Marital status and stage of cancer at diagnosis: A systematic review

Early cancer detection is fundamental to the promotion of better health in the community, but disparities remain in the likelihood of cancer being detected at an early stage, some of which relate to socio‐demographic factors such as marital status. The aim of this study was to conduct a systematic review of research on the association between marital status and stage at diagnosis of different types of cancer. A comprehensive systematic literature search was run in the Medline and Scopus databases (from January 1990 to June 2014), identifying 245 and 208 articles on PubMed and Scopus respectively. Of these 453 studies, 18 were judged eligible for this systematic review. A quality assessment was performed on the studies using the 22 items in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. This review confirmed the important influence of being married on the earlier detection of cancer. None of the studies considered identified more cases of cancer in a later stage among married patients, and the majority of them reported a statically significant association between marital status and stage at diagnosis, with a positive effect of marriage on the likelihood of cancer being diagnosed at an early stage, for various types of malignancy. In particular, our meta‐analysis showed that the unmarried have higher odds of having a later stage of breast cancer (OR = 1.287 95% CI: 1.025–1.617) or melanoma (OR = 1.350 95% CI: 1.161–1.570) at diagnosis. Specific interventions should be developed for the unmarried population to improve their chances of any neoplasms being diagnosed at an early stage, thereby reducing health disparities in the population at large.     

A Prospective Trial of Risk Factors for Sulfonylurea-Induced Hypoglycemia in Type 2 Diabetes Mellitus

Context.— Retrospective studies have identified oral sulfonylureas, age, and fasting as major risk factors for hypoglycemia in patients with type 2 diabetes. Sulfonylureas may be withheld from elderly patients out of concern for hypoglycemia. Objective.— To evaluate the hypoglycemic effects of maximum doses of once-daily second-generation sulfonylureas administered to fasting elderly patients. Design.— A prospective, randomized, double-blind clinical trial. Setting.— The University of New Mexico General Clinical Research Center. Patients.— Fifty-two sulfonylurea-treated subjects with type 2 diabetes with a mean (SD) age of 65.1 (5.7) years. Interventions.— Subjects were randomly assigned to glyburide or glipizide gastrointestinal therapeutic system (GITS). Each subject participated in three 23-hour fasting studies after the sequential administration of 1 week of placebo and 1 week of 10 mg and 1 week of 20 mg of the assigned sulfonylurea. Main Outcome Measures.— Occurrence of hypoglycemia (defined as plasma glucose level <3.33 mmol/L [60 mg/dL]) and hormonal parameters during the final 9 hours of the 23-hour fast in patients who had taken sulfonylureas vs placebo. Results.— No hypoglycemia was observed during 156 fasting studies. Plasma glucose level was decreased (nadir, 4.9 mmol/L [88 mg/dL] for a 20-mg dose of glyburide vs 8.3 mmol/L [150 mg/dL] for placebo; nadir, 5.8 mmol/L [105 mg/dL] for a 20-mg dose of glipizide GITS vs 8.7 mmol/L [157 mg/dL] for placebo), and serum insulin was increased in the sulfonylurea studies compared with placebo (P<.001). Plasma glucose parameters did not differ between the 2 sulfonylureas, but C peptide concentrations were increased in the glyburide group compared with glipizide GITS in the 20-mg study (P=.05). Concentrations of epinephrine were increased in the sulfonylurea studies compared with placebo (P<.001). Epinephrine secretion increased when glucose concentration fell below the mean (SD) level of 9.10 (2.66) mmol/L (164 [48] mg/dL) in the 10-mg study and 8.77 (2.83) mmol/L (158 [51] mg/dL) in the 20-mg study. Conclusions.— Fasting was well tolerated among these elderly patients with type 2 diabetes treated with sulfonylureas. Older age should not be considered a contraindication to sulfonylurea treatment for diabetes. Stimulation of epinephrine secretion at normal or elevated plasma glucose levels appears to be the primary mechanism of protection against hypoglycemia in this study.      

Management of Darier's disease

Darier's disease is an uncommon inherited cutaneous disease which is difficult to manage, especially in adolescence. The warty keratotic papules irritate, smell and look unsightly. Histologically, the condition is characterized by the presence of focal acantholytic dyskeratosis. Treatment is unsatisfactory, particularly in patients with erosive flexural disease, but retinoids reduce the hyperkeratosis. Now the mutation causing Darier's disease has been identified, there is a real possibility of more effective treatment in the future.     

