Antimicrobial and Synergistic Effects of Syzygium cumini, Moringa oleifera, and Tinospora cordifolia Against Different Candida Infections.

Introduction The burden of multiple drug resistance in human pathogens has necessitated the search for and development of antimicrobial agents with a wide range of structural classes and potentials to selectively act on the several mechanisms of actions exhibited by the pathogens. However, most synthetic antimicrobial agents have been linked with adverse side effects and high costs, furthering the need to explore more options. Syzygium cumini, Moringa oleifera, and Tinospora cordifolia are three medicinal plants used in traditional medicine systems for various infectious diseases. They contain various phytochemicals that exhibit antimicrobial activities against various bacteria, fungi, and parasites. The mechanisms of their antimicrobial action may involve the disruption of microbial cell walls and membranes, the inhibition of microbial enzyme and biofilm formation, the modulation of microbial gene expression and quorum sensing, and the induction of microbial cell death. Therefore, the present study evaluated the potentials of aqueous and ethanol extracts of S. cumini, M. oleifera, and T. cordifolia in managing infections as measured by their inhibitory effects on species. Materials and method Syzygium cumini, M. oleifera, and T. cordifolia were obtained and authenticated, and their aqueous and ethanol extracts were prepared. The antibacterial properties of the aqueous and ethanol extracts were examined. In addition to broth microdilution and biofilm development experiments, we also employed disk diffusion and agar-well diffusion techniques. The inocula of various species, including krusei, parapsilosis, utilis, albicans, and glabrata, were prepared for these assays. The synergistic effect of plant extracts with fluconazole was also evaluated. Results Syzygium cumini, M. oleifera, and T. cordifolia emerge as promising sources for the development of effective and sustainable antimicrobial interventions. Interestingly, the aqueous and ethanol extracts were effective against the selected species. Also, the synergistic combination of plant extracts with fluconazole was observed to triple the potency of the extracts. Furthermore, the potency of the plant extract as an antifungal and synergistic agent was ranked as S. cumini > M. oleifera > T. cordifolia. Conclusively, the plant extracts are effective in the management of opportunistic fungal infections.

Pediatric multiple sclerosis: an integrated outlook at the interplay between genetics, environment and brain-gut dysbiosis.

Multiple sclerosis (MS) is a debilitating autoimmune condition caused by demyelination, neurodegeneration and persistent inflammation of the central nervous system. Pediatric multiple sclerosis (PMS) is a relatively rare form of the disease that affects a significant number of individuals with MS. Environmental exposures, such as viral infections and smoking, can interact with MS-associated human leukocyte antigens (HLA) risk alleles and influence the immune response. Upregulation of immune response results in the disruption of immune balance leading to cascade of inflammatory events. It has also been established that gut microbiome dysbiosis poses a higher risk for pro-inflammation, and it is essentially argued to be the greatest environmental risk factor for MS. Dysbiosis can cause an unusual response from the adaptive immune system and significantly contribute to the development of disease in the host by activating pro-inflammatory pathways that cause immune-mediated disorders such as PMS, rendering the body more vulnerable to foreign attacks due to a weakened immune response. All these dynamic interactions between biological, environmental and genetic factors based on epigenetic study has further revealed that upregulation or downregulation of some genes/enzyme in the central nervous system white matter of MS patients produces a less stable form of myelin basic protein and ultimately leads to the loss of immune tolerance. The diagnostic criteria and treatment options for PMS are constantly evolving, making it crucial to have a better understanding of the disease burden on a global and regional scale. The findings from this review will aid in deepening the understanding of the interplay between genetic and environmental risk factors, as well as the role of the gut microbiome in the development of pediatric multiple sclerosis. As a result, healthcare professionals will be kept abreast of the early diagnostic criteria, accurately delineating other conditions that can mimic pediatric MS and to provide comprehensive care to individuals with PMS based on the knowledge gained from this research.

Evaluating phase II results of Baxdrostat, an aldosterone synthase inhibitor for hypertension.

