Exploring variations in glycolytic and gluconeogenic enzymes and isoforms across breast cancer cell lines and tissues.

It is well established that tumour cells undergo metabolic changes to acquire biological advantage over normal cells with activation of the glycolytic pathway, a process termed "Warburg effect". Enzyme isoforms are alternative enzymatic forms with the same function but with different biochemical or epigenetic features. Moreover, isoforms may have varying impacts on different metabolic pathways. We challenge ourselves to analyse the glycolytic and gluconeogenic enzymes and isoforms in breast cancer, a complex and heterogeneous pathology, associated with high incidence and mortality rates especially among women. We analysed epithelial and tumour cell lines by RT-PCR and compared values to a publicly available database for the expression profile of normal and tumour tissues (Gepia) of enzymes and enzymatic isoforms from glycolytic and gluconeogenic pathways. Additionally, GeneMANIA was used to evaluate interactions, pathways, and attributes of each glycolytic/gluconeogenic steps. The findings reveal that the enzymes and enzymatic isoforms expressed in cell culture were somewhat different from those in breast tissue. We propose that the tumor microenvironment plays a crucial role in the expression of glycolytic and gluconeogenic enzymes and isoforms in tumour cells. Nonetheless, they not only participate in glycolytic and gluconeogenic enzymatic activities but may also influence other pathways, such as the Pentose-Phosphate-Pathway, TCA cycle, as well as other carbohydrate, lipid, and amino acid metabolism.

Distinguishing health-related parameters between metabolically healthy and metabolically unhealthy obesity in women.

BACKGROUND: Obesity represents a global health crisis, yet a dichotomy is emerging with classification according to the metabolic state into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). This study aimed to identify distinctive systemic clinical/endocrinological parameters between MHO individuals, employing a comprehensive comparative analysis of 50 biomarkers. Our emphasis was on routine analytes, ensuring cost-effectiveness for widespread use in diagnosing metabolic health. SUBJECTS/METHODS: The study included 182 women diagnosed with obesity referred for bariatric surgery at the Endocrinology, Diabetes, and Metabolism Service of São João Hospital and University Centre in Portugal. MUO was defined by the presence of at least one of the following metabolic disorders: diabetes, hypertension, or dyslipidemia. Patients were stratified based on the diagnosis of these pathologies. RESULTS: Significantly divergent health-related parameters were observed between MHO and MUO patients. Notable differences included: albumin (40.1 ± 2.2 vs 40,98 ± 2.6 g/L, p value = 0.017), triglycerides (110.7 ± 51.1 vs 137.57 ± 82.6 mg/dL, p value = 0.008), glucose (99.49 ± 13.0 vs 119.17 ± 38.9 mg/dL, p value < 0.001), glycated hemoglobin (5.58 ± 0.4 vs 6.15 ± 1.0%, p value < 0.001), urea (31.40 ± 10.0 vs 34.61 ± 10.2 mg/dL, p value = 0.014), total calcium (4.64 ± 0.15 vs 4.74 ± 0.17 mEq/L, 1 mEq/L = 1 mg/L, p value < 0.001), ferritin (100.04 ± 129.1 vs 128.55 ± 102.1 ng/mL, p value = 0.005), chloride (104.68 ± 1.5 vs 103.04 ± 2.6 mEq/L, p value < 0.001), prolactin (13.57 ± 6.3 vs 12.47 ± 7.1 ng/mL, p value = 0.041), insulin (20.36 ± 24.4 vs 23.87 ± 19.6 µU/mL, p value = 0.021), c peptide (3.78 ± 1.8 vs 4.28 ± 1.7 ng/mL, p value = 0.003), albumin/creatinine ratio (15.41 ± 31.0 vs 48.12 ± 158.7 mg/g creatinine, p value = 0.015), and whole-body mineral density (1.27 ± 0.1 vs 1.23 ± 0.1 g/cm2, p value = 0.016). CONCLUSIONS: Our findings highlight potential additional parameters that should be taken into consideration alongside the commonly used biomarkers for classifying metabolic health in women. These include albumin, urea, total calcium, ferritin, chloride, prolactin, c-peptide, albumin-creatinine ratio, and whole-body mineral density. Moreover, our results also suggest that MHO may represent a transitional phase preceding the development of the MUO phenotype.

Compliance and initiative: A discussion on the relationship between standards and activities in radiopharmaceutical production.

