Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Spatially selective narrow band and broadband absorption in Ag/SiO2/Ag based trilayer thin films by oblique angle deposition of SiO2layer.

We have experimentally demonstrated spatially selective absorption in Ag-SiO2-Ag based trilayer thin films by tuning the deposition angle of SiO2layer. These structures generate cavity resonance which can be tuned across the substrate locations due to spatially selective thickness and refractive index of silicon oxide (SiO2) film sandwiched between metallic silver (Ag) mirrors. Spatially selective property of SiO2film is obtained by oblique angle deposition technique using an electron beam evaporation system. The resonance wavelength of absorption in this trilayer structure shifts across the substrate locations along the direction of oblique deposition. The extent of shift in resonance increases with increase in angle of deposition of SiO2layer. 4.14 nm mm-1average shift of resonance wavelength is observed when SiO2is deposited at 40° whereas 4.76 nm mm-1average shift is observed when SiO2is deposited at 60°. We observed that the width of resonance increases with angle of deposition of the cavity layer and ultimately the resonant absorption disappears and becomes broadband when SiO2is deposited at glancing angle deposition (GLAD) configuration. Our study reveals that there is a suitable range of oblique angle of deposition from 40° to 60° for higher spatial tunability and resonant absorption whereas the absorption becomes broadband for glancing angle deposition.

Environmental Consequences of Intensive Aquaculture Practices at Moyna Purba Medinipur West Bengal India with Special Reference to Carbon Footprint and Carbon Sequestration.

Moyna of Purba Medinipur district is widely known as an aquaculture hub of West Bengal, India. Though very good production is achievable from this fish culture system, management practices are inappropriate, which could create the sustainability problem of this culture system. The present study was thus undertaken for the estimation of plankton population, water quality, carbon footprint and carbon sequestration of this intensive aquaculture practices. Information on spawn to fry, fry to fingerlings and grow-out culture were collected through the structured questionnaire from the fish farmers. The plankton density, primary productivity, carbon footprint and carbon sequestration were analyzed using standard procedures. The phytoplankton, zooplankton and primary productivity were maximum at the stocking period and minimum during the middle of culture period. The lowest feed conversion ratio (FCR) was noticed with the minimum amount of feed applied in the pond. The CO2-e emission ranged from 0.56 to 4.89 kg CO2-e/kg fish (av. 2.13) for the production levels of 5.0 to 10.7 t/ha/yr. The pond water developed salinity and ammonium-N increased from 0.01 to 0.50 mg/l. The ponds with high feed loading (28 to 32 t/ha/yr) had the highest average sediment accumulation rate (11.0 ± 3.0 cm/yr) and carbon sequestration (704 ± 30 g C/m2/yr).

Analysis of Postural Control following Anterior Cruciate Ligament Reconstruction with Ipsilateral Peroneus Longus Tendon Graft.

Introduction: Harvesting peroneus longus for ACL reconstruction is thought to create ankle instability which could add to postural instability from an ACL injury. This apprehension prevents its use as a graft of primary choice for many surgeons. To date, there is no evidence available describing changes in postural control after its use in ACL reconstruction. The purpose of the study was to analyse the changes in postural control in the form of static and dynamic body balance after ACL reconstruction with Peroneus Longus Tendon Graft and compare it with the unaffected limb at different time intervals. Materials and methods: Thirty-one participants with ACL injury were selected and subjected to an assessment of static and dynamic balance before and after ACL reconstruction using the HUMAC balance system. Outcome measures for Centre of Pressure (COP) assessment were average velocity, path length, stability score, and time on target. Comparison of scores was done pre-operatively as well as at three- and six-months post-reconstruction with Peroneus longus tendon graft. Results: Static balance of the affected limb showed significant improvement with a decrease in average velocity (F=4.522, p=0.026), path length (F=4.592: p=0.024) and improvement of stability score (F=8.283, p=0.001). Dynamic balance measured by the time on the target variable also showed significant improvement at six-month follow-up (F=10.497: p=0.000). There was no significant difference between the affected and non-affected limb when compared at the different time intervals. Conclusion: The static and dynamic balance, which is impaired after ACL injury, improves with ACL reconstruction with PLT autologous graft. Hence PLTG can be safely used as a graft for ACL reconstruction without affecting postural control and body balance.

Nanoparticle Mediated Gene Therapy: A Trailblazer Armament to Fight CNS Disorders.

