O-ß-D-glucoside(3), 11ß,13-dihydroonopordopicrin(4), 11ß,13-dihydrosalonitenolide(5), 8α-hydroxy-ß-eudesmol(6), syringin(7), dihydrosyringin(8), 3,4,3',4'-tetrahydroxy-δ-truxinate(9),(+)-pinoresinol(10), phillygenin(11), syringaresinol(12), kaeperferol(13), quercetin(14), luteolin(15), hyperin(16), 4,5-O-dicaffeoylquinic acid(17), 1H-indole-3-carboxaldehyde(18), benzyl-ß-D-glucopyranoside(19), and N-(2'-phenylethyl) isobutyramide(20). Among them, compound 1 is a new norsesquiterpenoid, and compounds 2-5, 7-8, and 18-20 are isolated from this plant for the first time.

Uterine serous carcinoma: assessing association between genomics and patterns of metastasis.

Background: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial carcinoma which has been increasing at alarming rates, particularly among Asian, Hispanic and Black women. USC has not been well characterized in terms of mutational status, pattern of metastases and survival. Objective: To investigate the association between sites of recurrence and metastases of USC, mutational status, race, and overall survival (OS). Methods: This single-center retrospective study evaluated patients with biopsy-proven USC that underwent genomic testing between January 2015 and July 2021. Association between genomic profile and sites of metastases or recurrence was performed using χ2 or Fisher's exact test. Survival curves for ethnicity and race, mutations, sites of metastasis/recurrence were estimated using the Kaplan-Meier method and compared with log-rank test. Cox proportional hazard regression models were used to examine the association between OS with age, race, ethnicity, mutational status, and sites of metastasis/recurrence. Statistical analyses were performed using SAS Software Version 9.4. Results: The study included 67 women (mean age 65.8 years, range 44-82) with 52 non-Hispanic women (78%) and 33 Black women (49%). The most common mutation was TP53 (55/58 women, 95%). The peritoneum was the most common site of metastasis (29/33, 88%) and recurrence (8/27, 30%). PR expression was more common in women with nodal metastases (p=0.02) and non-Hispanic women (p=0.01). ERBB2 alterations were more common in women with vaginal cuff recurrence (p=0.02), while PIK3CA mutation was more common in women with liver metastases (p=0.048). ARID1A mutation and presence of recurrence or metastases to the liver were associated with lower OS (Hazard Ratio (HR): 31.87; 95%CI: 3.21, 316.9; p<0.001 and HR: 5.66; 95%CI: 1.2, 26.79; p=0.01, respectively). In the bivariable Cox model, the presence of metastasis/recurrence to the liver and/or the peritoneum were both independent significant predictors of OS (HR: 9.8; 95%CI: 1.85-52.7; p=0.007 and HR: 2.7; 95%CI: 1.02-7.1; p=0.04, respectively). Conclusions: TP53 is often mutated in USC, which most commonly metastasize and recur in the peritoneum. OS was shorter in women with ARID1A mutations and with metastasis/recurrence to the liver. The presence of metastasis/recurrence to liver and/or peritoneum were independently associated with shorter OS.

Endometrial carcinoma: association between mutational status, sites of metastasis, recurrence, and correlation with overall survival.

PURPOSE: To investigate the association between sites of endometrial carcinoma (EC) recurrence and metastases, mutational status, race, and overall survival (OS). METHODS: This single-center retrospective study evaluated patients with biopsy-proven EC that underwent genomic molecular testing between January 2015 and July 2021. Association between genomic profile and sites of metastases or recurrence was performed using Pearson's chi-squared or Fisher exact test. Survival curves for ethnicity and race, mutations, sites of metastases or recurrence were estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard regression models were used. RESULTS: The study included 133 women [median age 64 years (IQR 57-69)]. The most common mutation was TP53 (65/105 patients, 62%). The most common site of metastasis was the peritoneum (35/43, 81%). The most common recurrence was in lymph nodes (34/75, 45%). Mutations of TP53 and PTEN were significantly associated with Black women (p = 0.048, p = 0.004, respectively). In the univariable Cox regression analyses, TP53 mutation and presence of recurrence or metastases to the peritoneum were associated with lower OS (HR 2.1; 95% CI 1.1, 4.3; p = 0.03/ HR 2.9; 95% CI 1.6, 5.4; p = 0.0004; respectively). On multivariable Cox proportional hazards model ER expression (HR 0.4; 95% CI 0.22, 0.91; p = 0.03), peritoneal recurrence or metastases (HR 3.55; 95% CI 1.67, 7.57; p = 0.001), and Black race (HR 2.2; 95% CI 1.1, 4.6; p = 0.03) were significant independent predictors of OS. CONCLUSIONS: The integration of EC mutational status and clinicopathological risk assessment demonstrated potential implications on the patterns of metastasis, recurrence, and OS.

