Optimal Drug Regimen and Combined Drug Therapy and Its Efficacy in the Treatment of COVID-19: A Within-Host Modeling Study.

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19.

Optimal Control Studies on Age Structured Modeling of COVID-19 in Presence of Saturated Medical Treatment of Holling Type III.

COVID-19 pandemic has caused the most severe health problems to adults over 60 years of age, with particularly fatal consequences for those over 80. In this case, age-structured mathematical modeling could be useful to determine the spread of the disease and to develop a better control strategy for different age groups. In this study, we first propose an age-structured model considering two different age groups, the first group with population age below 30 years and the second with population age above 30 years, and discuss the stability of the equilibrium points and the sensitivity of the model parameters.

Surface Plasmon-Coupled Dual Emission Platform for Ultrafast Oxygen Monitoring after SARS-CoV-2 Infection.

The outbreak of the COVID-19 pandemic has had a major impact on the health and well-being of people with its long-term effect on lung function and oxygen uptake. In this work, we present a unique approach to augment the phosphorescence signal from phosphorescent gold(III) complexes based on a surface plasmon-coupled emission platform and use it for designing a ratiometric sensor with high sensitivity and ultrafast response time for monitoring oxygen uptake in SARS-CoV-2-recovered patients. Two monocyclometalated Au(III) complexes, one having exclusively phosphorescence emission (λ = 578 nm) and the other having dual emission, fluorescence (λ = 417 nm) and phosphorescence (λ = 579 nm), were studied using the surface plasmon-coupled dual emission (SPCDE) platform for the first time, which showed 27-fold and 17-fold enhancements, respectively.

New Concepts in the Management of Charcot Neuroarthropathy in Diabetes.

Charcot Neuroarthropathy (CN) is an uncommon, debilitating and often underdiagnosed complication of chronic diabetes mellitus though, it can also occur in other medical conditions resulting from nerve injury. Till date, the etiology of CN remains unknown, but enhanced osteoclastogenesis is believed to play a central role in the pathogenesis of CN, in the presence of neuropathy. CN compromises the overall health and quality of life.

The role of Lp-PLA and biochemistry parameters as potential biomarkers of coronary artery disease in Asian South-Indians: a case-control study.

Background: Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Lipoprotein associated phospholipase A (Lp-PLA) is an emerging biomarker for inflammation that has shown association with CAD. Its significance in the Asian Indian population is not clearly known.

Interactions between maternal killer cell immunoglobulin receptor genes and foetal HLA ligand genes contribute to type 1 diabetes susceptibility in Han Chinese.

In this study, we aimed to test the hypothesis that KIR haplotypes (that interact with HLA class I molecules) are associated with susceptibility in patients with T1DM in utero through maternal-foetal interaction of KIR and their HLA class I ligands in Han Chinese population. We determined the KIR genes and KIR/ligand gene combination frequencies in 59 Han Chinese children with T1D and their mothers and compared it with 159 healthy control children and their mothers. The absence of KIR-2DS1 in the mother and the presence of HLA-C2 ligand in the child were negatively associated with type 1 diabetes in the child.

Non-HLA type 1 diabetes genes modulate disease risk together with HLA-DQ and islet autoantibodies.

The possible interrelations between human leukocyte antigen (HLA)-DQ, non-HLA single-nucleotide polymorphisms (SNPs) and islet autoantibodies were investigated at clinical onset in 1-34-year-old type 1 diabetes (T1D) patients (n=305) and controls (n=203). Among the non-HLA SNPs reported by the Type 1 Diabetes Genetics Consortium, 24% were supported in this Swedish replication set including that the increased risk of minor PTPN22 allele and high-risk HLA was modified by GAD65 autoantibodies. The association between T1D and the minor AA+AC genotype in ERBB3 gene was stronger among IA-2 autoantibody-positive patients (comparison P=0.

Killer immunoglobulin receptor genes and their HLA-C ligand are associated with Type 1 diabetes in an Eastern Indian population.

Aim: Killer immunoglobulin-like receptors (KIRs) and their interaction with HLA class I ligands have been shown to be associated with Type 1 diabetes mellitus. The aim of our study was to investigate the influence of KIR genes and their HLA-C ligands for susceptibility to Type 1 diabetes in patients from Eastern India.

Methods: A total of 135 patients with Type 1 diabetes and 98 healthy subjects from Eastern India were typed for KIR genes and HLA-C ligands using PCR-based genotyping.

KIR genotyping in the selected population in Andhra Pradesh (India).

Background: The population is not always homogeneous in relation to the representation and functioning of genes. Therefore, the presence of allogenicity is a universal phenomenon. The profound variability is noticed among the members of the human population with reference to the resistance against infections and late onset of diseases.

SNPs in the exons of Toll-like receptors are associated with susceptibility to type 1 diabetes in Chinese population.

