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BackgroundFavipiravir is administered orally, even against airborne RNA viruses, in a loading-dose/maintenance dose regimen. We investigated whether—(a) pulmonary delivery of favipiravir would generate high concentrations in the luminal side of the respiratory tract; and (b) avoiding first-pass metabolism by the liver by inhaled drug would generate comparable pharmacokinetics (PK) with doses significantly smaller than the oral maintenance dose.MethodsA dry powder inhalation (DPI) of favipiravir formulated by mixing with Inhalac 400® was prepared and characterized. Inhalations of ~ 120 µg dose strength, with or without a prior oral loading dose were administered to mice. Comparator mice received human-equivalent oral doses (3 mg). Three mice per sampling time point were sacrificed and favipiravir concentrations in the blood plasma, bronchio-alveolar lavage fluid (BALF) and lung tissue homogenate determined by HPLC.ResultsOne-compartment PK modeling of concentration–time data indicated that the area under the curve (AUC0-24 h) generated in the BALF recovered from mice receiving inhalations of ~ 1/25th of the oral dose subsequent to an oral loading dose was 86.72 ± 4.48 µg⋅mL−1⋅h. This was consistently higher than the AUC observed in the BALF of orally-dosed mice (56.71 ± 53.89 µg mL−1⋅h). In blood serum, the respective values of AUC were 321.55 ± 124.91 and 354.71 ± 99.60 µg⋅mL−1⋅h.ConclusionPulmonary delivery of significantly smaller doses of favipiravir generates meaningful drug disposition and pharmacokinetics at the site of respiratory viral infections. We provide the rationale for designing a self-administered, non-invasive, low-cost, targeted drug delivery system against airborne RNA virus infection.

Background It is unclear whether Vitamin D is efficacious as a host-directed therapy (HDT) for patients of tuberculosis (TB). We investigated pulmonary delivery of the active metabolite of Vitamin D 3 , i.e., 1, 25-dihydroxy vitamin D 3 (calcitriol) in a mouse model of infection with Mycobacterium tuberculosis (Mtb). Methods We optimized a spray drying process to prepare a dry powder inhalation (DPI) of calcitriol using a Quality by Design (QbD) approach. We then compared outcomes when Mtb-infected mice were treated with inhaled calcitriol at 5 ng/kg as a stand-alone intervention versus DPI as adjunct to standard oral anti-tuberculosis therapy (ATT). Results The DPI with or without concomitant ATT markedly improved the morphology of the lungs and mitigated histopathology in both the lungs and the spleens. The number of nodular lesions on the lung surface decreased from 43.7 ± 3.1 to 22.5 ± 3.9 with the DPI alone and to 9.8 ± 2.5 with DPI + ATT. However, no statistically significant induction of host antimicrobial peptide cathelicidin or reduction in bacterial burden was seen with the DPI alone. DPI + ATT did not significantly reduce the bacterial burden in the lungs compared to ATT alone. Conclusions We concluded that HDT using the low dose calcitriol DPI contributed markedly to mitigation of pathology, but higher dose may be required to evoke significant induction of bactericidal host response and bactericidal activity in the lung.

A large number (about 1200) of mycobacteriophages (phages) have been isolated on Mycobacterium smegmatis mc2155. Their genome analysis shows high sequence diversity; therefore, based on nucleotide sequence similarity and genomic architecture, the related phages have been grouped in clusters and sub-clusters. However, a deeper study of mycobacteriophages has been conducted only for a few clusters. This study explores the traits of phages belonging to the B1 sub-cluster. We have attempted to functionally annotate and experimentally characterize B1 phages to get an insight into their biology and explore their therapeutic potential. Analysis of B1 sub-cluster phage genomes to understand their key characteristics & lifestyle and to determine the putative function of hypothetical proteins (HPs), we developed a framework with a specific set of computational tools available online. For the experimental characterization, mycobacteriophages were isolated from environmental samples and were examined for their morphology, lysogeny status, effect on biofilm and activity against drug-resistant M. smegmatis. The B1 sub-cluster phages were identified by PCR using the specific primers. We have predicted the function of about 55% of the 77 representative proteins in B1 phages, which were previously deemed hypothetical. We studied ten B1 phages (Phages 1-10) which included their morphological characteristics, lysogeny status and antibiofilm activity. TEM analysis, showing an average head & tail size of 65 nm and 202.12 nm, respectively. The turbid morphology of several plaques suggested these phages to be temperate. To verify, we tested their potential to lysogenize M. smegmatis and later found the spontaneous release from the putative lysogens. Interestingly, a putative RepA-like protein was identified in B1 phage genomes, indicating a possibility of extrachromosomal replication of prophages. Further, the impact of Phages 1-10 on M. smegmatis biofilm was found to be potent; the highest inhibitory and disruptive effect of phages (at a fixed titre of 108 pfu/ml) was 64% and 46%, respectively. Also, all ten phages could kill 4XR1 (the isoniazid-resistant M. smegmatis strain). We believe this combination of experimental analysis and exploration of genomic features of mycobacteriophages belonging to a sub-cluster can provide deeper insights into mycobacteriophage biology and also help in understanding their therapeutic potential.

