The Role of Sex Differences in Autophagy in the Heart During Coxsackievirus B3-Induced Myocarditis

Under normal conditions, autophagy maintains cardiomyocyte health and integrity through turnover of organelles. During stress, oxygen and nutrient deprivation, or microbial infection, autophagy prolongs cardiomyocyte survival. Sex differences in induction of cell death may to some extent explain the disparity between the sexes in many human diseases. However, sex differences in gene expression, which regulate cell death and autophagy, were so far not taken in consideration to explain the sex bias of viral myocarditis. Coxsackievirus B3 (CVB3)-induced myocarditis is a sex-biased disease, with females being substantially less susceptible than males and sex hormones largely determine this bias. CVB3 was shown to induce and subvert the autophagosome for its optimal viral RNA replication. Gene expression analysis on mouse and human, healthy and CVB3-infected, cardiac samples of both sexes, suggests sex differences in autophagy-related gene expression. This review discusses the aspects of sex bias in autophagy induction in cardiomyocytes.     

Plant secondary siRNA production determined by microRNA-duplex structure

Processing of microRNA (miRNA) precursors results in the release of a double-stranded miRNA/miRNA* duplex. The miRNA or guide strand, is loaded onto the Argonaute (AGO) effector, and the miRNA* or passenger strand is typically degraded. The loaded AGO-containing RNA-induced silencing complex specifically recognizes a target mRNA, leading to its degradation or translational inhibition. In plants, miRNA-mediated cleavage of a target triggers in some cases the production of secondary small interfering RNAs (siRNAs), which in turn can silence other genes in trans. This alternative pathway depends on the length of the miRNA and the specific AGO in the effector complex. However, 22-nt miRNAs are sufficient, but not essential for this pathway. Using a combination of computational and experimental approaches, we show that transitivity can be triggered when the small RNA that is not retained in AGO is 22-nt long. Moreover, we demonstrate that asymmetrically positioned bulged bases in the miRNA:miRNA* duplex, regardless of miRNA or miRNA* length, are sufficient for the initiation of transitivity. We propose that the RNA-induced silencing complex reprogramming occurs during the early steps of miRNA loading, before the miRNA duplex is disassembled and the guide strand is selected.     

Clinical risk factors related to failures with zirconia-based restorations: An up to 9-year retrospective study

Objectives

The first objective of this study was to retrospectively evaluate zirconia-based restorations (ZBR). The second was to correlate failures with clinical parameters and to identify and to analyse chipping failures using fractographic analysis.

Methods

147 ZBR (tooth- and implant-supported crowns and fixed partial dentures (FPDs)) were evaluated after a mean observation period of 41.5 ± 31.8 months. Accessorily, zirconia implant abutments (n = 46) were also observed. The technical (USPHS criteria) and the biological outcomes of the ZBR were evaluated. Occlusal risk factors were examined: occlusal relationships, parafunctional habits, and the presence of occlusal nightguard. SEM fractographic analysis was performed using the intra-oral replica technique.

Results

The survival rate of crowns and FPDs was 93.2%, the success rate was 81.63% and the 9-year Kaplan–Meier estimated success rate was 52.66%. The chipping rate was 15% and the framework fracture rate was 2.7%. Most fractographic analyses revealed that veneer fractures originated from occlusal surface roughness. Several parameters were shown to significantly influence veneer fracture: the absence of occlusal nightguard (p = 0.0048), the presence of a ceramic restoration as an antagonist (p = 0.013), the presence of parafunctional activity (p = 0.018), and the presence of implants as support (p = 0.026). The implant abutments success rate was 100%.

Conclusions

The results of the present study confirm that chipping is the first cause of ZBR failure. They also underline the importance of clinical parameters in regards to the explanation of this complex problem. This issue should be considered in future prospective clinical studies.

Clinical significance

Practitioners can reduce chipping failures by taking into account several risk parameters, such as the presence of a ceramic restoration as an antagonist, the presence of parafunctional activity and the presence of implants as support. The use of an occlusal nightguard can also decrease failure rate.     

Sensitivity and discriminatory ability of the Ankylosing Spondylitis Disease Activity Score in patients treated with etanercept or sulphasalazine in the ASCEND trial

Objectives. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite clinical tool combining subjective and objective measures. Using data from the randomized double-blind Ankylosing Spondylitis Study Comparing Enbrel with Sulfasalazine Dosed Weekly (ASCEND) trial, we tested ASDAS validity and assessed its capacity to discriminate between treatment effects and change-from-baseline improvements. Methods. These post hoc analyses were conducted in patients who received etanercept (50?mg/week) or SSZ (≤3?g/day) for 16 weeks. The ASDAS was tested for its capacity to discriminate between those who achieved and did not achieve Assessment of Spondyloarthritis International Society (ASAS) partial remission and ASAS20. Week 16 adjusted treatment differences and effect sizes of improvement from baseline of 42 outcomes were calculated. Results. Means for ASDAS were less than half in patients with ASAS partial remission compared with patients without partial remission across the entire study population (1.2 vs 2.6; P?相似文献   

Factors Influencing Patients’ Willingness to Pay for New Technologies in Hip and Knee Implants

Rising implant prices and evolving technologies are important factors contributing to the increased cost of arthroplasty. Assessing how patients value arthroplasty, new technologies, and their perceived outcomes is critical in planning cost-effective care, as well as evaluating new-technologies. One hundred one patients undergoing arthroplasty took part in the survey. We captured demographics, spending practices, knowledge of implants, patient willingness to pay for implants, and preferences related to implant attributes. When patients were asked if they would be satisfied with “standard of care” prosthesis, 80% replied “no”. When asked if they would pay for a higher than “standard of care” prosthesis, 86% replied “yes”. The study demonstrated that patients, regardless of their socio-economic status, are not satisfied with standard of care implants when newer technologies are available, and they may be willing to share in the cost of their prosthesis. Patients also prefer the option to choose what they perceive to be a higher quality or innovative implant even if the “out of pocket” cost is higher.     

Increased parietal activity after training of interference control

Recent studies suggest that computerized cognitive training leads to improved performance in related but untrained tasks (i.e. transfer effects). However, most study designs prevent disentangling which of the task components are necessary for transfer. In the current study, we examined whether training on two variants of the adaptive dual n-back task would affect untrained task performance and the corresponding electrophysiological event-related potentials (ERPs). Forty three healthy young adults were trained for three weeks with a high or low interference training variant of the dual n-back task, or they were assigned to a passive control group. While n-back training with high interference led to partial improvements in the Attention Network Test (ANT), we did not find transfer to measures of working memory and fluid intelligence. ERP analysis in the n-back task and the ANT indicated overlapping processes in the P3 time range. Moreover, in the ANT, we detected increased parietal activity for the interference training group alone. In contrast, we did not find electrophysiological differences between the low interference training and the control group. These findings suggest that training on an interference control task leads to higher electrophysiological activity in the parietal cortex, which may be related to improvements in processing speed, attentional control, or both.