Association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Egyptian children and adolescents.

BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.

Induction of tomato plant biochemical immune responses by the synthesized zinc oxide nanoparticles against wilt-induced Fusarium oxysporum.

The current study used zinc oxide nanoparticles (ZnO-NPs) to protect the tomato plant against Fusarium wilt. Gamma rays were used to synthesize ZnO-NPs, and the designed ZnO-NPs were characterized using high-resolution transmission electron microscopy (HRTEM), scanning electron microscope (SEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDX), and ultraviolet-visible (UV-Vis.) spectroscopy. We found that the 20 kGy dose is the most effective for ZnO-NPs synthesis, with the highest O.D. = 1.65 (diluted 3 times) at 400 nm. The scale of ZnO-NPs ranged from 10.45 to 75.25 nm with an average diameter of 40.20 nm. The results showed that the designed ZnO-NPs showed promising activity as a potent inducer of plant physiological immunity against Fusarium wilt disease. Likewise, ZnO-NPs significantly reduced the wilt disease symptoms incidence by 28.57% and high protection by 67.99% against F. oxysporum. Additionally, infected tomato plants treated with ZnO-NPs show improved shoot length (44.71%), root length (40.0%), number of leaves (60.0 %), chlorophyll a (36.93%), chlorophyll b (16.46%), and carotenoids (21.87%) versus infected plants. Notably, in the treatment of tomato seedlings, the beneficial effects of ZnO-NPs extended to increase not only in osmolyte contents but also total phenol contents in comparison with control plants. In conclusion, the designed ZnO-NPs can control Fusarium wilt disease and improve and develop biochemical compounds responsible for defense against fusarial infection.

Chitosan-enclosed SLN improved SV-induced hepatocellular cell carcinoma death by modulation of IQGAP gene expression, JNK, and HDAC activities.

BACKGROUND: Hepatocellular carcinoma (HCC) is a global life-threatening problem and therapeutic interventions are still encountered. IQGAP genes are involved in HCC oncogenesis. The modulatory effect of statins on the expression of IQGAP genes is still unclear. This study aims to study the effect of free SV and chitosan (CS) decorated simvastatin (SV) loaded solid lipid nanoparticles (C-SV-SLNs) on HCC mortality. METHODS AND RESULTS: Plain, SV-SLN, and C-SV- SLN were prepared and characterized in terms of particle size (PS), zeta potential (ZP), and polydispersity index (PDI). The biosafety of different SLN was investigated using fresh erythrocytes, moreover, cytotoxicity was investigated using HepG2 cell lines. The effect of SLNs on IQGAPs gene expression as well as JNK, HDAC6, and HDAC8 activity was investigated using PCR and MOE-docking. The current results displayed that SV-SLNs have nanosized, negative ZP and are homogenous, CS decoration shifts the ZP of SLN into cationic ZP. Furthermore, all SLNs exhibited desirable biosafety in terms of no deleterious effect on erythrocyte integrity. SV solution and SV-SLN significantly increase the mortality of HepG2 compared to undertreated cells, however, the effect of SV-SLN is more pronounced compared to free SV. Remarkably, C-SV-SLN elicits high HepG2 cell mortality compared to free SV and SV-SLN. The treatment of HepG2 cells with SV solution, SV-SLN, or C-SV-SLN significantly upregulates the IQGAP2 gene with repression of IQGAP1 and IQGAP3 genes. MOE-docking studies revealed both SV and tenivastatin exhibit interactions with the active sites of JNK, HDAC6, and HDAC8. Moreover, tenivastatin exhibited greater interactions with magnesium and zinc compared to SV. CONCLUSIONS: This research provides novel insights into the therapeutic potential of SV, SV-SLN and C-SV-SLNs in HCC treatment, modulating critical signaling cascades involving IQGAPs, JNK, and HDAC. The development of C-SV-SLNs presents a promising strategy for effective HCC therapy.

