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Introduction: Breast cancer survivors often experience pre and post-treatment physical and psychological symptoms, negatively affecting their quality of life. Regular physical exercise is associated with better quality of life and lower recurrence of cancer, and therefore all oncological patients are recommended to practice it in a regular basis. Despite this, breast cancer survivors have low adherence to physical exercise. The purpose of this study is to identify barriers, facilitators and preferences of Chilean breast cancer survivors to practice physical exercise., Methods: Phenomenological qualitative study of 12 in-depth interviews with adjuvant radiation therapy concluded at least three months ago., Results: Breast cancer survivors ignored the benefits of physical exercise during and after treatment. The barriers were physical symptoms, psychological barriers, sociocultural barriers, health system barriers, disinformation and sedentary lifestyle. Facilitators were coping with physical symoptoms, psychological issues, having information and active lifestyle. The preferences were painless and familiar exercises. Preferred exercise was walking., Conclusions: Breast cancer survivors may adhere to physical exercise despite barriers when certain facilitators are present, which may be promoted by the health team when reporting the benefits of the physical exercise, prescribing personalized, safe and painless physical exercise and educating both patient and her family about the role of the physical exercise in cancer recovering process., Competing Interests: The authors declare that there are no potential conflicts of interest in relation to the research, authorship and/or publication of this study., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

The Tropical Andes, one of the world's most biodiverse regions, is vital for ecological research and conservation. However, while researchers in Bolivia, Ecuador, and Peru contribute significantly to scientific knowledge, their publication rates in academic journals have historically lagged behind neighboring nations. A multifaceted strategy was employed to understand and address the publication divide in the Tropical Andes region. This approach focused on regional researchers and consisted of a three-day workshop to improve scientific writing skills, offer publication insights, and equip researchers with tools to overcome obstacles. A series of surveys were also conducted to explore the challenges faced by local researchers and their proposed solutions, covering topics such as participant demographics, factors contributing to lower publication rates, personal barriers, proposed strategies for improving publications, specific topics of interest, participant satisfaction, most valuable workshop topics, and future recommendations. The workshop had an overwhelming response, with over 500 interested participants registering in just a few days, mostly experienced professionals, highlighting the need for such initiatives in the region. About two-thirds had ready-to-publish materials, highlighting the potential impact of targeted interventions on unlocking untapped knowledge. The surveys revealed the challenges contributing to the publication divide, including insufficient training, cultural emphasis on economic development, language barriers, limited resource access, lack of institutional support, high publishing costs, and time and financial constraints. The most common personal barriers were insufficient knowledge and experience in the publication process, lack of self-confidence, and fears of rejection. Proposed solutions include conducting training workshops, fostering collaborative networks, improving resource accessibility, and an institutional and cultural shift that encourages publishing. Addressing challenges faced by experienced professionals in the Tropical Andes by understanding individual needs, fostering support, and demystifying the publication process offers a promising path to closing the publication divide and unlocking the region's valuable scientific contributions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Valdez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Kidney-specific with-no-lysine kinase 1 (KS-WNK1) is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies have suggested that it could play a role in regulating potassium renal excretion by modulating the activity of the Na + -Cl - cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal-potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low-potassium diet. In this study, we investigated the role of KS-WNK1 in regulating potassium excretion under extreme changes in potassium intake. After following a zero-potassium diet (0KD) for 10 days, KS-WNK1 -/- mice had lower plasma levels of K + and Cl - while exhibiting higher urinary excretion of Na + , Cl - , and K + compared with KS-WNK1 +/+ mice. After 10 days of 0KD or normal-potassium diet (NKD), all mice were challenged with a high-potassium diet (HKD). Plasma K + levels markedly increased after the HKD challenge only in mice previously fed with 0KD, regardless of genotype. KSWNK1 +/+ mice adapt better to HKD challenge than KS-WNK1 -/- mice after a potassium-retaining state. The difference in the phosphorylated NCC-to-NCC ratio between KS-WNK1 +/+ and KS-WNK1 -/- mice after 0KD and HKD indicates a role for KS-WNK1 in both NCC phosphorylation and dephosphorylation. These observations show that KS-WNK1 helps the distal convoluted tubule to respond to extreme changes in potassium intake, such as those occurring in wildlife. NEW & NOTEWORTHY The findings of this study demonstrate that kidney-specific with-no-lysine kinase 1 plays a role in regulating urinary electrolyte excretion during extreme changes in potassium intake, such as those occurring in wildlife.  .

