Unveiling Annona Reticulata's Bioactive Arsenal for Enhanced Antibiotic Effects.

OBJECTIVE: To study the antibacterial and phytochemical activities of bioactive elements in the leaves of Annona reticulata Linn, a historically used Bangladeshi medicinal plant. METHODS: Shade-dried and crushed plant leaves were soaked with various solvents to obtain samples for different chemical analyses. All extracts were selected for antimicrobial, physicochemical, and Pharmacological investigations. The antimicrobial activity was evaluated using disc diffusion assay, and broth microdilution methods determined potentiation of the activities of the antibiotic antibacterial activity of the plant extracts was investigated using either gram-positive or gram-negative pathogenic wild-type bacteria. RESULTS: From the initial phytochemical and pharmacological studies, it was clear that all extracts, methanol, chloroform, and ethyl acetate, of the leaves of A. reticulata, were proven to process potent bioactive constituents. While differential antimicrobial properties were found to be possessed by all extracts, methanolic extract was the most potent one against all tested microorganisms. It also has potentiated the activities of antibiotics in E. coli. CONCLUSION: Bioactive constituents in the plant extracts were shown to possess phytochemical and antimicrobial activities. More investigation is needed to segregate the chemical components responsible for the respective phytochemical and antimicrobial activities.

Citrus limon L. (lemon) seed extract shows neuro-modulatory activity in an in vivo thiopental-sodium sleep model by reducing the sleep onset and enhancing the sleep duration.

Citrus limon L. is an ingenious alternative medication and has a broad scope in managing several health conditions as part of natural remedies. Recently, medicinal plants have witnessed incredible consideration worldwide in the field of neuroscience for remedial intervention. The present work has investigated the phytochemical compounds and neuropharmacological potential of the seed extract of Citrus limon as a step to partially validate its formulations as nutraceuticals using an in vivo model. Diverse phytochemical groups such as alkaloids, glycosides, flavonoids, tannins, gums, saponins, steroids were qualitatively identified through colorimetric methods utilizing standard compounds. The neuropharmacological properties were studied in Swiss albino mice with the sleep time induced by thiopental sodium taken as an end-point, in standard hole cross, hole board, and open-field experiments at varying doses of 50 and 100 mg/kg body weight. Phytochemical screening showed that alkaloids, flavonoids, saponins, tannins, steroids, and glycosides are present in the aqueous extract of the seed. The extracts demonstrated a significant reduction in sleep onset and enhanced the sleep duration in a dose-dependent manner in thiopental sodium-induced sleeping time, along with a marked decrease in unconstrained locomotors and explorative properties in both hole cross and open field tests. Moreover, in the hole board study, the extracts minimized the count of head dips observed in the treated mice. The results shown in this study demonstrate that Citrus limon extracts have neuropharmacological properties that can be further examined for their potential role as an adjuvant with conventional medications or nutraceuticals.

A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells.

Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics.

Comparing COVID-19 physical distancing policies: results from a physical distancing intensity coding framework for Botswana, India, Jamaica, Mozambique, Namibia, Ukraine, and the United States.

