Effects of high-intensity interval training on cardiometabolic biomarkers in patients with prostate cancer undergoing active surveillance: a randomized controlled trial.

PURPOSE: To report the effects of a 12-week high-intensity interval training (HIIT) program on cardiometabolic biomarkers in patients with prostate cancer on active surveillance (AS) from the Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial. METHODS: Fifty-two men with prostate cancer on AS were randomized to either an exercise (HIIT; n = 26) or usual care (UC; n = 26) group. The HIIT intervention consisted of progressive, supervised, aerobic HIIT at an intensity of 85 to 95% VO2peak for 28 to 40 min per session performed three times/week for 12 weeks. Blood samples were collected at baseline and postintervention to analyze cardiometabolic biomarkers. Analysis of covariance was used to examine between-group mean differences. RESULTS: Blood data were obtained from 49/52 (94%) participants at postintervention. Participants were aged 63.4 ± 7.1 years and 40% were obese. The HIIT group attended 96% of the planned exercise sessions. No significant between-group changes in weight were observed after the intervention. Compared to UC, HIIT significantly improved total cholesterol (-0.40 mmol/L; 95% confidence interval[CI], -0.70 to -0.10; p = 0.011), non-high-density lipoprotein-c (-0.35 mmol/L; 95% CI, -0.60 to -0.11; p = 0.006), insulin (-13.6 pmol/L; 95% CI, -25.3 to -1.8; p = 0.025), insulin-like growth factor (IGF)-1 (-15.0 ng/mL; 95% CI, -29.9 to -0.1; p = 0.048), and IGF binding protein (IGFBP)-3 (152.3 ng/mL; 95% CI, 12.6 to 292.1; p = 0.033). No significant differences were observed for fasting glucose, HbA1c, other lipid markers, IGFBP-1, adiponectin, and leptin. CONCLUSIONS: The ERASE Trial showed that a 12-week aerobic HIIT program improved several cardiometabolic biomarkers in patients with prostate cancer on AS that may contribute to cardiovascular health benefits and potentially influence signaling pathways in the progression of prostate cancer. Further research is needed to confirm the effects of exercise on cardiometabolic markers in men with prostate cancer on AS and determine if these effects are associated with improved long-term clinical outcomes.

The impact of delayed processing of chilled whole blood specimens on the measurement of nutritional biomarkers in the UK National Diet and Nutrition Survey rolling programme.

BACKGROUND: The logistics of timely processing of blood specimens remains a barrier in population health studies to the generation of micronutrient status data. OBJECTIVE: To test a blood specimen processing protocol that includes overnight postage with cooling and its effect on nutritional biomarker concentrations. METHODS: This study was embedded within the UK National Diet and Nutrition Survey (NDNS). Paired specimens were collected from 64 participants (16 y+). One set of specimens was processed within 2-hours of collection ["field"] and paired samples mailed in an insulated box with cold packs using an overnight postal service to a central laboratory ["postal"]. Specimen processing protocols were aligned across field sites and the central laboratory. Specimens were frozen and later analysed using established methods for vitamins, minerals, lipids, ferritin and C-reactive protein (CRP). Percent difference was calculated between protocols and compared with quality specifications determined from intra- and inter-individual variation. RESULTS: In the postal protocol, ferritin (6%(3, 8)) (geometric mean percent difference(95% CI)) (P=0.002) and zinc (4%(1, 6)) (P=0.004) were higher compared with the field protocol. Retinol (-3%(-4, -1) (P<0.0001)) and selenium (-3%(-5, -1) (P=0.003)) concentrations were lower in the postal protocol whereas total (2%(1, 3)) and HDL (4%(2, 5)) cholesterol were higher (P<0.0001) than in the field protocol. Percent differences were within the optimum quality specification for the majority of biomarkers, but ferritin, zinc and selenium fell outside of the optimum limits. Higher ferritin concentration in the postal protocol led to a decrease in the proportion of specimens with ferritin concentration <15 µg/L from 13% to 9%. CONCLUSIONS: The majority of micronutrient biomarkers, serum lipids and CRP were minimally affected by delayed processing when cooled. The study suggests acceptable stability of nutritional biomarkers within the described protocol, which can provide accurate data for nutritional biomarkers commonly measured in studies and surveys.

Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study.

Background: There is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency. Objectives: This study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine. Methods: Hospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically. Clinical case reports were reviewed by 3 pediatricians, who determined TRD or non-TRD status. Children in a community comparison group were matched by age, sex, and residence. Venous whole blood ThDP and MTh were determined by high-performance liquid chromatography fluorescence detection and ETKac in washed erythrocytes by ultraviolet spectrophotometry. Associations between biomarkers were assessed using Spearman correlations, and biomarker cutoffs predictive of TRD and ETKac >1.25 were explored using area under the receiver operating characteristic curve framework. Results: Thiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children (P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants <6 mo had MTh <90 µg/L. ThDP and ETKac, but not MTh, were significantly different between 152 children with TRD and 122 without TRD, but overlapping distributions undermined prediction of individual responses to thiamine. Conclusions: Although ETKac, ThDP, and MTh are useful biomarkers of population thiamine status, none of the biomarkers reliably identified individual children with TRD. ThDP is more practical for population assessment because preparing washed erythrocytes is not required.This trial was registered at clinicaltrials.gov as NCT03626337.

Chinese version of the Tendency to Avoid Physical Activity and Sport (TAPAS) scale: testing unidimensionality, measurement invariance, concurrent validity, and known-group validity among Taiwanese youths.

BACKGROUND AND OBJECTIVES: Psychosocial factors affect individuals' desire for physical activity. A newly developed instrument (Tendency to Avoid Physical Activity and Sport; TAPAS) has been designed to assess the avoidance of physical activity. Considering cultural differences could be decisive factors, the present study aimed to translate and validate the TAPAS into Chinese (Mandarin) for Taiwanese youths, and further cultural comparisons are expected. METHODS: Standard translation procedure (i.e., forward translation, back translation, and reconciliation) was used to translate the English TAPAS into the Chinese TAPAS. Following translation, 608 youths (mean [SD] age 29.10 [6.36] years; 333 [54.8%] women) participated in the study via a snowballing sampling method with an online survey. All participants completed the Chinese TAPAS and additional instruments assessing weight stigma and psychological distress. Confirmatory factor analysis (CFA) was used to examine the factor structure of the Chinese TAPAS and multigroup CFA to examine measurement invariance across gender (men vs. women) and weight status (overweight vs. non-overweight). Pearson correlations were used to examine the concurrent validity; independent t-tests between gender groups and weight status groups were used to examine the known-group validity. RESULTS: Consistent with the English version, the Chinese TAPAS was found to have a one-factor structure evidenced by CFA results. The structure was invariant across gender and weight status groups evidenced by multigroup CFA results. Concurrent validity was supported by significant associations with the related constructs assessed (r = 0.326 to 0.676; p < 0.001). Known-group validity was supported by the significant differences in TAPAS total scores between gender and weight status groups (p = 0.004 and < 0.001; Cohen's d = 0.24 and 0.48). CONCLUSION: The Chinese version of the TAPAS is a valid and reliable instrument assessing individuals' avoidance of physical activity and sports due to underlying psychosocial issues among Taiwanese youths. It is anticipated to be applied within a large Asian population, as well as cross-cultural comparisons, for further explorations in health, behavioral and epidemiological research and practice.

Risk Factors for Second Primary Cancer in a Prospective Cohort of Endometrial Cancer Survivors: an Alberta Endometrial Cancer Cohort Study.

