Maternal perception of factors that interfere with breastfeeding of preterm newborns. / Percepção materna sobre os fatores que interferem na amamentação de prematuros.

PURPOSE: to verify the association between the perception of mothers of premature infants regarding the features that may interfere with breastfeeding and the mother's socioeconomic data, pregnancy and the baby's clinical data. METHODS: observational, descriptive and analytical quali-quantitative cross-sectional study. One hundred and fourteen mothers of premature infants were included and data were collected through questionnaires, applied at hospital discharge, and analysis of medical records. Maternal responses about the interference observed in the breastfeeding process were categorized by content analysis and associated with socioeconomic, pregnancy and baby data. RESULTS: the mothers' perceptions regarding the factors that interfere with the baby's feeding at the mother's breast were divided into four semantic categories: clinical and/or physical conditions of the baby; clinical, physical and/or psycho-emotional conditions of the mother; support network; and strategies for initiating and/or maintaining breastfeeding. Education, paternal presence, having other children and having breastfed them were associated with the maternal perception that their clinical, physical and/or psycho-emotional conditions interfere with breastfeeding. In addition, the support network was associated with exclusive breastfeeding at discharge. CONCLUSION: education, paternal presence, multiparity and having breastfed previous children influenced the maternal perception that their clinical, physical and/or psycho-emotional conditions interfere with breastfeeding. In addition, mention of the support network was associated with exclusive breastfeeding at discharge.

OBJETIVO: verificar a associação entre a percepção das mães de prematuros a respeito dos fatores que podem interferir no aleitamento e as características socioeconômicas da mãe, da gestação e clínicas do recém-nascido. MÉTODO: estudo qualiquantitativo observacional, descritivo e analítico do tipo transversal. Foram incluídas 114 mães de prematuros. Os dados foram coletados por meio de questionários, aplicados à alta hospitalar e análise dos prontuários. As respostas maternas sobre as interferências observadas no processo do aleitamento foram categorizadas por análise de conteúdo e associadas aos dados socioeconômicos, da gestação e do recém-nascido (RN). RESULTADOS: as percepções das mães quanto aos fatores que interferem na alimentação do RN ao seio materno foram divididas em quatro categorias semânticas: condições clínicas e/ou físicas do RN; condições clínicas, físicas e/ou psicoemocionais da mãe; rede de apoio; e estratégias para iniciar e/ou manter o aleitamento materno. Escolaridade, presença paterna, possuir outros filhos e tê-los amamentado apresentaram associação com a percepção materna de que suas condições clínicas, físicas e ou psicoemocionais interferem no aleitamento. Além disso, a rede de apoio esteve associada ao aleitamento materno exclusivo à alta. CONCLUSÃO: escolaridade, presença paterna, multiparidade e ter amamentado filhos anteriores influenciaram a percepção materna de que suas condições clínicas, físicas e ou psicoemocionais apresentam interferência no aleitamento. Além disso, a menção à rede de apoio esteve associada com o aleitamento materno exclusivo à alta.

Association between positive serology for COVID-19 and chagas cardiomyopathy progression: The SaMi-Trop project.

BACKGROUND: Chagas Disease (CD) can cause Chagas cardiomyopathy. The new coronavirus disease (COVID-19) also affects the cardiovascular system and may worsen Chagas cardiomyopathy. However, the cardiac evolution of patients with CD infected by COVID-19 is not known. Thus, the objective of this study is to assess, within one year, whether there was cardiac progression after COVID-19 in CD. METHODS: Longitudinal study with CD patients. The outcome was cardiac progression, defined as the appearance of new major changes in the current ECG compared to the previous ECG considered from the comparison of electrocardiograms (ECGs) performed with an interval of one year. Positive Anti-SARS-CoV2 Serology was the independent variable of interest. For each analysis, a final multiple model was constructed, adjusted for sociodemographic, clinical, and pandemic-related characteristics. RESULTS: Of the 404 individuals included, 22.8 % had positive serology for COVID-19 and 10.9 % had cardiac progression. In the final model, positive serology for COVID-19 was the only factor associated with cardiac progression in the group as a whole (OR = 2.65; 95 % CI = 1.27-5.53) and for new-onset cardiomyopathy in the group with normal previous ECG (OR = 3.50; 95 % CI = 1.21-10.13). CONCLUSION: Our study shows an association between COVID-19 and progression of Chagas cardiomyopathy, evaluated by repeated ECGs, suggesting that COVID-19 accelerated the natural history of CD.

