Incidence of SARS-CoV-2 Co-infections During the Second Wave in Sub-Himalayan Region, India.

Introduction The second wave of the coronavirus disease 2019 (COVID-19) pandemic in India, which started from April 2021, has been more severe and deadly than the first wave. The aim of this prospective study was to determine the possibility of other respiratory pathogens contributing towards the severity and hospitalization in the current second wave. Materials and methods Nasopharyngeal and oropharyngeal swab samples were collected and processed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR). These samples were further processed for detection of co-infection in SARS CoV-2 patients by BioFire® Filmarray® 2.0 (bioMérieux, USA). Results We screened 77 COVID-19-positive patients admitted to All India Institute of Medical Sciences (AIIMS), Rishikesh and found cases of co-infections in five (6.49 %) patients. Conclusion Our finding suggests that co-infections had no or minimal role in augmenting the second wave of the COVID-19 pandemic in India, and the emergence of new variants may be the probable cause.

Antibacterial Potential of Gold Nanoparticles Synthesized From Leaf Extract of Syzygium cumini Against Multidrug-Resistant Urinary Tract Pathogens.

BACKGROUND: Urinary tract infection (UTI) is one of the most commonly encountered bacterial infections. Due to the misuse or excessive use of antibiotics, the upsurge of multidrug-resistance cases in UTIs has now become a global threat to public health. Exploring a newer or safer treatment using green synthesized nanoparticles (NPs) is another substitute for eliminating multidrug-resistant pathogens. METHODOLOGY: Leaf extract of Syzygium cumini was used for green synthesis of gold NPs. Synthesis of Syzygium cumini gold nanoparticles (ScAu-NPs) was achieved by optimizing various reaction parameters. These ScAu-NPs were characterized through UV-visible spectroscopy, transmission electron microscope, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction. ScAu-NPs were then processed for antibacterial activity against clinically isolated multidrug-resistant pathogens like Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecalis. RESULTS: Characterization of NPs revealed that biosynthesized NPs were spherical in shape. FTIR spectroscopy showed the presence of phenolics and aromatic compounds. Biosynthesized NPs exhibit good antibacterial activity with a significant bacterial reduction seen against all bacterial isolates compared to the controls. CONCLUSION: From the results of the present study, the formulation of biosynthesized ScAu-NPs can be utilized in drug development for eliminating infections caused by multidrug-resistant pathogens.

Quality Assessment of Pre-Clinical Studies of Chimeric Antigen Receptor T-Cell Therapy Products: A Point of Focus on Safety.

BACKGROUND: Serious adverse reactions have been reported with the use of Chimeric Antigen Receptor (CAR) T-cell therapy in a clinical setting despite the success of these products in pre- clinical stages of development. OBJECTIVE: We evaluated the quality of available pre-clinical safety data of CAR T-cell therapy products. METHODS: A 21 items safety checklist was designed specifically for CAR T-cell. Literature was searched using search/MeSH terms in PubMed (October 2019 - February 2020). Studies were screened from title and abstract. Original pre-clinical researches related to CAR T-cell anti-cancer therapy were included. RESULTS: Of the search results, 152 studies (3 in vivo, 39 in vitro, and 110 combined) were included. Only 7.9% of studies were specifically designed to evaluate/ improve product safety. Eleven studies included target antigen(s), and no study included co-stimulatory molecule(s) expressed exclusively by the tumor tissue and/or CAR T-cells. One study used CRISPR-Cas9 for CAR gene insertion. The use of switch-off mechanism and purity assessment of CAR T-cell products were reported in 13.2% and 8.6% studies, respectively. Of the 113 studies with in vivo components, immuno- competent animal models were used in 24.8%. Measurements of blood pressure, temperature, body weight, and serum cytokines were reported in 0, 2.7, 29.2, and 27.4% studies, respectively. The tissue distribution and CAR T-cells persistence were reported in 26.5% of studies. The surface expression level of CAR, functional characterization of the product, and use of control were reported in >90% of studies. CONCLUSION: The majority of the checklist parameters were not reported in the pre-clinical publications to be adequately predictive of the safety of CAR T-cells in a clinical setting.

Indian Medicinal Herbs and Formulations for Alzheimer's Disease, from Traditional Knowledge to Scientific Assessment.

Cognitive impairment, associated with ageing, stress, hypertension and various neurodegenerative disorders including Parkinson's disease and epilepsy, is a major health issue. The present review focuses on Alzheimer's disease (AD), since it is the most important cause of cognitive impairment. It is characterized by progressive memory loss, language deficits, depression, agitation, mood disturbances and psychosis. Although the hallmarks of AD are cholinergic dysfunction, ß-amyloid plaques and neurofibrillary tangle formation, it is also associated with derangement of other neurotransmitters, elevated levels of advanced glycation end products, oxidative damage, neuroinflammation, genetic and environmental factors. On one hand, this complex etiopathology makes a response to commonly used drugs such as donepezil, rivastigmine, galantamine and memantine less predictable and often unsatisfactory. On the other hand, it supports the use of herbal medicines due to their nonspecific antioxidant and anti-inflammatory activity and specific cholinesterase inhibitory activity. The popularity of herbal medicines is also increasing due to their perceived effectiveness, safety and affordability. In the present article, the experimental and clinical evidence have been reviewed for various Indian herbal medicines such as Centella asiatica, Bacopa monnieri, Curcuma longa, Clitoria ternatea, Withania somnifera, Celastrus paniculatus, Evolvulus alsinoides, Desmodium gangeticum, Eclipta alba, Moringa oleifera and Convolvulus pluricaulis, which have shown potential in cognitive impairment. Some commonly available herbal formulations for memory impairment in India have also been reviewed.

A pilot study to assess oxidative and inflammatory markers as early indicator for response to chemotherapy in non-small cell lung cancer.

WHAT IS KNOWN AND OBJECTIVE: Oxidative stress and inflammation are known to be high in non-small cell lung cancer (NSCLC). However, association of change in their levels with treatment response remains unaddressed. The present study evaluated change in blood levels of oxidative stress and inflammatory markers in NSCLC patients, after first course of platinum-based chemotherapy. METHODS: This prospective cohort study enrolled newly diagnosed NSCLC patients receiving either pemetrexed-carboplatin (group A) or paclitaxel-carboplatin (group B). Blood levels of malondialdehyde (MDA), reduced glutathione (GSH), interleukin-6 (IL-6), C-reactive protein (CRP) and interleukin-10 (IL-10) were measured at baseline and after first cycle. Response to treatment was noted after 2nd or 4th cycle, as available. Subgroup analysis was done (group B), based on paclitaxel dose/formulation. RESULTS: Of the 85 patients screened, 38 were enrolled with a mean age of 56.7 ± 9.2 years. Baseline levels of oxidative and inflammatory markers were not different between the groups and did not change significantly within the groups. Significant reduction in IL-6 was seen with three-weekly paclitaxel-carboplatin (from median 81.3 [range 8.6, 1006] pg/mL to 51.8 [11.4, 99.5] pg/mL; P = .025). C-reactive protein levels reduced with weekly nab-paclitaxel (P = .043). Change in levels did not relate with therapeutic response except for IL-6 which decreased in patients with partial response (from 102.6 [8.1, 1006] pg/mL to 38.9 [8.4, 99.5] pg/mL; P = .036). WHAT IS NEW AND CONCLUSION: Although the levels of oxidative and inflammatory markers varied following chemotherapy, trend indicates that IL-6 may be a potential marker of treatment response in NSCLC patients.