Uveal melanoma incidence and survival analysis in Portugal between 2013 and 2022.

PURPOSE: This study aims to provide a comprehensive overview of the clinical characteristics and epidemiology of uveal melanoma (UM) in the Portuguese population, evaluated at the National Reference Centre (NRC). METHODS: A prospective observational study was conducted, involving patients consecutively diagnosed with UM at the Portuguese NRC between July 2013 and December 2022. The study collected data on demographic and tumour characteristics, clinical staging according to the American Joint Committee on Cancer (AJCC), treatment approaches, local disease control, patient survival, and the occurrence of distant metastases. RESULTS: The study included a total of 316 patients, 53.8% female. The mean age at diagnosis was 61.8±14.2 years, and 75.0% of patients presented with symptoms. The mean annual age-adjusted incidence of uveal melanoma in Portugal between 2014 and 2022 was 2.4 cases per million (95% confidence interval [CI]: 2.1-2.8). For choroidal/ciliary body tumours, the overall cumulative survival and distant metastases-free survival (DMFS) rates at 5 years were 84.9% (95% CI: 78.7-91.1) and 79.4% (95%CI: 72.8-86.0), respectively. Notably, higher AJCC stages at presentation, the need for enucleation, and increased tumour thickness were associated with lower DSS and DMFS rates. CONCLUSION: This study represents the most extensive analysis of UM epidemiology within the Portuguese population. The findings underscore the importance of early diagnosis and treatment in UM, as lower AJCC stages and smaller tumour thickness at diagnosis correlate with improved DSS and DMFS.

Assessment of Zn and Cu in piglets' liver and kidney: impact in fecal Enterococcus spp.?

Zinc and copper have been used as growth promotors in alternative to antibiotics in pig's diet. The aim was the ascertainment of the Zn and Cu concentrations in piglets' liver and kidney and their impact in the reduced susceptibility to Zn, Cu, and antibiotics in enterococci, used as microbiota biomarker. Zn and Cu were determined in the livers and kidneys of 43 piglets slaughtered in Portugal, by flame atomic absorption spectrometry. Enterococci were isolated from feces for determining the identification of species (E. faecalis, E. faecium, and Enterococcus spp.); susceptibility to vancomycin, ciprofloxacin, linezolid, tigecycline, ampicillin, imipenem, and metals; and Cu tolerance genes. In piglets with Zn and Cu high or toxic levels, enterococci had reduced susceptibility to ions, reinforced by the presence of Cu tolerance genes and by resistance to antibiotics. The study relevance is to show the relationship between these metals' levels and decreased susceptibility to Cu, Zn, and antibiotics by enterococci. From the results, it could be supposed that the piglets were being fed with high doses of Zn and Cu which could select more resistant bacteria to both antibiotics and metals that could spread to environment and humans.

In Vitro Characterization of Reversine-Treated Gingival Fibroblasts and Their Safety Evaluation after In Vivo Transplantation.

Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.

Comparison of in-office and at-home bleaching techniques: An umbrella review of efficacy and post-operative sensitivity.

Objectives: The objective of this umbrella review is to evaluate the efficacy and adverse effects of different teeth whitening techniques in-office (IO) and at-home (AH), regarding chromatic changes and teeth sensitivity. Materials and methods: The search was carried out from several databases. The included studies were all systematic reviews with or without meta-analysis of RCT or quasi-RCT. The participants were patients that underwent external dental bleaching in permanent vital teeth. The interventions were in-office (IO) bleaching techniques and at-home (AT) bleaching techniques with different bleaching agents and concentrations. Results: The search resulted in a total of 257 articles, and 28 SR were included in the qualitative analysis and nine in the quantitative analysis. There is no difference between in-office and at-home techniques in terms of color change (p = 0.95) and post-treatment sensitivity (p = 0.85). There is similarity risk and intensity of teeth sensitivity between AH and IO bleaching. IO bleaching with light-activated systems with low concentrations of bleaching agent showed similar results to IO bleaching techniques with high concentrated bleaching gels. With the application of the criteria of the AMSTAR 2 tool, the reviews were considered critically low to high. Conclusions: There are no significant differences in terms of color change between the different bleaching techniques compared. Teeth sensitivity is always present regardless of the technique used. The use of light activation systems did not increase the intensity and risk of post-operative sensitivity.

