In obese hypertensives cholecalciferol inhibits circulating TH17 cells but not macrophage infiltration on adipose tissue.

In arterial hypertension, increased Th17 cells and reduced Tregs are the hallmarks of immunological dysfunction and the basis for the investigation of immunomodulatory drugs. Although cholecalciferol is not a primary immunomodulator, it has recognized action on immune cells, leading us to hypothesise if cholecalciferol can induce a more tolerogenic phenotype in obese hypertensives. In a phase-2, single-centre, randomised, open, 24-week trial, we assigned adults with obesity-associated hypertension and vitamin D deficiency to receive usual therapy plus 50,000 IU/week of cholecalciferol or usual therapy alone. The primary endpoint was the percentual variation in T CD4+, T CD8+, Tregs, and Th17 cells. Secondary endpoints included the percentual variation in Th1, Tc1, Tc17, and monocytes and variation in the number of perivascular and non-perivascular macrophages, T CD4+ and T CD8+ lymphocytes in subcutaneous abdominal adipose tissue. A control group of 12 overweight normotensives was also evaluated for peripheral immune cells. A total of 36 obese hypertensives were randomised, 18 in each group. In comparison with normotensive controls, hypertensives presented higher percentages of T lymphocytes (p = 0.016), Tregs (p = 0.014), and non-classical monocytes (p < 0.001). At week 24, Th17 cells increased in control group (p = 0.017) but remained stable in cholecalciferol group. For Tregs, downregulation towards the values of normotensive controls was observed (p = 0.003), and in multivariate analysis, an increased loading in the setting of the cells of adaptive immunity observed (eigenvalue 1.78, p < 0.001). No changes were documented for monocytes. In adipose tissue, a baseline negative correlation between vitamin D and perivascular macrophages was observed (r = -0.387, p = 0.024) that persisted in the control group (r = -0.528, p = 0.024) but not in the cholecalciferol group, which presented an increase in non-perivascular macrophages (p = 0.029) at week 24. No serious adverse events were reported for all the participants. In this trial, we found that supplementation with cholecalciferol interfered with peripheral and adipose tissue immune cell profile, downregulating peripheral Th17 cells, but increasing the number of infiltrating subcutaneous adipose tissue macrophages. (Funded by Núcleo Estudos Hipertensão da Beira Interior; EudraCT number: 2015-003910-26).

Characterization of the Portuguese population diagnosed with retinoblastoma.

The purpose of this study is to characterize demographically and genetically the Portuguese population with retinoblastoma; to report the clinical stage at presentation and its impact on survival and ocular preservation rate and, finally, to assess the incidence of retinoblastoma in Portugal. Retrospective observational study including children consecutively diagnosed with retinoblastoma at the Portuguese National Referral Center of Intraocular Tumors, between October 2015 and October 2020. Twenty-eight children were diagnosed with retinoblastoma at our center, 15 hereditary from which 12 presented with bilateral retinoblastoma and 3 were unilateral. The overall mean age at diagnosis was 13.6 ± 11.1 months with hereditary retinoblastomas diagnosed slightly earlier at 9.6 ± 6.3 months. A familial history of retinoblastoma was found in only 4 (14.3%) of the cases. A pathogenic mutation in the RB1 gene was found in 13 (46.4%) of the children. The most frequent sign at referral was leukocoria in 71.4% of patients. Considering the ICRB classification of the tumors, 84.6% of non-hereditable hereditary retinoblastomas were referred to our center in advanced stages. In the group of hereditable retinoblastomas 86.7% presented with one of the eyes with advanced intraocular retinoblastoma. Fourteen children had one eye enucleated due to retinoblastoma. No deaths were registered during the study period. Considering the incidence analysis, we registered a year-of-birth controlled incidence analysis of 4.04 per 100.000 living births (IC 95% 1.59-6.49). This is the first characterization of the Portuguese Population diagnosed with Retinoblastoma in the National Reference Center.

Obsessive-compulsive disorder as a visual processing impairment.

OCD has been hypothesized to involve the failures in both cognitive and behavioral inhibitory processes. There is evidence that the hyperactivation of cortical-subcortical pathways may be involved in the failure of these inhibitory systems associated with OCD. Despite this consensus on the role of frontal-subcortical pathways in OCD, recent studies have been showing that brain regions other than the frontal-subcortical loops may be needed to understand the different cognitive and emotional deficits in OCD. Some studies have been finding evidence for decreased metabolic activity in areas such as left inferior parietal and parieto-occipital junction suggesting the possible existence of visual processing deficits. While there has been inconsistent data regarding visual processing in OCD, recent studies have been claiming that these patients have abnormal patterns of visual processing social rich stimuli, particularly emotional arousing stimuli. Thus, in this article, we hypothesize that the fronto-subcortical activation consistently found in OCD may be due to a deactivation of occipital/parietal regions associated with visual-perceptual processing of incoming social rich stimuli. Additionally, this dissociation may be more evident as the emotional intensity of the social stimulus increases.