Evaluation of the supply of Duddingtonia flagrans for the control of gastrointestinal parasites in sheep.

Parasitic resistance imposes alternative control methods, like nematophagous fungi. In this study, two experiments were conducted supplying Duddingtonia flagrans aiming to evaluate the biological control of parasites in sheep. In the first, 24 sheep naturally infected by gastrointestinal nematodes were allocated, in randomized blocks, following the treatments: control or treated group, 0.5g/animal product containing D. flagrans, chlamydospores. Weight, body score, Famacha©, egg count per gram of feces (EPG), and larval percentage were evaluated. In the second experiment, D. flagrans (0.25 and 0.5g product) was infested with manure, plus or not protein concentrate, in a completely randomized design. In both experiments the dose was intentionally lower than recommended. Recovery and larval identification were performed. The SAS analyzed the variables by the MIXED procedure, repeated measures in time. Weight, body score, hematocrit, and Famacha© did not show differences between treatments (p>0.05); however, EPG (p<0.001) and the percentage of larvae identified in coproculture were different. In the second experiment, the inclusion of the fungus did not influence the recovery of larvae (p>0.05). In both experiments, colonization and advancement of the fungus were visualized. Under the experimental conditions, the fungus D. flagrans was not effective in the biological control of parasitic infection in sheep.

Assessment of the adaptive capacity of Morada Nova ewes with different coat coloration.

Coat color is a factor affecting heat tolerance in tropical ruminant and a particular coat color can determine which is more resilient to environmental changes. The aim of this study was to measure the level of adaptation of Morada Nova sheep with different coat color by using an Adaptability Index (AI). Adult ewes were used, including two different coat colors of Morada Nova sheep (red and white) with mean of body weight of 28.02 ± 5.70 kg and 31.47 ± 3.41 kg, respectively. Physiology parameters, hematology, electrolytes, acid-base status, mineral, renal functions, metabolites, enzymes, and proteins were measured. AI was designed using a multivariate approach (principal component analysis) to "weigh" the influence of each variable in the animal responses. The variables more important for adaptive aspects of Red Morada Nova were: haematology, electrolytes and acid-base status. The hemoglobin (HG), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), sodium (Na+), oxygen pressure (PO2), glucose (GLU) and albumin (ALB) were significantly higher in Red Morada Nova sheep and hydrogen carbonate (HCO3), base excess (BE), total carbon dioxide concentration (TCO2) and URE were significantly higher in the white phenotype. The variables more important for adaptive aspects of White Morada Nova sheep were: (K+), total protein (TP), PO2, HG, cholesterol (CHO), rectal temperature (RT) and glucose (GLU). Both phenotypes showed a high adaptation level, however, a higher value was generated for the Red Morada Nova sheep (81.97). This study concludes that both phenotypes of the Morada Nova sheep breed are well adapted to the climatic condition of the Brazilian tropical region using different adaptive mechanisms.

Exertional Stress-induced Pathogenic Luminal Content Translocation - Friend or Foe?

The incidence of perturbed gastrointestinal integrity, as well as resulting systemic immune responses and gastrointestinal symptoms, otherwise known as exercised-induced gastrointestinal syndrome (EIGS), is common among individuals who partake in prolonged exercise. EIGS may cause the translocation of pathogenic material, including whole bacteria and bacterial endotoxins, from the lumen into circulation, which may progress into clinical consequences such as sepsis, and potentially subsequent fatality. However, further investigation is warranted to assess the possibility of food allergen and/or digestive enzyme luminal to circulatory translocation in response to exercise, and the clinical consequences. Findings from this narrative literature review demonstrate evidence that whole bacteria and bacterial endotoxins translocation from the gastrointestinal lumen to systemic circulation occurs in response to exercise stress, with a greater propensity of translocation occurring with accompanying heat exposure. It has also been demonstrated that food allergens can translocate from the lumen to systemic circulation in response to exercise stress and initiate anaphylaxis. To date, no research investigating the effect of exercise on the translocation of digestive enzymes from the lumen into systemic circulation exists. It is evident that EIGS and consequential pathogenic translocation presents life-threatening clinical implications, warranting the development and implementation of effective management strategies in at-risk populations.

Does Age Influence Gastrointestinal Status Responses to Exertional-heat Stress?

