Archives of internal medicine research最新文献

Tuberculous meningitis (TBM), the most severe manifestation of extrapulmonary tuberculosis, poses significant global health challenges due to its high mortality rates and complex pathophysiology. This review synthesizes recent findings on TBM, covering epidemiology, pathogenesis, clinical manifestations, diagnostics, and management strategies. TBM disproportionately affects immunocompromised populations, including individuals with HIV, with the highest mortality observed in low-resource settings. Pathogenesis involves Mycobacterium tuberculosis breaching the blood-brain barrier, eliciting a granulomatous inflammatory response that contributes to neurotoxicity. Advances in diagnostics, such as next-generation sequencing and novel imaging techniques, have improved early detection and treatment guidance. Management strategies emphasize multidrug regimens, adjunctive corticosteroids, and emerging therapies like intrathecal administration and nanoparticle-based drug delivery. Host-directed therapies targeting immune modulation and oxidative stress show promise in improving outcomes, particularly for drug-resistant TBM. Despite advancements, diagnostic delays, treatment resistance, and high rates of neurological effects underscore the need for further research. Preventive strategies focusing on early diagnosis, modifiable risk factor management, and public health interventions are critical to reducing global burden of TBM. This review highlights the importance of integrating innovative diagnostics, tailored treatments, and preventive measures to address the challenges of TBM and improve patient outcomes.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can be managed with a range of therapeutic treatments. Methotrexate (MTX) is a first-line treatment for RA; however, its metabolism in RA patients can be complicated by multiple factors. Therefore, understanding these specific factors is crucial for optimizing the efficacy of MTX to provide improved therapeutic outcomes for patients. This article explores existing literature to examine how MTX metabolism in RA patients is impacted by other commonly used medications for RA. Additionally, the review explores the role of genetics by investigating the impact that single nucleotide polymorphisms (SNPs) have on MTX metabolism. Key findings from this review highlight how MTX metabolism can be enhanced or impaired based on specific combination therapies and how alternative treatments are considered with MTX treatment failure. MTX metabolism can also vary across different racial, ethnic, and population-based groups due to the presence of distinct SNPs in their genetic profiles. These results underscore the importance of personalized treatment approaches when treating RA patients with MTX, as its metabolism is influenced by factors such as drug interactions and SNPs. Future research is needed to expand our understanding of these factors to further improve therapeutic outcomes in RA patients.

Bioaerosols-airborne particles of biological origin such as bacteria, fungi, viruses, and allergens-are increasingly recognized as critical environmental factors in the pathogenesis of airway diseases, particularly asthma. This article provides current understanding of how bioaerosols interact with the airway epithelium to initiate acute immune responses, promote chronic inflammation, and drive airway remodeling. Key mechanisms include disruption of mucociliary clearance, activation of innate immune receptors such as TLRs and PRRs, and the role of surfactant proteins SP-A and SP-D in modulating allergic inflammation. Chronic exposure leads to cytokine-mediated fibrosis and smooth muscle hypertrophy, contributing to steroid-resistant asthma. Genetic polymorphisms, especially in innate immunity genes like TLR2, TLR4, and CD14, influence individual susceptibility. The complexity of bioaerosol composition, coupled with environmental variability and lack of standardized exposure thresholds, presents challenges for effective monitoring. However, emerging strategies such as source control, improved ventilation, HEPA filtration, UV disinfection, and real-time airborne pathogen detection offer promising avenues for exposure mitigation. This comprehensive review underscores the need for interdisciplinary approaches to better understand and manage bioaerosol-related respiratory health risks.