We examined associations between modifiable and non-modifiable cancer-related risk factors measured at endometrial cancer diagnosis and during early survivorship (~3 years post-diagnosis) with second primary cancer (SPC) risk among 533 endometrial cancer survivors in the Alberta Endometrial Cancer Cohort using Fine and Gray sub-distribution hazard models. During a median follow-up of 16.7 years (interquartile range (IQR)=12.2-17.9), 89 (17%) participants developed a SPC with breast (29%), colorectal (13%) and lung (12%) cancers being the most common. Dietary glycemic load before endometrial cancer diagnosis (≥90.4 vs. <90.4 g/day: sub-hazard ratios (sHR)=1.71, 95% confidence intervals (CI)=1.09-2.69) as well as older age (≥60 vs. <60: sHR=2.48, 95% CI=1.34-4.62) and alcohol intake (≥2 drink/week vs. none: sHR=3.81, 95% CI=1.55-9.31) during early survivorship were associated with increased SPC risk. Additionally, reductions in alcohol consumption from prediagnosis to early survivorship significantly reduced SPC risk (sHR=0.34, 95% CI=0.14-0.82). With one-in-six survivors developing a SPC, further investigation of SPC risk factors and targeted surveillance options for high-risk survivors could improve long-term health outcomes in this population. Reductions in dietary glycemic load and alcohol intake from prediagnosis to early survivorship showed promising risk reductions for SPCs and could be important modifiable risk factors to target among endometrial cancer survivors.

Early Implementation of Exercise to Facilitate Recovery After Breast Cancer Surgery: A Randomized Clinical Trial.

Importance: Recovery of shoulder function following breast cancer surgery is crucial for physical functioning and quality of life. While early implementation of shoulder rehabilitation exercises may enhance recovery, the optimal timing and exercise program remain unclear. Objective: To investigate whether an early exercise intervention, initiated 1 day postsurgery and continued for 1 month through subsequent visits, could improve shoulder range of motion (ROM) and strength in patients with breast cancer. Design, Setting, and Participants: A parallel-group, 2-arm randomized clinical trial was conducted between June 2020 and October 2021 at the Breast Cancer Center in Seoul, South Korea. Fifty-six patients (of 119 screened) with early-stage breast cancer who were scheduled for partial or total mastectomy were randomized into a tailored resistance exercise group (n = 28) or a usual care group (n = 28). Data were analyzed from November 2021 to June 2022. Interventions: The exercise intervention commenced 1 day postsurgery and consisted of 4 supervised exercise education sessions corresponding with surgeon visits and daily home-based exercises for the first postoperative month. Tailored programs, including stretching and strength exercises, were adjusted based on individual shoulder function recovery status. Main Outcomes and Measures: Primary end points were shoulder ROM and strength at 1 and 6 months postsurgery. Physical activity, body composition, and quality of life were assessed at 6 months. Results: Of 56 patients randomized (mean [SD] age, 50.3 [6.6] years), 54 completed the trial (96%), with 100% and 97% compliance to supervised and home-based exercise sessions, respectively. At 1 month postsurgery, 19 (67.9%) in the exercise group had fully recovered shoulder strength compared to 1 (3.6%) in the usual care group (P < .001). At 6 months, 22 (78.6%) in the exercise group had fully recovered shoulder ROM and 24 (85.7%) had fully recovered strength compared to 6 (21.4%) and 5 (17.9%), respectively, in the usual care group (P < .001). The exercise group exhibited less loss in muscle mass and improved physical activity and quality of life compared to the usual care group. Conclusion and Relevance: In this trial, 1-month tailored exercise program, initiated immediately after breast cancer surgery and supplemented with supervised sessions coinciding with surgeon visits, significantly improved shoulder function in patients with breast cancer. Trial Registration: WHO International Clinical Trials Registry identifier: KCT0006997.

Effects of exercise during active surveillance for prostate cancer: A systematic review and meta-analysis.

PURPOSE: The efficacy of exercise in men with prostate cancer (PCa) on active surveillance (AS) remains unclear. In this meta-analysis, we aimed to examine the effects of exercise in PCa patients on AS. METHODS: A literature search was conducted in PubMed, EMBASE, and the Cochrane Library using search terms, including exercise, PCa, AS, and randomized controlled trials (RCTs). The means and standard deviations for peak oxygen consumption (VO2peak), prostate-specific antigen (PSA) levels, and quality of life (QoL) were extracted for the intervention and control groups. A random-effects model was used to summarize the effects of exercise. RESULTS: Of the 158 identified studies, six RCTs with 332 patients were included. The interventions included lifestyle modifications (aerobic exercise + diet) in three studies and different exercise modalities in three studies. The intervention duration was 2-12 months; three interventions were supervised and three were self-directed. The pooled weighted mean difference between exercise and usual care for VO2peak was 1.42 mL/kg/min (95% confidence interval [CI]: 0.30 to 2.54, P ≤ 0.001). A non-significant effect was observed for QoL (pooled standardized mean difference [SMD]: 0.24, 95% CI: - 0.03 to 0.51, P = 0.08) which became statistically significant and stronger after excluding one outlier study (P < 0.001). Exercise also had a positive effect on PSA levels (pooled SMD: - 0.43, 95% CI: - 0.87 to 0.01, P = 0.05). CONCLUSION: Exercise improves cardiorespiratory fitness and may improve QoL and PSA levels in men with PCa on AS. Further studies with larger sample sizes are warranted to obtain more reliable results.