INTRODUCTION: Hypertension, a global health concern, poses a significant risk for other cardiovascular diseases. While lifestyle modifications and interventions like the Dietary Approaches to Stop Hypertension (DASH) diet offer some respite, their maintenance can be challenging. Recently, the spotlight has turned toward the renin-angiotensin-aldosterone system, a crucial player in the pathophysiology of hypertension. Contrary to other drugs, Baxdrostat, an innovative aldosterone synthase inhibitor (ASI), targets aldosterone synthesis, mitigating negative systemic effects. AREAS COVERED: Baxdrostat showcases rapid absorption, high oral bioavailability, and significant selectivity for aldosterone synthase which presents a proactive approach to hypertension management by reducing aldosterone levels. Early trials have demonstrated its potential in lowering blood pressure in resistant hypertension cases. Current clinical trials are also exploring its application in primary aldosteronism and chronic kidney disease, with preliminary findings indicating its promise as a novel antihypertensive agent. This article encapsulates the current state of knowledge regarding Baxdrostat, encompassing its uses, ongoing clinical trials, and potential future clinical applications. EXPERT OPINION: Future research endeavors will play a pivotal role in unveiling the effectiveness and safety profile of this novel medication. Thus, positioning the baxdrostat as a valuable addition to the armamentarium of antihypertensive agents, especially for patients with complex, multifactorial hypertensive conditions.

Changing a Community: A Holistic View of the Fundamental Human Needs and Their Public Health Impacts.

There are many approaches to changing a community to ensure it serves the people's fundamental needs. For example, enabling equitable access to critical aspects of the community, such as quality healthcare, high-quality education, and job training, is vital for promoting community safety through enhancing tolerance and respect for diversity. However, creating a community that serves the fundamental needs of the people demands a substantive investment of effort. Understanding the nature of these efforts requires discussion of community engagement, examining community networks and their role in fostering cooperative action, enhancing public safety, and identifying the structures of involvement and pertinent routes for developing community land. Understanding such efforts entails knowing the issues related to gentrification and disbandment. These hands-on possibilities can help avert the possibility of people being pushed out of their community settings. These insights further shed light on how the family unit and larger community are able to create collective unity and foster each member's responsibility in community service provision that promotes community integration. Examining how violence and other factors affect a community's collective power is necessary to determine how a community can avoid such violence and encourage positive changes at the individual and family levels to promote community cooperation and safety. Essentially, changing a community can yield significant improvements in public health. Addressing factors such as access to nutritious food, healthcare, physical activity, and social amenities and fostering social cohesion through community engagement can collectively contribute to reducing the burden of chronic diseases and promoting overall well-being. This review provides insight into crucial issues that have long plagued the societal disconnect between the local community and the leadership, policymakers, or other authoritative institutions that govern them, thus affecting the implementation of strategic social and public health initiatives. We will also explore strategies to mitigate these potential pitfalls.

An Integrated Review of Carpal Tunnel Syndrome: New Insights to an Old Problem.

Carpal tunnel syndrome (CTS) is a common entrapment neuropathy characterized by pain, numbness, and impaired function of the hand due to compression of the median nerve at the level of the wrist. Although CTS can develop from repetitive strain, injury, or medical conditions, there are also congenital and genetic risk factors that can predispose individuals to the condition. With respect to anatomical factors, some individuals are born with a smaller carpal tunnel, which increases their susceptibility to median nerve compression. Variations in specific genes, such as those encoding proteins involved in extracellular matrix remodeling, inflammation, and nerve function, have also been linked to an increased risk for CTS. CTS is associated with a high cost of health care maintenance and loss of work productivity. Therefore, it is vital that primary care physicians fully understand the anatomy, epidemiology, pathophysiology, etiology, and risk factors of CTS, so they can be proactive in prevention, diagnosing, and guiding proper treatment. This integrated review also provides insights into how biological, genetic, environmental, and occupational factors interact with structural elements to determine who is most likely to acquire and suffer from CTS. Keeping health practitioners abreast of all the factors that could impact CTS should go a long way in decreasing the health care and socioeconomic burden of CTS.

Right Subclavian Artery With Kommerell's Diverticulum: A Rare Cause of Dysphagia.