ASSOCIATION BETWEEN ANXIETY AND DEPRESSION IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD).

BACKGROUND: This study aimed to assess the frequency and intensity of anxious and depressive symptoms in patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This is a descriptive and cross-sectional study, resulting from 106 patients from the Hepatology outpatient clinic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil without a history of alcohol abuse, verified by the alcohol use disorders identification test (AUDIT). These were assessed using the sociodemographic data sheet, Hospital Anxiety and Depression Scale (HADS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Scale (HAM-D). RESULTS: A total of 69.8% were women and 30.2% were men, with a mean age of 61 years. The majority (71.7%) discovered MASLD through routine exams, presenting as comorbidities: Type 2 diabetes mellitus (59.4%), Dyslipidemia (49.1%), Arterial hypertension (68.9%), Obesity (61.3%) and Metabolic syndrome [MetS (63.2%)]. The HADS scale indicates 34% probability of anxiety and 33% depressive symptoms. The Hamilton's scales of intensity indicates 63.9% severe anxiety and 54.3% severe depression. There is also a relationship between anxiety, depression and the female gender, as well as between depression and MetS. CONCLUSION: The findings point to the presence of anxiety and depression in more than one third of MASLD patients, most with severe symptoms. The group is concentrated in the elderly, with many comorbidities, including MetS. There was a positive correlation between anxiety, depression and being female; also, being significant between MetS and depression.

Cendakimab in Patients With Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine implicated in atopic dermatitis (AD) pathogenesis, by inhibiting binding to its receptors (IL13R-α1 and IL13R-α2). Proof-of-concept work in AD supports using cendakimab for type 2 inflammatory diseases. Objective: To evaluate the efficacy and safety of cendakimab compared with placebo in patients with moderate to severe AD. Design, Setting, and Participants: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial was conducted from May 2021 to November 2022. Adult patients with moderate to severe AD and inadequate response to topical medications were enrolled at 69 sites in 5 countries (US [n = 26], Japan [n = 17], Canada [n = 9], Poland [n = 9], and Czech Republic [n = 8]). Data were analyzed between April 25, 2023, and October 16, 2023. Interventions: Patients were randomized (1:1:1:1) to receive subcutaneous cendakimab, 360 mg, every 2 weeks; 720 mg, every 2 weeks; 720 mg, once weekly; or placebo. Main Outcome and Measure: Mean percentage change in Eczema Area and Severity Index scores from baseline to week 16. Hierarchical testing with multiplicity adjustment was performed for 720 mg, once weekly vs placebo, then 720 mg, every 2 weeks vs placebo, and then 360 mg, every 2 weeks vs placebo. Results: Overall, 221 patients were randomized, and 220 received study drug (95 women [43%]; mean [SD] age, 37.7 [13.9] years; 720 mg, once weekly [54 (24%)]; 720 mg, every 2 weeks [55 (25%)]; 360 mg, every 2 weeks [55 (25%)]; placebo [56 (26%)]). The primary efficacy end point was met for cendakimab, 720 mg, once weekly vs placebo (-84.4 vs -62.7; P = .003) but missed statistical significance for 720 mg, every 2 weeks (-76.0 vs -62.7; P = .06). The treatment effect for 360 mg, every 2 weeks (-16.3; nominal P = .03 vs placebo) was comparable with 720 mg, once weekly (-21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted. Of patients with treatment-emergent adverse events leading to discontinuation, 4 (7.4%) received 720 mg, once weekly; 2 (3.6%) 720 mg, every 2 weeks; 1 (1.8%) 360 mg, every 2 weeks; and 2 (3.6%) placebo. Conclusions and Relevance: The results of this randomized clinical trial indicated that cendakimab was effective, generally safe, and well-tolerated in patients with moderate to severe AD. The primary end point was met with a significant reduction in Eczema Area and Severity Index scores with 720 mg, once weekly at week 16. Cendakimab demonstrated progressive AD improvement at all doses during 16 weeks of treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04800315.

