Total Tumor Load to assist in the decision for additional axillary surgery in the positive sentinel node breast cancer patients

The Total Tumor Load (TTL) concept has been demonstrated to accurately predict the status of the non-sentinel lymph nodes (NSLN) in breast cancer patients. In 2019, our center implemented the TTL cut-off of 30,000 CK19 mRNA copies/μL as sole criterion for deciding on performing ALND. This retrospective, unicentric, study analyzed 87 cT1-3N0 breast cancer patients treated consecutively in a period of two years and aimed to evaluate the performance of this criterion. Secondary objectives included the comparison of the criterion versus our previous Clinical Decision Rule (CDR) versus ACOSOG Z0011 criteria for avoiding an ALND in proportion of patients spared an ALND and in proportion of patients left with a surgically untreated metastasized axilla. An interim analysis revealed new TTL cut-offs for deciding on performing an ALND. The 30,000 CK19 mRNA copies/μL criterion yielded an area under the ROC Curve (AUC) of 0.849, a false positive (FP) rate of 30.1% and a positive predictive value (PPV) of 38.9%. The 30,000 CK19 mRNA copies/μL criterion spared 58.6% of the patients an ALND versus 41.4% with CDR versus 73.6% with Z0011 and left 0.0% patients with a surgically untreated metastasized axilla versus 21.4% with CDR versus 42.9% with Z0011. The new TTL cut-off of 260,000 CK19 mRNA copies/μL for deciding on an ALND yielded an AUC of 0.753, a FP rate of 13.7% and a PPV of 47.4%. This new criterion spared 78.2% of the study sample an ALND and left 35.7% of metastasized axillae surgically untreated. This study emphasizes the need to find a new balance between locoregional control and the morbidity associated with Berg levels I + II axillary lymph node dissection.Corrigendum to “Total Tumor Load to assist in the decision for additional axillary surgery in the positive sentinel node breast cancer patients” [Surg. Oncol. 45 (2022) 101882]: The authors regret . The authors would like to apologise for any inconvenience caused

Implementing Low-Cost, Community-Based Exercise Programs for Middle-Aged and Older Patients with Type 2 Diabetes: What Are the Benefits for Glycemic Control and Cardiovascular Risk?

Background: The purpose of this study was to analyze the effects of a long-term, community-based, combined exercise program developed with low-cost exercise strategies on glycemic control and cardiovascular risk factors in middle-aged and older patients with type 2 diabetes. Methods: Participants (n = 124; 63.25 ± 7.20 years old) engaged in either a 9-month supervised exercise program (n = 39; consisting of combined aerobic, resistance, agility/balance, and flexibility exercise; three sessions per week; 70 min per session) or a control group (n = 85) who maintained their usual care. Glycemic control, lipid profile, blood pressure, anthropometric profile, and the 10-year risk of coronary artery disease were assessed before and after the 9-month intervention. Results: A significant time * group interaction effect (p < 0.001) was identified in the values of the glycated hemoglobin, fasting plasma glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body mass index, waist circumference, and the 10-year risk of coronary artery disease. Conclusions: A long-term, community-based, combined exercise program developed with low-cost exercise strategies was effective in inducing significant benefits on glycemic control, lipid profile, blood pressure, anthropometric profile, and the 10-year risk of coronary artery disease in middle-aged and older patients with type 2 diabetes. Clinical Trial Identification Number: ISRCTN09240628.We gratefully acknowledge the participants of the study and Cova da Beira Hospital Centre for the possibility to perform this research. This study was supported by a grant from the Portuguese Foundation for Science and Technology (SFRH/BD/47733/2008)

High-Intensity Interval Training Versus Moderate-Intensity Continuous Training in Middle-Aged and Older Patients with Type 2 Diabetes: A Randomized Controlled Crossover Trial of the Acute Effects of Treadmill Walking on Glycemic Control

Background: This study aimed to compare the acute effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) on glycemic control in middle-aged and older patients with type 2 diabetes (T2D), using treadmill walking as aerobic exercise mode. Methods: Fifteen patients with T2D (60.25 ± 3.14 years; glycated hemoglobin 7.03 ± 0.33%; medicated with metformin and/or gliptins), participated in a randomized controlled crossover trial. They underwent three experimental conditions (treadmill walking HIIT session (5 × (3 min at 70% of heart rate reserve (HRR) + 3 min at 30% HRR)); treadmill walking MICT session (30 min at 50% HRR); and a control session of rest (CON)) in random order and in the postprandial state. Measurements of capillary blood glucose (BG) were taken immediately before, during, and until 50 min after the experimental conditions. Results: Both HIIT and MICT treadmill walking sessions reduced BG levels during exercise and laboratory 50 min recovery period compared to CON (time*condition interaction effect; p < 0.001). The effect of HIIT was greater compared with MICT (p = 0.017). Conclusions: Treadmill walking HIIT seems a safe and more effective exercise strategy on immediate acute glycemic control compared with MICT in middle-aged and older patients with T2D under therapy with metformin and/or gliptins. Trial Registration Number: ISRCTN09240628.This research was funded by the Portuguese Foundation for Science and Technology (grant number SFRH/BD/47733/2008), and the APC was funded by the authors