BACKGROUND: Understanding the differences in timing and composition of physical distancing policies is important to evaluate the early global response to COVID-19. A physical distancing intensity monitoring framework comprising 16 domains was recently published to compare physical distancing approaches across 12 U.S. States. We applied this framework to a diverse set of low and middle-income countries (LMICs) (Botswana, India, Jamaica, Mozambique, Namibia, and Ukraine) to test the appropriateness of this framework in the global context and to compare the policy responses in these LMICs with a sample of U.S. States during the first 100-days of the pandemic. RESULTS: The LMICs in our sample adopted wide ranging physical distancing policies. The highest peak daily physical distancing intensity during this period was: Botswana (4.60); India (4.40); Ukraine (4.40); Namibia (4.20); Mozambique (3.87), and Jamaica (3.80). The number of days each country stayed at peak policy intensity ranged from 12-days (Jamaica) to more than 67-days (Mozambique). We found some key similarities and differences, including substantial differences in whether and how countries expressly required certain groups to stay at home. Despite the much higher number of cases in the US, the physical distancing responses in our LMIC sample were generally more intense than in the U.S. States, but results vary depending on the U.S. State. The peak policy intensity for the U.S. 12-state average was 3.84, which would place it lower than every LMIC in this sample except Jamaica. The LMIC sample countries also reached peak physical distancing intensity earlier in outbreak progression compared to the U.S. states sample. The easing of physical distancing policies in the LMIC sample did not discernably correlate with change in COVID-19 incidence. CONCLUSIONS: This physical distancing intensity framework was appropriate for the LMIC context with only minor adaptations. This framework may be useful for ongoing monitoring of physical distancing policy approaches and for use in effectiveness analyses. This analysis helps to highlight the differing paths taken by the countries in this sample and may provide lessons to other countries regarding options for structuring physical distancing policies in response to COVID-19 and future outbreaks.

Implementation of the Treat All Policy Among Persons with HIV Infection Enrolled in Care But Not on Antiretroviral Therapy - India, May 2017-June 2018.

Since September 2015, the World Health Organization has recommended antiretroviral therapy (ART) for all persons with human immunodeficiency virus (HIV) infection, regardless of clinical stage or CD4 count (1). This Treat All policy was based on evidence that ART initiation early in HIV infection as opposed to waiting for the CD4 count to decline to certain levels (e.g., <500 cells/mm3, per previous guidelines), was associated with reduced morbidity, mortality, and HIV transmission (2-4). Further, approximately half of persons enrolled in non-ART care that included monitoring for HIV disease progression (i.e., in pre-ART care) were lost to follow-up before becoming ART-eligible (5). India, the country with the third largest number of persons with HIV infection in the world (2.1 million), adopted the Treat All policy on April 28, 2017. This report describes implementation of Treat All during May 2017-June 2018, by India's National AIDS Control Organization (NACO) and partners, by facilitating ART initiation among persons previously in pre-ART care at 46 ART centers supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR)* in six districts in the states of Maharashtra and Andhra Pradesh. Partners supported these 46 ART centers in identifying and attempting to contact persons who were enrolled in pre-ART care during January 2014-April 2017, and educating those reached about Treat All. ART center-based records were used to monitor implementation indicators, including ART initiation. A total of 9,898 (39.6%) of 25,007 persons previously enrolled in pre-ART care initiated ART; among these 9,898 persons, 6,315 (63.8%) initiated ART after being reached during May 2017-June 2018, including 1,635 (16.5%) who had been lost to follow-up before ART initiation. NACO scaled up efforts nationwide to build ART centers' capacity to implement Treat All. Active tracking and tracing of persons with HIV infection enrolled in care but not on ART, combined with education about the benefits of early HIV treatment, can facilitate ART initiation.

The experimental significance of isorhamnetin as an effective therapeutic option for cancer: A comprehensive analysis.

Isorhamnetin (C16H12O7), a 3'-O-methylated derivative of quercetin from the class of flavonoids, is predominantly present in the leaves and fruits of several plants, many of which have traditionally been employed as remedies due to its diverse therapeutic activities. The objective of this in-depth analysis is to concentrate on Isorhamnetin by addressing its molecular insights as an effective anticancer compound and its synergistic activity with other anticancer drugs. The main contributors to Isorhamnetin's anti-malignant activities at the molecular level have been identified as alterations of a variety of signal transduction processes and transcriptional agents. These include ROS-mediated cell cycle arrest and apoptosis, inhibition of mTOR and P13K pathway, suppression of MEK1, PI3K, NF-κB, and Akt/ERK pathways, and inhibition of Hypoxia Inducible Factor (HIF)-1α expression. A significant number of in vitro and in vivo research studies have confirmed that it destroys cancerous cells by arresting cell cycle at the G2/M phase and S-phase, down-regulating COX-2 protein expression, PI3K, Akt, mTOR, MEK1, ERKs, and PI3K signaling pathways, and up-regulating apoptosis-induced genes (Casp3, Casp9, and Apaf1), Bax, Caspase-3, P53 gene expression and mitochondrial-dependent apoptosis pathway. Its ability to suppress malignant cells, evidence of synergistic effects, and design of drugs based on nanomedicine are also well supported to treat cancer patients effectively. Together, our findings establish a crucial foundation for understanding Isorhamnetin's underlying anti-cancer mechanism in cancer cells and reinforce the case for the requirement to assess more exact molecular signaling pathways relating to specific cancer and in vivo anti-cancer activities.