Kommerell's diverticulum is an embryologic developmental anomaly of the aortic arch wherein a diverticulum arises from either the left or the right aortic arch. It results due to the persistence of the remnant of the fourth dorsal aortic arch. We present a case of a 66-year-old female presenting with complaints of throat pain and difficulty swallowing. A computed tomography (CT) scan of the neck with contrast revealed an incidental finding of an aberrant right subclavian artery with associated diverticula of Kommerell, measuring up to 1 cm, causing a mass effect on the esophagus and posterior trachea. A diagnosis of dysphagia lusoria was established, and an upper gastrointestinal (GI) series revealed narrowing of the esophagus from posterior extrinsic compression. The patient was discharged home for nutrition optimization with a percutaneous endoscopic gastrostomy (PEG) tube due to significant weight loss from the inability to swallow before proceeding with surgery to repair the aberrant right subclavian artery.

A Case of Thrombotic Thrombocytopenic Purpura and ST-Elevation Myocardial Infarction: An Unusual Correlation.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially devastating blood disorder depicted by thrombocytopenia, fever, widespread small vessel hemolytic anemia, and neurological symptoms. The involvement of the renal and neurological systems is frequently reported in TTP; however, TTP-induced acute coronary syndrome is not widely reported. We describe a case of myocardial infarction induced by TTP in a patient who presented with the typical manifestation of acute coronary syndrome. Echocardiogram revealed a myocardial injury, and detailed investigations revealed increased levels of troponin I, lactate dehydrogenase, diminished levels of haptoglobin and von Willebrand factor-cleaving protease, and schistocytes on peripheral smear, suggestive of TTP-induced myocardial infarction. His condition was stabilized after commencing plasmapheresis, steroids, and rituximab. The initial steps in the management of this patient involve the prompt administration of steroids and the urgent start of plasmapheresis to increase platelet count.

Cerebral Sinus Thrombosis and Immune Thrombocytopenia Post COVID-19 Vaccination: A Case Report and Narrative Review.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the adenoviral vector COVID-19 vaccine is a rare adverse event. Although the risk of VITT following the COVID-19 vaccine appears to be low, early diagnosis and management can be lifesaving. We present a case of VITT in a young female who presented with persistent headaches and fevers followed by anisocoria and right-sided hemiplegia. Initial imaging was unremarkable, and labs showed thrombocytopenia and elevated d-dimers. Repeat imaging revealed thrombosis in the left transverse and superior sagittal sinuses, and she was diagnosed with VITT. She received combined treatment with intravenous immunoglobulins and systemic anticoagulation, resulting in an increased platelet count and resolution of her neurological symptoms.

Aldosterone Synthase Inhibitors and Dietary Interventions: A Combined Novel Approach for Prevention and Treatment of Cardiovascular Disease.

Systemic hypertension (HTN) is the hallmark of cardiovascular disease and the forerunner of heart failure. These associations have been established over decades of research on essential HTN. Advancements in the treatment of patients diagnosed with HTN, consisting of alpha- or beta-adrenergic receptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide, or aldosterone receptor blockers known as anti-mineralocorticoids, in the presence or absence of low sodium salt diets, often fail to control blood pressure adequately to prevent morbidity and mortality. Low sodium diets have had limited success in controlling HTN because low sodium intake is associated with renin-angiotensin-aldosterone system upregulation. Therefore, upregulating aldosterone secretion, sodium, and water retention which, in turn, moves the blood pressure back toward the range of HTN dictated by the baroreceptor reset value, as a compensatory mechanism, especially in resistant HTN. These impediments to blood pressure control in HTN may have been effectively circumvented by the advent of a new class of drugs known as aldosterone synthase inhibitors, represented by baxdrostat. The mechanism of action of baxdrostat as an aldosterone synthase inhibitor demonstrates the inextricable linkage between sodium and blood pressure regulation. Theoretically, combining a low sodium diet with the activity of this aldosterone synthesis inhibitor should alleviate the adverse effect of renin-angiotensin-aldosterone system upregulation. Aldosterone synthesis inhibition should also decrease the oxidative stress and endothelial dysfunction associated with HTN, causing more endothelial nitric oxide synthesis, release, and vasorelaxation. To the best of our knowledge, this is the first systematic review to summarize evidence-based articles relevant to the use of a novel drug (aldosterone synthase inhibitor) in the treatment of HTN and cardiovascular disease. Making the current database of relevant information on baxdrostat and other aldosterone synthase inhibitors readily available will, no doubt, aid physicians and other medical practitioners in their decision-making about employing aldosterone synthase inhibitors in the treatment of patients.

