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Objective: This research aims to optimize the solid lipid nanoparticles by using full factorial design to improve the delivery of rivastigmine tartrate (RT), which is used for the treatment of Alzheimer’s disease (AD). Solid lipid nanoparticles (SLNs) are attracting importance for drug developers due to their performance. The outcome of this research will lead to improvements in drug release and solubility of RT for better therapeutic effect. Methods: Four different methods were used to prepare solid lipid nanoparticles of rivastigmine tartrate, namely the modified solvent emulsification technique, the microemulsion cooling technique, the solvent injection technique, and the homogenization/ultrasonication technique. Glyceryl monostearate (GMS) was used as a lipid; Compritol 888, tween 80, and span 40 were used as surfactants, co-surfactants, and stabilizers, respectively. Results: SLNs were evaluated for zeta potential, particle size, polydispersity index, surface morphology, Fourier Transform Infrared Spectroscopy (FTIR), and differential scanning calorimetry (DSC). Entrapment efficiency and drug loading were also estimated. Solubility study of rivastigmine tartrate in different solid lipids as well as the in vitro drug release, was studied. The particle size of SLNs was found to range between 138.22+0.01 nm and 172.79+0.23 nm. The zeta potential of the optimized formulation was found to be in the the-24+0.01mV range, indicating a stable formulation. A scanning electron microscope indicates a clear spherical structure without any aggregation. Entrapment efficiency was determined to be 69.27+0.22%. The RT-SLNs showed significant retention in memory when compared with RT solution (standard formulation), which may be attributed to the lipid nature and nanostructure of the delivery system that may probably result in more accumulation of the drug in the brain to show better effect. Conclusion: The current study concludes that the microemulsion cooling technique is the best method for patient compliance and stability with all desired characteristics parameters.

Asthma affects nearly 260 million people worldwide, where severe asthma cases represent the most difficult to treat due to corticosteroid insensitivity. Severe asthma is associated with higher levels of TH17 and TH1 responses, accompanied by neutrophil dominated inflammation. Better understanding of the immune responses to airway allergens that promote or protect against severe asthma is critical for identifying ways to treat these patients. Single nucleotide polymorphisms in theATG5gene, which encodes for a protein required for the cellular recycling process of autophagy, has been associated with higher risk for developing severe asthma. However, the exact role for ATG5 during allergic inflammation and whether other autophagy proteins are involved remains elusive. Using genetic tools to dissect the roles for ATG5 in innate immune cells in house dust mite (HDM)-challenged mice, we have identified a specific role for ATG5 in CD11c+lung macrophages and dendritic cells for suppressing TH17 responses and neutrophil accumulation. We found that this role for ATG5 in CD11c+cells to regulate neutrophil accumulation during allergic airway inflammation also required other autophagy proteins but did not involve regulation of inflammasome, despite higher levels of IL-1β and Caspase 1 in the lungs of mice lacking autophagy in innate immune cells. Our data support a role for autophagy in CD11c+lung macrophages and dendritic cells to promote an immune response to airway allergens that is associated with less severe asthma by suppressing TH17 responses and neutrophil accumulation in the lung.

An Ayurvedic polyherbal formulation (Ayush-64) was repurposed for use in mild to moderate COVID-19 cases based on the supportive evidence obtained from a pilot study on its effect on Influenza like illness (ILI) and molecular docking study which revealed that several compounds isolated from Ayush-64 demonstrated antiviral activity. The study aims at evaluating the effect of an Ayurvedic intervention (Ayush-64) in mild to moderate COVID-19 patients. A prospective single arm, pilot study in mild to moderate COVID-19 patients. The study was conducted at Chaudhary Brahm Prakash Ayurved Charak Sansthan (CBPACS), New Delhi, India. A total of 37 COVID-19 participants confirmed through RT-PCR were included in the study. The proportion of participants with negative SARS-CoV-2 on nasal or throat swab in a 2-day consecutive real-time RT-PCR test was evaluated as the secondary outcome. In the study, 86.1% of participants demonstrated clinical recovery with 14 days of use of Ayush-64 as stand-alone treatment without any other conventional medicines, out of which 75% clinically recovered within 8 days. Further, 69.4% of participants turned negative by the 15th day, out of which 50% became COVID-19 negative on the 8th day. No AE/ ADR was observed during the study. Ayush-64 may significantly facilitate clinical improvement in terms of duration for clinical recovery and attaining negative conversion in mild to moderate COVID-19 cases.

