Direct and indirect impact of COVID-19 pandemic on maternal mortality at tertiary care institute of north India

Background: During COVID-19 pandemic, healthcare services and infrastructures have been utilized primarily in screening and management of COVID-19 infected patients that might have compromised routine antenatal health care services especially in low- and middle-income countries. This study was planned to know impact of COVID-19 pandemic on antenatal care and maternal mortality at our institute. Methods: This retrospective cohort study compared labour room and maternal mortality statistics before (group ‘A’) and after declaration of COVID-19 pandemic in our country (group ‘B’). One year data (from 1st April, 2019 to 31st March, 2020) before declaration of lockdown in India on 24th March, 2020 was compared with (group ‘B’) data of 1 year after first nation wise lockdown (from 1st April, 2020 to 31st March 2021). Outcomes which were studied included impact on Institutional delivery, cesarean section and still birth rate along with maternal mortality ratio and its causes in both the groups. Modifiable factors such as level-I, level-II, and level-III delay were also considered. Results: There was 66% decline (fall from 5867 before to 1985 during pandemic) observed in institutional delivery, statistically significant rise observed in still birth (p=0.0030) and cesarean section rate (p=0.0007) during pandemic. Maternal mortality ratio (MMR) increased from 649 to 1786 per one lac live birth (64% rise, p=0.0001) during COVID-19 pandemic. Demographic profiles of deceased women were comparable between both the groups. Hypertensive disorder of pregnancy remained the leading direct cause of maternal mortality. COVID-19 associated maternal mortality observed during second wave of pandemic. Delay in seeking care remains the leading indirect cause of maternal mortality like before (23/38,61% versus 21/35,60%, p=1 before and during pandemic). Conclusions: COVID-19 pandemic resulted in fall in institutional delivery and rise still birth rate and maternal mortality ratio. Gestational hypertension remained the leading cause of maternal mortality during COVID-19 pandemic. Type 1 delay was the leading modifiable factor of maternal mortality before and during pandemic. Hence, it is recommended to strengthen health care services at primary health centers and redeployment of staff involved in obstetrical care should be strictly abandoned for timely care and referrals of complicated cases from peripheral health center

Immunomodulatory effects of IFN-[alpha] on dendritic cells: implications for HIV-1/HCV pathogenesis and treatment

