Adverse childhood experiences and the development of Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed. Caregivers of individuals with DSRD with onset of symptoms between age 10 and 30 years and DS alone were administered the ACEs questionnaire via an online REDCap survey. A total of 159 responses were collected after excluding incomplete surveys and those not meeting criteria for DSRD. Individuals with DSRD were not more likely to experience ACEs (p = 0.18, 95% confidence interval [CI]: 0.43–1.17). In those with ACEs prior to the onset of symptoms, the median time prior was 7 months (interquartile range: 5–10). Individuals with DSRD were more likely to report three or more ACEs (52, 33%) compared to those with DS alone (39, 22%) (p = 0.02, 95% CI: 1.08–2.87). Exposure to ACEs were not predictive of response to particular therapeutic interventions although those with multiple ACEs 3 months prior to the onset of symptoms was associated with lower response rates to benzodiazepines and immunotherapy (p = 0.02, 95% CI: −3.64–−1.13). This study provides preliminary data that individuals with DSRD experience ACEs at a similar rate to individuals with only DS alone, although three or more ACEs, often preceding the onset of symptoms, was more prevalent in individuals with DSRD.     

Brain-derived neurotrophic factor improves blood glucose control and alleviates fasting hyperglycemia in C57BLKS-Lepr(db)/lepr(db) mice

Systemic administration of brain-derived neurotrophic factor (BDNF) decreases nonfasted blood glucose in obese, non-insulin-dependent diabetic C57BLKS-Lepr(db)/lepr(db) (db/db) mice, with a concomitant decrease in body weight. By measuring percent HbA1c in BDNF-treated and pair-fed animals, we show that the effects of BDNF on nonfasted blood glucose levels are not caused by decreased food intake but reflect a significant improvement in blood glucose control. Furthermore, once established, this effect can persist for weeks after cessation of BDNF treatment. Oral glucose tolerance tests were performed to examine the effects of BDNF on blood glucose control in the fasted state and after an oral glucose challenge. BDNF treatment normalized fasting blood glucose from initially hyperglycemic levels and also showed evidence for beneficial, although less marked, effects on the ability to remove exogenous glucose from blood. One means to lower fasting blood glucose is to reduce the glucose output of peripheral tissues that normally play a part in the maintenance of fasting hyperglycemia. Because the liver is the major endogenous source of glucose in blood during fasting, and because hepatic weight and glucose output are increased in type 2 diabetes, we evaluated the effects of BDNF on liver tissue. BDNF reduced the hepatomegaly present in db/db mice, in association with reduced liver glycogen and reduced liver enzyme activity in serum, supporting the possible involvement of liver tissue in the mechanism of action for BDNF.     

Laparoscopic wedge resection of the gastric wall for gastric benign tumour. The collaboration of the laparoscopic surgeon and the endoscopist

INTRODUCTION: By the introduction of the laparoscopy for the management of gastric pathology many techniques are applied by now. In these techniques the collaboration of the endoscopist and the laparoscopic surgeon is mandatory. AIMS OF THE STUDY: To emphasise the necessity of the collaboration of the endoscopist and the laparoscopic surgeon for the management of the gastric pathology using the double lifting and wedge resection technique. METHOD: A case of a female with 2 x 2.5 cm submucosal tumour is presented. The tumour was located in the antrum. After the onset of the general anaesthesia the gastroscope was introduced to locate the position of the tumour, the free edges of the tumour were elevated by a double lifting method and the tumour was resected by a laparoscopic linear stapler. The process of the proper resection was all through observed and directed by the view of the gastroscope. CONCLUSION: Correct wedge resection of the gastric wall can be safely performed, if the correct gastroscopic control is present. The collaboration of the endoscopist and the laparoscopic surgeon seems to be mandatory, thus avoiding the hazards arising from the use of tattooing.     