Discordance Between the Initial Diagnosis of Sarcomas and Subsequent Histopathological Revision and Molecular Analyses in a Sarcoma Reference Center in Brazil.

PURPOSE: To investigate the discordance in sarcoma diagnoses between nonspecialized institutions following revision by dedicated sarcoma pathologists at a reference center in Brazil and the relevance of molecular pathology in this context. METHODS: We conducted a retrospective analysis of sarcoma samples initially analyzed at outside laboratories and subsequently reviewed by two specialized pathologists between January 2014 and December 2020. After obtaining demographic and tumor characteristics, pathology results were matched and classified as complete discordance (CD; benign v malignant, sarcoma v other malignancies), partial concordance (similar diagnosis of connective tumor, but different grade/histological subtype/differentiation), and complete concordance (CC). The concordance for histology or grade, and the role of molecular assessments supporting the diagnosis were also independently determined. Statistical analyses were conducted through the kappa coefficient of agreement and adherence by χ2 test, χ2 test by Person, and Fisher exact test. RESULTS: In total, 197 cases were included, with samples obtained predominately from male patients (57.9%) and localized/primary tumors (86.8%). Following revision, the most frequent final diagnoses were undifferentiated pleomorphic sarcoma (17.8%), well-differentiated/dedifferentiated liposarcoma (8.6%), and leiomyosarcoma (7.6%). CD was found in 13.2%, partial discordance in 45.2%, and CC in 41.6% of reviews (P < .001). We found a concordance for histology or grade of 53.5% (P < .001) and 51.8% (P < .001), respectively. Molecular assessments, comprising next-generation sequencing panels (79.5%) and fluorescent in situ hybridization (20.5%), were performed in 44 (22.3%) cases, with findings classified as of diagnostic relevance in 31.8%. CONCLUSION: In nearly 60% of the cases, the initial sarcoma diagnosis was modified when revised by a reference center and dedicated pathologists, assisted by molecular pathology techniques. These results justify the assembly of referral networks in countries with limited health care resources.

Effect of Detraining on Muscle Strength, Functional Capacity, Mental Health, and Body Composition in Individuals with Spinal Cord Injury.

Spinal cord injury (SCI) is a condition that significantly affects the quality of life (QoL) of individuals, causing motor, physiological, social, and psychological impairments. Physical exercise plays a crucial role in maintaining the health and functional capacity of these individuals, helping to minimize the negative impacts of SCI. The aim of this study was to evaluate the effect of detraining (DT) (reduction or cessation of physical exercise) during the pandemic on five individuals with thoracic SCI. We assessed muscle strength using strength tests, functional capacity using a functional agility test, mental health using anxiety and depression inventories, and body composition using dual-energy X-ray absorptiometry (DEXA). The results after 33 months of DT showed significant losses in functional agility and MS, as well as a worsening in symptoms of anxiety and depression. It was observed that total body mass and fat mass (FM) exhibited varied behaviors among the individuals. Similarly, the results for lean body mass were heterogeneous, with one participant showing significant deterioration. It is concluded that DT caused by the pandemic worsened the physical and mental condition of individuals with SCI, highlighting the importance of continuous exercise for this population and underscoring the need for individual assessments to fully understand the impacts of DT.

Medication Adherence in Adults with Chronic Diseases in Primary Healthcare: A Quality Improvement Project.

