Exploring the potential of quercetin in Alzheimer's Disease: Pharmacodynamics, Pharmacokinetics, and Nanodelivery systems.

Alzheimer's disease (AD) is a primary cause of dementia that affects millions of people worldwide and its prevalence is likely to increase largely in the coming decades. Multiple complex pathways, such as oxidative stress, tau and amyloid-beta (Aß) pathology, and cholinergic dysfunction, are involved in the pathogenesis of Alzheimer's disease. The conventional treatments provide only symptomatic relief and not a complete cure for the disease. On the other hand, recent studies have looked into the possibility of flavonoids as an effective therapeutic strategy for treating AD. Quercetin, a well-known flavonol, has been extensively studied for AD treatment. Therefore, this review mainly focuses on the pharmacokinetics properties of quercetin and its modes of action, such as antioxidant, anti-inflammatory, anti-amyloidogenic, and neuroprotective properties, which are beneficial in treating AD. It also highlights the nano delivery systems of quercetin, including liposomes, nanostructures lipid carriers, solid lipid nanoparticles, nanoemulsions, microemulsions, self-emulsifying drug delivery systems, and nanoparticles reported for AD treatment. The remarkable potential of quercetin nanocarriers has been reflected in enhancing its bioavailability and therapeutic efficacy. Therefore, clinical studies must be conducted to explore it as a therapeutic strategy for Alzheimer's disease.

Serial evaluation of antibody titres in patients recovered from COVID-19 and their correlation with disease severity.

On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic. According to the findings of various studies conducted around the world, the serological response varies greatly among different populations, with the determinants of variable response still unknown, including the role of disease severity, which is thought to have a definite correlation. The purpose of this study was to assess serial SARS-CoV-2 IgG antibody response in COVID-19 patients and correlate it with disease severity. It was a longitudinal observational study in which 45 patients (age >18 yrs), were enrolled who had recovered from COVID-19 and were reporting to the post-COVID Care OPD Clinic. Patients who had been on long-term immunosuppressive therapy prior to SARS-CoV-2 infection were not eligible. All patients had not been immunized against SARS-CoV-2 and had no history of contact with recent COVID-19 cases. The patients underwent serial blood tests to determine serum IgG titers specific for SARS-CoV-2 at 30, 60, and 90 days after being diagnosed with COVID-19. Chemiluminescence was used to perform a semi-quantitative evaluation of the SARS-CoV-2 IgG antibody. At 30 days after confirmed SARS-CoV-2 infection, 98.78% had detectable serum IgG levels, and sero-reversion (loss of previously detectable antibodies) occurred in 2.5% at 60 days and 90 days. Serum IgG was found to peak at 30 days out of the three time points of measurement (30, 60, and 90 days from diagnosis). Serum IgG levels at 90 days were significantly lower than those at 30 days (p<0.0001) and 60 days (p=0.002). The current study's findings shed light on the presence and persistence of serum SARS-CoV-2-specific IgG antibodies following a natural infection. The findings point to a long-lasting immune response with increasing severity of initial COVID-19 disease.

Pattern of drug resistance among patients of pulmonary tuberculosis.

BACKGROUND: Drug resistant tuberculosis (DR-TB), particularly multidrug resistance (MDR-TB) and extensive drug resistance (XDR-TB) pose a serious threat to public health. This study aimed to identify drug resistance in pulmonary tuberculosis patients and to see their association with diabetes, human immunodeficiency virus (HIV), previous history of tuberculosis (TB) and family history of TB. METHOD: Sputum specimens obtained from 11,874 pulmonary tuberculosis patients were subjected to smear microscopy, cartridge based nucleic acid amplification test (CBNAAT) and liquid culture (LC). Smear positive isolates were subjected to first line Line probe assay (FL-LPA) for isoniazid and rifampicin resistance. FL- LPA positive isolates were subjected to second line Line probe assay (SL-LPA) for fluoroquinolones and second line injectable drug resistance. RESULT: Out of 11,874 microbiologically confirmed cases of pulmonary tuberculosis, 976 (8.2%) had a drug resistant tuberculosis. Five patterns of drug resistance were identified monoisoniazid; 394 (3.32%), rifampicin; 461 (3.88%) (monorifampicin; 383 (3.22%)), multidrug; 73 (0.61), extensivedrug; 11 (0.09) and others; 37 (0.31). Previous history of tuberculosis was significantly associated with rifampicin resistance and MDR-TB. Family history of tuberculosis contact was strongly associated with rifampicin resistance, MDR-TB and XDR-TB. CONCLUSION: There has been an increasing trend in drug resistance in the recent years, particularly in retreatment cases. This study highlights the pattern of drug resistance and need to detect resistance among all tuberculosis cases, in order to interrupt transmission and control this emerging epidemic.

Impact of the COVID-19 Pandemic on the Overall Health of Patients With Pre-diabetes and Diabetes.

Coronavirus disease 2019 (COVID-19) impacted those with chronic diseases worldwide, especially those with diabetes. Very few studies have explored the effect of COVID-19 on diabetic patients' health markers. The present retrospective study compared various health markers of diabetic patients before and during the COVID-19 pandemic. Patients (N = 511) displayed a significant increase in systolic blood pressure, hemoglobin A1c (HbA1c), diabetic medications, and dose of insulin (p < 0.05) as well as a decrease in low density lipoprotein (LDL) levels (p = 0.04). When patients were stratified by body mass index (BMI), those in higher BMI categories were more negatively impacted during the pandemic than those in lower categories. Results display the impact that COVID-19 had on the general well-being of diabetic patients, and should encourage providers to increase telehealth visits when in-person visits are not possible.

