Efficacy and utility of antifibrinolytics in pediatric spine surgery: a systematic review and network meta-analysis.

Antifibrinolytics have gained increasing attention in minimizing blood loss and mitigating the risks associated with massive transfusions, including infection and coagulopathy in pediatric patients undergoing spine surgery. Nevertheless, the selection of optimal agent is still a matter of debate. We aim to review the utility of these agents and compare the efficacy of antifibrinolytics in pediatric and adolescent spine surgeries. A comprehensive search was performed in Scopus, Web of Science, and MEDLINE databases for relevant works. Studies providing quantitative data on predefined outcomes were included. Primary outcome was perioperative bleeding between the groups. Secondary outcomes included transfusion volume, rate of complications, and operation time. Twenty-eight studies were included in the meta-analysis incorporating 2553 patients. The use of Tranexamic acid (RoM: 0.71, 95%CI: [0.62-0.81], p < 0.001, I2 = 88%), Aprotinin (RoM: 0.54, 95%CI: [0.46-0.64], p < 0.001, I2 = 0%), and Epsilon-aminocaproic acid (RoM: 0.71, 95%CI: [0.62-0.81], p < 0.001, I2 = 60%) led to a 29%, 46%, and 29% reduction in perioperative blood loss, respectively. Network meta-analysis revealed higher probability of efficacy with Tranexamic acid compared to Epsilon-aminocaproic acid (P score: 0.924 vs. 0.571). The rate of complications was not statistically different between each two antifibrinolytic agent or antifibrinolytics compared to placebo or standard of care. Our network meta-analysis suggests a superior efficacy of all antifibrinolytics compared to standard of care/placebo in reducing blood loss and transfusion rate. Further adequately-powered randomized clinical trials are recommended to reach definite conclusion on comparative performance of these agents and to also provide robust objective assessments and standardized outcome data and safety profile on antifibrinolytics in pediatric and adolescent pediatric surgeries.

EBV associated T- and NK-cell lymphoproliferative diseases: A comprehensive overview of clinical manifestations and novel therapeutic insights.

EBV is a ubiquitous virus that infects nearly all people around the world. Most infected people are asymptomatic and do not show serious sequelae, while others may develop Epstein-Barr virus (EBV)-positive T and NK-cell lymphoproliferations characterised by EBV-infected T or NK cells. These disorders are more common in Asian and Latin American people, suggesting genetic predisposition as a contributing factor. The revised WHO classification classifies the lymphoproliferative diseases as: extranodal NK/T-cell lymphoma nasal type (ENKTL), aggressive NK-cell leukemia (ANKL), primary EBV-positive nodal T or NK cell lymphoma (NNKTL), systemic EBV-positive T-cell lymphoproliferative disease of childhood (STCLC), systemic chronic active EBV infection (sys CAEBV), hydroa-vacciniforme (HV) and severe mosquito bite allergy (SMBA). Recent advances in the molecular pathogenesis of these diseases have led to the development of new therapeutic strategies. Due to the infrequency of the diseases and broad clinicopathological overlap, the diagnosis and classification are challenging for both clinicians and pathologists. In this article, we aim to review the recent pathological findings which can be helpful for designing new drugs, clinical presentations and differential diagnoses, and suggested therapeutic interventions to provide a better understanding of these rare disorders.

A global study of the association of cesarean rate and the role of socioeconomic status in neonatal mortality rate in the current century.

