Virus/Allergen Interactions in Asthma

Understanding the underlying mechanisms that cause and exacerbate allergic asthmatic disease is of great clinical interest. Clinical studies have revealed that allergies and viral respiratory illnesses are strongly linked to the inception and exacerbation of asthma, and suggest the possibility that there are interactive inflammatory mechanisms. Recent work has revealed a number of mechanisms of virus and allergen cross-talk that may play a role in the pathophysiology of allergic asthma, including (1) deficiency in virus-induced interferon responses, (2) defective epithelial barrier function, (3) increased release of epithelium-derived cytokines (e.g., thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, IL-33), (4) dysregulation of lymphocytes [e.g., innate lymphoid cells (ILCs), regulatory T cells (Tregs)], and (5) altered activation of purinergic receptors. One or more of these processes may provide targets for new therapeutics to treat allergic asthma and prevent disease exacerbation.     

Residues Glu2181-Val2243 Contain a Major Determinant of the Inhibitory Epitope in the C2 Domain of Human Factor VIII

The human blood coagulation factor VIII C2 domain (Ser2173-Tyr2332)contains an epitope recognized by most polyclonal inhibitory anti-factor VIII alloantibodies and autoantibodies. We took advantage of the differential reactivity of inhibitory antibodies with human andporcine factor VIII and mapped a major determinant of the C2 epitope byusing a series of active recombinant hybrid human/porcine factor VIIImolecules. A series of five C2-specific human antibodies and a murineanti-factor VIII monoclonal antibody, NMC-VIII/5, inhibited a hybridcontaining a substitution of porcine sequence for Glu2181-Val2243significantly less than human factor VIII. In contrast, four of thefive patient antibodies and NMC-VIII/5 inhibited a hybrid containing asubstitution of porcine sequence for Thr2253-Tyr2332 equally well ashuman factor VIII. Thus, a major factor VIII inhibitor epitopedeterminant is bounded by Glu2181-Val2243 at theNH₂-terminal end of the C2 domain. Because C2 inhibitorsblock the binding of factor VIII to phospholipid and von Willebrandfactor, for which binding sites have been localized to Thr2303-Tyr2332,these results imply that the segment bounded by Glu2181-Val2243 also isinvolved in these macromolecular interactions.     

Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus

Hospital-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health burden dominated by a small number of bacterial clones. The pandemic EMRSA-16 clone (ST36-II) has been widespread in UK hospitals for 20 y, but its evolutionary origin and the molecular basis for its hospital association are unclear. We carried out a Bayesian phylogenetic reconstruction on the basis of the genome sequences of 87 S. aureus isolates including 60 EMRSA-16 and 27 additional clonal complex 30 (CC30) isolates, collected from patients in three continents over a 53-y period. The three major pandemic clones to originate from the CC30 lineage, including phage type 80/81, Southwest Pacific, and EMRSA-16, shared a most recent common ancestor that existed over 100 y ago, whereas the hospital-associated EMRSA-16 clone is estimated to have emerged about 35 y ago. Our CC30 genome-wide analysis revealed striking molecular correlates of hospital- or community-associated pandemics represented by mobile genetic elements and nonsynonymous mutations affecting antibiotic resistance and virulence. Importantly, phylogeographic analysis indicates that EMRSA-16 spread within the United Kingdom by transmission from hospitals in large population centers in London and Glasgow to regional health-care settings, implicating patient referrals as an important cause of nationwide transmission. Taken together, the high-resolution phylogenomic approach used resulted in a unique understanding of the emergence and transmission of a major MRSA clone and provided molecular correlates of its hospital adaptation. Similar approaches for hospital-associated clones of other bacterial pathogens may inform appropriate measures for controlling their intra- and interhospital spread.     

Etanercept and anakinra can prolong febrile episodes in patients with hyperimmunoglobulin D and periodic fever syndrome

Hyperimmunoglobulin D and periodic fever syndrome (HIDS) is a rare, hereditary autoinflammatory condition, characterized by recurrent inflammatory episodes. There is no proven treatment for HIDS, but various drugs including, non-steroidal anti-inflammatory drugs, colchicine, steroids, statins and thalidomide have all been tried. Recently, some patients have demonstrated a good clinical response to either etanercept or anakinra. We report a case of a 10-year-old girl who experienced prolonged and severe inflammatory attacks, when she was treated with etanercept, and later with anakinra.     

Prevalence of Symptoms of Gastroesopahgeal Reflux in a Cohort of Saudi Arabians: A Study of 1265 Subjects

Background/Aims:

In this study, we aimed to determine the prevalence of gastroesophageal reflux disease (GERD) in the general population of the capital city of Riyadh and to assess its association with other factors including age, smoking, body mass index (BMI), asthma, as well as the presence of other co-morbid diseases.

Materials and Methods:

We used the Gastroesophageal Reflux Disease Questionnaire (GerdQ) for diagnosing GERD, based on a GerdQ score of 8 or more. Riyadh was divided into four quadrants, and from each area, a single shopping mall was chosen randomly to conduct our surveys. Data collected included age, sex, history of smoking, history of asthma or any other medical condition, dietary habits, monthly household income, history and frequency of heartburn, epigastric pain, regurgitation of food, nausea, sleep disturbance from heartburn, the use of common over-the-counter antacids for the control of their symptoms, and their height and weight.

Results:

Over a 4-week period from the 19 December 2012 to 17 January 2013, a total of 1265 individuals were included in the survey. The mean age was 29.97 ± 11.58 years. Females formed 67.81% of the respondents and 62.73% had one or more episodes of heartburn per week. Based on a cutoff GERDQ score of 8, the prevalence of GERD in the surveyed population was 45.4%. GERD was more prevalent in older individuals (mean age 31.9 vs. 30.0 years, P < 0.001) and in those with a higher BMI (27.29 vs. 26.31 kg/m², P = 0.02). There was no difference between males (45.43%) and females (45.13%) (P = 0.92); there was a trend of a higher prevalence in smokers (51.63% vs. 44.41%), but it did not reach statistical significance (P = 0.09).

Conclusion:

Symptoms suggestive of GERD as determined by the translated GerdQ are prevalent among this study population.