The emergence of Plasmodium falciparum resistance raises an urgent need to find new antimalarial drugs. Here, we report the rational repurposing of the anti-hepatitis C virus drug, alisporivir, a nonimmunosuppressive analog of cyclosporin A, against artemisinin-resistant strains of P. falciparum. In silico docking studies and molecular dynamic simulation predicted strong interaction of alisporivir with PfCyclophilin 19B, confirmed through biophysical assays with a K(d) value of 354.3 nM. Alisporivir showed potent antimalarial activity against chloroquine-resistant (PfRKL-9 with resistance index [Ri] 2.14 ± 0.23) and artemisinin-resistant (PfKelch13(R539T) with Ri 1.15 ± 0.04) parasites. The Ri is defined as the ratio between the IC(50) values of the resistant line to that of the sensitive line. To further investigate the mechanism involved, we analyzed the expression level of PfCyclophilin 19B in artemisinin-resistant P. falciparum (PfKelch13(R539T)). Semiquantitative real-time transcript, Western blot, and immunofluorescence analyses confirmed the overexpression of PfCyclophilin 19B in PfKelch13(R539T). A 50% inhibitory concentration in the nanomolar range, together with the targeting of PfCyclophilin 19B, suggests that alisporivir can be used in combination with artemisinin. Since artemisinin resistance slows the clearance of ring-stage parasites, we performed a ring survival assay on artemisinin-resistant strain PfKelch13(R539T) and found significant decrease in parasite survival with alisporivir. Alisporivir was found to act synergistically with dihydroartemisinin and increase its efficacy. Furthermore, alisporivir exhibited antimalarial activity in vivo. Altogether, with the rational target-based Repurposing of alisporivir against malaria, our results support the hypothesis that targeting resistance mechanisms is a viable approach toward dealing with drug-resistant parasite.

SummaryHost autophagy had been associated with the control ofMycobacterium tuberculosis(Mtb) infection due to its ability to sequesters microorganisms through a process termed “xenophagy”1–4. Xenophagy purportedly limits Mtb replication within infected macrophages1–4. However, studies in mice using a standard low-dose infection model demonstrated that xenophagy in infected phagocytes is not required to control Mtb pathogenesis5,6. Instead, an autophagy-independent function of ATG5 in myeloid cells controls low-dose Mtb infection through limiting neutrophilic inflammation5. Hitherto, anin vivorole for autophagy during Mtb infection remained to be elucidated. We report herein that autophagy in myeloid cells mediates protection against high-dose Mtb infection, providing the first evidence for a role for autophagy in myeloid cells during Mtb infectionin vivo. With the exception of ATG5, the autophagy proteins required to control high-dose Mtb infection are dispensable for host defense against a standard low-dose Mtb infection. Specifically, autophagy is required in CD11c+cells, but is dispensable in neutrophils, to control a high-dose Mtb infection in the lung. The role for autophagy is not to directly degrade Mtb in macrophages through xenophagy, but mainly to limit myeloid-derived suppressor cell accumulation and to promote sustained protective T cell responses. Together, our data highlight a novel role for autophagy in controlling Mtb infection, distinct from that of Atg5 during low-dose Mtb infection, or any previously reported roles for autophagy. In addition, our finding that the result of a pathogen-plus-susceptibility gene interaction is dependent on pathogen burden has important implications on our understanding of how Mtb infection in humans can lead to a spectrum of outcomes, the variables that contribute to autophagy gene function during infection and inflammation, and the potential use of autophagy modulators in clinical medicine.

Here, we report the photoluminescence and thermoluminescent properties of Dy-activated Ca2 ZnSi2 O7 phosphors synthesized using the solid-state method. The synthesized phosphors showed hardystonite type structure, and had micron-sized particles. Fourier transform infrared spectroscopy (FTIR) showed the existence of the functional groups and confirmed the formation of phosphor and photoluminescence techniques. The phosphors under excitation at 239 nm exhibited green-yellow emission spectra in the region 481-575 nm corresponding to the 4 F9/2 →6 H15/2 and 4 F9/2 →6 H13/2 transitions of Dy3+ ions. The Commission Internationale de l'Eclairage (CIE) coordinates were achieved to be (0.25, 0.27), which was narrowly close to the white region. Thermoluminescence (TL) glow curve analysis of prepared Dy3+ -activated Ca2 ZnSi2 O7 phosphors were recorded for different ultraviolet (UV) light exposure times and found to have a linear response with dose. The TL glow curves, recorded with various UV exposure times ranging from 5 to 25 min, showed a linear response with dosage. The corresponding kinetic parameters were also calculated using a computerized glow curve deconvolution (CGCD) technique. Activation energy was observed to enhance the increase in the peak temperature and its value was substantially higher for the third peak fitted using CGCD. The obtained results indicated that the synthesized pristine phosphors could be potentially used for lighting, displays, and dosimetric applications.

