Incidence,Prevalence, Etiology,and Prognosis of First-Time Chronic Pancreatitis in Young Patients: A Nationwide Cohort Study

Background/Aims  

Publications on etiology of chronic pancreatitis (CP) are infrequent. Etiologies today encompass genetic disorders. We wanted to describe etiologies of today and identify patients with genetic disorders like hereditary pancreatitis (HP), mutations in Serine Protease Inhibitor Kazal type1 (SPINK1), and the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) among patients formerly considered to have idiopathic CP.     

Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor

Background  

KRAS mutations represent key alterations in colorectal cancer development and lead to constitutive EGFR signaling. Since EGFR inhibition represents a therapeutic strategy in advanced colorectal cancer, KRAS mutation analysis has quickly been introduced as a treatment-predictive test.     

An observational study of slimming behavior in Denmark in 1992 and 1998

OBJECTIVE: To elucidate how frequent weight-loss attempts are made, the methods used to achieve weight loss, and the extent to which the outcome is positive. RESEARCH METHODS AND PROCEDURES: Two independent interviews were conducted in 1992 and in 1998, each with 1200 randomly selected adult subjects. Each survey was designed to ensure an equal distribution of age, gender, and geographical regions in Denmark. RESULTS: The proportion of subjects having attempted weight loss did not change from 1992 to 1998, although the prevalence of overweight and obesity increased from 1992 (overweight, 30%; obesity, 6%) to 1998 (overweight, 35%; obesity, 8%). Almost twice as many women (61%) than men (32%) had attempted weight loss (p < 0.0001). Slimming occurred more often in subjects <50 years (51%) than >50 years (39%) (p < 0.0001), although overweight and obesity were more frequent in the elderly. Over-the-counter diet pills or meal replacements were associated with a negative outcome of slimming treatment (p < 0.0001). DISCUSSION: Approximately half of all adult Danes have attempted weight loss, particularly women and individuals <50 years. This finding is inconsistent with the fact that overweight and obesity are more prevalent in men and in individuals >50 years. Changes in habitual diet and increased physical activity are the most prevalent modes of slimming, whereas the use of over-the-counter diet pills or meal replacements has decreased from 1992 to 1998. This development may have a positive impact on future body- weight-management strategies.     

Causes and prevention of dental caries: a perspective on cases and incidence

PURPOSE: The purpose of the present paper is: 1) to review recent concepts of the causes of caries; 2) to illustrate parameters of causes of cases and of incidence; and 3) to outline the consequences for caries prevention and oral health promotion. The paper is divided in three sections. Section 1 reviews recent theories of the causes of caries and summarizes that it is necessary to make a clear distinction between the causes of a case of caries and causes of occurrence of caries in populations. Cases relate to the reasons why individuals get sick, while incidence relates to why so many (or so few) within a population get sick. In section 2 the difference between the causes of a case and of the occurrence in a population is illustrated. A new social epidemiology moves beyond the focus on individual level risk factors to a multi-level perspective. Applied to oral diseases the paradigm of social epidemiology bridges our understanding of the biological determinants of caries with an understanding of the societal determinants of caries. Social epidemiology is the branch of epidemiology that studies the social distribution and social determinants of states of health. Individuals are embedded in societies and populations. In section 3 the insight acquired above is applied to the choice of disease-preventive and oral health-promotive strategies. Prevention of caries and promotion of oral health must be rooted in the understanding of caries as it occurs in populations.     

Nuclear export inhibitors and kinase inhibitors identified using a MAPK-activated protein kinase 2 redistribution screen

Redistribution (BioImage) A/S, S?borg, Denmark) is a novel high-throughput screening technology that monitors translocation of specific protein components of intracellular signaling pathways within intact mammalian cells, using green fluorescent protein as a tag. A single Redistribution assay can be used to identify multiple classes of compounds that act at, or upstream of, the level of the protein target used in the primary screening assay. Such compounds may include both conventional and allosteric enzyme inhibitors, as well as protein-protein interaction modulators. We have developed a series of Redistribution assays to discover and characterize compounds that inhibit tumor necrosis factor-alpha biosynthesis via modulation of the p38 mitogen-activated protein kinase (MAPK) pathway. A primary assay was designed to identify low-molecular-weight compounds that inhibit the activation-dependent nuclear export of the p38 kinase substrate MAPK-activated protein kinase 2 (MK2). Hits from the primary screen were categorized, using secondary assays, either as direct inhibitors of MK2 nuclear export, or as inhibitors of the upstream p38 MAPK pathway. Activity profiles are presented for a nuclear export inhibitor, and a compound that structurally and functionally resembles a known p38 kinase inhibitor. These results demonstrate the utility of Redistribution technology as a pathway screening method for the identification of diverse and novel compounds that are active within therapeutically important signaling pathways.     

Effects of zinc pyrithione and copper pyrithione on microbial community function and structure in sediments

The effects of the new antifouling biocides, zinc pyrithione (ZPT) and copper pyrithione (CPT), on microbial communities in estuarine sediments were studied in microcosms. As functional endpoints, fluxes of nutrients (NO3-, NH4+, HPO4(2-), Si(OH)4) and protein synthesis ([14C]leucine incorporation) were used, whereas molecular fingerprinting methods (polymerase chain reaction/denaturing gradient gel electrophoresis) were used to describe the bacterial community structure. The lowest-observed-effect concentration (LOEC) for ZPT was 0.001 nmol/g dry sediment for the phosphate flux and total DNA content, whereas the LOEC for CPT was 0.1 nmol/g dry sediment for the nitrate flux and total DNA content. Nitrate fluxes increased significantly following additions of both ZPT and CPT, whereas ammonium fluxes decreased significantly after ZPT addition, suggesting changes in the nitrification and denitrification processes. The total DNA content decreased significantly following addition of both ZPT and CPT, but at the highest addition of ZPT (10 nmol ZPT/g dry sediment), an increase in total DNA content was found. Increased protein synthesis and bacterial diversity were also observed at this concentration of ZPT, suggesting growth of tolerant opportunistic species.