The role of microRNA profiling in prognosticating progression in Ta and T1 urinary bladder cancer

ObjectiveTo analyze microRNA profile in Ta and T1 urinary bladder cancers in combination and separately and to relate this to the risk of later developing higher-stage disease.Materials and methodsFormalin-fixed, paraffin-embedded samples of 44 Ta and 42 T1 bladder cancers representing cases with and without stage progression during follow-up were collected and microRNA expression levels were measured by microarray analysis.ResultsIn a comparison between the progressors and controls, in the Ta/T1 group, miR-10a-5p and miR-31-5p were differentially expressed. miR-10a-5p was also correlated to time to progression (P = 0.00012). In the subgroup analysis, 3 microRNAs, miR-10a-5p, miR-31-5p, and miR-130a-3p, were differentially expressed among Ta tumors and had a fold change of more than 1.5 (P<0.038). The comparison concerning microRNA expression between the progressors and controls in category T1 cancers revealed no significant differences.ConclusionsProfiling revealed that certain microRNAs predicted the risk of developing higher-stage disease among patients with Ta cancers. Lower miR-10a-5p expression in Ta progressing tumors indicates that this microRNA could be important for later malignant potential among this group of patients.     

Predictors of improvement in diastolic function after transcatheter aortic valve implantation

Background

Aortic stenosis is associated with concentric left ventricle (LV) hypertrophy or remodeling resulting in impaired diastolic function and elevated left-sided filling pressure. We investigated the changes in LV geometry and LV filling hemodynamics, giving emphasis to parameters associated with changes in diastolic function after transcatheter aortic valve implantation (TAVI).

Methods

Comprehensive diastolic assessment was performed before and six months after TAVI in 70 patients with severe aortic stenosis. Patients with any degree of mitral stenosis or >mild left-sided valvular regurgitation were excluded.

Results

In the entire cohort six months after TAVI, LV end-diastolic diameter increased (44.1 ± 6 versus 45 ± 6 mm, P = 0.02), whereas LV mass and relative wall thickness (RWT) decreased (270.1 ± 76 versus 245.1 ± 75 g and 0.53 ± 0.15 versus 0.46 ± 0.1, respectively; P < 0.0001 for both). Lateral e′ increased (5.8 ± 2 versus 6.6 ± 3 cm/s, P = 0.03) and left atrium (LA) volume, E/e′ ratio, and systolic pulmonary pressure decreased (88.1 ± 30 versus 80 ± 28 cc, 18 ± 7.8 versus 16.3 ± 5.5, and 42.7 ± 14.9 versus 38.7 ± 12 mmHg, respectively; P < 0.05 for all), suggesting reduction in LA pressure. The improvement in LA volume and E/e′ was almost exclusively seen in patients with LV hypertrophy before TAVI (P < 0.05 both), as opposed to patients with concentric remodeling.

Conclusions

In our preliminary study, TAVI resulted in LV and LA reverse remodeling, and improved LV relaxation and LA filling pressure in patients with severe aortic stenosis and concentric hypertrophy. Patients with concentric remodeling at baseline seem to have limited improvement in LV diastolic function and filling pressure following TAVI, but larger clinical trials would be required to conclude if they have no improvement at all.     

The Portal Vertex of KSHV Promotes Docking of Capsids at the Nuclear Pores

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related herpesvirus. Like other herpesviruses, the KSHV icosahedral capsid includes a portal vertex, composed of 12 protein subunits encoded by open reading frame (ORF) 43, which enables packaging and release of the viral genome into the nucleus through the nuclear pore complex (NPC). Capsid vertex-specific component (CVSC) tegument proteins, which directly mediate docking at the NPCs, are organized on the capsid vertices and are enriched on the portal vertex. Whether and how the portal vertex is selected for docking at the NPC is unknown. Here, we investigated the docking of incoming ORF43-null KSHV capsids at the NPCs, and describe a significantly lower fraction of capsids attached to the nuclear envelope compared to wild-type (WT) capsids. Like WT capsids, nuclear envelope-associated ORF43-null capsids co-localized with different nucleoporins (Nups) and did not detach upon salt treatment. Inhibition of nuclear export did not alter WT capsid docking. As ORF43-null capsids exhibit lower extent of association with the NPCs, we conclude that although not essential, the portal has a role in mediating the interaction of the CVSC proteins with Nups, and suggest a model whereby WT capsids can dock at the nuclear envelope through a non-portal penton vertex, resulting in an infection ‘dead end’.     

