Prevention of nodules and enhancement of antibody response to genetically engineered recombinant vaccine against Human Chorionic Gonadotropin (hCG) for contraception.

Objective: Human Chorionic Gonadotropin (hCG) plays a crucial role in embryo implantation and in maintenance of pregnancy. An immuno-contraceptive approach involves the use of a recombinant hCGß-LTB vaccine formulated with adjuvant Mycobacterium indicus pranii (MIP), to prevent pregnancy without disturbing ovulation, hormonal profiles, and menstrual cycles in women. The present work in mice was designed to address issues encountered in clinical trials conducted with hCGß-LTB vaccine, with focus on two primary concerns. Firstly, it aimed to determine the optimal vaccine dosage required to induce a high level of anti-hCG antibodies. Secondly, it aimed to assess the safety profile of the vaccine, specifically injection site reactions in the form of nodules, observed in some of the subjects.Methods and Results: Studies undertaken indicate that a 2 µg dose of the protein version of the vaccine, administered in mice through the intramuscular route, can induce high anti-hCG titres. Furthermore, administering a booster dose enhances the antibody response. Our findings suggest that the concentration and frequency of administration of the adjuvant MIP can also be reduced without compromising vaccine efficacy.Conclusion: The issue of nodule formation at the injection site can be mitigated either by administering the vaccine along with MIP intramuscularly or injecting hCG vaccine and MIP at separate intradermal sites. Thus, protein vaccine administered at a 2µg dose via the intramuscular route addresses both efficacy and safety concerns.

The Phase I/II clinical trials initiated with the recombinant hCG vaccine in women revealed inadequate antibody titres in all subjects, alongside the development of nodules at the injection sites in some participants. Studies were undertaken in mice to propose potential strategies for mitigating injection site reactions and enhancing the antibody response. It was concluded that the optimum dose of the protein version of the vaccine to get high antibody titres, is 2 µg administered intramuscularly while upholding safety standards.

Thermodynamic, kinetic, and equilibrium studies of Cu(II), Cd(II), Ni(II), and Pb(II) ion biosorption onto treated Ageratum conyzoid biomass.

The issue of environmental contamination, particularly caused by the existence of heavy metal particles, is a major and widely recognized subject that receives substantial global attention. The remediation of Cu(II), Cd(II), Ni(II), and Pb(II) ionic metal particles from synthetic wastewater using chemically treated plant leaves of Ageratum conyzoides (TAC) as a biosorbent was investigated. The biosorption process was implemented utilizing a batch system, wherein several operational parameters were considered, including temperature, pH, agitation time, biosorbent dosage, and initial concentration of the metal ion. Langmuir, Freundlich, Temkin, and D-R isotherm models were used to evaluate equilibrium data. The analyzed parameter exhibits characteristics that were best fitted with the Langmuir isotherm. The observed biosorption capacities (qm) of Cu(II), Pb(II), Ni(II), and Cd(II) ions on the TAC were measured as 51.573, 30.49, 33.53, and 35.91 mg/g, respectively, at a temperature of 22 °C. The affinity sequence of these metal ions follows the order Cu(II) > Pb(II) > Ni(II) > Cd(II). The measured values for the biosorption free energy change (ΔG) of Cu(II), Pb(II), Cd(II), and Ni(II) metal ions ranged from -1.017 to -4.723, -1.368 to -3.612, -2.785 to -5.21, and -1.047 to -5.135 kJ/mol, respectively. The enthalpy (ΔH) for Cu(II), Pb(II), Cd(II), and Ni(II) were determined to be +19.33, +6.82, +14.83, and +38.07 kJ/mol, respectively. Similarly, the corresponding entropy changes (ΔS) for the same series of metal ions were recorded as +0.075, +0.064, +0.063, and +0.135 kJ/mol.K. The pseudo-second-order kinetic models yielded superior outcomes in comparison to the pseudo-first-order kinetic models. The findings of the experiment indicated that the TAC demonstrates favorable efficacy in extracting all four metal ions. Hence, the utilization of biomass derived from Ageratum conyzoides leaves has proven to be a viable and economically feasible approach for biosorption of all four metals.