This study investigated how a standard could become reality-based in a workplace where certain types of deviations are not permitted, such as a radiopharmaceutical production unit. Compliance with standards is necessary to ensure the safety of individuals who manufacture such substances as well as the security of patients receiving treatment. In this qualitative case study, an ergonomic analysis of work (also known as activity analysis) was performed, with noncompliance recorded in internal audits as a starting point: the lack of double-checking in radiopharmaceutical synthesis cassette assembly. Field observations and self-confrontation interviews with workers from a production unit were conducted to analyze the activities. Although a double-check did not occur, the radiopharmaceutical synthesis operator apparently developed another risk control strategy, focusing his attention to the equipment assembly details, which necessitated continuous control and verification actions to ensure that there were no problems at this stage of production. A multilevel approach was used to demonstrate how the safety and quality of production processes based on standard compliance only become effective and adherent to the activity after resolving various conflicts at work, including control systems (external and internal audits), work collectives, the contradiction of the activity itself, and the discussion of singular situations arising daily. This study contributes to the discussion on workplace safety considering standardization and advances the discussion on changing perspectives regarding rule compliance.

Implementação da Prática Avançada de Enfermagem no enfrentamento do atraso vacinal: um relato de experiência / Implementation of Advanced Practice Nursing in coping with vaccine delay: an experience report

OBJETIVO: Descrever a implementação de práticas avançadas de enfermagem para abordar o atraso na imunização em crianças menores de dois anos de idade. MÉTODO: Trata-se de um relato de experiência que monitorou a situação vacinal de crianças menores de dois anos e descreveu práticas avançadas de enfermagem para melhorar a adesão à vacinação. RESULTADOS: Foi monitorado o estado vacinal das crianças e realizadas ações e intervenções individuais e coletivas, como consultas individuais, buscas ativas, ligações telefônicas e mensagens via aplicativo de celular, educação continuada e produção de materiais educativos para conscientização entre a comunidade, pais/responsáveis e profissionais de saúde sobre a importância de manter o calendário vacinal atualizado, conforme proposto pelo Programa Nacional de Imunizações. CONCLUSÃO: As intervenções neste relatório demonstraram implicações importantes para a saúde pública e podem sugerir que as práticas avançadas de enfermagem têm um impacto positivo na melhoria da cobertura vacinal.

OBJECTIVE: To describe the implementation of advanced practice nursing to address delayed immunization in children under two years of age. METHOD: This experience report monitored the immunization status of children under two years of age and described advanced practice nursing to improve immunization compliance. RESULTS: The immunization status of children was monitored, and individual and collective actions and interventions were carried out, such as individual consultations, active searches, telephone calls and messages via a mobile phone application, ongoing education, and the production of educational materials to raise awareness among the community, parents/guardians and health professionals about the importance of keeping the immunization schedule up to date, as proposed by the Brazilian National Immunization Program. CONCLUSION: The interventions in this report have demonstrated important public health implications and may suggest that advanced nursing practices positively impact improving immunization coverage.

Bilateral breast cancer and the influence of body mass index in clinicopathological features and overall survival.

BACKGROUND: Breast cancer (BC) and obesity are two closely associated pathologies with increasing incidence and mortality rates. Bilateral Breast Cancer (BBC) displays a low incidence rate within BC and obesity represents a major risk factor. OBJECTIVE: The aim of this study is to analyzed BBC clinicopathological features distribution and determine the potential influence of obesity in BBC in these same features and overall survival. METHODS: Clinicopathological information was obtained from 42 cases of women with BBC diagnosed in IPO-Porto. To evaluate the frequency distribution of the clinicopathological data, a chi-square goodness of fit test was performed for BBC cases. A chi-square test of independence was applied for BMI stratification. Cox regression was performed for overall survival. Statistical significance was set at p-value < 0.05. RESULTS: Distribution of BBC clinicopathological features was found to be statistically significant in family history (p-value < 0.001), BBC type (p-value < 0.001), stage (p-value = 0.005), differentiation grade (p-value < 0.001), receptor expression (p-value < 0.001) and histological type (p-value = 0.031). In comparison to the statistical expected results, we observed an increased cases of absence of family history and less cases of metachronous BBC. Histological types between tumours of BBC were mostly concordant. All cases presented concordant receptor expression. Analysis stratified by BMI revealed that obese women were diagnosed later, although without statistical significance. All obese women presented poor differentiation grade (n = 6). Overweight patients display a tendency to a better overall survival with lower tumour stages and lower differentiation grades. CONCLUSIONS: Our results reveal the same receptor expression between contralateral tumours. Also, most tumours share the same histological type. When stratified by BMI, we observed a tendency for overweight women to have improved overall survival.