Stroke is a leading cause of long-term disability, and enhancing neural plasticity is a central strategy in promoting functional recovery. This review examines a range of interventions that target plasticity to improve outcomes in stroke survivors. Neural plasticity is assessed using neuroimaging tools, such as fMRI, EEG, and fNIRS, as well as clinical scales, including the Fugl-Meyer Assessment (FMA) and the Modified Rankin Scale (mRS). Biomarkers, like brain-derived neurotrophic factor (BDNF), GABA, and nerve growth factor (NGF), are also useful for predicting patient outcomes. These tools offer insight into recovery potential and intervention effectiveness. The interventions discussed include physical therapy, cognitive behavioral therapy (CBT), dietary support, and emerging technologies such as virtual reality, video games, and exoskeleton-assisted training. Pharmacological strategies, including Levodopa, selective serotonin reuptake inhibitors (SSRIs), and ginkgo diterpene lactone meglumine (GDLM), have shown mixed results, while stem cell therapies remain under investigation. Physical therapy remains the foundational treatment, but other interventions may provide added benefit depending on patient characteristics. This review highlights the need for a personalized, multidimensional approach to stroke rehabilitation. Continued research is necessary to refine these therapies and optimize recovery through tailored treatment strategies.

Multiple Sclerosis is a chronic neurological disorder characterized by progressive disability, with falls being a significant consequence of its physical and cognitive impairments. This review explores the major contributors to fall risk in individuals with multiple sclerosis and explores the broader implications of these factors, such as the fear of falling. The primary factors associated with fall risk include gait abnormalities, cognitive dysfunction, and fatigue. These factors often interact, leading to mobility limitations and diminishing overall quality of life. Interventions to mitigate fall risk in multiple sclerosis have shown varying degrees of success. Exercise and rehabilitation strategies improve physical function and balance, while cognitive-behavioral therapy addresses fatigue and associated symptoms. Self-management programs empower patients to take an active role in symptom management, though their effectiveness varies. Disease-modifying therapies are the primary treatment for slowing disease progression, indirectly reducing fall risk. Emerging technologies show promise in enhancing mobility and safety, while machine learning algorithms offer the potential for predicting fall risk in multiple sclerosis populations. This review underscores the need for a comprehensive approach to fall prevention in multiple sclerosis. Healthcare providers can develop personalized strategies to improve mobility, reduce fall incidence, and enhance the quality of life for individuals with multiple sclerosis. Further research is essential to refine these interventions and optimize long-term outcomes.

Type 2 Diabetes Mellitus therapy has evolved over the years to now include a new class of therapeutics, semaglutide. This article reviews the mechanism of action and formulation of semaglutide therapy, potential benefits, contraindications, adverse effects, and drug interactions. Oral and subcutaneous semaglutide therapies have shown effectiveness in improving glycemic control, weight loss, and reducing cardiovascular risks associated with diabetes mellitus. Semaglutide has also shown potential in being used as a therapeutic strategy in Alzheimer's disease due to its anti-neuroinflammatory effects and being used to treat polycystic ovary syndrome. However, semaglutide therapy is also associated with concerning adverse effects like acute pancreatitis, anesthetic risks like pulmonary aspiration or residual gastric content, acute kidney injury, acute gallbladder injury, nonarteritic anterior ischemic optic neuropathy and diabetic retinopathy. Contraindications of semaglutide include history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and pregnancy. Drug interactions to consider with semaglutide therapy include those also used in diabetes treatment, like metformin, as well as anti-psychotics, due to anti-psychotics associated weight gain. The findings of this article emphasize the need for a cross-disciplinary approach to understand the molecular mechanisms and clinical implications of semaglutide on patients with complex medical histories and treatment regimens. The potential anesthetic risks of semaglutide therapy warrant careful consideratiion with ethical concerns. Further studies can assess if there is a need to modify pre-operative guidelines to account for patient using semaglutide and how delayed gastric emptying and constitpation will affect surgical outcomes and complications. While semaglutide therapy for diabetes mellitus has been established, there is a need for extensive research on repurposing semaglutide in neurodegenerative disease treatment.