Reducing NICU Unplanned Extubations From Tube Dislodgement.

OBJECTIVES: Unplanned extubations (UEs) can be a frequent problem and are associated with adverse outcomes. This quality improvement initiative sought to reduce UEs from tube dislodgement in a level IV NICU utilizing methods applicable to other ICUs and performed with minimal monetary funds. METHODS: From January 2019 to July 2023, an interdisciplinary quality improvement team used the Model for Improvement and performed sequential interventions to improve the outcome measure of UEs per 100 ventilator days. Process measures included adherence to a modified, site-specific UE care bundle derived from the Solutions for Patient Safety network, whereas the number of endotracheal tube-related pressure injuries was used as a balancing measure. Statistical process control charts and established rules for special cause variation were applied to analyze data. RESULTS: Sequential interventions reduced the rate of UEs from a baseline of 2.3 to 0.6 UEs per 100 ventilator days. Greater than 90% adherence with the UE care bundle and apparent cause analysis form completion occurred since December 2020. There were no endotracheal tube-related pressure injuries. CONCLUSIONS: A sustained reduction in UEs was demonstrated. Leveraging a multidisciplinary team allowed for continuous UE analysis, which promoted tailored consecutive interventions. UE care bundle audits and the creation of a postevent debrief guide, which helped providers share a common language, were the most impactful interventions. Next steps include disseminating these interventions to other ICUs across our hospital enterprise. These low-cost interventions can be scalable to other NICUs and PICUs.

A nonionic microemulsion co-loaded with atorvastatin and quercetin: Simultaneous spectroscopic analysis and payload release kinetics.

In this study, we have co-loadedatorvastatin (ATR) and quercetin (QCT) in a nonionic microemulsion. After developing a derivative ratio spectrophotometric technique for simultaneous analysis of ATR and QCT, pseudoternary phase diagram was constructed utilizing1:4 d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and ethanol as surfactant and cosurfactant, respectively. Oleic acid was used as oil phase. Structural characterization of the formulation was carried out along a water dilution line created in monophasic region. Characterizations at these dilution points were performed using dynamic light scattering and polarized light microscopy. The average hydrodynamic size of the optimized formulation was found to be 18.9 nm and it did not change upon loading of ATR and QCT. In vitro release was assessed for the formulations loaded with different ratios of ATR and QCT, and the data were fitted to different mathematical models. Interestingly, we noticed differences in release kinetics during changes in dose ratios, particularly for QCT. Higuchi kinetics, observed at equal dose, shifted to Korsmeyer-Peppas model at higher QCT-ATR ratio (2:1 and 4:1). This difference is attributable to the ability of QCT molecules of overwhelming the interface at higher concentrations. Altogether, our observations highlight that the ratio of payloads should be selected carefully in order to avoid unpredictable release patterns.

Stereogenic Harmony Fabricated Mechanoresponsive Homochiral Triphenylalanine Analogues with Synergistic Antibacterial Performances: A Potential Weapon for Dermal Wound Management.

The wound recovery phenomenon remains as one of the long challenging concerns worldwide. In search of user-friendly dressing materials, in this report, we fabricated a rational combinatorial strategy utilizing stereogenic harmony in a triphenylalanine fragment and appending it to δ-amino valeric acid at the N-terminus (hydrogelators I-VII) such that a potential scaffold could be fished out from the design. Our investigations revealed that all the hydrogelators displayed not only excellent self-healing performance as well as high mechanical strength at physiological pH but also mechanical stress-triggered gel-sol-gel transition properties. The structural and morphological investigation confirmed the presence of ß-sheet-like assemblies stabilized by intermolecular H-bonding and π-π interactions. Moreover, these scaffolds showed substantial antibacterial as well as antifungal efficacy against common wound pathogens, i.e, four Gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans, B. subtilis, E. fecalis), four Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, P. aerugonosa, Proteus spp.), and two fungal strains (C. albicans and A. niger). The manifestation of consistent antioxidant properties might be due to the enhancement of amphiphilicity in hydrogelators, which has led to the generation of reactive oxygen species (ROS) in a facile manner, a probable mechanism to damage the microbial membrane, the driving force behind the antimicrobial efficacy. Also, the constructs exhibited proteolytic resistance and remarkable biocompatibility toward mammalian cells. Thus, based on the above benchmarks, the homochiral hydrogelator IV was seived out from a pool of seven, and we proceeded toward its in vivo evaluation using full-thickness excisional wounds in Wister rats. The scaffolds also accentuated the re-epithelialization as well in comparison to the negative control, thereby facilitating the wound closure process in a very short span of time (10 days). Overall, our in vitro and in vivo analysis certifies hydrogelator IV as an ideal dressing material that might hold immense promise for future wound care management.