Long-Term Outcomes of Ultrasound-Guided Hydrodistension for Adhesive Capsulitis: A Prospective Observational Study.

Ultrasound-guided hydrodistention has been established as an effective minimally invasive treatment option for glenohumeral joint adhesive capsulitis (AC). Nonetheless, the long-term outcomes of the procedure have not yet been established. A total of 202 patients with AC were prospectively recruited and followed up for a total of 2 years. Pain and functionality were assessed with the use of the visual analogue scale (VAS) and the disabilities of the arm, shoulder, and hand (DASH) score, respectively, at the beginning and the end of the follow-up period. The relapse of AC over the 2-year period and the effect of diabetes were also evaluated in the treatment cohort. The Mann-Whitney U test was used to compare mean scores at the two time points, and Cox survival analysis and χ2 test were used to assess the effect of diabetes on AC relapse. VAS and DASH scores were significantly lower at 2 years compared with the beginning of the follow-up period (p < 0.001). Diabetes was diagnosed in 38/202 patients (18.8%) and was found to be significantly associated with recurrence of the disease (p < 0.001). In conclusion, in this observational study, we have demonstrated that ultrasound-guided hydrodistention is linked to excellent long-term outcomes for the treatment of AC, which are significantly worse in patients with diabetes.

Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes-Obesity as a Crucial Player.

Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine.

Does body mass index influence surgical options and overall survival in breast cancer patients?

Obesity is a relevant risk factor in breast cancer (BC), but little is known about the effects of overweight and obesity in surgical outcomes of BC patients. The aim of this study is to analyse surgical options and associated overall survival (OS) in overweight and obese women with BC. In this study, 2143 women diagnosed between 2012 and 2016 at the Portuguese Oncology Institute of Porto (IPO-Porto) were included, and the clinicopathological information was retrieved from the institutional database. Patients were stratified by body mass index (BMI). Statistical analysis included Pearson's chi-squared test with statistical significance set at p < 0.05. Multinomial, binary logistic regression and cox proportional-hazards model were also performed to calculate odd ratios and hazard ratios with 95% confidence intervals for adjusted and non-adjusted models. The results revealed no statistical difference in histological type, topographic localization, tumour stage and receptor status and in the number of surgical interventions. Overweight women have increased probability to be subjected to sentinel node biopsy. Obese and overweight women are more likely to be submitted to conservative surgery and contrariwise, less likely to undergo total mastectomy. Patients submitted to conservative surgery and not submitted to total mastectomy had a favourable OS although without statistical significance. No significant differences were observed in OS when stratified by BMI. Our results revealed significant variations regarding the surgical options in overweight and obese patients, but these were not translated in OS difference. More research is recommended to better address treatment options in overweight and obese BC patients (AU)

The Influence of Adipocyte Secretome on Selected Metabolic Fingerprints of Breast Cancer Cell Lines Representing the Four Major Breast Cancer Subtypes.

Molecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.

Evaluation of the Removal and Effects of Cylindrospermopsin on Ripened Slow Sand Filters.

The occurrence of toxic blooms of cyanobacteria has been a matter of public health interest due to the cyanotoxins produced by these microorganisms. Cylindrospermopsin (CYN) is a cyanotoxin of particular concern due to its toxic effects on humans. This study investigated the removal and effects of CYN in ripened slow sand filters (SSFs) treating water from Paranoá Lake, Brasilia, Brazil. Four pilot-scale SSFs were ripened and operated for 74 days. Two contamination peaks with CYN were applied along the filtration run. The improvement of any of the evaluated water quality parameters was not affected by the presence of CYN in the raw water. The SSFs efficiently removed CYN, presenting concentrations lower than 0.8 µg/L in the filtered water. The microbiota of the SSFs were dominated by protozoa of the genus Euglypha and amoebas of the genera Arcella, Centropyxis, and Amoeba, together with some groups of rotifers. These microorganisms played a crucial role in removing total coliforms and E. coli. In addition, CYN was not identified as a determining factor in the microbiota composition.

Left ventricle endomyocardial fibrosis: a case report.