Combined low-carbohydrate diet and long-term exercise in hypoxia in type 2 diabetes: A randomized controlled trial protocol to assess glycemic control, cardiovascular risk factors and body composition

Background: Cardiovascular disease is the leading cause of mortality associated with diabetes, which is characterized by chronic hyperglycemia. Low-carbohydrate diet has gained popularity as an intervention in patients with type 2 diabetes mellitus, acting to improve glycemic profile and serum lipids. In its turn, exercise in hypoxia induces specific adaptations, mostly modulated via hypoxia-induced transcription factor signaling cascade, which increases with exposure to altitude, and promotes angiogenesis, glycogen supply, glucose tolerance, and raises GLUT-4 expression. Aim: Given that hyperglycemia decreases HIF-1 and it is better controlled when following a low-carbohydrate diet, this study aims to examine the hypothesis that a combination of both low-carbohydrate diet and chronic exercise in hypoxia in type 2 diabetes mellitus is associated with improved glycemic control and cardiovascular parameters, whose protocol is described. Methods: Patients with type 2 diabetes mellitus ( n=48) will be recruited and randomized into one of the three groups: (a) Control group: Control diet (low-fat and moderate-carbohydrate diet)+exercise in normoxia; (2) exercise in hypoxia group: Control diet+exercise in hypoxia; (3) intervention group: Low-carbohydrate diet (low-carbohydrate and high-fat diet)+exercise in hypoxia. Before and after 8 weeks of interventions, cardiopulmonary tests (Bruce protocol), body composition and blood pressure will be evaluated. Blood samples will be collected to measure hypoxia-induced transcription factor, C-reactive protein, glycemic and lipid profiles. Summary: This will be the first trial to examine the isolated and combined effect of chronic exercise in hypoxia and low-carbohydrate diet in type 2 diabetes mellitus. This trial will help to fill a significant research gap, guide future research and contribute to the combined nutrition and exercise approach to type 2 diabetes mellitus. </jats:p

Validation of the Subjective Happiness Scale in People with Chronic Kidney Disease

Objetivo: Validar as propriedades psicométricas da Subjective Happiness Scale (SHS) em pessoas com Doença Renal Crônica (DRC) em programa de hemodiálise. Método: Trata-se de um estudo metodológico. A amostra randomizada foi constituída por 171 pessoas com DRC submetida a hemodiálise em duas clinicas na região de Lisboa, Portugal. Os dados foram colhidos de maio a junho de 2015. Foram avaliadas as propriedades psicométricas: validade (construto, convergente e discriminativa), fidedignidade por meio da consistência interna (α de Cronbach) e estabilidade (Coeficiente de Correlação Intraclasse e Coeficiente de Correlação de Spearman-Brown). Resultados: Os resultados suportam a estrutura unifatorial, com uma confiabilidade (α=0,90). Além disso, esta escala está positivamente correlacionada com a Escala de Satisfação com a Vida (r=0,60; p<0,001), apoiando assim a sua validade de critério. Conclusões: A versão portuguesa da SHS é válida e reprodutível em pessoas com DRC.info:eu-repo/semantics/publishedVersio

Validación de la “Subjective Happiness Scale” en Personas con Enfermedad Renal Crónica

Objective: To explore the psychometric properties of the Subjective Happiness Scale (SHS) in patients with Chronic Kidney Disease (CKD) undergoing hemodialysis. Methods: This is a methodological study. The random sample included 171 patients with CKD under hemodialysis program in two clinics in the region of Lisbon, Portugal. Data was collected between May and June 2015. The following psychometric properties were evaluated: validity (construct, convergent and discriminant), reliability through internal consistency (Cronbach α) and stability (intraclass correlation coefficient and Spearman-Brown correlation coefficient). Results: The results support the unifactorial structure, with reliability (α = 0.90). In addition, this scale is positively correlated with the Satisfaction Life Scale (r = 0.60; p <0.001), supporting the validity criteria. Conclusions: The Portuguese version of the SHS is valid and reproducible in patients with CKD.info:eu-repo/semantics/publishedVersio

A genetic interaction of NRXN2 with GABRE, SYT1 and CASK in migraine patients: a case-control study

