Antiviral Wolbachia strains associate with Aedes aegypti endoplasmic reticulum membranes and induce lipid droplet formation to restrict dengue virus replication.

Wolbachia are a genus of insect endosymbiotic bacteria which includes strains wMel and wAlbB that are being utilized as a biocontrol tool to reduce the incidence of Aedes aegypti-transmitted viral diseases like dengue. However, the precise mechanisms underpinning the antiviral activity of these Wolbachia strains are not well defined. Here, we generated a panel of Ae. aegypti-derived cell lines infected with antiviral strains wMel and wAlbB or the non-antiviral Wolbachia strain wPip to understand host cell morphological changes specifically induced by antiviral strains. Antiviral strains were frequently found to be entirely wrapped by the host endoplasmic reticulum (ER) membrane, while wPip bacteria clustered separately in the host cell cytoplasm. ER-derived lipid droplets (LDs) increased in volume in wMel- and wAlbB-infected cell lines and mosquito tissues compared to cells infected with wPip or Wolbachia-free controls. Inhibition of fatty acid synthase (required for triacylglycerol biosynthesis) reduced LD formation and significantly restored ER-associated dengue virus replication in cells occupied by wMel. Together, this suggests that antiviral Wolbachia strains may specifically alter the lipid composition of the ER to preclude the establishment of dengue virus (DENV) replication complexes. Defining Wolbachia's antiviral mechanisms will support the application and longevity of this effective biocontrol tool that is already being used at scale.IMPORTANCEAedes aegypti transmits a range of important human pathogenic viruses like dengue. However, infection of Ae. aegypti with the insect endosymbiotic bacterium, Wolbachia, reduces the risk of mosquito to human viral transmission. Wolbachia is being utilized at field sites across more than 13 countries to reduce the incidence of viruses like dengue, but it is not well understood how Wolbachia induces its antiviral effects. To examine this at the subcellular level, we compared how different strains of Wolbachia with varying antiviral strengths associate with and modify host cell structures. Strongly antiviral strains were found to specifically associate with the host endoplasmic reticulum and induce striking impacts on host cell lipid droplets. Inhibiting Wolbachia-induced lipid redistribution partially restored dengue virus replication demonstrating this is a contributing role for Wolbachia's antiviral activity. These findings provide new insights into how antiviral Wolbachia strains associate with and modify Ae. aegypti host cells.

Coxiella co-opts the Glutathione Peroxidase 4 to protect the host cell from oxidative stress-induced cell death.

The causative agent of human Q fever, Coxiella burnetii, is highly adapted to infect alveolar macrophages by inhibiting a range of host responses to infection. Despite the clinical and biological importance of this pathogen, the challenges related to genetic manipulation of both C. burnetii and macrophages have limited our knowledge of the mechanisms by which C. burnetii subverts macrophages functions. Here, we used the related bacterium Legionella pneumophila to perform a comprehensive screen of C. burnetii effectors that interfere with innate immune responses and host death using the greater wax moth Galleria mellonella and mouse bone marrow-derived macrophages. We identified MceF (Mitochondrial Coxiella effector protein F), a C. burnetii effector protein that localizes to mitochondria and contributes to host cell survival. MceF was shown to enhance mitochondrial function, delay membrane damage, and decrease mitochondrial ROS production induced by rotenone. Mechanistically, MceF recruits the host antioxidant protein Glutathione Peroxidase 4 (GPX4) to the mitochondria. The protective functions of MceF were absent in primary macrophages lacking GPX4, while overexpression of MceF in human cells protected against oxidative stress-induced cell death. C. burnetii lacking MceF was replication competent in mammalian cells but induced higher mortality in G. mellonella, indicating that MceF modulates the host response to infection. This study reveals an important C. burnetii strategy to subvert macrophage cell death and host immunity and demonstrates that modulation of the host antioxidant system is a viable strategy to promote the success of intracellular bacteria.

