Comparison of Immune Correlates, Age Related Changes and Proteomic Profiling of Healthy Individuals Receiving Influenza Vaccines

The burden of influenza related infections is substantial, both in terms of illness, lives lost and economic impact on society. The degree of impact of influenza related infections is much higher in the elderly population where it is a leading cause of catastrophic disability; greatly affecting the quality of life of elderly persons above 65 years of age. Vaccination is the mainstay for control and prevention of influenza infections. There are two vaccine formulations that are licensed for use at present. The inactivated influenza vaccines (TIIV) which have been used for 60 years in all age groups and the new live attenuated influenza vaccine (LAIV) which is only recommended for use in individuals between 2-49 years of age. The mechanisms by which these two vaccines provide immunity in pre-vaccinated individuals have not been investigated in detail. In our study we looked at the different immune correlates of vaccine responses and studied the mechanism by which these two vaccines provide immunity. We investigated age related changes in immune response to inactivated influenza vaccines between young and elderly. We also attempted to identify serum specific vaccine and age related immune senescence markers using mass spectrometric approach by using the MALDI-TOF MS technique. We found contrasting immune responses induced by the two vaccines in different arms of the immune system. Our results showed that using antibody titer as the only standard to measure vaccine efficacy may lead to a bias towards parentarally administered vaccines. Our study showed significant age related differences in both humoral and cell mediate immune responses in the cohort immunized with inactive influenza vaccine. Elderly showed a decline in IFN-γ secretion as a result of age related decline in the function of influenza specific memory T cells. A positive correlation was observed between Th 1 T cell response and antibody response only in the elderly which suggested an important role of IFN-γ to antibody response in elderly. Our study did not find any relationship in baseline levels of IL-10, IL-6, TNF-α and 1L-1β cytokines affecting T cell or antibody response in the elderly which suggests that immune response to vaccination is not affected in the elderly due to a change in these cytokines with age. We also demonstrated that MALDI-TOF MS technique was not feasible in identifying vaccine response or immune senescence markers in healthy vaccinated individuals

Electro-Gene Transfer to Skin Using a Noninvasive Multielectrode Array

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene-expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest that EP with MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications

Enhanced Killing Effect of Nanosecond Pulse Electric Fields on PANC1 and Jurkat Cell Lines in the Presence of Tween 80

We investigated the effects of nanosecond pulse electric fields (nsPEFs) on Jurkat and PANC1 cells, which are human carcinoma cell lines, in the presence of Tween 80 (T80) at a concentration of 0.18% and demonstarted an enhanced killing effect. We used two biological assays to determine cell viability after exposing cells to nsPEFs in the presence of T80 and observed a significant increase in the killing effect of nsPEFs. We did not see a toxic effect of T80 when cells were exposed to surfactant alone. However, we saw a synergistic effect when cells exposed to T80 were combined with the nsPEFs. Increasing the time of exposure for up to 8 h in T80 led to a significant decrease in cell viability when nsPEFs were applied to cells compared to control cells. We also observed cell type-specific swelling in the presence of T80. We suggest that T80 acts as an adjuvant in facilitating the effects of nsPEFs on the cell membrane; however, the limitations of the viability assays were addressed. We conclude that T80 may increase the fragility of the cell membrane, which makes it more susceptible to nsPEF-mediated killing

"The fruits of independence": Satyajit Ray, Indian nationhood and the spectre of empire

Challenging the longstanding consensus that Satyajit Ray's work is largely free of ideological concerns and notable only for its humanistic richness, this article shows with reference to representations of British colonialism and Indian nationhood that Ray's films and stories are marked deeply and consistently by a distinctively Bengali variety of liberalism. Drawn from an ongoing biographical project, it commences with an overview of the nationalist milieu in which Ray grew up and emphasizes the preoccupation with colonialism and nationalism that marked his earliest unfilmed scripts. It then shows with case studies of Kanchanjangha (1962), Charulata (1964), First Class Kamra (First-Class Compartment, 1981), Pratidwandi (The Adversary, 1970), Shatranj ke Khilari (The Chess Players, 1977), Agantuk (The Stranger, 1991) and Robertsoner Ruby (Robertson's Ruby, 1992) how Ray's mature work continued to combine a strongly anti-colonial viewpoint with a shifting perspective on Indian nationhood and an unequivocal commitment to cultural cosmopolitanism. Analysing how Ray articulated his ideological positions through the quintessentially liberal device of complexly staged debates that were apparently free, but in fact closed by the scenarist/director on ideologically specific notes, this article concludes that Ray's reputation as an all-forgiving, ‘everybody-has-his-reasons’ humanist is based on simplistic or even tendentious readings of his work

Periodically aperiodic pattern of SARS-CoV-2 mutations underpins the uncertainty of its origin and evolution

