Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study.

OBJECTIVE: To determine the incidence of and mortality from bullous pemphigoid and pemphigus vulgaris in the United Kingdom. DESIGN: Retrospective historical cohort study. SETTING: Computerised medical records from the health improvement network, a large population based UK general practice database. PARTICIPANTS: Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age, sex, and practice matched controls. MAIN OUTCOME MEASURES: Incidence and mortality compared with the control population by calendar period, age group, sex, geographical region, and degree of social deprivation. RESULTS: 869 people with bullous pemphigoid and 138 people with pemphigus vulgaris were identified. The median age at presentation for bullous pemphigoid was 80 (range 23-102) years, and 534 (61%) patients were female. The median age at presentation for pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female. Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence of bullous pemphigoid increased over time; the average yearly increase was 17% (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0 to 1.2) occurred. The risk of death for patients with bullous pemphigoid was twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2). CONCLUSIONS: Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The reasons for the changes in incidence are not clearly understood but have implications for identifying causative factors. Both disorders are associated with a high risk of death. Previous estimates may have underestimated the risk of death associated with these diseases

Whey Protein Augments Leucinemia and Post-Exercise p70S6K1 Activity Compared to a Hydrolysed Collagen Blend When in Recovery From Training With Low Carbohydrate Availability

We examined the effects of whey versus collagen protein on skeletal muscle cell signalling responses associated with mitochondrial biogenesis and protein synthesis in recovery from an acute training session completed with low carbohydrate (CHO) availability. In a repeated measures design (after adhering to a 36-h exercise-dietary intervention to standardise pre-exercise muscle glycogen), eight males completed a 75-min non-exhaustive cycling protocol and consumed 22 g of a hydrolysed collagen blend (COLLAGEN) or whey (WHEY) protein 45 min prior to exercise, 22 g during exercise and 22 g immediately post-exercise. Exercise decreased (P0.05) was observed for p53, Parkin and Beclin1 mRNA. Exercise suppressed (P<0.05) p70S6K1 activity in both conditions immediately post-exercise (≈ 25 fmol.min-1.mg-1). Post-exercise feeding increased p70S6K1 activity at 1.5 h post-exercise (P<0.05), the magnitude of which was greater (P <0.05) in WHEY (180 ± 105 fmol.min-1.mg-1) versus COLLAGEN (73 ± 42 fmol.min-1.mg-1). We conclude that protein composition does not modulate markers of mitochondrial biogenesis when in recovery from a training session deliberately completed with low CHO availability. In contrast, whey protein augments post-exercise p70S6K activity compared with hydrolysed collagen, as likely mediated via increased leucine availability

Are pediatric Open Access journals promoting good publication practice? An analysis of author instructions

<p>Abstract</p> <p>Background</p> <p>Several studies analyzed whether conventional journals in general medicine or specialties such as pediatrics endorse recommendations aiming to improve publication practice. Despite evidence showing benefits of these recommendations, the proportion of endorsing journals has been moderate to low and varied considerably for different recommendations. About half of pediatric journals indexed in the Journal Citation Report referred to the Uniform Requirements for Manuscripts of the International Committee of Medical Journal Editors (ICMJE) but only about a quarter recommended registration of trials. We aimed to investigate to what extent pediatric open-access (OA) journals endorse these recommendations. We hypothesized that a high proportion of these journals have adopted recommendations on good publication practice since OA electronic publishing has been associated with a number of editorial innovations aiming at improved access and transparency.</p> <p>Methods</p> <p>We identified 41 journals publishing original research in the subject category "Health Sciences, Medicine (General), Pediatrics" of the Directory of Open Access Journals <url>http://www.doaj.org</url>. From the journals' online author instructions we extracted information regarding endorsement of four domains of editorial policy: the Uniform Requirements for Manuscripts, trial registration, disclosure of conflicts of interest and five major reporting guidelines such as the CONSORT (Consolidated Standards of Reporting Trials) statement. Two investigators collected data independently.</p> <p>Results</p> <p>The Uniform Requirements were mentioned by 27 (66%) pediatric OA journals. Thirteen (32%) required or recommended trial registration prior to publication of a trial report. Conflict of interest policies were stated by 25 journals (61%). Advice about reporting guidelines was less frequent: CONSORT was referred to by 12 journals (29%) followed by other reporting guidelines (MOOSE, PRISMA or STARD) (8 journals, 20%) and STROBE (3 journals, 7%). The EQUATOR network, a platform of several guideline initiatives, was acknowledged by 4 journals (10%).</p> <p>Journals published by OA publishing houses gave more guidance than journals published by professional societies or other publishers.</p> <p>Conclusions</p> <p>Pediatric OA journals mentioned certain recommendations such as the Uniform Requirements or trial registration more frequently than conventional journals; however, endorsement is still only moderate. Further research should confirm these exploratory findings in other medical fields and should clarify what the motivations and barriers are in implementing such policies.</p

The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption

Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification

Orally available Mn porphyrins with superoxide dismutase and catalase activities

Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize reactive oxygen and nitrogen species, which have been implicated in the pathogenesis of many serious diseases. Both classes of mimetic are protective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins, have been shown to be orally bioavailable. In this study, EUK-418 and several new analogs (the EUK-400 series) were synthesized and shown to exhibit superoxide dismutase, catalase, and peroxidase activities in vitro. Some also protected PC12 cells against staurosporine-induced cell death. All EUK-400 compounds were stable in simulated gastric fluid, and most were substantially more lipophilic than the salen Mn complexes EUK-189 and EUK-207, which lack oral activity. Pharmacokinetics studies demonstrate the presence of all EUK-400 series compounds in the plasma of rats after oral administration. These EUK-400 series compounds are potential oral therapeutic agents for cellular damage caused by oxidative stress

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051