Neurological, cardiac, musculoskeletal, and renal manifestations of scleroderma along with insights into its genetics, pathophysiology, diagnostic, and therapeutic updates.

Background: Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. Methodology: A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Results: Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti-centromere antibodies, and anti-topoisomerase antibodies, are important for classifying diseases and predicting their outcomes. Discussion: The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Conclusion: Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

Association of Parkinson's disease to Parkinson's plus syndromes, Lewy body dementia, and Alzheimer's dementia.

Background: Parkinson's disease (PD) is a condition that affects movement and is usually seen in those over the age of 50. It is caused by the death of dopaminergic neurons, particularly in the substantia nigra. PD has shifted from being perceived as an uncommon condition to a significant neurological illness, mostly due to the increasing number of elderly individuals and the impact of environmental factors. Parkinson's plus syndromes, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism (VaP), provide difficulties in distinguishing them clinically from PD since they have similar characteristics. Methodology: A thorough examination was performed utilizing the PubMed, Medline, Scopus, and Web of Science databases. The search utilized specific keywords like "Parkinson's disease," "Parkinson's plus syndrome," "Lewy body dementia," "Alzheimer's dementia," "progressive supranuclear palsy," and "multiple system atrophy." The selection criteria were aimed at English-language literature, with a particular focus on examining the connection between PD and associated disorders or dementias. Results and Discussion: Parkinson's plus syndromes, such as PSP, MSA, CBD, and VaP, exhibit unique clinical characteristics, imaging results, and diverse reactions to levodopa. This makes it difficult to distinguish them from PD. LBD is characterized by Lewy bodies containing α-synuclein, which leads to both motor and cognitive deficits. PD and Alzheimer's disease (AD) exhibit a complex interaction, including common pathogenic processes, genetic predispositions, and clinical characteristics of dementia. Conclusion: The interrelatedness of PD, Parkinson's plus syndromes, LBD, and AD highlights the significance of comprehending shared disease-causing processes. Aberrant protein clumping, impaired functioning of mitochondria, increased oxidative stress, and inflammation in the brain are common factors which can be addressed for specific treatments. More research is essential for understanding complicated connections and developing effective therapies for these sophisticated neurological illnesses.

Precision Medicine Approaches in Cardiology and Personalized Therapies for Improved Patient Outcomes: A systematic review.

Personalized medicine is a novel and rapidly evolving approach to clinical practice that involves making decisions about disease prediction, prevention, diagnosis, and treatment by utilizing modern technologies. The concepts of precision medicine have grown as a result of ongoing developments in genomic analysis, molecular diagnostics, and technology. These advancements have enabled a deeper understanding and interpretation of the human genome, allowing for a personalized approach to clinical care. The primary objective of this research is to assess personalized medicine in terms of its indications, advantages, practical clinical uses, potential future directions, problems, and effects on healthcare. An extensive analysis of the scientific literature regarding this topic demonstrated the new medical approach's relevance and usefulness, as well as the fact that personalized medicine is becoming increasingly prevalent in various sectors. The online, internationally indexed databases PubMed and Cochrane Reviews were used to conduct searches for and critically evaluate the most relevant published research including original papers and reviews in the scientific literature. The findings suggest that precision medicine has a lot of potential and its implementation lowers the incidence of stroke as well as coronary heart disease and improves patient health in cardiology.

Association of multiple sclerosis with stroke: A comprehensive review.

Background: Multiple sclerosis (MS) is a chronic immune-mediated disorder characterized by the degradation of the myelin sheath in the central nervous system. Research indicates that individuals with MS exhibit a higher susceptibility to stroke compared to the general population. This association is rooted in shared underlying mechanisms, specifically involving neuroinflammatory processes. Methodology: We performed an extensive search on PubMed, MEDLINE, Embase, Scopus, and Google Scholar using specific terms. The search terms included variations of "multiple sclerosis," "stroke," "cerebrovascular disease," "vascular risk factors," "disease-modifying therapies," and "neuroinflammation." The search was limited to articles published from January 1, 2000, up to 31 May, 2023. Results and Discussion: Stroke, a global health burden characterized by significant mortality and adult disability, underscores the critical importance of understanding the link between MS and stroke. Despite a growing body of research establishing an elevated risk of stroke in MS patients, notable information gaps persist. Limited prospective multicenter studies on stroke incidence in MS patients contribute to an incomplete understanding of the precise relationship between these two conditions. Conclusion: In conclusion, this review underscores the critical need for a thorough understanding of the complex relationship between MS and stroke. The identified risk factors and the influence of MS DMTs on stroke risk necessitate further investigation to inform evidence-based preventive and therapeutic strategies. Bridging the existing information gaps through prospective multicenter studies is imperative for a comprehensive understanding of this association. The development of targeted diagnostic and therapeutic approaches for acute stroke risk in MS patients is paramount to mitigate the impact of these debilitating conditions. Ultimately, this review serves as a foundation for future efforts to enhance preventative measures and therapeutic interventions, thereby improving the overall quality of life for individuals with MS susceptible to strokes.

