The Role of Circadian Rhythms in Stroke: A Narrative Review.

Stroke, a debilitating condition often leading to long-term disability, poses a substantial global concern and formidable challenge. The increasing incidence of stroke has drawn the attention of medical researchers and neurologists worldwide. Circadian rhythms have emerged as pivotal factors influencing stroke's onset, pathogenesis, treatment, and outcomes. To gain deeper insights into stroke, it is imperative to explore the intricate connection between circadian rhythms and stroke, spanning from molecular mechanisms to pathophysiological processes. Despite existing studies linking circadian rhythm to stroke onset, there remains a paucity of comprehensive reviews exploring its role in pathogenesis, treatment, and prognosis. This review undertakes a narrative analysis of studies investigating the relationship between circadian variation and stroke onset. It delves into the roles of various physiological factors, including blood pressure, coagulation profiles, blood cells, catecholamines, cortisol, and the timing of antihypertensive medication, which contribute to variations in circadian-related stroke risk. At a molecular level, the review elucidates the involvement of melatonin, circadian genes, and glial cells in the pathophysiology. Furthermore, it provides insights into the diverse factors influencing stroke treatment and outcomes within the context of circadian variation. The review underscores the importance of considering circadian rhythms when determining the timing of stroke interventions, emphasizing the necessity for personalized stroke management strategies that incorporate circadian rhythms. It offers valuable insights into potential molecular targets and highlights areas that require further exploration to enhance our understanding of the underlying pathophysiology. In comparison to the published literature, this manuscript distinguishes itself through its coverage of circadian rhythms' impact on stroke across the entire clinical spectrum. It presents a unique synthesis of epidemiological, clinical, molecular, and cellular evidence, underscoring their collective significance.

Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment.

Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and expectoration. Airway mucus function as a native immune system of the lung that severs to trap particulate matter and pathogens and allows them to clear from the lung via cough and ciliary transport. Chronic mucus hypersecretion (CMH) is the main factor contributing to the increased risk of morbidity and mortality in specific subsets of COPD patients. It is, therefore, primarily important to develop medications that suppress mucus hypersecretions in these patients. Although there have been some advances in COPD treatment, more work remains to be done to better understand the mechanism underlying airway mucus hypersecretion and seek more effective treatments. This review article discusses the structure and significance of mucus in the lungs focusing on gel-forming mucins and the impacts of CMH in the lungs. Furthermore, we summarize the article with pharmacological and nonpharmacological treatments as well as novel and interventional procedures to control CMH in COPD patients.

The crisis of physician well-being in Nepal: a multifaceted dilemma demanding urgent intervention.

The healthcare system in Nepal faces challenges despite the establishment of numerous medical colleges and an increasing number of doctors. The distribution of medical colleges is disproportionately concentrated in urban areas, leaving rural populations without quality health care. The mental well-being of physicians is a growing concern, with studies indicating high levels of burnout, stress, and depression among healthcare workers, worsened by the Coronavirus Disease 2019 (COVID-19) pandemic. Rising suicide rates among medical professionals highlight the severity of burnout and depression in the healthcare sector. Factors contributing to this crisis include inadequate recruitment in government hospitals, a shortage of healthcare professionals, and inefficiencies in resource distribution. Attacks on physicians have become alarmingly frequent, necessitating comprehensive studies to understand the challenges faced by different specialties and the impact of rural versus urban settings. To address these issues, prompt filling of vacant positions in government hospitals and prioritizing physicians' mental health is crucial. The government should offer competitive salaries, effective management, and supportive working environments to combat the brain drain. Initiatives inspiring professionals to stay in Nepal, along with maintaining the National Health Insurance Program and controlling healthcare privatization, are necessary. Resilience training, professional programs, and improved infrastructure in government medical colleges are vital. This crisis demands global attention and a national study to evaluate burnout, depression, and suicide among healthcare professionals. By addressing these challenges and supporting the well-being of healthcare workers, Nepal can work toward a sustainable healthcare system that provides quality care for all.

A peek behind the curtain in the diagnosis and management of COVID­19­Associated Mucormycosis (CAM).

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/without mechanical ventilators and corticosteroids administration. The current review aims to outline the journey of patients with CAM as well as the advantages and disadvantages of the currently available diagnostic techniques. It also discussed the current status of treatment options and caveats in the management of mucormycosis. Multidisciplinary team, early diagnosis, controlling the predisposing condition(s), complete surgical debridement, effective antifungal therapies (e.g., amphotericin B, isavuconazole, and posaconazole), and implementing antifungal stewardship programs are imperative in CAM cases.

The role of 5-lipoxygenase in the pathophysiology of COVID-19 and its therapeutic implications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as coronavirus disease 2019 (COVID-19) causes cytokine release syndrome (CRS), leading to acute respiratory distress syndrome (ARDS), acute kidney and cardiac injury, liver dysfunction, and multiorgan failure. Although several studies have discussed the role of 5-lipoxygenase (5-LOX) in viral infections, such as influenzae and SARS, it remains unexplored in the pathophysiology of COVID-19. 5-LOX acts on free arachidonic acid (AA) to form proinflammatory leukotrienes (LTs). Of note, numerous cells involved with COVID-19 (e.g., inflammatory and smooth muscle cells, platelets, and vascular endothelium) widely express leukotriene receptors. Moreover, 5-LOX metabolites induce the release of cytokines (e.g., tumour necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and interleukin-1ß [IL-1ß]) and express tissue factor on cell membranes and activate plasmin. Since macrophages, monocytes, neutrophils, and eosinophils can express lipoxygenases, activation of 5-LOX and the subsequent release of LTs may contribute to the severity of COVID-19. This review sheds light on the potential implications of 5-LOX in SARS-CoV-2-mediated infection and the anticipated therapeutic role of 5-LOX inhibitors.

"Knowledge regarding cardiopulmonary resuscitation among health assistants in Nepal: A cross-sectional study".

BACKGROUND: Health assistants play a crucial role in healthcare delivery, particularly in remote and rural areas of Nepal. They should have adequate lifesaving and resuscitation skills. Therefore, assessing their cardiopulmonary resuscitation (CPR) knowledge is essential. OBJECTIVE: To evaluate the knowledge of CPR among health assistants (HAs) in Nepal and explore if there were variations in knowledge scores based on the demographic characteristics of the participants. METHODS: A quantitative cross-sectional research design was used. The study population included HAs registered with the Nepal Health Professional Council (NHPC) who completed three years of training. Non-probability convenience sampling was employed. Data was collected using an online survey based on the 2020 American Heart Association guidelines. Demographic information and participants' knowledge levels were noted. RESULTS: The study involved 500 HAs, with the majority being male and working in government hospitals. Most participants were from Madhesh Province, and the median age was 26 years. Only a fraction of the participants had received training in CPR, and none of them had ever performed CPR. The median knowledge scores were higher among males and among respondents from Madhesh, Lumbini, Karnali, and Sudhurpaschim provinces. The HA's knowledge of the correct depth of CPR compression for children (21%) and infants (17.4%) was limited. CPR scores were different according to variables like training, theory understanding, and practice duration, among others. The findings highlighted the need for more practical training and regular refresher courses to enhance HAs ability to provide life-saving interventions. CONCLUSION: The study revealed less CPR knowledge and a lack of practical training among HAs in Nepal. To improve healthcare outcomes, providing practical training and ongoing education on CPR is crucial. The findings can contribute to curriculum development and policy changes in healthcare delivery.