Feasibility and effectiveness of a two-tiered intervention involving training and a new consultation model for patients with palliative care needs in primary care: A before-after study.

BACKGROUND: Evidence suggests that involving General Practitioners in the care of patients with palliative care needs may improve patient outcomes. AIM: To evaluate whether a two-tiered intervention involving training in palliative care and a new consultation model in primary care for patients with palliative care needs is feasible and could reduce patients' symptom burden. DESIGN: Before-after study including an internal pilot. SETTING/PARTICIPANTS: Nine general practitioners working in a health region in Portugal and 53 patients with palliative care needs from their patient lists were recruited. General Practitioners received training in palliative care and used a new primary palliative care consultation model, with medical consultations every 3 weeks for 12 weeks. The primary outcome was physical symptom burden, self-reported using the Integrated Palliative care Outcome Scale (IPOS) patient version (min.0-max.1000). Secondary outcomes included emotional symptoms (min.0-max.400) and communication/practical issues (min.0-max.300). RESULTS: Of the 35/53 patients completed the 12-week intervention (mean age 72.53 years, SD = 13.45; 54.7% female). All had advanced disease: one third had cancer (n = 13), one third had congestive heart failure (n = 12); others had chronic kidney disease and chronic obstructive pulmonary disease. After the 12 weeks of intervention, there was a reduction in physical symptom burden [mean difference from baseline of 71.42 (95%CI 37.01-105.85) with a medium-large effect size (0.71], and in emotional symptom burden [mean difference 42.86 (95%CI 16.14-69.58), with a medium effect size (0.55)]. No difference was found for communication/practical issues. CONCLUSIONS: Our intervention can be effective in reducing patients' physical and emotional symptoms. TRIAL REGISTRATION: ClinicalTrials.gov ID - NCT05244590. Registration: 14th February 2022.

Effect of Preoperative Home-Based Exercise Training on Quality of Life After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial.

BACKGROUND: Preoperative exercise training is recommended for improvement of clinical outcomes after lung cancer (LC) surgery. However, its effectiveness in preventing postoperative decline in quality of life (QoL) remains unknown. This study investigated the effect of preoperative home-based exercise training (PHET) on QoL after LC surgery. METHODS: Patients awaiting LC resection were randomized to PHET or a control group (CG). The PHET program combined aerobic and resistance exercise, with weekly telephone supervision. Primary outcome was QoL-assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) at baseline, before surgery, and 1 month after surgery. The secondary outcomes were hospital length of stay and physical performance. The main analysis included a factorial repeated-measures analysis of variance. Additionally, the proportion of patients experiencing clinical deterioration from baseline to post-surgery was assessed. RESULTS: The study included 41 patients (68.1 ± 9.3 years; 68.3% male) in the intention-to-treat analysis (20 PHET patients, 21 CG patients). A significant group × time interaction was observed for global QoL (p = 0.004). Between-group differences in global QoL were statistically and clinically significant before surgery (mean difference [MD], 13.5 points; 95% confidence interval [CI], 2.4-24.6; p = 0.019) and after surgery (MD, 12.4 points; 95% CI, 1.3-23.4; p = 0.029), favoring PHET. Clinical deterioration of global QoL was reported by 71.4% of the CG patients compared with 30 % of the PHET patients (p = 0.003). Between-group differences in favor of PHET were found in pain and appetite loss as well as in physical, emotional and role functions after surgery (p < 0.05). Compared with CG, PHET was superior in improving preoperative five-times sit-to-stand and postoperative exercise capacity (p < 0.05). No between-group differences in other secondary outcomes were observed. CONCLUSION: The study showed that PHET can effectively prevent the decline in QoL after LC surgery.

