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  • Impact of combined training with different exercise intensities on inflammatory and lipid markers in type 2 diabetes : a secondary analysis from a 1-year randomized controlled trial
    Publication . Magalhães, João P.; Santos, Diana A.; Correia, Inês; Hetherington-Rauth, Megan; Ribeiro, Rogério; Raposo, João F.; Matos, Andreia; Bicho, Manuel; Sardinha, Luís B.
    Background: Exercise is a well-accepted strategy to improve lipid and infammatory profle in individuals with type 2 diabetes (T2DM). However, the exercise intensity having the most benefts on lipids and infammatory markers in patients with T2DM remains unclear. We aimed to analyse the impact of a 1-year combined high-intensity interval training (HIIT) with resistance training (RT), and a moderate continuous training (MCT) with RT on infammatory and lipid profle in individuals with T2DM. Methods: Individuals with T2DM (n=80, aged 59 years) performed a 1-year randomized controlled trial and were randomized into three groups (control, n=27; HIIT with RT, n=25; MCT with RT, n=28). Exercise sessions were super‑ vised with a frequency of 3 days per week. Infammatory and lipid profles were measured at baseline and at 1-year follow-up. Changes in infammatory and lipid markers were assessed using generalized estimating equations. Results: After adjusting for sex, age and baseline moderate-to-vigorous physical activity (MVPA), we observed a time-by-group interaction for Interleukin-6 (IL-6) in both the MCT with RT (β=−0.70, p=0.034) and HIIT with RT (β=−0.62, p=0.049) groups, whereas, only the HIIT with RT group improved total cholesterol (β=−0.03, p=0.045) and LDL-C (β=−0.03, p=0.034), when compared to control. No efect was observed for C-reactive protein (CRP), cortisol, tumour necrosis factor-α (TNF-α), soluble form of the haptoglobin-hemoglobin receptor CD163 (sCD163), triglycerides and HDL-C in both groups (p>0.05). Conclusions: Favorable adaptations on IL-6 were observed in both the HIIT and MCT combined with RT groups fol‑ lowing a long-term 1-year exercise intervention in individuals with T2DM. However, only the HIIT with RT prevented further derangement of total cholesterol and LDL-C, when compared to the control group. Therefore, in order to encourage exercise participation and improve infammatory profle, either exercise protocols may be prescribed, however, HIIT with RT may have further benefts on the lipid profle.
  • Expression of receptor activator of NFkB (RANK) drives stemness and resistance to therapy in ER+HER2- breast cancer
    Publication . Fernandes Gomes, Inês; Almeida, Bernardo P. De; Dâmaso, Sara; Mansinho, André; Correia, Inês; Henriques, Sara; Duarte, Raquel; Vilhais, Guilherme; Félix, Pedro; Alves, Patrícia; Corredeira, Patrícia; Barbosa-Morais, Nuno; Costa, Luis; Casimiro, Sandra
    The role of RANKL-RANK pathway in progesterone-driven mammary carcinogenesis and triple negative breast cancer tumorigenesis has been well characterized. However, and despite evidences of the existence of RANK-positive hormone receptor (HR)-positive breast tumors, the implication of RANK expression in HR-positive breast cancers has not been addressed before. Here, we report that RANK pathway affects the expression of cell cycle regulators and decreases sensitivity to fulvestrant of estrogen receptor (ER)-positive (ER+)/HER2- breast cancer cells, MCF-7 and T47D. Moreover, RANK overexpressing cells had a staminal and mesenchymal phenotype, with decreased proliferation rate and decreased susceptibility to chemotherapy, but were more invasive in vivo. In silico analysis of the transcriptome of human breast tumors, confirmed the association between RANK expression and stem cell and mesenchymal markers in ER+HER2- tumors. Importantly, exposure of ER+HER2- cells to continuous RANK pathway activation by exogenous RANKL, in vitro and in vivo, induced a negative feedback effect, independent of RANK levels, leading to the downregulation of HR and increased resistance to hormone therapy. These results suggest that ER+HER2- RANK-positive cells may constitute an important reservoir of slow cycling, therapy-resistance cancer cells; and that RANK pathway activation is deleterious in all ER+HER2- breast cancer cells, independently of RANK levels.
