Endoscopic Versus Open Carpal Tunnel Release: An Umbrella Review and a Meta-analysis.

INTRODUCTION: Whether endoscopic carpal tunnel release (ECTR) versus open carpal tunnel release (OCTR) has superior outcomes remains a controversial topic. Therefore, we sought to perform an umbrella review and meta-analysis to compare ECTR and OCTR with regards to (1) postoperative functional ability, (2) operative outcomes, and (3) time to return to work. METHODS: A PubMed, Scopus, and Cochrane database search was conducted for all meta-analyses comparing ECTR and OCTR performed between 2000 and 2022 in accordance to PRISMA and Joanna Briggs Institute guidance for umbrella reviews. The primary outcomes were as follows: (1) functional ability-symptoms severity, postoperative grip strength, postoperative pinch strength, 2-point discrimination, and pain; (2) operative outcomes-operation time, total complications, nerve injury, and scar-related complication; and (3) time to return to work. Quality was assessed using the Assessment of Multiple Systematic Reviews. Pooled analysis was performed to compare several clinical outcome measures between groups, depending on the availability of data using Review Manager Version 5.2.11. RESULTS: A total of 9 meta-analyses were included, 5 were of high quality and 4 were moderate quality. For functional ability, ECTR was associated with better pinch strength after 3 months (0.70, 95% confidence interval [CI] = 0.00, 1.40, P = 0.05) and 6 months (0.77, 95% CI = 0.14, 1.40, P = 0.02, I2 = 84%). For return to work, OCTR was associated with longer return to work compared with ECTR (-10.89, 95% CI = -15.14, -6.64, P < 0.00001, I2= 83%). There were no significant differences between OCTR and ECTR in the hand function, symptom severity, grip strength, pain, operation time, and total complications. CONCLUSIONS: In an umbrella review and meta-analysis of ECTR versus OCTR, ECTR was associated with a higher pinch strength, and a shorter time to return to work. Differences in major complications, such as nerve injury, were unclear due to statistical inconsistency and bias.

Barriers toward xenotransplantation in Arab World.

Organ transplant is a crucial therapeutic strategy offering a life-saving and transformative medical intervention. It provides an opportunity to improve their quality of life and increase their lifespan. The shortage of organs remains a critical global challenge, leading to a prolonged waiting times for organ receivers, which contributes to an increase in morbidity and mortality rates. Hence, xenotransplantation offered a promising solution to the global shortage of organs through the use of animal organs, leading to an increase in donor availability, reducing waiting times, minimizing organ trafficking, improving genetic engineering advancements, and driving scientific innovation. Even though xenotransplantation has many benefits in the clinical setting, it has many barriers that are hindering its achievements and constraining its occurrence. Some barriers to xenotransplant are general, such as the immunological barrier, while others are specific to certain regions due to local causes. The Arab region exhibits disparities in clinical settings compared to the global context, marked by the huge economic crisis and a shortage of trained healthcare professionals. Considering the huge resources and advancements needed in the field of xenotransplantation, this review aims to explore the specific barriers toward xenotransplantation in the Arab countries, highlighting the challenges to overcome these barriers.

Autophagy regulates the release of exercise factors and their beneficial effects on spatial memory recall.

Exercise promotes learning and memory recall as well as rescues cognitive decline associated with aging. The positive effects of exercise are mediated by circulatory factors that predominantly increase Brain Derived Neurotrophic Factor (BDNF) signaling in the hippocampus. Identifying the pathways that regulate the release of the circulatory factors by various tissues during exercise and that mediate hippocampal Mus musculus Bdnf expression will allow us to harness the therapeutic potential of exercise. Here, we report that two weeks of voluntary exercise in male mice activates autophagy in the hippocampus by increasing LC3B protein levels (p = 0.0425) and that autophagy is necessary for exercise-induced spatial learning and memory retention (p < 0.001; exercise + autophagy inhibitor chloroquine CQ versus exercise). We place autophagy downstream of hippocampal BDNF signaling and identify a positive feedback activation between the pathways. We also assess whether the modulation of autophagy outside the nervous system is involved in mediating exercise's effect on learning and memory recall. Indeed, plasma collected from young exercise mice promote spatial learning (p = 0.0446; exercise versus sedentary plasma) and memory retention in aged inactive mice (p = 0.0303; exercise versus sedentary plasma), whereas plasma collected from young exercise mice that received the autophagy inhibitor chloroquine diphosphate failed to do so. We show that the release of exercise factors that reverse the symptoms of aging into the circulation is dependent on the activation of autophagy in young animals. Indeed, we show that the release of the exercise factor, beta-hydroxybutyrate (DBHB), into the circulation, is autophagy-dependent and that DBHB promotes spatial learning and memory formation (p = 0.0005) by inducing hippocampal autophagy (p = 0.0479). These results implicate autophagy in peripheral tissues and in the hippocampus in mediating the effects of exercise on learning and memory recall and identify DBHB as a candidate endogenous exercise factor whose release and positive effects are autophagy-dependent.

