Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis

Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.

Protective effect of co-enzyme Q10 on testicular tissue and sperm parameters in adult male rats treated with Sunset Yellow FCF

Objective:To determine the protective effect of co-enzyme Q10(CoQ10)on testicular tissue and sperm parameters in male rats treated with SunsetYellow FCF.Methods:Sixty male Sprague-Dawley rats were randomly divided into 6 groups of the control,CoQ10(10 mg/kg/day),low dose of Sunset Yellow(2.5 mg/kg),high dose of Sunset Yellow(70 mg/kg),low dose of Sunset Yellow(2.5 mg/kg)plus CoQ10,and high dose of Sunset Yellow(70 mg/kg)plus CoQ10.The drugs were administered via daily oral gavages for 6 weeks.At the end of the experiment,sperm analysis,stereological and histological assessments of the testis were carried out.Results:The normal morphology(by 41.1%)and progressive spermatozoa(by 74.8%),testicle volume(by 33.4%),lumen volume(by 38.3%),interstitial tissue volume(by 44.7%),seminiferous tubule volume(by 40.7%),and number of spermatogonia(by 53.9%)and Leydig cells(by 70.7%)reduced in the rats that received high doses of Sunset Yellow in comparison to the control group.Nonetheless,all these alterations were recovered by CoQ10 treatment in the CoQ10 plus high dose of Sunset Yellow group.Furthermore,low doses of Sunset Yellow did not affect different parameters of the testis and sperm.Conclusions:CoQ10 could,to some extent,prevent structural changes of the testis induced by the high dose of SunsetYellow.

Overview on signal transduction cascades regulation roles of garlic and its bioactive constituents

High-throughput technologies in combination with modern exciting advancements in mass spectrometry-based proteomics and data analysis pipelines have empowered comprehensive characterization of disease phenotypes and their mechanistic regulation by dietary agents and bioactive molecules at unprecedented dimensionality and resolution.Extra-ordinary breakthroughs in the field of nutrigenomics have leveraged our understanding altogether to a new level of maturity.Interdisciplinary researchers have extensively analyzed health promoting and pharmacologically significant properties of garlic(Allium sativum).Importantly,garlic and its biologically active chemicals targeted oncogenic signaling cascades.In this mini-review we have attempted to summarize how garlic and its bioactive constituents regulated signal transduction cascades in cell culture studies and tumor-bearing mice.

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.

Liver surface depressions in the presence of diaphragmatic muscular bands on trans-illumination

Traditional descriptions of liver anatomy refer to a smooth,convex surface contacting the diaphragm.Surface depressions are recognized anatomic variants.There are many theories to explain the cause of the depressions.We discuss the theory that these are caused by hypertrophic muscular bands in the diaphragm.

Contribution of Anti-p63 Antibodies in the Interpretation of Benign Label Prostatic Biopsies

Introduction: Prostate cancer is the second most common cancer in men. The diagnosis is most often based on the prostate biopsies’ analysis and on histological criteria recognizable on standard coloring. In some cases, the use of immunohistochemistry is important. Objectives: This paper aims to specify the p63 phenotypic profile of lesions diagnosed benign, with minimal suspect foci, difficult to interpret, HGPIN (high grade intraepithelial neoplasia) and LGPIN (low-grade prostatic intraepithelial neoplasia) and evaluate the manual technique of p63 immunohistochemistry. Patients and Method: This was a retrospective, descriptive study of prostate biopsies recorded in the PAC service of the HALD from January 1st, 2018 to December 31st, 2018. It was completed by a manual immunohistochemical study of the blocks enrolled from November 19th to December 4th, 2020 in the PAC department of the HPD. The studied parameters were: registry number, age, clinical stage, prostate volume, PSA level, microscopic appearance and p63 immunohistochemical profile. Results: Our study included 60 prostate biopsies. The ages of our patients varied from 45 to 77 years, with an average of 64.2 years and a standard deviation of 6.2. The majority of patients were at clinical stage cT2b (33%) with a prostate volume varying between 33.15 and 169.4 cc. The minimum value of PSA in our series is 5 ng/ml, the maximum being 100 ng/ml with an average level of 24.1 ng/ml and a standard deviation of 21.2. Our series included 50 adenomyomatous hyperplasias, 7 adenomyomatous hyperplasias associated with chronic prostatitis, 2 HGPIN and 1 LGPIN. After re-reading we found 5 discordant cases, which corresponded to minimal suspect foci (kappa = 0.5098). The p63 marking was informative in 53 cases, i.e. 88%, and non-informative in 7 cases, i.e. 12%. Among the uninformative markings, 2 were due to lack of tissue adhesion to the slides. Among the informative markings, 11 were negative. p63 immunohistochemistry was useful in all suspected foci and detected 6 other minimal foci of adenocarcinoma. Conclusion: The immunostaining with the anti-p63 antibody in the prostate cancer diagnosis is of considerable benefit. It made it possible to correct 11.3% of benign diagnosis in minimal malignant focus in our context. Despite the difficulties associated with the manual technique, it is possible to have an informative rate, similar to the automatic technique.