The Physical Activity and Cancer Control (PACC) framework: update on the evidence, guidelines, and future research priorities.

BACKGROUND: We proposed the Physical Activity and Cancer Control (PACC) framework in 2007 to help organise, focus, and stimulate research on physical activity in eight cancer control categories: prevention, detection, treatment preparation/coping, treatment coping/effectiveness, recovery/rehabilitation, disease prevention/health promotion, palliation, and survival. METHODS: This perspective paper provides a high-level overview of the scientific advances in physical activity research across cancer control categories, summarises current guidelines, updates the PACC framework, identifies remaining and emerging knowledge gaps, and provides future research directions. RESULTS: Many scientific advances have been made that are reflected in updated physical activity guidelines for six of the cancer control categories apart from detection and palliation. Nevertheless, the minimal and optimal type, dose, and timing of physical activity across cancer control categories remain unknown, especially for the understudied population subgroups defined by cancer type, age, race/ethnicity, and resource level of regions/countries. CONCLUSION: To achieve the full benefit of physical activity in cancer control, future research should use innovative study designs that include diverse at-risk populations and understudied cancer sites. Additionally, effective behaviour change strategies are needed to increase physical activity levels across populations that use implementation science to accelerate the translation from evidence generation into practical, real-world interventions.

Lead compound profiling for small molecule inhibitors of the REV1-CT/RIR Translesion synthesis Protein-Protein interaction.

Translesion synthesis (TLS) is a cellular mechanism through which actively replicating cells recruit specialized, low-fidelity DNA polymerases to damaged DNA to allow for replication past these lesions. REV1 is one of these TLS DNA polymerases that functions primarily as a scaffolding protein to organize the TLS heteroprotein complex and ensure replication occurs in the presence of DNA lesions. The C-Terminal domain of REV1 (REV1-CT) forms many protein-protein interactions (PPIs) with other TLS polymerases, making it essential for TLS function and a promising drug target for anti-cancer drug development. We utilized several lead identification strategies to identify various small molecules capable of disrupting the PPI between REV1-CT and the REV1 Interacting Regions (RIR) present in several other TLS polymerases. These lead compounds were profiled in several in vitro potency and PK assays to identify two scaffolds (1 and 6) as the most promising for further development. Both 1 and 6 synergized with cisplatin in a REV1-dependent fashion and demonstrated promising in vivo PK and toxicity profiles.

Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer's disease (BenfoTeam).

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

Transient crosslinking controls the condensate formation pathway within chromatin networks.

The network structure of densely packed chromatin within the nucleus of eukaryotic cells acts in concert with nonequilibrium processes. Using statistical physics simulations, we explore the control provided by transient crosslinking of the chromatin network by structural-maintenance-of-chromosome (SMC) proteins over (i) the physical properties of the chromatin network and (ii) condensate formation of embedded molecular species. We find that the density and lifetime of transient SMC crosslinks regulate structural relaxation modes and tune the sol-vs-gel state of the chromatin network, which imparts control over the kinetic pathway to condensate formation. Specifically, lower density, shorter-lived crosslinks induce sollike networks and a droplet-fusion pathway, whereas higher density, longer-lived crosslinks induce gellike networks and an Ostwald-ripening pathway.

Exercise Across the Phases of Cancer Survivorship: A Narrative Review.