The effects of the interplay between vitamins, antibiotics, and gut microbiota on the pathogenesis and progression of dementia: A systematic review and meta-analysis.

Background: Given that there is already evidence of a neural network that connects the brain and gut and that the gut microbiota actively modulates gut health, it is crucial to know which foods, supplements, and medications to use or avoid when treating any disease that causes dementia or cognitive impairment. Previous research has examined the relationships between vitamins, antibiotics, and gut microbiota and the correlations between these factors and dementia. The question arises of how these three factors interact together and if evidence suggests one element is more important than the others in the pathogenesis and development of dementia. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards were followed when conducting this review. The papers' publication dates varied from (2012-2022). Cochrane/EMBASE, PEDro, and PubMed/Medline databases were searched. The precise terms "gut microbiota," vitamins," antibiotics," and "dementia" were included in the search method, along with the conjunctions "OR" and "AND." Results: Gut dysbiosis has a significant impact on cognition, brain function, and the development and progression of dementia. The two most popular probiotics used in studies linked to cognition benefits were Lactobacillus and Bifidobacterium. Numerous scales were used to evaluate cognition, but the mini-mental state examination was the most popular, and the most prevalent impairment was Alzheimer's disease. The supplements with the most significant impact on gut microbiota were vitamin B-12 and folic acid. Conclusion: This systematic review concluded that vitamins, gut microbiota and antibiotics have a close association with the development of dementia. More research is required to establish causality and elucidate the underlying mechanisms because there is still little evidence connecting the interactions of vitamins, medications, and microbiota with dementia. The complexity of interactions between genetics, lifestyle factors, and comorbidities, as well as the heterogeneity of dementia, may make it more challenging to interpret the findings.

Parkinson's disease updates: Addressing the pathophysiology, risk factors, genetics, diagnosis, along with the medical and surgical treatment.

After only Alzheimer's disease (AD), Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. The incidence of this disease increases with age, especially for those above 70 years old. There are many risk factors that are well-established in the contribution to the development of PD, such as age, gender, ethnicity, rapid eye movement sleep disorder, high consumption of dairy products, traumatic brain injury, genetics, and pesticides/herbicides. Interestingly, smoking, consumption of caffeine, and physical activities are the protective factors of PD. A deficiency of dopamine in the substantia nigra of the brainstem is the main pathology. This, subsequently, alters the neurotransmitter, causing an imbalance between excitatory and inhibitory signals. In addition, genetics is also involved in the pathogenesis of the disease. As a result, patients exhibit characteristic motor symptoms such as tremors, stiffness, bradykinesia, and postural instability, along with non-motor symptoms, including dementia, urinary incontinence, sleeping disturbances, and orthostatic hypotension. PD may resemble other diseases; therefore, it is important to pay attention to the diagnosis criteria. Parkinson's disease dementia can share common features with AD; this can include behavioral as well as psychiatric symptoms, in addition to the pathology being protein aggregate accumulation in the brain. For PD management, the administration of pharmacological treatment depends on the motor symptoms experienced by the patients. Non-pharmacological treatment plays a role as adjuvant therapy, while surgical management is indicated in chronic cases. This paper aims to review the etiology, risk factors, protective factors, pathophysiology, signs and symptoms, associated conditions, and management of PD.

Juvenile multiple sclerosis: addressing epidemiology, diagnosis, therapeutic, and prognostic updates along with cognitive dysfunction and quality of life.