Pre-anaesthetic clinical examination influences anaesthetic protocol in dogs undergoing general anaesthesia and sedation.

OBJECTIVES: Identify whether pre-anaesthetic clinical examination influences anaesthetic and analgesic agents and techniques protocol in dogs presented for general anaesthesia and sedation at a large referral hospital. MATERIALS AND METHODS: In this prospective clinical audit, 554 dogs, undergoing general anaesthesia or sedation for surgical, diagnostic or imaging procedures were included. Multiple attending anaesthetists completed a questionnaire divided into four sections (American Society of Anesthesiologists physical status classification, anaesthetic and analgesic agents and techniques protocol, pre-anaesthetic clinical examination findings and changes made to the anaesthetic protocol). The attending anaesthetist was able to review the patient's history before planning the anaesthetic and analgesic agents and techniques protocol. The patients were examined and changes in American Society of Anesthesiologists physical status classification or anaesthetic protocol were recorded. RESULTS: The initial anaesthetic and analgesic agents and techniques protocol was altered in 23.3% (n=129/554) of cases following a pre-anaesthetic clinical examination, but American Society of Anesthesiologists physical status reclassification occurred in only 8.0% (n=37/464) of cases. Multivariable logistic regression analysis showed that pre-anaesthetic clinical examination performed by European College of Veterinary Anaesthesia and Analgesia diplomates (odds ratio 5.8, 95% confidence interval 2.0 to 17.2), compared to anaesthesia interns, and the presence of an audible heart murmur (odds ratio 2.4, 95% confidence interval 1.4 to 4.4) were factors linked to changes in anaesthetic and analgesic agents and techniques protocol, whereas for each one kilogram increase in patient's weight, the odds of a change in anaesthetic and analgesic agents and techniques protocol to occur decreased by 1.7% (odds ratio 0.98, 95% confidence interval 0.97 to 1.0). CLINICAL SIGNIFICANCE: Pre-anaesthetic clinical examination has impact on American Society of Anesthesiologists physical status classification, therefore estimation of patient's anaesthetic risk, and influences anaesthetic and analgesic agents and techniques protocol choice.

Computed tomography colonography versus colonoscopy for the diagnosis of colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer (CRC) is a significant cause of morbidity and mortality. Optical colonoscopy (OC) is the first choice of investigation for assessing the state of the colon and it is excellent for CRC screening. Newer technologies such as computed tomography colonography (CTC) may also be useful in CRC screening. This systematic review compares the benefits of CTC and OC for CRC screening. This review includes all the available randomized clinical trials comparing CTC and OC for CRC screening in asymptomatic patients. Three studies were included in the systematic review and were submitted for meta-analysis. In the analysis of participation rates, only 2,333 of 8,104 (29%) patients who were invited for screening underwent the CTC, and only 1,486 of the 7,310 (20%) patients who were invited for screening underwent OC. The absolute risk difference in participation rate in the two procedures was 0.1 (95% CI, 0.05-0.14) in favor of CTC. In the analysis of advanced colorectal neoplasia (ACN) detection rates, 2,357 patients undergoing CTC and 1,524 patients undergoing OC were included. Of these, 135 patients (5.7%) who underwent a CTC and 130 patients (8.5%) who underwent an OC were diagnosed with ACN. The absolute risk difference in ACN detection rate in the two procedure types was -0.02 (with a 95% CI between -0.04 and -0.00) in favor of OC. CTC is an option for CRC screening in asymptomatic patients. However, as CTC was inferior in detecting ACN, it should not replace OC, which remains the gold standard.

Gastrointestinal Transcriptomic Response of Metabolic Vitamin B12 Pathways in Roux-en-Y Gastric Bypass.

OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency. METHODS: During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9±6.2 years; body mass index, 46.5±5.3 kg/m2) with adult-onset type 2 diabetes (fasting plasma glucose ≥126 mg/dl; hemoglobin A1c≥6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR). RESULTS: Gene expression levels with significant changes (P≤0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P≤0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold). CONCLUSIONS: RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.