Is hybrid therapy more efficient in the eradication of Helicobacter pylori infection? A systematic review and meta-analysis.

INTRODUCTION: Hybrid therapy (HT) is a non-bismuth quadruple therapy created to surpass Helicobacter pylori's (H. pylori) resistance rates to antibiotics. HT has excellent eradication rates, as well as a very good compliance and safety profile. We aim to compare HT with sequential therapy (ST) and concomitant therapy (CT) for the eradication of H. pylori. METHODS: This systematic review was conducted following the principles of the PRISMA guidelines. Literature was electronically searched on the CENTRAL library, PubMed, Embase, Scopus, LILACS, and ClinicalTrials.gov. Only randomized controlled trials were included. The primary outcome evaluated was eradication rate of H. pylori. The secondary outcomes evaluated were adverse events and compliance rates. Meta-analyses were performed with Cochrane Review Manager 5.4. The Mantel-Haenszel method was used to estimate the pooled relative risk and 95% confidence interval of the eradication rates between HT and other regimens, as well as the secondary outcomes. RESULTS: 10 studies were included, comprising 2993 patients. The mean eradication rates achieved by HT with intention-to-treat (ITT) and per-protocol (PP) analyses were, respectively, 86% (range: 79.2-90.8%) and 91.7% (range: 82.6-96.1%). No statistically significant difference was found in ITT eradication rate between HT and CT (relative risk: 1; 95% CI: 0.96- 1.03) and between HT and ST (relative risk: 1.02; 95% CI: 0.92-1.14). PP analysis revealed similar results. HT was associated with higher compliance rates than CT and slightly lower than ST. As far as adverse events are concerned, this meta-analysis demonstrated a higher occurrence of adverse events on the group of patients treated with CT when compared with HT. HT and ST showed similar results. CONCLUSION: HT has similar eradication, compliance and adverse event rates when compared to ST, but a better safety profile than the CT.

Development of an in chemico high-throughput screening method for the identification of skin sensitization potential.

It is well established that chemical-peptide conjugation represents the molecular initiating event (MIE) in skin sensitization. This MIE has been successfully exploited in the development of in chemico peptide reactivity assays, with the Direct Peptide Reactivity Assay (DPRA) being validated as a screening tool for skin sensitization hazard as well as an OECD test guideline. This test relies on the use of a high-performance liquid chromatography/ultraviolet detection method to quantify chemical-peptide conjugation through measurement of the depletion of two synthetic peptides containing lysine or cysteine residues, which is labor-intensive and time-consuming. To improve assay throughput, sensitivity, and accuracy, we have developed a spectrophotometric assay for skin sensitization potential based on MIE measurement-the ProtReact assay. ProtReact is also a cheaper, faster, simpler, and more accessible alternative for the DPRA, giving comparable results. A set of 106 chemicals was tested with ProtReact and the peptide depletion values compared with those reported for the DPRA. The predictive capacity of both assays was evaluated with human reference data. ProtReact and DPRA assays show similar predictive capacities for hazard identification (75% and 74%, respectively), although ProtReact showed a higher specificity (86% versus 74%, respectively) and lower sensitivity (69% versus 73%). Overall, the results show that ProtReact assay described here represents an efficient, economic, and accurate assay for the prediction of skin sensitization potential of chemical haptens.

Myopia control: short-term effect of 0.01% atropine vs. defocus incorporated multiple segment lenses-a retrospective study in European children.