Juvenile multiple sclerosis (JMS) is a rare but significant subtype of multiple sclerosis (MS) that affects a small percentage of patients under the age of 10 and 3-5% of all MS patients. Despite its rarity, JMS poses unique challenges in terms of diagnosis, treatment, and management, as it can significantly impact a child or adolescent's physical, cognitive, and emotional development. JMS presents with a varying spectrum of signs and symptoms such as coordination difficulties and permanent cognitive dysfunctions and may include atypical clinical features such as seizures, acute disseminated encephalomyelitis, and optic neuritis, making diagnostic evaluations challenging. Whilst the biology of JMS shares similarities with adult-onset MS, there exist notable distinctions in disease progression, clinical manifestations, and ultimate prognoses. The International Pediatric MS Study Group (IPMSSG) was founded in 2005 to improve understanding of JMS, but there remains a lack of knowledge and guidelines on the management of this condition. This review summarizes the current knowledge on JMS, including its epidemiology, clinical presentations, diagnostic challenges, current treatment options, and outcomes. Current treatment options for JMS include disease-modifying therapies, but JMS can also result in impaired quality of life and psychiatric comorbidity, highlighting the need for comprehensive care for affected children. Through gathering and analyzing scattered studies and recent updates on JMS, the authors aim to address the gaps in current knowledge on JMS and provide an improved understanding of appropriate care for affected children. By doing so, this review hopes to contribute to improving the quality of life and outcomes for JMS patients.

Role of Probiotics in the Management of Helicobacter pylori.

The global prevalence of Helicobacter pylori (H. pylori) is estimated to be around 4.4 billion, with the majority of individuals affected in developing countries. Chronic infection of the gram-negative bacterium results in several gastrointestinal pathologies such as chronic gastritis, peptic ulcer, and cancer. Probiotics compete directly with H. pylori and help restore the gut microbial environment; these living microorganisms are comparatively more effective than the standard triple antibiotic regimen in the management of symptoms related to the pathogenic bacteria. The need for alternative therapy is better explained by the increasing rate of antibiotic resistance and the lowering of patient compliance to the standard treatment. Adjuvant administration of probiotics to H. pylori eradication therapy is associated with a higher H. pylori eradication rate, decreased diarrhea-related treatment, less common self-reported side effects, and higher treatment compliance. Therefore, with the ongoing and future resistance to antibiotics, this systematic review aims to investigate the use and efficacy of probiotics when used alone or in conjunction with the current guideline treatment. A literature search was conducted using Pubmed, MEDLINE, and Cochrane for peer-reviewed articles published between January 1, 2016 and April 2022. MeSH terms used were: "H. pylori," "H. pylori and probiotics," "Probiotics," "H. pylori treatment," "Mechanism of Action" with subheadings as "clinical manifestations," "treatment," and "diagnosis." All literature reviews, original papers, and case reports were included. This search strategy aimed to find literature that could describe the transmission and mechanism of action of H. pylori, the current treatment guidelines, and the efficacy of probiotics in eradicating H. pylori.

Retraction: Comparison of Outcomes of Percutaneous Nephrolithotomy (PCNL) Between Adults and Pediatrics Population: A Single-Center Retrospective Study.

[This retracts the article DOI: 10.7759/cureus.22690.].

Comparison of Outcomes of Percutaneous Nephrolithotomy (PCNL) Between Adults and Pediatrics Population: A Single-Center Retrospective Study.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) has almost completely replaced open surgery for kidney stones because of continuous advancements in the method since the first PCNL was performed in 1976. The aim of this study is to compare the characteristics and outcomes of adult patients and pediatric patients who had undergone PCNL. METHODOLOGY: A retrospective study was conducted at the Sindh Institute of Urology and Transplantation (SIUT) Hospital in Karachi, Pakistan. It included the data of patients who underwent PCNL from January 2015 to January 2022 at the SIUT hospital. The primary outcome variable was the stone-free rate (SFR). Secondary outcomes included length of hospital stay, and complications were assessed using modified Clavien classification system Results: There is no significant difference in the SFR at discharge between pediatric and adult patients (86.67% vs 88.69%, p=0.634). There is no significant difference between the two groups in relation to the total length of hospital stay (p=0.446). Moreover, 12.50% and 11.11% of adults and children developed complications, respectively, after the procedure. The percentages are not significantly different between the two groups (p=0.266). CONCLUSION: The current study using standardized and consistent PCNL techniques shows that SFR is similar in both adults and children, and there is no difference in complications between adults and children.

The Role and Efficacy of Coenzyme Q10 in the Management of Erectile Dysfunction in a Hypertensive Male: An Interventional Study.

