Symptom flares in women with chronic pelvic pain: Questionnaire study within a cohort study (translational research in pelvic pain (TRiPP)).

OBJECTIVE: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). DESIGN: Cross-sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. SETTING: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP). POPULATION OR SAMPLE: A total of 100 participants. METHODS: Descriptive and comparative analysis from flares questionnaire. MAIN OUTCOME MEASURES: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP. RESULTS: We received 100 responses of 104 questionnaires sent. Seventy-six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non-painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome. CONCLUSIONS: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden.

Recommendations on visit duration and sample number requirements for an automated head chamber system.

Automated head chamber systems (AHCS; GreenFeed, C-Lock Inc., Rapid City, SD) increasingly are being used for measuring the gas flux of unrestrained cattle. There are a wide range of recommendations for what constitutes a "good" visit (i.e., duration) to an AHCS and how many visits are required for the AHCS to quantify gas fluxes accurately and precisely. Accordingly, the purpose of this experiment was to investigate the effects of visit duration thresholds and the subsequent effects of these thresholds on the number of visits needed to provide adequate estimates of carbon dioxide (CO2) and methane (CH4) emissions, and oxygen (O2) consumption by beef cattle. This analysis utilized data from three previously published experiments with grazing beef steers and one experiment with finishing beef steers, with 103 steers total. When comparing all available visits, there was excellent agreement [Lin's concordance correlation coefficient (CCC) ≥ 0.96] between visits ≥ 3 min in duration and those ≥ 2 min for the three gases in all four experiments. When data from all four experiments were pooled, there was excellent agreement between visits ≥ 3 min and those ≥ 2 min and ≥ 1 min for all gases (CCC ≥ 0.96). These results suggest that estimates from visits ≥ 2 min are like those from visits ≥ 3 min. Next, we investigated if including visits ≥ 2 min or ≥ 1 min would increase the minimal number of visits required to provide excellent agreement with the "gold-standard" (mean of all visits ≥ 3 min). For this, we used only one of the experiments and randomly selected visits per animal ranging from n = 5 to 60, in increments of 5. The sole experiment was used because all animals had more than 60 visits. We then assessed the agreement between the "gold-standard" (mean of all visits ≥ 3 min [144 ±â€…55.01 visits per steer]) estimates of CO2, O2, and CH4. The minimum number of visits required to achieve excellent agreement (CCC ≥ 0.90) to the "gold-standard" estimate for all gases was 30 visits ≥ 3 min in duration, or 40 visits ≥ 2 min in duration. Visits ≥ 1 min in duration did not achieve excellent agreement, even when 60 were used. Based on these results, we recommend excluding visits < 3 min in duration with 30 minimum visit records per animal. However, if researchers choose to implement a 2-min visit duration threshold then 40 visit records are needed per animal.

GreenFeed systems (C-Lock Inc., Rapid City, SD) are being increasingly used for measuring carbon dioxide (CO2) and methane (CH4) emissions and oxygen consumption (O2) of free-roaming cattle. These systems utilize averages of multiple visits to provide estimates of daily gas flux. There currently exists a range of recommendations for what constitutes a "good" visit to GreenFeed. Additionally, the number of recommended visits required to achieve adequate estimates of these gas fluxes appears to be dependent on the minimum visit duration that is used. To date, there has been only one experiment that has investigated visit duration and the recommended number of visits for CO2 and CH4 emissions and to our knowledge this has not been assessed for O2 consumption. Based on the results of this experiment, we recommend using a 3-min minimum visit duration threshold with 30 visit records per animal. If researchers choose to use a 2-min visit duration threshold, then 40 visit records per animal are recommended.

Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Use of Circulating Tumor DNA to Guide Decision-making in Adjuvant Colon Cancer.

PURPOSE OF REVIEW: The use of circulating tumor DNA (ctDNA) assays to guide clinical decision-making in early-stage colon cancer is an area of rapidly advancing active research. With assays clinically available, clinicians must be informed how to best use this novel tool to treat patients. RECENT FINDINGS: Recent observational and prospective studies have suggested that ctDNA has potential to guide clinical decision-making in early-stage colon cancer by detecting minimal residual disease (MRD) and predicting recurrence risks. MRD-negative patients may be able to de-escalate or forgo adjuvant chemotherapy (ACT) without compromising disease-free survival or overall survival, while MRD-positive patients may benefit significantly from ACT. Recent and ongoing studies have given reason for optimism about the future of ctDNA as a useful biomarker for clinicians treating early-stage colon cancer. Data thus far are mostly limited to observational studies; inconsistent results highlight the need for caution. As more evidence emerges, ctDNA may become standard of care for colon cancer patients.