Central nervous system (CNS) disorders account for boundless socioeconomic burdens with devastating effects among the population, especially the elderly. The major symptoms of these disorders are neurodegeneration, neuroinflammation, and cognitive dysfunction caused by inherited genetic mutations or by genetic and epigenetic changes due to injury, environmental factors, and disease-related events. Currently available clinical treatments for CNS diseases, i.e., Alzheimer's disease, Parkinson's disease, stroke, and brain tumor, have significant side effects and are largely unable to halt the clinical progression. So gene therapy displays a new paradigm in the treatment of these disorders with some modalities, varying from the suppression of endogenous genes to the expression of exogenous genes. Both viral and non-viral vectors are commonly used for gene therapy. Viral vectors are quite effective but associated with severe side effects, like immunogenicity and carcinogenicity, and poor target cell specificity. Thus, non-viral vectors, mainly nanotherapeutics like nanoparticles (NPs), turn out to be a realistic approach in gene therapy, achieving higher efficacy. NPs demonstrate a new avenue in pharmacotherapy for the delivery of drugs or genes to their selective cells or tissue, thus providing concentrated and constant drug delivery to targeted tissues, minimizing systemic toxicity and side effects. The current review will emphasize the role of NPs in mediating gene therapy for CNS disorders treatment. Moreover, the challenges and perspectives of NPs in gene therapy will be summarized.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Ribociclib Nanostructured Lipid Carrier Aimed for Breast Cancer: Formulation Optimization, Attenuating In Vitro Specification, and In Vivo Scrutinization.

PURPOSE: The current investigation is on the explicit development and evaluation of nanostructured lipidic carriers (NLCs) through the oral route to overcome the inherent lacuna of chemotherapeutic drug, in which Ribociclib (RBO) was used for breast cancer to diminish the bioavailability issue. METHOD: The RBO-NLCs were prepared using the solvent evaporation method and optimized method by the Box-Behnken design (BBD). Various assessment parameters characterized the optimized formulation and their in vivo study. RESULTS: The prepared NLCs exhibited mean particle size of 114.23 ± 2.75 nm, mean polydispersity index of 0.649 ± 0.043, and high entrapment efficiency of 87.7 ± 1.79%. The structural analysis by TEM revealed the spherical size of NLCs and uniform drug distribution. An in vitro drug release study was established through the 0.1 N HCl pH 1.2, acetate buffer pH 4.5, and phosphate buffer pH 6.8 with % cumulative drug release of 86.71 ± 8.14, 85.82 ± 4.58, and 70.98 ± 5.69%, was found respectively, compared with the RBO suspension (RBO-SUS). In vitro intestinal gut permeation studies unveiled a 1.95-fold gain in gut permeation by RBO-NLCs compared with RBO-SUS. In vitro lipolysis suggests the drug availability at the absorption site. In vitro haemolysis study suggests the compatibility of NLCs to red blood cells compared to the suspension of the pure drug. The confocal study revealed the depth of penetration of the drug into the intestine by RBO-NLCs which was enhanced compared to RBO-SUS. A cell line study was done in MCF-7 and significantly reduced the IC50 value compared to the pure drug. The in vivo parameters suggested the enhanced bioavailability by 3.54 times of RBO-NLCs as compared to RBO-SUS. CONCLUSION: The in vitro, ex vivo, and in vivo results showed a prominent potential for bioavailability enhancement of RBO and effective breast cancer therapy.

Hypertension in Young Adults in India: Perspectives and Therapeutic Options amongst Clinician's in a Cross Sectional Observational Study.

BACKGROUND: The prevalence of hypertension in the young adult population is rising in India. Increased arterial stiffness due to RAAS activation and increased sympathetic overactivity due to stress have been implicated as primary factors for the same. This study was aimed to understand the Indian clinician's perspective on approach to management of hypertension in young adults. METHODS: A cross sectional observational survey using a structured questionnaire was conducted online with 2287clinicians (cardiologists, diabetologists, consultant physicians and family physicians). RESULTS: The prevalence of hypertension was 10-30% as per opinion of 64.8% clinicians. The top three risk factors for hypertension in young were perceived to be smoking, mental stress and obesity. Around 57.4% respondents opined that both increased heart rate and systolic blood pressure were markers of sympathetic overactivity. More than 60% respondents across specialities preferred ARBs to treat hypertension in young adults. Amongst the ARBs, telmisartan was the preferred ARB by >80% respondents. Metoprolol was the preferred beta blocker by almost 64% respondents. The objective of selection of beta-blocker by majority of clinicians due to sympathetic overactivity. Telmisartan and Metoprolol single pill combination achieved the BP goal in 40-60% of patients as reported by 41.3% of the physicians. The combination therapy was well tolerated in young hypertensive patients. CONCLUSIONS: Initiation of an early and appropriate antihypertensive treatment in young population may lower the burden of cardiovascular disease in this population. ARBs and beta -blockers were the preferred class of anti-hypertensive drugs in the cohort of young hypertensive patients .

