Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles

IntroductionLocal and regional recurrence after surgical intervention is a significant problem in cancer management. The multistage theory of carcinogenesis precisely places the presence of histologically normal but mutated premalignant lesions surrounding the tumor - field cancerization, as a significant cause of cancer recurrence. The relationship between tissue dynamics, cancer initiation and cancer recurrence in multistage carcinogenesis is not well known.MethodsThis study constructs a computational model for cancer initiation and recurrence by combining the Moran and branching processes in which cells requires 3 or more mutations to become malignant. In addition, a spatial structure-setting is included in the model to account for positional relativity in cell turnover towards malignant transformation. The model consists of a population of normal cells with no mutation; several populations of premalignant cells with varying number of mutations and a population of malignant cells. The model computes a stage of cancer detection and surgery to eliminate malignant cells but spares premalignant cells and then estimates the time for malignant cells to re-emerge.ResultsWe report the cellular conditions that give rise to different patterns of cancer initiation and the conditions favoring a shorter cancer recurrence by analyzing premalignant cell types at the time of surgery. In addition, the model is fitted to disease-free clinical data of 8,957 patients in 27 different cancer types; From this fitting, we estimate the turnover rate per month, relative fitness of premalignant cells, growth rate and death rate of cancer cells in each cancer type.DiscussionOur study provides insights into how to identify patients who are likely to have a shorter recurrence and where to target the therapeutic intervention

Evaluation of serum sex hormones and CD4+ count among HIV patients on HAART, HAART naive patients and apparently healthy subjects in Sokoto, Nigeria

Background: Acquired Immunodeficiency Syndrome (AIDS) is a chronic disease associated with Human Immunodeficiency Virus (HIV) which progressively induces depletion of CD4+ T cells, and increased vulnerability to opportunistic infections. Previous reported studies associated HIV-infected men with sexual dysfunction; hypogonadism is the most common endocrinological disorders. Its prevalence remains poorly defined and widely ranging from different studies.Methods: This study evaluated a total of 135 serum sex hormones (testosterone, estrogen, follicle stimulating hormone and luteinizing hormone) and its correlation with CD4+ counts among HIV patients on HAART, HAART naïve patients and negative control subjects (n=45). CD4+ cell counts were estimated using standard flow cytometry method and serum sex hormones by competitive enzyme immunoassay technique.Results: There were significantly lower testosterone and CD4+ levels (p<0.05) among HIV positive HAART naïve men compared to negative control. LH and FSH indicated significant increased (p<0.05) among HIV positive men on HAART.Conclusions: Antiretroviral therapy improves sexual functions in males infected with human immunodeficiency virus. Hence, further study to evaluate its effects on other sexual behaviors

Immunological and anti-oxidant profiles of malarial children in Abuja, Nigeria

BACKGROUND: The clinical symptoms, cellular immune response, and serum cytokine homeostasis during falciparum malaria among children living in endemic regions depend on the parasite densities. This study aims to evaluate the CD4(+) and CD8(+) T cells, leucocytes subpopulations, IL-6, IL-10 and biomarkers of oxidative stress among children infected with varying grades of malaria attending the University of Abuja Teaching Hospital and National Hospital, Abuja, Nigeria. MATERIALS AND METHODS: This case-control study involved blood samples collected from 165 children (between 5 and 12 years). This comprised 45 children with mild malaria, 40 each with moderate, severe malaria and apparently healthy (control). Serum cytokines, ferritin, malonaldehyde (MDA), ascorbate, α-tocopherol levels were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). Leucocytes differentials and CD4(+)/CD8(+) T cells counts were enumerated by automated hematology analyzer and flow cytometry, respectively. RESULTS: All malarial children had only Plasmodium falciparum. The male to female ratio of children with mild malaria was 1.5:1 (mean ± SD age of 8.5 ± 1.9 years). However, other groups had 1:1 male to female ratio and mean ages of 9.2 ± 2.3, 9.8 ± 2.2, 8.5 ± 1.5 for children with moderate, severe malaria and control, respectively. There was a positive but not significant association of neutrophils and monocytes with the 3 grades of malaria parasitemia (p>0.05). There was a negative and significant correlation between severe malaria and lymphocyte count (p = 0.048; r = −0.647). However, there was positive and significant correlation between eosinophil with moderate (p = 0.03; r = 0.994) and severe malaria (p = 0.006; r = 0.825). There was a significant decline in serum ascorbate with increased malaria density (p<0.0001). However, there was no difference in the serum α-tocopherol concentration within the 4 groups of children (p = 0.182). Serum ferritin and MDA significantly elevated with an increase in malaria density (p<0.0001). There was a significant decline in CD4(+) T and CD8(+) T cells counts with an increase in malaria densities (p<0.0001). Serum IL-10 and IL-6 significantly elevated with increased malaria density (p<0.0001). CONCLUSION: Based on these findings, severe malaria was significantly associated with declined CD4(+) and CD8(+) T cell counts, upregulation of IL-6, and high serum levels of oxidative stress biomarkers