Atopic dermatitis (AD), also known as eczema, is an inflammatory dermatologic condition that results in inflamed, itchy skin lesions. The development of this condition is governed by a variety of genetic and environmental factors including lifestyle habits. The severity of atopic dermatitis has been attributed to be affected by various lifestyle factors, prompting the interest in utilizing lifestyle modifications as a form of treatment for atopic dermatitis symptoms. Many research studies have been conducted to investigate the effects of different factors such as sleep, stress, diet, smoking and tobacco use, exposure to various temperatures and humidity levels, and skincare and cosmetic products on atopic dermatitis symptoms, and how certain habits can be modified to manage AD conditions. Current studies have demonstrated the significant impact some lifestyle modifications can elicit with improving atopic dermatitis, while also discussing other lifestyle factors that require further research to determine their effects on AD. This review article summarizes the findings in the current literature that investigates the role of different lifestyle habits on the severity and exacerbation of atopic dermatitis, and explores the mechanisms in which these behaviors can trigger AD.

Glucocorticoids are the cornerstone of asthma therapy due to their potent anti-inflammatory action. However, a subset of severe asthmatics do not respond to the standard glucocorticoid treatment. Such phenomenon is referred to as glucocorticoid insensitivity (GCI). From a clinical point of view, GCI is characterized by the reduced therapeutic response with improvement of less than 10-15% in lung function parameters, such as FEV1, upon the administration of an adequate glucocorticoid dose. The mechanisms underlying GCI involve disrupted glucocorticoid receptor (GR) signaling, overexpression of the dominant-negative GRβ isoform, increased activity of pro-inflammatory transcription factors such as NF-κB and AP-1, and abnormal GR phosphorylation by kinases such as p38 MAPK. These altered molecular pathways undermine the anti-inflammatory effects of glucocorticoids on immune and structural airway cells, thus maintaining the chronicity of airway inflammation and remodeling. GCI can be of innate genetic origin, as in the case of GR mutations, or acquired through environmental exposures, including viral infections, smoking, and long-term exposure to pollutants in the environment. GCI represents a big challenge in the management of asthma, since a large proportion of cases do not achieve an adequate level of control with the standard treatment options. Recent advances in the understanding of the molecular mechanisms underlying GCI have enabled the development of novel therapeutic strategies, including biologic therapies targeting interleukin-5 and IL-13, Janus kinase inhibitors, and small-molecule drugs aimed at restoring GR function. This article presents a critical discussion on the current state of knowledge regarding the glucocorticoid resistance mechanisms in asthma, identifying the clinical effects of new therapeutic strategies, with special emphasis on the need for personalized treatment regimens to improve outcomes in glucocorticoid insensitivity.

The review delves into the methods for the quantitative assessment of intracellular effectors and cellular response of Receptor for Advanced Glycation End products (RAGE), a vital transmembrane receptor involved in a range of physiological and pathological processes. RAGE bind to Advanced Glycation End products (AGEs) and other ligands, which in turn activate diverse downstream signaling pathways that impact cellular responses such as inflammation, oxidative stress, and immune reactions. The review article discusses the intracellular signaling pathways activated by RAGE followed by differential activation of RAGE signaling across various diseases. This will ultimately guide researchers in developing targeted and effective interventions for diseases associated with RAGE activation. Further, we have discussed how PCR, western blotting, and microscopic examination of various molecules involved in downstream signaling can be leveraged to monitor, diagnose, and explore diseases involving proteins with unique post-translational modifications. This review article underscores the pressing need for advancements in molecular approaches for disease detection and management involving RAGE.

Atopic dermatitis is a heterogenous inflammatory skin illness that may last for long time and affect people of different racial and ethnic backgrounds. The condition primarily appears in infants and young children. There are people living with atopic dermatitis in every country and every ethnic group, although the frequency of the disease varies greatly. Due to the varied clinical presentations that atopic dermatitis can have, it can be challenging to characterize and diagnose the disease, particularly in adults. Nevertheless, there exists a dearth of information pertaining to the various presentations of atopic dermatitis among individuals from diverse racial and cultural groups. This critical review article offers a succinct and comprehensive overview of the current findings on the epidemiology of atopic dermatitis with regards to ethnic and racial disparities. The findings hold potential significance in advancing the development of targeted treatments for personalized medicine approaches and enhancing the quality of life for patients with atopy.