This meta-data exploration aimed to determine the impact of exertional-heat stress (EHS) on gastrointestinal status of masters age and young adult endurance athletes. Sixteen MASTERS (mean: 44y) and twenty-one YOUNG (26y) recreational endurance athletes completed 2 h of running at 60% ˙V O2max in 35˚C ambient conditions. Blood samples were collected pre-, immediately and 1 h post-EHS, and analyzed for markers of exercise-induced gastrointestinal syndrome (EIGS). Thermo-physiological measures and gastrointestinal symptoms (GIS) were recorded every 10-20 min during EHS. Peak Δ pre- to post-EHS did not substantially differ (p>0.05) between MASTERS and YOUNG for intestinal epithelial injury [I-FABP: 1652pg/ml vs. 1524pg/ml, respectively], bacterial endotoxic translocation [sCD14: -0.09µg/mL vs. 0.84µg/mL, respectively], lipopolysaccharide-binding protein [LBP: 0.26µg/mL vs. 1.76µg/mL, respectively], and systemic inflammatory response profile (SIR-Profile: 92.0arb.unit vs. 154arb.unit, respectively). A significantly higher peak Δ pre- to post-EHS in endogenous endotoxin anti-body IgM (p=0.042), and pro-inflammatory cytokine IL-1ß (p=0.038), was observed in YOUNG compared to MASTERS. No difference was observed between incidence (81% and 80%, respectively) and severity (summative accumulation: 21 and 30, respectively) of reported GIS during EHS between MASTERS and YOUNG. Pathophysiology of EIGS in response to EHS does not substantially differ with age progression, since masters and younger adult endurance athletes responded comparably.

Flavonoids and phenolic acids from sugarcane: Distribution in the plant, changes during processing, and potential benefits to industry and health.

Sugarcane (Saccharum sp.) plants are grown in warmer climates throughout the world and processed to produce sugar as well as other useful byproducts such as molasses and bagasse. Sugarcane is rich in (poly)phenols, but there has been no attempt to critically evaluate the published information based on the use of suitable methodologies. The objective of this review is to evaluate the quantitative and qualitative (poly)phenolic profiles of individual parts of the sugarcane plant and its multiple industrial products, which will help develop new processes and uses for sugarcane (poly)phenols. The quantitative analysis involves the examination of extraction, concentration, and analytical techniques used in each study for each plant part and product. The qualitative analysis indicates the identification of various (poly)phenols throughout the sugarcane processing chain, using only compounds elucidated through robust analytical methodologies such as mass spectrometry or nuclear magnetic resonance. In conclusion, sugarcane (poly)phenols are predominantly flavonoids and phenolic acids. The main flavonoids, derivatives of apigenin, luteolin, and tricin, with a substantial proportion of C-glycosides, are consistently found across all phases of sugarcane processing. The principal phenolic acids reported throughout the process include chlorogenic acids, as well as ferulic and caffeic acids mostly observed after hydrolysis. The derivation of precise quantitative information across publications is impeded by inconsistencies in analytical methodologies. The presence of multiple (poly)phenols with potential benefits for industrial applications and for health suggests sugarcane could be a useful provider of valuable compounds for future use in research and industrial processes.

Compilations and updates on residual feed intake in sheep.

The increasing global demand for food and the strong effect of climate change have forced animal science to advance regarding new methods of selection in search of more efficient animals in production systems. Feed consumption represents more than 70% of the costs of sheep farms, and more efficient animals can increase the farmers' profitability. One of the main measures of feed efficiency is estimated residual feed intake (RFI), created in 1963 by Robert Koch for estimation in cattle and later adapted for sheep. Animals with negative RFI values (RFI-) are more efficient than animals with positive values (RFI+), with influence on the variables of performance, carcass quality and production of enteric gases. The RFI is the most common and accepted metric of the feed efficiency trait for genetic selection, since it is independent of growth traits, unlike the feed conversion ratio. The purpose of this review article was to present updated literature information on the relationship of RFI estimates with performance measures, molecular markers, greenhouse gas production and feed efficiency, the technical aspects and physiological basis of metabolic in sheep.

Performance, feed efficiency, feeding behavior, and cortisol concentration of lambs ranked for Residual Feed Intake and Residual Intake and Gain.