Asymptomatic gastric bacterial overgrowth after bariatric surgery: are long-term metabolic consequences possible?

BACKGROUND: Patients with postbariatric bacterial overgrowth were reinvestigated after a follow-up of 15 years. It was hypothesized that systemic associations analogous to those reported for whole gut microbiome would be revealed. METHODS: Patients (n = 37, 70.3 % females, 42.4 ± 9.9 years old, preoperative BMI 53.5 ± 10.6 kg/m(2), current BMI 32.8 ± 10.8 kg/m(2)), all submitted to RYGB on account of morbid obesity, were followed during 176.8 ± 25.7 months. Blood tests included fasting blood glucose, HbA1c, liver and pancreatic enzymes, and lipid fractions. Bacterial overgrowth was diagnosed by quantitative culture of gastric fluid in both the excluded remnant and the gastric pouch, with the help of double-balloon enteroscopy. Absolute counts of aerobes and anaerobes in both gastric reservoirs were correlated with nutritional and biochemical measurements, aiming to identify clinically meaningful associations. RESULTS: Patients denied diarrhea, abdominal pain, weight loss, or other symptoms related to bacterial overgrowth. Biochemical profile including enzymes was also acceptable, indicating a stable condition. Positive correlation of bacterial count in either segment of the stomach was demonstrated for BMI and gamma-glutamyl transferase, whereas negative correlation occurred regarding fasting blood glucose. CONCLUSIONS: An antidiabetic role along with deleterious consequences for weight loss and liver function are possible in such circumstances. Such phenotype is broadly consistent with reported effects for the whole gut microbiome. Prospective controlled studies including molecular analysis of gastrointestinal fluid, and simultaneous profiling of the entire microbiome, are necessary to shed more light on these findings.

Phase-contrast and magnification radiography at diagnostic X-ray energies using a pseudo-microfocus X-ray source.

OBJECTIVE: To investigate the use of conventional diagnostic X-ray tubes for applications in which specialist microfocus sources are normally required. METHODS: A conventional diagnostic X-ray tube was used in conjunction with a range of apertures to investigate improvements in spatial resolution using a line-pairs test object. Phase-contrast effects were investigated by varying source-to-object and object-to-receptor distances using a 2-French catheter as a clinically realistic test object. RESULTS: For magnification radiography using a computed radiography receptor and conventional X-ray tube with a 1-mm nominal focus size, the limiting spatial resolution was improved from 3.55 line-pairs per millimetre, for a conventional contact image, to 5.6 line-pairs per millimetre, for a ×2 magnified view with a 250-µm aperture. For inline phase-contrast radiography, phase contrast enhancement of a 2-French catheter was demonstrated, and the expected trends with variations in source-to-object and object-to-receptor distances were found. Images of a neonatal phantom demonstrated a subtle improvement in visibility of a superimposed 1-French catheter simulating a percutaneously inserted central catheter for no increase in patient radiation dose. CONCLUSION: Spatial resolution improvement and visible phase contrast can be produced in clinically relevant objects using a pseudo-microfocus geometry at X-ray energies in the normal diagnostic range, using conventional diagnostic X-ray tubes and image receptors. The disadvantages of the proposal are the large distances required to produce phase contrast and limitations imposed by the resulting tube loading. ADVANCES IN KNOWLEDGE: It is possible to use conventional diagnostic X-ray equipment in applications that normally require microfocus X-ray sources. This presents some possibilities for clinical applications.

Factors influencing disease phenotype and penetrance in HFE haemochromatosis.