COVID-19 lockdown: a rare opportunity to establish baseline pollution level of air pollutants in a megacity, India.

This paper analyses air quality data from megacity Delhi, India, during different periods related to the COVID-19, including pre-lockdown, lockdown and unlocked (post-lockdown) (2018-2020) to determine what baseline levels of air pollutants might be and the level of impact that could be anticipated under the COVID-19 lockdown emission scenario. The results show that air quality improved significantly during the lockdown phases, with the most significant changes occurring in the transportation and industrially dominated areas. A pronounced decline in PM2.5 and PM10 up to 63% and 58%, respectively, was observed during the lockdown compared to the pre-lockdown period in 2020. When compared to 2018 and 2019, they were lower by up to 51% and 61%, respectively, dropping by 56% during unlock. Some pollutants (NOx and CO) dropped significantly during lockdown, while SO2 and O3 declined only slightly. Moreover, when compared between the different phases of lockdown, the maximum decline for most of the pollutants and air quality index occurred during the lockdown phase 1; thus, this period was used to report the COVID-19 baseline threshold values (CBT; threshold value is the upper limit of baseline variation). Of the various statistical methods used median + 2 median absolute deviation (mMAD) was most suitable, indicating CBT values of 143 and 75 ug/m3 for PM10 and PM2.5, respectively. This results although preliminary, but it gives a positive indication that temporary lockdown can be considered as a boon to mitigate the damage we have done to the environment. Also, this baseline levels can be helpful as a first line of information to set future target limits or to develop effiective management policies for achieving better air quality in urban centres like Delhi. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-021-03142-3.

Fabrication of TiO2-based broadband single-layer anti-reflection coating by collimated glancing angle deposition technique.

Single-sided TiO2 thin films were prepared using a modified glancing angle deposition (GLAD) technique. An additional flux collimation plate was introduced into the GLAD arrangement to enhance the degree of collimation of depositing vapour flux. Enhancement in the ballistic growth of film on the substrate was observed with increasing distance from the vapour source. The substrate position near to the vapour source (i.e. bottom region) showed a high refractive index (RI, ∼1.336 @ 550 nm wavelength) and lower average film transmittance (∼94.5% in 400-900 nm wavelength range) compared to the others. In contrast, the TiO2 coating deposited at a distant position from the source (i.e. top region) showed a remarkably low RI (∼1.190 @ 550 nm wavelength) and excellent anti-reflection over a broad spectral region with a maximum average transmittance (∼95.3% in 400-900 nm wavelength) compared to the other substrate positions. The reduction in film RI was correlated qualitatively with the morphological alterations in the coating for different substrate positions. With a further increase in distance from the vapour source, an ultimate reduction in the RI of TiO2 to ∼1.101 was observed, which was ∼50% lower than the bulk TiO2 value (∼2.221 @ 550 nm wavelength). The present study reports the lowest RI of TiO2 together with fabrication of a TiO2-based broadband single-layer anti-reflection coating.

Curcumin Loaded Ethosomal Gel for Improved Topical Delivery: Formulation, Characterization and Ex-vivo Studies.

BACKGROUND: Curcumin is a curcuminoid, which is an active constituent of turmeric and is obtained from the rhizomes of Curcuma longa, family Zingiberaceae. Curcumin modulates the activity of various transcription factors and regulates the expression of inflammatory enzymes, cell survival proteins, adhesion molecules and cytokines by binding to a variety of proteins and inhibiting the activity of various kinases. Curcumin falls in the BCS class IV drug, with poor solubility and poor permeability which makes it very challenging to utilize the maximum therapeutic potential of this moiety Objective: The major aim of the study was to enhance transdermal penetration of curcumin via ethosomal gel and to overcome the barriers of poor permeability of transdermal drug delivery. METHODS: Curcumin loaded ethosomes were prepared with varying quantities of ethanol and soya lecithin by the cold method and were optimised based on entrapment efficiency, vesicular size and Ex-vivo studies. Optimised ethosomal formulation was further incorporated into a gel and was evaluated. Ex-vivo studies were performed with the ethosomal gel of curcumin and was compared with simple drug solution. RESULTS: Prepared ethosomal system showed a vesicle size ranging from 211 to 320 nm with spherical, smooth surface and entrapment efficiency of 87 to 91%. Optimised ethosomal system (ET3) was incorporated into gel and was further evaluated. CONCLUSION: The findings of the research work suggested that the ethosomal gel holds excellent potential for transdermal delivery of curcumin.