Introduction Erectile dysfunction (ED) is a prevalent medical condition that affects millions of men globally. A number of pharmacological and complementary options are used in the management of ED, including Coenzyme Q10 (CoQ10). Oxidative stress has been linked to the progression of ED, and Co Q10 protects against oxidative damages and improves erectile function as well as the activity of antioxidant enzymes. This study aimed to determine the efficacy of CoQ10 in the treatment of erectile dysfunction in hypertensive males. Method An open-labeled parallel arm interventional study was conducted in the cardiology unit of Hayatabad Medical Complex Hospital, Peshawar, Pakistan, from March 2020 to March 2021. Hypertensive male patients (n = 230) were randomly allocated to either receiving 200-gram CoQ10 daily along with their current antihypertensive therapy (n=104) or anti-hypertensive treatment only (n=105). The patient's erectile function was assessed at baseline and three months using the International Index of Erectile Function Test (IIEF-5) during the study period. Result Of the total 230, 209 (90.87%) patients were included in the final analysis. There were no significant differences in demographics, history of illness, co-morbid conditions, and current medication of both groups. After three months, 21 (20.1%) participants scored more than 17 in the IIEF-5 and no longer had ED. Overall, no significant difference was found in the mean IIEF-5 score between the study group and control group (14.41 ± 4.49 Vs. 15.61 ± 4.82; p=0.06). However, in subgroup analysis, significant improvement in the study group was seen in participants with mild ED (p=0.03). Conclusion With the demonstration of its efficacy in hypertensive patients with mild ED, co-enzyme Q10 supplementation can be proposed as a potential candidate in patients with long-term hypertension and can play a role in erectile dysfunction.

Association between Spontaneous Otoacoustic Emission and Psychoacoustic measures.

AIM: The aim of the present study was to evaluate the association of presence and absence of spontaneous otoacoustic emissions (SOAEs) on different psycho-acoustic measures such as intensity discrimination, gap detection test, duration discrimination test, modulation detection for sinusoidal amplitude modulated noise at 8, 20, 60, and 100 Hz. METHOD: Sixty adults with hearing sensitivity within normal limits were divided into two groups; group 1 consisted of participants with SOAEs present and group 2 consisted of participants with SOAEs absent. All the participants were tested for presence of SOAEs and different psycho-acoustic measures. RESULTS: The present study results showed no significant difference on intensity discrimination, gap detection test, duration discrimination test, modulation detection for sinusoidal amplitude modulated noise at 8, 20, 60, and 100 Hz in presence and absent of SOAE. CONCLUSION: The findings reveals that the presence or absence of SOAE did not influence or enhance the psychophysical performance at most comfortable level in individuals having normal hearing.

Effect of pre-existing left bundle branch block on post-procedural outcomes of transcatheter aortic valve replacement: a meta-analysis of comparative studies.

BACKGROUND: As an established procedure for patients with aortic valve stenosis and a high surgical risk profile, transcatheter aortic valve replacement (TAVR) can be associated with conductance abnormalities. However, data regarding the impact of pre-existing left bundle branch block (LBBB) on post-TAVR outcome is scarce. OBJECTIVES: We conducted this meta-analysis to pool available data in the literature on the impact of pre-existing LBBB on the clinical outcomes of patients undergoing TAVR. METHODS: We queried Medline/PubMed, Scopus, and Cochrane Library to identify comparative studies of patients with and without a pre-existing LBBB undergoing TAVR for aortic stenosis. Risk ratio (RR) and the corresponding 95% confidence interval (95% CI) were estimated to measure the effect of pre-existing LBBB on developing post-procedure stroke, permanent pacemaker implantation (PPM), or moderate/severe aortic regurgitation (AR). RESULTS: Data of three clinical trials encompassing 4,668 patients undergoing TAVR were included in this meta-analysis. Patients with pre-existing LBBB prior to TAVR had an increased risk of developing moderate/severe AR (RR = 1.04 [0.79-1.37]; P = 0.77), stroke (RR = 1.72 [0.61-4.85]; P = 0.31), and a need for PPM implantation (RR = 4.43 [0.43-45.64]; P = 0.21) following TAVR. CONCLUSION: Preexisting LBBB seems to increase the risk of developing stroke, aortic regurgitation, and the need for a permanent pacemaker implantation. However, due to scarcity of data and high heterogeneity among the current studies, further clinical trials are warranted.

Optimized adenovirus-antibody complexes stimulate strong cellular and humoral immune responses against an encoded antigen in naive mice and those with preexisting immunity.

The immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity. In vitro and in vivo assays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 10(11) adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND(50)) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND(50) formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P = 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND(50)) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND(50)) and humoral (0.0005 ND(50)) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.