Evidence of mental health-related morbidities and its association with socio-economic status among previously hospitalized patients with symptoms of COVID-19 in Bangladesh.

Introduction: The long-term impact of COVID-19 on mental health, particularly in relation to socio-economic vulnerabilities, has received little attention. This study reports the prevalence of mental health-related symptoms among previously hospitalized patients after recovery from COVID-19, and its association with socio-economic status (SES). Methods: Data collection of this cross-sectional study was conducted during February-April 2021, among previously hospitalized patients with COVID-19 like symptoms, on average six months after their discharge from the hospital. Using DASS-21, a validated scale to document symptoms of depression, anxiety, and stress, information on mental health-related symptoms were recorded from 481 respondents along with sociodemographic and economic information through telephone interviews. Chi-square tests were performed to identify significant group differences. Multinomial logistic regression analyzed the association between the changes in socioeconomic characteristics and mental health-related symptoms. Relative index of inequality (RII), slope index of inequality (SII), and concentration index (CIX) were applied to capture relevant inequalities in relation to mental health-related symptoms. Results: Eleven percent of the respondents reported changes in employment status, nearly half changes in income and expenditure. Forty-five percent reported symptoms of depression, anxiety and/or stress, and 12% reported coexistence of all three symptoms. Women [Adjusted Odds Ratio, AOR: 2.95; 95% Confidence Interval, CI: 1.39-5.68], and those who reported changes in occupation [AOR: 3.04; 95% CI: 1.01-9.08] and expenditure [AOR: 2.46; 95% CI: 1.12-5.37] were more likely to report all three mental health-related symptoms compared to men and those without changes in occupation and expenditure. The older age group was less likely [AOR: 0.96; 95%CI: 0.93-0.99] to report coexistence of all three symptoms compared to their younger counterparts. Negative values of concentration index (CIX) indicate that any one mental health-related symptom was significantly concentrated among those with lower expenditure and poor SES. Conclusion: This study will help in addressing mental health-related challenges after recovery from COVID-19 among the identified vulnerable groups through relevant community-based and clinical response, including counseling services, in Bangladesh and similar LMIC contexts.

Experiences of aftermath of COVID-19 in relation to social, financial and health related aspects among previously hospitalized patients: a qualitative exploration.

Background: There is increasing evidence of long-term consequences of COVID-19. The world has seen multidimensional impact of the pandemic and Bangladesh is no exception to that. Policymakers in Bangladesh laid out strategies to curb the initial spread of COVID-19. However, long-term consequences of COVID-19 received little or no attention in the country. Evidence suggests that people presumed to be recovered face multidimensional post-covid consequences. This study aimed to describe the aftermath of COVID-19 in relation to social, financial and health related aspects among previously hospitalized patients. Methods: This descriptive qualitative study includes participants (n = 14) who were previously hospitalized for COVID-19 and returned home after recovery. The participants were part of a mixed method study from which they were purposively selected. Semi-structured in-depth interviews were conducted over telephone. Inductive content analysis was used to analyze the data. Results: Twelve sub-categories emerged from the data analysis which converged into five main categories. The main categories included perspective on physical health, financial struggle, life adjustment, interplay between different domains, and spontaneous support. Conclusion: The lived experiences of COVID-19 recovered patients highlighted multidimensional impact on their daily lives. Physical and psychological wellbeing found to be related to the effort of restoring financial status. People's perception about life altered due to pandemic, for few the pandemic was an opportunity to grow while others found it difficult to accept the hardship. Such multidimensional post COVID-19 impact on people's lives and wellbeing holds considerable implication for response and mitigation plan for future related pandemics.