Utilizing gas flux from automated head chamber systems to estimate dietary energy values for beef cattle fed a finishing diet.

Dietary net energy for maintenance (NEm) and gain (NEg) can be estimated using calculations based on live performance or adjusted-final body weight, which is calculated based on carcass characteristics. These values are commonly referred to as performance-adjusted (pa) NEm (paNEm) and NEg (paNEg). The NEm and NEg of a diet can also be estimated by adding recovered energy (RE) with heat production (HP) derived from an automated head chamber system (AHCS), which we will term gas-adjusted (ga) NEm (gaNEm) and NEg (gaNEg). Furthermore, HP from the Brouwer equation requires an estimate of urinary nitrogen (UN) excretion, which can be calculated based on N intake, blood urea N, UN concentration, and urine creatinine, or it could be zeroed. Alternatively, HP can be calculated using an alternative equation based on the respiratory quotient. Demonstrating agreement between pa and ga derived dietary energy values provides an opportunity to validate using the AHCS for energetic experiments and this comparison has not been conducted previously. Accordingly, the objective of this experiment was to assess the agreement between live and carcass paNEm and paNEg with gaNEm and gaNEg, where HP was calculated using 4 different approaches. Estimates of HP were not different (P = 0.99) between the 4 approaches employed, indicating that all options investigated are appropriate. Live paNEm and paNEg had a higher agreement (Lin's concordance correlation coefficient [CCC] = 0.91) with gaNEm and gaNEg than carcass values (CCC ≤ 0.84). These results suggest that researchers can implement the AHCS to provide good estimates of dietary energy values in finishing beef cattle that are unrestrained.

Automated head chamber systems (AHCS) implemented into beef cattle research allow estimation of gas flux, heat production (HP), and calculated gas-adjusted dietary net energy for maintenance (gaNEm) and gain (gaNEg) values when paired with recovered energy. However, a comparison between AHCS-derived values and performance-adjusted NEm (paNEm) and NEg (paNEg) from either live performance (live paNEm and paNEg) or carcass data (carcass paNEm and paNEg) has not been conducted. Accordingly, the objectives of this experiment were to evaluate the agreement between gaNEm and gaNEg, estimated using different approaches for calculating HP, with live paNEm and paNEg or carcass paNEm and paNEg. Accounting for urinary nitrogen or methane when calculating HP does not appreciably influence HP estimates or subsequent calculations to estimate dietary NEm and NEg. There was excellent agreement between live paNEm and gaNEm, and between paNEg and gaNEg. Measures of precision, accuracy, and agreement were lower for carcass than for live-derived values when compared to gaNEm and gaNEg but were still acceptable. These results suggest that researchers can implement the AHCS to provide estimates of HP, gas flux, and estimates of dietary energy values in unrestrained finishing beef cattle-fed diets ranging in crude protein content (10.8% to 12.5%). Additional research is warranted on the use of the AHCS to conduct energetic studies across varying diets and production systems, particularly grazing systems.

Association between COVID-19 vaccination and menstruation: a state of the science review.

INTRODUCTION: Menstrual health is a key patient-reported outcome beyond its importance as a general indicator of health and fertility. However, menstrual function was not measured in the clinical trials of COVID-19 vaccines. The purpose of this review was to synthesise the existing literature on the relationship between COVID-19 vaccination and menstrual health outcomes. METHODS: A PubMed search to 31 October 2023 identified a total of 53 publications: 11 prospective cohort studies, 11 retrospective cohort studies or registry-based cohort studies, and 31 cross-sectional or retrospective case-control studies. RESULTS: Identified studies were generally at moderate-to-high risk of bias due to retrospective design, interviewer bias, and failure to include a non-vaccinated control group. Nonetheless, the bulk of the literature demonstrates that COVID-19 vaccine is associated with temporary changes in menstrual characteristics (cycle length and flow) and menstrual pain. Follicular phase (at the time of vaccination) is associated with greater increases in cycle length. Evidence suggests temporary post-vaccine menstrual changes in adolescents, abnormal vaginal bleeding in postmenopausal individuals, and a potential protective effect of using hormonal contraception. CONCLUSIONS: In this review we found evidence supporting an association between the COVID-19 vaccine and menstrual health outcomes. Given the importance of menstrual function to overall health, we recommend that all future vaccine trials include menstruation as a study outcome. Future vaccine studies should include rigorous assessment of the menstrual cycle as an outcome variable to limit sources of bias, identify biological mechanisms, and elucidate the impact of stress.