Hepatic grooves:An observational study at laparoscopic surgery

BACKGROUND In traditional descriptions,the upper surface of the liver is smooth and convex,but deep depressions are variants that are present in 5%-40%of patients.We sought to determine the relationship between surface depressions and the diaphragm.AIM To use exploratory laparoscopy to determine the relationship between surface depressions and the diaphragm.METHODS An observational study was performed in all patients undergoing laparoscopic upper gastro-intestinal operations between January 1,2023 and January 20,2024.A thirty-degree laparoscope was used to inspect the liver and diaphragm.When surface depressions were present,we recorded patient demographics,presence of diaphragmatic bands,rib protrusions and/or any other source of compression during inspection.RESULTS Of 394 patients,343 had normal surface anatomy,and 51(12.9%)had prominent surface depressions on the liver.There was no significant relationship between the presence of surface depressions and gender nor the presence of rib projections.However,there was significant association between the presence of surface depressions and diaphragmatic muscular bands(P<0.001).CONCLUSION With these data,the diaphragmatic-band theory has gained increased importance over other theories for surface depressions.Further studies are warranted using cross sectional imaging to confirm relationships with intersectional planes as well as beta-catenin assays in the affected liver parenchyma.

Sonographic Evaluation of Normal Anatomy of Fetal Central Nervous System in Mid-Trimester

The central nervous system is a common site for congenital anomalies. Neural tube defects (NTDs) such as anencephaly, encephalocele and spina bifida are among the most common central nervous system congenital anomalies. They result from failure of closure of the neural tube during embryonic development. The neural tube formation starts during the fourth week (22 - 23 days) after fertilization and fuses approximately between the days 25th and 27th. Most of NTDs result from genetic factors and environmental factors which are poorly understood. Diagnostic sonography can show a detailed visualization of the fetal intracranial anatomy such as the cerebral hemispheres, midbrain, thalami, and lateral ventricles. They also can measure the ratio between lateral ventricular and cerebral hemispheric width. It might show as well, the ratio between gestation, the rapid growth of the cerebral hemispheres and the expansion of the cerebral ventricles. The ultrasound during pregnancy plays a prominent and influential role in the prenatal evaluation of the central nervous system. It gives an excellent window for viewing and evaluating the fetal central nervous system during the second trimester through the lateral ventricles and transthalamic view, thus effectively contributing in the diagnosis and treatment of its congenital anomalies.

Anatomy Education: Perceptions and Experiences of Nigerian Anatomists towards Contributing to Programme and Career Advancements

Anatomy, a foremost basic medical science (BMS) has evolved in content and context, while remaining the most fundamental BMS subject. Stakeholders have continually made efforts especially in recent time to achieve an evolution of this subject. The primary aim of this work was to study the perceptions and experiences of Anatomists towards contributing to programme and career advancements. Following ethical approval, structured questionnaire was administered to Nigerian anatomists using a Google form. It is a total population study. The questionnaire had 13 sections, with each section addressing a theme that was integral to the subject of research interest. The last section collected free responses as qualitative information. After indicating informed consent, 106 anatomists properly completed and returned the questionnaires. Statistical and quantitative analyses of results were done. The most popular field amongst respondents was Neuroscience (60.9%);followed by Histology or Microscopic Anatomy (53.6%), Embryology or developmental anatomy (35.5%), Gross anatomy (34.5%) and Histochemistry (30.9%). About half of Nigerian anatomists involved in the study had a PhD degree. Training emphasized the cognitive domains the most. Consequently, emphasis should be laid on the psychomotor (skills) and the affective domain (attitude) to improve capacity, competences, and the job prospects of trainees. The consensus was that the programme trained students and prepared graduates as medical educators, scientists, and researchers. Anatomy has significant potential to contribute to development with proper programme design, emphasis on research, teaching and applied services competencies, effective policy formulation and implementation and adherence to best practices.

Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo

Background: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol(PEG) crosslinked decellularized single liver lobe scaffolds(DLSs), and establish its suitability as a graft for long-term liver tissue engineering. Methods: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate(SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor(VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells(HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. Results: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young’s modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. Conclusions: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

Current opinion on the regulation of small intestinal magnesium absorption

Magnesium(Mg^(2+))has an important role in numerous biological functions,and Mg^(2+)deficiency is associated with several diseases.Therefore,adequate intestinal absorption of Mg^(2+)is vital for health.The small intestine was previously thought to absorb digested Mg^(2+)exclusively through an unregulated paracellular mechanism,which is responsible for approximately 90%of total Mg^(2+)absorption.Recent studies,however,have revealed that the duodenum,jejunum,and ileum absorb Mg^(2+)through both transcellular and paracellular routes.Several regulatory factors of small intestinal Mg^(2+)uptake also have been explored,e.g.,parathyroid hormone,fibroblast growth factor-23,apical acidity,proton pump inhibitor,and pH-sensing channel and receptors.The mechanistic factors underlying proton pump inhibitor suppression of small intestinal Mg^(2+),such as magnesiotropic protein dysfunction,higher mucosal bicarbonate secretion,Paneth cell dysfunction,and intestinal inflammation,are currently being explored.The potential role of small intestinal microbiomes in Mg^(2+)absorption has also been proposed.In this article,we reviewed the current knowledge on the mechanisms and regulatory factors of small intestinal Mg^(2+)absorption.

Gallbladder perforation with fistulous communication

BACKGROUND The management of gallbladder perforation(GBP)with fistulous communication(Neimeier type I)is controversial.AIM To recommend management options for GBP with fistulous communication.METHODS A systematic review of studies describing the management of Neimeier type I GBP was performed according to the PRISMA guidelines.The search strategy was conducted in Scopus,Web of Science,MEDLINE,and EMBASE(May 2022).Data extraction was obtained for patient characteristics,type of intervention,days of hospitalization(DoH),complications,and site of fistulous communication.RESULTS A total of 54 patients(61%female)from case reports,series,and cohorts were included.The most frequent fistulous communication occurred in the abdominal wall.Patients from case reports/series had a similar proportion of complications between open cholecystectomy(OC)and laparoscopic cholecystectomy(LC)(28.6 vs 12.5;P=0.569).Mortality was higher in OC(14.3 vs 0.0;P=0.467)but this proportion was given by only one patient.DoH were higher in OC(mean 26.3 d vs 6.6 d).There was no clear association between higher rates of complications of a given intervention in cohorts,and no mortality was observed.CONCLUSION Surgeons must evaluate the advantages and disadvantages of the therapeutic options.OC and LC are adequate options for the surgical management of GBP,with no significant differences.

A U-Net-Based CNN Model for Detection and Segmentation of Brain Tumor

Human brain consists of millions of cells to control the overall structure of the human body.When these cells start behaving abnormally,then brain tumors occurred.Precise and initial stage brain tumor detection has always been an issue in the field of medicines for medical experts.To handle this issue,various deep learning techniques for brain tumor detection and segmentation techniques have been developed,which worked on different datasets to obtain fruitful results,but the problem still exists for the initial stage of detection of brain tumors to save human lives.For this purpose,we proposed a novel U-Net-based Convolutional Neural Network(CNN)technique to detect and segmentizes the brain tumor for Magnetic Resonance Imaging(MRI).Moreover,a 2-dimensional publicly available Multimodal Brain Tumor Image Segmentation(BRATS2020)dataset with 1840 MRI images of brain tumors has been used having an image size of 240×240 pixels.After initial dataset preprocessing the proposed model is trained by dividing the dataset into three parts i.e.,testing,training,and validation process.Our model attained an accuracy value of 0.98%on the BRATS2020 dataset,which is the highest one as compared to the already existing techniques.