Exercise has long been recognized as an important component of treatment for various diseases. However, the benefits and risks of exercise interventions must be carefully evaluated to ensure the former outweighs the latter. As cancer patients undergo diverse treatment modalities with distinct objectives, a systematic approach partitioning the cancer journey into distinct phases is necessary to inform tailored exercise prescriptions. This narrative review summarizes exercise benefits and mechanisms for cancer patients and survivors across four distinct survivorship periods-before surgery, after surgery and before adjuvant treatment, during nonsurgical treatment (adjuvant and neoadjuvant), and during extended survival. In summary, exercise reduces the risks of complications and declines in physical functioning while improving fatigue, quality of life, and the ability to manage treatment effects. Although additional research is warranted, existing evidence is sufficient to integrate exercise into clinical oncology practice and cancer survivorship programs.

Derivation of human primary prostate epithelial cell lines by differentially targeting the CDKN2A locus along with expression of hTERT.

Prostate cancer (PCa) is the most common cancer diagnosed in men worldwide and the second leading cause of cancer-related deaths in US males in 2022. Prostate cancer also represents the second highest cancer mortality disparity between non-Hispanic blacks and whites. However, there is a relatively small number of prostate normal and cancer cell lines compared to other cancers. To identify the molecular basis of PCa progression, it is important to have prostate epithelial cell (PrEC) lines as karyotypically normal as possible. Our lab recently developed a novel methodology for the rapid and efficient immortalization of normal human PrEC that combines simultaneous CRISPR-directed inactivation of CDKN2A exon 2 (which directs expression of p16INK4A and p14ARF) and ectopic expression of an hTERT transgene. To optimize this methodology to generate immortalized lines with minimal genetic alterations, we sought to target exon 1α of the CDKN2A locus so that p16INK4A expression is ablated while p14ARF expression remains unaltered. Here we describe the establishment of two cell lines: one with the above-mentioned p16INK4A only loss, and a second line targeting both products in the CDKN2A locus. We characterize the potential lineage origin of these new cell lines along with our previously obtained clones, revealing distinct gene expression signatures. Based on the analyses of protein markers and RNA expression signatures, these cell lines are most closely related to a subpopulation of basal prostatic cells. Given the simplicity of this one-step methodology and the fact that it uses only the minimal genetic alterations necessary for immortalization, it should also be suitable for the establishment of cell lines from primary prostate tumor samples, an urgent need given the limited number of available prostate cancer cell lines.

Associations between health-related fitness and patient-reported symptoms in newly diagnosed breast cancer patients.

BACKGROUND: Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life, treatment outcomes, and survival. Preventing and managing breast cancer-related symptoms soon after diagnosis is essential. The purpose of this study was to investigate the associations between health-related fitness (HRF) and patient-reported symptoms in newly diagnosed breast cancer patients. METHODS: This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of diagnosis. HRF measures included peak cardiopulmonary fitness (peak volume of oxygen consumption (VO2peak)), maximal muscular strength and endurance, flexibility, and body composition. Symptom measures included depression, sleep quality, and fatigue. Adjusted multivariable logistic regression was performed for analyses. RESULTS: Of 1458 participants, 51.5% reported poor sleep quality, 26.5% reported significant fatigue, and 10.4% reported moderate depression. In multivariable-adjusted models, lower relative VO2peak was independently associated with a greater likelihood of all symptom measures, including moderate depression (p < 0.001), poor sleep quality (p = 0.009), significant fatigue (p = 0.008), any symptom (p < 0.001), and multiple symptoms (p < 0.001). VO2peak demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest quartile. The strength of the threshold associations varied by the symptom measure with odds ratios ranging from ∼1.5 for poor sleep quality to ∼3.0 for moderate depression and multiple symptoms. Moreover, lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner (p = 0.001), and higher body weight was independently associated with poor sleep quality in an inverted U pattern (p = 0.021). CONCLUSION: Relative VO2peak appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diagnosed breast cancer patients. Other HRF parameters may also be important for specific symptoms. Exercise interventions targeting different HRF components may help newly diagnosed breast cancer patients manage specific symptoms and improve outcomes.

Serum IgG Immunoglobulin Levels are Associated with Reduced PCR Detection of Mycoplasma bovis in Naturally Infected American Bison (Bison bison).

