Human immunodeficiency virus type-1 Tat protein induces secretory leukocyte protease inhibitor expression in African green monkey but not human cells

African monkeys are resistant to HIV-1 infection due to intrinsic restriction mechanisms found in their cells. However, although they can be infected by monkey-adapted modified HIV-1 particles that are designed to overcome known restriction factors, virus numbers drop to undetectable levels in immunocompetent animals. These results indicate the possibility of the presence of yet unidentified factor(s) that restrict HIV-1 in old-world monkey (OWM) cells after integration of the viral genome into the host cell chromosome. In the light of these findings, we hypothesized that OWMs might have evolved resistance mechanism(s) against HIV-1 by switching specific gene(s) on in response to the synthesis of viral proteins in infected cells. In an attempt to mimic post-infection status, we expressed HIV-1 Tat gene in African green monkey cells and compared the whole proteome with normal cells and identified secretory leukocyte protease inhibitor (SLPI), a protein with known extracellular anti-HIV-1 activity, as an over-expressed protein in the presence of HIV-1 Tat protein by 2D-PAGE and mass spectrometry analysis. We also showed that overexpression of SLPI in the presence of HIV-1 Tat was specific to monkey cells. Our results also suggest that SLPI had a previously undiscovered intracellular anti-HIV activity in addition to its extracellular activity.

     

Evaluation of Cardiac Functions and Atrial Electromechanical Delay in Children With Adenotonsillar Hypertrophy

Deterioration of the right ventricular (RV) functions and the increase in the pulmonary arterial pressure (PAP) of children with moderate to severe adenotonsillar hypertrophy (ATH) have been well described. In addition to these complications, this study aimed to investigate the influence of ATH on the conduction system. The study investigated 46 patients with a diagnosis of ATH and 46 healthy control subjects. Conventional echocardiography, P-wave dispersion (Pd), tissue Doppler imaging (TDI) findings, and atrial electromechanical delay (AED) were compared between the patients and the control subjects before and after adenotonsillectomy. The maximum P-wave duration and Pd were significantly higher in the patients than in the control subjects (p < 0.001). The patient group showed significantly greater RV end-diastolic dimension (p = 0.01), right atrial area (p < 0.001), and mean PAP (p = 0.03) but lower E/A ratios for the mitral (p = 0.04) and tricuspid (p = 0.01) valves and a shorter pulmonary flow trace acceleration time (p = 0.03). The tricuspid annular-plane systolic excursion was similar between these groups (p = 0.21). In the patient group, TDI studies showed significantly lower E′/A′ ratios for the tricuspid lateral (p = 0.006) and mitral septal (p = 0.003) segments than in the control group. The myocardial performance index was lower for the mitral lateral, mitral septal, and tricuspid lateral segments in patient group (p < 0.001). Similarly, AED was prolonged in the patient group at all three segments (p < 0.001). Also, the patient group showed a significantly longer interatrial (p = 0.03) and intraatrial (p = 0.04) electromechanical delay. However, all the electro- and echocardiographic parameters were similar between the patients and the control subjects after adenotonsillectomy (p > 0.05). The prolongations in P-wave duration, Pd, and inter- and intraatrial electromechanical delays were first shown in this population. The cardiac changes induced by ATH-associated hypoxia may facilitate arrhythmias during the long term.     

Analysis of C-shaped Canals by Panoramic Radiography and Cone-beam Computed Tomography: Root-type Specificity by Longitudinal Distribution

Introduction

The purpose of this study was to document the characteristics of C-shaped canal systems in permanent mandibular second molars using a combination of orthopantomogram (OPT) and cross-sectional cone-beam computed tomographic (CBCT) imaging.

Methods

Two hundred participants (94 men and 106 women, mean age = 35 years) who underwent both routine CBCT and OPT examinations were enrolled. One endodontist and 1 oral radiologist examined the images of 339 mandibular second molars and described the radiographic features of C-shaped canals from OPT images as confirmed by CBCT imaging. Root morphology was classified as nonfused (NFRI–II) or fused (FRI–III) based on OPT images. Cross-sectional root canal configurations (C1–C5) were identified from CBCT imaging at 3 different levels (coronal, middle, and apical). Frequency distributions of root morphology and root canal configurations were compared at each level, and interobserver reliability was tested using the Cohen kappa test.

Results

Of the 339 teeth, 29 (8.6 %) had C-shaped root canal systems. Most of the root canals were NFR type (86%); only 2% had C-shaped root canals (all NFRII). In the FR category, 23 teeth with C-shaped canals were equally distributed between the FRI and FRII subtypes. Interobserver agreement was almost perfect (κ = 0.89 and κ = 0.91; right and left second molars, respectively). Per CBCT imaging, the most common configuration was C3 at all levels; no C5 case was detected.