Multi-Level Deep Generative Adversarial Networks for Brain Tumor Classification on Magnetic Resonance Images

The brain tumor is an abnormal and hysterical growth of brain tissues,and the leading cause of death affected patients worldwide.Even in this technol-ogy-based arena,brain tumor images with proper labeling and acquisition still have a problem with the accurate and reliable generation of realistic images of brain tumors that are completely different from the original ones.The artificially created medical image data would help improve the learning ability of physicians and other computer-aided systems for the generation of augmented data.To over-come the highlighted issue,a Generative Adversarial Network(GAN)deep learn-ing technique in which two neural networks compete to become more accurate in creating artificially realistic data for MRI images.The GAN network contains mainly two parts known as generator and discriminator.Commonly,a generator is the convolutional neural network,and a discriminator is the deconvolutional neural network.In this research,the publicly accessible Contrast-Enhanced Mag-netic Resonance Imaging(CE-MRI)dataset collected from 2005-to 2020 from different hospitals in China consists of four classes has been used.Our proposed method is simple and achieved an accuracy of 96%.We compare our technique results with the existing results,indicating that our proposed technique outper-forms the best results associated with the existing methods.

Enhanced Adaptive Brain-Computer Interface Approach for Intelligent Assistance to Disabled Peoples

Assistive devices for disabled people with the help of Brain-Computer Interaction(BCI)technology are becoming vital bio-medical engineering.People with physical disabilities need some assistive devices to perform their daily tasks.In these devices,higher latency factors need to be addressed appropriately.Therefore,the main goal of this research is to implement a real-time BCI architecture with minimum latency for command actuation.The proposed architecture is capable to communicate between different modules of the system by adopting an automotive,intelligent data processing and classification approach.Neuro-sky mind wave device has been used to transfer the data to our implemented server for command propulsion.Think-Net Convolutional Neural Network(TN-CNN)architecture has been proposed to recognize the brain signals and classify them into six primary mental states for data classification.Data collection and processing are the responsibility of the central integrated server for system load minimization.Testing of implemented architecture and deep learning model shows excellent results.The proposed system integrity level was the minimum data loss and the accurate commands processing mechanism.The training and testing results are 99%and 93%for custom model implementation based on TN-CNN.The proposed real-time architecture is capable of intelligent data processing unit with fewer errors,and it will benefit assistive devices working on the local server and cloud server.

Next generation drug connectivity mapping for acquiring therapeutic agents to differentially regulate myelination

The need for new therapeutic approaches:Conventional drug discovery is a lengthy and expensive process,taking decades and billions of dollars to get a drug from bench to bedside.Much of the costs incurred are at the pre-clinical stages,between drug design and synthesis to delineating the cellular“Mechanisms of Action”(MoA).Notably,there is a very high risk of failure,and only a very small proportion of therapeutic agents reach later-phase clinical trials.Accordingly,drug repositioning has become a valuable strategy aimed at fast-tracking treatments into clinical use and improving the chances of therapeutic success.A novel addition to this approach is connectivity mapping,which defines cell-specific transcriptional responses to small molecules in disease-dependent contexts.This commentary outlines how some of the latest innovations in connectivity mapping can be exploited for drug repurposing.

Liver Ailment Prediction Using Random Forest Model

Today,liver disease,or any deterioration in one’s ability to survive,is extremely common all around the world.Previous research has indicated that liver disease is more frequent in younger people than in older ones.When the liver’s capability begins to deteriorate,life can be shortened to one or two days,and early prediction of such diseases is difficult.Using several machine learning(ML)approaches,researchers analyzed a variety of models for predicting liver disorders in their early stages.As a result,this research looks at using the Random Forest(RF)classifier to diagnose the liver disease early on.The dataset was picked from the University of California,Irvine repository.RF’s accomplishments are contrasted to those of Multi-Layer Perceptron(MLP),Average One Dependency Estimator(A1DE),Support Vector Machine(SVM),Credal Decision Tree(CDT),Composite Hypercube on Iterated Random Projection(CHIRP),K-nearest neighbor(KNN),Naïve Bayes(NB),J48-Decision Tree(J48),and Forest by Penalizing Attributes(Forest-PA).Some of the assessment measures used to evaluate each classifier include Root Relative Squared Error(RRSE),Root Mean Squared Error(RMSE),accuracy,recall,precision,specificity,Matthew’s Correlation Coefficient(MCC),F-measure,and G-measure.RF has an RRSE performance of 87.6766 and an RMSE performance of 0.4328,however,its percentage accuracy is 72.1739.The widely acknowledged result of this work can be used as a starting point for subsequent research.As a result,every claim that a new model,framework,or method enhances forecastingmay be benchmarked and demonstrated.