PURPOSE: To compare 0.01% atropine with DIMS spectacle lenses in the prevention of myopia progression in European children. METHODS: This was a retrospective study including data from pediatric European patients with myopia. From November 2021 to March 2022, only 0.01% atropine was prescribed because DIMS lenses were still not available in Portugal. From March to October 2022, only DIMS spectacle lenses were prescribed due to patients' parents' preference. Myopia progression endpoints were axial length (AL) and spherical equivalent (SE) differences between before and 6 months after treatment. AL and SE evolution were compared using a general linear model with repeated measures. RESULTS: The study included 98 eyes from 50 patients: 47 in the atropine group and 51 in the DIMS group. There were no statistically significant differences between groups in terms of initial AL, initial SE, sex or age. The mean AL elongation at 6 months was 0.057 mm in the atropine group (SD = 0.118) and 0.002 mm (SD = 0.077) in the DIMS group. SE progression was - 0.098 (SD = 0.232) D in the atropine group and - 0.039 (SD = 0.105) D in the DIMS group. AL elongation was significantly lower in the DIMS lens group (p = 0.038, partial Eta2 = 0.045). There was no difference in SE progression between groups (p = 0.302, partial Eta2 = 0.011). CONCLUSION: Comparison between 0.01% atropine eyedrops and DIMS spectacle lenses for slowing the progression of myopia favored DIMS lenses in terms of AL elongation in a short-term follow-up. There was no difference in terms of SE between groups.

Bulk-Fill Resins versus Conventional Resins: An Umbrella Review.

Currently, composite resins have become the material of choice for the restoration of posterior teeth. Although bulk-fill resins represent a tempting alternative due to their lower complexity and faster use, some dentists are reluctant to use this material. The objective is to compare the performance of bulk-fill resins and conventional resins in direct restorations of posterior teeth based on the literature. The databases that were used to carry out the research were PubMed/MEDLINE, Embase, the Cochrane Library and the WOS. This umbrella literature review complies with PRISMA standards and assesses the quality of studies using the AMSTAR 2 tool. With the application of the criteria of the AMSTAR 2 tool, the reviews were considered low to moderate. The overall meta-analysis, although without statistical significance, favours mostly the use of conventional resin, as it is about five times more likely to obtain a favourable result than bulk-fill resin. Bulk-fill resins result in a simplification of the clinical process of posterior direct restorations, which is an advantage. The performance in terms of several properties of bulk-fill resins and conventional resins showed that they present similar behaviour.

Ostial vs. wide area circumferential ablation guided by the Ablation Index in paroxysmal atrial fibrillation.

AIMS: Pulmonary vein isolation (PVI) guided by the Ablation Index (AI) has shown high acute and mid-term efficacy in the treatment of paroxysmal atrial fibrillation (AF). Previous data before the AI-era had suggested that wide-area circumferential ablation (WACA) was preferable to ostial ablation. However, with the use of AI, we hypothesize that ostial circumferential ablation is non-inferior to WACA and can improve outcomes in paroxysmal AF. METHODS AND RESULTS: Prospective, multicentre, non-randomized, non-inferiority study of consecutive patients were referred for paroxysmal AF ablation from January 2020 to September 2021. All procedures were performed using the AI software, and patients were separated into two different groups: WACA vs. ostial circumferential ablation. Acute reconnection, procedural data, and 1-year arrhythmia recurrence were assessed. During the enrolment period, 162 patients (64% males, mean age of 60 ± 11 years) fulfilled the study inclusion criteria-81 patients [304 pulmonary vein (PV)] in the WACA group and 81 patients (301 PV) in the ostial group. Acute PV reconnection was identified in 7.9% [95% confidence interval (CI), 4.9-11.1%] of PVs in the WACA group compared with 3.3% (95% CI, 1.8-6.1%) of PVs in the ostial group [P < 0.001 for non-inferiority; adjusted odds ratio 0.51 (95% CI, 0.23-0.83), P = 0.05]. Patients in the WACA group had longer ablation (35 vs. 29 min, P = 0.001) and procedure (121 vs. 102 min, P < 0.001) times. No significant difference in arrhythmia recurrence was seen at 1-year of follow-up [11.1% in WACA vs. 9.9% in ostial, hazard ratio 1.13 (95% CI, 0.44-1.94), P = 0.80 for superiority]. CONCLUSION: In paroxysmal AF patients treated with tailored AI-guided PVI, ostial circumferential ablation is not inferior to WACA with regard to acute PV reconnection, while allowing quicker procedures with less ablation time.