(1) Background: Medication adherence is influenced by a variety of intricate factors, presenting hurdles for nurses working to improve it among adults with chronic conditions. Pinpointing the reasons for non-adherence is crucial for customizing interventions. The objective of this quality improvement project was to improve medication adherence among adults with chronic diseases in primary healthcare by promoting evidence-based practices, identifying barriers and facilitators to compliance, and developing strategies to ensure optimal adherence through engaging the nursing team, enhancing knowledge, and evaluating the effectiveness of the implemented strategies. (2) Methods: This study was a quality improvement project that utilized the JBI Evidence Implementation framework, the Practical Application of Clinical Evidence System, and the Getting Research into Practice audit tool across three phases: (i) forming a project team and conducting a baseline audit, (ii) offering feedback via the GRiP tool, and (iii) conducting a follow-up audit to assess best practice outcomes. The study was conducted between September 2021 and March 2022 in the community care unit of Algarve Regional Health Administration, targeting adults with chronic illnesses. (3) Results: A total of 148 individuals were audited, including 8 nurses, 70 baseline patients, and 70 post-implementation patients. Initial compliance with key best practices was low, with several criteria at 0% compliance at baseline. Post-intervention, we observed significant improvements; compliance with key best practices improved dramatically, with many reaching 100%. Notable improvements included enhanced patient education on medication management, regular medication adherence assessments, and increased engagement of healthcare professionals in adherence activities. (4) Conclusions: This quality improvement project demonstrated that structured, evidence-based interventions could significantly enhance medication adherence among adults with chronic diseases. The success of the project highlights the potential of similar strategies to be applied broadly in primary healthcare settings to improve health outcomes.

The impact of preservation solutions for static cold storage on kidney transplantation outcomes: Results of a Brazilian nationwide multicenter study.

This study evaluated the current practices of selecting cold storage preservation solutions in Brazil and their impact on delayed graft function (DGF) incidence and 1-year outcomes in kidney transplant recipients. A retrospective cohort study was conducted, including 3,134 brain-dead deceased donor kidney transplants performed between 2014 and 2015 in 18 Brazilian centers. The most commonly used preservation solution was Euro-collins (EC, 55.4%), followed by Histidine-tryptophan-ketoglutarate (HTK, 30%) and Institut Georges Lopez (IGL-1, 14.6%). The incidence of DGF was 54.4%, with 11.7% of patients requiring dialysis for more than 14 days, indicating prolonged DGF. Upon adjusting for confounding variables, HTK demonstrated a significantly lower risk of DGF than EC (OR 0.7350.82500.926), as did IGL-1 (OR 0.6050.7120.837). Similar protective effects were observed for prolonged DGF when comparing HTK (OR 0.4780.5990.749) and IGL-1 (OR 0.4780.6810.749) against EC. No significant association was found between preservation solutions and 1-year death-censored graft survival. In conclusion, EC was the most frequently used cold storage perfusion solution, demonstrating a higher incidence and duration of DGF compared with HTK and IGL-1, but with no impact on 1-year graft survival.

Strength training as a non-pharmacological alternative to improve body composition, and quality of life in people with spinal cord injury: A systematic review.

INTRODUCTION: Spinal cord injuries (SCI) have physiological, emotional, and economic consequences in the lives of affected people. Resistance training (RT) is efficient in improving several physiological factors, quality of life, and body composition. Due to the scarce literature on the analysis of isolated RT, the objective of this systematic review is to evaluate the effects of RT without the association of other techniques, in aspects related to the quality of life and body composition of people with SCI. EVIDENCE ACQUISITION: The research was carried out in databases such as Pubmed, Cochrane, and Web of Science using the terms ("Spinal cord injury") AND (("Resistance Training") OR ("Strength training")). Given the lack of evidence on the subject, no deadline was set for the study to be eligible for analysis. EVIDENCE SYNTHESIS: The search for the articles was carried out in November of 2023 and returned 470 results, of which 315 remained after the elimination of duplicates, with 281 being excluded after title analysis. A total of 34 abstracts were analyzed and 29 studies were excluded, leaving 5 complete articles for thorough analysis. CONCLUSIONS: After analyzing the main results, we concluded that RT promotes significant improvements in body composition, pain, stress and depression symptoms, increased functionality, physical awareness, and quality of life.