Exosomes in viral infection:Effects for pathogenesis and treatment strategies

Exosomes are small vesicles that carry molecules from one cell to another.They have many features that make them interesting for research,such as their stability,low immunogenicity,size of the nanoscale,toxicity,and selective delivery.Exosomes can also interact with viruses in diverse ways.Emerging research highlights the significant role of exosomes in viral infections,particularly in the context of diseases like COVID-19,HIV,HBV and HCV.Understanding the intricate interplay between exosomes and the human immune system holds great promise for the development of effective antiviral therapies.An important aspect is gaining clarity on how exosomes influence the immune system and enhance viral infectivity through their inherent characteristics.By leveraging the innate properties of exosomes,viruses exploit the machinery involved in exosome biogenesis to set replication,facilitate the spread of infection,and eliminate immune responses.They can either help or hinder viral infection by modulating the immune system.This review summarizes the recent findings on how exosomes mediate viral infection and how they can be used for diagnosis or therapy.This could lead to new clinical applications of exosomes in disease management.

Non-Chemotherapy Medullary Aplasia in the Pediatric Oncology Unit of the Gabriel Touré Teaching Hospital, Bamako

Objectives: The main objective was to study the epidemiological, diagnostic and therapeutic aspects of medullary aplasia (MA). Methods: This was a prospective and descriptive retro study conducted from January 1, 2008 to December 31, 2018 in the pediatric oncology unit of the pediatrics department of the Gabriel Touré teaching Hospital in Bamako. Results: We collected 29 children’s cases out of 1632 admissions during the study period, representing a frequency of 1.8% and an incidence of 2.6 cases per year. The sex ratio was 2.6. The 11 - 15 age group accounted for 45%, with an average age of 8.93 years. The majority of fathers (55.2%) and mothers (62.1%) had received no education;they were mainly farmers (62.1%) and housewives (86.2%). The average consultation time was 92.21 days. Anemia was the reason for consultation in 69% of cases. Pallor was present on admission in 96.5%;infectious syndrome accounted for 79.3%, anemic syndrome for 51.7% and hemorrhagic syndrome for 27.6%;the three syndromes were associated in 27.6%. Malaria was associated with bone marrow aplasia in 58.6%. Anemia was present in 93.1%, neutropenia in 65.5% and thrombocytopenia in 86.2%. All had received a labile blood product (LBP) transfusion, and 24 (83%) had received antibiotics. Patients were treated with corticosteroids (58.6%), androgens (20.7%) and immunosuppressants (20.7%). The death rate was 34.6%. At last count, 15 (83%) had discontinued treatment, 2 (11%) were undergoing treatment and 1 (6%) was in remission. Conclusion: Effective treatment of MA requires improved technical facilities and better economic conditions for parents.

Severe Coital Accident: A Rare Case of Simultaneous Fracture of the Penis and a Complete Urethral Rupture at the University Hospital of Bouake

Cavernous body fracture is a rare urological emergency. Its association with complete rupture of the urethra remains exceptional. This is a report of simultaneous penile fracture and complete rupture of the urethra following a misstep in coitus. It is about a 41-year-old young adult, admitted to the surgical emergency department of the University Hospital of Bouaké on March 2, 2020 for penile pain associated with acute retention of urine. The clinical examination confirmed the diagnosis of a corpus cavernosa fracture associated with a ruptured urethra. The patient underwent cystostomy, right cavernoraphy and urethrorrhaphy. The postoperative follow-up was straightforward and the patient was discharged from the hospital on D3 postoperatively. The urethral catheter was removed on D21 postoperatively. With a follow-up of 1 year, the patient presents a good erection and does not report any voiding disorder.