Attenuated intracellular survival of Mycobacterium tuberculosis (Mtb) secretory gene mutants exemplifies their role as virulence factors. Mtb peptidyl prolyl isomerase A (PPiA) assists in protein folding through cis/trans isomerization of prolyl bonds. Here, we show that PPiA abets Mtb survival and aids in disease progression by exploiting host-associated factors. While the deletion of PPiA has no discernable effect on bacillary survival in a murine infection model, it compromises the formation of granuloma-like lesions and promotes host cell death through ferroptosis. Overexpression of PPiA enhances the bacillary load and exacerbates pathology in mice lungs. Importantly, PPiA interacts with the integrin α5β1 receptor through a conserved surface-exposed RGD motif. The secretion of PPiA as well as interaction with integrin contributes to disease progression by upregulating multiple host matrix metalloproteinases. Collectively, we identified a novel nonchaperone role of PPiA that is critical in facilitating host–pathogen interaction and ensuing disease progression.

Objective: The aim of the present study was to investigate the psychiatric distress, including stress, anxiety, and depression levels, among COVID-19 positive patients who were admitted between 01 July 2020 to 31 August 2020 to the COVID-19 isolation ward of the Uttar Pradesh University of Medical Sciences, Saifai, Etawah India. Participants included 100 patients, with 55 males and 45 females. The majority of admitted patients (81%) were illiterate. Out of 100 patients, 83 were married, 16 were unmarried, and only 1 was a widow. Methods: Levels of anxiety, depression, and stress level were noted in admitted patients using Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire (PHQ-9) depression assessment, and Perceived Stress Scale 4 (PSS-4) assessment techniques, respectively. Results: Patient Health Questionnaire (PHQ-9) depression assessment results showed minimal, mild, and moderate depression in 9, 25, and 66 patients, respectively, with a 10.6 median score of PHQ-9. Mild, moderate, and severe anxiety (GAD-7 score) was present in 22, 28, and 50 of the patients surveyed. The mean Perceived Stress Scale 4 (PSS-4) was also analyzed, and it reported 6.1 values. The results of the study demonstrated that the patients had a high label of psychiatric distress, but still, admitted patients believe that they will come out from this pandemic condition. Conclusion: Although patients claimed psychiatric distress and mental health illness, they still denied the requirement of any mental health professionals to minimize stress levels and were satisfied with the medical facilities available in a hospital located in a rural area.

Hydroponics is the modern solution for modern problems. Due to extensive traditional agriculture and various man made activities like deforestation. Fertile and arable land is decreasing day by day. While transporting the food we eat, so much of fossil fuels goes into transportation. The volume of water which is used in conventional farming is shocking. For the irrigation in these conventional farming, large volume of water is needed and water is one of the most crucial resource to be saved. Loads of chemical fertilizers and pesticides that are used in conventional farming flows into the water bodies and make them polluted. To tackle these problems hydroponics can be used as the effective method. In hydroponics plants are grown in a room without the use of any soil. Plants do not require soil for their growth all they need is water and various micro and macro nutrients that are present in soil. In hydroponics water and these nutrients are provided to the plants directly. With the effect of which plants do not have to spend their energy in the expansion of their root system for the search of water and minerals. The use this energy for the production of better food products. Hydroponics have numerous advantages over soil base farming. In this paper all the advantages, history, types and basic components of hydroponics has been explained.

Previous cross-sectional studies reported positive effects of meditation on the brain areas related to attention and executive function in the healthy elderly population. Effects of long-term regular meditation in persons with mild cognitive impairment (MCI) and Alzheimer’s disease dementia (AD) have rarely been studied. In this study, we explored changes in cortical thickness and gray matter volume in meditation-naïve persons with MCI or mild AD after long-term meditation intervention. MCI or mild AD patients underwent detailed clinical and neuropsychological assessment and were assigned into meditation or non-meditation groups. High resolution T1-weighted magnetic resonance images (MRI) were acquired at baseline and after 6 months. Longitudinal symmetrized percentage changes (SPC) in cortical thickness and gray matter volume were estimated. Left caudal middle frontal, left rostral middle frontal, left superior parietal, right lateral orbitofrontal, and right superior frontal cortices showed changes in both cortical thickness and gray matter volume; the left paracentral cortex showed changes in cortical thickness; the left lateral occipital, left superior frontal, left banks of the superior temporal sulcus (bankssts), and left medial orbitofrontal cortices showed changes in gray matter volume. All these areas exhibited significantly higher SPC values in meditators as compared to non-meditators. Conversely, the left lateral occipital, and right posterior cingulate cortices showed significantly lower SPC values for cortical thickness in the meditators. In hippocampal subfields analysis, we observed significantly higher SPC in gray matter volume of the left CA1, molecular layer HP, and CA3 with a trend for increased gray matter volume in most other areas. No significant changes were found for the hippocampal subfields in the right hemisphere. Analysis of the subcortical structures revealed significantly increased volume in the right thalamus in the meditation group. The results of the study point out that long-term meditation practice in persons with MCI or mild AD leads to salutary changes in cortical thickness and gray matter volumes. Most of these changes were observed in the brain areas related to executive control and memory that are prominently at risk in neurodegenerative diseases.

