Objective To translate into and validate for Portuguese the "International Consultation on

Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternative for multiple sclerosis (MS). Despite advances in clinical management, knowledge about mechanisms involved with clinical remission post transplantation is still limited. Abnormal microRNA and gene expression patterns were described in MS and have been suggested as disease biomarkers and potential therapeutic targets. Here we assessed T-and B-cell reconstitution, microRNAs and immunoregulatory gene expression after AHSCT. Early immune reconstitution was mainly driven by peripheral homeostatic proliferation. AHSCT increased CD4 + CD25 hi FoxP3 + regulatory T-cell counts and expression of CTLA-4 and GITR (glucocorticoid-induced TNFR) on CD4 + CD25 hi T cells. We found transient increase in exhausted PD-1 + T cells and of suppressive CD8 + CD28 − CD57 + T cells. At baseline, CD4 + and CD8 + T cells from MS patients presented upregulated miR-16, miR-155 and miR-142-3p and downregulated FOXP3, FOXO1, PDCD1 and IRF2BP2. After transplantation, the expression of FOXP3, FOXO1, PDCD1 and IRF2BP2 increased, reaching control levels at 2 years. Expression of miR-16, miR-155 and miR-142-3p decreased towards normal levels at 6 months post therapy, remaining downregulated until the end of follow-up. These data strongly suggest that AHSCT normalizes microRNA and gene expression, thereby improving the immunoregulatory network. These mechanisms may be important for disease control in the early periods after AHSCT.

High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit. After AHSCT, both patient groups presented increased regulatory T-cell subset counts, early expansion of central- and effector-memory CD8(+)T-cells and late thymic reactivation. However, the non-progression group presented early expansion of PD-1(+)CD8(+)T-cells and of PD-1-expressing CD19(+) B-cells. Here, we suggest that along with increased numbers of regulatory T-cell subsets, PD-1 inhibitory signaling is one possible immunoregulatory mechanism by which AHSCT restores immune tolerance in MS patients.

Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8+ T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity. In median follow-up of 78 (range 15–106) months, all patients became insulin-independent, resuming insulin after median of 43 (range 6–100) months. Patients were retrospectively divided into short- or prolonged-remission groups, according to duration of insulin independence. For the entire follow-up, CD3+CD4+ T-cell numbers remained lower than baseline in both groups, whereas CD3+CD8+ T-cell levels did not change, resulting in a CD4/CD8 ratio inversion. Memory CTL comprehended most of T cells detected on long-term follow-up of patients after AHSCT. B cells reconstituted to baseline levels at 2–3 months post-AHSCT in both patient groups. In the prolonged-remission-group, baseline islet-specific T-cell autoreactivity persisted after transplantation, but regulatory T cell counts increased. Patients with lower frequencies of autoreactive islet-specific T cells remained insulin-free longer and presented greater C-peptide levels than those with lower frequencies of these cells. Therefore, immune monitoring identified a subgroup of patients with superior clinical outcome of AHSCT. Our study shows that improved immunoregulation may balance autoreactivity endorsing better metabolic outcomes in patients with lower frequencies of islet-specific T cells. Development of new strategies of AHSCT is necessary to increase frequency and function of T and B regulatory cells and decrease efficiently autoreactive islet-specific T and B memory cells in type 1 diabetes patients undergoing transplantation.

the FSFI English version has been translated into Portuguese and culturally adapted, being reliable to evaluate the sexual response of Brazilian women.

Objective: To evaluate the reliability and responsiveness (internal and external) of the Portuguese version of the ICIQ-SF. We assessed the responsiveness of the ICIQ-SF after surgical procedures for the treatment of stress urinary incontinence.Materials and Methods: Prospective open label study in 2 tertiary referral centers. Sixty-one patients of both genders (54 female and 7 male) were enrolled. Patients were treated using surgical procedures, mostly with synthetic sling (82%). Patients were assessed before surgery and at least 1 month postoperatively using the ICIQ-SF in its translated and validated Portuguese version. Patients also underwent pre-operative urodynamic tests, Stamey incontinence grading and pad usage assessments. After surgery, patients underwent stress tests, Stamey incontinence grading and pad usage assessments.Results: The mean age was 57.2 (± 11.6) years and the mean duration of follow-up was 7.2 months (± 4.5). Objective parameters such as urodynamic tests (by means of VLPP) and pad usage had significant correlation with changes in post-treatment scores on the ICIQ-SF (p = 0.0062 and p < 0.0001 respectively). The responsiveness expressed in terms of standardized effect sizes (SES) and standardized response means (SRM) was large for both questionnaires (p < 0.0001).Conclusion: The results showed high responsiveness (large effect sizes I and II) for the Portuguese version of the ICIQ-SF, indicating that this instrument is suitable for measuring outcomes in clinical trials for Brazilian patients with stress urinary incontinence.

Transvaginal electrical stimulation of the pelvic floor is an effective and safe treatment to women with SUI without sphincter deficiency, with significant reduction of the frequency of urinary leakage.

Vaginal delivery was associated with a decrease in pelvic floor muscle strength and endurance 45 days after delivery when compared to elective cesarean section as well as emergency cesarean section.