Effect of disease, freezing of gait, and dopaminergic medication in the biomechanics of trunk and upper limbs in the gait of Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) causes gait abnormalities that may be associated with an arm swing reduction. Medication and freezing of gait (FoG) may influence gait characteristics. However, these comparisons do not consider differences in gait speed and clinical characteristics in individuals with PD. OBJECTIVE: This study aims to analyze the effect of FoG and medication on the biomechanics of the trunk and upper limbs during gait in PD, controlling for gait speed and clinical differences between groups. METHODS: Twenty-two people with a clinical diagnosis of idiopathic PD in ON and OFF medication (11 FoG), and 35 healthy participants (control) were selected from two open data sets. All participants walked on the floor on a 10-m-long walkway. The joint and linear kinematic variables of gait were compared: (1) Freezers and nonfreezers in the ON condition and control; (2) Freezers and nonfreezers in the OFF condition and control; (3) Group (freezers and nonfreezers) and medication. RESULTS: The disease affects the upper limbs more strongly but not the trunk. The medication does not significantly influence the joint characteristics but rather the linear wrist displacement. The FoG does not affect trunk movement and partially influences the upper limbs. The interaction between medications and FoG suggests that the medication causes more substantial improvement in freezers than in nonfreezers. CONCLUSION: The study shows differences in the biomechanics of the upper limbs of people with PD, FoG, and the absence of medication. The future rehabilitation protocol should consider this aspect.

WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.

Mental health in Brazil in times of neoliberalism and pandemic: retrogression and resistance.

This study analyzes aspects of mental health in Brazil as an active political field involving a range of social segments and actors from opposing fields in a context of advancing neoliberalism and pandemic. The analysis begins in 2016, when fiscal austerity entered the national agenda, and proceeds through the pandemic until the present day, when both phenomena continue to prevail, even if the intensity of the pandemic is now reduced. In the ambit of mental health, the national policy based on the principles of the psychiatric reform has suffered severe setbacks. Nonetheless, despite state-sponsored efforts to discourage social control and public participation, important sectors of society are engaged in active resistance.

Fishing profile and commercial landings of shark and batoids in a global elasmobranchs conservation hotspot.

This paper describes the fishing profile and the temporal variation in the commercial landings of elasmobranchs in a global hotspot for their conservation and investigates the variables that influenced the landings. Census data on commercial catches were obtained between April 2008 and October 2010 from nine landing sites in Bragança (Pará, northern Brazil). Five vessel types, four fishing gears, and eight fishing techniques engaged with elasmobranch capture were identified. A total of 2,357 landings were recorded, with a total production of 354 t. The highest yields were recorded in 2009, with sharks being harvested mostly by small and medium-sized vessels, and batoids, by small vessels and canoes. Drifting nets and longlines played a prominent role in elasmobranch fisheries. The results show that the landings were influenced by days at sea, which is common in tropical fisheries. The elasmobranch data series is discontinuous as statistics are absent for most fishing sites albeit imperative for proper management, as well as relevant for decision-makers focusing on their conservation.

Noninvasive assessment of liver fibrosis can predict clinical outcomes at late follow-up after a sustained virological response in HCV patients?

OBJECTIVES: The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS: A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS: At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION: Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Effect of botulinum toxin type a combined with physical therapy on functional capacity in children with spastic cerebral palsy: a randomized controlled clinical trial.

OBJECTIVE: Investigate the effects of botulinum toxin type A (BoNT-A) combined with physical therapy on functional capacity in children with spastic cerebral palsy (CP). METHODS: Twenty-four children with spastic CP were treated with either BoNT-A and physical therapy or physical therapy alone. RESULTS: Significant differences (p < 0.05) were found after 30 days of treatment for the Berg Scale, Timed Up and Go (TUG) test, Ashworth Scale and Pediatric Evaluation of Disability Inventory (PEDI) and after three months for the Berg Scale, TUG test and PEDI. No significant differences (p > 0.05) were found in the control group. DISCUSSION: BoNT-A combined with physical therapy leads to significant improvements in spasticity and functionality in children with CP within a period of three months from the onset of treatment.