Dulaglutide reduces oxidative DNA damage and hypermethylation in the somatic cells of mice fed a high-energy diet by restoring redox balance, inflammatory responses, and DNA repair gene expressions.

Obesity is an established risk factor for numerous malignancies, although it remains uncertain whether the disease itself or weight-loss drugs are responsible for a greater predisposition to cancer. The objective of the current study was to determine the impact of dulaglutide on genetic and epigenetic DNA damage caused by obesity, which is a crucial factor in the development of cancer. Mice were administered a low-fat or high-fat diet for 12 weeks, followed by a 5-week treatment with dulaglutide. Following that, modifications of the DNA bases were examined using the comet assay. To clarify the underlying molecular mechanisms, oxidized and methylated DNA bases, changes in the redox status, levels of inflammatory cytokines, and the expression levels of some DNA repair genes were evaluated. Animals fed a high-fat diet exhibited increased body weights, elevated DNA damage, oxidation of DNA bases, and DNA hypermethylation. In addition, obese mice showed altered inflammatory responses, redox imbalances, and repair gene expressions. The findings demonstrated that dulaglutide does not exhibit genotoxicity in the investigated conditions. Following dulaglutide administration, animals fed a high-fat diet demonstrated low DNA damage, less oxidation and methylation of DNA bases, restored redox balance, and improved inflammatory responses. In addition, dulaglutide treatment restored the upregulated DNMT1, Ogg1, and p53 gene expression. Overall, dulaglutide effectively maintains DNA integrity in obese animals. It reduces oxidative DNA damage and hypermethylation by restoring redox balance, modulating inflammatory responses, and recovering altered gene expressions. These findings demonstrate dulaglutide's expediency in treating obesity and its associated complications.

Protective role of iron oxide nanocomposites on disease index, and biochemical resistance indicators against Fusarium oxysporum induced-cucumber wilt disease: In vitro, and in vivo studies.

Recently nanocomposites have become a super-growth inducers as well as vital antifungal agents, which enhance plant growth and suppress plant diseases. A new strategy regarding the fabrication of humic acid (H) and boron (B) conjugated Fe2O3 nanocomposites was performed. Fe2O3 NP-B and Fe2O3 NP-H were synthesized in the presence of gamma-rays (as a direct reducing agent). Gamma-rays provoked reduction of metal ions due to the liberated reducing electrons, (e-aq), in aqueous solutions which can be considered as a direct reduction. Antifungal potential against Fusarium oxysporum, the causative agent of wilt disease in cucumber was determined. Disease index percent, metabolic resistance indicators in cucumber plant as response to promotion of systemic resistance (SR) were recorded. Results illustrated that both Fe2O3 NPs-B and Fe2O3 NPs-H nanocomposites had antifungal activity against F. oxysporumin vitro as well as in vivo. Results revealed that minimum inhibitory concentrations of Fe2O3 NPs-B and Fe2O3 NPs-H nanocomposites were 0.25 and 0.125 mM, respectively. Application of Fe2O3 NPs-B (0.25 mM) and Fe2O3 NPs-H (0.125 mM) appeared highly reduced the cucumber wilt disease symptoms incidence caused by F. oxysporum, and recorded disease severity by 83.33%. Fe2O3 NPs-B was the best treatment reducing disease indexes by 20.83% and gave highly protection against wilt disease by 75.0% and came next Fe2O3 NPs-H which reduced disease indexes by 25% and gave 69.99% protection against disease. Fe2O3 NPs-B and Fe2O3 NPs-H treatments improved morphological traits, photosynthetic pigments, osmolytes, total phenol and antioxidant enzymes activities in both infected and non-infected plants. The beneficial effects of the synthesized Fe2O3 NPs-B and Fe2O3 NPs-H nanocomposites were extended to increase not only the total phenol, and total soluble protein contents but also the activities of peroxidase (POD), and polyphenol oxidase (PPO) enzymes of the healthy and infected cucumber plants in comparison with control.

Ziziphus spina-christi extract-stabilized novel silver nanoparticle synthesis for combating Fusarium oxysporum-causing pepper wilt disease: in vitro and in vivo studies.

