Ureteral obstruction promotes proliferation and differentiation of the renal urothelium into a bladder-like phenotype

The renal urothelium, the monolayered epithelium that covers the papilla, is the direct target of increased pressure during obstruction, yet most studies have mainly focused on tubules, fibroblasts, and inflammatory cells. We studied this epithelium in a unilateral ureteral obstruction mouse mode land found that it was disrupted and had broken tight junctions, enlarged intercellular space, with loss of apicaluroplakins, and marginal lumen desquamation. Shortly after obstruction these urothelial cells proliferated, peaking at day 2. By day 14, the renal urothelium was transformed into a multilayered barrier with newly synthesized uroplakins including the de novo induction of uroplakin II. This proliferation was found to be fibroblast growth factor (FGF)dependent. Renal urothelial cells constitutively express the FGF receptor 2, and obstruction activated the receptor by phosphorylation. Treatment with FGF receptor 2-antisense or vitamin A (an inhibitor of the MAP kinase in the FGFR2 pathway) decreased renal urothelial cell proliferation. Among known FGF receptor 2 ligands, only FGF7 was upregulated.Infusion of FGF7 into control mice caused the formation of a multilayered structure at 7 days, resembling the urothelium 14 days following obstruction. Thus, the pressure/stretching of renal monolayered urothelial cells is a very efficient trigger for proliferation, causing the formation of a bladder-like multistratified barrier with enhanced apical uroplakin plaques. Presumably, this ensures efficient barrier protection and repair.     

Predictors of Early Stroke or Death in Patients Undergoing Transcatheter Aortic Valve Implantation

Background/ObjectiveWhile postoperative stroke is a known complication of Transcatheter Aortic Valve Implantation (TAVI), predictors of early stroke occurrence have not been specifically reviewed. The objective of this study was to estimate the predictors and incidence of stroke during the first 30 days post-TAVI.MethodsA cohort of 506 consecutive patients having undergone TAVI between January 2017 and June 2019 was extracted from a prospective database. Preoperative, intraoperative and postoperative characteristics were analyzed by univariate analysis followed by logistic regression to find predictors of the occurrence of stroke or death within the first 30 days after the procedure.ResultsIncidence of stroke within 30 days post-TAVI was 4.9%, [CI 95% 3.3–7.2], i.e., 25 strokes. Four out of the 25 patients (16%) with a stroke died within 30 days post-TAVI. After logistic regression analysis, the predictors of early stroke related to TAVI were: CHA2Ds2VASc score ≥ 5 (odds ratio [OR] 2.62; 95% CI: 1.06–6.49; p = .037), supra-aortic access vs. femoral access (OR: 9.00, 95%CI: 2.95–27.44; p = .001) and introduction post-TAVI of a single vs. two or three antithrombotic agents (OR: 5.13; CI 95%: 1.99 to 13.19; p = .001). Over the 30-day period, bleeding occurred in 28 patients (5.5%), in 25 of whom, it was associated with femoral or iliac artery access injury. Anti-thrombotic regimen was not associated with bleeding; two patients out of 48 (4.1%) bled with a single anti-thrombotic regimen vs. 26 patients out of 458 (5.6%) with a dual or triple anti-thrombotic regimen (p = 0.94). The overall 30-day mortality rate was 3.9%, [95% CI 2.5–6.0]. Patients with a single post-TAVI antithrombotic agent (OR: 44.07 [CI 95% 13.45–144.39]; p < .0001) and patients with previous coronary artery bypass surgery or coronary artery stenting (OR: 6.16, [CI 95% 1.99–21.29]; p = .002) were at significantly higher risk of death within the 30-day period.ConclusionIn this large-scale single-center retrospective study, a single post-TAVI antithrombotic regimen independently predicted occurrence of early stroke or death. Dual or triple antithrombotic regimen was not associated with a higher risk of bleeding and should be considered as an option in patients undergoing TAVI.     

Molecular epidemiology of Staphylococcus aureus strains isolated from inpatients with infected diabetic foot ulcers in an Algerian University Hospital

Staphylococcus aureus is the most common pathogen cultured from diabetic foot infection (DFI). The consequence of its spread to soft tissue and bony structures is a major causal factor for lower-limb amputation. The objective of the study was to explore ecological data and epidemiological characteristics of S. aureus strains isolated from DFI in an Algerian hospital setting. Patients were included if they were admitted for DFI in the Department of Diabetology at the Annaba University Hospital from April 2011 to March 2012. Ulcers were classified according to the Infectious Diseases Society of America/International Working Group on the Diabetic Foot classification system. All S. aureus isolates were analysed. Using oligonucleotide arrays, S. aureus resistance and virulence genes were determined and each isolate was affiliated to a clonal complex. Among the 128 patients, 277 strains were isolated from 183 samples (1.51 isolate per sample). Aerobic Gram-negative bacilli were the most common isolated organisms (54.9% of all isolates). The study of ecological data highlighted the extremely high rate of multidrug-resistant organisms (MDROs) (58.5% of all isolates). The situation was especially striking for S. aureus [(85.9% were methicillin-resistant S. aureus (MRSA)], Klebsiella pneumonia (83.8%) and Escherichia coli (60%). Among the S. aureus isolates, 82.2% of MRSA belonged to ST239, one of the most worldwide disseminated clones. Ten strains (13.7%) belonged to the European clone PVL+ ST80. ermA, aacA-aphD, aphA, tetM, fosB, sek, seq, lukDE, fnbB, cap8 and agr group 1 genes were significantly associated with MRSA strains (p <0.01). The study shows for the first time the alarming prevalence of MDROs in DFI in Algeria.     