INTRODUCTION: Caesarean section (C/S) rates have significantly increased across the world over the past decades. In the present population-based study, we sought to evaluate the association between C/S and neonatal mortality rates. MATERIAL AND METHODS: This retrospective ecological study included longitudinal data of 166 countries from 2000 to 2015. We evaluated the association between C/S rates and neonatal mortality rate (NMR), adjusting for total fertility rate, human development index (HDI), gross domestic product (GDP) percentage, and maternal age at first childbearing. The examinations were also performed considering different geographical regions as well as regions with different income levels. RESULTS: The C/S rate and NMR in the 166 included countries were 19.97% ± 10.56% and 10 ± 10.27 per 1000 live birth, respectively. After adjustment for confounding variables, C/S rate and NMR were found correlated (r = -1.1, p < 0.001). Examination of the relationship between C/S rate and NMR in each WHO region resulted in an inverse correlation in Africa (r = -0.75, p = 0.005), Europe (r = -0.12, p < 0.001), South-East Asia (r = -0.41, p = 0.01), and Western Pacific (r = -0.13, p = 0.02), a direct correlation in America (r = 0.06, p = 0.04), and no correlation in Eastern Mediterranean (r = 0.01, p = 0.88). Meanwhile, C/S rate and NMR were inversely associated in regions with upper-middle (r = -0.15, p < 0.001) and lower-middle (r = -0.24, p < 0.001) income levels, directly associated in high-income regions (r = 0.02, p = 0.001), and not associated in low-income regions (p = 0.13). In countries with HDI below the centralized value of 1 (the real value of 0.9), the correlation between C/S rate and NMR was negative while it was found positive in countries with HDI higher than the mentioned cut-off. CONCLUSIONS: This study indicated that NMR associated with C/S is dependent on various socioeconomic factors such as total fertility rate, HDI, GDP percentage, and maternal age at first childbearing. Further attentions to the socioeconomic status are warranted to minimize the NMR by modifying the C/S rate to the optimum cut-off.

Hepatitis C virus DNA vaccines: a systematic review.

BACKGROUND: Vaccination against HCV is an effective measure in reduction of virus-related public health burden and mortality. However, no prophylactic vaccine is available as of yet. DNA-based immunization is a promising modality to generate cellular and humoral immune responses. The objective of this study is to provide a systematic review of HCV DNA vaccines and investigate and discuss the strategies employed to optimize their efficacies. METHODS: MEDLINE (PubMed), Web of Science, Scopus, ScienceDirect, and databases in persian language including the Regional Information Centre for Science & Technology (RICeST), the Scientific Information Database and the Iranian Research Institute for Information Science and Technology (IranDoc) were examined to identify studies pertaining to HCV nucleic acid vaccine development from 2000 to 2020. RESULTS: Twenty-seven articles were included. Studies related to HCV RNA vaccines were yet to be published. A variety of strategies were identified with the potential to optimize HCV DNA vaccines such as incorporating multiple viral proteins and molecular tags such as HBsAg and Immunoglobulin Fc, multi-epitope expression, co-expression plasmid utilization, recombinant subunit immunogens, heterologous prime-boosting, incorporating NS3 mutants in DNA vaccines, utilization of adjuvants, employment of less explored methods such as Gene Electro Transfer, construction of multi- CTL epitopes, utilizing co/post translational modifications and polycistronic genes, among others. The effectiveness of the aforementioned strategies in boosting immune response and improving vaccine potency was assessed. CONCLUSIONS: The recent progress on HCV vaccine development was examined in this systematic review to identify candidates with most promising prophylactic and therapeutic potential.

Safety and efficacy of apixaban vs. enoxaparin in thromboprophylaxis after spinal stenosis and degenerative spine surgery.

INTRODUCTION: Degenerative spine surgeries often require postoperative immobilization or reduced mobility, predisposing patients to the formation of thrombosis and higher risk of thromboembolic complications. Despite the significance of this issue, there remains a lack of consensus on the optimal anticoagulant agent for postoperative thromboprophylaxis in spinal stenosis and degenerative spine surgeries. Low molecular weight heparins and direct Xa inhibitors represent two anticoagulant groups with high chemoprophylactic potential. METHODS: This study included a prospective cohort of patients undergoing posterior decompressive surgery with or without instrumentation for degenerative spine disease and/or spinal stenosis. Patients receiving postoperative prophylactic Enoxaparin and Apixaban were selected to evaluate the rate of complications, as assessed by Clavien-Dindo classification, thromboembolic events, and 30-day mortality, readmission, and reoperation rate between the two anticoagulants. RESULTS: 130 patients were included in the analysis. 65 patients received Apixaban and Enoxaparin in each group. Mean age of the participants was 57.6±11.0. 83.1% underwent laminectomy and posterior spinal fusion, while 22 patients underwent decompressive surgery only. The incidence of venous thromboembolism (P-value=0.403), deep vein thrombosis (p-value=0.999), hematoma formation (p-value=0.403), surgical site infection (p-value=0.901), readmission (p-value=0.545), reoperation (p=0.510), mortality (p=0.648), and complications rate (p-value=0.232) were not statistically different between Enoxaparin and Apixaban. DISCUSSION: Both Apixaban and Enoxaparin may be viable options for postoperative thromboprophylaxis in spine surgeries with comparable efficacy and safety profile. Future research endeavors should investigate the efficacy of these agents in comparison to placebo in a randomized setting.

