Comparison of recent updates in genetics, immunology, biomarkers, and neuroimaging of primary-progressive and relapsing-remitting multiple sclerosis and the role of ocrelizumab in the management of their refractory cases.

Background: Primary-progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) are two frequent multiple sclerosis (MS) subtypes that involve 10%-15% of patients. PPMS progresses slowly and is diagnosed later in life. Both subtypes are influenced by genetic and environmental factors such as smoking, obesity, and vitamin D insufficiency. Although there is no cure, ocrelizumab can reduce symptoms and delay disease development. RRMS is an autoimmune disease that causes inflammation, demyelination, and disability. Early detection, therapy, and lifestyle changes are critical. This study delves into genetics, immunology, biomarkers, neuroimaging, and the usefulness of ocrelizumab in the treatment of refractory patients of PPMS. Method: In search of published literature providing up-to-date information on PPMS and RRMS, this review conducted numerous searches in databases such as PubMed, Google Scholar, MEDLINE, and Scopus. We looked into genetics, immunology, biomarkers, current breakthroughs in neuroimaging, and the role of ocrelizumab in refractory cases. Results: Our comprehensive analysis found considerable advances in genetics, immunology, biomarkers, neuroimaging, and the efficacy of ocrelizumab in the treatment of refractory patients. Conclusion: Early detection, timely intervention, and the adoption of lifestyle modifications play pivotal roles in enhancing treatment outcomes. Notably, ocrelizumab has demonstrated potential in symptom control and mitigating the rate of disease advancement, further underscoring its clinical significance in the management of MS.

Newer modalities in the management of Alzheimer's dementia along with the role of aducanumab and lecanemab in the treatment of its refractory cases.

Alzheimer's disease (AD) is a common neurological condition characterized by a gradual and progressive decline in memory, language, emotion, and cognition. It mainly affects elderly people. Due to the effects of AD, pharmaceutical medications and anticholinesterases have been vigorously promoted and approved by the FDA as a form of AD therapy. However, it was progressively found that these drugs did not address the underlying causes of AD pathogenesis; rather, they focused on the symptoms in order to enhance patients' cognitive outcomes. Consequently, a hunt for superior disease-modifying options is launched. Designing new therapeutic agents requires a thorough understanding of the neuroprotective processes and varied functions carried out by certain genes, and antibodies. In this comprehensive review article, we give an overview of the history of Alzheimer's disease, the significance of the blood-brain barrier in determining the scope of treatment options, as well as the advantages and disadvantages of the current therapeutic treatment options for stem cell therapy, immunotherapy, regenerative therapy, and improved Alzheimer's disease care and diagnosis. We have also included a discussion on the potential role of aducanumab and Lecanemab as a cutting-edge therapy in refractory Alzheimer's disease patients. Lecanemab has been recently approved by the FDA for the treatment of Alzheimer's disease.

The Role of Microbiome in Brain Development and Neurodegenerative Diseases.

Hundreds of billions of commensal microorganisms live in and on our bodies, most of which colonize the gut shortly after birth and stay there for the rest of our lives. In animal models, bidirectional communications between the central nervous system and gut microbiota (Gut-Brain Axis) have been extensively studied, and it is clear that changes in microbiota composition play a vital role in the pathogenesis of various neurodevelopmental and neurodegenerative disorders, such as Autism Spectrum Disorder, Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, anxiety, stress, and so on. The makeup of the microbiome is impacted by a variety of factors, such as genetics, health status, method of delivery, environment, nutrition, and exercise, and the present understanding of the role of gut microbiota and its metabolites in the preservation of brain functioning and the development of the aforementioned neurological illnesses is summarized in this review article. Furthermore, we discuss current breakthroughs in the use of probiotics, prebiotics, and synbiotics to address neurological illnesses. Moreover, we also discussed the role of boron-based diet in memory, boron and microbiome relation, boron as anti-inflammatory agents, and boron in neurodegenerative diseases. In addition, in the coming years, boron reagents will play a significant role to improve dysbiosis and will open new areas for researchers.

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboranes, and BODIPY, for the treatment of different human diseases.In addition, we also describe the synthesis, key structure-activity relationship, and associated biological activities, such as antimicrobial, antituberculosis, antitumor, antiparasitic, antiprotozoal, anti-inflammatory, antifolate, antidepressant, antiallergic, anesthetic, and anti-Alzheimer's agents, as well as proteasome and lipogenic inhibitors. This compilation could be very useful in the exploration of novel boron-derived compounds against different diseases, with promising efficacy and lesser side effects.

Bevacizumab and Sinus Venous Thrombosis: A Literature Review.