This study aimed to evaluate the performance, feed efficiency, feeding behavior, and cortisol concentrations of lambs ranked into different groups of Residual Feed Intake (RFI) and Residual Intake and Gain (RIG). Forty Santa Inês lambs with a mean initial age of 120 ± 30 days and mean initial (IBW) and final body weight (FBW) of 28.9 ± 3.2 and 43.7 ± 3.9 kg, respectively, were used. The animals were fed at an automatic feed and water station (Intergado®) for 60 days and classified at the end of the experiment as low-RFI/RIG, medium-RFI/RIG, and high-RFI/RIG according to RFI and RIG. Performance, feed efficiency measures, ingestive behavior, temperament, and cortisol concentrations were measured, and Pearson's correlation analysis was performed to evaluate the relationship between the variables studied. The variables that differed most between RFI groups were dry matter intake, feed conversion, and feed efficiency, with better values in efficient animals (RFI-). Regarding the RGI groups, the average daily gain of animals classified as RIG- was 19.37% lower than that of animals classified as RIG± and 39.28% lower than that of animals classified as RIG+. Only the hourly feeding rate per day (p = 0.04) differed significantly between RFI and RIG classes, while no differences were observed for the ingestive behavior variables or cortisol. The number of visits to the feed bunk (total, with or without intake) showed no correlation with any performance or efficiency measure. Identifying animals ranked into different RFI and RIG classes shows that more efficient animals have a lower feed intake for the same weight gain and spend less time at the feed bunk.

Disseminated cancer cells in breast cancer: Mechanism of dissemination and dormancy and emerging insights on therapeutic opportunities.

Metastatic spread in breast cancer patients is the major driver of cancer-related deaths. A unique subset of cells disseminated from pre-invasive or primary tumor lesions are recognized as the main seeds for metastatic outgrowth. Disseminated cancer cells (DCCs) can migrate to distant organs and settle in a dormant state for a prolonged period until they emerge to overt metastases. Understanding the biology of breast cancer cells dissemination, dormancy and reactivation to form overt metastases has become an important focus. In this review, we discuss the recent advancements of molecular pathways involving breast cancer cell dissemination, role of chemokine-chemokine receptor networks in DCCs migration, DCCs phenotypic heterogeneity and unique genes signatures in tumor dormancy, microenvironmental regulation and specific niches that favors DCCs homing and dormancy. In addition, we also discuss recent findings relating to the role of immune response on DCC dissemination and dormancy. With recent advances in the field of immunotherapy/targeted therapy and its beneficial effects in cancer treatment, this review will focus on their impact on DCCs, reversal of stemness, tumor dormancy and metastatic relapse.

Plasma measurements of the dual sugar test reveal carbohydrate immediately alleviates intestinal permeability caused by exertional heat stress.

The aim of this set of randomised cross-over studies was to determine the impact of progressive heat exposure and carbohydrate or protein feeding during exertional stress on small intestine permeability using a dual sugar test. In our previous work, and typically in the field, recovery of lactulose and l-rhamnose is measured cumulatively in urine. This follow-up study exploits our novel high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) protocol to accurately quantify the sugars in plasma. Endurance-trained participants completed experimental trial A (ET-A; n = 8), consisting of 2 h running at 60% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ in temperate, warm and hot ambient conditions, and/or experimental trial B (ET-B; n = 9), consisting of 2 h running at 60% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ in the heat while consuming water, carbohydrate or protein. Blood samples were collected and plasma lactulose (L) and l-rhamnose (R) appearance, after dual sugar solution ingestion at 90 min of exercise, was quantified by HPAEC-PAD to measure plasma L/R and reveal new information about intestinal permeability immediately post-exercise and during recovery. In ET-A, plasma L/R increased immediately post-exercise in hot compared with temperate and warm conditions, while, in ET-B, carbohydrate alleviated this, and this information was otherwise missed when measuring urine L/R. Consuming carbohydrate or protein before and during exercise attenuated small intestine permeability throughout recovery from exertional heat stress. We recommend using the dual sugar test with quantification of plasma sugars by HPAEC-PAD at intervals to maximise intestinal permeability data collection in exercise gastroenterology research, as this gives additional information compared to urinary measurements. KEY POINTS: Intestinal permeability is typically assessed using a dual sugar test, by administering a drink containing non-metabolisable sugars (e.g. lactulose (L) and l-rhamnose (R)) that can enter the circulation by paracellular translocation when the epithelium is compromised, and are subsequently measured in urine. We demonstrate that our recently developed ion chromatography protocol can be used to accurately quantify the L/R ratio in plasma, and that measuring L/R in plasma collected at intervals during the post-exercise recovery period reveals novel acute response information compared to measuring 5-h cumulative urine L/R. We confirm that exercising in hot ambient conditions increases intestinal epithelial permeability immediately after exercise, while consuming carbohydrate or protein immediately before and during exercise attenuates this. We recommend using our dual sugar absorption test protocol to maximise intestinal epithelial permeability data collection in exercise gastroenterology research and beyond.