The effect of COVID-19 on Multiple Sclerosis relapse: A systematic review and meta-analysis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic autoimmune disease, affecting over 2.5 million people worldwide. There has been growing concern about the impact of COVID-19 on the clinical course of MS. However, these findings remain controversial, and there is a lack of high-quality evidence to establish the relationship between COVID-19 and MS. METHODS: A comprehensive search was done to identify relevant studies reporting relapse rate in patients with MS (pwMS), those comparing the relapse rate of COVID-19 pwMS and MS controls, and studies investigating the effect of COVID-19 on relapse rate of pwMS. The results were presented as proportion of COVID-19 pwMS experiencing relapse and odds ratio determining the impact of COVID-19 on relapse rate. RESULTS: Fourteen studies were included in the analyses. The proportion of COVID-19 positive pwMS with relapse was 7.71 per 100 cases (95 % confidence interval, CI: 4.41-13.89, I2=96 %). Quantitative evaluation of studies with pwMS without COVID-19 did not demonstrate a statistically significant difference in relapse rate of patients with COVID-19 (OR: 0.75, 95 %CI: 0.44-1.29, I2= 54 %). Subgroup and sensitivity analyses did not alter the lack of significance of association between COVID-19 and MS relapse. Sensitivity analysis excluding the outlying study was largely in favor of no difference between the groups (OR:1.00, 95 %CI: 0.72-1.38, I2=34 %) CONCLUSION: The results of this review does not suggest that COVID-19 influences the relapse rate in pwMS. While the findings alleviate the concerns regarding the co-occurrence of the diseases, further studies are needed to investigate the effects of confounding factors.

Impact of Depression on Postoperative Medical and Surgical Outcomes in Spine Surgeries: A Systematic Review and Meta-Analysis.

Introduction: The relationship between psychiatric disorders, including depression, and invasive interventions has been a topic of debate in recent literature. While these conditions can impact the quality of life and subjective perceptions of surgical outcomes, the literature lacks consensus regarding the association between depression and objective perioperative medical and surgical complications, especially in the neurosurgical domain. Methods: MEDLINE (PubMed), EMBASE, PsycINFO, and the Cochrane Library were queried in a comprehensive manner from inception until 10 November 2023, with no language restrictions, for citations investigating the association between depression and length of hospitalization, medical and surgical complications, and objective postoperative outcomes including readmission, reoperation, and non-routine discharge in patients undergoing spine surgery. Results: A total of 26 articles were considered in this systematic review. Upon pooled analysis of the primary outcome, statistically significantly higher rates were observed for several complications, including delirium (OR:1.92), deep vein thrombosis (OR:3.72), fever (OR:6.34), hematoma formation (OR:4.7), hypotension (OR:4.32), pulmonary embolism (OR:3.79), neurological injury (OR:6.02), surgical site infection (OR:1.36), urinary retention (OR:4.63), and urinary tract infection (OR:1.72). While readmission (OR:1.35) and reoperation (OR:2.22) rates, as well as non-routine discharge (OR:1.72) rates, were significantly higher in depressed patients, hospitalization length was comparable to non-depressed controls. Conclusions: The results of this review emphasize the significant increase in complications and suboptimal outcomes noted in patients with depression undergoing spinal surgery. Although a direct causal relationship may not be established, addressing psychiatric aspects in patient care is crucial for providing comprehensive medical attention.