The novelty of the present study is studying the ability of aqueous Ziziphus spina-christi leaves' extract (ZSCE) to produce eco-friendly and cost-effective silver nanoparticles (Ag NPs) against Fusarium wilt disease. Phytochemical screening of ZSCE by HPLC showed that they contain important antimicrobial substances such as Rutin, Naringin, Myricetin, Quercetin, Kaempferol, Hesperidin, Syringeic, Eugenol, Pyrogallol, Gallic and Ferulic. Characterization methods reveal a stable Ag NPs with a crystalline structure, spherical in shape with average particle size about 11.25 nm. ZSCE and Ag NPs showed antifungal potential against F. oxysporum at different concentrations with MIC of Ag NPs as 0.125 mM. Ag NPs treatment was the most effective, as it gave the least disease severity (20.8%) and the highest protection rate (75%). The application of ZSCE or Ag NPs showed a clear recovery, and its effectiveness was not limited for improving growth and metabolic characteristics only, but also inducing substances responsible for defense against pathogens and activating plant immunity (such as increasing phenols and strong expression of peroxidase and polyphenol oxidase as well as isozymes). Owing to beneficial properties such as antifungal activity, and the eco-friendly approach of cost and safety, they can be applied in agricultural field as novel therapeutic nutrients.

Bioactive compounds and biomedical applications of endophytic fungi: a recent review.

Human life has been significantly impacted by the creation and spread of novel species of antibiotic-resistant bacteria and virus strains that are difficult to manage. Scientists and researchers have recently been motivated to seek out alternatives and other sources of safe and ecologically friendly active chemicals that have a powerful and effective effect against a wide variety of pathogenic bacteria as a result of all these hazards and problems. In this review, endophytic fungi and their bioactive compounds and biomedical applications were discussed. Endophytes, a new category of microbial source that can produce a variety of biological components, have major values for study and broad prospects for development. Recently, endophytic fungi have received much attention as a source for new bioactive compounds. In addition, the variety of natural active compounds generated by endophytes is due to the close biological relationship between endophytes and their host plants. The bioactive compounds separated from endophytes are usually classified as steroids, xanthones, terpenoids, isocoumarins, phenols, tetralones, benzopyranones and enniatines. Moreover, this review discusses enhancement methods of secondary metabolites production by fungal endophytes which include optimization methods, co-culture method, chemical epigenetic modification and molecular-based approaches. Furthermore, this review deals with different medical applications of bioactive compounds such as antimicrobial, antiviral, antioxidant and anticancer activities in the last 3 years.

Assessment of the potency and effectiveness of a heptavalent oil-adjuvanted (ISA 206) foot-and-mouth disease vaccine in Egypt.

Foot-and-mouth disease (FMD) is a serious highly contagious viral disease affecting all cloven-hoofed animals, and outbreaks can have a severe economic impact. An inactivated heptavalent oil-adjuvanted FMD vaccine (Aphtovac-7, MEVAC) was prepared from the foot-and-mouth disease virus (FMDV) strains A-Iran05, A-Africa-IV, O-PanAsia2, O-Manisa, O-EA3, SAT-2 Gharbia, and SAT-2 LIB-12. The vaccine potency and effectiveness were evaluated in three groups of 6- to 8-month-old calves and 200 adult dairy cattle under field conditions. All animals were vaccinated with the vaccine preparation, and the three groups of calves were challenged after 28 days by intradermolingual inoculation with 104 50% tissue culture infective dose (TCID50) of FMDV serotype A, O, or SAT-2. Mock-vaccinated calves (two per group) served as unvaccinated controls during the challenge test. Adult dairy cattle were tested for seroconversion using a virus neutralization test at 30, 60, and 120 days post-vaccination. All calves displayed complete protection against challenge with the different serotypes of FMDV when compared to the control groups. Serum samples collected after the primary and booster immunizations at 30 days post-vaccination contained high titers of protective antibodies (≥ 1/32; i.e. 1.5 log10). Antibodies persisted until the end of the study period (120 days), with a peak value around 60 days post-vaccination. The heptavalent FMD vaccine preparation was found to be potent and capable of providing a protective immune response under both experimental and field conditions.