Mycoplasma bovis (M. bovis) is an important pathogen of American bison (Bison bison), associated with high morbidity and mortality epizootics of respiratory and reproductive disease. Despite the significant negative impact on bison health, little is known about the kinetics of disease and the host immune response to infection. To address these questions, a cohort of bison calves was created and serially sampled 5 times, once every 2-3 mo, over a 12-mo period. At each sampling period nasal swab samples were collected and tested by PCR for the presence of M. bovis. Serum samples were also collected and assessed for M. bovis-specific antibodies using both a commercial and an in-house ELISA. Overall, 19/41 bison (46.3%) had positive PCR tests, and 31/41 (75.6%) were seropositive. Over the course of the study, the frequency of PCR-positive nasal swabs and the ELISA scores decreased, although serum samples remained positive for at least 6 mo following the final positive PCR test. Bison were grouped according to results from the in-house ELISA into high-responder (n=7), low-responder (n=5), and seronegative (n=7) groups. M. bovis-specific IgG antibody levels were significantly elevated in the high-responder group compared to the low-responder and seronegative groups. The differences were statistically significant for 3/5 sampling periods. A trend toward increased IgG2 levels was observed in the high-responder group. High total IgG responses correlated with a decline in positive PCR tests from nasal swabs. These data provide evidence that a strong humoral response is beneficial and is probably involved in the clearance of M. bovis from bison.

Evaluating Two Sampling Methods for Mycoplasma Bovis Diagnosis in American Bison (Bison bison).

Mycoplasma bovis is a bacterial pathogen endemic to cattle. In the early 2000s, M. bovis emerged as a cause of respiratory disease in American bison (Bison bison), causing significant morbidity and mortality. Bison herds that experience an outbreak of M. bovis are at higher risk for subsequent outbreaks, suggesting that chronic, subclinical infections can be established. Antemortem testing is therefore crucial to disease management; however, the precise sampling method to maximize detection of M. bovis in bison is unknown. We evaluated two sample types-superficial nasal swabs and deep nasopharyngeal swabs-collected from apparently healthy or symptomatic bison from January 2021 through December 2022. We used real-time PCR to detect M. bovis in 76/938 bison (8.1%) from 11 herds. For bison testing positive on at least one swab type, M. bovis was detected in 63/76 (82.8%) deep nasopharyngeal swabs and 29/73 (38.1%) superficial nasal swabs. Agreement between swabs for positive bison was 21% (n=16, kappa coefficient 0.319). We conclude that deep nasopharyngeal swabbing is more sensitive than superficial nasal swabbing for detection of M. bovis in bison and that low agreement between methods may be related to stage of infection. We further tested pooled samples by PCR and found that pooling of up to five samples can be effective to increase throughput and minimize costs. Management of wild bison relies on the ability to relocate animals to maintain gene flow and healthy populations. Sensitive and specific diagnostic tests are needed to inform decisions and minimize risk of transmission, especially from subclinical carriers. This study provides valuable insight that will inform best practices for M. bovis testing, thereby supporting the conservation of bison as healthy wildlife, which in turn promotes ecological restoration, safeguards cultural practices of Tribal Nations, and upholds the bison as a unique American icon.

Right ventricular preload and afterload challenge induces contractile dysfunction and arrhythmia in isolated hearts of dystrophin-deficient male mice.

Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy due to mutations in the dystrophin gene. Diaphragmatic weakness in DMD causes hypoventilation and elevated afterload on the right ventricle (RV). Thus, RV dysfunction in DMD develops early in disease progression. Herein, we deliver a 30-min sustained RV preload/afterload challenge to isolated hearts of wild-type (Wt) and dystrophic (Dmdmdx-4Cv) mice at both young (2-6 month) and middle-age (8-12 month) to test the hypothesis that the dystrophic RV is susceptible to dysfunction with elevated load. Young dystrophic hearts exhibited greater pressure development than wild type under baseline (Langendorff) conditions, but following RV challenge exhibited similar contractile function as wild type. Following the RV challenge, young dystrophic hearts had an increased incidence of premature ventricular contractions (PVCs) compared to wild type. Hearts of middle-aged wild-type and dystrophic mice had similar contractile function during baseline conditions. After RV challenge, hearts of middle-aged dystrophic mice had severe RV dysfunction and arrhythmias, including ventricular tachycardia. Following the RV load challenge, dystrophic hearts had greater lactate dehydrogenase (LDH) release than wild-type mice indicative of damage. Our data indicate age-dependent changes in RV function with load in dystrophin deficiency, highlighting the need to avoid sustained RV load to forestall dysfunction and arrhythmia.

