Epidemiological & clinical characteristics & early outcome of COVID-19 patients in a tertiary care teaching hospital in India: A preliminary analysis.

BACKGROUND & OBJECTIVES: In this study we describe the epidemiological data, comorbidities, clinical symptoms, severity of illness and early outcome of patients with coronavirus disease 2019 (COVID-19) from a tertiary care teaching hospital in New Delhi, India. METHODS: In this preliminary analysis of a prospective observational study, all adult patients admitted to the screening intensive care unit (ICU) of the institute who fulfilled the WHO case definition of COVID-19 and confirmed to have SARS-CoV-2 infection by reverse transcription-polymerase chain reaction were included. Demographics, clinical data and 24 h outcome were assessed. RESULTS: The preliminary analysis of 235 patients revealed that the mean age was 50.7±15.1 yr and 68.1 per cent were male. Fever (68.1%), cough (59.6%) and shortness of breath (71.9%) were the most common presenting symptoms. Hypertension (28.1%) and diabetes mellitus (23.3%) were the most common associated comorbid illnesses. Patients with mild, moderate, severe and critical illness were 18.3, 32.3, 31.1 and 18.3 per cent, respectively, at the time of ICU admission. The proportions (95% confidence interval) of patients requiring any form of oxygen therapy, oxygen therapy by high-flow nasal cannula and invasive mechanical ventilation were 77, 21.7 and 25.5 per cent, respectively, within 24 h of hospital admission. The 24 h ICU mortality was 8.5 per cent, and non-survivors had higher respiratory rate (P <0.01, n=198) and lower baseline oxyhaemoglobin saturation (P <0.001, n=198) at presentation and higher baseline serum lactate (P <0.01, n=122), total leucocyte count (P <0.001, n=186), absolute neutrophil count (P <0.001, n=132), prothrombin time (P <0.05, n=54) and INR (P <0.05, n=54) compared to survivors. INTERPRETATION & CONCLUSIONS: Nearly half of the patients presented with severe and critical disease and required high-flow nasal oxygen or invasive mechanical ventilation at admission. Severity of the presenting respiratory illness, haematological parameters and lactate rather than age or presence of comorbidity predicted early death within 24 h.

Nanopore Sequencing of RAGE Gene Polymorphisms and Their Association with Type 2 Diabetes.

The receptor for advanced glycation end products (RAGE) is a transmembrane protein that interacts with its ligands, advanced glycation end products (AGEs). AGEs are elevated in diabetes and diabetic complications, leading to increased oxidative stress and activation of pro-inflammatory pathways facilitated by AGE-RAGE signaling. Polymorphisms in the RAGE gene can potentially affect AGE-RAGE interaction and its downstream signaling, which plays a crucial role in the progression of diabetes and its complications. In this study, we used nanopore sequencing for genotyping of RAGE polymorphism and identified a maximum number of 33 polymorphisms, including two previously unreported novel mutations in a cohort of healthy, type 2 diabetics without nephropathy and type 2 diabetics with nephropathy in order to identify associations. Two novel RAGE polymorphisms in the intron 8 and 3'UTR region at genomic locations 32181834 and 32181132, respectively, were detected with a low frequency. For four previously reported polymorphisms, cross-validation by PCR-RFLP showed 99.75% concordance with nanopore sequencing. Analysis of genotype distribution and allele frequencies revealed that five single nucleotide polymorphisms, i.e., rs1800625, rs3131300, rs3134940, rs2070600, and rs9391855, were associated with an increased risk for type 2 diabetes.

Evaluation of the immunogenicity of liposome encapsulated HVR1 and NS3 regions of genotype 3 HCV, either singly or in combination.

BACKGROUND: Hepatitis C virus displays a high rate of mutation and exists as a quasispecies in infected patients. In the absence of an effective universal vaccine, genotype-specific vaccine development represents an alternative. We have attempted to develop a genotype 3 based, liposome encapsulated HCV vaccine with hypervariable region-1 (HVR1) and non-structural region-3 (NS3) components. RESULTS: HCV RNA extracted from serum samples of 49 chronically infected patients was PCR amplified to obtain HVR1 region. These amplified products were cloned to obtain 20 clones per sample in order to identify the quasispecies pattern. The HVR1 consensus sequence, along with three variants was reverse transcribed to obtain peptides. The peptides were checked for immunoreactivity individually, as a pool or as a single peptide tetramer interspersed with four glycine residues. Anti-HCV positivity varied from 42.6% (tetramer) to 92.2% (variant-4) when 115 anti-HCV positive sera representing genotypes 1, 3, 4 and 6 were screened. All the 95 anti-HCV negatives were scored negative by all antigens. Mice were immunized with different liposome encapsulated or Al(OH)3 adjuvanted formulations of HVR1 variants and recombinant NS3 protein, and monitored for anti-HVR1 and anti-NS3 antibody titres, IgG isotypes and antigen specific cytokine levels. A balanced Th1/Th2 isotyping response with high antibody titres was observed in most of the liposome encapsulated antigen groups. The effect of liposomes and aluminium hydroxide on the expression of immune response genes was studied using Taqman Low Density Array. Both Th1 (IFN-gamma, Il18) and Th2 (Il4) genes were up regulated in the liposome encapsulated HVR1 variant pool-NS3 combination group. In-vitro binding of the virus to anti-HVR1 antibodies was demonstrated. CONCLUSION: The optimum immunogen was identified to be combination of peptides of HVR1 consensus sequence and its variants along with pNS3 encapsulated in liposomes, which could generate both cellular and humoral immune responses in mice deserving further evaluation in a suitable cell culture system/non-human primate model.

Patient perceptions of co-morbidities in inflammatory arthritis.