Vaccination approach to prevent Argulus siamensis infection-success, challenges and preparedness.

•Argulosis, a disease caused by Argulus spp. of ectoparasites in scaly fish, is a global concern for aquaculture industry.•The resistance of the parasite to anti-parasitic drugs and the quantum of loss has been felt world-wide.•The current scenario of management and the development in vaccination are discussed herewith.

Diversity of virulence-associated genes in pathogenic Aeromonas hydrophila isolates and their in vivo modulation at varied water temperatures.

Most environmental parameters have no consistent effect on the expression of bacterial genes responsible for their virulence. However, as fish are poikilothermic, the possibility of temperature variation having a pronounced effect on the expression of virulence-associated gene(s) of bacteria infecting the host needs to be investigated. In this study, the diversity of virulence genes in seven Aeromonas hydrophila isolates collected from diseased fish from different parts of India was characterized, and the effect of temperature variation on the extent of expression of their virulence was investigated. All bacterial isolates were screened for a total of nine bacterial virulent genes {aerolysin, hemolysin, cytoen, outer membrane protein TS (Omp TS), elastase, flagellin, lipase, ß hemolysin and type 3 secretion system}, and the diversity in their presence or absence were marked at a particular in vitro condition. Three bacterial isolates (nos. 1, 7 and 2) were selected for further study, based on their ability to cause varied mortalities (20-100%) in Labeo rohita juveniles in intraperitoneal challenge study. Further, three isolates were injected intraperitoneally into L. rohita fingerlings at three different temperatures (i.e., 20, 28 and 37 °C) and at 6 h post-challenge, the kidney samples were collected to measure the levels of all nine bacterial virulence genes using semi-quantitative PCR. The maximum level of amplicons of virulence genes in all three A. hydrophila isolates was noticed at 28 °C as compared to 37 °C and 20 °C. It was also observed that haemolysin played a more prominent role in the expression of virulence, when compared to cytoen gene. Hence, it was concluded that water temperature does play a crucial role in governing virulence gene expression, and a temperature of 28 °C would be considered as suitable for looking into the pathogenicity of A. hydrophila for conducting any challenge study with this organism in tropical environment.

Treatment and management strategies of onychomycosis.

Onychomycosis is one of the most prevalent and severe nail fungal infections, which is affecting a wide population across the globe. It leads to variations like nail thickening, disintegration and hardening. Oral and topical drug delivery systems are the most desirable in treating onychomycosis, but the efficacy of the results is low, resulting in a relapse rate of 25-30%. Due to systemic toxicity and various other disadvantages associated with oral therapy like gastrointestinal, hepatotoxicity, topical therapy is commonly used. Topical therapy improves patient compliance and reduces the cost of treatment. However, due to poor penetration of topical therapy across the nail plate, research is focused on different chemical, mechanical and physical methods to improve drug delivery. Penetration enhancers like Thioglycolic acid, Hydroxypropyl-ß-cyclodextrin (HP-ß-CD), Sodium lauryl sulfate (SLS), carbocysteine, N-acetylcysteine etc. have shown results enhancing the drug penetration across the nail plate. Results with physical techniques such as iontophoresis, laser and Photodynamic therapy are quite promising, but the long-term suitability of these devices is in need to be determined. In this article, a brief analysis of the treatment procedures, factors affecting drug permeation across nail plate, chemical, mechanical and physical devices used to increase the drug delivery through nails for the onychomycosis management has been achieved.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson's Disease.

Parkinson's disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson's disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson's disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson's disease.

Ultraviolet and Infrared luminescent Au-rich nanostructure growth in SiO2 by burrowing and inverse Oswald ripening process.