A quality improvement initiative to reduce antibiotic use in transient tachypnea of the newborn.

OBJECTIVE: Evidence suggests that antibiotics are unnecessary in infants with transient tachypnea of the newborn (TTN) that are low-risk for early-onset sepsis. The aim was to reduce ampicillin and gentamicin days of therapy (DOT) in infants with suspected TTN by 10% within 12 months. STUDY DESIGN: We used the Model for Improvement to test interventions from August 2019 to September 2021 to decrease antibiotic utilization in low-risk infants with TTN. Interventions included the creation of an evidence-based clinical pathway, admission huddles, and prescriber audit and feedback. RESULTS: We reduced ampicillin and gentamicin use by 26% and 23%, respectively. In 123 infants with suspected TTN, we sequentially decreased starting antibiotics in this group from 71% to 41%, 13% and 0%. There were no cases of missed bacteremia. CONCLUSION: Creation of a multidisciplinary antimicrobial stewardship QI team and subsequent interventions were successful in safely reducing antibiotic use in infants with TTN.

A Homochiral Diphenylalanine Analog Based Mechanoresponsive Hydrogel: An Insight Towards Its Wound Healing Efficacy.

Deciphering the most promising strategy for the evolution of potential wound-healing therapeutics is one of the greatest challenging affairs to date. The development of peptide-based smart scaffolds with innate antimicrobial, anti-inflammatory, and antioxidant properties is an appealing way out. Aligned to the goal a set of Hydrogelators I-IV were developed utilizing the concept of chiral orchestration in diphenylalanine fragment, such that the most potent construct with all the bench marks namely mechanoresponsiveness, biocompatibility, consistent antimicrobial and antioxidant properties, could be fished out from the design. Interestingly, our in vitro Antifungal and Lipid peroxidation analysis identified the homochiral isomer Boc-δ-Ava-L-Phe-L-Phe-OH (Hydrogelator I), as an ideal candidate for the wound healing experiment, so we proceeded for the in vivo histopathological and antioxidant measurements in Wister rats. Indeed the wound images obtained from the different sets of animals on the 14th day of treatment demonstrated that with increased recovery time, hydrogelator I displayed a significant reduction in the lesion diameter compared to the marketed drug, and negative control. Even the histopathological measurements using H & E staining demonstrated diminished tissue destruction, neutrophil infiltration necrosis, and lymphatic proliferation in the hydrogelators, in comparison to others, backed by in vivo lipid peroxidation data. Overall our investigation certifies hydrogelator I as an effective therapeutic for managing the wound healing complication.

Tinospora cordifolia Miers enhances the immune response in mice immunized with JEV-vaccine: A network pharmacology and experimental approach.