Background: Neutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, and there are scarce data on their evolution during the disease. We studied circulating NET markers in patients with COVID-19 throughout their hospitalization., Methods: We prospectively included 93 patients (201 blood samples), evaluating the disease severity in 3 evolutionary phases (viral, early, and late inflammation). Of these, 72 had 180 samples in various phases. We also evaluated 55 controls with similar age, sex and comorbidities. We measured 4 NET markers in serum: cfDNA, CitH3, and MPO-DNA and NE-DNA complexes; as well as neutrophil-related cytokines IL-8 and G-CSF., Results: The COVID-19 group had higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), and cfDNA, MPO-DNA, and NE-DNA (7.87 vs 2.56 ng/mL; 0.80 vs 0.52 and 1.04 vs 0.72, respectively, p < 0.001 for all) than the controls throughout hospitalisation. cfDNA was the only NET marker clearly related to severity, and it remained higher in non-survivors during the 3 phases. Only cfDNA was an independent risk factor for mortality and need for intensive care. Neutrophil count, IL-8, and G-CSF were significantly related to severity. MPO-DNA and NE-DNA showed significant correlations (r: 0.483, p < 0.001), including all 3 phases and across all severity grades, and they only remained significantly higher on days 10-16 of evolution in those who died. Correlations among the other NET markers were lower than expected., Conclusions: The circulating biomarkers of NETs were present in patients with COVID-19 throughout hospitalization. cfDNA was associated with severity and mortality, but the three other markers showed little or no association with these outcomes. Neutrophil activity and neutrophil count were also associated with severity. MPO-DNA and NE-DNA better reflected NET formation. cfDNA appeared to be more associated with overall tissue damage; previous widespread use of this marker could have overestimated the relationship between NETs and severity. Currently, there are limitations to accurate NET markers measurement that make it difficult to assess its true role in COVID-19 pathogenesis., (© 2024. The Author(s).)

Background: Peritoneal dialysis (PD)-related infections, such as peritonitis, exit site, and tunnel infections, substantially impair the sustainability of PD. Accordingly, PD-related infection is the top-priority research outcome for patients and caregivers. While PD nurse trainers teach patients to perform their own PD, PD training curricula are not standardized or informed by an evidentiary base and may offer a potential approach to prevent PD infections. The Targeted Education ApproaCH to improve Peritoneal Dialysis outcomes (TEACH-PD) trial evaluates whether a standardized training curriculum for PD nurse trainers and incident PD patients based on the International Society for Peritoneal Dialysis (ISPD) guidelines reduces PD-related infections compared to usual training practices., Methods: The TEACH-PD trial is a registry-based, pragmatic, open-label, multi-center, binational, cluster-randomized controlled trial. TEACH-PD will recruit adults aged 18 years or older who have not previously undergone PD training at 42 PD treatment units (clusters) in Australia and New Zealand (ANZ) between July 2019 and June 2023. Clusters will be randomized 1:1 to standardized TEACH-PD training curriculum or usual training practice. The primary trial outcome is the time to the first occurrence of any PD-related infection (exit site infection, tunnel infection, or peritonitis). The secondary trial outcomes are the individual components of the primary outcome, infection-associated catheter removal, transfer to hemodialysis (greater than 30 days and 180 days), quality of life, hospitalization, all-cause death, a composite of transfer to hemodialysis or all-cause death, and cost-effectiveness. Participants are followed for a minimum of 12 months with a targeted average follow-up period of 2 years. Participant and outcome data are collected from the ANZ Dialysis and Transplant Registry (ANZDATA) and the New Zealand Peritoneal Dialysis (NZPD) Registry. This protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines., Discussion: TEACH-PD is a registry-based, cluster-randomized pragmatic trial that aims to provide high-certainty evidence about whether an ISPD guideline-informed standardized PD training curriculum for PD nurse trainers and adult patients prevents PD-related infections., Trial Registration: ClinicalTrials.gov NCT03816111. Registered on 24 January 2019., (© 2023. Crown.)