Retrospective Study of Treatment Patterns and Natural History of Patients with T1a/b N0 Triple-Negative Breast Cancers: A Single-Institution Experience.

INTRODUCTION: T1a/b, node-negative (node-), triple-negative breast cancers (TNBCs) are underrepresented in randomized drug-approving clinical trials. Given their low incidence, the clinicopathological features, natural history, and treatment patterns of these tumors remain insufficiently understood. METHODS: We conducted a single-institution retrospective cohort study of patients with T1a/b, N0, M0 TNBCs. Deidentified patient- and tumor-related data were collected and summarized. Kruskal-Wallis, χ2, or Fisher exact tests were used to evaluate associations of interest. Kaplan-Meier methods, log-rank tests, and Cox's proportional hazards models were applied for survival analyses. RESULTS: Of 108 cases of node- TNBCs measuring ≤2 cm, 34 node- T1a/b tumors were included in our analysis. All cases had an intermediate to high histological grade, and most had a Ki-67 score of ≥20%. All patients received adjuvant chemotherapy, and many underwent mastectomy (47%). Docetaxel combined with cyclophosphamide was the most common adjuvant chemotherapy regimen (75%). We did not observe significant associations between improved outcomes and treatment with anthracycline-containing regimens. Among patients with node- pT1a/b tumors, the estimated 3-year recurrence-free survival (RFS) and distant RFS rates were both 96.3% (95% CI: 76.5-99.5), and the overall survival rate was estimated to be 100% (95% CI: 100-100). There were no cases of local recurrences observed. CONCLUSIONS: In our cohort, all patients with T1a/b node- TNBCs were treated with adjuvant chemotherapy and had favorable outcomes even when treated with anthracycline-sparing regimens.

A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience.

INTRODUCTION: Alpelisib is approved in combination with endocrine therapy (ET) to treat patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) progressive metastatic breast cancer (MBC). The SOLAR-1 trial demonstrated the efficacy of this oral agent and showed that, while alpelisib improves outcomes compared to placebo, it is also associated with clinically relevant adverse events (AEs). There is a pressing need for improved knowledge on the effectiveness and tolerability of this agent in real-world patient populations. METHODS: We conducted a retrospective cohort study of patients with HR+, HER2- MBC treated with alpelisib and ET. We assessed the safety, tolerability, and effectiveness of alpelisib in a real-world population. Deidentified patient-, tumor-, and outcome-related data, including AEs, were collected and summarized. Kaplan-Meier methods were applied for survival analyses, and stratified analyses of interest were conducted. A p value <0.05 was considered statistically significant. RESULTS: A total of 76 women treated with alpelisib + ET were included in our cohort. Most had been previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and chemotherapy for MBC. The estimated median progression-free survival was 5.2 months (95% CI, 4.1-8.0). The median overall survival was longer among patients without prior everolimus therapy (hazard ratio, 4.28 [95% CI, 1.64-11.16]; p = 0.0012), and no significant outcome differences were observed between patients treated with different starting doses of alpelisib. Approximately 31.6% of patients permanently discontinued alpelisib due to AEs, and 32.9% had at least one dose reduction. The most common grade 3/4 AEs were hyperglycemia (21%), fatigue (13.2%), and diarrhea (10.5%). CONCLUSIONS: For progressive HR+, HER2- MBC, alpelisib + ET showed effectiveness in a real-world patient population that was comparable to published clinical trial data, regardless of starting dose. However, the effectiveness of alpelisib following previous everolimus exposure may be limited and, hence, should be a consideration to decide sequencing of therapy in these patients. Patients treated with alpelisib are at risk for clinically relevant AEs and require close monitoring.

Clinical and Prognostic Impact of the Warburg Effect in Esophageal Carcinoma: Monocarboxylate Transporters as Candidates for Therapeutic Targeting.