Postprandial Hypotension: An Underreported Silent Killer in the Aged.

Orthostatic hypotension (OH) is one of the most common autonomic dysfunctions, with high prevalence in populations of elderly, hypertensive, diabetic, or Parkinson's patients. Evidence is emerging that OH co-occurs with postprandial hypotension (PPH); a greater prevalence of PPH than of OH is reported for Parkinson's disease patients. OH is diagnosed by measuring the blood pressure changes associated with postural changes and often produces alterations in consciousness or other such bothersome symptoms as fainting. PPH is diagnosed by measuring the blood pressure changes associated with ingesting high carbohydrate test meals. Because of the time lag between food ingestion and absorption, PPH is often not reported as symptomatic and, therefore, not diagnosed as PPH. OH and PPH are independent predictors for all causes of mortality. Relative underdiagnosis may qualify PPH as a "silent killer" disease. This review is aimed at providing updates on the epidemiology, pathophysiology, and clinical aspects associated with the diagnosis and treatment of PPH. Highlighting the current gaps in knowledge and research about PPH is expected to make medical practitioners more cognizant of the dangers of underdiagnosis and motivate future research to identify individuals and populations at high risk for PPH and its sequelae.

Cardiac Rehabilitation and Cardiopulmonary Fitness in Children and Young Adults With Congenital Heart Diseases: A Critically Appraised Topic.

Public health guidelines and a myriad of studies have proven that exercise is beneficial in the alleviation of various cardio-metabolic diseases. Congenital heart disease (ConHD) is one of the most frequently occurring congenital structural malfunctions in the pediatric population, affecting nine of every 1,000 live births. Only a few studies have established the impact of a structured exercise program on cardiopulmonary fitness in diverse groups of patients with ConHD. It is also alarming to know that a substantial number of these patients and their caregivers often remain very wary of exercise. Anxiety about exercise may increase the risk of developing morbid obesity and other long-term health complications of ConHD. The present review of a critically appraised topic is undertaken to answer the question, "Does structured exercise intervention (cardiac rehabilitation) improve cardiorespiratory fitness in children and young adults with ConHD?" Exercise science and the medical literature were searched for studies that engaged the use of aerobic exercise in patients with different ConHD diagnoses. The search yielded four studies after screening with the inclusion and exclusion criteria, which were further narrowed to three studies after a full-text review. These studies yielded results showing significant increments in peak exercise workload, duration, power output, peak oxygen uptake, or improved tissue oxygenation and muscle strength after an exercise training intervention. It is noteworthy that a group identified as "cyanotic palliated" exhibited the most significant impairment both at baseline and after the exercise intervention. This review provides level 1b medical evidence that a structured exercise program may improve cardiopulmonary fitness in patients with ConHD, which is likely to be beneficial to their overall physical, motor, and psychosocial development. The results of this review may be useful for alleviating the anxiety of patients and their caregivers about participation in structured exercise programs. This review should also motivate future research investigations to develop clinical guidelines for the management of patients with ConHD by adding exercise prescriptions to their daily therapeutic regimens.

Rhino-Orbital Cerebral Mucormycosis in a Non-diabetic Patient Following COVID-19 Infection: A Case Report and Literature Review.

Rhino-orbital cerebral mucormycosis has been commonly seen during the coronavirus disease 2019 (COVID-19) pandemic. Several factors responsible for etiology and pathophysiology have been identified, among which corticosteroids and diabetes have contributed to the lion's share of the outbreak of mucormycosis. In this report, we discuss a case of a 41-year-old non-diabetic male with a recent convalescence from COVID-19 infection presented with gradual vision loss and loss of sensations in his right eye. He was found to have periorbital swelling, restriction of extraocular movements in all gazes, chemosis, ptosis of the right eye, and right maxillary sinus tenderness. His serum investigations, radiologic findings, and blood culture were indicative of rhino-orbital cerebral mucormycosis. He was started on systemic liposomal amphotericin B immediately and underwent aggressive surgical debridement. A high index of clinical suspicion, aggressive multifaceted management, and follow-up are needed to have successful outcomes, thereby lowering the morbidity of coronavirus-associated mucormycosis.