This investigation reported a one-step green synthesis of nickel oxide nanoparticles (NiO NPs) using aloe vera leaves extract solution for their application in a supercapacitor. This method used aloe vera leaves as a reducing agent, which is very simple and cost-effective. The synthesized NPs were thoroughly characterized using various techniques. The X-ray diffraction analysis unequivocally confirmed the crystalline nature; field emission scanning electron microscopy and transmission electron microscopy images showed different shapes and forms of an agglomerated cluster of synthesized NPs. The absorption spectra were recorded from UV visible spectroscopy, while Fourier transform infrared spectroscopy provided insights into the functional groups present. Electrochemical assessments were carried out via cyclic voltammetry, galvanostatic charging-discharging and electrochemical impedance spectroscopy. These experiments were performed using a 2 M KOH electrolyte within a 1.0 V potential window. Impressively, the single electrode displayed a remarkable specific capacitance of 462 F g −1 at a scan rate of 1 mV s −1 and 336 F g −1 at a current density of 0.76 A g −1 . Further, a symmetric two-electrode device (NiO||NiO) has been successfully fabricated by employing a separator between the electrodes. The device exhibited an exceptional specific capacitance of approximately 239 F g −1 , along with an energy density of 47.8 Wh kg −1 and a power density of 545 W kg −1 at 1 A g −1 current density within a 1.2 V potential window. The fabricated device also shows a retention capacity of 89% at 10 A g −1 after 2000 cycles with 114% of columbic efficiency. The present study underscores the effectiveness of the green synthesis approach in producing NiO NPs and establishes their potential as highly promising candidates for supercapacitor applications, showcasing both excellent electrochemical performance in a three-electrode system and remarkable stability in a practical two-electrode device. The results collectively highlight the efficacy of the green approach in producing NiO NPs, establishing its potential as a highly promising candidate for supercapacitor application.

MnO2 is the most favorable material in power storage due to its technological significance and potential applications in pseudocapacitance (due to various oxidative states allowing efficient charge transfer to meet energy demands), where its properties are considerably influenced by its structure and surface morphology. In the present study, a facile hydrothermal route was used to produce different phases of MnO2 (α, β, and γ) with different morphologies. The electrochemical performance of the synthesized phases was studied in aqueous sodium sulfate as an electrolyte. X-ray diffraction, UV–Vis spectroscopy, and Fourier-transform infrared spectroscopy were used to characterize the synthesized material. The surface morphology and topography were examined using field-emission scanning electron microscopy. The direct band gap of α-, β-, and γ-MnO2 was found to be 1.86 eV, 1.08 eV, and 1.68 eV, lying in the semiconducting range, further enhancing the electrochemical performance. It was found that α-MnO2 had a maximum specific capacitance of 138 F/g at 1 A/g, and the symmetric device fabricated using α-MnO2 had a specific capacitance of 86 F/g at 1 A/g.

Diabetic Retinopathy (DR) affects about 27% of patients with diabetes globally. According to the World Health Organization (WHO), DR is responsible for37 million cases of blindness worldwide. The SMART India study (October 2020-August 2021) documented the prevalence of diabetes, and DR in people40 years and above across ten Indian states and one Union Territory by conducting community screening. About 90% of people with sight threatening diabetic retinopathy (STDR) were referred from this screening study to eye hospitals for management, but failed to attend. This qualitative study, a component of the SMART India study, explored perceptions of referred patients regarding their susceptibility to eye related problems in diabetes and the benefits/barriers to seeking care. Perceived barriers from the viewpoint of ophthalmologists were also explored. Guided by the Health Beliefs Model (HBM), 20 semi structured interviews were carried out with consenting patients diagnosed with STDR. They included nine patients who had sought care recruited from eight eye hospitals across different states in India and eleven patients who did not seek care. Eleven ophthalmologists also participated. Four themes of analysis based on the HBM were, understanding of DR and its treatment, perceptions about susceptibility and severity, perceived barriers, perceived benefits and cues to action. Findings revealed poor understanding of the effects of diabetes on the eye contributing to low risk perception. Prohibitive costs of treatment, difficulties in accessing care services and poor social support were major barriers to seeking care. Ophthalmologists acknowledged that the absence of symptoms and the slow progressive nature of the disease deluded patients into thinking that they were fine. The study attests to the need for greater health literacy around diabetes, DR and STDR; for making treatment more affordable and accessible and for the development of effective patient education and communication strategies towards increasing compliance.

Energy, water, and healthy air are the basic needs to survive, and all these resources are intricately connected. Modern lifestyle activities and growing energy demands cause more consumption of fossil fuels and contamination of water and air. The inappropriate discharge of a substantial biomass waste byproduct worsened these problems, mainly in developing nations. The carbonization process can resolve all these problems by converting biomass waste into valuable advanced materials. One of the innovative materials is porous activated carbons derived from various biomass and widely utilized as adsorbents of many pollutants and robust energy storage in supercapacitors with a reported specific capacitance of up to 720 F g −1 . The highest adsorption capacity of ~ 2600 mg g −1 for contaminants was attained using biomass-derived activated carbon with > 99% removal efficiency and a high surface area of ~ 3700 m 2  g −1 . In this, the review not only summarizes the most advanced progress in biomass-derived activated carbon and its role in waste water treatment, energy storage, and air purification but also focuses on the essential factors that affect efficiency towards these specific applications for future demands. Graphical abstract

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019–2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107–131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.

Molybdenum disulfide (MoS2), the second most thoroughly investigated two-dimensional material after graphene, has attracted considerable interest in energy storage applications owing to its exceptional qualities, including its unique crystal structure, low electronegativity, and high specific capacity. In this study, we showed that a simple ball-milling procedure causes significant improvement in the capacitive properties of the bulk MoS2 (BL-MoS2). We characterized the material before and after the milling process using X-ray diffraction (XRD) and a BET surface area analyzer to find the material’s structural, crystalline features, and surface area, respectively. We prepared electrodes of BL-MoS2 and ball-milled MoS2 (BM-MoS2) for electrochemical investigation. The charge storage characteristics were examined using cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS). The BM-MoS2 and BL-MoS2 have a specific capacitance of 114 F/g and 96 F/g, respectively.