Search

Torque teno virus (TTV) is a promising novel marker for quantifying the immune function in solid organ recipients, whose diagnostic accuracy of acute rejection (AR) and infection after kidney transplantation (KT) has not been evaluated. We performed a systematic review and meta‐analysis to evaluate the diagnostic accuracy of TTV for discriminating AR and infection after KT. Eleven studies were included in the meta‐analysis. Seven studies focused on the diagnostic accuracy of TTV for AR, and the pooled analysis indicated patients who developed AR had a significant lower TTV viral DNA load (log10 copies/mL, MD: −0.74, p < 0.01). The pooled sensitivity, specificity, and area under the receiver operating characteristics curve for TTV in AR differentiation were 0.61 (0.36−0.82), 0.81 (0.64−0.91), and 0.79 (0.75−0.82), respectively. The overall diagnostic odds ratio (DOR) was 6.74 (2.60−17.50), positive likelihood ratio (PLR) was 3.22 (1.75−5.95), and negative likelihood ratio (NLR) was 0.48 (0.27−0.84), respectively. Similarly, seven studies investigated the infection discrimination and found that patients who subsequently developed posttransplant infection had higher plasma TTV DNA loads (log10 copies/mL, MD: 0.65; p < 0.01) than those remaiing infection‐free. Pooled sensitivity, specificity, and area under the receiver operating characteristics curve for TTV in infection differentiation were 0.72 (0.39−0.91), 0.57 (0.30−0.80), and 0.68 (0.64−0.72), respectively. The overall DOR was 3.28 (95% confidence interval [CI]: 2.08−5.17), the pooled PLR and NLR were 1.65 (95% CI: 1.25−2.18) and 0.50 (95% CI: 0.29−0.86), respectively. TTV might be a modest indicator for risk stratification of AR after KT, but it is a poor to discriminate posttransplant infection. [ABSTRACT FROM AUTHOR]

Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non‐pathogenic virus, has been proposed as marker of functional immunity: higher loads correspond to over‐immunosuppression, and lower loads to under‐immunosuppression. This review offers an overview of the current evidence of the association between TTV‐load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer‐reviewed articles were assessed investigating the association between TTV‐load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)‐tool was used to assess the risk of bias. Meta‐analysis with random‐effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV‐load was measured longitudinally, within the first 2 years post‐transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV‐load and infections, whereas 13 out of 15 reported an association between low TTV‐load and rejection. Meta‐analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03–1.32; HR: 1.05, 95% CI: 0.97–1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87–0.94; HR: 0.74, 95% CI: 0.71–0.76) per 1 log TTV‐load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta‐analysis indicates that blood TTV‐load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT. [ABSTRACT FROM AUTHOR]

Chronic hypobaric hypoxia in high‐altitude areas is closely related to the occurrence of many neurological diseases. Among these diseases, epilepsy is a common disease of the nervous system that is difficult to diagnose and treat, with a long treatment cycle. As of 2019, there were more than 70 million epilepsy patients worldwide, including 10 million in China. Studies have shown that chronic hypoxia promotes the occurrence and development of epilepsy, and elucidation of the relationship between chronic hypoxia and epilepsy is important for studying the pathogenesis of epilepsy and exploring the potential characteristics of epilepsy and new drug targets for epilepsy. In this article, we review the factors that may cause increased seizure susceptibility in chronic hypoxia and consider the potential relationship between chronic hypobaric hypoxia and seizure susceptibility in high‐altitude areas and prospects surrounding related research in the future. [ABSTRACT FROM AUTHOR]

New reliable biomarkers are needed to improve individual risk assessment for post‐transplant infection, acute graft rejection and other immune‐related complications after solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo‐HSCT). One promising strategy relies on the monitoring of replication kinetics of virome components as functional surrogate for the net state of immunosuppression. Torque Teno Virus (TTV) is a small, non‐enveloped, circular, single‐stranded DNA anellovirus with no attributable pathological effects. A major component of the human blood virome, TTV exhibits various features that facilitate its application as immune biomarker: high prevalence rates, nearly ubiquitous distribution, stable viral loads with little intra‐individual variability, insensitivity to antiviral drugs, and availability of commercial PCR assays for DNA quantification. The present review summarizes the available studies supporting the use of post‐transplant TTV viremia to predict patient and graft outcomes after SOT and allo‐HSCT. Taken together, this evidence suggests that high or increasing TTV DNA levels precede the occurrence of infectious complications in the SOT setting, whereas low or decreasing viral loads are associated with the development of acute rejection. The interpretation in allo‐HSCT recipients is further complicated by complex interplay with the underlying disease, conditioning regimen, and timing of recovery of lymphocyte counts, although TTV kinetics may act as a marker of immunological reconstitution at the early post‐transplant period. The standardization of PCR methods and reporting units for TTV DNAemia and the results from ongoing interventional trials evaluating a TTV load‐guided strategy to adjust immunosuppressive therapy are achievements expected in the coming years. [ABSTRACT FROM AUTHOR]

Natural polyphenols are being tested both in preclinical and clinical settings for the treatment of different neurological disorders. The article describes the outcome of three polyphenols, resveratrol, epigallocatechin gallate, and quercetin, in preclinical animal models of epilepsy (both acute and chronic) and epileptogenesis. In theory, the antioxidant and neuroprotective properties of these natural polyphenols might be valuable in the management of acute seizures and the prevention of epileptogenesis. It is fascinating to observe that these polyphenols have a capacity to alter various signaling processes involved in the pathogenesis of epilepsy. The antiepileptic or antiseizure potential with these molecules delivers a mixed outcome. Some studies have demonstrated the usefulness of these molecules in preclinical models of epilepsy; however, contrary to the findings also exist. These molecules have poor bioavailability that may remain as the limiting factor in their clinical effects. The use of nanotechnology and other techniques have been tested to enhance bioavailability and brain penetration. There are no randomized double-blinded clinical studies establishing their antiepileptic effects in humans. It is concluded that more preclinical mechanism-based studies are needed to deliver a more certain picture regarding the use of natural polyphenols in the treatment of epilepsy. [ABSTRACT FROM AUTHOR]

An author index for the Volume 23 , Supplement 2 of the June 2016 issue of the "European Journal of Neurology" is presented.

SUMMARY For real-time and embedded systems, limiting the consumption of time and memory resources is often an important part of the requirements. Being able to predict bounds on the consumption of such resources during the development process of the code can be of great value. In this paper, we focus mainly on memory-related bounds. Recent research results have advanced the state of the art of resource consumption analysis. In this paper, we present a toolset that makes it possible to apply these research results in practice for (real-time) systems enabling JAVA developers to analyse symbolic loop bounds, symbolic bounds on heap size and both symbolic and numeric bounds on stack size. We describe which theoretical additions were needed in order to achieve this. We give an overview of the capabilities of the RESANA (Radboud University Nijmegen, The Netherlands) toolset that is the result of this effort. The toolset can not only perform generally applicable analyses, but it also contains a part of the analysis that is dedicated to the developers' (real-time) virtual machine, such that the results apply directly to the actual development environment that is used in practice. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]