OBJECTIVE: Longer life expectancy has resulted in people living with an increasing number of co-morbidities. The average individual with inflammatory arthritis has two co-morbidities, which contribute to higher mortality, poorer functional outcomes and increased health-care utilization and cost. A number of studies have investigated the prevalence of co-morbidities, whereas this study was designed to look at patient perspectives. METHODS: The study comprised two parts: a patient questionnaire and an interview. Individuals with physician-verified inflammatory arthritis along with one or more Charlson co-morbidities were invited to participate. In-depth data were obtained by interviews with 12 willing participants. RESULTS: One hundred and forty-six individuals were recruited; 50 (35%) had one co-morbidity, 69 (48%) had two and 25 (17%) had more than four co-morbidities. Seventy-seven individuals (53%) reported that co-morbidities affected their health as much as their arthritis, and 82 (56%) reported dependence on others for activities of daily living. Lack of education was highlighted by 106 (73%) participants. Qualitative data provided further support for the challenges, with participants highlighting the lack of time to discuss complex or multiple problems, with no-one coordinating their care. This, in turn, led to polypharmacy and insufficient discussion around drug and disease interactions, complications and self-help measures. CONCLUSION: This study highlights the challenges for individuals with inflammatory arthritis who suffer with multiple co-morbidities. The challenges result from limited resources or support within the current health-care environments. Individuals highlighted the poor quality of life, which is multifactorial, and the need for better educational strategies and coordination of care to improve outcomes.

Relevance of Split In vitro Fertilization-Intracytoplasmic Sperm Injection Method of Insemination in Normozoospermic and Mildly Oligospermic Men: A Retrospective Study.

BACKGROUND: Use of intracytoplasmic sperm injection (ICSI) is generally considered redundant in cases of normozoospermia, or mild male factor cases of infertility and conventional method of insemination is advocated. However, there is a risk of low fertilization or total fertilization failure (TFF) and to avoid this, split in vitro fertilization (IVF)-ICSI method of insemination is advised. In our study, we have shown that not only TFF is avoided with split method of insemination, but also cancellation of embryo transfer (ET) can be avoided in a significant number of IVF cycles. AIMS: This study aimed to assess whether the IVF-ICSI split insemination method was able to reduce the risk of ET cancellation in couples with normal or mild sperm characteristics. SETTINGS AND DESIGN: It is a retrospective study including a total of 107 split insemination cycles done at our center. MATERIALS AND METHODS: The female partner's age was under 37 years, and at least ten oocytes were retrieved in all cycles. Sibling oocytes were randomly allocated to IVF or ICSI. Statistical analysis was carried out using Graphpad Prism, Instat. RESULTS AND CONCLUSION: The fertilization rate in oocytes kept in conventional IVF was significantly higher (79.8%) compared to that of oocytes injected through ICSI (69.1%). Only one couple had TFF. In majority of the cycles, i.e., 97 out of 107 cycles, the mode of insemination did not affect the fertilization rate or embryo quality. Nearly 28% of the cycles were saved from ET cancellation by adopting the split insemination method. "Split IVF-ICSI" approach can save a significant number of ART cycles and is found to be cost-effective as it avoids incurring the cost of two ART cycles.

Rheological and Electrical Study of a Composite Material Based on an Epoxy Polymer Containing Cyclotriphosphazene.

In this work, we have studied, formulated, prepared, and characterized the rheological and electrical behavior of a composite material based on an epoxy resin Diglycidyl Ether of Bisphenol A (DGEBA) reinforced with hexaglycidyl cyclotriphosphazene (HGCP). The epoxy system was cured with 4,4'-methylene dianiline (MDA). DGEBA-HGCP-MDA epoxy composite materials with reinforced HGCP which varied from 5% to 10% by weight were prepared by mixing in the molten state. The morphology was evaluated by SEM. The rheological behavior was studied using small deformation rheology. The electrical characterization was carried out with a frequency variation range from 1 Hz to 100 KHz at room temperature. These measurements revealed that the rheological and electrical behaviors strongly depend on the quantity of HGCP in the DGEBA matrix. The linear viscoelastic properties study reveals that the modulus of elasticity G' is dependent on the amount of HGCP present in the epoxy resin DGEBA. The capacitance-frequency measurements suggest a distribution of localized states in the band gap of the blends.

Complete genome sequences of hepatitis C virus subtype 3i and 3a subtype isolates from India.

AIM: Hepatitis C virus (HCV), a major causative agent of chronic hepatitis, is classified into six major genotypes. Genotype 3 HCV infection is more sensitive to interferon therapy. In India, genotype 3, particularly subtype 3a, HCV infections are common. Three novel HCV subtypes i.e., 3g, 3j, and 3i were identified from India based on partial genomic sequences. This report provides full genome sequences of one isolate each of subtypes 3i and 3a. METHODS: Serum samples positive for subtype 3i and 3a HCV RNA based on core region genomic sequences were studied. Complete HCV genomes were amplified as 11 overlapping PCR fragments and sequenced. RESULTS: The complete genomic sequence of Indian HCV 3i isolate clustered with other genotype 3 sequences, and was closer to subtypes 3b and 3a (80.5% and 79.1% [SD 0.4%] nucleotide identity). Nucleotide similarities were the highest in the core region (86.1-88.7%), and the least in the E2 region (69.4-70.7%). Phylogenetic tree analysis confirmed the existence of a separate subtype 3i. The Indian HCV 3a isolate's complete genomic sequences clustered with previously known genotype 3a sequences with a nucleotide similarity of 91.1% (SD 0.2%). Neither isolates showed evidence of recombination of different HCV genotypes. CONCLUSION: The information on complete genomic sequences of the genotype 3 HCV isolates should be helpful in future studies on HCV evolution and classification, and for development of newer therapeutic and preventive strategies against this infection.