Rituximab alleviates increased disomic sperm in DBA/1J mouse models of rheumatoid arthritis via restoration of redox imbalance.

Compared to the general population, patients with arthritis have a higher risk of fertility abnormalities, which have deleterious effects on both reproductive function and pregnancy outcomes, especially in patients wishing to conceive. These may be due to the disease itself or those of drug therapies. Despite the increasing use of rituximab in arthritis, limited data are available on its potential to induce aneuploidy in germ cells. Therefore, the aim of the current investigation was to determine if repeated treatment with rituximab affects the incidence of aneuploidy and redox imbalance in arthritic mouse sperm. Mice were treated with 250 mg/kg rituximab once weakly for 3 weeks, and then sperm were sampled 22 days after the last dose of rituximab. Fluorescence in situ hybridization assay with chromosome-specific DNA probes was used to evaluate the disomic/diploid sperm. Our results showed that rituximab had no aneuploidogenic effect on the meiotic stage of spermatogenesis. Conversely, arthritis induced a significantly high frequency of disomy, and treatment of arthritic mice with rituximab reduced the increased levels of disomic sperm. The occurrence of total diploidy was not significantly different in all groups. Reduced glutathione and8-hydroxydeoxyguanosine, markers of oxidative stress were significantly altered in arthritic animals, while rituximab treatment restored these changes. Additionally, arthritis severity was reduced after rituximab treatment. We conclude that rituximab may efficiently alleviate the arthritis-induced effects on male meiosis and avert the higher risk of abnormal reproductive outcomes. Therefore, treating arthritic patients with rituximab may efficiently inhibit the transmission of genetic anomalies induced by arthritis to future generations.

A comparative study between staple line reinforcement during laparoscopic sleeve gastrectomy and no reinforcement: an Egyptian experience.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become an increasingly popular bariatric procedure. LSG still conveys some risks, including early staple line complications such as bleeding and leaks. It has been proposed that staple line complications can be reduced by staple line reinforcement (SLR). This study aimed to compare the short-term efficacy and safety of the SLR during LSG by oversewing versus no SLR in an Egyptian cohort over a period of 11 years. PATIENTS AND METHODS: This is a retrospective study that analyzed data from patients undergoing LSG by the same surgeon over a period of 11 years. The patients' early postoperative complications were compared according to performing SLR. RESULTS: The SLR group showed significantly longer surgery time (p = 0.021) and a lower rate of postoperative bleeding (p = 0.027). All leakage cases occurred in the non-SLR group (0.7% vs. 0.0%) without statistical significance (p = 0.212). The two mortality cases occurred in the non-SLR group. The LOS was comparable in the two groups (p = 0.289). CONCLUSION: This study confirms the short-term benefits of SLR by oversewing during LSG in terms of a lower incidence of 30-day morbidity, particularly bleeding, and lower rates of reoperation, with a clinically questionable longer operation time.

A Facile Synthesis and Molecular Characterization of Certain New Anti-Proliferative Indole-Based Chemical Entities.

Cancer cells frequently develop drug resistance, which leads to chemotherapeutic treatment failure. Additionally, chemotherapies are hindered by their high toxicity. Therefore, the development of new chemotherapeutic drugs with improved clinical outcomes and low toxicity is a major priority. Several indole derivatives exhibit distinctive anti-cancer mechanisms which have been associated with various molecular targets. In this study, target compounds 4a-q were obtained through the reaction of substituted benzyl chloride with hydrazine hydrate, which produces benzyl hydrazine. Subsequently, the appropriate substituted benzyl hydrazine was allowed to react with 1H-indole-2-carboxylic acid or 5-methoxy-1H-indole-2-carboxylic acid using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as a coupling agent. All compounds exhibited cytotoxicity in three cell lines, namely, MCF-7, A549, and HCT. Compound 4e exhibited the highest cytotoxicity, with an average IC50 of 2 µM. Moreover, a flow cytometry study revealed a significantly increased prevalence of Annexin-V and 7-AAD positive cell populations. Several derivatives of 4a-q showed moderate to high cytotoxicity against the tested cell lines, with compound 4e having the highest cytotoxicity, indicating that it may possess potential apoptosis-inducing capabilities.