Objective: Toll-like receptors (TLRs) recognize a wide range of pathogen-associated molecular patterns (PAMP) and mount the initiation of immune response. Single nucleotide polymorphisms (SNPs) in exons of genes encoding TLRs might be responsible for the generation of an abnormal immune response which could lead to autoimmune diseases. In this study, we investigated the SNPs in TLRs in a Chinese population, and we hypothesized that SNPs in TLRs are associated with type 1 diabetes (T1D), an autoimmune disease caused by destruction of insulin producing pancreatic β-cells, in the studied population.

CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population.

Background: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).

Killer cell immunoglobulin-like receptor along with HLA-C ligand genes are associated with type 1 diabetes in Chinese Han population.

Objective: Killer cell immunoglobulin-like receptor (KIR) genes and their putative ligands human leukocyte antigen (HLA)-C genes have been associated with type 1 diabetes (T1D). We hypothesize that KIR genes and their ligands HLA-C genes are important in T1D aetiology.

Research Design And Methods: KIR and HLA-C ligand genotyping was performed in 259 T1D patients and 262 healthy children.

Anthropometric measurements for the prediction of the metabolic syndrome: a cross-sectional study on adolescents and young adults from southern india.

Objectives: To determine which anthropometric measurement correlates best with the metabolic abnormalities associated with the metabolic syndrome in adolescents and young adults.

Design: Cross-sectional study.

Setting: Schools, high schools and universities.

HLA class II alleles and haplotypes in Lithuanian children with type 1 diabetes and healthy children (HLA and type 1 diabetes).

Objective: Type 1 diabetes mellitus is a slowly progressive autoimmune disease. The genetic background of type 1 diabetes mellitus is polygenic with the major disease locus located in the human leukocytes antigen (HLA) region. High risk and protective alleles, haplotypes, and genotypes have been determined in Lithuanian children with type 1 diabetes mellitus and healthy children.

Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix.

Background: The link between squamous cell cervical carcinoma and human papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk association is uncertain and the importance of other high-risk HPV (HRHPV) types is unclear.

Methods: In two prospective nested case-control series among women participating in cytologic screening in Sweden, we collected 2,772 cervical smears from 515 women with cancer in situ (CIS), 315 with invasive squamous cell carcinoma (SCC), and individually matched controls. All smears were tested for HPV with PCR assays, and the median follow-up until diagnosis was 5 to 7 years.

Prospective study of human papillomavirus and risk of cervical adenocarcinoma.

Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma.

The association between the PTPN22 1858C>T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies.

The single nucleotide polymorphism 1858C>T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations. Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies. In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) measure of association was dependent on HLA or autoantibodies against the islet autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, islet antigen-2, or islet cell.

[Killer cell immunoglobin-like receptor and its ligand gene polymorphisms in Hunan Han patients with type 1 diabetes].

Objective: To investigate the association of Killer cell immunoglobin-like receptor (KIR) gene and KIRs'ligand (HLA-C) gene polymorphisms with type 1 diabetes (T1DM).

Methods: Using polymerase chain reaction-sequence specific primer (PCR-SSP) to detect KIR and HLA-C genotype in 180 T1DM patients and 199 healthy controls from Hunan Han population.

Results: (1) The frequencies of KIR 2DL1 (98.

Prevention of beta-cell destruction in autoimmune diabetes: current approaches and future prospects.

Type 1 diabetes (T1D) is an autoimmune disease resulting from the destruction of pancreatic beta-cells. The main aim of treatment should be to prevent beta-cell destruction and preserve existing beta-cells in individuals with progressive autoimmunity. This can be achieved in several ways and in this chapter the authors have reviewed recent approaches that are currently being tested in animal models and human T1D patients under the following categories: i) antigen based therapy, ii) antibody-based therapy iii) other forms of therapy and iv) failed therapies.

Alternative routes of insulin delivery.

Parenteral route of insulin administration has been the mode of treatment for all Type 1 diabetics and Type 2 diabetics with complications. Patient compliance has really been a major concern for this route of administration. Several alternative routes of administration are under consideration for effective glycemic control, including oral, inhaled, buccal, nasal, and patch routes.

Diabetes--role of epigenetics, genetics, and physiological factors.

Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues. The genome of an individual is always influenced by parental, embryonic, tissue-specific, and environmental epigenomes and the same must have been the possible reason for invariable inquiries relating to familial, environmental and life style patterns in the preliminary investigations of diabetic complications. Unprecedented methylation of lysine residues of histones and cytosines of CpG islands of promoter DNA impede the transcription of genes and homocysteine is the metabolic key player of methyl groups.

Epigenetics and epigenetic mechanisms in disease with emphasis on autoimmune diseases.

Epigenetics deals with molecular heritable patterns relating to chromatin, which exists in two alterable and inter-convertible states. The two conformations of chromatin i.e.

Type 1 diabetes versus type 2 diabetes with onset in persons younger than 20 years of age.

Type 1 diabetes (T1D) is the most common form of diabetes in children in Western countries. There have been no large studies of childhood diabetes from India. We undertook the MEDI study (Multicenter Survey of Early Onset Diabetes in India) to assess the proportion of various subtypes of diabetes among the young subjects presenting to the endocrinology divisions of seven large teaching hospitals in different regions of India.