HIV-1/HCV co-infection is a significant burden on global economy and public health. Highly active antiretroviral treatment (HAART) against HIV-1 is fairly effective. On the other hand, first generation direct acting antiviral drugs against HCV have improved cure rates but high cost and development of drug resistance are important concerns. Therefore PEGylated interferon (PEG-IFN) and ribavirin (RBV) are still essential components of anti-HCV treatment, and identification of host factors that predict IFN/RBV treatment response is imperative. In my thesis research, we investigated the host genetic and immunological correlates of successful treatment response. We also investigated the mechanisms by which PEG-IFN is able to clear the virus (in responders). Impaired dendritic cell (DC) and T cell responses are associated with HCV persistence. It has been shown that IFN/RBV treatment enhances HCV-specific T cell functions and it is likely that functional restoration of DCs is the underlying cause. To test this hypothesis, we utilized an antibody cocktail (consisting of DC maturation, adhesion and other surface markers) to perform comprehensive phenotypic characterization of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in a cohort of HIV-1/HCV co-infected individuals undergoing IFN/RBV treatment. Our results showed that pretreatment frequencies of mDCs were lower in non-responders (NRs) compared to responders (SVRs) and healthy controls. The treatment was able to restore the frequency of mDCs in NRs, but it downregulated the frequency of CCR7+, CD54+ and CD62L+ mDCs. Pretreatment pDC frequencies were lower in NRs and decreased further upon treatment. NRs exhibited reduced frequency of CCR7+ pDCs and increased pDC PD-L1/CD86 ratio as a result of treatment. These findings demonstrate that functional state of DCs before/during therapy influences the treatment outcome. We also show that before treatment, PBMCs from SVRs secrete higher amounts of IFN-γ compared to controls and NRs. Upon genotyping IFNL3 polymorphisms rs12979860, rs4803217 and ss469415590, we found rs12979860 to be a better predictor of treatment outcome. Collectively, this part of the study led to identification of important correlates of IFN/RBV treatment response in patients. Next, we wanted to investigate how the expression of interferon-stimulated genes (ISGs) affects the treatment outcome. It is already known that high pre-treatment expression of ISGs in liver is a good predictor of poor response to IFN/RBV treatment, but there is no clear consensus regarding the correlation between ISGs expression in PBMCs and treatment outcome. We compared the expression of forty-six ISGs between NRs and SVRs both before and at week 4 of IFN/RBV treatment. We found that the pre-treatment levels of sixteen ISGs were moderately higher in SVRs compared to NRs. At week 4 of IFN/RBV treatment, nineteen ISGs were upregulated and fifteen ISGs were downregulated in SVRs. Next, we identified miRNAs whose expression can be regulated by IFN-Α in PBMCs. miR-155 was one of the many miRNAs upregulated by IFN-Α and its expression varied between NRs and SVRs both before and at week 4 of treatment. Overall, our results indicated that lower miR-155 expression and higher levels of ISGs could be predictive of treatment success. Besides their well-appreciated role in direct antiviral defense, IFN-Α plays a critical role in the regulation of innate and adaptive immune response. Immunomodulatory properties of IFN-Α are facilitated by its action on DCs, professional antigen presenting cells critical to generation of protective immunity. Various microRNAs are known to regulate DC functions but it remains unclear whether IFN-Α exerts its effects on DCs through miRNAs. In this study, we examined miRNA expression patterns in myeloid and plasmacytoid DCs in response to IFN-α and observed miR-221 downregulation via IFN induced STAT3 inhibition in both. Using in silico approaches followed by experimental validation, BCL2L11, CDKN1C, and SOCS1 were identified as miR-221 targets. Moreover, miR-221 overexpression in mDCs enhanced their secretion of proinflammatory cytokines IL-6 and TNF-α. In PBMCs isolated from HIV-1/HCV co-infected patients on standard IFN-α therapy, pre-treatment levels of miR-221 were significantly lower in non-responders compared to responders and healthy controls. Also, in patients PBMCs, miR-221 and CDKN1C, CD54, IL-6 and TNF-α levels correlated similarly as observed earlier in mDCs. In addition, we isolated total liver cells and kupffer cells (antigen presenting cells in liver) from HCV infected individuals as well as individuals with alcoholic cirrhosis. We found that both total liver cells and kupffer cells from HCV-infected individuals had significantly higher miR-221 levels compared to cirrhotic patients which might indicate HCV-mediated impairment in IFN signaling. Overall, this part of our study demonstrated the role of IFN-α/miR-221 axis in HCV pathogenesis and response to IFN-based treatments. Collectively, during my thesis research, we were able to demonstrate the correlation between miR-221 and miR-155 expression in PBMCs and response to PEG-IFN/RBV treatment. We were also able to characterize the DC phenotype and ISGs expression (in PBMCs) of NRs and SVRs both before and during the treatment. We are confident that this work will prove to be beneficial for both diagnostic purposes and for understanding of the role of DCs in HCV pathogenesis.Ph.D., Biological Sciences -- Drexel University, 201

Laccase: Microbial Sources, Production, Purification, and Potential Biotechnological Applications

Laccase belongs to the blue multicopper oxidases and participates in cross-linking of monomers, degradation of polymers, and ring cleavage of aromatic compounds. It is widely distributed in higher plants and fungi. It is present in Ascomycetes, Deuteromycetes and Basidiomycetes and abundant in lignin-degrading white-rot fungi. It is also used in the synthesis of organic substance, where typical substrates are amines and phenols, the reaction products are dimers and oligomers derived from the coupling of reactive radical intermediates. In the recent years, these enzymes have gained application in the field of textile, pulp and paper, and food industry. Recently, it is also used in the design of biosensors, biofuel cells, as a medical diagnostics tool and bioremediation agent to clean up herbicides, pesticides and certain explosives in soil. Laccases have received attention of researchers in the last few decades due to their ability to oxidize both phenolic and nonphenolic lignin-related compounds as well as highly recalcitrant environmental pollutants. It has been identified as the principal enzyme associated with cuticular hardening in insects. Two main forms have been found: laccase-1 and laccase-2. This paper reviews the occurrence, mode of action, general properties, production, applications, and immobilization of laccases within different industrial fields

A critical review of standards to examine the parameters of Child-Friendly Environment (CFE) in parks and open space of planned neighborhoods : a case of Lucknow City, India