Effectiveness of telehealth versus in-person care during the COVID-19 pandemic: a systematic review.

In this systematic review, we compared the effectiveness of telehealth with in-person care during the pandemic using PubMed, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from March 2020 to April 2023. We included English-language, U.S.-healthcare relevant studies comparing telehealth with in-person care conducted after the onset of the pandemic. Two reviewers independently screened search results, serially extracted data, and independently assessed the risk of bias and strength of evidence. We identified 77 studies, the majority of which (47, 61%) were judged to have a serious or high risk of bias. Differences, if any, in healthcare utilization and clinical outcomes between in-person and telehealth care were generally small and/or not clinically meaningful and varied across the type of outcome and clinical area. For process outcomes, there was a mostly lower rate of missed visits and changes in therapy/medication and higher rates of therapy/medication adherence among patients receiving an initial telehealth visit compared with those receiving in-person care. However, the rates of up-to-date labs/paraclinical assessment were also lower among patients receiving an initial telehealth visit compared with those receiving in-person care. Most studies lacked a standardized approach to assessing outcomes. While we refrain from making an overall conclusion about the performance of telehealth versus in-person visits the use of telehealth is comparable to in-person care across a variety of outcomes and clinical areas. As we transition through the COVID-19 era, models for integrating telehealth with traditional care become increasingly important, and ongoing evaluations of telehealth will be particularly valuable.

Society for Endometriosis and Uterine Disorders Forum: Adenomyosis Today, Paris, France, December 12, 2023.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of Defense, or the United States Government. This symposium was supported by Sumitomo Pharma. However, the authors received no support for the creation of this manuscript, and the manuscript was created, revised and submitted solely by the authors recognized above.

Buckling forces and the wavy folds between pleural epithelial cells.

Cell shapes in tissues are affected by the biophysical interaction between cells. Tissue forces can influence specific cell features such as cell geometry and cell surface area. Here, we examined the 2-dimensional shape, size, and perimeter of pleural epithelial cells at various lung volumes. We demonstrated a 1.53-fold increase in 2-dimensional cell surface area and a 1.43-fold increase in cell perimeter at total lung capacity compared to residual lung volume. Consistent with previous results, close inspection of the pleura demonstrated wavy folds between pleural epithelial cells at all lung volumes. To investigate a potential explanation for the wavy folds, we developed a physical simulacrum suggested by D'Arcy Thompson in On Growth and Form. The simulacrum suggested that the wavy folds were the result of redundant cell membranes unable to contract. To test this hypothesis, we developed a numerical simulation to evaluate the impact of an increase in 2-dimensional cell surface area and cell perimeter on the shape of the cell-cell interface. Our simulation demonstrated that an increase in cell perimeter, rather than an increase in 2-dimensional cell surface area, had the most direct impact on the presence of wavy folds. We conclude that wavy folds between pleural epithelial cells reflects buckling forces arising from the excess cell perimeter necessary to accommodate visceral organ expansion.

Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance).

While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of ZNF331 promoter hypermethylation (mZNF331) as a prognostic and predictive marker in colon cancer. We examined the association of mZNF331 with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. ZNF331 promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of mZNF331 in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. mZNF331 was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with mZNF331 compared to unmethylated ZNF331 (unmZNFF31). There was no significant difference in disease-free or overall survival between patients with mZNF331 versus unmZNF331 colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by ZNF331 methylation status. While ZNF331 promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of mZNF331 as a prognostic and predictive marker.

Baseline characteristics and recruitment for SWOG S1820: altering intake, managing bowel symptoms in survivors of rectal cancer (AIMS-RC).

