Activities of flavonoids for the cleavage of DNA in the presence of Cu(II): correlation with generation of active oxygen species.

The activities of several flavonoids and the related nonflavonoid compound epicatechin were compared with respect to Cu(II)-induced strand scission of DNA by using two different assays. The same series of compounds was used to study the stoichiometry of Cu(II) reduction in the absence of DNA. The compounds were compared for their ability to generate superoxide, hydrogen peroxide and the Cu(II)-dependent production of hydroxyl radicals. Flavonoids were examined to assess the production of a charge-transfer complex with Cu and the rate of decay of the complexes were compared. All the compounds tested had some ability to cause DNA strand scission in the presence of Cu(II), with myricetin being the most active and galangin the least active. The ability to cause such scission correlated with the rate of decay of the charge-transfer complex, the ability to generate active oxygen species and with the stoichiometry of Cu(II) binding. Analysis of the data in the light of the structural differences between the flavonoids led to a discussion of alternative Cu(II)-sequestering mechanisms.     

Influence of caseload and surgical speciality on outcome following surgery for colorectal cancer: a review of evidence Part 2: Long-term outcome

OBJECTIVE: We reviewed recent literature to assess the impact of hospital caseload, surgeon's caseload and education on long-term outcome following colorectal cancer surgery. METHOD: We searched the MEDLINE and Cochrane Library databases for relevant literature starting from 1992. We selected hospital caseload, surgeon's caseload and surgeon's education, type of hospital, and surgeon's experience as variables of interest. Measures of outcome were recurrence-free survival and overall survival, and for rectal cancer frequency of permanent stoma. We reviewed the 34 studies according to tumour location: colonic cancer, rectal cancer, or colorectal cancer. We described the studies individually and performed a meta-analysis whenever it was considered appropriate. RESULTS: For colonic cancer, overall survival improved with increasing hospital caseload, odds ratio (OR) 1.22 [95% confidence interval (CI) 1.16-1.28], and surgeon's education. For rectal cancer, overall survival improved with increasing hospital caseload, OR 1.38 (95% CI 1.19-1.60), and, possibly by surgeon' education and experience. Cancer-free survival was strongly influenced by surgeon's education. The colostomy rate was less in high caseload hospitals, OR 0.76 (95% CI 0.68-0.85). For colorectal cancer, overall survival improved with surgeon's education. CONCLUSION: The data have provided evidence that long-term survival following colorectal cancer surgery in general improved significantly with increasing hospital caseload and surgeon's education.     

Enteric pathogens and their isolation at a cancer hospital in Pakistan

Diarrhoeal diseases remain a major cause of mortality and morbidity in developing countries. However, due to lack of funds, supply problems and some inexperience, some laboratories have difficulty identifying a causative agent in stool samples. In the year following the opening of the Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Pakistan, the microbiology department had not isolated a single enteric pathogen. From January 1996, new culture techniques were introduced, with a resulting increase (10%) in identification of these pathogens. In addition, the introduction of formol-ether concentration made a significant contribution to the number of intestinal parasites seen. This report demonstrates how simple microbiology methods made a difference to the running of the department and, ultimately, to the patients.     

Identification of a type 1 diabetes-associated CD4 promoter haplotype with high constitutive activity

CD4 is a candidate gene in autoimmune diseases, including Type 1 diabetes mellitus (T1DM), because the CD4 receptor is crucial for appropriate antigen responses of CD4(+) T cells. We previously found linkage between a CD4-1188(TTTTC)(5-14) promoter polymorphism and T1DM. In the present study, we screened the human CD4 promoter for mutations and identified three frequent single nucleotide polymorphisms (SNPs): CD4-181C/G, CD4-521C/G and CD4-1050T/C. The SNPs are in strong linkage disequilibrium (LD) and association with the CD4-1188(TTTTC)(5-14) alleles, and we observed nine CD4 promoter haplotypes, of which four are frequent. We genotyped the SNPs in 253 Danish T1DM families (1129 individuals) and found evidence for linkage and association of a CD4 (A4(-1188)T(-1050)G(-521)C(-181)) haplotype to T1DM. In reporter studies, we show that (1) the T1DM-associated CD4 haplotype encodes high constitutive promoter activity and (2) the CD4-181G variant encodes higher stimulated promoter activity than the CD4-181C variant. This difference is in part neutralized in the frequently occurring CD4 promoter haplotypes by the more upstream genetic variants. Thus, we report functional impact of a novel CD4-181C/G SNP on stimulated CD4 promoter activity and the identification of a novel CD4 haplotype with high constitutive promoter activity that is linked and associated with T1DM.     

Three months of COVID‐19: A systematic review and meta‐analysis

The pandemic of 2019 novel coronavirus (SARS‐CoV‐2019), reminiscent of the 2002‐SARS‐CoV outbreak, has completely isolated countries, disrupted health systems and partially paralyzed international trade and travel. In order to be better equipped to anticipate transmission of this virus to new regions, it is imperative to track the progress of the virus over time. This review analyses information on progression of the pandemic in the past 3 months and systematically discusses the characteristics of SARS‐CoV‐2019 virus including its epidemiologic, pathophysiologic, and clinical manifestations. Furthermore, the review also encompasses some recently proposed conceptual models that estimate the spread of this disease based on the basic reproductive number for better prevention and control procedures. Finally, we shed light on how the virus has endangered the global economy, impacting it both from the supply and demand side.