Comparative Analysis of the Prognostic Significance of IDH,TERT, EGFR and MGMT Status in Patients with Adult Non-H3-Altered Grade 4 Gliomas: A Prospective Cohort Study.

INTRODUCTION: Gliomas continue to have a dismal prognosis. A myriad of genetic alterations has been described in this subset of tumors over the last decades. The integrative interpretation of the biomarker constellation for individual patients remains unclear. This study aims to evaluate the impact of some known genetic factors as prognostic biomarkers in grade 4 gliomas. METHODS: Adult non-H3-altered grade 4 gliomas who underwent maximal safe resection accompanied by adjuvant therapy were successively enrolled since January 2019 till January 2021. Patient data were documented preoperatively and during the follow-up visits. The genetic profiling of the tumors included Isocitrate Dehydrogenase (IDH)-1 and IDH-2 mutation, MGMT promoter methylation rate, EGFR gene amplification and telomerase reverse transcriptase gene promoter (TERTp) mutation. RESULTS: Mean Overall survival (OS) and Progression-free survival (PFS) were 14.45 ± 5.13 months (3-24 months) and 10.66 ± 4.87 months respectively. TERTp-mutant group had a significantly lower OS (10.9 vs. 15.9) and PFS (6.9 vs. 12.3) than TERTp wildtype group. In the TERT-mutant group, those with concomitant IDH wildtype tumor had higher OS and PFS, comparable to those with both TERTp and IDH wildtype tumors. In multivariate analysis, IDH mutation and TERTp wildtype status were predictive of longer OS and PFS. While IDH and absence of TERTp mutation were associated with KPS > 80 across the follow-ups, their predictive values were inferior to preoperative KPS scores. CONCLUSIONS: TERTp mutation and IDH-wildtype status were associated with worse OS and PFS and lower follow-up KPS score in surgically resected gliomas, while MGMT and EGFR status did not have considerable prognostic value in this study.

Prediction of post-delivery hemoglobin levels with machine learning algorithms.

Predicting postpartum hemorrhage (PPH) before delivery is crucial for enhancing patient outcomes, enabling timely transfer and implementation of prophylactic therapies. We attempted to utilize machine learning (ML) using basic pre-labor clinical data and laboratory measurements to predict postpartum Hemoglobin (Hb) in non-complicated singleton pregnancies. The local databases of two academic care centers on patient delivery were incorporated into the current study. Patients with preexisting coagulopathy, traumatic cases, and allogenic blood transfusion were excluded from all analyses. The association of pre-delivery variables with 24-h post-delivery hemoglobin level was evaluated using feature selection with Elastic Net regression and Random Forest algorithms. A suite of ML algorithms was employed to predict post-delivery Hb levels. Out of 2051 pregnant women, 1974 were included in the final analysis. After data pre-processing and redundant variable removal, the top predictors selected via feature selection for predicting post-delivery Hb were parity (B: 0.09 [0.05-0.12]), gestational age, pre-delivery hemoglobin (B:0.83 [0.80-0.85]) and fibrinogen levels (B:0.01 [0.01-0.01]), and pre-labor platelet count (B*1000: 0.77 [0.30-1.23]). Among the trained algorithms, artificial neural network provided the most accurate model (Root mean squared error: 0.62), which was subsequently deployed as a web-based calculator: https://predictivecalculators.shinyapps.io/ANN-HB . The current study shows that ML models could be utilized as accurate predictors of indirect measures of PPH and can be readily incorporated into healthcare systems. Further studies with heterogenous population-based samples may further improve the generalizability of these models.

Assessment of the impact of frailty on adverse surgical outcomes in patients undergoing surgery for intracranial tumors using modified frailty index: A systematic review and meta-analysis.