Can individuals with schizophrenia be instructed to deliberately feign memory deficits?

Introduction. Neuropsychological tests are increasingly applied in research studies and clinical practice in psychiatry. In this context, the detection of poor effort is crucial to adequately interpret data. We measured schizophrenia patients' performance on a memory test designed to detect excessive malingering (the “21-Item Test”), before examining whether a second group of schizophrenia patients would excessively malinger on this test when given an incentive to feign memory impairment.

Methods. Two independent studies including respectively 49 schizophrenia patients and 100 controls (study 1) and 25 schizophrenia patients and 25 controls (study 2) were conducted. In study 1, participants were asked to complete the 21-Item Test to the best of their ability. In study 2, participants were given a hypothetical scenario in which having a memory impairment would be financially advantageous for them, before completing the 21-Item Test.

Results. In study 1, no participant scored at levels indicative of excessive malingering. In study 2, 84% of controls but only 36% of patients scored at excessive levels of malingering, and these patients had higher executive functioning than patients who did not excessively malinger, although it should be noted that a significantly greater proportion of patients excessively malingered in study 2 compared to study 1.

Conclusions. These results indicate that schizophrenia patients do not normally feign excessive memory impairment during psychological testing. Furthermore, they are less able and/or less inclined to excessively malinger than controls in situations where a memory impairment would be advantageous, perhaps indicating a better ability to malinger without detection. Potential clinical implications are discussed.     

Temporal association between sleep apnea–hypopnea and sleep bruxism events

There is some evidence suggesting that obstructive sleep apnea–hypopnea syndrome is concomitant with sleep bruxism. The aim of this study was to investigate the temporal association between sleep apnea–hypopnea events and sleep bruxism events. In an open observational study, data were gathered from 10 male subjects with confirmed obstructive sleep apnea–hypopnea syndrome and concomitant sleep bruxism. Polysomnography and audio‐video recordings were performed for 1 night in a sleep laboratory. Breathing, brain, heart and masticatory muscle activity signals were analysed to quantify sleep and sleep stage duration, and number and temporal distribution of apnea–hypopnea events and sleep bruxism events. Apnea–hypopnea events were collected within a 5‐min time window before and after sleep bruxism events, with the sleep bruxism events as the pivotal reference point. Two temporal patterns were analysed: (i) the interval between apnea–hypopnea events termination and sleep bruxism events onset, called T1; and (ii) the interval between sleep bruxism events termination and apnea–hypopnea events onset, called T2. Of the intervals between sleep bruxism events and the nearest apnea–hypopnea event, 80.5% were scored within 5 min. Most intervals were distributed within a period of <30 s, with peak at 0–10 s. The T1 interval had a mean length of 33.4 s and was significantly shorter than the T2 interval (64.0 s; P < 0.05). Significantly more sleep bruxism events were scored in association with the T1 than the T2 pattern (P < 0.05). Thus, in patients with concomitant obstructive sleep apnea–hypopnea syndrome and sleep bruxism, most sleep bruxism events occurred after sleep apnea–hypopnea events, suggesting that sleep bruxism events occurring close to sleep apnea–hypopnea events is a secondary form of sleep bruxism.     

Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study

The incidence of thrombosis in the purely obstetric form of antiphospholipid syndrome is uncertain. We performed a 10-year observational study of 1592 nonthrombotic women who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal death at or beyond the 10th week of gestation. We compared the frequencies of thrombotic events among women positive for antiphospholipid Abs (n = 517), women carrying the F5 6025 or F2 rs1799963 polymorphism (n = 279), and women with negative thrombophilia screening results (n = 796). The annual rates of deep vein thrombosis (1.46%; range, 1.15%-1.82%), pulmonary embolism (0.43%; range, 0.26%-0.66%), superficial vein thrombosis (0.44%; range, 0.28%-0.68%), and cerebrovascular events (0.32%; range, 0.18%-0.53%) were significantly higher in aPLAbs women than in the other groups despite low-dose aspirin primary prophylaxis. Women carrying 1 of the 2 polymorphisms did not experience more thrombotic events than women who screened negative for thrombophilia. Lupus anticoagulant was a risk factor for unprovoked proximal and distal deep and superficial vein thrombosis and women in the upper quartile of lupus anticoagulant activity had the highest risk. Despite data suggesting that aPLAbs may induce pregnancy loss through nonthrombotic mechanisms, women with purely obstetric antiphospholipid syndrome are at risk for thrombotic complications.