Pediatric glioma treatment can be confounded by eloquent anatomical location and pathologic and genetic characteristics. Current literature suggests that the vascular endothelial growth factor (VEGF) inhibitor bevacizumab has been linked to enhancing disease control; however, its safety and effectiveness are unknown. Bevacizumab has been linked with an increased incidence of intratumoral hemorrhage as well as arterial and venous thromboembolism. A rare adverse effect of chemotherapeutic treatment with bevacizumab is sinus venous thrombosis (SVT), with only a few cases reported to date. This review highlights the pathophysiology of bevacizumab, its rare and life-threatening side effect of SVT, and future recommendations.

Predictors of Hospitalization for Manic Episode in Alzheimer's Dementia: Inputs From an Inpatient Case-Control Study.

Objectives The correlates of manic episodes in dementia have not been systematically studied. The primary goal of our study is to compare the sociodemographic characteristics and psychiatric comorbidities in Alzheimer's dementia (AD) inpatients with manic episodes versus without manic episodes, and to evaluate the demographic predictors and risk factors for manic episodes in AD inpatients. Methods We conducted a case-control study using the Nationwide Inpatient Sample of 34,285 AD patients (age ≥60 years). Subsequently, the cases i.e., AD inpatients with a manic episode (N = 1,035) and the controls (without a manic episode, N = 1,035), were extracted using propensity-score matching based on age. The cases did not have a past psychiatric history of bipolar disorders. We used the logistic regression model to evaluate the odds ratio (OR) of association between pre-existing psychiatric comorbidities and manic episodes and evaluate the demographic predictors of manic episodes in AD inpatients. Results A higher proportion of AD inpatients with manic episodes were females (63.8%), whites (85.2%), and from low-income families below the 50th percentile (63%). Females were more likely to be hospitalized for manic episodes (OR 1.33; 95% CI 1.09-1.64) than males. AD inpatients with manic episodes had a higher risk of presenting with suicidal behaviors (OR 1.88; 95% CI 1.23-2.86). A significantly higher proportion of AD inpatients with manic episodes had comorbid tobacco use (5.3% vs. 3.4%) and cannabis use (1.4% vs. 0%) compared to those without manic episodes. Conclusion Females with AD had a greater risk of being hospitalized for manic episodes. These patients have an 88% higher risk of suicidal behaviors during the manic presentation and have comorbid tobacco and cannabis use. Early diagnosis and management of manic episodes in at-risk AD patients are important to improve the quality of life (QoL) and outcomes.

Fracture Nonunions and Delayed Unions Treated With Low-Intensity Pulsed Ultrasound Therapy: A Clinical Series.

The incidence of nonunion of fractures has been steadily rising owing to improved life expectancy following severe injuries along with rising cases of polytrauma. Once a nonunion is established, the chances of spontaneous healing are deemed to be quite low. Fracture nonunion continues to be a challenge in clinical practice with nonunions having a considerable impact on patient's quality of life causing both functional and psychosocial disability. Low-Intensity Pulsed Ultrasound (LIPUS) therapy is being projected as a viable and non-interventional alternative to surgical management of nonunions and delayed unions. LIPUS therapy is being widely recommended as a standalone treatment option for the treatment of established nonunions and delayed unions as it is believed to promote healing in all phases of fracture healing viz., inflammatory, intramembranous ossification, chondrogenesis, endochondral ossification and remodelling. In the current scenario of varying results and unclear clinical role of LIPUS therapy, we present a prospective case series of fracture nonunions and delayed unions treated with LIPUS therapy at a large District General Hospital.

Fecal Microbiota Transplantation: A Microbiome Modulation Technique for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia and the fifth leading cause of death among the elderly. AD involves parts of the brain that can lead to progressive memory loss and impaired language skills and cognitive thinking, affecting one's ability to carry out daily activities. Aging, bad dietary habits, family history, as well as altered gut microbiota composition may play a role in the pathogenesis of AD. Although the association between the imbalance of gut microbiota and AD is still difficult to determine, it has been suggested that dysbiosis can lead to the increased secretion of lipopolysaccharides and amyloid, which may impair the permeability of the intestine and the blood-brain barrier. Moreover, it can progress the process of neuroinflammation, amyloid-beta formation, and ultimately neuronal death. Microbiota-targeted interventions such as personalized diet, probiotics, or fecal microbiota transplantation (FMT) might represent a potential therapeutic option for AD. This review article discusses the procedure of FMT and its possible side effects on the recipient's body. In addition, we review the role of FMT in the context of its application in various nervous system-related disorders (AD, Parkinson's disease, multiple sclerosis).