BACKGROUND: Tinospora cordifolia Miers. (TC) (Giloya/Guduchi) is a native Indian herb, reported for its wide array of medicinal activities including immunomodulatory activity. However, the exact pharmacological mechanism of TC as an immunomodulatory agent remains unclear. Central to this, to the best of our knowledge, no study has explored the immunoadjuvant potential of TC in response to the Japanese encephalitis (JE) vaccines. PURPOSE: The study aims to explore the immunoadjuvant potential of TC ethanolic extract in response to the JE vaccine and illustrates its potential mechanism of immunomodulation using an integrated approach of network pharmacology and in-vivo experimental study. STUDY DESIGN AND METHODS: Initially, the extract was prepared and the components of TC were identified through high-resolution liquid chromatography mass spectrometry (HR-LC/MS). The compounds were then screened for network pharmacology analysis. Next, the drug and disease targets were identified and the network was constructed using Cytoscape 3.7.2 to obtain different signalling pathways of TC in JEV. We then evaluated the immunoadjuvant potential of TC ethanolic extract in mice immunized with inactivated JE vaccine (SA-14-14-2 strain). BALB/c mice were supplemented with TC extract (30 and 100 mg/kg, i.g.), daily for 56 days, marked with immunization on 28th day of the study, by JE vaccine. Blood was collected for flow cytometry and haematological analysis (total and differential cell counts). The surface expression of immune-cell markers (CD3+, CD4+, CD19+, CD11c+, CD40+) were evaluated on day 0 (pre-immunization), day 14 and 28 post-immunization. Additionally, inflammatory cytokines (IFN-γ+/IL-17A+) were evaluated post-14 and 28 days of immunization. RESULTS: The HR-LC/MS analysis identified the presence of glycosides, terpenoids, steroids and alkaloids in the TC extract. Through network analysis, 09 components and 166 targets were obtained, including pathways that involve toll-like receptor signalling, pattern-recognition receptor signalling, cytokine receptor and cytokine mediated signalling, etc. The in-vivo results showed that preconditioning with TC ethanolic extract significantly elevated the haematological variables (leucocyte count) as well as the surface expression of CD markers (B and T cell subsets) on day 0 (pre-immunization), day 14 and 28 post-immunization. Furthermore, preconditioning of TC demonstrated a dose-dependant augmentation of immune cells (CD3+, CD4+, CD19+, CD11c+) and inflammatory cytokines (IFN-γ+/IL-17A+) on day 14 and 28 post-immunization when compared to vaccine alone group. CONCLUSION: Results showed that preconditioning with TC extract before immunization might play a potential role in enhancing the cell-mediated as well as humoral immunity. Altogether, the combinatorial approach of network pharmacology and in-vivo animal experimentation demonstrated the immunoadjuvant potential of TC in response to JEV vaccine.

Long Term Treatment of Corticostreroids May Cause Hepatotoxicity and Oxidative Damage: A Case Controlled Study.

Arthritis is a clinical condition, which mainly affects the structure and function joints. During this condition the joints gets swelled and stiffed resulting into development of pain and morbidity. Corticosteroids are frequently prescribed to manage various clinical conditions including the chronic inflammatory diseases such as arthritis. The steroidal drug also causes certain adverse effects depending on the dose, the route of administration and duration of treatment. However, a systematic investigation on the biochemical consequences of steroids as a therapeutic has not been carried out. In the present study we analyzed certain parameters associated to oxidative stress, liver function and energy metabolism has been done in the blood plasma of the arthritis patients who were using steroidal drugs (methylprednisolone and deflazacort) up to 168 days for the treatment of the disease. The results indicated increase in level of MDA and decrease in the activities of SOD, CAT and LDH. The activities of AST and ALT were found to be significantly enhanced over the increase in the treatment period. These results suggested that corticosteroids may induce lipid peroxidation, oxidative stress and liver toxicity in the arthritis patients in the dose and duration dependent manner. The use of antioxidants as supplements to the anti-arthritis agents could play a role in suppressing the oxidative stress mediated adverse effects. However, extensive research is required to explore for safer medication devoid of steroids to cure arthritis.

Acetyl transferase EP300 deficiency leads to chronic replication stress mediated by defective fork protection at stalled replication forks.