BACKGROUND: Endomyocardial fibrosis is a grim disease. It is the most common restrictive cardiomyopathy worldwide, but the exact etiology and pathogenesis both remain unknown. Endomyocardial fibrosis is recurrently associated with chronic eosinophilia and probable dietary, environmental, and infectious factors, which contribute not only to the onset of the disease (an inflammatory process) but also to its progression and maintenance (endomyocardial damage and scar formation). The trademark of the disease is the fibrotic obliteration of the affected ventricle. The combination of such processes produces focal or diffuse endocardial thickening and fibrosis, which leads to restrictive physiology. Endomyocardial fibrosis affects the apices of the right and the left ventricle in around 50% of cases and most often extends to the posterior leaflet of the mitral valve. Sometimes it involves the papillary muscle and chordae tendineae, causing atrioventricular valve dysfunction. The fibrosis does not affect extracardiac organs. This cardiomyopathy is most recurrent in tropical areas of the world. CASE PRESENTATION: A 67-year-old Black male with past medical history of schistosomiasis infection in childhood presented with progressive dyspnea, lower extremity edema, and weakness for 2 years. He was diagnosed with endomyocardial fibrosis. The echocardiogram showed an increased thickness in the septum (17 mm) and free left ventricular wall (15 mm), obliteration of the left ventricular apex and inflow tract, and mitral valve regurgitation. Cardiac magnetic resonance imaging revealed apical left ventricle wall thickening with left ventricular apical obliteration associated with enlargement of the respective atrium. Delayed enhancement imaging showed endomyocardium enhancement involving left ventricular apex, mitral valve regurgitation due to annulus dilation, and a thrombus at left ventricular apex. He underwent open heart surgery with mitral valve replacement, endocardial decortication, endomyocardiectomy, and two-vessel coronary artery bypass grafting as preoperative coronary angiogram showed mild right coronary artery and proximal left anterior descending artery severe lesions. Postoperative course was uncomplicated, and he was discharged successfully from the hospital. Six months after surgery, he was New York Heart Association functional class I. CONCLUSION: The purpose of this case report is to illustrate the aspects of endomyocardial fibrosis by reporting a case of this entity. In conclusion, progress in imaging techniques and treatment in a reference institution for cardiac diseases contribute to earlier diagnosis and survival in patients with endomyocardial fibrosis.

Serum inflammatory biomarkers are associated with increased choroidal thickness in keratoconus.

Inflammation may play a significant role in Keratoconus (KC), but the relationship between inflammatory markers and choroidal thickness (CT) is unknown. The purpose of this study was to evaluate serum inflammatory markers and correlate them with the choroidal profile of KC patients and control subjects. Forty patients with KC and 26 age-matched control subjects were enrolled in a cross-sectional case-control study. Choroidal profile was studied with a Spectralis Heidelberg apparatus and venous blood samples were collected. Neutrophil/lymphocyte ratio (NLR), monocyte/HDL ratio (MHR), platelet/lymphocyte ratio (PLR) and systemic immune inflammation index (SII) were calculated. Serum inflammatory biomarkers IL-1, IL-6 and TNF-alfa were also analyzed. KC group presented thicker choroids in each evaluated point when compared to the control group (subfoveal CT 417.38 ± 79.79 vs 299.61 ± 76.13, p < 0.001 for all measured locations). Mean values of NLR, PLR and SII were significantly higher in patients with KC (NLR p = 0.001; PLR p = 0.042; SII p = 0.007). Although KC patients presented higher mean levels of MHR, IL-1, IL-6 and TNF-α than control group, no significant differences were achieved. Positive correlations were found between subfoveal CT and NLR and SII (0.408, p = 0.001 and 0.288, p = 0.019 respectively). The results presented are in favor of a relationship between the increased CT and inflammatory mechanisms in KC patients. The elevated serum inflammatory indices NLR, SII and PLR provide additional evidence of a role for systemic inflammation in the pathophysiology of KC.

Faecalibacterium prausnitzii in Differentiated Thyroid Cancer Patients Treated with Radioiodine.