Chitosan-graphene quantum dot based active film as smart wound dressing.

Graphene quantum dots (GQDs), are biocompatible materials, with mechanical strength and stability. Chitosan, has antibacterial and anti-inflammatory properties, and biocompatibility. Wound healing is a challenging process especially in chronic diseases and infection. In this study, films consisting of chitosan and graphene quantum dots were developed for application in infected wounds. The chitosan-graphene films were prepared in the acidic solution followed by slow solvent evaporation and drying. The chitosan-graphene films were characterized by the scanning electron microscopy, x-ray diffraction, atomic force microscopy, Raman spectroscopy and thermogravimetric analysis. The films' was evaluated by the wound healing assays, hemolytic potential, and nitrite production, cytokine production and swelling potential. The obtained films were flexible and well-structured, promoting cell migration, greater antibacterial activity, lower hemolytic activity, and maintaining wound moisture. Our data suggested that the use of graphene quantum dot-containing chitosan films would be an efficient and promising way in combating wounds.

Mesoporous silica nanoparticles: Their potential as drug delivery carriers and nanoscavengers in Alzheimer's and Parkinson's diseases.

Worldwide, populations face significant burdens from neurodegenerative disorders (NDDs), especially Alzheimer's and Parkinson's diseases. Although there are many proposed etiologies for neurodegenerative disorders, including genetic and environmental factors, the exact pathogenesis for these disorders is not fully understood. Most patients with NDDs are given lifelong treatment to improve their quality of life. There are myriad treatments for NDDs; however, these agents are limited by their side effects and difficulty in passing the blood-brain barrier (BBB). Furthermore, the central nervous system (CNS) active pharmaceuticals could offer symptomatic relief for the patient's condition without providing a complete cure or prevention by targeting the disease's cause. Recently, Mesoporous silica nanoparticles (MSNs) have gained interest in treating NDDs since their physicochemical properties and inherent ability to pass BBB make them possible drug carriers for several drugs for NDDs treatment. This paper provides insight into the pathogenesis and treatment of NDDs, along with the recent advances in applying MSNs as fibril scavengers. Moreover, the application of MSNs-based formulations in enhancing or sustaining drug release rate, and brain targeting via their responsive release properties, besides the neurotoxicity of MSNs, have been reviewed.

Presentation and outcomes of acute appendicitis during COVID-19 pandemic: lessons learned from the Middle East-a multicentre prospective cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a striking impact on healthcare services in the world. The present study aimed to investigate the impact of the COVID-19 pandemic on the presentation management and outcomes of acute appendicitis (AA) in different centers in the Middle East. METHODS: This multicenter cohort study compared the presentation and outcomes of patients with AA who presented during the COVID-19 pandemic in comparison to patients who presented before the onset of the pandemic. Demographic data, clinical presentation, management strategy, and outcomes were prospectively collected and compared. RESULTS: Seven hundred seventy-one patients presented with AA during the COVID pandemic versus 1174 in the pre-COVID period. Delayed and complex presentation of AA was significantly more observed during the pandemic period. Seventy-six percent of patients underwent CT scanning to confirm the diagnosis of AA during the pandemic period, compared to 62.7% in the pre-COVID period. Non-operative management (NOM) was more frequently employed in the pandemic period. Postoperative complications were higher amid the pandemic as compared to before its onset. Reoperation and readmission rates were significantly higher in the COVID period, whereas the negative appendicectomy rate was significantly lower in the pandemic period (p = 0.0001). CONCLUSION: During the COVID-19 pandemic, a remarkable decrease in the number of patients with AA was seen along with a higher incidence of complex AA, greater use of CT scanning, and more application of NOM. The rates of postoperative complications, reoperation, and readmission were significantly higher during the COVID period.