BACKGROUND: Modified frailty index (MFI) is an emerging quantitative measure of frailty; however, the quantified risk of adverse outcomes in surgeries for intracranial tumors associated with increasing MFI scores has not been thoroughly reviewed in a comprehensive manner. METHODS: MEDLINE (PubMed), Scopus, Web of Science, and Embase were searched to identify observational studies on the association between 5 and 11 item-modified frailty index (MFI) and perioperative outcomes for neurosurgical procedures including complications, mortality, readmission, and reoperation rate. Primary analysis pooled all comparisons with MFI scores greater than or equal to 1 versus non-frail participants using mixed-effects multilevel model for each outcome. RESULTS: In total, 24 studies were included in the review and 19 studies with 114,707 surgical operations were included in the meta-analysis. While increasing MFI scores were associated with worse prognosis for all included outcomes, reoperation rate was only significantly higher in patients with MFI ≥ 3. Among surgical pathologies, glioblastoma was influenced by a greater extent to the impact of frailty on complications and mortality that most other etiologies. In agreement with qualitative evaluation of the included studies, meta-regression did not reveal association between mean age of the comparisons and complications rate. CONCLUSION: The results of this meta-analysis provides quantitative risk assessment of adverse outcomes in neuro-oncological surgeries with increased frailty. The majority of literature suggests that MFI is a superior and independent predictor of adverse outcomes compared to age.

Diagnostic value of ophthalmic artery Doppler indices for prediction of preeclampsia at 28-32 weeks of gestation.

OBJECTIVE: The aim of this study was to examine the diagnostic value of ophthalmic artery Doppler indices in predicting preeclampsia along with other markers in the third trimester of pregnancy. METHODS: Normotensive pregnancies were included during 28-32 weeks of gestation to undergo uterine and ophthalmic artery Doppler ultrasound. Maternal and fetal characteristics were documented at the visit between the 28 and 32 weeks of gestation, and pregnancy-associated plasma protein A (PAPP-A) values in the first trimester were collected to be integrated into a multiparametric prediction model. RESULTS: Of 795 included participants, 48 cases progressed to preeclampsia. All assessed ophthalmic Doppler parameters including first and second peak systolic velocities (PSVs), second to first peak ratio (PR), and pulsatility index (PI), were statistically different in patients who developed preeclampsia later on. The average PR (sensitivity: 100% [95% CI, 0.81-1.00]; specificity: 90% [95% CI, 0.86-0.93]) and PI between the eyes, PAPP-A multiple of median and uterine artery PI were determined to be the most important predictors of PE, which were subsequently integrated into a multiple regression model (sensitivity: 94% [95% CI, 0.70-1.00]; specificity: 93% [95% CI, 0.89-0.96]). CONCLUSION: This study provided a screening method for individuals at higher risk of progressing to preeclampsia in the third trimester of pregnancy.

Bowel obstruction in body-packing: A case report and literature review.

INTRODUCTION AND IMPORTANCE: The body packer swallows or embeds drugs in body cavities in a purposeful way. Packets usually contain of opium, cocaine, cannabis and amphetamines. The significant complications of body packing usually are symptoms of drug toxicity due to leaking or ruptured packets or symptoms of ingesting relatively large foreign bodies. Herein, we present a case of heroin body-packing that resulted in subsequent bowel obstruction. CASE PRESENTATION: A 30-year-old male, who was brought from the prison to the emergency department, complained of abdominal pain. After the absence of intoxication symptoms and insignificant plain abdominal radiograph results, abdominal computed tomography (CT) scan revealed the presence of ingested packets in the stomach as well as in the patient's small intestine. Therefore, the decision of surgery was immediately made for the patient, and during the surgery, the drug packets were entirely removed. The patient was discharged in good general condition three days after his surgery. CLINICAL DISCUSSION: Body packers are in considerable risk as rupture of packet inside the body and risk of obstruction that both of them may be fatal. Patients should be monitored for complications, possible early treatment, and removal or assistance in expulsion drug packets from the body. Initially on plain abdominal radiographs, classic findings suggest the presence of drug packets. CONCLUSION: In case of an inconclusive plain abdominal radiograph, further investigation with CT is indicated, with an almost 100 % sensitivity. For symptomatic patients, bowel obstruction and acute drug toxicity are the two most common indications for surgical intervention.

Identification of novel miRNAs potentially involved in the pathogenesis of adult T-cell leukemia/lymphoma using WGCNA followed by RT-qPCR test of hub genes.