Objective: To compare clinical and functional variables among 3 groups of children and adolescents: subjects at clinical high risk for psychosis (CHR-P) who also have obsessive-compulsive symptoms (OCS), CHR-P patients without OCS, and healthy controls (HC)., Methods: A total of 128 CHR-P patients and 98 HC between the ages of 10 and 17 years were recruited as part of a multicenter prospective longitudinal study conducted in Spain between January 1, 2011, and December 31, 2018, with diagnoses made for CHR-P using the Scale of Prodromal Symptoms (SOPS). Two groups were obtained based on Leyton Obsessional Inventory-Child Version (LOI-CV) scores: 64 CHR-P patients with OCS (OCS+) and 64 CHR-P patients without OCS (OCS-). Clinical variables were analyzed with a generalized linear model., Results: Overall, 128 CHR-P patients, 64 (50%) with OCS (mean ± SD age = 15.5 ± 1.4 years, 34.4% male), 64 CHR-P patients without OCS (mean ± SD age = 15.1 ± 1.9 years, 34.4% male), and 98 HC (mean ± SD age = 15.5 ± 1.5 years, 42.9% male), of whom 19 (19.5%) had OCS, were included. Generalized linear model analysis revealed significant differences between the groups. The OCS+ group showed more severe prodromal symptoms ( P  = .007), worse functioning at baseline ( P  = .044) and during the previous year ( P  = .004), and more dysmorphophobic symptoms ( P  < .001) compared to the OCS- group. OCS+ patients were also more frequently treated with antidepressants ( P  = .004) than were OCS- patients., Conclusions: In our sample, among children and adolescents with CHR-P, the prevalence of OCS was high (50%). OCS+ subjects had a more severe clinical and functional profile than OCS- subjects. Early detection and treatment of these symptoms can lead to better outcomes for these patients., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

The Pediatric Index of Mortality 3 (PIM3) is a scale that estimates the risk of mortality in children admitted to the Pediatric Intensive Care Unit (PICU) within the first hour of admission., Objective: to validate the PIM3 scale in pediatric population admitted to PICU at altitudes over 2,500 meters above sea level (m.a.s.l.), and to evaluate whether lactate and the oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) index improve its ability to predict mortality., Patients and Method: A prospective multicenter study was carried out in 10 PICUs in Colombia between November 2016 and June 2017. Variables were collected for the calculation of PIM3, serum lactate, and SpO2/FiO2 index. Their discrimination capacity was validated with the area under the ROC curve and calibration using the Hosmer Lemeshow goodness-of-fit test., Results: 2,803 admissions were included, with an overall mortality of 4.8% and a standardized mortality ratio of 1.1 (95%CI 1.00-1.3). PIM3 showed low calibration (p < 0.001) and adequate discrimination for the studied population (ROC 0.84; 95%CI 0.83-0.86). The addition of serum lactate and SpO2/FiO2 allowed a good calibration (p = 0.75) and maintained a high discrimination of mortality (ROC 0.86; 95%CI 0.84-0.87)., Conclusions: The performance of the PIM3 scale has adequate discrimination, but low calibration in children admitted to PICU at above 2500 m. a. s. l. Lactate and SpO2/FiO2 variables improved its predictive ability.

Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish, Danio rerio. Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formation in vitro in 3T3-L1 pre-adipocyte cells. In vivo in zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Severe COVID-19 entails a dysregulated immune response, most likely inflammation related to a lack of virus control. A better understanding of immune toxicity, immunosuppression balance, and COVID-19 assessments could help determine whether different clinical presentations are driven by specific types of immune responses. The progression of the immune response and tissular damage could predict outcomes and may help in the management of patients., Methods: We collected 201 serum samples from 93 hospitalised patients classified as moderately, severely, and critically ill. We differentiated the viral, early inflammatory, and late inflammatory phases and included 72 patients with 180 samples in separate stages for longitudinal study and 55 controls. We studied selected cytokines, P-selectin, and the tissue damage markers lactate dehydrogenase (LDH) and cell-free DNA (cfDNA)., Results: TNF-α, IL-6, IL-8, and G-CSF were associated with severity and mortality, but only IL-6 increased since admission in the critical patients and non-survivors, correlating with damage markers. The lack of a significant decrease in IL-6 levels in the critical patients and non-survivors in the early inflammatory phase (a decreased presence in the other patients) suggests that these patients did not achieve viral control on days 10-16. For all patients, lactate dehydrogenase and cfDNA levels increased with severity, and cfDNA levels increased in the non-survivors from the first sample (p = 0.002) to the late inflammatory phase (p = 0.031). In the multivariate study, cfDNA was an independent risk factor for mortality and ICU admission., Conclusions: The distinct progression of IL-6 levels in the course of the disease, especially on days 10-16, was a good marker of progression to critical status and mortality and could guide the start of IL-6 blockade. cfDNA was an accurate marker of severity and mortality from admission and throughout COVID-19 progression., (© 2023. The Author(s).)

