Quercetin@Gd3+ doped Prussian blue nanocubes induce the pyroptotic death of MDA-MB-231 cells: combinational targeted multimodal therapy, dual modal MRI, intuitive modelling of r1-r2 relaxivities.

Quercetin (Qu), a potential bioflavonoid has gained considerable interest as a promising chemotherapeutic drug which can inhibit the proliferation of triple-negative breast cancer (TNBC) cells due to its regulation of the expression of tumor-suppressor gene metastasis and antioxidant property. Notably, Qu exhibits a very negligible cytotoxic effect on normal cells, even with high-dose treatment, while it is shows high affinity to TNBC. However, the efficiency of Qu is limited clinically due to its poor bioavailability, caused by its low aqueous solubility (2.15 µg mL-1 at 25 °C), rapid gastrointestinal digestion and chemical instability in alkaline and neutral media. Herein, polydopamine (PDA)-coated, NH2-PEG-NH2 and hyaluronic acid (HA)-functionalized Gd3+-doped Prussian blue nanocubes (GPBNC) are reported as a multifunctional platform for the codelivery of Qu as a chemotherapeutic agent and GPBNC as a photodynamic (PDT) and photothermal (PTT) agent with improved therapeutic efficiency to overcome theses barriers. PDA, NH2-PEG-NH2 and HA stabilize GPBNC@Qu and facilitate bioavailability and active-targeting, while absorption of near infrared (NIR) (808 nm; 1 W cm-2) induces PDT and PTT activities and dual T1-T2-weighted magnetic resonance imaging (MRI) with high relaxometric parameters (r1 10.06 mM-1 s-1 and r2 24.96 mM-1 s-1 at a magnetic field of 3 T). The designed platform shows a pH-responsive Qu release profile and NIR-induced therapeutic efficiency of ∼79% in 20 minutes of irradiation, wherein N-terminal gardermin D (N-GSDMD) and a P2X7-receptor-mediated pyroptosis pathway induces cell death, corroborating the up-regulation of NLRP3, caspase-1, caspase-5, N-GSDMD, IL-1ß, cleaved Pannexin-1 and P2X7 proteins. More interestingly, the increasing relaxivity values of Prussian blue nanocubes with Gd3+ doping have been explained on the basis of Solomon-Bloembergen-Morgan theory, considering inner- and outer-sphere relaxivity, wherein crystal defects, coordinated water molecules, tumbling rate, metal to water proton distance, correlation time, magnetisation value etc. play a significant role. In summary, our study suggests that GPBNC could be a beneficial nanocarrier for theranostic purposes against TNBC, while our conceptual study clearly demonstrates the role of various factors in increasing relaxometric parameters.

Understanding social problems during lockdown and its relationship to perceived stress - An online survey among adult residents of India.

CONTEXT: Nationwide lock down imposed due to Covid 19 might bring about various social problems, constraints in availing essential services, difficulty in taking care of morbid elderly persons and inaccessibility to health care which can lead to stress. AIMS: To identify social problems among adult Indian residents during lockdown period, to assess perceived stress among them and to identify the factors associated with it. SETTINGS AND DESIGN: The study was conducted through the online platform using a google form among adult residents of India. Perceived stress was assessed by Perceived Stress Scale 10. STATISTICAL ANALYSIS USED: Data were analysed using SPSS version 16.0., using chi square, Odd's Ratio and binary logistic regression. RESULTS: One fourth of the respondents faced economic problem, 11.7% of them had experienced some sort of violence and worsening of familial relationship. The problems encountered in seeking care were chi square test due to non availability of transportation facilities and health services. Overall 80.78% of the respondents were observed to have moderate and high levels of perceived stress. Multivariate analysis revealed single marital status, owing a debt and experiencing violence had 1.62, 1.8 and 9 times higher odds of having moderate to high perceived stress. Violence was identified as its chief correlate. CONCLUSIONS: The present study found negative economic and social consequences on the Indian population and also posed an enormous psychological stress due to sudden lock down in pandemic situation.

A study on the preference of teaching methods among medical undergraduate students in a tertiary care teaching hospital, India.

BACKGROUND: In medical education, the learning-teaching method is an active process in which both students and teachers have to work mutually to enlighten the knowledge. Currently, in India, there is an increase in the enrollment of students in medical fields and thus medical educators face the challenge of teaching larger classes in a short period. Furthermore, it is observed that there is a lack of consensus about the best teaching and learning methods for medical students. This study aims to assess the preference of teaching methods and identify the reason for absenteeism among medical undergraduate students in a tertiary care teaching hospital. MATERIALS AND METHODS: A cross-sectional study was conducted among 246 medical undergraduate students in a tertiary care teaching hospital from August 2019 to October 2019. A pretested, validated self-administered questionnaire was used to assess the preference of teaching methods. The data were analyzed using SPSS-IBM software 23. RESULTS: The majority of the students belonged to 20-21 years of age group. Most of the students preferred practical demonstration (81.3%) as the preferred method of teaching and computer with a liquid crystal display projector as ideal media for teaching (63.8%). Boring/monotonous teaching class was found (73.5%) to be an important cause for absenteeism among medical undergraduate students. CONCLUSION: The results indicate that the medical student's preference is changing from passive learning to active learning. We conclude by linking these emerging perceptions with suggestions to help drive excellence in medical education.

