Impact of experimental endogenous gram-negative peritonitis on the pancreas of the rat as evaluated by cationic trypsin-like immunoreactivity in peritoneal fluid and serum and by electron microscopy of pancreatic tissue

Endogenous gram-negative peritonitis leading to septic shock was induced in rats by a defined perforation of the coecum. Cationic trypsin-like immunoreactivity (CTLI) was measured in peritoneal fluid and serum by a radioimmunoassay method. Five, 10, and 15 h after the coecal perforation, CTLI in peritoneal fluid was significantly higher than before the coecal perforation and also higher than in the corresponding control rats. Moreover, CTLI in serum was under the same conditions significantly higher 10 and 15 h after the induction of peritonitis. Gel chromatography of peritoneal fluid and serum during peritonitis showed free CTLI and CTLI bound to both alpha-1-antitrypsin and alpha-2-macroglobulin, whereas only free CTLI could be detected in serum from control rats. These findings were accompanied by local ultrastructural changes in the acinar cells as evaluated by electron microscopy. The pathophysiologic implications of the findings are discussed.     

FRAX and mandibular sparse trabeculation as fracture predictors: a longitudinal study from 1980 to 2002

The fracture assessment tool (FRAX) is widely used for predicting fractures, but better methods are needed. The aim of this study was to determine whether visual assessments of mandibular trabecular bone could improve FRAX predictions. Three age‐cohorts of women were examined twice – 499 women in 1980/1981 and 412 women in 1992/1993; 397 participated in both examinations. Information on 10‐yr fracture events was available, and bone trabeculation was assessed in radiographs as ‘dense’, ‘mixed’, or ‘sparse’. Fracture assessment tool values, without bone mineral density (BMD), were calculated twice. Both sparse trabeculation and FRAX >15% were associated with a twofold higher risk for future fracture in the younger group and with a three‐ to fourfold higher risk for future fracture in the older group. For those with both FRAX >15% and sparse trabeculation, the relative risk (RR) for a fracture in the next 10 yr was 5.9 (95% CI: 3.5–9.8) in the younger group and 22.7 (95% CI: 5.6–92) in the older group. If either FRAX >15% or sparse trabeculation was present, the RR was 2.6 (95% CI: 1.7–4.1) in the younger group and 15.7 (95% CI: 3.9–6.4) in the older group. We concluded that FRAX >15%, without BMD measurements, was an effective fracture predictor, and mandibular sparse trabeculation had a substantial additive effect. Together, FRAX plus mandibular sparse trabeculation predicts major osteoporotic fractures to approximately the same extent as does FRAX with BMD measurements.     

Eating self-efficacy as predictor of long-term weight loss and obesity-specific quality of life after sleeve gastrectomy: A prospective cohort study

Background

A person's confidence to control eating, eating self-efficacy (ESE), has been identified as a target for long-term weight management in nonsurgical weight loss interventions, but has to a limited extent been studied after bariatric surgery.

De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females

Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes. A single hypomorphic missense variant p.(Ser37Pro) was previously associated with Ogden syndrome in eight affected males from two different families. This rare disorder is characterized by a highly recognizable phenotype, global developmental delay and results in death during infancy. In an attempt to explain the discrepant phenotype, we used in vitro N-terminal acetylation assays which suggested that the severity of the phenotype correlates with the remaining catalytic activity. The variant in the Ogden syndrome patients exhibited a lower activity than the one seen in the boy with intellectual disability, while the variant in the girl was the most severe exhibiting only residual activity in the acetylation assays used. We propose that N-terminal acetyltransferase deficiency is clinically heterogeneous with the overall catalytic activity determining the phenotypic severity.     

Serum Galectin-3 and Subsequent Risk of Coronary Heart Disease in Subjects With Childhood-Onset Type 1 Diabetes: A Cohort Study

OBJECTIVETo study whether serum galectin-3 and other biomarkers of inflammation predict coronary heart disease (CHD) in subjects with long-standing childhood-onset type 1 diabetes.RESEARCH DESIGN AND METHODSA population-based nationwide cohort of 299 subjects with type 1 diabetes diagnosed in Norway at <15 years of age during 1973–1982 was examined in 2002–2003 at a mean age of 33 years (range 21–44), with mean diabetes duration of 24 years (range 19–30). Subjects were followed through 31 December 2017 for their first CHD event registered by a hospitalization or cause of death using nationwide registries. Stored serum samples were available for 296 subjects and analyzed for interleukin-6 (IL-6), IL-6 receptor, IL-18, hs-CRP, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), galectin-3, and high-sensitivity troponin T. Adjusted hazard ratios (aHRs) for CHD per SD increase in biomarker were estimated using Cox regression.RESULTSOf 295 subjects, 40 (13.6%) had a documented CHD event during a mean follow-up of 14.4 years (range 0.5–16). IL-6 (aHR 1.32 [95% CI 1.07–1.63]), galectin-3 (aHR 1.44 [95% CI 1.09–1.80]), and TIMP-1 (aHR 1.37 [95% CI 1.04–1.81]) were significant predictors of CHD after adjustment for conventional risk factors.CONCLUSIONSGalectin-3 was significantly associated with future CHD in subjects with type 1 diabetes, and if the results are replicated in larger studies, it may aid in prediction together with conventional risk factors for CHD.     

Educational Inequalities in Post‐Hip Fracture Mortality: A NOREPOS Studys

Hip fractures are associated with high excess mortality. Education is an important determinant of health, but little is known about educational inequalities in post‐hip fracture mortality. Our objective was to investigate educational inequalities in post‐hip fracture mortality and to examine whether comorbidity or family composition could explain any association. We conducted a register‐based population study of Norwegians aged 50 years and older from 2002 to 2010. We measured total mortality according to educational attainment in 56,269 hip fracture patients (NORHip) and in the general Norwegian population. Both absolute and relative educational inequalities in mortality in people with and without hip fracture were compared. There was an educational gradient in post‐hip fracture mortality in both sexes. Compared with those with primary education only, the age‐adjusted relative risk (RR) of mortality in hip fracture patients with tertiary education was 0.82 (95% confidence interval [CI] 0.77–0.87) in men and 0.79 (95% CI 0.75–0.84) in women. Additional adjustments for Charlson comorbidity index, marital status, and number of children did not materially change the estimates. Regardless of educational attainment, the 1‐year age‐adjusted mortality was three‐ to fivefold higher in hip fracture patients compared with peers in the general population without fracture. The absolute differences in 1‐year mortality according to educational attainment were considerably larger in hip fracture patients than in the population without hip fracture. Absolute educational inequalities in mortality were higher after hip fracture compared with the general population without hip fracture and were not mediated by comorbidity or family composition. Investigation of other possible mediating factors might help to identify new targets for interventions, based on lower educational attainment, to reduce post‐hip fracture mortality. © 2015 American Society for Bone and Mineral Research.