Haemochromatosis is predominantly associated with the HFE p.C282Y homozygous genotype, which is present in approximately 1 in 200 people of Northern European origin. However, not all p.C282Y homozygotes develop clinical features of haemochromatosis, and not all p.C282Y homozygotes even present abnormal iron parameters justifying venesection therapy. This situation was not apparent from initial genotype/phenotype correlation studies as there was a selection bias of patients. Only those patients with a significant iron burden were included in these early studies. It is now largely accepted that the p.C282Y/p.C282Y genotype is necessary for the development of HFE haemochromatosis. However, this genotype provides few clues as to why certain symptoms are associated with the disease. Expression of iron overload in people with this genotype depends on the complex interplay of environmental factors and modifier genes. In this review, we restrict our discussion to work done in humans giving examples of animal models where this has helped clarify our understanding. We discuss penetrance, explaining that this concept normally does not apply to autosomal recessive disorders, and discuss the usefulness of different biochemical markers in ascertaining iron burden. Hepcidin, a peptide synthesized primarily by the liver, has been identified as the central regulator in iron homeostasis. Consequently, understanding its regulation is the key. We conclude that the main goal now is to identify important modifiers that have a significant and unambiguous effect on iron storage.

Advances in mammographic imaging.

Breast imaging in the UK is currently undergoing a major change, with the widespread implementation of full-field digital mammography (FFDM) equipment. This article looks at some of the advanced imaging techniques that have become possible following the development of FFDM units. These techniques may prove to be useful additions to standard mammography for some groups of women.

An investigation into the effects of suboptimal viewing conditions in screen-film mammography.

The ability of an observer to detect objects on a radiograph is influenced by the conditions under which the image is viewed. Therefore, to ensure that as much diagnostically relevant information as possible can be extracted from the image, it is important that satisfactory viewing conditions for the task are established and maintained. Factors that are thought to be important are the luminance of the image, glare and ambient light. Together, these factors lead to the formation of reflection on the image, which may degrade the observer's performance. The purpose of this study was to explore, in a systematic manner, the effect of the factors outlined above on the performance of an observer conducting a threshold contrast-detail diameter test. Each factor was investigated separately with attempts made to minimize the confounding effects of other factors. When examined individually, viewing box luminance, ambient light and glare were found to have little effect on the contrast-detail performance of the observers. Reflection was found to have a significant effect, particularly non-uniform reflection, and the magnitude of the effect was related to the contrast degradation factor and reflection modulation. These quantities, which are derived from basic photometric measurements, may be used to develop a protocol to assess viewing conditions in screen-film mammography.

Successful algorithm for selective liver biopsy in the right hepatic lobe live donor (RHLD).

Routine versus selective predonation liver biopsy (LBx) remains controversial for assuring the safety of right hepatic lobe live donor (RHLD). Between December 1999 and March 2007, 403 potential RHLD were evaluated; 142 donated. Indications for selective LBx were: abnormal liver function tests or imaging studies, body mass index (BMI) >28, history of substance abuse or family history of immune mediated liver disease. All donors had a LBx at the time of surgery. Of 403 potential RLD, 149(36.9%) were accepted as donors, 25(6.3%) had their recipient receive a deceased donor graft, 94(23.4%) were rejected, 52(12.9%) stopped the evaluation process, 76(18.8%) withdrew from the process and 7(1.7%) are currently completing evaluation. Eighty-seven (21.5%) met criteria and were biopsied. Seventy-three (83.9%) had either normal (n = 24) or macrosteatosis <10% (n = 49); 51 of these donated. Abnormal LBx eliminated 15 potential donors. No significant abnormalities were found in donation biopsies of donors not meeting algorithm criteria. Three of 87 (3.4%) had complications requiring overnight admission (2 for pain, 1 for bleeding; transfusion not required). Use of this algorithm resulted in 78% of potential donors avoiding biopsy and potential complications. No significant liver pathology was identified in donors not meeting criteria for evaluation LBx. Routine predonation LBx is unnecessary in potential RHLD.

Endoscopic findings in the excluded stomach after Roux-en-Y gastric bypass surgery.