BACKGROUND: Faecalibacterium prausnitzii, one of the most important bacteria of the human gut microbiota, produces butyrate (a short-chain fatty acid). Short-chain fatty acids are known to influence thyroid physiology and thyroid cancer's response to treatment. We aimed to analyze the relative abundance of Faecalibacterium prausnitzii on the gut microbiota of differentiated thyroid cancer patients compared to controls and its variation after radioiodine therapy (RAIT). METHODS: Fecal samples were collected from 37 patients diagnosed with differentiated thyroid cancer before and after radioiodine therapy and from 10 volunteers. The abundance of F. prausnitzii was determined using shotgun metagenomics. RESULTS: Our study found that the relative abundance of F. prausnitzii is significantly reduced in thyroid cancer patients compared to volunteers. We also found that there was a mixed response to RAIT, with an increase in the relative and absolute abundances of this bacterium in most patients. CONCLUSIONS: Our study confirms that thyroid cancer patients present a dysbiotic gut microbiota, with a reduction in F. prausnitzii's relative abundance. In our study, radioiodine did not negatively affect F. prausnitzii, quite the opposite, suggesting that this bacterium might play a role in resolving radiation aggression issues.

The Effects of Ionizing Radiation on Gut Microbiota: What Can Animal Models Tell Us?-A Systematic Review.

BACKGROUND: The gut microbiota is relatively stable; however, various factors can precipitate an imbalance that is known to be associated with various diseases. We aimed to conduct a systematic literature review of studies reporting the effects of ionizing radiation on the composition, richness, and diversity of the gut microbiota of animals. METHODS: A systematic literature search was performed in PubMed, EMBASE, and Cochrane library databases. The standard methodologies expected by Cochrane were utilized. RESULTS: We identified 3531 non-duplicated records and selected twenty-nine studies after considering the defined inclusion criteria. The studies were found to be heterogeneous, with significant differences in the chosen populations, methodologies, and outcomes. Overall, we found evidence of an association between ionizing radiation exposure and dysbiosis, with a reduction of microbiota diversity and richness and alterations in the taxonomic composition. Although differences in taxonomic composition varied across studies, Proteobacteria, Verrucomicrobia, Alistipes, and Akkermancia most consistently reported to be relatively more abundant after ionizing radiation exposure, whereas Bacteroidetes, Firmicutes, and Lactobacillus were relatively reduced. CONCLUSIONS: This review highlights the effect of ionizing exposure on gut microbiota diversity, richness, and composition. It paves the way for further studies on human subjects regarding gastrointestinal side effects in patients submitted to treatments with ionizing radiation and the development of potential preventive, therapeutic approaches.

In vitro manipulation of the bacterial community to improve the performance of bioflocs in aquaculture systems.

Although biofloc technology is already recognized as advantageous and practical for aquaculture for the effects of maintaining water quality and improving the health status and resistance of cultivated animals against pathogens, little is known about the way of action involved. This study aimed to evaluate the performance of bacterial groups as inducers in the formation of flocs compared to a system with spontaneous formation. Therefore, three microsystems were built in 3L tanks with constant aeration to induce the biofloc aggregation with addition of bacterial consortiuns with differentiated functions. It was used a control, without addition of bacterial consortium; B1 with addition of probiotic bacteria consortium; and B2, with adding nitrifying bacteria consortium. During the experimental period were evaluated physicochemical variables and quantifications of bacterial cultivable groups: Heterotrophic Bacteria and Vibrio. Also was the microscopic characterization of the flakes and tests of antimicrobial activity against pathogenic bacteria. Systems B1 and B2 showed promising results in relation to control (spontaneous bioflocs), showing more homogeneous flake formation, antimicrobial activity against the tested pathogens and greater biological diversity in the systems. The bacteria used in these tests were able to optimize the formation of microbial aggregates, showing potential for application in cultivation systems, in order to obtain improvements in productivity.

The use of innovative targeted angiogenic therapies for ischemic diabetic foot ulcer repair: From nanomedicine and microRNAs toward hyperbaric oxygen therapy.

Diabetes mellitus is a metabolic disease that has a high prevalence worldwide and is characterized by chronic hyperglycemia leading to the development of vascular or nonvascular complications. It is these complications that result in huge mortality rates in patients with diabetes, especially vascular ones. This work focuses on diabetic foot ulcers (DFUs), which are one of the most common complications of type 2 diabetes mellitus (T2DM) and cause significant morbidity, mortality, and healthcare costs. The healing of DFUs is hindered by deregulation of nearly all phases of this process because of the hyperglycemic environment. Although therapies currently exist to treat a patient with DFU, they are proving inadequate. In the present work, angiogenesis is highlighted as part of the proliferative phase, which, when diminished, plays an important role in the impaired healing of DFU and other chronic wounds. Therefore, the search for new therapeutic strategies targeting angiogenesis is of great interest. In this study, we provide an overview of molecular targets with therapeutic potential and therapies that act on angiogenesis. To this end, a search of articles in PubMed and Scopus databases from 2018 to 2021 was performed to review angiogenesis as a therapeutic target for DFU. Growth factors, microRNAs, and signaling pathways were investigated as molecular targets, and negative pressure, hyperbaric oxygen therapy, and the use of nanomedicine were explored as therapies.