Various lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have contributed to prolongation of the coronavirus disease 2019 (COVID-19) pandemic. Several non-synonymous mutations in SARS-CoV-2 proteins have generated multiple SARS-CoV-2 variants. In our previous report, we have shown an evenly uneven distribution of unique protein variants of SARS-CoV-2 is geo-location or demography-specific. However, the correlation between the demographic transmutability of the SARS-CoV-2 infection and mutations in various proteins remains unknown due to hidden symmetry/asymmetry in the occurrence of mutations. This study tracked how these mutations are emerging in SARS-CoV-2 proteins in six model countries and globally. In a geo-location, considering the mutations having a frequency of detection of at least five hundred in each SARS-CoV-2 protein; we studied the country-wise percentage of invariant residues. Our data revealed that since October 2020, highly frequent mutations in SARS-CoV-2 have been observed mostly in the Open Reading Frames (ORF) 7b and ORF8, worldwide. No such highly frequent mutations in any of the SARS-CoV-2 proteins were found in the UK, India, and Brazil, which does not correlate with the degree of transmissibility of the virus in India and Brazil. However, we have found a signature that SARS-CoV-2 proteins were evolving at a higher rate, and considering global data, mutations are detected in the majority of the available amino acid locations. Fractal analysis of each protein's normalized factor time series showed a periodically aperiodic emergence of dominant variants for SARS-CoV-2 protein mutations across different countries. It was noticed that certain high-frequency variants have emerged in the last couple of months, and thus the emerging SARS-CoV-2 strains are expected to contain prevalent mutations in ORF3a, membrane, and ORF8 proteins. In contrast to other beta-coronaviruses, SARS-CoV-2 variants have rapidly emerged based on demographically dependent mutations. Characterization of the periodically aperiodic nature of the demographic spread of SARS-CoV-2 variants in various countries can contribute to the identification of the origin of SARS-CoV-2

Topical Gene Electrotransfer to the Epidermis of Hairless Guinea Pig by Non-invasive Multielectrode Array

Topical gene delivery to the epidermis has the potential to be an effective therapy for skin disorders, cutaneous cancers, vaccinations and systemic metabolic diseases. Previously, we reported on a non-invasive multielectrode array (MEA) that efficiently delivered plasmid DNA and enhanced expression to the skin of several animal models by in vivo gene electrotransfer. Here, we characterized plasmid DNA delivery with the MEA in a hairless guinea pig model, which has a similar histology and structure to human skin. Significant elevation of gene expression up to 4 logs was achieved with intradermal DNA administration followed by topical non-invasive skin gene electrotransfer. This delivery produced gene expression in the skin of hairless guinea pig up to 12 to 15 days. Gene expression was observed exclusively in the epidermis. Skin gene electrotransfer with the MEA resulted in only minimal and mild skin changes. A low level of human Factor IX was detected in the plasma of hairless guinea pig after geneelectrotransfer with the MEA, although a significant increase of Factor IX was obtained in the skin of animals. These results suggest geneelectrotransfer with the MEA can be a safe, efficient, non-invasive skin delivery method for skin disorders, vaccinations and potential systemic diseases where low levels of gene products are sufficient

The New Keynesian business cycle achievements and challenges

The New-Keynesian (NK) business cycle model has presented itself as a potential “workhorse” model for business cycle analysis. This paper seeks to assess afresh the performance of the baseline NK model and its various extensions. The main theme of the paper is that although the dynamic NK literature has secured a robust defence to criticism arising, inter alia, on account of lack of microfoundations, it still has a long way to go in terms of providing a fully satisfactory model of the business cycle. In this regard, it is conjectured that explicitly accounting for the role of heterogeneity in business- cycle dynamics could lead towards a viable solution.info:eu-repo/semantics/publishedVersio

The SCARE Statement: Consensus-based surgical case report guidelines

AbstractIntroductionCase reports have been a long held tradition within the surgical literature. Reporting guidelines can improve transparency and reporting quality. However, recent consensus-based guidelines for case reports (CARE) are not surgically focused. Our objective was to develop surgical case report guidelines.MethodsThe CARE statement was used as the basis for a Delphi consensus. The Delphi questionnaire was administered via Google Forms and conducted using standard Delphi methodology. A multidisciplinary group of surgeons and others with expertise in the reporting of case reports were invited to participate. In round one, participants stated how each item of the CARE statement should be changed and what additional items were needed. Revised and additional items from round one were put forward into a further round, where participants voted on the extent of their agreement with each item, using a nine-point Likert scale, as proposed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) working group.ResultsIn round one, there was a 64% (38/59) response rate. Following adjustment of the guideline with the incorporation of recommended changes, round two commenced and there was an 83% (49/59) response rate. All but one of the items were approved by the participants, with Likert scores 7–9 awarded by >70% of respondents. The final guideline consists of a 14-item checklist.ConclusionWe present the SCARE Guideline, consisting of a 14-item checklist that will improve the reporting quality of surgical case reports

Science with the Daksha High Energy Transients Mission

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in