In-service teachers' TPACK development through an adaptive e-learning environment (ALE).

Due to the effects of the COVID-19 crisis on educational institutions, schools had to close and switch to online education. Training in-service teachers to incorporate and utilize technology as part of Internet-based instructions was a challenge and pressing necessity. TPACK is an essential framework for comprehending how teachers employ technology in teaching. Despite the significance of adaptive learning environments in recent years, research has not addressed how to use these environments to improve the TPACK of in-service teachers, particularly during crises. Consequently, our objective was to design an adaptive learning environment that provides in-service math, science, and English teachers with substantial and continuing support for each TPACK component. A total of 173 in-service teachers were divided into two groups: an experimental group of 83 who used adaptive learning and a control group of 90 who used Zoom techniques. TPACK questionnaires were administered before and after the experiment. The experimental group improved TPACK more than the control group. All teachers believed that adaptive learning training helped them to build technology-integrated lesson plans. This study provides ideas and practices for developing an adaptive learning environment for the in-service teachers' TPACK development. The challenges to adaptive learning environments have been highlighted, identifying the potential for future investigations.

New Family of Carbohydrate-Binding Modules Defined by a Galactosyl-Binding Protein Module from a Cellvibrio japonicus Endo-Xyloglucanase.

Carbohydrate-binding modules (CBMs) are usually appended to carbohydrate-active enzymes (CAZymes) and serve to potentiate catalytic activity, for example, by increasing substrate affinity. The Gram-negative soil saprophyte Cellvibrio japonicus is a valuable source for CAZyme and CBM discovery and characterization due to its innate ability to degrade a wide array of plant polysaccharides. Bioinformatic analysis of the CJA_2959 gene product from C. japonicus revealed a modular architecture consisting of a fibronectin type III (Fn3) module, a cryptic module of unknown function (X181), and a glycoside hydrolase family 5 subfamily 4 (GH5_4) catalytic module. We previously demonstrated that the last of these, CjGH5F, is an efficient and specific endo-xyloglucanase (M. A. Attia, C. E. Nelson, W. A. Offen, N. Jain, et al., Biotechnol Biofuels 11:45, 2018, https://doi.org/10.1186/s13068-018-1039-6). In the present study, C-terminal fusion of superfolder green fluorescent protein in tandem with the Fn3-X181 modules enabled recombinant production and purification from Escherichia coli. Native affinity gel electrophoresis revealed binding specificity for the terminal galactose-containing plant polysaccharides galactoxyloglucan and galactomannan. Isothermal titration calorimetry further evidenced a preference for galactoxyloglucan polysaccharide over short oligosaccharides comprising the limit-digest products of CjGH5F. Thus, our results identify the X181 module as the defining member of a new CBM family, CBM88. In addition to directly revealing the function of this CBM in the context of xyloglucan metabolism by C. japonicus, this study will guide future bioinformatic and functional analyses across microbial (meta)genomes. IMPORTANCE This study reveals carbohydrate-binding module family 88 (CBM88) as a new family of galactose-binding protein modules, which are found in series with diverse microbial glycoside hydrolases, polysaccharide lyases, and carbohydrate esterases. The definition of CBM88 in the carbohydrate-active enzymes classification (http://www.cazy.org/CBM88.html) will significantly enable future microbial (meta)genome analysis and functional studies.

Repetitive Transcranial Magnetic Stimulation for Treating Chronic Neuropathic Pain: a Systematic Review.