INTRODUCTION: Esophageal cancer (EC) seems to display increased glycolytic activity, but clinical studies on the expression/prognostic significance of glycometabolism-related proteins, as well as functional assays, are missing. METHODS: Expression of 10 glycolytic biomarkers was evaluated by immunohistochemistry in tissue sections from 95 patients. Two esophageal squamous cell carcinoma (ESCC) cell lines were used to assess the effect of monocarboxylate transporter (MCT) downregulation on cell viability and extracellular lactate/glucose accumulation. RESULTS: Expression of MCT1, MCT4, CD147, and GLUT1 was significantly associated with an ESCC histopathology, while a poor clinicopathological profile was seen in GLUT1- and LDHA-positive EC cases. In the ESCC group, MCT1 immunoreactivity is associated with high TNM stage and metastasis. The 3-year overall survival (OS) rate was significantly influenced by MCT4 and CAIX positivity and HKII negativity. Those biomarkers were considered independent prognostic factors of OS in multivariate analysis. Dual inhibition of MCT1/4 expression decreased cell viability and extracellular lactate accumulation in ESCC cells. CONCLUSION: Elevated glycolytic rates correlate with a poor clinicopathological profile in EC patients. MCT4 and CAIX positivity independently predict a worse prognosis. Due to the lack of information on treatment modalities, we could not further infer the role of these biomarkers in predicting response to therapy, which needs to be assessed in future studies. In addition, MCT1/4 targeting should be performed both "in vitro" and "in vivo" to further explore its impact on tumor growth and response to classical therapies. HKII expression and function, particularly in the tumor stroma, should be investigated.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Historical line of airglow observations at Comandante Ferraz Brazilian Station: measurements of temperature and studies on gravity waves.

The thermal dynamics of the upper atmosphere, especially in the mesosphere, have been improving our understanding about the effects of climate change, as well as how the dynamics and general circulation in the upper atmosphere are driven by different types of waves, such as the atmospheric gravity waves, planetary waves and atmospheric tides. In order to study the upper atmospheric temperature variability and gravity waves, several research groups have been employing the remote technique of observing the airglow emissions originated in the upper mesosphere and lower thermosphere, besides emissions from the ionosphere. INPE's airglow group started the studies on emissions from the upper atmosphere to investigate temperature and dynamics in the mesosphere, thermosphere/ionosphere at the end of 70's. However, only in 2001 this group sent the first airglow experiment to the Brazilian Antarctic Station Comandante Ferraz (EACF) to measure the OH (8-3) emission and temperature. From that year to 2014, several other experiments were carried out at EACF, not only to measure the temperature and airglow intensities, but also to observe gravity waves, winds and other related phenomena. This paper presents airglow experiments at EACF from 2001 to the present, including illustrations, examples of already published results, and unpublished data.

Classification of a patient's caries activity based on lesion activity assessment among adults: findings from a prospective cohort study.

OBJECTIVE: To investigate whether the classification of a patient's caries activity based on lesion activity assessment can predict the increment and progression of coronal and root caries lesions among adults. METHODS: This population-based prospective cohort study followed 413 individuals (mean age 54.1) from southern Brazil for 4 years. Data collection included a questionnaire and clinical examination to record coronal/root caries and gingival recession. The main outcomes were caries increment measured as decayed, missing and filled tooth surfaces (DMFS) and caries progression (surface-level analysis). The main predictor variable was patients' caries activity at baseline ("caries-inactive" or "caries-active"). Negative binomial regression models (unadjusted and adjusted) were used. RESULTS: Caries-active individuals were more likely to present DMFS increment than caries-inactive ones when migrations among DMFS components were considered (IRR [incidence risk ratio] = 1.26, 95%CI [confidence interval] = 1.01-1.58). On the other hand, no such association was found when these migrations were disregarded. The risk for coronal caries progression on filled surfaces was 90% higher among caries-active patients (IRR=1.9; 95%CI=1.4-2.6). In addition, patient's caries activity was able to predict higher risk for root caries progression in newly exposed root surfaces (IRR=1.9; 95%CI=1.0-3.6). CONCLUSION: The classification of a patient's caries activity based on lesion activity was able to foresee lesion progression on the coronal and root surfaces more susceptible to caries among adults. Clinical relevance Classifying a patient's caries activity is a useful tool for the clinical management of dental caries in adults.