PURPOSE: Many survivors of rectal cancer experience persistent bowel dysfunction. There are few evidence-based symptom management interventions to improve bowel control. The purpose of this study is to describe recruitment and pre-randomization baseline sociodemographic, health status, and clinical characteristics for SWOG S1820, a trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention. METHODS: SWOG S1820 aimed to determine the preliminary efficacy, feasibility, and acceptability of AIMS-RC, a symptom management intervention for bowel health, comparing intervention to attention control. Survivors with a history of cancers of the rectosigmoid colon or rectum, within 6-24 months of primary treatment completion, with a post-surgical permanent ostomy or anastomosis, and over 18 years of age were enrolled. Outcomes included total bowel function, low anterior resection syndrome, quality of life, motivation for managing bowel health, self-efficacy for managing symptoms, positive and negative affect, and study feasibility and acceptability. RESULTS: The trial completed accrual over a 29-month period and enrolled 117 participants from 34 institutions across 17 states and one US Pacific territory. At baseline, most enrolled participants reported self-imposed diet adjustments after surgery, persistent dietary intolerances, and bowel discomfort post-treatment, with high levels of constipation and diarrhea (grades 1-4). CONCLUSIONS: SWOG S1820 was able to recruit, in a timely manner, a study cohort that is demographically representative of US survivors of rectal cancer. Baseline characteristics illustrate the connection between diet/eating and bowel symptoms post-treatment, with many participants reporting diet adjustments and persistent inability to be comfortable with dietary intake. GOV REGISTRATION DATE: 12/19/2019. GOV IDENTIFIER: NCT#04205955.

Assigned group work is associated with increased student motivation and perceptions of belonging in an asynchronous online physiology laboratory course.

With the rise of online instruction, a better understanding of the factors that contribute to belonging and motivation in these contexts is essential to creating optimal learning environments. Although group work is known to be beneficial to student success, few studies have investigated its role in the context of asynchronous online courses. The present study addresses this gap through a survey of 146 undergraduate students in an asynchronous online physiology lab over two semesters, one with required group work and one without group work. Students were surveyed to evaluate the influence of group work on their motivation and sense of belonging, as well as their perceptions of inclusive and exclusive features of the course. Students assigned to groups had a higher sense of belonging (P = 0.006) and beliefs about their competence (P = 0.002) and perceived lower effort and psychological costs associated with the course (P = 0.04 and 0.04, respectively) compared to students not assigned to groups. Students assigned to groups reported that peer interactions made them feel included in the course (70% of coded responses) while those not assigned to groups valued instructor interactions (51% of coded responses) as inclusive. Negative peer interactions were commonly reported as exclusive by students assigned to groups (28% of coded responses) while a lack of peer interactions (23% of coded responses) made students not assigned to groups feel excluded. These data indicate that assigning groups in asynchronous online courses is an effective way to increase student motivation and perceptions of belonging.NEW & NOTEWORTHY This study explores the effect of assigned group work in an asynchronous online physiology laboratory course on student motivation and belonging. Students' perceptions of belonging and competence-related beliefs were higher, and effort and psychological costs were lower, when assigned to groups compared to students not assigned to groups. Students assigned to groups noted peer interactions as the most inclusive aspect of the course, whereas instructor interactions were noted as inclusive by those not assigned group work.

Proteomes of plasmodium knowlesi early and late ring-stage parasites and infected host erythrocytes.