Mucormycosis and COVID-19 pandemic: Clinical and diagnostic approach.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is yet to be controlled worldwide, especially in India. The second wave of coronavirus disease 2019 (COVID-19) led to panic and confusion in India, owing to the overwhelming number of the population that fell prey to this highly infectious virus of recent times. In the second wave of COVID-19, the patients had to fight both the virus and opportunistic infections triggered by fungi and bacteria. Repeated use of steroids, antibiotics, and oxygen masks during the management of severely and critically ill COVID-19 patients nurtured opportunistic infections such as mucormycosis. Despite mucormycosis being a decades-old disease, it has gained notice of its widespread occurrence in COVID-19 patients throughout India. Instances of mucormycosis are usually unearthed in immunocompromised individuals and are caused by the inhalation of filamentous fungi, either from the natural environment or through supportive care units. In the recent outbreak during the second wave of COVID-19 in India, it has been seen to cause secondary infection as it grows along with the treatment of COVID-19. Furthermore, COVID-19 patients with comorbidities such as diabetes were more likely to have the mucormycosis co-infection because of their challenged immune systems' inability to fight it. Despite the hype, mucormycosis still remains neglected and least studied, which is predominantly due to all focus on diagnostics, vaccine, and therapeutic research. In this review, we emphasize mainly on the association of mucormycosis in COVID-19 patients. We also present the molecular mechanism of mucormycosis for a better understanding of the fungal infections in patients who have recently been infected with SARS-CoV-2. Better understanding of fungal pathogens, immediate diagnosis, and management of the infections are crucial in COVID-19 patients, as high mortalities have been recorded in co-infected patients despite recovery from COVID-19.

Exploring the Recent Trends in Management of Dementia and Frailty: Focus on Diagnosis and Treatment.

Dementia and frailty increase health adversities in older adults, which are topics of growing research interest. Frailty is considered to correspond to a biological syndrome associated with age. Frail patients may ultimately develop multiple dysfunctions across several systems, including stroke, transient ischemic attack, vascular dementia, Parkinson's disease, Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, cortico-basal degeneration, multiple system atrophy, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. Patients with dementia and frailty often develop malnutrition and weight loss. Rigorous nutritional, pharmacological, and non-pharmacological interventions generally are required for these patients, which is a challenging issue for healthcare providers. A healthy diet and lifestyle instigated at an early age can reduce the risk of frailty and dementia. For optimal treatment, accurate diagnosis involving clinical evaluation, cognitive screening, essential laboratory evaluation, structural imaging, functional neuroimaging, and neuropsychological testing is necessary. Diagnosis procedures best apply the clinical diagnosis, identifying the cause(s) and the condition(s) appropriate for treatment. The patient's history, caregiver's interview, physical examination, cognitive evaluation, laboratory tests, and structural imaging should best be involved in the diagnostic process. Varying types of physical exercise can aid the treatment of these disorders. Nutrition maintenance is a particularly significant factor, such as exceptionally high-calorie dietary supplements and a Mediterranean diet to support weight gain. The core purpose of this article is to investigate trends in the management of dementia and frailty, focusing on improving diagnosis and treatment. Substantial evidence builds the consensus that a combination of balanced nutrition and good physical activity is an integral part of treatment. Notably, more evidence-based medicine knowledge is required.

Natural therapeutics and nutraceuticals for lung diseases: Traditional significance, phytochemistry, and pharmacology.

BACKGROUND: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities. PURPOSE: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease. METHODS: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases. RESULTS: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases. CONCLUSION: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2.