Background: Migraine is a multifactorial disorder that is more frequent (two to four times) in women than in men. In recent years, our research group has focused on the role of neurotransmitter release and its regulation. Neurexin (NRXN2) is one of the components of the synaptic vesicle machinery, responsible for connecting intracellular fusion proteins and synaptic vesicles. Our aim was to continue exploring the role and interaction of proteins involved in the control and promotion of neurotransmission in migraine susceptibility. Methods: A case-control study was performed comprising 183 migraineurs (148 females and 35 males) and 265 migraine-free controls (202 females and 63 males). Tagging single nucleotide polymorphisms of NRXN2 were genotyped to assess the association between NRXN2 and migraine susceptibility. The χ 2 test was used to compare allele frequencies in cases and controls and odds ratios were estimated with 95% confidence intervals. Haplotype frequencies were compared between groups. Gene-gene interactions were analysed using the Multifactor Dimensionality Reduction v2.0. Results: We found a statistically significant interaction model (p = 0.009) in the female group between the genotypes CG of rs477138 (NRXN2) and CT of rs1158605 (GABRE). This interaction was validated by logistic regression, showing a significant risk effect [OR = 4.78 (95%CI: 1.76–12.97)] after a Bonferroni correction. Our data also supports a statistically significant interaction model (p = 0.011) in the female group between the GG of rs477138 in NRXN2 and, the rs2244325's GG genotype and rs2998250’s CC genotype of CASK. This interaction was also validated by logistic regression, with a protective effect [OR = 0.08 (95%CI: 0.01–0.75)]. A weak interaction model was found between NRXN2-SYT1. We have not found any statistically significant allelic or haplotypic associations between NRXN2 and migraine susceptibility.This work was funded by Sociedade Portuguesa de Cefaleias (SPC), Fundação para a Ciência e Tecnologia (FCT; PTDC/MEC-NEU/29468/2017), Tecnifar fellowships and by European Commission and European Regional Development Fund under the project 'Análisis y correlación entre la epigenética y la actividad cerebral para evaluar el riesgo de migraña crónica y episódica en mujeres' (Cooperation Programme Interreg V-A Spain-Portugal, POCTEP 2014–2020, by the Ministerio de Ciencia, Innovación y Universidades)

Motivations and barriers to prosthesis users participation in physical activity, exercise and sport : a review of the literature

The UK will host the Paralympics in 2012 and the Commonwealth Games in 2014 showcasing the talents of elite athletes and aiming to inspire the population to become involved. However, low levels of physical activity (PA) are prevalent: only 40% of men and 28% of women meet the minimum UK recommendations. The limb absent population is no exception. To determine if people with limb amputations are participating in physical activity and sport; whether post-amputation activity levels match pre-amputation levels; and if there are motivations and barriers to participation. Study design: Literature review Five reviewers systematically search of peer reviewed and gray literature in seven bibliographic databases and the Cochrane Library. Results: Following rigorous elimination, 12 articles were finally included in the review and critically appraised. Four themes were identified: components, rehabilitation outcomes, body image and motivations and barriers to participation. People with limb absence are not participating in PA conducive to health benefits, and only a minority participate in exercise and sports. Participation following amputation does not mirror that of pre-amputation levels, and more barriers than motivations exist to adopting and maintaining a physically active lifestyle. This literature review aims to inform those involved in rehabilitation and ongoing care of those with limb absence about what motivates or precludes their participation in physical activity, exercise and sport. Such knowledge could be applied to improving health and well being in this population

The Role of Liquid Biopsy in Early Diagnosis of Lung Cancer

Liquid biopsy is an emerging technology with a potential role in the screening and early detection of lung cancer. Several liquid biopsy-derived biomarkers have been identified and are currently under ongoing investigation. In this article, we review the available data on the use of circulating biomarkers for the early detection of lung cancer, focusing on the circulating tumor cells, circulating cell-free DNA, circulating micro-RNAs, tumor-derived exosomes, and tumor-educated platelets, providing an overview of future potential applicability in the clinical practice. While several biomarkers have shown exciting results, diagnostic performance and clinical applicability is still limited. The combination of different biomarkers, as well as their combination with other diagnostic tools show great promise, although further research is still required to define and validate the role of liquid biopsies in clinical practice.This work is financed by the ERDF—European Regional Development Fund through the Operational Programme for Competitiveness and Internationalization—COMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT—Fundação para a Ciência e a Tecnologia within project POCI-01-0145-FEDER-030263. Authors thank Abílio Cunha and Francisco Correia for the illustration work. NC-M acknowledges the Portuguese Foundation for Science and Technology under Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

Structural and biophysical insights into the mode of covalent binding of rationally designed potent BMX inhibitors.

The bone marrow tyrosine kinase in chromosome X (BMX) is pursued as a drug target because of its role in various pathophysiological processes. We designed BMX covalent inhibitors with single-digit nanomolar potency with unexploited topological pharmacophore patterns. Importantly, we reveal the first X-ray crystal structure of covalently inhibited BMX at Cys496, which displays key interactions with Lys445, responsible for hampering ATP catalysis and the DFG-out-like motif, typical of an inactive conformation. Molecular dynamic simulations also showed this interaction for two ligand/BMX complexes. Kinome selectivity profiling showed that the most potent compound is the strongest binder, displays intracellular target engagement in BMX-transfected cells with two-digit nanomolar inhibitory potency, and leads to BMX degradation PC3 in cells. The new inhibitors displayed anti-proliferative effects in androgen-receptor positive prostate cancer cells that where further increased when combined with known inhibitors of related signaling pathways, such as PI3K, AKT and Androgen Receptor. We expect these findings to guide development of new selective BMX therapeutic approaches