BACKGROUND: Adult T-cell Lymphoma/Leukemia (ATLL) is characterized by the malignant proliferation of T-cells in Human T-Lymphotropic Virus Type 1 and a high mortality rate. Considering the emerging roles of microRNAs (miRNAs) in various malignancies, the analysis of high-throughput miRNA data employing computational algorithms helps to identify potential biomarkers. METHODS: Weighted gene co-expression network analysis was utilized to analyze miRNA microarray data from ATLL and healthy uninfected samples. To identify miRNAs involved in the progression of ATLL, module preservation analysis was used. Subsequently, based on the target genes of the identified miRNAs, the STRING database was employed to construct protein-protein interaction networks (PPIN). Real-time quantitative PCR was also performed to validate the expression of identified hub genes in the PPIN network. RESULTS: After constructing co-expression modules and then performing module preservation analysis, four out of 15 modules were determined as ATLL-specific modules. Next, the hub miRNA including hsa-miR-18a-3p, has-miR-187-5p, hsa-miR-196a-3p, and hsa-miR-346 were found as hub miRNAs. The protein-protein interaction networks were constructed for the target genes of each hub miRNA and hub genes were identified. Among them, UBB, RPS15A, and KMT2D were validated by Reverse-transcriptase PCR in ATLL patients. CONCLUSION: The results of the network analysis of miRNAs and their target genes revealed the major players in the pathogenesis of ATLL. Further studies are required to confirm the role of these molecular factors and to discover their potential benefits as treatment targets and diagnostic biomarkers.

Case report: Bilateral spinal neurofibromatosis.

Spinal neurofibromatosis (SNF) is a rare form of Neurofibromatosis in which neurofibromas exist bilaterally throughout all spinal roots. Despite previous attempts made to characterize and classify the disease as a separate clinical form of the disease, the low incidence rate of the disease and scarcity of previous reports calls for further studies and reports to elaborate this clinical entity. The patient in this report was a 36-year-old man presenting with lower limb weakness, unsteady gait, and paresthesia. The patient also presented with multiple cutaneous café-au-lait spots, cutaneous neurofibromas, and a large neurocutaneous neurofibroma of right facial nerve. Magnetic resonance imaging (MRI) of spine revealed bilateral spinal neurofibromas across all spinal cord roots. MRI study of head revealed no abnormalities in the brain and optic tract. The patient fulfilled both NIH criteria as well as revised criteria for NF1. Despite total spinal cord involvement, surgical intervention was withheld from the patient due to high propensity of recurrence as seen with previous attempts in removing peripheral neurofibromas, slow progression of symptoms, and lack of significant pain and impairment. SNF is often described as a form of disease with infrequent presentation of classical NF1 symptoms other than spinal tumors. The case presented here however, presented with several cutaneous neurofibromas and café-au-lait spots. Considering the positive outcome of surgical intervention in a few other reports, the decision to surgically intervene should be left to the clinical judgement of the participating surgeon, patient preference and socioeconomic background in a case-by-case manner.

Contribution of obesity and cardiometabolic risk factors in developing cardiovascular disease: a population-based cohort study.

This study aims to assess the effects of central and general adiposity on development of cardiovascular diseases (CVDs) mediated by cardiometabolic risk factors and to analyze their degree of dependency for mediating their effects. To this end, data from the the Tehran Lipid and Glucose Study cohort with 6280 participants were included in this study. The hazard ratios were calculated using a 2-stage regression model in the context of a survival model. Systolic blood pressure (BP), total serum cholesterol, and fasting plasma glucose were designated as mediators. Assessing the interactions revealed that BP was the most important mediator for general ( (HRNIE: 1.11, 95% CI 1.17-1.24) and central obesity (CO) (HRNIE: 1.11, 95% CI 1.07-1.15) with 60% and 36% proportion of the effects mediated in the total population, respectively. The proportion of mediated risk for all three metabolic risk factors was 46% (95% CI 31-75%) for overweight, 66% (45-100%) for general obesity and 52% (39-87%) for central obesity. BP was the most important mediator for overweight and central obesity in men, comprising 29% and 36% of the risk, respectively. The proportion of the risk mediated through all three metabolic risk factors in women was 23% (95% CI 13-50%) for overweight, 36% (21-64%) for general obesity and 52% (39-87%) for central obesity. Based on the results of this study, cardiometabolic mediators have conciliated more than 60% of the adverse effects of high BMI on CVDs in men. Controlling the metabolic risk factors in women does not efficiently contribute to decreasing CVDs as effectively.