HYPOTHESIS: After gastric bypass surgery performed because of morbid obesity, the excluded stomach can rarely be endoscopically examined. With the advent of a new apparatus and technique, possible mucosal changes can be routinely accessed and monitored, thus preventing potential benign and malignant complications. DESIGN: Prospective observational study in a homogeneous population with nonspecific symptoms. SETTING: Outpatient clinic of a large public academic hospital. PATIENTS: Forty consecutive patients (mean +/- SD age, 44.5 +/- 10.0 y ears; 85.0% women) were seen at a mean +/- SD of 77.3 +/- 19.4 months after Roux-en-Y gastric bypass surgery. INTERVENTION: Elective double-balloon enteroscopy of the excluded stomach was performed. MAIN OUTCOME MEASURES: Rate of successful intubation, endoscopic findings, and complications. RESULTS: The excluded stomach was reached in 35 of 40 patients (87.5%). Mean +/- SD time to enter the organ was 24.9 +/- 14.3 minutes (range, 5-75 minutes). Endoscopic findings were normal in 9 patients (25.7%), whereas in 26 (74.3%), various types of gastritis (erythematous, erosive, hemorrhagic erosive, and atrophic) were identified, primarily in the gastric body and antrum. No cancer was documented in the present series. Tolerance was good, and no complications were recorded during or after the intervention. CONCLUSIONS: The double-balloon method is useful and practical for access to the excluded stomach. Although cancer was not noted, most of the studied population had gastritis, including moderate and severe forms. Surveillance of the excluded stomach is recommended after Roux-en-Y gastric bypass surgery performed because of morbid obesity.

Increased gastric cytokine production after Roux-en-Y gastric bypass for morbid obesity.

HYPOTHESIS: Mucosal cytokines may be involved in the process of gastric bacterial contamination that may occur after Roux-en-Y bypass for morbid obesity in both gastric chambers, with inflammation and gastritis mostly in the excluded stomach. DESIGN: A prospective observational study in a homogeneous population with nonspecific complaints. SETTING: Outpatient clinic of a large, public, academic hospital. PATIENTS: Subjects (n = 37; 26 [70.3%] female; mean +/- SD age, 42.4 +/- 9.9 years) seen a mean +/- SD of 7.3 +/- 1.4 years after Roux-en-Y gastric bypass and nonoperated on morbidly obese control subjects (n = 10; 7 [70%] female; mean +/- SD age, 44.0 +/- 8.9 years). INTERVENTION: Enteroscopy was performed to collect samples for cytokine assays and bacteriologic studies. MAIN OUTCOME MEASURES: Concentrations of tumor necrosis factor alpha and transforming growth factor beta in the gastric mucosa of both chambers in patients undergoing Roux-en-Y gastric bypass and correlation with bacterial overgrowth and Helicobacter pylori infection. RESULTS: High microbial counts (>10(5) colony-forming units per milliliter) were detected in 22 (59.5%) and 7 (18.9%) of the 37 samples from the functional pouch and excluded reservoir, respectively; and H pylori investigation was positive in 6 of 37 samples (16.2%). The tumor necrosis factor alpha concentration (mean +/- SD, 2.1 +/- 1.9 pg/g of protein) and the transforming growth factor beta concentration (mean +/- SD, 24.2 +/- 12.8 pg/g of protein) in the excluded stomach, but not in the proximal pouch, were elevated with regard to the corpus or antrum of controls, and correlation with bacterial overgrowth and with H pylori infection was demonstrated. CONCLUSION: Overexpression of tumor necrosis factor alpha and transforming growth factor beta occurred in the distal stomach, positive cytokine correlation with microbial invasion by H pylori and nonspecific germs was seen, and further studies addressing phenotypic and genotypic changes of gastric mucosa are recommended.

Microbial flora of the stomach after gastric bypass for morbid obesity.