Exposure to Zika and chikungunya viruses impacts aspects of the vectorial capacity of Aedes aegypti and Culex quinquefasciatus.

Zika (ZIKV) and chikungunya (CHIKV) are arboviruses that cause infections in humans and can cause clinical complications, representing a worldwide public health problem. Aedes aegypti is the primary vector of these pathogens and Culex quinquefasciatus may be a potential ZIKV vector. This study aimed to evaluate fecundity, fertility, survival, longevity, and blood feeding activity in Ae. aegypti after exposure to ZIKV and CHIKV and, in Cx. quinquefasciatus exposed to ZIKV. Three colonies were evaluated: AeCamp (Ae. aegypti-field), RecL (Ae. aegypti-laboratory) and CqSLab (Cx. quinquefasciatus-laboratory). Seven to 10 days-old females from these colonies were exposed to artificial blood feeding with CHIKV or ZIKV. CHIKV caused reduction in fecundity and fertility in AeCamp and reduction in survival and fertility in RecL. ZIKV impacted survival in RecL, fertility in AeCamp and, fecundity and fertility in CqSLab. Both viruses had no effect on blood feeding activity. These results show that CHIKV produces a higher biological cost in Ae. aegypti, compared to ZIKV, and ZIKV differently alters the biological performance in colonies of Ae. aegypti and Cx. quinquefasciatus. These results provide a better understanding over the processes of virus-vector interaction and can shed light on the complexity of arbovirus transmission.

WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.

Enhancement of Acetate-Induced Apoptosis of Colorectal Cancer Cells by Cathepsin D Inhibition Depends on Oligomycin A-Sensitive Respiration.

Colorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest in its use for CRC prevention/therapy. We previously uncovered that acetate-induced mitochondrial-mediated apoptosis in CRC cells is significantly enhanced by the inhibition of the lysosomal protease cathepsin D (CatD), which indicates both mitochondria and the lysosome are involved in the regulation of acetate-induced apoptosis. Herein, we sought to determine whether mitochondrial function affects CatD apoptotic function. We found that enhancement of acetate-induced apoptosis by CatD inhibition depends on oligomycin A-sensitive respiration. Mechanistically, the potentiating effect is associated with an increase in cellular and mitochondrial superoxide anion accumulation and mitochondrial mass. Our results provide novel clues into the regulation of CatD function and the effect of tumor heterogeneity in the outcome of combined treatment using acetate and CatD inhibitors.

Drug-induced osteoporosis and mechanisms of bone tissue regeneration through trace elements.

Osteoporosis is associated with an imbalance in bone formation, with certain drugs used in disease treatment being implicated in its development. Supplementation with trace elements may contribute to bone regeneration, offering an alternative approach by enhancing bone mineral density (BMD) and thereby thwarting the onset of osteoporosis. This review aims to assess the mechanisms through which trace elements such as copper (Cu), iron (Fe), selenium (Se), manganese (Mn), and zinc (Zn) are linked to increased bone mass, thus mitigating the effects of pharmaceuticals. Our findings underscore that the use of drugs such as aromatase inhibitors (AIs), proton pump inhibitors (PPIs), antiretrovirals, glucocorticoids, opioids, or anticonvulsants can result in decreased BMD, a primary contributor to osteoporosis. Research indicates that essential elements like Cu, Fe, Se, Mn, and Zn, through various mechanisms, can bolster BMD and forestall the onset of the disease, owing to their protective effects. Consequently, our study recommends a minimum daily intake of these essential minerals for patients undergoing treatment with the aforementioned drugs, as the diverse mechanisms governing the effects of trace elements Cu, Fe, Mn, Se, and Zn facilitate bone remodeling.