A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis.

Candida vaginitis is a frequent clinical diagnosis with up to 8% of women experiencing recurrent vulvovaginal candidiasis (RVVC) globally. RVVC is characterized by at least three episodes per year. Most patients with RVVC lack known risk factors, suggesting a role for genetic risk factors in this condition. Through integration of genomic approaches and immunological studies in two independent cohorts of patients with RVVC and healthy individuals, we identified genes and cellular processes that contribute to the pathogenesis of RVVC, including cellular morphogenesis and metabolism, and cellular adhesion. We further identified SIGLEC15, a lectin expressed by various immune cells that binds sialic acid-containing structures, as a candidate gene involved in RVVC susceptibility. Candida stimulation induced SIGLEC15 expression in human peripheral blood mononuclear cells (PBMCs) and a polymorphism in the SIGLEC15 gene that was associated with RVVC in the patient cohorts led to an altered cytokine profile after PBMC stimulation. The same polymorphism led to an increase in IL1B and NLRP3 expression after Candida stimulation in HeLa cells in vitro. Last, Siglec15 expression was induced by Candida at the vaginal surface of mice, where in vivo silencing of Siglec15 led to an increase in the fungal burden. Siglec15 silencing was additionally accompanied by an increase in polymorphonuclear leukocytes during the course of infection. Identification of these pathways and cellular processes contributes to a better understanding of RVVC and may open new therapeutic avenues.

Angiographic findings of the multicenter Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL): sirolimus-eluting stents inhibit restenosis irrespective of the vessel size.

BACKGROUND: Restenosis remains the major limitation of coronary catheter-based intervention. In small vessels, the amount of neointimal tissue is disproportionately greater than the vessel caliber, resulting in higher restenosis rates. In the Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) trial, approximately 40% of the vessels were small (<2.5 mm). The present study evaluates the relationship between angiographic outcome and vessel diameter for sirolimus-eluting stents. METHODS AND RESULTS: Patients were randomized to receive either an 18-mm bare metal Bx VELOCITY (BS group, n=118), or a sirolimus-eluting Bx VELOCITY stent (SES group, n=120). Subgroups were stratified into tertiles according to their reference diameter (RD; stratum I, RD <2.36 mm; stratum II, RD 2.36 mm to 2.84 mm; stratum III, RD >2.84 mm). At 6-month follow-up, the restenosis rate in the SES group was 0% in all strata (versus 35%, 26%, and 20%, respectively, in the BS group). In-stent late loss was 0.01+/-0.25 versus 0.80+/-0.43 mm in stratum I, 0.01+/-0.38 versus 0.88+/-0.57 mm in stratum II, and -0.06+/-0.35 versus 0.74+/-0.57 mm in stratum III (SES versus BS). In SES, the minimal lumen diameter (MLD) remained unchanged (Delta -0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, DeltaMLD <-0.72 mm) in 3% of the lesions. Multivariate predictors for late loss were treatment allocation (P<0.001) and postprocedural MLD (P= 0.008). CONCLUSIONS: Sirolimus-eluting stents prevent neointimal proliferation and late lumen loss irrespective of the vessel diameter. The classic inverse relationship between vessel diameter and restenosis rate was seen in the bare stent group but not in the sirolimus-eluting stent group.

[Atrial septal defect percutaneous transvenous occlusion with the buttoned device]. / Oclusão percutânea transvenosa de comunicação interatrial mediante utilização do buttoned device.

PURPOSE: To analyse the experience with the use of Sideris' device for percutaneous transvenous occlusion of atrial septal defect (ASD). METHODS: Thirty six procedures of ASD occlusion were performed in 32 patients; 27 (84.4%) female and five (15.6%) male, mean age of 16 years (4-61). All patients had secundum atrial septal defects with clinical and hemodynamic compromise. The ASD diameter measured < 31 mm and occupied less than 50% of the septal length in all cases. The basic device was used in 28 (87.5%) patients and the self centered model in four (12.5%). The direct implant technique was employed in 15 (41.7%) procedures while in the other 21 (58.3%) an over a wire technique was used. The size of the device was selected according with the Sideris' normogram. RESULTS: Occlusion of the defect was achieved in 29 patients (90.63%). In two (6.25%) the position of the device was not adequate and in one (3.12%) the device embolized to the pulmonary artery. In these three cases the device was removed surgically during the defect closure. There was neither morbidity nor mortality in this series. Trivial or small residual shunt was detected with color flow mapping in three (9.4%) patients immediately after the procedure. In 22 patients with 12 months follow-up, trivial residual shunt was present in only one (4.5%). Structural modification of the device was detected in one patient, however with complete ASD occlusion and neither clinical nor hemodynamic disturbance. CONCLUSION: The Sideris' device is safe and efficient for ASD occlusion in selected patients. Although there is a relatively high incidence of residual shunt immediately after the procedure, the shunt itself tends to become smaller or disappear during the follow-up and it does not preclude clinical and hemodynamic improvement.

Eficácia anti-hipertensiva da nifedipina. Avaliação clinica e ergometrica / Antihypertensive efficacy of nifedipine. Clinical and ergometric evaluation

O presente ensaio avalia a eficacia da nifedipina em 10 pacientes com hipertensao arterial, leve ou moderada, submetidos a avaliacao clinica, ergometrica e ecocardiografica em estudo duplamente cego, cruzado e aleatorio. Nao se verificaram modificacoes importantes nas variaveis ecocardiograficas, exceto no diametro diastolico. Do mesmo modo, nao variaram o consumo do oxigenio e a frequencia cardiaca. O duplo produto apresentou diferencas significativas entre os periodos basal e com nifedipina, (p < 0,05). A pressao arterial apresentou modificacoes importantes sob uso de nifedipina em relacao ao periodo controle, sendo tais alteracoes estatisticamente significativas, (p < 0,05). As variacoes verificadas sob uso de placebo nao foram estatisticamente significativas.Conclui-se que nifedipina e uma droga util no controle de pacientes com hipertensao leve e moderada, quer em repouso, quer sob exercicio, sendo os efeitos colaterais observados leves com a dose de 30 mg diarios