Comparison of Suture-Based and Collagen-Based Vascular Closure Devices for Large Bore Arteriotomies-A Meta-Analysis of Bleeding and Vascular Outcomes.

BACKGROUND: Large bore access procedures rely on vascular closure devices to minimize access site complications. Suture-based vascular closure devices (S-VCD) such as ProGlide and ProStar XL have been readily used, but recently, newer generation collagen-based vascular closure devices (C-VCD) such as MANTA have been introduced. Data on comparisons of these devices are limited. METHODS: PubMed, Scopus and Cochrane were searched for articles on vascular closure devices using keywords, ("Vascular closure devices" OR "MANTA" OR "ProStar XL" OR "ProGlide") AND ("outcomes") that resulted in a total of 875 studies. Studies were included if bleeding or vascular complications as defined by Valve Academic Research Consortium-2 were compared between the two types of VCDs. The event level data were pooled across trials to calculate the Odds Ratio (OR) with 95% CI, and analysis was done with Review Manager 5.4 using random effects model. RESULTS: Pooled analyses from these nine studies resulted in a total of 3410 patients, out of which 2855 were available for analysis. A total of 1229 received C-VCD and 1626 received S- VCD. Among the patients who received C-VCD, the bleeding complications (major and minor) were similar to patients who received S-VCD ((OR: 0.70 (0.35-1.39), p = 0.31, I2 = 55%), OR: 0.92 (0.53-1.61), p = 0.77, I2 = 65%)). The vascular complications (major and minor) in patients who received C-VCD were also similar to patients who received S-VCD ((OR: 1.01 (0.48-2.12), p = 0.98, I2 = 52%), (OR: 0.90 (0.62-1.30), p = 0.56, I2 = 35%)). CONCLUSIONS: Bleeding and vascular complications after large bore arteriotomy closure with collagen-based vascular closure devices are similar to suture-based vascular closure devices.

'Personalizing' shorter regimens: Need of the hour.

INTRODUCTION: The launch of injectable shorter regimens under Programmatic Management of Drug Resistant Tuberculosis (PMDT) guidelines 2017 under Revised National Tuberculosis Control Program (RNTCP) was a welcome step as it decreased the duration of treatment significantly in Drug Resistant Tuberculosis (DRTB) patients. The objective of the present study was to evaluate the treatment outcomes of patients started on injectable shorter regimens from March 2018 to May, 2019. METHODS: Retrospective study which scrutinized medical records of 85 patients started on injectable shorter regimen was conducted. Necessary information on possible patient and disease related predicting factors like age, gender, weight, HIV status, presence of diabetes mellitus (DM), anemia, gap between diagnosis and initiation of treatment, duration of intensive phase (IP) and time of sputum conversion was retrieved, and analyzed for possible association with treatment outcomes. RESULTS: 56.5% had successful treatment outcomes. Age, gender, BMI, diabetic/anemic status and gap between diagnosis and initiation of treatment had no statistically significant relationship with the final outcomes. Duration of IP, sputum conversion and time of outcome during the course of illness emerged as significant factors in successful outcomes. CONCLUSION: The injectable shorter regimens were suitable for a variety of population irrespective of demographic disparities. Patients need to be followed closely as microbiological parameters serve as early indicators of unsuccessful outcomes. These regimens can serve as an alternate choice in patients not tolerating the all oral shorter Bedaquiline containing shorter regimen. Similar such options with combinations of different drugs for individualizing treatment regimens is the need of the hour.

Another rare presentation of allergic bronchopulmonary aspergillosis in a high burden tuberculosis country.

Mediastinal lymphadenopathy is often associated with tuberculosis, especially in a high burden country like India. We present a case of an asymptomatic female, who had mediastinal lymphadenopathy and middle lobe collapse, both of which pointed towards a diagnosis of tuberculosis. Patient was later diagnosed as a case of allergic bronchopulmonary aspergillosis (ABPA) on basis of clinical, radiological and serological findings. Hence, even in a high burden country and in background of bronchial asthma, ABPA should be kept as a differential diagnosis in patients presenting with mediastinal lymphadenopathy.

Prevalence of aspergillus skin hypersensitivity in allergic rhinitis.

Allergic rhinitis (AR) is a chronic allergen specific, IgE-mediated hypersensitivity disorder which significantly impairs the quality of life in affected patients. Many aeroallergens and molds are responsible for AR. This study was  conducted to find prevalence of Aspergillus fumigatus skin hypersensitivity in patients of AR by skin prick test (SPT).  150 clinically diagnosed AR patients visiting our OPD were enrolled. Skin hypersensitivity for Aspergillus f. was done by SPT in all the enrolled patients. Chi square test and Student’s t-test were applied for statistical analysis. Out of 150 patients, 60 (40%) were positive for Aspergillus fumigatus SPT. Majority of the positive patients had persistent AR and among those 39/60 (65%) had moderate to severe persistent AR and 12/60 (20%) had mild persistent AR.  Our study concluded that there is high (40%) prevalence of Aspergillus f. skin hypersensitivity among AR patients. The hypersensitivity to Aspergillus f. was found more in severe AR patients and it was statistically significant.

Pleural effusion. An unfamiliar presentation of ABPA.

Pleural effusion is rarely encountered in patients of allergic bronchopulmonary aspergillosis (ABPA). We report the case of a 17-year-old male who presented with complaints of fever, cough and increasing shortness of breath for 3 weeks. Patient had breathlessness with seasonal variation. Patient had right lower lobe consolidation with pleural effusion which did not respond to antibiotics. Pleural fluid was exudate with neutrophilic predominance and low ADA. Skin prick test for Aspergillus fumigatus was positive, both total IgE and specific IgE against Aspergillus fumigatus were raised.