Background: Ayush-64 is an Ayurvedic formulation, developed and patented by Central Council of Research in Ayurvedic Sciences (CCRAS). In the present study, we repurposed it for use in mild to moderate COVID-19 cases based on a pilot study against Influenza like illness (ILI) and molecular docking study which revealed that several compounds isolated from Ayush-64 demostrated antiviral activity. Purpose: To evaluate the role of Ayush-64 in clinical recovery of mild to moderate COVID-19 pattientsStudy Design: A single arm, pilot study in mild to moderate COVID-19 patientsMethods: The study was conducted from 20th June, 2020 to 11th August, 2020 at Chaudhary Brahm Prakash Ayurved Charak Sansthan (CBPACS), New Delhi, India involving 37 confirmed COVID-19 participants. Ayush 64 tablets in the dose of two tablets (500 mg each) thrice daily was given to the participants for a duration of either 8 or 14 days. Number of participants showing ‘clinical recovery’ was set as primary outcome. Percentage of participants with negative SARS-CoV-2 on nasal or throat swab in a 2-day consecutive real time RT-PCR test was evaluated as secondary outcome. Result: In the study 86.1% participants have shown clinical recovery after 14 days intervention of Ayush-64, out of which 75% clinically recovered within 7 days. Finding of RT-PCR test has shown that 69.4% participants turned negative till 15th day, out of which 50% became negative on 8th day. No AE/ ADR was observed during the course of the study.Conclusion: Ayush-64 is a safe treatment option in mild to moderate COVID-19 cases and is likely to significantly facilitate clinical improvement in terms of duration for clinical recovery and attaining negative conversion, without any ADR/AE.

Here, we report the photoluminescence and thermoluminescent properties of Dy-activated Ca

Back ground & Purpose: Many countries in Asia as well as developed countries like England, Australia and USA were attacked by the rampant COVID-19.This observational study was conducted to analyze the rate of transmission, death to case ratio, doubling time, role of temperature and other preventive measures on these variables. Methodology: Data of the variables were collected from World Health Organization online daily progress reports on COVID-19 and other reliable Internet sources on a daily basis from 30-03-2020 till 20-04-2020. Results & Conclusion: The transmission was maximum in Turkey, Iran, China, Russia, India, Israel, Japan, South Korea, Saudi Arabia, and Pakistan whereas minimum in Yemen, Bhutan, Laos, Timor-Leste, Nepal, Mongolia, Syria, Maldives, Myanmar, and Cambodia. There were no confirmed cases reported in Turkmenistan, Tajikistan and North Korea. Temperature didn’t appear to be influencing the transmission and death rate due to COVID-19 in Asian countries. There is a positive correlation between the environmental temperatures, preventive measures, lock down and the doubling time of COVID-19 in Asian countries. KEY WORDS: - COVID -19, ASIA, Doubling time, Death – to - case ratio, Temperature

The present study was conducted to assess the effect of computer assisted teaching on knowledge gain of students on GCS with Coma patient. An experimental design was chosen with pre-test and post-test of experimental and control group. The sample size was 60 B.Sc. Nursing 3rd Year students divided into two groups as 30 in experimental and 30 in control group. The tools used for conducting the study included demographic data, self-structured questionnaire to assess knowledge of experimental and control group. The experimental group was given computer assisted teaching as an intervention and the control group was used for comparison only without interventions. The data were analyzed with statistics and unpaired t-test was done. The study clearly shows that there was a significant gain in knowledge of students in experimental group with computer assisted teaching which emphasizes that GCS is helpful to assess the level of consciousness. Therefore, the students can be benefited with computer assisted teaching to improve knowledge on GCS and they can practice these interventions in clinical area in future. It is a true experimental study with 30 samples each in control and experimental group of BSc nursing third year student to assess the effect of computer assisted teaching on knowledge gain of the students regarding glass coma scale. The study group showed rise in knowledge score with CAT where as the control group did not demonstrate increase in post test knowledge score as this was not exposed to the intervention. Therefore computer assisted teaching helps in imparting knowledge subject and improving the score. The Purpose of the research was to improve knowledge on GCS so that student can assess the condition of unconscious patient and it will help in improving in nursing care and also they can assess the prognosis of the condition of the patient and planning nursing care accordingly.