The emerging malaria parasite Plasmodium knowlesi threatens the goal of worldwide malaria elimination due to its zoonotic spread in Southeast Asia. After brief ex-vivo culture we used 2D LC/MS/MS to examine the early and late ring stages of infected Macaca mulatta red blood cells harboring P. knowlesi. The M. mulatta clathrin heavy chain and T-cell and macrophage inhibitor ERMAP were overexpressed in the early ring stage; glutaredoxin 3 was overexpressed in the late ring stage; GO term differential enrichments included response to oxidative stress and the cortical cytoskeleton in the early ring stage. P. knowlesi clathrin heavy chain and 60S acidic ribosomal protein P2 were overexpressed in the late ring stage; GO term differential enrichments included vacuoles in the early ring stage, ribosomes and translation in the late ring stage, and Golgi- and COPI-coated vesicles, proteasomes, nucleosomes, vacuoles, ion-, peptide-, protein-, nucleocytoplasmic- and RNA-transport, antioxidant activity and glycolysis in both stages. SIGNIFICANCE: Due to its zoonotic spread, cases of the emerging human pathogen Plasmodium knowlesi in southeast Asia, and particularly in Malaysia, threaten regional and worldwide goals for malaria elimination. Infection by this parasite can be fatal to humans, and can be associated with significant morbidity. Due to zoonotic transmission from large macaque reservoirs that are untreatable by drugs, and outdoor biting mosquito vectors that negate use of preventive measures such as bed nets, its containment remains a challenge. Its biology remains incompletely understood. Thus we examine the expressed proteome of the early and late ex-vivo cultured ring stages, the first intraerythrocyte developmental stages after infection of host rhesus macaque erythrocytes. We used GO term enrichment strategies and differential protein expression to compare early and late ring stages. The early ring stage is characterized by the enrichment of P. knowlesi vacuoles, and overexpression of the M. mulatta clathrin heavy chain, important for clathrin-coated pits and vesicles, and clathrin-mediated endocytosis. The M. mulatta protein ERMAP was also overexpressed in the early ring stage, suggesting a potential role in early ring stage inhibition of T-cells and macrophages responding to P. knowlesi infection of reticulocytes. This could allow expansion of the host P. knowlesi cellular niche, allowing parasite adaptation to invasion of a wider age range of RBCs than the preferred young RBCs or reticulocytes, resulting in proliferation and increased pathogenesis in infected humans. Other GO terms differentially enriched in the early ring stage include the M. mulatta cortical cytoskeleton and response to oxidative stress. The late ring stage is characterized by overexpression of the P. knowlesi clathrin heavy chain. Combined with late ring stage GO term enrichment of Golgi-associated and coated vesicles, and enrichment of COPI-coated vesicles in both stages, this suggests the importance to P. knowlesi biology of clathrin-mediated endocytosis. P. knowlesi ribosomes and translation were also differentially enriched in the late ring stage. With expression of a variety of heat shock proteins, these results suggest production of folded parasite proteins is increasing by the late ring stage. M. mulatta endocytosis was differentially enriched in the late ring stage, as were clathrin-coated vesicles and endocytic vesicles. This suggests that M. mulatta clathrin-based endocytosis, perhaps in infected reticulocytes rather than mature RBC, may be an important process in the late ring stage. Additional ring stage biology from enriched GO terms includes M. mulatta proteasomes, protein folding and the chaperonin-containing T complex, actin and cortical actin cytoskeletons. P knowlesi biology also includes proteasomes, as well as nucleosomes, antioxidant activity, a variety of transport processes, glycolysis, vacuoles and protein folding. Mature RBCs have lost internal organelles, suggesting infection here may involve immature reticulocytes still retaining organelles. P. knowlesi parasite proteasomes and translational machinery may be ring stage drug targets for known selective inhibitors of these processes in other Plasmodium species. To our knowledge this is the first examination of more than one timepoint within the ring stage. Our results expand knowledge of both host and parasite proteins, pathways and organelles underlying P. knowlesi ring stage biology.

Plant-Based Diets and Disease Progression in Men With Prostate Cancer.

Importance: Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer. Objective: To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality. Design, Setting, and Participants: This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023. Exposures: Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ. Main Outcomes and Measures: The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality. Results: Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7. Conclusions and Relevance: In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.

Inhibition of EGFR/ErbB does not protect against C. difficile toxin B.