Does body mass index influence surgical options and overall survival in breast cancer patients?

Obesity is a relevant risk factor in breast cancer (BC), but little is known about the effects of overweight and obesity in surgical outcomes of BC patients. The aim of this study is to analyse surgical options and associated overall survival (OS) in overweight and obese women with BC. In this study, 2143 women diagnosed between 2012 and 2016 at the Portuguese Oncology Institute of Porto (IPO-Porto) were included, and the clinicopathological information was retrieved from the institutional database. Patients were stratified by body mass index (BMI). Statistical analysis included Pearson's chi-squared test with statistical significance set at p < 0.05. Multinomial, binary logistic regression and cox proportional-hazards model were also performed to calculate odd ratios and hazard ratios with 95% confidence intervals for adjusted and non-adjusted models. The results revealed no statistical difference in histological type, topographic localization, tumour stage and receptor status and in the number of surgical interventions. Overweight women have increased probability to be subjected to sentinel node biopsy. Obese and overweight women are more likely to be submitted to conservative surgery and contrariwise, less likely to undergo total mastectomy. Patients submitted to conservative surgery and not submitted to total mastectomy had a favourable OS although without statistical significance. No significant differences were observed in OS when stratified by BMI. Our results revealed significant variations regarding the surgical options in overweight and obese patients, but these were not translated in OS difference. More research is recommended to better address treatment options in overweight and obese BC patients.

Increased Galactosidase Beta 1 Expression as a Senescent Key Factor in ß-Cells Function Modulation at the Early Steps of Type 2 Diabetes.

BACKGROUND: In type 2 diabetes, insulin resistance is observed, and ß-cells are incapable of responding to glycemia demands, leading to hyperglycemia. Although the nature of ß-cells dysfunction in this disease is not fully understood, a link between the induction of pancreatic ß-cell premature senescence and its metabolic implications has been proposed. This study aimed to understand the relationship between diabetes and pancreatic senescence, particularly at the beginning of the disease. METHODS: C57Bl/6 J mice were fed two different diets, a normal diet and a high-fat diet, for 16 weeks. Pancreatic histomorphology analysis, insulin quantification, inflammation parameters, and senescence biomarkers for the experimental animals were assessed at weeks 12 and 16. RESULTS: The results proved that diabetes onset occurred at week 16 in the High Fat Diet group, supported by glycaemia, weight and blood lipid levels. Increased ß-cells size and number accompanied by increased insulin expression were observed. Also, an inflammatory status of the diabetic group was noted by increased levels of systemic IL-1ß and increased pancreatic fibrosis. Finally, the expression of galactosidase-beta 1 (GLB1) was significantly increased in pancreatic ß-cells. CONCLUSION: The study findings indicate that senescence, as revealed by an increase in GLB1 expression, is a key factor in the initial stage of diabetes.

The Impact of Flavonoid-Loaded Nanoparticles in the UV Protection and Safety Profile of Topical Sunscreens.

Excessive UV radiation exposure is harmful to skin cells since sunburn is accompanied by oxidative burst, leading to a rapid increase in skin cancer. However, the insufficient UV photoprotection of approved sunscreens and the negative impact of their compositions on ecosystems and human health makes the utility of sunscreen a questionable recommendation. Therefore, discovering UV filters with significant antioxidant activity and improved topical performance and photostability is an urgent need. Recently, the use of nanosized natural molecules incorporated in sunscreens has been a scientific hot topic, as it has been suggested that they provide a synergistic effect with synthetic UV filters, improving overall SPF and antioxidant activity, higher retention on the epidermis, and less toxicity. The aim of this review was to verify the usefulness of sunscreens incorporating flavonoid-loaded nanoparticles. A literature review was performed, where original and review articles published in the last 6 years were analyzed. Formulations containing nanosized flavonoids with improved UVA photoprotection and safer toxicological profiles, associated or not with synthetic filters, are promising sunscreens and more clinical investigation must be performed to validate these findings.