Exercise and Dietary Factors Mediate Neural Plasticity Through Modulation of BDNF Signaling.

The term "neural plasticity" was first used to describe non-pathological changes in neuronal structure. Today, it is generally accepted that the brain is a dynamic system whose morphology and function is influenced by a variety of factors including stress, diet, and exercise. Neural plasticity involves learning and memory, the synthesis of new neurons, the repair of damaged connections, and several other compensatory mechanisms. It is altered in neurodegenerative disorders and following damage to the central or peripheral nervous system. Understanding the mechanisms that regulate neural plasticity in both healthy and diseased states is of significant importance to promote cognition and develop rehabilitation techniques for functional recovery after injury. In this minireview, we will discuss the mechanisms by which environmental factors promote neural plasticity with a focus on exercise- and diet-induced factors. We will highlight the known circulatory factors that are released in response to exercise and discuss how all factors activate pathways that converge in part on the activation of BDNF signaling. We propose to harness the therapeutic potential of exercise by using BDNF as a biomarker to identify novel endogenous factors that promote neural plasticity. We also discuss the importance of combining exercise factors with dietary factors to develop a lifestyle pill for patients afflicted by CNS disorders.

Optimization and Application of a Multiplex Digital PCR Assay for the Detection of SARS-CoV-2 Variants of Concern in Belgian Influent Wastewater.

Since the beginning of the COVID-19 pandemic, the wastewater-based epidemiology (WBE) of SARS-CoV-2 has been used as a complementary indicator to follow up on the trends in the COVID-19 spread in Belgium and in many other countries. To further develop the use of WBE, a multiplex digital polymerase chain reaction (dPCR) assay was optimized, validated and applied for the measurement of emerging SARS-CoV-2 variants of concern (VOC) in influent wastewater (IWW) samples. Key mutations were targeted in the different VOC strains, including SΔ69/70 deletion, N501Y, SΔ241 and SΔ157. The presented bioanalytical method was able to distinguish between SARS-CoV-2 RNA originating from the wild-type and B.1.1.7, B.1.351 and B.1.617.2 variants. The dPCR assay proved to be sensitive enough to detect low concentrations of SARS-CoV-2 RNA in IWW since the limit of detection of the different targets ranged between 0.3 and 2.9 copies/µL. This developed WBE approach was applied to IWW samples originating from different Belgian locations and was able to monitor spatio-temporal changes in the presence of targeted VOC strains in the investigated communities. The present dPCR assay developments were realized to bring added-value to the current national WBE of COVID-19 by also having the spatio-temporal proportions of the VoC in presence in the wastewaters.

Engineering transcriptional regulation in Escherichia coli using an archaeal TetR-family transcription factor.