Mutations in the epigenetic regulator and global transcriptional activator, E1A binding protein (EP300), is being increasingly reported in aggressive hematological malignancies including adult T-cell leukemia/lymphoma (ATLL). However, the mechanistic contribution of EP300 dysregulation to cancer initiation and progression are currently unknown. Independent inhibition of EP300 in human cells results in the differential expression of genes involved in regulating the cell cycle, DNA replication and DNA damage response. Nevertheless, specific function played by EP300 in DNA replication initiation, progression and replication fork integrity has not been studied. Here, using ATLL cells as a model to study EP300 deficiency and an p300-selective PROTAC degrader, degrader as a pharmacologic tool, we reveal that EP300-mutated cells display prolonged cell cycle kinetics, due to pronounced dysregulations in DNA replication dynamics leading to persistent genomic instability. Aberrant DNA replication in EP300-mutated cells is characterized by elevated replication origin firing due to increased replisome pausing genome-wide. We demonstrate that EP300 deficiency results in nucleolytic degradation of nascently synthesized DNA at stalled forks due to a prominent defect in fork stabilization and protection. This in turn results in the accumulation of single stranded DNA gaps at collapsed replication forks, in EP300-deficient cells. Inhibition of Mre11 nuclease rescues the ssDNA accumulation indicating a dysregulation in downstream mechanisms that restrain nuclease activity at stalled forks. Importantly, we find that the absence of EP300 results in decreased expression of BRCA2 protein expression and a dependency on POLD3-mediated error-prone replication restart mechanisms. The overall S-phase abnormalities observed lead to under-replicated DNA in G2/M that instigates mitotic DNA synthesis. This in turn is associated with mitotic segregation defects characterized by elevated micronuclei formation, accumulation of cytosolic DNA and transmission of unrepaired inherited DNA lesions in the subsequent G1-phase in EP300-deficient cells. We demonstrate that the DNA replication dynamics of EP300-mutated cells ATLL cells recapitulate features of BRCA-deficient cancers. Altogether these results suggest that mutations in EP300 cause chronic DNA replication stress and defective replication fork restart results in persistent genomic instability that underlie aggressive chemo-resistant tumorigenesis in humans.

Stabilization of lysozyme in aqueous dispersion of graphene oxide sheets.

This study examines the effect of surface oxygen groups upon ability of graphene oxide (GO) sheets in suppressing the fibrillation of lysozyme (LYZ). Graphite was oxidized using 6 and 8 wt equivalents of KMnO4, and as produced sheets were abbreviated as GO-06 and GO-08, respectively. Particulate characteristics of sheets were characterized by light scattering and electron microscopic techniques, and their interaction with LYZ was analysed by circular dichroism (CD) spectroscopy. After ascertaining acid-driven conversion of LYZ to fibrillary form, we have shown that the fibrillation of dispersed protein can be prevented by adding GO sheets. Inhibitory effect could be attributed to binding of LYZ over the sheets via noncovalent forces. A comparison between GO-06 and GO-08 samples showed superior binding affinity of the latter. Higher aqueous dispersibility and density of oxygenated groups in GO-08 sheets would have facilitated the adsorption of protein molecules, thus making them unavailable for aggregation. Pre-treatment of GO sheets with Pluronic 103 (P103, a nonionic triblock copolymer), caused reduction in the adsorption of LYZ. P103 aggregates would have rendered the sheet surface unavailable for the adsorption of LYZ. Based on these observations, we conclude that fibrillation of LYZ can be prevented in association with graphene oxide sheets.

Detection and modulation of neurodegenerative processes using graphene-based nanomaterials: Nanoarchitectonics and applications.

Neurodegenerative disorders (NDDs) are caused by progressive loss of functional neurons following the aggregation and fibrillation of proteins in the central nervous system. The incidence rate continues to rise alarmingly worldwide, particularly in aged population, and the success of treatment remains limited to symptomatic relief. Graphene nanomaterials (GNs) have attracted immense interest on the account of their unique physicochemical and optoelectronic properties. The research over the past two decades has recognized their ability to interact with aggregation-prone neuronal proteins, regulate autophagy and modulate the electrophysiology of neuronal cells. Graphene can prevent the formation of higher order protein aggregates and facilitate the clearance of such deposits. In this review, after highlighting the role of protein fibrillation in neurodegeneration, we have discussed how GN-protein interactions can be exploited for preventing neurodegeneration. A comprehensive understanding of such interactions would contribute to the exploration of novel modalities for controlling neurodegenerative processes.

Protective Effect of Methanolic Extract of Euglena tuba Against Dalton Lymphoma Induced Oxidative Stress in BALB/c Mice.