Amino Acid-Based Beverage Interventions Ameliorate Exercise-Induced Gastrointestinal Syndrome in Response to Exertional-Heat Stress: The Heat Exertion Amino Acid Technology (HEAAT) Study.

The study aimed to determine the effects of two differing amino acid beverage interventions on biomarkers of intestinal epithelial integrity and systemic inflammation in response to an exertional-heat stress challenge. One week after the initial assessment, participants (n = 20) were randomly allocated to complete two exertional-heat stress trials, with at least 1 week washout. Trials included a water control trial (CON), and one of two possible amino acid beverage intervention trials (VS001 or VS006). On VS001 (4.5 g/L) and VS006 (6.4 g/L), participants were asked to consume two 237-ml prefabricated doses daily for 7 days before the exertional-heat stress, and one 237-ml dose immediately before, and every 20 min during 2-hr running at 60% maximal oxygen uptake in 35 °C ambient conditions. A water volume equivalent was provided on CON. Whole blood samples were collected pre-, immediately post-, 1 and 2 hr postexercise, and analyzed for plasma concentrations of cortisol, intestinal fatty acid protein, soluble CD14, and immunoglobulin M (IgM) by ELISA, and systemic inflammatory cytokines by multiplex. Preexercise resting biomarker concentrations for all variables did not significantly differ between trials (p > .05). A lower response magnitude for intestinal fatty acid protein (mean [95% CI]: 249 [60, 437] pg/ml, 900 [464, 1,336] pg/ml), soluble CD14 (-93 [-458, 272] ng/ml, 12 [-174, 197] ng/ml), and IgM (-6.5 [-23.0, 9.9] MMU/ml, -10.4 [-16.2, 4.7] MMU/ml) were observed on VS001 and V006 compared with CON (p < .05), respectively. Systemic inflammatory response profile was lower on VS001, but not VS006, versus CON (p < .05). Total gastrointestinal symptoms did not significantly differ between trials. Amino acid beverages' consumption (i.e., 4.5-6.4 g/L), twice daily for 7 days, immediately before, and during exertional-heat stress ameliorated intestinal epithelial integrity and systemic inflammatory perturbations associated with exercising in the heat, but without exacerbating gastrointestinal symptoms.

The Impact of a Short-Term Ketogenic Low-Carbohydrate High-Fat Diet on Biomarkers of Intestinal Epithelial Integrity and Gastrointestinal Symptoms.

Endurance exercise can disturb intestinal epithelial integrity, leading to increased systemic indicators of cell injury, hyperpermeability, and pathogenic translocation. However, the interaction between exercise, diet, and gastrointestinal disturbance still warrants exploration. This study examined whether a 6-day dietary intervention influenced perturbations to intestinal epithelial disruption in response to a 25-km race walk. Twenty-eight male race walkers adhered to a high carbohydrate (CHO)/energy diet (65% CHO, energy availability = 40 kcal·kg FFM-1·day-1) for 6 days prior to a Baseline 25-km race walk. Athletes were then split into three subgroups: high CHO/energy diet (n = 10); low-CHO, high-fat diet (LCHF: n = 8; <50 g/day CHO, energy availability = 40 kcal·kg FFM-1·day-1); and low energy availability (n = 10; 65% CHO, energy availability = 15 kcal·kg FFM-1·day-1) for a further 6-day dietary intervention period prior to a second 25-km race walk (Adaptation). During both trials, venous blood was collected pre-, post-, and 1 hr postexercise and analyzed for markers of intestinal epithelial disruption. Intestinal fatty acid-binding protein concentration was significantly higher (twofold increase) in response to exercise during Adaptation compared to Baseline in the LCHF group (p = .001). Similar findings were observed for soluble CD14 (p < .001) and lipopolysaccharide-binding protein (p = .003), where postexercise concentrations were higher (53% and 36%, respectively) during Adaptation than Baseline in LCHF. No differences in high CHO/energy diet or low energy availability were apparent for any blood markers assessed (p > .05). A short-term LCHF diet increased intestinal epithelial cell injury in response to a 25-km race walk. No effect of low energy availability on gastrointestinal injury or symptoms was observed.

Imbalanced data preprocessing techniques for machine learning: a systematic mapping study.