  • Effects of combined training with different intensities on vascular health in patients with type 2 diabetes : a 1-year randomized controlled trial
    Publication . Magalhães, João P.; Melo, Xavier; Correia, Inês; Ribeiro, Rogério T.; Raposo, João; Dores, Hélder; Bicho, Manuel; Sardinha, Luís B.
    Background: Exercise, when performed on a regular basis, is a well-accepted strategy to improve vascular function in patients with type 2 diabetes. However, the exercise intensity that yields maximal adaptations on structural and functional indices in patients with type 2 diabetes remains uncertain. Our objective was to analyze the impact of a 1-year randomized controlled trial of combined high-intensity interval training (HIIT) with resistance training (RT) vs. a combined moderate continuous training (MCT) with RT on structural and functional arterial indices in patients with type 2 diabetes. Methods: Patients with type 2 diabetes (n=80) were randomized into an exercise intervention with three groups: control, combined HIIT with RT and combined MCT with RT. The 1-year intervention had 3 weekly exercise sessions. High-resolution ultrasonography of the common carotid artery and central and peripheral applanation tonometry were used to assess the changes in structural and functional arterial indices. Generalized estimating equations were used to model the corresponding outcomes. Results: After adjusting the models for sex, baseline moderate-to-vigorous physical activity, and mean arterial pressure changes, while using the intention-to-treat analysis, a signifcant interaction was observed on the carotid intimamedia thickness (cIMT) for both the MCT (β=−4.25, p<0.01) and HIIT group (β=−3.61, p<0.01). However, only the HIIT observed favorable changes from baseline to 1-year on peripheral arterial stifness indices such as carotid radial arterial pulse wave velocity (β=−0.10, p=0.044), carotid to distal posterior tibial artery pulse wave velocity (β=−0.14, p<0.01), and on the distensibility coefcient (β=−0.00, p<0.01). No efect was found for hemodynamic variables after the intervention. Conclusions: Following a 1-year intervention in patients with type 2 diabetes, both the MCT and HIIT group reduced their cIMT, whereas only the HIIT group improved their peripheral arterial stifness indices and distensibility coefcient. Taken together, HIIT may be a meaningful tool to improve long-term vascular complications in type 2 diabetes.
  • Sensor based sleep patterns and reported sleep quality in breast cancer patients undergoing neoadjuvant chemotherapy
    Publication . Malveiro, Carla; Boavida, Sofia; Cargaleiro, Catarina; Bernardino, Ana Vilelas; Correia, Inês; Reis, Cátia; Matos, Leonor; Sardinha, Luís B.; Cardoso, Maria João; Saint-Maurice, Pedro F.
    Breast cancer is the most diagnosed cancer in women worldwide and its treatment often leads to the onset of sleep disturbances. While much research has focused on chemotherapy's impact on overall sleep quality through subjective measures, less attention has been given to its effects on specific sleep metrics such as duration, timing, continuity, and naps. This preliminary study addresses this gap by assessing sleep duration, timing, and regularity, using the Emfit QS device over 100 consecutive days in 24 breast cancer patients undergoing neoadjuvant chemotherapy. Additionally, we incorporated the Pittsburgh Sleep Quality Index (PSQI) to measure reported sleep quality. Our results suggest that chemotherapy may influence the duration for time spent in bed (ptrend = 0.02) measured by the Emfit QS. Duration in bed decreased over the first seven weeks (e.g., 9.3 h/day at week 1 vs. 8.5 h/day at week 8), and increased thereafter to similar amounts as those recorded in week 1 (9.0 h/day at week 15). Sleep timing and regularity, also measured by the Emfit QS, remained unchanged. Overall sleep quality, as measured by the PSQI, did not change over time. However, our analysis of the individual components of the PSQI revealed that sleep disturbances increased as treatment progressed from week 1 to week 8 (1.3 ± 0.6 to 1.7 ± 0.6; p = 0.01), concurrently with an increase in insomnia symptoms. Approximately, 33%, 63%, and 73% reported having insomnia symptoms at week 1, 8, and 15. These findings highlight critical periods during treatment when patients are vulnerable to disrupted sleep. Future research should focus on interventions to mitigate sleep disturbances, improving patient well-being and overall quality of life.