医学情报信息跨平台数据整合的应用研究

本文结合国内外医学专题数据库的实际情况,面对目前网络信息量异常庞大,信息检索中遇到的困难,分析了在异构数据库和不同的操作平台环境中,专题数据库整合问题,提出了应用数据融合技术、数据仓库技术等,实现医学情报检索精、准、快、全。重点论述了医学专题数据库整合的建设思路和实现跨库检索的方法。     

Relationship of genotype to phenotype in fibroblast-derived transmitochondrial cell lines carrying the 3243 mutation associated with the MELAS encephalomyopathy: shift towards mutant genotype and role of mtDNA copy number

Transmitochondrial cell lines were isolated by fusing mtDNA-less rho degrees 206 cells with enucleated fibroblasts derived from four members of a pedigree carrying in their muscle varying proportions of the mutation at position 3243 in the tRNA(Leu(UUR)) gene associated with the MELAS encephalomyopathy. The mitochondrial transformants derived from an asymptomatic individual were all homoplasmic for wild-type mtDNA. The proportion of wild-type transformants derived from clinically affected members of the pedigree appeared to decrease in correspondence with an increase in severity of the clinical symptoms of the cell donor. Furthermore, the average proportion of wild-type mtDNA in the transformants derived from each member of the pedigree was very similar to that found in mtDNA from the fibroblasts of that individual, suggesting that the distribution of genotypes in the transformants reflected fairly closely that in the fibroblasts. The genotype and phenotype of ten transformants derived from one severely affected individual were investigated during continuous culture up to 17-24 weeks after the transformation step. Six heteroplasmic clones showed a progressive increase in the proportion of mutant mtDNA, whereas the mitochondrial genotype remained constant in four clones apparently homoplasmic for wild-type mtDNA or nearly homoplasmic for mutant mtDNA. An analysis of the rate of repopulation of rho degrees 206 cells with fibroblast-derived mtDNA revealed a large variability among different transformants, with the full re-establishment of the control ratio of mtDNA to nuclear DNA being observed between approximately 6 weeks and more than 22 weeks after the transformation step. An increase in rate of O2 consumption generally accompanied the increase in mtDNA copy number of the transformants, pointing to the important role of the mtDNA copy number in determining the phenotype of a cell. The observation that a very small amount of wild-type mtDNA (2 to 5% of the control level), coexisting with strongly predominant mutant mtDNA, conferred upon the transformants a substantial respiratory capacity (50% or more) and the evidence of proportionality between O2 consumption rate and mtDNA copy number, which occurred at widely different mutant to wild-type mtDNA ratios, strongly suggest a contribution of the mutant mtDNA to the cell respiratory competence.      

Acceleration of Small Intestine Development and Remodeling of the Microbiome Following Hyaluronan 35 kDa Treatment in Neonatal Mice

The beneficial effects of human milk suppressing the development of intestinal pathologies such as necrotizing enterocolitis in preterm infants are widely known. Human milk (HM) is rich in a multitude of bioactive factors that play major roles in promoting postnatal maturation, differentiation, and the development of the microbiome. Previous studies showed that HM is rich in hyaluronan (HA) especially in colostrum and early milk. This study aims to determine the role of HA 35 KDa, a HM HA mimic, on intestinal proliferation, differentiation, and the development of the intestinal microbiome. We show that oral HA 35 KDa supplementation for 7 days in mouse pups leads to increased villus length and crypt depth, and increased goblet and Paneth cells, compared to controls. We also show that HA 35 KDa leads to an increased predominance of Clostridiales Ruminococcaceae, Lactobacillales Lactobacillaceae, and Clostridiales Lachnospiraceae. In seeking the mechanisms involved in the changes, bulk RNA seq was performed on samples from the terminal ileum and identified upregulation in several genes essential for cellular growth, proliferation, and survival. Taken together, this study shows that HA 35 KDa supplemented to mouse pups promotes intestinal epithelial cell proliferation, as well as the development of Paneth cells and goblet cell subsets. HA 35 KDa also impacted the intestinal microbiota; the implications of these responses need to be determined.     

Audit of dermatological content of U.K. undergraduate curricula

Background Recommendations for the dermatology content (learning outcomes) of the core undergraduate curriculum were sent to all U.K. medical schools in June 2006. Objective To carry out an audit of the content of the core curriculum in each U.K. medical school against the recommendations for a core undergraduate dermatology curriculum (the criteria) published by the British Association of Dermatologists, to identify areas of good practice and to gather evidence for developing the learning and teaching of dermatology. Methods A questionnaire was circulated to the dermatology teaching leads of all U.K. medical schools (29) and one Irish medical school. Questions which the teaching leads were unable to answer were sent to the relevant deans and responses incorporated into the results. All curricula should include the essential learning outcomes that focus on clinical skills; as this was an audit to benchmark current practice, we did not set standards for the other recommendations for a core curriculum. Results Replies were received from teaching leads in 29 of the 30 medical schools and from 16 of the deans. Essential clinical skills such as taking a dermatological history and examining the skin were included in the curricula of most, but not all, medical schools. Areas of good practice include teaching on tumours, acne and psoriasis, but we found some surprising omissions including the diagnosis of meningococcaemia. Our data suggest that some students have little exposure to dermatology, but dermatology teaching takes place in secondary care in all medical schools. Knowledge‐based assessments are used by 27 medical schools. Conclusions Curricula should be strengthened so that the recommended learning outcomes feature in the core curricula of all medical schools. Teaching leads in all specialties, including those in the community, should communicate so that learning and teaching are integrated horizontally and vertically. The results should provide a baseline for future audits.