Machine Learning (ML) algorithms have been increasingly replacing people in several application domains-in which the majority suffer from data imbalance. In order to solve this problem, published studies implement data preprocessing techniques, cost-sensitive and ensemble learning. These solutions reduce the naturally occurring bias towards the majority sample through ML. This study uses a systematic mapping methodology to assess 9927 papers related to sampling techniques for ML in imbalanced data applications from 7 digital libraries. A filtering process selected 35 representative papers from various domains, such as health, finance, and engineering. As a result of a thorough quantitative analysis of these papers, this study proposes two taxonomies-illustrating sampling techniques and ML models. The results indicate that oversampling and classical ML are the most common preprocessing techniques and models, respectively. However, solutions with neural networks and ensemble ML models have the best performance-with potentially better results through hybrid sampling techniques. Finally, none of the 35 works apply simulation-based synthetic oversampling, indicating a path for future preprocessing solutions.

Th1 cytokine interferon gamma improves response in HER2 breast cancer by modulating the ubiquitin proteasomal pathway.

HER2 breast cancer (BC) remains a significant problem in patients with locally advanced or metastatic BC. We investigated the relationship between T helper 1 (Th1) immune response and the proteasomal degradation pathway (PDP), in HER2-sensitive and -resistant cells. HER2 overexpression is partially maintained because E3 ubiquitin ligase Cullin5 (CUL5), which degrades HER2, is frequently mutated or underexpressed, while the client-protective co-chaperones cell division cycle 37 (Cdc37) and heat shock protein 90 (Hsp90) are increased translating to diminished survival. The Th1 cytokine interferon (IFN)-γ caused increased CUL5 expression and marked dissociation of both Cdc37 and Hsp90 from HER2, causing significant surface loss of HER2, diminished growth, and induction of tumor senescence. In HER2-resistant mammary carcinoma, either IFN-γ or Th1-polarizing anti-HER2 vaccination, when administered with anti-HER2 antibodies, demonstrated increased intratumor CUL5 expression, decreased surface HER2, and tumor senescence with significant therapeutic activity. IFN-γ synergized with multiple HER2-targeted agents to decrease surface HER2 expression, resulting in decreased tumor growth. These data suggest a novel function of IFN-γ that regulates HER2 through the PDP pathway and provides an opportunity to impact HER2 responses through anti-tumor immunity.

Effects of adding aerobic physical activity to strengthening exercise on hip osteoarthritis symptoms: protocol for the PHOENIX randomised controlled trial.

BACKGROUND: Hip osteoarthritis (OA) is a leading cause of musculoskeletal pain. Exercise is a core recommended treatment. Most evidence is based on muscle-strengthening exercise, but aerobic physical activity has potential to enhance clinical benefits. The primary aim of this study is to test the hypothesis that adding aerobic physical activity to a muscle strengthening exercise leads to significantly greater reduction in hip pain and improvements in physical function, compared to a lower-limb muscle strengthening exercise program alone at 3 months. METHODS: This is a superiority, 2-group, parallel randomised controlled trial including 196 people with symptomatic hip OA from the community. Following baseline assessment, participants are randomly allocated to receive either i) aerobic physical activity and muscle strengthening exercise or; ii) muscle strengthening exercise only. Participants in both groups receive 9 consultations with a physiotherapist over 3 months. Both groups receive a progressive muscle strengthening exercise program in addition to advice about OA management. The aerobic physical activity plan includes a prescription of moderate intensity aerobic physical activity with a goal of attaining 150 min per week. Primary outcomes are self-reported hip pain assessed on an 11-point numeric rating scale (0 = 'no pain' and 10 = 'worst pain possible') and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index physical function subscale) at 3 months. Secondary outcomes include other measures of self-reported pain (assessed at 0, 3, 9 months), self-reported physical function (assessed at 0, 3, 9 months), performance-based physical function (assessed at 0, 3 months), joint stiffness (assessed at 0, 3, 9 months), quality of life (assessed at 0, 3, 9 months), muscle strength (assessed at 0, 3 months), and cardiorespiratory fitness (assessed at 0, 3 months). Other measures include adverse events, co-interventions, and adherence. Measures of body composition, serum inflammatory biomarkers, quantitative sensory measures, anxiety, depression, fear of movement and self-efficacy are included to explore causal mechanisms. DISCUSSION: Findings will assist to provide an evidence-based recommendation regarding the additional effect of aerobic physical activity to lower-limb muscle strengthening on hip OA pain and physical function. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry reference: ACTRN 12619001297112. Registered 20th September 2019.