Home-Based Preoperative Exercise Training for Lung Cancer Patients Undergoing Surgery: A Feasibility Trial.

BACKGROUND: Clinical guidelines recommend prehabilitation with exercise training to optimize recovery after lung cancer surgery. However, the lack of access to facility-based exercise programs is a major barrier to routine participation. This study aimed to assess the feasibility of a home-based exercise intervention before lung cancer resection. METHODS: We conducted a prospective, two-site feasibility study, including patients scheduled for lung cancer surgery. Exercise prescription involved aerobic and resistance training with telephone-based supervision. The primary endpoint was overall feasibility (recruitment rate, retention rate, intervention adherence and acceptability). Secondary endpoints included safety and effects on health-related quality of life (HRQOL) and physical performance, evaluated at baseline, after the exercise intervention and 4-5 weeks after surgery. RESULTS: Over three months, 15 patients were eligible, and all agreed to participate (recruitment rate: 100%). A total of 14 patients completed the exercise intervention, and 12 patients were evaluated postoperatively (retention rate: 80%). The median length of the exercise intervention was 3 weeks. Patients performed an aerobic and resistance training volume higher than prescribed (median adherence rates of 104% and 111%, respectively). A total of nine adverse events occurred during the intervention (Grade 1, n = 8; Grade 2, n = 1), the most common being shoulder pain. After the exercise intervention, significant improvements were observed in the HRQOL summary score (mean difference, 2.9; 95% confidence interval [CI], from 0.9 to 4.8; p = 0.049) and the five-times sit-to-stand test score (median difference, -1.5; 95% CI, from -2.1 to -0.9; p = 0.001). After surgery, no significant effects on HRQOL and physical performance were observed. CONCLUSION: A short-term preoperative home-based exercise intervention is feasible before lung cancer resection and may enhance accessibility to prehabilitation. Clinical effectiveness should be investigated in future studies.

Effectiveness of Intra-Arterial Chemotherapy for the Treatment of Intraocular Retinoblastoma: Relevance of a Multidisciplinary Setting.

Purpose: We aim to report about effectiveness and safety in the context of our centers' setting in the management of retinoblastoma with intra-arterial chemotherapy (IAC) in a 5-year retrospective analysis of the Portuguese population. Patients and Methods: Retrospective analysis of consecutive cases of retinoblastoma selected to initiate IAC between 2015 and 2020, at the Portuguese National Reference Center. All included patients underwent complete ophthalmological evaluation under anesthesia with fundus photography. Diagnosis and classification of retinoblastoma was made according to the International Classification of Intraocular Retinoblastoma (ICRB). The patients were further divided into two groups: Group I for primary IAC and Group II for secondary IAC. Tumor recurrence or relapses, systemic metastasis and deaths were documented. Main efficacy outcome included ocular salvage and recurrence-free survival rates estimated using the Kaplan-Meier method. Results: Twenty-eight eyes (19 eyes included in Group I and 9 eyes included in Group II) were eligible and a total of 130 IAC procedures were performed, with a median number of sessions of 4 (range 1-8) for each treated eye, during a median follow-up of 21 months (range 4-64). Of the included eyes, 22 (78.6%) were preserved. An overall survival of 100% was achieved. Considering the preserved eyes, the overall median decimal visual acuity achieved at the last visit was 0.15 (range 0.02-0.8). Three patients had permanent adverse events related to IAC (cataract, vitreous hemorrhage and choroidal ischemia). Considering the survival analysis of recurrence, the mean survival without recurrence was 84.2% for Group I and 66.7% for Group II, and the mean survival without enucleation was 78.6% (no events in Group II). Conclusion: IAC has been shown to be an effective and safe treatment for children with intraocular retinoblastoma. This study demonstrates that IAC is effective even in moderate sample sizes, when a multidisciplinary approach is available.