Synthetic biology requires well-characterized biological parts that can be combined into functional modules. One type of biological parts are transcriptional regulators and their cognate operator elements, which enable to either generate an input-specific response or are used as actuator modules. A range of regulators has already been characterized and used for orthogonal gene expression engineering, however, previous efforts have mostly focused on bacterial regulators. This work aims to design and explore the use of an archaeal TetR family regulator, FadRSa from Sulfolobus acidocaldarius, in a bacterial system, namely Escherichia coli. This is a challenging objective given the fundamental difference between the bacterial and archaeal transcription machinery and the lack of a native TetR-like FadR regulatory system in E. coli. The synthetic σ70-dependent bacterial promoter proD was used as a starting point to design hybrid bacterial/archaeal promoter/operator regions, in combination with the mKate2 fluorescent reporter enabling a readout. Four variations of proD containing FadRSa binding sites were constructed and characterized. While expressional activity of the modified promoter proD was found to be severely diminished for two of the constructs, constructs in which the binding site was introduced adjacent to the -35 promoter element still displayed sufficient basal transcriptional activity and showed up to 7-fold repression upon expression of FadRSa. Addition of acyl-CoA has been shown to disrupt FadRSa binding to the DNA in vitro. However, extracellular concentrations of up to 2 mM dodecanoate, subsequently converted to acyl-CoA by the cell, did not have a significant effect on repression in the bacterial system. This work demonstrates that archaeal transcription regulators can be used to generate actuator elements for use in E. coli, although the lack of ligand response underscores the challenge of maintaining biological function when transferring parts to a phylogenetically divergent host.

Current state of clinical trials regarding liver transplant rejection.

BACKGROUND: Liver transplant (LT) is the second most common transplant intervention. The rate of acute cellular rejection (ACR) is 15-25% after LT, while being higher in chronic rejection (CR). Clinical trials had a major role in getting more potent and selective immunosuppressive medications. Our study plays an important role by evaluating and tracking clinical trials related to liver transplant rejection, focusing on interventional therapeutic trials. METHODS: On October 28, we searched Clinicaltrials.gov for interventional clinical trials related to liver transplant rejection. A total of 27 clinical trials included in this study. Characteristics on each trial were collected, and availability of linked publications was searched using Medline/PubMed and Embase/Scopus. Content of publications was reviewed and main findings were summarized. RESULTS: Majority of trials were completed (15 out of 27). Eleven trials had between 11 and 50 participants, and 10 had above 100. The study duration was between 1 and 4 years for the majority of trials (16 trials), with an average of 3.77 years. Most of the trials were done in Europe/UK/Russia (n = 12). The results were provided in 9 trials but published in 4, showing the possible tolerogenic efficacy of MSC in liver transplantation, increased success of immunosuppression (IS) withdrawal after sirolimus addition, efficacy of Alemtuzumab, normal graft function and stability within 1 year of immunosuppression withdrawal. CONCLUSION: This study revealed a low number of trials, lack of variety in location and low publishing rates. The focus of trials was mainly towards side effects and safety of immunosuppressants, and their withdrawal. These trials reached results that must be built on to reach definitive guidelines and treatment strategies. This highlights the need for better management of human and financial resources, in order to reach new and more effective therapeutic strategies, leading to the decrease in rate of LTR.

The Arab Countries' Contribution to the Research of Neurodegenerative Disorders.

BACKGROUND: Neurodegenerative diseases are disorders in which nerve cells start to lose function due to different causes. Like many other illnesses, they are considered to be highly prevalent in the 22 Arabic-speaking countries known to constitute the Arab world. The two most prevalent neurodegenerative disorders are Alzheimer's disease and Parkinson's disease. AIM: The aim of this paper is to assess the amount of research dedicated to neurodegenerative diseases by the Arab countries during a 15-year period, between 2005 and 2019. METHODS: The number of publications by each Arab country as well as some non-Arab speaking countries was retrieved from PubMed. Publications in top 10 neuroscience journals were also tracked using the same method with each journal's name included. The numbers were then normalized with respect to the average population and average gross domestic product (GDP) in each country to eliminate bias. RESULTS: Arab countries were shown to contribute only 1,311 (0.774%) of the 169,330 articles published worldwide on neurodegenerative disorders. These 1,311 also constitute only 0.660% of the 198,869 Arab publications during the indicated period. Saudi Arabia had the highest contribution to these numbers with more than one-quarter the number of publications on neurodegenerative disorders. Approximately one-third of all neurodegenerative disease-related articles were associated with Alzheimer's disease, whereas one-fifth were related to Parkinson's disease. For the top 10 neuroscience journals, only a minimal contribution by Arab countries was noted. CONCLUSION: Although an increase in the number of articles by the Arab world was noted from 2013 onward, the contribution of the Arab countries on the subject to the number of publications still seems to be insufficient.