Gender differences in the sleep variables contributing to excessive daytime sleepiness among patients with obstructive sleep apnea

Sleep and Breathing - Excessive daytime sleepiness (EDS) is a main symptom in patients with obstructive sleep apnea (OSA); however, patients with OSA&nbsp;have significant variability in their...     

Effects of surgery for obstructive sleep apnea on cognitive function and driving performance

Background

Obstructive sleep apnea (OSA) is associated with a significantly increased risk of motor vehicle accidents in addition to such cognitive impairments as attention and memory deficits. The aim of the study was to examine the effect of upper airway surgery for OSA on driving and cognitive function.

Methods

Adult patients who underwent surgery for OSA at a tertiary medical center in 2016–2019 were prospectively recruited. Patients were assessed before and 3–6 months after surgery with a self-report and neurocognitive battery and a driving simulation platform.

Results

The cohort included 32 patients of average age 46.9 ± 11.6 years. During the 3 years before treatment, 9 patients had been involved in road accidents and 18 were detained by police for traffic violations. After surgery, there was a significant decrease in the Epworth Sleepiness Scale (13.7 vs. 8.1, p 0.043) and a significant reduction in time to completion of the Color Trail Test (part 1: 21.4 vs 18.7 s, p = 0.049; part 2: 46.8 vs 40.5 s, p = 0.038). Improvements in divided attention and selective attention response times were noted on the advanced stages of the Useful Field of Vision Scale (p = 0.013, p = 0.054). Before surgery, patients showed a high tendency to drive over the speed limit and to cross the dividing line to the opposite lane on the simulation test. Nevertheless, all considered themselves good drivers. These tendencies decreased after treatment.

Conclusions

Surgery for OSA can significantly improve driving performance and cognitive function.

     

Actual Colonic Perforation in Virtual Colonoscopy: Report of a Case

Computed tomography colonography, also termed virtual colonoscopy, is a new imaging method to investigate the colon, which may be a potential alternative to the conventional endoscopic colonoscopy in some cases. The high safety profile of this imaging method was considered as an additional advantage of this procedure. A case of colonic perforation in computed tomography colonography is presented, highlighting a potential risk related to this procedure. It is assumed that perforation was the result of overinflation of air into an obstructed colon caused by a lesion at the rectosigmoid junction. Thus, it is suggested that in such cases, air insufflation should be gradual, thereby minimizing the risk of perforation.     

Enhancement of antigen-induced T-cell proliferation by soluble CD26/dipeptidyl peptidase IV.

The addition of a soluble recombinant CD26 (sCD26) enhanced proliferation of peripheral blood lymphocytes induced by the recall antigen tetanus toxoid. sCD26 itself did not provide a mitogenic signal and did not augment the proliferative response of T cells to other mitogenic stimuli such as phytohemagglutinin and anti-CD3. Dipeptidyl peptidase IV-negative sCD26 did not have this enhancement effect, implying a requirement for enzyme activity. It was found that there exists a large variation in the levels of human plasma sCD26/dipeptidyl peptidase IV in vivo which may regulate T-cell activity. Peripheral blood lymphocytes from individuals whose plasma sCD26 was high and responded strongly to tetanus toxoid stimulation were insensitive to the enhancing effects of exogenously added sCD26. This suggests that plasma sCD26 had modulated the responsiveness of T cells of these individuals in vivo and that the endogenous plasma sCD26 regulates immune responses by allowing antigen-specific T cells to exert a maximal response to their specific antigen.     

Methotrexate treatment of rheumatoid arthritis: is a fortnightly maintenance schedule enough?

In 15 patients with rheumatoid arthritis who were in clinical remission the weekly regimen of methotrexate treatment was changed to fortnightly without a change in dose. A total of 13 patients completed a 12 month trial. No change in clinical or laboratory parameters occurred. There was no change in the use of analgesics or non-steroidal anti-inflammatory drugs and the patients remained in remission. Two patients had to be withdrawn after two and four months respectively because of a flare in disease activity. It is suggested that in most patients with rheumatoid arthritis who are treated with methotrexate and whose disease activity is stable a fortnightly regimen can be permitted without affecting drug efficacy.     

Computed tomographic demonstration of calcification of the ligamenta flava of the lumbosacral spine in ankylosing spondylitis.

An axial computed tomographic (CT) scan of the lumbosacral regions was performed in 65 patients. The patient population was divided into two groups. The first (control) group included 40 elderly patients without calcification of the ligamenta flava. The second group included 25 patients with ankylosing spondylitis. More than 90% of those in the second group showed calcified lumbosacral ligamenta flava. In two patients these calcifications produced spinal stenosis. The diagnostic and practical importance of these findings are discussed.