Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome

Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance

Appearance of remodelled and dendritic cell-rich alveolar-lymphoid interfaces provides a structural basis for increased alveolar antigen uptake in chronic obstructive pulmonary disease.

RATIONALE: The alveolar pathology in chronic obstructive pulmonary disease (COPD) involves antigen-driven immune events. However, the induction sites of alveolar adaptive immune responses have remained poorly investigated. OBJECTIVES: To explore the hypothesis that interfaces between the alveolar lumen and lymphoid aggregates (LAs) provide a structural basis for increased alveolar antigen uptake in COPD lungs. METHODS: Lung samples from patients with mild (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I), moderate-severe (GOLD II-III), and very severe (GOLD IV) COPD were subjected to detailed histological assessments of adaptive immune system components. Never smokers and smokers without COPD served as controls. RESULTS: Quantitative histology, involving computerised three-dimensional reconstructions, confirmed a rich occurrence of alveolar-restricted LAs and revealed, for the first time, that the vast majority of vascular or bronchiolar associated LAs had alveolar interfaces but also an intricate network of lymphatic vessels. Uniquely to COPD lungs, the interface epithelium had transformed into a columnar phenotype. Accumulation of langerin (CD207)(+) dendritic cells occurred in the interface epithelium in patients with COPD but not controls. The antigen-capturing capacity of langerin(+) dendritic cells was confirmed by increased alveolar protrusions and physical T cell contact. Several of these immune remodelling parameters correlated with lung function parameters. CONCLUSIONS: Severe stages of COPD are associated with an emergence of remodelled and dendritic cell-rich alveolar-lymphoid interfaces. This novel type of immune remodelling, which predicts an increased capacity to respond to alveolar antigens, is suggested to contribute to aggravated inflammation in COPD

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n = 676) and controls (n = 309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA). LVAb at 75th percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4th quartile LVAb were found in 25% (170/676) of which 64% were < 10 (n = 108, p < 0.0001), and 27% were < 5 (n = 45; p < 0.0001) years old. The 4th quartile LVAb in children < 10 years of age correlated to HLA DQ2/8, 8/8, and 8/X (p < 0.0001). Furthermore, in the group with 4th quartile LVAb, 55% were IAA positive (p = 0.01) and correlation was found between 4th quartile LVAb and IAA in children < 10 years of age (p = 0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4th quartile LVAb correlated with IAA; and 3) there was a correlation between 4th quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D

Peritonitis secondary to traumatic duodenal laceration in the presence of a large pancreatic pseudocyst: a case report

<p>Abstract</p> <p>Introduction</p> <p>A pancreatic pseudocyst is a common sequela of severe acute pancreatitis. Commonly, it presents with abdominal pain and a mass in the epigastrium several weeks after the acute episode and can be managed conservatively, endoscopically or surgically. We report a patient with a pancreatic pseudocyst awaiting endoscopic therapy who developed a life-threatening complication following a rather innocuous trauma to the abdomen.</p> <p>Case presentation</p> <p>A 23-year-old Asian male student presented as an emergency with an acute abdomen a week after a minor trauma to his upper abdomen. The injury occurred when he was innocently punched in the abdomen by a friend. He experienced only moderate discomfort briefly at the time. His past medical history included coeliac disease and an admission four months previously with severe acute pancreatitis. He was hospitalized for 15 days; his pancreatitis was thought to be due to alcohol binge drinking on weekends. Ultrasound scanning showed no evidence of gallstone disease. Five days after the trauma, he became anorexic, lethargic and feverish and started vomiting bilious content. Seven days post-trauma, he presented to our emergency department with severe abdominal pain. An emergency laparotomy was performed where a transverse linear duodenal laceration was found at the junction of the first and second part of his duodenum, with generalized peritonitis. His stomach and duodenum were stretched over a large pancreatic pseudocyst posterior to his stomach. It was postulated that an incomplete duodenal injury (possibly a serosal tear) occurred following the initial minor trauma, which was followed by local tissue necrosis at the injury site resulting in a delayed presentation of generalized peritonitis.</p> <p>Conclusion</p> <p>This is the first reported case of a traumatic duodenal laceration following minor blunt trauma in the presence of a large pancreatic pseudocyst. Minor blunt abdominal trauma in a normal healthy adult would not be expected to result in a significant duodenal injury. In the presence of a large pseudocyst, however, the stretching of the duodenum over the pseudocyst had probably predisposed the duodenum to this injury. Patients awaiting therapeutic interventions for their pancreatic pseudocysts should be warned about this unusual but life-threatening risk following minor blunt abdominal trauma.</p

Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease

Peer reviewe

What promotes sustainability in Safe Community programmes?

<p>Abstract</p> <p>Background</p> <p>The theory and practice of safety promotion has traditionally focused on the safety of individuals. This study also includes systems, environments, and organizations. Safety promotion programmes are designed to support community health initiatives taking a bottom-up approach. This is a long-term and complex process. The aim of this study was to try to empirically identify factors that promote sustainability in the structures of programmes that are managed and coordinated by the local government.</p> <p>Methods</p> <p>Four focus group sessions with local government politicians and administrators in designated Safe Communities were conducted and analyzed using qualitative content analysis.</p> <p>Results</p> <p>Collaboration was found to be the basis for sustainability. Networks, enabling municipalities to exchange ideas, were reported to positively influence the programmes. Personal contacts rather than organizations themselves, determine whether collaboration is sustained. Participants reported an increase in cross-disciplinary collaboration among staff categories. Administrators and politicians were reported to collaborate well, which was perceived to speed up decision-making and thus to facilitate the programme work. Support from the politicians and the county council was seen as a prerequisite. Participants reported an increased willingness to share information between units, which, in their view, supports sustainability. A structure in which all local authorities' offices were located in close proximity to one another was considered to support collaboration. Appointing a public health coordinator responsible for the programme was seen as a way to strengthen the relational resources of the programme.</p> <p>Conclusion</p> <p>With a public health coordinator, the 'external' negotiating power was concentrated in one person. Also, the 'internal' programme strength increased when the coordination was based on a bureaucratic function rather than on one individual. Increased relational resources facilitated the transfer of information. A regular flow of information to policy-makers, residents, and staff was needed in order to integrate safety programmes into routines. Adopting a bottom-up approach requires that informal and ad hoc activities in information management be replaced by formalized, organizationally sanctioned routines. In contrast to injury prevention, which focuses on technical solutions, safety promotion tries to influence attitudes. Collaboration with the media was an area that could be improved.</p

Tissue-Specific Increases in 11β-Hydroxysteroid Dehydrogenase Type 1 in Normal Weight Postmenopausal Women

With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11βHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11βHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11βHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5α-tetrahydrocortisol+5β-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11βHSD1 activity. Postmenopausal women had higher 11βHSD1 gene expression in subcutaneous fat (P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher hepatic 11βHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11βHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women