Autophagy mediates ER stress and inflammation in Helicobacter pylori-related gastric cancer.

Autophagy is a cellular degradation mechanism, which is triggered by the bacterium Helicobacter pylori. A single nucleotide polymorphism (SNP) in the autophagy gene ATG16L1 (rs2241880, G-allele) has been shown to dysregulate autophagy and increase intestinal endoplasmic reticulum (ER) stress. Here, we investigate the role of this SNP in H.pylori-mediated gastric carcinogenesis and its molecular pathways. ATG16L1 rs2241880 was genotyped in subjects from different ethnic cohorts (Dutch and Australian) presenting with gastric (pre)malignant lesions of various severity. Expression of GRP78 (a marker for ER stress) was assessed in gastric tissues. The effect of ATG16L1 rs2241880 on H.pylori-mediated ER stress and pro-inflammatory cytokine induction was investigated in organoids and CRISPR/Cas9 modified cell lines. Development of gastric cancer was associated with the ATG16L1 rs2241880 G-allele. Intestinal metaplastic cells in gastric tissue of patients showed increased levels of ER-stress. In vitro models showed that H.pylori increases autophagy while reducing ER stress, which appeared partly mediated by the ATG16L1 rs2241880 genotype. H.pylori-induced IL-8 production was increased while TNF-α production was decreased, in cells homozygous for the G-allele. The ATG16L1 rs2241880 G-allele is associated with progression of gastric premalignant lesions and cancer. Modulation of H.pylori-induced ER stress pathways and pro-inflammatory mediators by ATG16L1 rs2441880 may underlie this increased risk.

Launois-Bensaude syndrome (Madelung's disease).

A case of Launois-Bensaude Syndrome (Madelung's disease) in a chronic alcoholic is presented and the typical features are discussed. This entity should be considered in patients who present with doughy, symmetrically distributed, adipose masses.

[Comparative study of the effectiveness of thermocoagulation, sclerotherapy and a combination of sclerotherapy and thermocoagulation in the treatment of acute peptic ulcer hemorrhage]. / Poredbeno istrazivanje ucinkovitosti termokoagulacije, skleroterapije i kombinacije skleroterapije i termokoagulacije u lijecenju akutnog krvarenja iz peptickog vrijeda.

During the 3 years of the trial (June, 1988--December, 1990), 128 patients underwent urgent diagnostic endoscopy and hemostasis for acute peptic-ulcer bleeding. In the first group consisting of 57 patients, hemostasis was carried out by thermocoagulation (heat probe), in the second one (54 patients) by injection sclerotherapy and in the third group, hemorrhage was controlled by a combination of heater probe and sclerotherapy. The first and second groups did not differ significantly in age, sex, hemoglobin values, size, location of an ulcer, and kind of bleeding lesions classified according to Forrest. The efficacy of thermocoagulation and injection sclerotherapy in the treatment of acute peptic-ulcer bleeding was compared. In the group of patients treated with the heater probe, the initial hemostasis was achieved in 56 (98%) patients, while rebleeding occurred in 6 (10.7%) patients. In the sclerotherapy group, the initial hemostasis was accomplished in 51 (94.4%) patients, while 8 (15.6%) patients experienced rebleeding. There was no statistically significant difference in ultimate hemostasis between the patients treated with heater probe (94.7%) and the sclerotherapy patients (88.8%). The incipient results of the treatment of bleeding peptic ulcers obtained by a combination of sclerotherapy and heater probe were extremely good, but the final conclusion will be brought after the research on a larger group of patients. The only patient that died during the treatment belonged to the sclerotherapy group.

Proactive approach in detecting elderly subjects with cognitive decline in general practitioners' practices.

BACKGROUND: Although cognitive decline is a common finding among the elderly and is considered a risk factor for developing dementia, it is rarely diagnosed by general practitioners (GPs). AIM: To evaluate cognitive function with the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in asymptomatic subjects in daily GP practice and compare subjects who confirmed having cognitive problems with subjects who did not. METHODS: 388 consecutive subjects >65 years of age who consulted their GP were interviewed and tested with MMSE and MoCA. RESULTS: None of the study subjects spontaneously complained of cognitive or memory problems. 155 subjects (39.94%) confirmed having cognitive problems and 233 (60.05%) did not even when asked. The prevalence of mild cognitive impairment (MCI) was 18.30% (95% CI 14.36-22.04) and the prevalence of cognitive impairment/no dementia (CIND) was 17.27% (95% CI 13.50-21.04). Delayed memory recall as a separate cognitive domain in MoCA was significantly worse in subjects with MCI (p = 0.00958) and in those with CIND (p = 0.0208). CONCLUSION: There is a significant number of patients in daily GP practices with unrecognized, but objectively verifiable, cognitive deficits who do not report having cognitive problems. They can be identified by assessment with MMSE and MoCA already in the GP practice.