Facial nerve regeneration using silicone conduits filled with ammonia-functionalized graphene oxide and frankincense-embedded hydrogel.

BACKGROUND: Silicone tube (ST) conduits have been accepted as a therapeutic alternative to direct nerve suturing in the treatment of nerve injuries; however, the search for optimal adjuncts to maximize the outcomes is still ongoing. Frankincense (Fr) and graphene oxide (GO) have both been cited as neuroregenerative compounds in the literature. This study assesses the efficacy of these materials using a ST conduit in a rat facial nerve motor neuron axotomy model, distal to the stylomastoid foramen. METHODS: Ammonia-functionalized graphene oxide (NH2-GO) and/or Fr extract were embedded in a collagen-chitosan hydrogel and were injected inside a ST. The ST was inserted in the gap between the axotomized nerve stumps. Return of function in eye closure, blinking reflex, and vibrissae movements were assessed and compared to control groups through 30 days following axotomy. To assess the histological properties of regenerated nerves, biopsies were harvested distal to the axotomy site and were visualized through light and fluorescence microscopy using LFB and anti-MBP marker, respectively. RESULTS: There was no significant difference in behavioral test results between groups. Histological analysis of the nerve sections revealed increased number of regenerating axons and mean axon diameter in NH2-GO group and decreased myelin surface area in Fr group. Using both NH2-GO and Fr resulted in increased number of regenerated axons and myelin thickness compared to the hydrogel group. CONCLUSIONS: The findings suggest a synergistic effect of the substances above in axon regrowth, notably in myelin regeneration, where Fr supposedly decreases myelin synthesis.

Comprehensive high-throughput meta-analysis of differentially expressed microRNAs in transcriptomic datasets reveals significant disruption of MAPK/JNK signal transduction pathway in Adult T-cell leukemia/lymphoma.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) infection may lead to the development of Adult T-cell leukemia/lymphoma (ATLL). To further elucidate the pathophysiology of this aggressive CD4+ T-cell malignancy, we have performed an integrated systems biology approach to analyze previous transcriptome datasets focusing on differentially expressed miRNAs (DEMs) in peripheral blood of ATLL patients. METHODS: Datasets GSE28626, GSE31629, GSE11577 were used to identify ATLL-specific DEM signatures. The target genes of each identified miRNA were obtained to construct a protein-protein interactions network using STRING database. The target gene hubs were subjected to further analysis to demonstrate significantly enriched gene ontology terms and signaling pathways. Quantitative reverse transcription Polymerase Chain Reaction (RTqPCR) was performed on major genes in certain pathways identified by network analysis to highlight gene expression alterations. RESULTS: High-throughput in silico analysis revealed 9 DEMs hsa-let-7a, hsa-let-7g, hsa-mir-181b, hsa-mir-26b, hsa-mir-30c, hsa-mir-186, hsa-mir-10a, hsa-mir-30b, and hsa-let-7f between ATLL patients and healthy donors. Further analysis revealed the first 5 of DEMs were directly associated with previously identified pathways in the pathogenesis of HTLV-1. Network analysis demonstrated the involvement of target gene hubs in several signaling cascades, mainly in the MAPK pathway. RT-qPCR on human ATLL samples showed significant upregulation of EVI1, MKP1, PTPRR, and JNK gene vs healthy donors in MAPK/JNK pathway. DISCUSSION: The results highlighted the functional impact of a subset dysregulated microRNAs in ATLL on cellular gene expression and signal transduction pathways. Further studies are needed to identify novel biomarkers to obtain a comprehensive mapping of deregulated biological pathways in ATLL.