Clostridioides difficile is a common cause of diarrhea and mortality, especially in immunosuppressed and hospitalized patients. C. difficile is a toxin-mediated disease, but the host cell receptors for C. difficile toxin B (TcdB) have only recently been revealed. Emerging data suggest TcdB interacts with receptor tyrosine kinases during infection. In particular, TcdB can elicit Epidermal Growth Factor Receptor (EGFR) transactivation in human colonic epithelial cells. The mechanisms for this function are not well understood, and the involvement of other receptors in the EGFR family of Erythroblastic Leukemia Viral Oncogene Homolog (ErbB) receptors remains unclear. Furthermore, in an siRNA-knockdown screen for protective genes involved with TcdB toxin pathogenesis, we show ErbB2 and ErbB3 loss resulted in increased cell viability. We hypothesize TcdB induces the transactivation of EGFR and/or ErbB receptors as a component of its cell-killing mechanism. Here, we show in vivo intrarectal instillation of TcdB in mice leads to phosphorylation of ErbB2 and ErbB3. However, immunohistochemical staining for phosphorylated ErbB2 and ErbB3 indicated no discernible difference between control and TcdB-treated mice for epithelial phospho-ErbB2 and phospho-ErbB3. Human colon cancer cell lines (HT29, Caco-2) exposed to TcdB were not protected by pre-treatment with lapatinib, an EGFR/ErbB2 inhibitor. Similarly, lapatinib pre-treatment failed to protect normal human colonoids from TcdB-induced cell death. Neutralizing antibodies against mouse EGFR failed to protect mice from TcdB intrarectal instillation as measured by edema, inflammatory infiltration, and epithelial injury. Our findings suggest TcdB-induced colonocyte cell death does not require EGFR/ErbB receptor tyrosine kinase activation.

Are Gait Patterns during In-Lab Running Representative of Gait Patterns during Real-World Training? An Experimental Study.

Biomechanical assessments of running typically take place inside motion capture laboratories. However, it is unclear whether data from these in-lab gait assessments are representative of gait during real-world running. This study sought to test how well real-world gait patterns are represented by in-lab gait data in two cohorts of runners equipped with consumer-grade wearable sensors measuring speed, step length, vertical oscillation, stance time, and leg stiffness. Cohort 1 (N = 49) completed an in-lab treadmill run plus five real-world runs of self-selected distances on self-selected courses. Cohort 2 (N = 19) completed a 2.4 km outdoor run on a known course plus five real-world runs of self-selected distances on self-selected courses. The degree to which in-lab gait reflected real-world gait was quantified using univariate overlap and multivariate depth overlap statistics, both for all real-world running and for real-world running on flat, straight segments only. When comparing in-lab and real-world data from the same subject, univariate overlap ranged from 65.7% (leg stiffness) to 95.2% (speed). When considering all gait metrics together, only 32.5% of real-world data were well-represented by in-lab data from the same subject. Pooling in-lab gait data across multiple subjects led to greater distributional overlap between in-lab and real-world data (depth overlap 89.3-90.3%) due to the broader variability in gait seen across (as opposed to within) subjects. Stratifying real-world running to only include flat, straight segments did not meaningfully increase the overlap between in-lab and real-world running (changes of <1%). Individual gait patterns during real-world running, as characterized by consumer-grade wearable sensors, are not well-represented by the same runner's in-lab data. Researchers and clinicians should consider "borrowing" information from a pool of many runners to predict individual gait behavior when using biomechanical data to make clinical or sports performance decisions.

Development and validation of a GT-seq panel for genetic monitoring in a threatened species using minimally invasive sampling.

Minimally invasive samples are often the best option for collecting genetic material from species of conservation concern, but they perform poorly in many genomic sequencing methods due to their tendency to yield low DNA quality and quantity. Genotyping-in-thousands by sequencing (GT-seq) is a powerful amplicon sequencing method that can genotype large numbers of variable-quality samples at a standardized set of single nucleotide polymorphism (SNP) loci. Here, we develop, optimize, and validate a GT-seq panel for the federally threatened northern Idaho ground squirrel (Urocitellus brunneus) to provide a standardized approach for future genetic monitoring and assessment of recovery goals using minimally invasive samples. The optimized panel consists of 224 neutral and 81 putatively adaptive SNPs. DNA collected from buccal swabs from 2016 to 2020 had 73% genotyping success, while samples collected from hair from 2002 to 2006 had little to no DNA remaining and did not genotype successfully. We evaluated our GT-seq panel by measuring genotype discordance rates compared to RADseq and whole-genome sequencing. GT-seq and other sequencing methods had similar population diversity and F ST estimates, but GT-seq consistently called more heterozygotes than expected, resulting in negative F IS values at the population level. Genetic ancestry assignment was consistent when estimated with different sequencing methods and numbers of loci. Our GT-seq panel is an effective and efficient genotyping tool that will aid in the monitoring and recovery of this threatened species, and our results provide insights for applying GT-seq for minimally invasive DNA sampling techniques in other rare animals.