Hunting genetic diseases: exploring a multistage approach to identifying disease loci

Genomic screen data for a hypothetical disease was used in a two-stage analysis to search for disease loci. We performed both trait-model-dependent and trait-model-free analyses to test their relative power. Results of our first-stage screen in 200 families suggested 13 regions for further analysis. Second-stage follow-up in another 200 families confirmed a single region on chromosome 3 near marker D3G045 with a combined lod score across all 400 families of 6.24 and a sib-pair maximum lod score (MLS) of 4.79. The MLS were highly correlated with both the autosomal dominant and autosomal recessive lod scores in all data sets, suggesting that both trait-model-dependent and trait-model-free methods can be useful for identifying candidate regions for complex disease loci. Reanalysis of the data using alternative sampling schemes suggested that sampling variation has a significant effect on locus detection.     

Release of bFGF, an endothelial cell survival factor, by osmotic shock.

PURPOSE: To test the effects of osmotic change on basic fibroblast growth factor (bFGF) release from cultured endothelial cells (ECs). METHODS: Bovine aortic and bovine retinal ECs were exposed to hypoosmotic shock for 2 minutes, were allowed to recover for 15 minutes, and had bFGF release assayed. The role of bFGF in cell recovery was assessed by including neutralizing antibody against bFGF or the addition of exogenous bFGF. Cell number and viability were determined under varying conditions. Apoptosis was assessed by immunoperoxidase detection of digoxigenin-labeled DNA. RESULTS: After shock and recovery, both ECs released significantly greater amounts of bFGF than untreated control. bFGF release after shock for 2 minutes was lower than release after shock and recovery. Bovine retinal endothelial (BRE) cell number was reduced at 48 hours after shock, recovery, and removal of released bFGF compared with cells left in the presence of released bFGF. Cell number was significantly lower when BRE cells were shocked and recovered in the presence of a neutralizing anti-bFGF antibody (P<0.05). Exogenous bFGF reversed this effect. Apoptosis was significantly increased in BRE cells shocked and recovered or in the presence of bFGF antibody (P<0.001). CONCLUSIONS: bFGF is released by cultured ECs in response to osmotically induced cell injury. These results support the concept of bFGF as a "wound" hormone and survival factor for ECs. In further compromised tissue, release of bFGF in this manner may play a role in the pathogenesis of disease.     

Inhibition of cathepsin D by tripeptides containing statine analogs.

Various analogs of statine, a remarkable amino acid component of the protease inhibitor pepstatine, were synthesized and evaluated as tripeptide derivatives for their activity against cathepsin D and HIV-1 protease.     

Intoxication by non-protein nitrogen compounds in rat feed

Last year our white rats (Wistar origin) showed acute behavioral and physiological changes followed by death in 70% of the animals. We detected that the malfunctions could be attributed to the new batch of laboratory rat pellets provided two weeks before. High levels of urea (260 mg/kg) and ammonia (540 mg/kg) were found in the feed while usual values in other similar feed were 48 mg/kg and 82 mg/kg respectively. Suspecting an ammonia intoxication, concentrations of ammonia and urea were determined in blood, brain and liver. Brain neurotransmitters and blood tryptophan and serotonine (5-HT) were also determined. Blood ammonia in rats fed the contaminated feed was about 100% higher than those fed the normal feed while liver and brain ammonia were three and four fold high respectively. Liver and brain urea were four to five fold and about 100% higher in the exposed group than in the group fed the control diet respectively. Blood 5-HT increased 62.33% in females and 99% in males whereas brain 5-HT increased 83.13% in females and 70.47% in males. But, we detected a 59.8% decrease in brain dopamine levels in females and a 38.65% decrease in males. Liver histology showed small droplets of fat stores mainly in centrolobular hepatocyte. No differences in blood or liver cholesterol concentrations were observed whereas liver triacylglycerides were significantly higher in intoxicated females. This study illustrates a problem of food borne intoxication that justifies the need for exhaustive analyses of even not usual compounds in every feed batch; moreover, it is demonstrated that rat behavior appears to be the earliest biomarker of ammonia exposure.