Comparing the profile of respiratory fungal pathogens amongst immunocompetent and immunocompromised hosts, their susceptibility pattern and correlation of various opportunistic respiratory fungal infections and their progression in relation to the CD4+T-cell counts.

INTRODUCTION: Invasive fungal infections are increasingly common in the nosocomial setting. MATERIALS AND METHODS: The patients were divided into two groups immunocompetent and immunocompromised that is, patients with significant neutropenia <500 neutrophils/µl for longer than 10 days. microscopy, culture, identification of isolates were done and some specilised tests on serum and BAL for antigen detection were performed. RESULTS: Majority of the patients were young adult males in this study. A higher prevalence of 26.7% was seen in immunocompromised patients. Amongst yeasts, Candida albicans was the predominant species followed by the National AIDS Control that is, Candida glabrata, Candida dubliniensis, Candida parapsilosis and Candida tropicalis in the same order. Amongst moulds, Aspergillus fumigatus was the most common species followed by Aspergillus flavus and Aspergillus niger. Mucor and Penicillium marneffei were seen in a lower prevalence. By Broth microdilution method, isolates of Candida spp. were most sensitive to caspofungin, amphotericin B, ketoconazole and fluconazole in the same order. Isolates of Aspergillus spp. were most sensitive to caspofungin, amphotericin B and itraconazole in the same order. By disc diffusion method, resistance to fluconazole was observed in 6.9% isolates of C. albicans. 50% of C. dubliniensis and 20% of C. glabrata showed resistance to fluconazole. A total mortality of 27.7% was observed during this study. This was distributed as 24.1%, 26.7%, 50%, 50%, 100% and 0% among by patients of candidiasis, aspergillosis, cryptococcosis, pneumocystosis, mucormycosis and penicilliosis. Fifteen per cent were lost to follow-up. CONCLUSION: Patterns of invasive fungal infections are changing in many ways. In the midst of these evolving trends, IFI of the respiratory tractcontinue to remain important causes of morbidity and mortality. Diagnostic tools can be adequately used only if the treating physician is aware of the propensity of patients to acquire a fungal infection. Thus, continuous awareness and education is crucial for successful management of patients. Judicious use of antifungal medications as prophylactic measures must be employed, particularly in the critically ill and patients of HIV.

Post-HAART tuberculosis in adults and adolescents with HIV in India: incidence, clinical and immunological profile.

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) was introduced in National AIDS Control Programme in 2004 to reduce the morbidity and mortality among those affected with HIV/AIDS. Tuberculosis, being an important coinfection, its emergence/occurrence in post-HAART period has potential implications. OBJECTIVE: Primary objectives were to study the incidence of post-HAART tuberculosis in HIV patients and to identify the possible risk factors. It was also intended to understand the clinical and immunological profile of this important condition. METHODOLOGY: Eligible adults and adolescents with HIV disease enrolled on HAART at Government Hospital of Thoracic Medicine, Tambaram Sanatorium, Chennai, from April, 2004 to March, 2007, formed the study population. They were monitored and screened for the occurrence of tuberculosis after commencing HAART. Clinical details and immunological profile of these patients were analysed. RESULTS: Two hundred and sixty-two patients (5.1%) of 5099 patients followed-up for one to four years were found to have Post HAART TB with 100-person year risk of 2.83. Post HAART TB occurred predominantly in men (67.6%) and in 31-44 years age group (69.8%) with 100-person year risk being 3.26 and 2.83 respectively. Pulmonary, Extra-pulmonary and disseminated tuberculosis were found to occur in the frequencies of 78%, 16% and 6% respectively. A total of 144 patients (54.9%) developed tuberculosis within six months and this number increased to 202 (77%) by 12 months. 230 patients (87.7%) had base level CD4 cell count < 200 / mm3. CONCLUSION: Tuberculosis was found to occur pre-dominantly in adult male patients with HIV during the first year after the initiation of HAART. Significantly, occurrence of Post HAART TB remained almost the same (5%) among patients treated for TB prior to the initiation of HAART.