Conclusions

OPT usage can assist in recognizing and diagnosing C-shaped root canal systems. Radicular fusion or proximity is a characteristic feature of C-shaped canal systems. However, nonfused root appearances should also be considered suspicious.     

Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

OBJECTIVES:

Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication.

METHODS:

Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the χ²-test.

RESULTS:

The short (S) allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (p<0.05). Out of the 69 total PE patients, 41 patients (59%) responded to therapy. There was no significant difference in the International Index of Erectile Function score at the end of therapy between the responder and nonresponder groups. The frequencies of the L allele and S allele were 20% and 39%, respectively, in the responder group (p<0.05).

CONCLUSION:

We conclude that premature ejaculation patients with the SS genotype respond well to selective serotonin reuptake inhibitor therapy. Further studies with large patient groups are necessary to confirm this conclusion.     

The only effects of recombinant follicle-stimulating hormone for ovulation induction in the pre-implantation period of rats

Objective The aim of this study was to evaluate the changes in follicular development, serum hormonal levels, and endometrium in the pre-implantation period of rats by using recombinant FSH (rFSH) without human chorionic gonadotropin (hCG). Methods Thirty female rats were studied in six groups of five specimens. Two groups determined as controls (groups 1 and 2). Two groups received constant doses of rFSH (groups 3 and 4) and other two decreasing doses (groups 5 and 6). One of the paired groups was mated. Uterus, ovaries, and blood samples were taken from non-mated groups (groups 1, 3, and 5) at the proestrus period and from mated groups (groups 2, 4, and 6) in the pre-implantation period. Results In non-mated groups antral follicles and corpus luteum periodicum and in mated groups antral follicles, corpus luteum periodicum, and corpus luteum graviditatis were increased in rFSH groups, especially in decreasing dose groups. Estradiol (E₂) levels were increased and progesterone (P)/E₂ ratio was significantly decreased in decreasing dose groups. Endometrium surface epithelium was columnar, irregular, and folded in rFSH groups. Endometrium glandular epithelium was cuboidal in all groups. In decreasing dose groups endometrial stroma was smooth and fibroblastic. Mitotic indices of endometrium surface, glandular epithelium, and stroma were significantly decreased in rFSH groups. Primary follicles and P levels showed no change. Conclusion It seems likely that decreasing doses of rFSH might be used in order to improve follicular development, although it has negative effects with E2 on endometrium in the pre-implantation period of rats.     

Effectiveness and safety of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single-tablet combination among HIV-infected patients in Turkey: results from a real world setting

BackgroundEfficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (E/C/F/TDF) in treatment-naïve and experienced patients with HIV infection was demonstrated in phase 3 trials. The primary objective of this study was to evaluate effectiveness and safety of E/C/F/TDF in real world settings.MethodsRetrospective, observational data collected by the Turkish ACTHIV-IST study group between May 2015 and December 2016 were analysed.ResultsA total of 387 patients were prescribed E/C/F/TDF; 210 patients with available data at 6th month were eligible; 91.5% were male, and mean age was 35.2 (SD: 10.8) years; 54.0% of males identified themselves as MSM. Sixty-three percent (133) of the study population were treatment-naïve patients, and 37% (77) were treatment experienced. HIV RNA level was below 100 copies/mL in 78.9% of treatment-naïve patients and 89.9% of treatment experienced patients at month 6. Median increase in CD4 T lymphocyte count was 218 copies/mL in treatment-naïve patients and remained stable or increased in treatment experienced patients. Adverse events were observed in 15% of the patients, and the regimen was discontinued in only six patients.ConclusionReal world data on the effectiveness and safety of E/C/F/TDF is comparable with the phase 3 trial results Adverse events are uncommon and manageable.     

Hemodynamic shear stress and its role in atherosclerosis

Atherosclerosis, the leading cause of death in the developed world and nearly the leading cause in the developing world, is associated with systemic risk factors including hypertension, smoking, hyperlipidemia, and diabetes mellitus, among others. Nonetheless, atherosclerosis remains a geometrically focal disease, preferentially affecting the outer edges of vessel bifurcations. In these predisposed areas, hemodynamic shear stress, the frictional force acting on the endothelial cell surface as a result of blood flow, is weaker than in protected regions. Studies have identified hemodynamic shear stress as an important determinant of endothelial function and phenotype. Arterial-level shear stress (>15 dyne/cm2) induces endothelial quiescence and an atheroprotective gene expression profile, while low shear stress (<4 dyne/cm2), which is prevalent at atherosclerosis-prone sites, stimulates an atherogenic phenotype. The functional regulation of the endothelium by local hemodynamic shear stress provides a model for understanding the focal propensity of atherosclerosis in the setting of systemic factors and may help guide future therapeutic strategies.