BACKGROUND: The normal stomach is virtually sterile but the effect of Roux-en-Y gastric bypass (RYGBP) on bacterial flora in the used (very small proximal pouch) and unused (large bypassed) gastric chambers is not known. In a prospective study, this variable was documented. METHODS: Bariatric subjects (n=37) were submitted to endoscopic examination of both gastric reservoirs via FUJINON enteroscope model EN-450P5, 7.3 +/- 1.4 years after RYGBP. Age was 42.4 +/- 9.9 years (70.2% females), preoperative BMI was 53.5 +/- 10.6, and current BMI was 32.6 +/- 7.8 kg/m2. Methods included quantitative culture of gastric secretion along with gastric pH and lactulose/hydrogen breath test. RESULTS: None of the subjects displayed diarrhea, malabsorption or other complaints suggestive of GI bacterial overgrowth. Elevated counts of bacteria and fungi were identified in both chambers, with predominance of aerobes and anaerobes, but not molds and yeasts, in the proximal stomach. Gram-positive cocci, bacilli and coccobacilli represented the majority of the isolates. Gastric pH was neutral (pH 7.0 +/- 0.2) in the proximal pouch, whereas the distal chamber mostly but not always conserved the expected acidity (pH 3.3 +/- 2.2, P<0.001). The breath test for bacterial overgrowth was positive in 40.5% of the population. CONCLUSIONS: 1) Frequent colonization of both gastric chambers was detected; 2) Aerobes, anaerobes and fungi were represented in both situations; 3) Gastric pH as well as bacterial count was higher in the functioning proximal stomach; 4) Breath test was positive in 40.5% of the subjects; 5) Clinical manifestation such as diarrhea, malabsorption or pneumonia were not demonstrated; 6) Further histologic and microbiologic studies of both the stomach and the small bowel are recommended.

Systemic inflammation in morbidly obese subjects: response to oral supplementation with alpha-linolenic acid.

BACKGROUND: Morbidly obese patients frequently display asymptomatic chronic activation of acute phase response, with potentially adverse metabolic and cardiovascular consequences. Nutritional preparations to improve this phenomenon have rarely been administered. Aiming to investigate the supplementation of flaxseed flour, a source of omega-3 fatty acids, a prospective randomized double-blind cross-over study was designed. METHODS: Outpatient obese subjects (n=41) were clinically and biochemically screened, and results for 24 randomized subjects are shown. Age was 40.8 +/- 11.6 years (83.3% females) and body mass index (BMI) was 47.1 +/- 7.2 kg/m2. Flaxseed flour (Farinha de Linhaca Dourada LinoLive, Cisbra, Brazil) in the amount of 30 g/day (5 g of alpha-linolenic acid - omega-3) and an equal mass of placebo (manioc flour) were administered for 2 weeks each. Variables included general biochemical investigation, white blood cell count (WBC), C-reactive protein (CRP), serum amyloid A (SAA) and fibronectin. RESULTS: No intolerance was registered. Body weight and general biochemical indices remained stable. Initial CRP and SAA were elevated (13.7 +/- 9.9 and 17.4 +/- 8.0 ). WBC (8100 +/- 2100/mm3) and fibronectin (463.2 +/- 61.3 mg/dL) were acceptable but in the upper normal range. Corresponding findings after supplementation of flaxseed were 10.6 +/- 6.2 mg/L, 14.3 +/- 9.2 mg/L, 7300 +/- 1800/mm3 and 412.8 +/- 38.6 respectively (P<0.05). No change during the control period regarding baseline occurred when placebo was randomized to be given first; however, when it followed omega-3 supplementation, CRP and SAA recovered, whereas WBC and fibronection remained depressed during those 2 weeks (7500 +/- 2100/mm3 and 393.2 +/- 75.8 mg/dL, P<0.05). CONCLUSIONS: 1) Various inflammatory markers were elevated in the studied population, although not necessarily exceeding the normal range; 2) Significant reduction could be demonstrated; 3) Some persistent effects of flaxseed supplement 2 weeks after discontinuation were observed.