Background: "Test-to-stay" (TTS) is an effective approach for keeping students in school post-exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To prepare for school-based SARS-CoV-2 testing, we implemented formative research to gather perspectives on school-based testing among school personnel, as well as caregivers of Black and Latino/a/x students given systemic racism, existing school inequalities, and the disproportionate effect of COVID-19 on Black and Latino/a/x populations., Methods: We conducted in-depth interviews with caregivers of K-12 grade Black and Latino/a/x students and focus group discussions with K-12 school personnel. We described the forthcoming school-based SARS-CoV-2 testing program and explored potential benefits and concerns, including concerns about testing-related stigma and discrimination, particularly toward Black and Latino/a/x students, and implementation recommendations., Results: Perceived testing benefits included school community reassurance and preventing school outbreaks. Concerns included potential student anxiety, classroom disruption, inaccurate results, and limited information for caregivers. Some participants mentioned that testing-related stigma and discrimination could happen based on the testing selection process or results but not due to race or ethnicity. Participants provided numerous testing recommendations, including suggestions to prevent negative outcomes., Conclusions: Participants believed that stigma and discrimination from SARS-CoV-2 testing is possible, although differential treatment based on race or ethnicity was not anticipated. Participants' narratives provide support for school-based testing and the testing component of TTS., (© 2022 American School Health Association.)

Rationale: MUC5AC (mucin 5AC, oligomeric gel-forming) and MUC5B (mucin 5B, oligomeric gel-forming) are the predominant secreted polymeric mucins in mammalian airways. They contribute differently to the pathogenesis of various muco-obstructive and interstitial lung diseases, and their genes are separately regulated, but whether they are packaged together or in separate secretory granules is not known. Objectives: To determine the packaging of MUC5AC and MUC5B within individual secretory granules in mouse and human airways under varying conditions of inflammation and along the proximal-distal axis. Methods: Lung tissue was obtained from mice stimulated to upregulate mucin production by the cytokines IL-1 β and IL-13 or by porcine pancreatic elastase. Human lung tissue was obtained from donated normal lungs, biopsy samples of transplanted lungs, and explanted lungs from subjects with chronic obstructive pulmonary disease. MUC5AC and MUC5B were labeled with antibodies from different animal species or, in mice only, by transgenic chimeric mucin-fluorescent proteins and imaged using widefield deconvolution or Airyscan fluorescence microscopy. Measurements and Main Results: In both mouse and human airways, most secretory granules contained both mucins interdigitating within the granules. Smaller numbers of granules contained MUC5B alone, and even fewer contained MUC5AC alone. Conclusions: MUC5AC and MUC5B are variably stored both in the same and in separate secretory granules of both mice and humans. The high fraction of granules containing both mucins under a variety of conditions makes it unlikely that their secretion can be differentially controlled as a therapeutic strategy. This work also advances knowledge of the packaging of mucins within secretory granules to understand mechanisms of epithelial stress in the pathogenesis of chronic lung diseases.

Background: This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS 2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published., Methods/design: The original protocol was published in BMC Nephrology ( https://doi.org/10.1186/s12882-019-1325-y ) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1-2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0-16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213 . Prospectively registered on 12 July 2018., (© 2022. The Author(s).)