The identification and pharmacological validation of plant-based lead compounds for the cure of different diseases including cancer have always been globally strived. In addition to possessing numerous medicinal properties, many of the phytochemicals display antioxidant potential activities. Reactive oxygen species (ROS) causeoxidative stress leading to several severe diseases such as cancer. The antioxidants are substances that fight against ROS to protect the cells from their damaging effects. In the present study, the effects of methanol extract of Euglena tuba(ETME) have been evaluated for its antioxidant and antitumor potential against Dalton's lymphoma (DL) introduced in BALB/cmice. After 24 h of intraperitoneal inoculation of DL cells in mice, ETME (300 mg kg-1 body weight) was administered intraperitoneally upto18 alternative days. On the 18th day, the mice were sacrificed; the blood and tissues (liver and brain) were collected to determine the tumor growth parameters including morphological, behavioural, haematological profile, and antioxidant indices. The results indicated that ETME exhibited significant antioxidative and antitumor properties when compared with the data from DL bearing mice. The results from the present study indicated that ETME contained remarkable antitumor efficacy, which was mediated through amelioration of oxidative stress. The data suggested that ETME could be used as a potential natural anticancer agent.

Design, development and characterization of resistive arm based planar and conformal metasurfaces for RCS reduction.

This paper reports the design, development and characterization of a broadband, polarization insensitive metasurface absorber in planar, cylindrically bent and 90° dihedral surface geometry. Four metallic patches loaded with eight lumped resistors are used, which has been optimized numerically using CST MICROWAVE STUDIO, as a unit cell of developed metasurface absorber, to achieve 20 dB reflection reduction for 51.21% fractional bandwidth (13.42-22.66 GHz) under normal incidence with 0.12 [Formula: see text] thickness (where [Formula: see text] corresponds to lower operating frequency). The numerical findings are also verified analytically using equivalent circuit analysis, which exhibits very good agreement. Polarization-insensitive characteristics are achieved using fourfold rotation symmetry of the designed structure. The fabricated prototype of the designed absorber is experimentally characterized, using free space measurement method and ABmm vector network analyzer (VNA) system, and fairly good agreement with numerical-analytical findings are reported. The major novelty of this study is the design and development of a broadband (13.42-22.66 GHz), polarization insensitive metasurface absorber that provides 20 dB reflection reduction numerically as well as experimentally in the whole band, which to the author's knowledge has not been observed till now. Also, keeping in mind the radar stealth applications, first time we have demonstrated both numerically and experimentally, different geometrical shapes of conformal metasurfaces that can be practically used in actual scenario.

Biochemical Characterization of Different Chemical Components of Parthenium hysterophorus and Their Therapeutic Potential against HIV-1 RT and Microbial Growth.

Parthenium hysterophorus possesses certain allelochemicals responsible for their medicinal effects. The presence of oils, polyphenols, alkaloids, terpenes, pseudoguaianolides, and histamines in P. hysterophorus has been shown to exhibit medicinal properties. However, the systematic biomedical properties of this plant are still unexplored. The extracts of leaves, stem, and flower of P. hysterophorus, both at low and high temperatures (equivalent to boiling points of different solvents) were prepared. The extracts prepared in hexane, ethylacetate, methanol, and water were analyzed spectrophotometrically and colorimetrically and resolved on TLC for the presence of phytochemicals. The analyses of the free radical quenching potential of plant extracts were done by DPPH assay. The total antioxidant capacity was determined by phosphomolybdate assay and the ferric reducing antioxidant power (FRAP) assay was used to determine the reduction potential of the extracts. The spectrophotometric and qualitative analysis of plant extracts demonstrated the presence of alkaloids, terpenoids, carbohydrates, and cardiac glycosides. The occurrence of more than one Rf values for extracts determined by TLC indicated the presence of more than one phytochemical compound. The P. hysterophorus extracts contained strong antioxidant activity. These extracts exhibited strong antimicrobial activity against Staphylococcus epidermis, Salmonela typhi, Neisseria gonococci or gonococci, Citrobacter, and Shigella flexineri. The evaluation of the antimicrobial potential of P. hysterophorus extracts was done by the disc diffusion method. These extracts also showed significant inhibition against HIV-1 RT activity. The anti-HIV-1 RT activity was done using Roche Kit. The P. hysterophorus extracts displayed the presence of many phytochemicals with strong antioxidant, antimicrobial, and anti-HIV-1 RT properties.