High-power short-duration versus low-power long-duration ablation guided by the ablation index.

AIMS: To compare the two different ablation strategies, both guided by the Ablation Index (AI), in the setting of atrial fibrillation (AF) ablation: high-power short-duration (HPSD) ablation using 40 W on the posterior wall and 50 W elsewhere versus low-power long-duration (LPLD) using 25 W posteriorly and 35 W elsewhere. METHODS: Prospective, multicenter nonrandomized, noninferiority study of consecutive patients referred for paroxysmal AF ablation from January 2018 to July 2019. Ablation was guided by the AI (≥500 for anterior segments, ≥450 for the roof and inferior segments and 400 posteriorly) and an interlesion distance (ILD) ≤ 6 mm. Patients were separated into two groups: HPSD vs LPLD. Acute reconnection (after adenosine trial) and 2-year outcomes were assessed. RESULTS: 160 patients (61% males, median age of 62 [IQR 51-69] years), fulfilled the study inclusion criteria - 80 patients (316 pulmonary veins [PV]) in the HPSD group and 80 patients (314 PV) in the LPLD. The probability of acute PV reconnection was similar between both groups: 2.2% in HPSD, 95%CI 0.6% to 3.8% vs. 3.4% in LPLD, 95%CI 1.4% to 5.4%; p < 0.001 for noninferiority. Median PV ablation time (20 min vs 30 min, p < 0.01) and procedure duration (80 min vs 100 min, p < 0.001) were shorter in the HPSD group. After a median follow-up of 26 months, arrhythmia recurrence was similar between groups (17.5% in HPSD group vs. 18.8% in LPLD group, p = 0.79). CONCLUSIONS: In paroxysmal AF patients treated with the Ablation Index, a HPSD strategy is noninferior to the more standard LPLD ablation, while allowing for quicker procedures with shorter ablation times.

Early surgical intervention versus conservative management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis.

OBJECTIVE: Timing of intervention for patients with asymptomatic severe aortic stenosis (AS) remains controversial. To compare the outcomes of early aortic valve replacement (AVR) versus watchful waiting (WW) in patients with asymptomatic severe AS. METHODS: We systematically searched PubMed, Embase and Cochrane databases, in December 2021, for studies comparing early AVR with WW in the treatment of asymptomatic severe AS. Random-effects meta-analysis was performed. RESULTS: Twelve studies were included in which two were randomised clinical trials. A total of 4130 patients were included, providing a 1092 pooled death events. Our meta-analysis showed a significantly lower all-cause mortality for the early AVR compared with WW group, although with a high amount of heterogeneity between studies in the magnitude of the effect (pooled OR 0.40; 95% CI 0.35 to 0.45, p<0.01; I²=61%). An early surgery strategy displayed a significantly lower cardiovascular mortality (pooled OR 0.33; 95% CI 0.19 to 0.56, p<0.01; I²=64%) and heart failure hospitalisation (pooled OR 0.19; 95% CI 0.10 to 0.39, p<0.01, I²=7%). However, both groups had similar rates of stroke (pooled OR 1.30; 95% CI 0.73 to 2.29, p=0.36, I²=0%) and myocardial infarction (pooled OR 0.49; 95% CI 0.19 to 1.27, p=0.14, I²= 0%). CONCLUSIONS: This study suggests that for patients with asymptomatic severe AS an early surgical intervention compared with a conservative WW strategy was associated with a lower heart failure hospitalisation and a similar rate of stroke or myocardial infarction, although with significant risk of bias. PROSPERO REGISTRATION NUMBER: CRD42021291144.

The impact of aquatic exercise programs on the systemic hematological and inflammatory markers of community dwelling elderly: A randomized controlled trial.