Immunological and Anti-oxidant Profiles of Malarial Children in Abuja, Nigeria

BACKGROUND: The clinical symptoms, cellular immune response, and serum cytokine homeostasis during falciparum malaria among children living in endemic regions depend on the parasite densities. This study aims to evaluate the CD4(+) and CD8(+) T cells, leucocytes subpopulations, IL-6, IL-10 and biomarkers of oxidative stress among children infected with varying grades of malaria attending the University of Abuja Teaching Hospital and National Hospital, Abuja, Nigeria. MATERIALS AND METHODS: This case-control study involved blood samples collected from 165 children (between 5 and 12 years). This comprised 45 children with mild malaria, 40 each with moderate, severe malaria and apparently healthy (control). Serum cytokines, ferritin, malonaldehyde (MDA), ascorbate, α-tocopherol levels were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). Leucocytes differentials and CD4(+)/CD8(+) T cells counts were enumerated by automated hematology analyzer and flow cytometry, respectively. RESULTS: All malarial children had only Plasmodium falciparum. The male to female ratio of children with mild malaria was 1.5:1 (mean ± SD age of 8.5 ± 1.9 years). However, other groups had 1:1 male to female ratio and mean ages of 9.2 ± 2.3, 9.8 ± 2.2, 8.5 ± 1.5 for children with moderate, severe malaria and control, respectively. There was a positive but not significant association of neutrophils and monocytes with the 3 grades of malaria parasitemia (p>0.05). There was a negative and significant correlation between severe malaria and lymphocyte count (p = 0.048; r = −0.647). However, there was positive and significant correlation between eosinophil with moderate (p = 0.03; r = 0.994) and severe malaria (p = 0.006; r = 0.825). There was a significant decline in serum ascorbate with increased malaria density (p<0.0001). However, there was no difference in the serum α-tocopherol concentration within the 4 groups of children (p = 0.182). Serum ferritin and MDA significantly elevated with an increase in malaria density (p<0.0001). There was a significant decline in CD4(+) T and CD8(+) T cells counts with an increase in malaria densities (p<0.0001). Serum IL-10 and IL-6 significantly elevated with increased malaria density (p<0.0001). CONCLUSION: Based on these findings, severe malaria was significantly associated with declined CD4(+) and CD8(+) T cell counts, upregulation of IL-6, and high serum levels of oxidative stress biomarkers

Leveraging on the genomics and immunopathology of SARS-CoV-2 for vaccines development: prospects and challenges

The incidence and case-fatality rates (CFRs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the etiological agent for Coronavirus Disease 2019 (COVID-19), have been rising unabated. Even though the entire world has been implementing infection prevention and control measures, the pandemic continues to spread. It has been widely accepted that preventive vaccination strategies are the public health measures for countering this pandemic. This study critically reviews the latest scientific advancement in genomics, replication pattern, pathogenesis, and immunopathology of SARS-CoV-2 infection and how these concepts could be used in the development of vaccines. We also offer a detailed discussion on the anticipated potency, efficacy, safety, and pharmaco-economic issues that are and will be associated with candidate COVID-19 vaccines

Leveraging on the genomics and immunopathology of SARS-CoV-2 for vaccines development: prospects and challenges

The incidence and case-fatality rates (CFRs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the etiological agent for Coronavirus Disease 2019 (COVID-19), have been rising unabated. Even though the entire world has been implementing infection prevention and control measures, the pandemic continues to spread. It has been widely accepted that preventive vaccination strategies are the public health measures for countering this pandemic. This study critically reviews the latest scientific advancement in genomics, replication pattern, pathogenesis, and immunopathology of SARS-CoV-2 infection and how these concepts could be used in the development of vaccines. We also offer a detailed discussion on the anticipated potency, efficacy, safety, and pharmaco-economic issues that are and will be associated with candidate COVID-19 vaccines