Raga todi intervention on state anxiety level in female young adults during COVID-19.

Raga todi, an Indian classical music raga is emerging as a therapeutic approach in mental health and well being. This study aims to assess the relationship of raga todi and state anxiety at the time of novel coronavirus spread across the globe. 30 young female adults of age 20-28 years were randomly assigned to experimental group and control group of 15 participants each to which a pre and post test of State Anxiety test of STAI-A was administered. Results stated that state anxiety is negatively correlated to the listening of raga todi. Thus, listening to raga todi could be useful in reducing the state anxiety level provoked by a stressful life event like the lethal coronavirus pandemic.

Technology: Saving and Enriching Life During COVID-19.

The pandemic of COVID-19 has arrested the life of 7.8 million people living on this earth. However, some people are more vulnerable to the risk of this deadly virus. The frailty of senior citizens put them at the top of this list. The past 6 months have not only presented a threat to their physical health but to mental health also. Although lockdown was necessary to check the spread of the coronavirus it culminated in an exponential rise in the problems of loneliness, anxiety, fear, helplessness, and depression. The present paper reviews the role of social networking sites, apps, and other digital platforms in saving and enriching the lives of the elderly, especially those who spent the lockdown alone and were devoid of a regular support system due to unavailability of transport and administrative restrictions on the movement of people. It also analyzes the efficiency of the virtual world in reducing their anxiety of being alone by connecting them with others and also make them feel empowered. The review is based on the online data collected about the insurgence in the percentage of elderly people using such platforms, recent studies analyzing the effects of the COVID 19 pandemic on senior citizens. Besides this personal telephonic discussions were conducted with some elderly people who spent their lockdown alone in their homes. The study was primarily focused on three objectives. Firstly it attempts to understand the ways in which senior citizens made use of social networking sites and various digital platforms for managing life better. Secondly, it analyses the process of adopting technology, and finally, it examined the width and depth of the impact technology created in their life and also the permanence of this change. The analysis clearly suggests an increase in the digital life of elderly people. The process moved in distinct stages from utter confusion to relative ease in using technology, thereby significantly reducing the loneliness, and bringing relatively stable change in the way they lead their life.

Care of inflammatory bowel disease patients during coronavirus disease-19 pandemic using digital health-care technology.

Background and Aim: Although telemedicine is an option for the care of inflammatory bowel disease (IBD) patients during the Coronavirus Disease (COVID)-19 pandemic, its feasibility and acceptability data are scant. Data on the frequency of COVID-19 among patients with IBD, quality of life (QOL), access to health care, psychological stress, and anxiety during the COVID-19 pandemic are scant. Methods: Video/audio consultation for IBD patients was undertaken after a web-based appointment, and data on acceptability, IBD control, Hospital Anxiety Depression Scale (HADS), and World Health Organization Quality of Life questionnaire (WHOQOL-Bref) were obtained electronically. IBD patients were assessed for COVID-19 symptoms or contact history and tested using reverse transcriptase polymerase chain reaction (RT-PCR) on naso- oro-pharyngeal swabs, and data were compared with 16,317 non-IBD controls. Results: Teleconsultation was feasible and acceptable. IBD patients had COVID-19 as frequently as non-IBD controls despite immunosuppressive therapy, possibly due to their awareness and preventive practices. Although the physical, psychological, and social QOL scores during the COVID-19 pandemic were comparable to the prepandemic period, the environmental scores were worse. Psychological tension and interference with work due to pain were lower during the pandemic, which might be influenced by the control of the disease. Conclusions: Teleconsultation is a feasible and acceptable alternative for IBD patients. They had COVID-19 as frequently as non-IBD controls despite a high frequency of immunosuppressive treatment, possibly due to their awareness of the disease and preventive practices. The QOL scores (except the environmental domains) and psychological issues were quite comparable or even better during the COVID-19 pandemic than earlier.

Chiral Orchestration: A Tool for Fishing Out Tripeptide-Based Mechanoresponsive Supergelators Possessing Anti-Inflammatory and Antimicrobial Properties.