Evidence shows that physical exercise is important in maintaining an efficient immune system during ageing. However, there are few studies that test the impact of aquatic exercise programs on the immune system. This study aims to analyze the impact of different physical exercise programs in aquatic environment on the systemic hematological and inflammatory markers of community dwelling elderly. One hundred and two elderly were randomly allocated into four groups: a continuous aerobic exercise group (AerG) (n = 25, 71.44 ± 4.84 years); an interval aerobic exercise group (IntG) (n = 28, 72.64 ± 5.22 years); a combined exercise group (ComG) (n = 29, 71.90 ± 5.67 years); a control group (CG) (n = 20, 73.60 ± 5.25 years). The AerG, IntG and ComG participants took part in three different aquatic exercise programs over a 28-weeks period. The CG participants maintained their usual routines during the same time period. Blood samples were collected from all participants in order to access hematologic indicators, by means of cell count, and the inflammatory profile by ELISA. After 28 weeks, significant differences were found for several hematologic variables in the AerG, IntG and ComG with increases in mean corpuscular hemoglobulin (MCH), mean corpuscular hemoglobulin concentration (MCHC), and hemoglobulin (Hb). Decreases in TNF-α levels were found for all exercising groups. An increase in IL-10 levels, granulocytes to lymphocytes ratio (GLR) and a decrease in the TNF-α/IL-10 ratio, were found for the IntG. For the ComG decreases were also found for the TNF-α, IL-1ß/IL-1ra ratios. The present study suggests that aquatic exercise programs were able to improve the inflammatory profile of the participants. Those in the exercise intervention groups showed a shift towards lower pro-inflammatory levels while the non-exercising group showed the opposite behaviour. The IntG and the ComG aquatic exercise programs appeared to be more effective than the AerG program in decreasing chronic low-grade inflammation by mediating the production of higher levels of anti-inflammatory cytokines. However, the differences found between the exercising groups were small and may not have clinical significance.

Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis.

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants-SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters' SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.

Peripheral biomarkers to diagnose obstructive sleep apnea in adults: A systematic review and meta-analysis.

BACKGROUND: Obstructive Sleep Apnea (OSA) has been recognized as a major health concern worldwide, given its increasing prevalence, difficulties in diagnosis and treatment, and impact on health, economy, and society. Clinical guidelines highlight the need of biomarkers to guide OSA clinical decision-making, but so far, without success. In this systematic review and meta-analysis, registered on the International Prospective Register of Systematic Reviews database (ID CRD42020132556), we proposed to gather and further explore candidates identified in the literature as potential OSA biomarkers. METHODS: Search strategies for eight different databases (PubMed/Medline, Cochrane Library, Biblioteca Virtual da Saúde, Web of Science, EMBASE, World Intellectual Property Organization database, and bioRxiV and medRxiV Preprint Servers) were developed. We identified studies exploring potential biomarkers of OSA, in peripheral samples of adults, with and without OSA, with no comorbidities defined in study inclusion criteria, published after the last systematic review and meta-analysis conducted on OSA biomarkers, until May 31st, 2020. Risk of bias was assessed through the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies. Demographic, clinical, and candidate biomarkers' data were collected and analyzed via random effects meta-analyses. FINDINGS: Among the 1512 unique studies screened, 120 met the inclusion criteria and 16 studies with low risk of bias were selected for meta-analyses. The selected 16 studies enrolled a total of 2156 participants, from which 1369 were diagnosed with OSA and 787 were disease-free controls. The assessed variables showed high heterogeneity. From the 38 biomarker candidates evaluated, only two were evaluated in more than one study. Most studies pinpointed candidates with more potential for OSA prognosis. ADAM29, FLRT2 and SLC18A3 mRNA levels in PBMCs, Endocan and YKL-40 levels in serum, and IL-6 and Vimentin levels in plasma revealed the most promising candidates for OSA diagnosis. INTERPRETATION: Although the current systematic review and meta-analysis allowed us to identify candidates to further explore as potential biomarkers in future studies, it is evident that OSA biomarkers research is still at an early stage. Most findings derive from small-size single-center study cohorts and single-candidate studies. We point several gaps in current OSA biomarker research that may guide into new directions and approaches towards the identification of OSA biomarkers.