Correlation between CNS Tuberculosis and the COVID-19 Pandemic: The Neurological and Therapeutic Insights.

The recent outbreak of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) from Wuhan, China, was caused by a single-stranded RNA virus which has kept the entire world stranded. The outbreak was first diagnosed with respiratory illness, but recent findings of acute necrotizing hemorrhage of brain, brain encephalopathy, and the presence of the virus in the cerebrospinal fluid (CSF) have unveiled its neuroinvasivness. Various clinical features related to the central nervous system (CNS) and peripheral nervous system (PNS) due to COVID-19 infection are now identified. We demonstrate here an apparent similarity in neurological disorders of COVID-19 with CNS tuberculosis, which suggests that some anti-tubercular drugs may be used as therapeutic agents against COVID-19 infection.

Askin (PNET) Tumor Unmasked by Trauma in a Young Male Patient.

A young male labourer developed pain at the site of blunt trauma over back of chest followed by fever, cough with expectoration, breathlessness and hemorrhagic pleural effusion in the side of injury. What could have been passed as a sequel of trauma turned out to be the consequences of an underlying rare and aggressive malignant tumor of the chest wall known as Askin tumor or Primitive Neuroectodermal Tumor (PNET). CT thorax with guided FNAC, debulking operation, histopathological examination followed by immunohistochemistry of the tumor tissue led to the final diagnosis. Chemotherapy was administered following surgical resection. The patient died within nine months after diagnosis.

First-line anti-tubercular drug resistance of mycobacterial strains from re-treatment cases that were smear-positive at 4(th) month onwards under the Revised National Tuberculosis Control Program.

BACKGROUND: Programmatic management of drug-resistant TB (PMDT) under the RNTCP is being implemented in West Bengal in a phased manner since 2011. During the initial years MDR-TB cases were identified based on criteria A. This study examines the first line anti-tubercular drug resistance pattern of mycobacteria cultured from sputum samples of MDR suspects who were retreatment cases smear positive from 4(th) month onwards. MATERIALS AND METHODS: In the following retrospective record based study, data on Drug Sensitivity Testing (DST) of sputum samples of MDR suspects between September 2011 and August 2012 were collected from the IRL Kolkata and analysed. Sputum samples, collected in the districts maintaining adequate aseptic containment measures, were decontaminated and centrifuged and the sediment inoculated on LJ medium. Probable M. tuberculosis colonies were identified by typical colony characteristics and Ziehl-Neelsen (ZN) staining. Sensitivity of the four 1(st) line drugs (Streptomycin, Isoniazid, Ethambutol and Rifampicin) was deduced by the economic variant of the proportion method. RESULTS: Of all the 917 MDR suspects whose sputum was examined, 64 mycobacteria culture positive strains (6.98%) were mono-resistant to any of the four first line anti-tubercular drugs. Among the mono-resistant strains 43 (4.69%) were resistant to Rifampicin while 12 (1.31%) were resistant to INH. There were a total 78 (8.51%) poly drug-resistant strains. MDR-TB strains were seen in 741 (80.81%) samples. CONCLUSION: The magnitude of drug resistance were very high among retreatment patients that were smear positive from 4(th) months onwards probably because of repeated courses of anti-tubercular drugs prior to drug sensitivity testing (DST). The decision of the PMDT to enlist all retreatment patients as MDR suspects at initiation will result in early identification and treatment of MDR-TB patients.

Immune thrombocytopenic purpura associated with pulmonary tuberculosis.

Thrombocytopenic purpura as a manifestation of pulmonary tuberculosis is very rare. We report a case of 25-year-old female who presented with thrombocytopenia-induced purpuric spots and an abnormal chest X-ray. There was no hepatosplenomegaly while the bone marrow examination revealed normal maturation of myeloid and erythroid series with increased megakaryocytes. Acid fast bacilli were seen in the sputum microscopy. A diagnosis of sputum smear positive pulmonary tuberculosis along with immune thrombocytopenia was made. High dose intravenous immunoglobulin therapy along with antituberculous drugs corrected the thrombocytopenia and also cured pulmonary tuberculosis. This case report illustrates the causal association between immune thrombocytopenia and tuberculosis.

Bifid sternum.

A bifid sternum is a rare congenital anomaly generally diagnosed as asymptomatic at birth. It is sometimes associated with other congenital anomalies. The sternal defects are best corrected surgically during the neonatal period within the first month of life. Sometimes the defect may be diagnosed only in adult life. We here report a case of bifid sternum which was diagnosed incidentally in a 23-year-old male.

An unusual presentation of extrapulmonary tuberculosis.

A 22 years old female presented with fever, respiratory distress and a rapidly enlarging, soft left postauricular lump for last two months. She was found anaemic, had a right supraclavicular, non-tender lymph node of about 2.5 cm diameter and mild hepatosplenomegaly. She had a positive Mantoux test, and normal chest x-ray. Ultrasonography of abdomen showed multiple pre-and para-aortic enlarged lymph nodes. Mild pericardial effusion was detected on echocardiography. Fine needle aspiration cytology from the right supraclavicular lymph node showed epithelioid cell granuloma. Excision and biopsy of the dermoid were carried out. The content was pus, which was smear-negative but culture-positive for acid-fast bacilli. The patient responded to antituberculous chemotherapy satisfactorily.