Social determinants of health inequalities in Bosnia and Herzegovina.

OBJECTIVE: To examine the social determinants of inequalities in health in Bosnia and Herzegovina in the post-conflict period, and to test if the relative effects vary across the two entities of the Federation of Bosnia and Herzegovina and the Republika Srpska. STUDY DESIGN: Cross-sectional data come from the first wave of the Bosnia and Herzegovina Household Panel Study conducted in 2001, which collected data from 7482 respondents aged 17 years and older based on over 3000 households. METHODS: Distributions and odds ratios for physical limitations and poor mental well-being were calculated over a number of known social determinants. Multivariate logistic regression and t-tests were used to compare risks across entities within the state of Bosnia and Herzegovina. RESULTS: The prevalence of poor mental well-being and physical limitations was significantly higher in the Republika Srpska. Significant differences in poor mental well-being and physical limitations were observed across most determinants within each entity, but only a few of these relative effects differed between entities. CONCLUSIONS: Efforts to tackle absolute differences in poor health between the entities within Bosnia and Herzegovina should be pursued, along with reducing social inequalities.

What to expect in the excluded stomach mucosa after vertical banded Roux-en-Y gastric bypass for morbid obesity.

Mucosal alterations after vertical banded Roux-en-Y gastric bypass have not been clearly evaluated. The aim of this paper was to analyze the histological findings and the presence of Helicobacter pylori in the excluded stomach. Forty consecutive patients who underwent Roux-en-Y gastric bypass longer than 36 months were selected for double-balloon enteroscopy. The excluded stomach was reached in 35/40 patients (88%). Morphological alterations were analyzed through hematoxilin and eosin and the presence of H. pylori was confirmed with Giemsa staining. Thirty patients (86%) were female, and the mean age was 43 years old. The mean postoperative time was 78 months (36-110 months). Histologically, all patients had chronic gastritis in the bypassed stomach, with pangastritis in 33/35 (94%). Five cases (5/35, 14%) presented atrophy and four of them also had intestinal metaplasia. Helicobacter pylori was detected in 7/35 (20%) of the excluded stomach and in 12/35 (34%) of the functional pouch. All patients positive for H. pylori in the excluded stomach were also positive in the functional pouch, p = 0.0005. Helicobacter pylori is still present in the excluded stomach after Roux-en-Y gastric bypass and might be considered for treatment. Histological findings indicated high prevalence of atrophy and intestinal metaplasia in this selected population.

Iron genes, iron load and risk of Alzheimer's disease.

BACKGROUND: Compound heterozygotes of the haemochromatosis gene (HFE) variants, H63D and C282Y, have raised transferrin saturation compared with that in the wild type. In the cohort of the Oxford Project To Investigate Memory and Ageing (OPTIMA), bicarriers of the HFE C282Y and the transferrin C2 gene variants are at five times greater risk of developing Alzheimer's disease; the addition of HFE H63D may raise the risk still further. OBJECTIVE: To investigate transferrin saturation by HFE and transferrin genotype among people without dementia-that is, controls and those with mild cognitive impairment (MCI)-and also among those with Alzheimer's disease. METHODS: Serum iron status and genotype were examined of 177 patients with Alzheimer's disease, 69 patients with MCI and 197 controls from the OPTIMA cohort. RESULTS: Although each of these variants alone had relatively little effect on iron status, the combination of either HFE C282Y and HFE H63D or of HFE C282Y and transferrin C2 markedly raised transferrin saturation in those without dementia, but had little effect in those with mature Alzheimer's disease. CONCLUSIONS: These combinations may raise the risk for Alzheimer's disease, owing to higher iron loads and therefore oxidative stress in the preclinical phase. If replicated, these findings will have implications for the prevention of Alzheimer's disease.