Much has been written and said about the promise and excitement of microphysiological systems, miniature devices that aim to recreate aspects of human physiology on a chip. The rapid explosion of the offerings and persistent publicity placed high expectations on both product manufacturers and regulatory agencies to adopt the data. Inevitably, discussions of where this technology fits in chemical testing paradigms are ongoing. Some end-users became early adopters, whereas others have taken a more cautious approach because of the high cost and uncertainties of their utility. Here, we detail the experience of a public-private collaboration established for testing of diverse microphysiological systems. Collectively, we present a number of considerations on practical aspects of using microphysiological systems in the context of their applications in decision-making. Specifically, future end-users need to be prepared for extensive on-site optimization and have access to a wide range of imaging and other equipment. We reason that cells, related reagents, and the technical skills of the research staff, not the devices themselves, are the most critical determinants of success. Extrapolation from concentration-response effects in microphysiological systems to human blood or oral exposures, difficulties with replicating the whole organ, and long-term functionality remain as critical challenges. Overall, we conclude that it is unlikely that a rodent- or human-equivalent model is achievable through a finite number of microphysiological systems in the near future; therefore, building consensus and promoting the gradual incorporation of these models into tiered approaches for safety assessment and decision-making is the sensible path to wide adoption., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bezoar is a term from Arabic "bāzahr" or ultimately from Middle Persian "p'tzhl" (pādzahr, "bezoar antidote" or less commonaly ægagropile or egagropile (2-4). It was believed to have the power of a universal antidote that works against any poison, and a glass containing a bezoar could neutralize any poison poured into it. In science, it is a mass of hair or undigested vegetable matter found in a human or animal intestines, similar to a hairball. Otherwise, the name could derive from a kind of Turkish goat whose name is just bezoar. Usually, it is found trapped in every part of the gastrointestinal system and must be distinguished by pseudobezoar, which is an nondigestible object voluntarily introduced into the digestive tract. The most common causes are a previous gastric surgery such as a gastric band (for weight loss) or gastric bypass, a reduced stomach acid (hypochlorhydria) or decreased stomach size, and a delayed gastric emptying, typically due to diabetes, autoimmune disorders, or mixed connective tissue disease. Seed bezoars are usually found in the rectum of patients without predisposing factors, causing constipation and pain. Rectal impaction is common after ingestion of seeds, while a true occlusion is rare. Although several cases of phytobezoars composed of various types of seeds are reported in the literature, bezoars of pumpkin seeds have rarely been reported. The authors report a case of fecal impaction by pumpkin seed bezoars with abdominal pain: a difficulty to void with subsequent rectal inflammation and hemorrhoid enlargement was observed. The patient underwent a successful manual disimpaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gentile, Vergara, Schiavone, Cestaro and Sivero.)

The cell wall integrity (CWI) MAPK pathway of budding yeast Saccharomyces cerevisiae is specialized in responding to cell wall damage, but ongoing research shows that it participates in many other stressful conditions, suggesting that it has functional diversity. The output of this pathway is mainly driven by the activity of the MAPK Slt2, which regulates important processes for yeast physiology such as fine-tuning of signaling through the CWI and other pathways, transcriptional activation in response to cell wall damage, cell cycle, or determination of the fate of some organelles. To this end, Slt2 precisely phosphorylates protein substrates, modulating their activity, stability, protein interaction, and subcellular localization. Here, after recapitulating the methods that have been employed in the discovery of proteins phosphorylated by Slt2, we review the bona fide substrates of this MAPK and the growing set of candidates still to be confirmed. In the context of the complexity of MAPK signaling regulation, we discuss how Slt2 determines yeast cell integrity through phosphorylation of these substrates. Increasing data from large-scale analyses and the available methodological approaches pave the road to early identification of new Slt2 substrates and functions.

Background: The Learning Environment (LE) influences the performance of students, learning, social life, mental health, and the future of work., Aim: To assess the learning environment (LE) among medical residents of 64 specialties., Material and Methods: Two validated instruments "Postgraduate Hospital Education Environment Measure" (PHEEM) and "Ambulatory Care Learning Educational Environment" (ACLEEM), and open questions were answered online by 1259 residents from 15 universities. A descriptive and analytical statistical analysis and semantic deductive-inductive analyses of open questions were performed., Results: LE was positive rather than negative (PHEEM of 100.5 points (79-116) and ACLEEM of 138.5 points (120-157)). An age over 32 years, male sex, studying in a private university, being in first year of residence and being in a non-surgical specialty were associated with a better PHEEM score (p < 0.05). For ACLEEM, the first year of specialty, a non-surgical specialty and studying in a private university were associated with better scores (p < 0.05). Two programs had excellent LE (Pathological Anatomy and Ophthalmology) and no specialty had a very poor performance or many problems. Aspects of teaching, clinical activities, and teachers were strengths reported by students. Aspects to improve were teaching, protected times and clinical activities., Conclusions: LE among medical specialties had more positive than negative features, but with areas that should be improved.