Degradation rates influence the ability of composite samples to represent 24-hourly means of SARS-CoV-2 and other microbiological target measures in wastewater.

The utility of using severe-acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA for assessing the prevalence of COVID-19 within communities begins with the design of the sample collection program. The objective of this study was to assess the utility of 24-hour composites as representative samples for measuring multiple microbiological targets in wastewater, and whether normalization of SARS-CoV-2 by endogenous targets can be used to decrease hour to hour variability at different watershed scales. Two sets of experiments were conducted, in tandem with the same wastewater, with samples collected at the building, cluster, and community sewershed scales. The first set of experiments focused on evaluating degradation of microbiological targets: SARS-CoV-2, Simian Immunodeficiency Virus (SIV) - a surrogate spiked into the wastewater, plus human waste indicators of Pepper Mild Mottle Virus (PMMoV), Beta-2 microglobulin (B2M), and fecal coliform bacteria (FC). The second focused on the variability of these targets from samples, collected each hour on the hour. Results show that SARS-CoV-2, PMMoV, and B2M were relatively stable, with minimal degradation over 24-h. SIV, which was spiked-in prior to analysis, degraded significantly and FC increased significantly over the course of 24 h, emphasizing the possibility for decay and growth within wastewater. Hour-to-hour variability of the source wastewater was large between each hour of sampling relative to the variability of the SARS-CoV-2 levels calculated between sewershed scales; thus, differences in SARS-CoV-2 hourly variability were not statistically significant between sewershed scales. Results further provided that the quantified representativeness of 24-h composite samples (i.e., statistical equivalency compared against hourly collected grabs) was dependent upon the molecular target measured. Overall, improvements made by normalization were minimal within this study. Degradation and multiplication for other targets should be evaluated when deciding upon whether to collect composite or grab samples in future studies.

Correlative analysis of wastewater trends with clinical cases and hospitalizations through five dominant variant waves of COVID-19.

Wastewater-based epidemiology (WBE) has been utilized to track community infections of Coronavirus Disease 2019 (COVID-19) by detecting RNA of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), within samples collected from wastewater. The correlations between community infections and wastewater measurements of the RNA can potentially change as SARS-CoV-2 evolves into new variations by mutating. This study analyzed SARS-CoV-2 RNA, and indicators of human waste in wastewater from two sewersheds of different scales (University of Miami (UM) campus and Miami-Dade County Central District wastewater treatment plant (CDWWTP)) during five internally defined COVID-19 variant dominant periods (Initial, Pre-Delta, Delta, Omicron and Post-Omicron wave). SARS-CoV-2 RNA quantities were compared against COVID-19 clinical cases and hospitalizations to evaluate correlations with wastewater SARS-CoV-2 RNA. Although correlations between documented clinical cases and hospitalizations were high, prevalence for a given wastewater SARS-CoV-2 level varied depending upon the variant analyzed. The correlative relationship was significantly steeper (more cases per level found in wastewater) for the Omicron-dominated period. For hospitalization, the relationships were steepest for the Initial wave, followed by the Delta wave with flatter slopes during all other waves. Overall results were interpreted in the context of SARS-CoV-2 virulence and vaccination rates among the community.

Sample Size Calculations for Comparing Groups with Binary Outcomes.

Sample size is a critical parameter for clinical studies. However, to many biomedical and psychosocial investigators, power and sample size analysis seems like a magic trick of statisticians. In this paper, we continue to discuss power and sample size calculations by focusing on binary outcomes. We again emphasize the importance of close interactions between investigators and biostatisticians in setting up hypotheses and carrying out power analyses.