Deciphering the most promising strategy for the evolution of microbial infection and inflammation-based therapeutics is one of the most challenging affairs to date. Development of peptide-based smart supergelators with innate antimicrobial and anti-inflammatory activities is an appealing way out. In this work, the hydrogelators Boc-δ-Ava-(X)-Phe-(Y)-Phe-OH (I: X = Y = L; II: X = L; Y = D; III: X = D; Y = L; IV: X = Y = D, Ava: δ-amino valeric acid) have been designed and fabricated by strategic chiral tuning to investigate the effect of alternation of configuration(s) of Phe residues in governing the fashion of self-aggregation and macroscopic properties of peptides. Interestingly, all of the molecules formed mechanoresponsive hydrogels under physiological conditions with a nanofibrillar network. The spectroscopic experiments confirmed the conformation of the hydrogelators to be supramolecular ß-sheets formed through the self-association of S-shaped constructs stabilized by noncovalent interactions. Indeed, the present work demonstrates a rational approach toward regulating the mechanical integrity of the hydrogels through systematic inclusion of d-amino acids at appropriate positions in the sequence. The hydrogelators were found to possess antimicrobial activity against both Gram-positive bacteria (Staphylococcus aureus and Streptococcus mutans) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia) while retaining their biocompatibility toward mammalian cells (as revealed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), hemolysis, and lipid peroxidation assays). These scaffolds also exhibited anti-inflammatory activities, as observed through in vitro MMP2/MMP9 inhibition studies and in vivo animal models, namely, the rat pouch model for acute inflammation. We anticipate that the discovery of these intelligent materials with multifunctional capabilities holds future promise as preferential therapeutics for the treatment of bacterial infections as well as associated inflammations arising alone or as side effects of biomaterial implants.

Kinetic characterization of rat brain acetylcholinesterase modulated by lead and cartap: the ameliorative effect of Citrus limon fruit juice.

OBJECTIVES: Human exposure to heavy metals and pesticides is a worldwide major health problem. These environmental pollutants have been considered as the most neurotoxic agents and responsible to causing neurological toxicity. Plant-based therapeutic supplement may be used in the event of toxicity. Citrus limon contains several useful bioactive ingredients including flavonoids, dietary fiber, carotenoids, vitamins, pectin, minerals, and essential oils, which are responsible for its therapeutic potential. In the present investigation, we have studied the toxicity of heavy metals such as lead (Pb) and a carbamate pesticide such as cartap (Cp) on rat brain acetylcholinesterase (AChE). METHODS: The chemical characterization of C. limon involved determination of total antioxidants and 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical scavenging activity using known methods. The AChE activity and its kinetic characterization were performed by assaying the enzyme activity at varying substrate concentrations, pH, temperature, and time of reaction. Its different kinetic parameters such as K i , V max, K m , K cat, and K cat/K m were determined by using standard procedures. The amelioration potential of the extract was evaluated on the neurotransmission system of rat brain AChE treated with Pb, Cp, and their combination (Pb-Cp), considering their 50% inhibitory concentration (IC50) values. RESULTS: The optimal activity of rat brain AChE was recorded at 25 µg of protein, pH of 7.4, substrate concentration [S] of 0.5 mM, and temperature of 37.4-40°C. The enzyme was stable for 10 min when incubated at 37.4 °C in vitro. The enzyme displayed 70% of its activity remaining even after 160 min of incubation in this condition. It may be stable up to 1 month when stored at -20°C. The IC50 values for Pb, Cp, and Pb-Cp were found to be 75, 2.9, and 5 mM, respectively. Pb, Cp, and Pb-Cp inhibited the activity of rat brain AChE in the noncompetitive, mixed, and uncompetitive manners, respectively, with their respective K i values to be 675, 2.37, and 22.72 mM. CONCLUSIONS: The results indicated that the Pb and Cp were able to cause significant alterations in the level and properties of AChE. However, the introduction of lemon juice on Pb- and Cp-treated AChE indicated protection of its activity from their adverse effects. The results may be useful in prospective therapeutic applications of lemon juice or as a food supplement to protect mammalian systems from adverse effects of these toxicants.