Suicide and mortality following self-harm in Culturally and Linguistically Diverse communities in Victoria, Australia: insights from a data linkage study.

Background: While cultural backgrounds are well-documented to be relevant to intentional self-harm, little is known about how cultural and linguistically diverse (CALD) backgrounds affect mortality outcomes following self-harm. Aim: This study aimed to compare the risk of all-cause mortality and suicide after intentional hospital admissions for self-harm among people from CALD (vs. non-CALD) backgrounds. Method: Linked hospital and mortality data in Victoria, Australia, was used to assess suicide and all-cause death after hospital admissions for self-harm among patients aged 15+ years. All-cause death was identified by following up on 42,122 self-harm patients (hospitalized between 01 July 2007 and 30 June 2019) until death or 15 February 2021. Suicide death was evaluated in 16,928 self-harm inpatients (01 January 2013 and 31 December 2017) until death or 28 March 2018. Cox regression models were fitted to compare mortality outcomes in self-harm patients from CALD vs. non-CALD backgrounds. Outcomes: During the follow-up periods, 3,716 of 42,122 (8.8%) participants died by any cause (by 15 February 2021), and 304 of 16,928 (1.8%) people died by suicide (by 28 March 2018). Compared to the non-CALD group, CALD intentional self-harm inpatients had a 20% lower risk of all-cause mortality (HR: 0.8, 95% CI: 0.7-0.9) and a 30% lower risk of suicide (HR: 0.7, 95% CI: 049-0.97). Specifically, being from North Africa/Middle East and Asian backgrounds lowered the all-cause mortality risk; however, the suicide risk in Asians was as high as in non-CALD people. Conclusion: Overall, people from CALD backgrounds exhibited lower risks of all-cause mortality and suicide following hospital admission for self-harm compared to the non-CALD group. However, when comparing risks based on regions of birth, significant variations were observed. These findings underscore the importance of implementing culturally tailored background-specific suicide preventive actions. The study focussed on outcomes following hospital admission for self-harm and did not capture outcomes for cases of self-harm that did not result in hospital admission. This limits generalisability, as some CALD people might avoid accessing healthcare after self-harm due to cultural factors. Future research that not limited to hospital data is suggested to build on the results.

The Nurse Practitioner Role in Complex Malignant Hematology: A Qualitative Descriptive Study.

OBJECTIVES: Internationally, there is limited evidence about the role and impact of nurse practitioners (NPs) in complex malignant hematology (CMH). In one Canadian CMH program, NPs have existed for 20 years but not been evaluated. This study aimed to understand stakeholder perceptions of CMH NP role structures, processes, and outcomes and the extent to which the role meets patient and health service needs. METHODS: A qualitative descriptive study was conducted, guided by the PEPPA-Plus framework. Purposive sampling was used to recruit stakeholders who participated in focus groups and interviews. Content analysis was used to analyze the data. RESULTS: Participants included patients (n = 8) and healthcare professionals (n = 27). Themes about structures related to evolution of the CMH Program, model of care, and need for strategic vision. Process themes related to provision of accessible, comprehensive, and holistic care and NP workload. Positive and negative outcomes and lack of outcome measurement were identified. CONCLUSION: Structures related to patient and NP characteristics, organizational change, staffing, and how NP work is organized impacts on NP role implementation and outcomes. Organizational structures can be strengthened to improve the model of care and NP role implementation and workload. Value-added NP contributions related to providing comprehensive care with attention to safety and social determinants of health. Research is needed to evaluate NP role outcomes in CMH. IMPLICATIONS FOR NURSING PRACTICE: The results can inform role design and organization policies and strategies to promote the recruitment, retention, and optimization of NP roles in CMH settings. Priorities for future research are also identified.

A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.