Abstract: The creation of cities has been one of the most phenomenal achievements of human endeavor. Adults are the major stakeholders for such achievements but the children are helpless and representationless. The current research paper aims at understanding the issues faced by the children in the rapidly urbanized world where the lack of child-friendly environments/open spaces for their outdoor activities is cause for concern. The research paper looked at various national and international norms, standards, and practices of parks and open spaces to identify various child-friendly environmental parameters. The research adopted the Delphi method as a tool for the validation of child-friendly environment parameters. It also used children’s drawings and essays to understand children’s perceptions about the child-friendly environment. It is observed that present government norms and policies do not adhere to those parameters. The research found that Lucknow city does not meet the defined quantitative norms and standards as laid out by the national norms and standards for open spaces and parks. The quality dimensions for planning a child-friendly environment are weakly addressed by cities and neighborhoods. The city neighborhoods lack the physical, cognitive, perceptional, emotional, and social dimensions of a child-friendly environment. There is a need to adopt suitable norms and standards with measurable parameters as part of various dimensions and implement these in creating a child-friendly environment in planned neighborhoods

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations

Studies of the mass composition of cosmic rays and proton-proton interaction cross-sections at ultra-high energies with the Pierre Auger Observatory

In this work, we present an estimate of the cosmic-ray mass composition from the distributions of the depth of the shower maximum (Xmax) measured by the fluorescence detector of the Pierre Auger Observatory. We discuss the sensitivity of the mass composition measurements to the uncertainties in the properties of the hadronic interactions, particularly in the predictions of the particle interaction cross-sections. For this purpose, we adjust the fractions of cosmic-ray mass groups to fit the data with Xmax distributions from air shower simulations. We modify the proton-proton cross-sections at ultra-high energies, and the corresponding air shower simulations with rescaled nucleus-air cross-sections are obtained via Glauber theory. We compare the energy-dependent composition of ultra-high-energy cosmic rays obtained for the different extrapolations of the proton-proton cross-sections from low-energy accelerator data

Study of downward Terrestrial Gamma-ray Flashes with the surface detector of the Pierre Auger Observatory

The surface detector (SD) of the Pierre Auger Observatory, consisting of 1660 water-Cherenkov detectors (WCDs), covers 3000 km2 in the Argentinian pampa. Thanks to the high efficiency of WCDs in detecting gamma rays, it represents a unique instrument for studying downward Terrestrial Gamma-ray Flashes (TGFs) over a large area. Peculiar events, likely related to downward TGFs, were detected at the Auger Observatory. Their experimental signature and time evolution are very different from those of a shower produced by an ultrahigh-energy cosmic ray. They happen in coincidence with low thunderclouds and lightning, and their large deposited energy at the ground is compatible with that of a standard downward TGF with the source a few kilometers above the ground. A new trigger algorithm to increase the TGF-like event statistics was installed in the whole array. The study of the performance of the new trigger system during the lightning season is ongoing and will provide a handle to develop improved algorithms to implement in the Auger upgraded electronic boards. The available data sample, even if small, can give important clues about the TGF production models, in particular, the shape of WCD signals. Moreover, the SD allows us to observe more than one point in the TGF beam, providing information on the emission angle

The dynamic range of the upgraded surface-detector stations of AugerPrime

The detection of ultra-high-energy cosmic rays by means of giant detector arrays is often limited by the saturation of the recorded signals near the impact point of the shower core at the ground, where the particle density dramatically increases. The saturation affects in particular the highest energy events, worsening the systematic uncertainties in the reconstruction of the shower characteristics. The upgrade of the Pierre Auger Observatory, called AugerPrime, includes the installation of an 1-inch Small PhotoMultiplier Tube (SPMT) inside each water-Cherenkov station (WCD) of the surface detector array. The SPMT allows an unambiguous measurement of signals down to about 250m from the shower core, thus reducing the number of events featuring a saturated station to a negligible level. In addition, a 3.8m2 plastic scintillator (Scintillator Surface Detector, SSD) is installed on top of each WCD. The SSD is designed to match the WCD (with SPMT) dynamic range, providing a complementary measurement of the shower components up to the highest energies. In this work, the design and performances of the upgraded AugerPrime surface-detector stations in the extended dynamic range are described, highlighting the accuracy of the measurements. A first analysis employing the unsaturated signals in the event reconstruction is also presented