We study the evolution of nanoparticle morphology through successive stages when Au-Si bilayer on SiO2 is irradiated with 500 keV Xe-ions and resulting luminescence in the UV, Visible and infrared range. An array of nanoscale island morphology is developed on the silica surface in the initial stage of evolution which undergoes gradual burrowing in the silica matrix accompanied by elongation of large ones in the direction of incident ions under cumulative ion irradiation. Burrowing is found to occur in order to minimize the surface free energy of the nanoparticles. Numerical simulation based on the unified thermal spike model shows formation of molten latent tracks due to ions energy release which drive the dewetting of the metal layer and further give mobility to nanoparticle atoms leading to burrowing in the later stage of evolution and elongation of large nanoparticles. Satellite nanoparticles are observed to grow around Au nanoparticles embedded in silica through nucleation of Au atoms dissolved in the matrix by incident ions. The varying diameters of the Au satellite nanoparticles seem to result in luminescence in the UV and infrared range. The observed structure may find application in surface enhanced Raman scattering, catalysis, and LEDs.

Identification and functional characterization of a g-type lysozyme gene of Labeo rohita, an Indian major carp species.

Lysozyme, an important secretory innate immune component, possesses antimicrobial activity against broad spectrum of bacteria and viruses. In the present study, complete CDs (558 bps) of g-type lysozyme of rohu (Labeo rohita) was amplified and translated for a putative protein of 185 amino acids. The domain architecture and tertiary structure was also predicted for the protein. Its expression profile was studied in three infection models (bacteria: Aeromonas hydrophila, poly I:C, a dsRNA viral analogue and an ectoparasite: Argulus siamensis) in liver and kidney tissues of rohu. An up-regulation of 630-fold and 420-fold of the gene was observed at 48 h in liver and anterior kidney tissues respectively, after A. hydrophila infection. Significant increase in transcript level was noticed in both liver (0.8-fold) and kidney (480-fold) after 1 h and 12 h of poly I:C induction, respectively. Similarly, expression of lysozyme g transcripts was increased 6000-fold after 7 d of A. siamensis infection in liver tissue. The recombinant protein of g-type lysozyme of rohu (rLr-lysG) of 20.19 kDa was produced in Escherichia coli system and the lysozyme activity of rLr-lysG was found to be most active at pH 6.0 and temperature 35 °C. The potential lytic activity was found to be against A. hydrophila (UL = 0.53) followed by for E. tarda (UL = 0.45) whereas the lytic activity was the least against S. aureus (UL = 0.35) and M. lysodeikticus (UL = 0.34), at pH 6.0 and temperature 35 °C. The normal serum level of protein was estimated using indirect ELISA and was found to be very low (0.12-0.15 µg/ml). These results suggested that g-type lysozyme of rohu might be a potent immunostimulant against microbial infections, with a major role in innate immunity.

Development of a western blot method for detection of fish ectoparasite Argulus siamensis antigens.

A study was undertaken to develop a western blot method for detection of immunogenic proteins of fish ectoparasite, Argulus siamensis for its further use as potential vaccine candidates. Argulus antigens were prepared by homogenization and injected to rohu (Labeo rohita) juveniles for development of immune serum. The serum was used to immunostain the antigens in western blot. The other reagents added in sequence were rabbit anti-rohu serum, goat anti-rabbit ALP conjugate and substrate (BCIP-NBT). However, similar banding patterns were observed with both control and immunized rohu serum. Hence, a possible cross-reaction was suspected and verified in number of western blot experiments. A typical cross-reaction observed was of rabbit serum reacting directly with Argulus antigens. Hence, the rabbit anti-rohu serum was replaced with guinea pig anti-rohu serum. Another cross-reaction of goat anti-guinea pig ALP conjugate with rohu serum was eliminated by using goat anti-rabbit ALP conjugate with guinea pig serum. Thus, the final western blot method consisting of Argulus antigens → rohu serum → guinea pig anti-rohu serum → goat anti-rabbit ALP conjugate → substrate, yielded distinguishing results between control and Argulus-immunized rohu serum samples. The developed test has tremendous downstream applications, particularly in immunoproteomic studies of Argulus antigens.

A study of electron and thermal transport in layered titanium disulphide single crystals.

We present a detailed study of thermal and electrical transport behavior of single crystal titanium disulphide flakes, which belong to the two dimensional, transition metal dichalcogenide class of materials. In-plane Seebeck effect measurements revealed a typical metal-like linear temperature dependence in the range of 85-285 K. Electrical transport measurements with in-plane current geometry exhibited a nearly T 2 dependence of resistivity in the range of 42-300 K. However, transport measurements along the out-of-plane current geometry showed a transition in temperature dependence of resistivity from T 2 to T 5 beyond 200 K. Interestingly, Au ion-irradiated TiS2 samples showed a similar T 5 dependence of resistivity beyond 200 K, even in the current-in-plane geometry. Micro-Raman measurements were performed to study the phonon modes in both pristine and ion-irradiated TiS2 crystals.