Given pharmacological interventions' limited efficacy and abundance of its adverse effects, the repetitive transcranial magnetic stimulation (rTMS) is considered a viable non-invasive option for managing chronic neuropathic pain of different origins with promising outcomes. PURPOSE OF REVIEW: The provision of a systematic review of current literature on rTMS for managing chronic neuropathic pain of different origins, and assess its efficacy and outcomes, highlighting the need for standard protocols for utilizing rTMS. RECENT FINDINGS: Variable stimulation modalities were trialed targeting the M1, DLPFC, and somatosensory cortices S1 and S2. The M1 yielded the best results in 11 of the studies. Frequency of stimulation was variable; however, optimal outcome was with higher frequencies ranging 10-20 Hz rather than low-frequency 1 Hz. Repetitive TMS can produce significant relief from chronic neuropathic pain. The lack of standard methods for rTMS, stimulatory parameters, and target stimulation site precludes concluding the optimal modality for stimulation. The practical algorithm by Lefaucheur and Nguyen (Neurophysiol Clin. 49(4):301-7, 2019) can guide setting standardized algorithms for rTMS. Defining optimal stimulation sites, frequencies, and pulses to maximize patient's pain relief and minimize required rTMS sessions requires further research.

Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent.

Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson's disease, Alzheimer's disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials.

Impact of referral pattern and timing of repair on surgical outcome after reconstruction of post-cholecystectomy bile duct injury: A multicenter study.

BACKGROUND: Bile duct injury (BDI) after cholecystectomy remains a significant surgical challenge. No guideline exists to guide the timing of repair, while few studies compare early versus late repair BDI. This study aimed to analyze the outcomes in patients undergoing immediate, intermediate, and delayed repair of BDI. METHODS: We retrospectively analyzed 412 patients with BDI from March 2015 to January 2020. The patients were divided into three groups based on the time of BDI reconstruction. Group 1 underwent an immediate reconstruction (within the first 72 hours post-cholecystectomy, n = 156); group 2 underwent an intermediate reconstruction (from 4 days to 6 weeks post-cholecystectomy, n = 75), and group 3 underwent delayed reconstruction (after 6 weeks post-cholecystectomy, n = 181). RESULTS: Patients in group 2 had significantly more early complications including anastomotic leakage and intra-abdominal collection and late complications including anastomotic stricture and secondary liver cirrhosis compared with groups 1 and 3. Favorable outcome was observed in 111 (71.2%) patients in group 1, 31 (41.3%) patients in group 2, and 157 (86.7%) patients in group 3 (P = 0.0001). Multivariate analysis identified that complete ligation of the bile duct, level E1 BDI and the use of external stent were independent factors of favorable outcome in group 1, the use of external stent was an independent factor of favorable outcome in group 2, and level E4 BDI was an independent factor of unfavorable outcome in group 3. Transected BDI and level E4 BDI were independent factors of unfavorable outcome. CONCLUSIONS: Favorable outcomes were more frequently observed in the immediate and delayed reconstruction of post-cholecystectomy BDI. Complete ligation of the bile duct, level E1 BDI and the use of external stent were independent factors of a favorable outcome.

Heterogeneity Aware Two-Stage Group Testing.

Group testing refers to the process of testing pooled samples to reduce the total number of tests. Given the current pandemic, and the shortage of test supplies for COVID-19, group testing can play a critical role in time and cost efficient diagnostics. In many scenarios, samples collected from users are also accompanied with auxiliary information (such as demographics, history of exposure, onset of symptoms). Such auxiliary information may differ across patients, and is typically not considered while designing group testing algorithms. In this paper, we abstract such heterogeneity using a model where the population can be categorized into clusters with different prevalence rates. The main result of this work is to show that exploiting knowledge heterogeneity can further improve the efficiency of group testing. Motivated by the practical constraints and diagnostic considerations, we focus on two-stage group testing algorithms, where in the first stage, the goal is to detect as many negative samples by pooling, whereas the second stage involves individual testing to detect any remaining samples. For this class of algorithms, we prove that the gain in efficiency is related to the concavity of the number of tests as a function of the prevalence. We also show how one can choose the optimal pooling parameters for one of the algorithms in this class, namely, doubly constant pooling. We present lower bounds on the average number of tests as a function of the population heterogeneity profile, and also provide numerical results and comparisons.