No abstract

Shigella is a major cause of morbidity, mortality, and growth retardation for children in developing countries. Emergence of antibiotic resistance among Shigellae demands the development of effective medicines. Previous studies found that the endogenous antimicrobial peptide LL-37 is down-regulated in the rectal epithelium of patients during shigellosis and that butyrate upregulates the expression of LL-37 in colonic epithelial cells in vitro and decreases severity of inflammation in experimental shigellosis. In this study, Shigella-infected dysenteric rabbits were treated with butyrate (0.14 mmol͞kg of body weight) twice daily for 3 days, and the expression levels of the rabbit homologue to LL-37, CAP-18, were monitored in the colon. Butyrate treatment resulted in (i) reduced clinical illness, severity of inflammation in the colon, and bacterial load in the stool, (ii) significant up-regulation of CAP-18 in the surface epithelium, and (iii) disappearance of CAP-18-positive cells in lamina propria. The active CAP-18 peptide was released in stool from its proform by butyrate treatment. In healthy controls, CAP-18 expression was localized predominantly to the epithelial surface of the colon. In infected rabbits, CAP-18 expression was localized to immune and inflammatory cells in the colon, whereas the ulcerated epithelium was devoid of CAP-18 expression. The combination of CAP-18 and butyrate was more efficient in killing Shigella in vitro than CAP-18 alone. Our findings indicate that oral butyrate treatment in shigellosis may be of clinical value because of induction of the endogenous cathelicidin CAP-18 in the colonic epithelium, stimulation of the release of the active peptide CAP-18, and promoting elimination of Shigella.antimicrobial peptides ͉ CAP-18 ͉ cathelicidin ͉ colon ͉ Shigella

The aim of this study is to show how Google's business model is concealed within Google Apps for Education (GAFE) as well as how such a bundle is perceived within one educational organisation, consisting of approximately 30 schools. The study consists of two parts: 1) a rhetorical analysis of Google policy documents and 2) an interview study in a Swedish educational organisation. By making an implicit demarcation between the two concepts (your) 'data' and (collected) 'information' Google can disguise the presence of a business model for online marketing and, at the same time, simulate the practices and ethics of a free public service institution. This makes it problematic for Swedish schools to implement Google Apps for Education, bearing in mind Google's surveillance practices for making profits on pupil's algorithmic identities. From a front end viewpoint of Google Apps for Education, the advantages of the services are evident to the users, and emerge in the study, whereas back end strategies are relatively hidden.

Homogenates of whole testis, isolated seminiferous tubules, testicular cytosol, conditioned media from seminiferous tubules obtained from intact or cryptorchid rats, as well as seminiferous tubules devoid of peritubular cells, showed high concentrations of interleukin-1 (IL-1). Cytosol from spleen showed low IL-1 activity, while no activity was found in cytosol from heart, kidney, prostate, ovary or liver. Interleukin-1 activity was not detected in spent medium from cultures of immature Sertoli cells (10-day-old rats) or from peritubular cells or in homogenates of interstitial cells from adult rats. Ultrogel AcA 44 gel chromatography and HPLC size exclusion chromatography exhibited a single peak of IL-1 activity corresponding to a relative molecular mass of 17,000-20,000 (Mr = 17-20 K). Similarly, chromatofocusing revealed only one peak of activity with an apparent isoelectric point of 5-6. It is concluded that the rat testis contains large amounts of an IL-1 alpha-like factor. The adult Sertoli cell or possibly germ cells are suggested as its primary source. Testicular IL-1-like activity is of particular interest in view of the intense cell proliferation during spermatogenesis, and the tendency to testicular relapse of acute lymphoblastic leukaemia.

Patients with AE exhibit enhanced expression of LL-37 in lesional skin compared with nonlesional, suggesting a role of LL-37 in AE that might be associated with the process of re-epithelialization.

Background-Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype. Methods and Results-This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110 KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29-41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=−0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (−10 beats per minute per added mutation; P<1.0×10). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted −7 beats per minute, P<0.0001. Conclusions-In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias. (Circ Arrhythm Electrophysiol. 2015;8:806-814.

Aims This study aimed to estimate the rate of cardiovascular (CV) events in the real world in patients at high risk of recurrent CV events similar to the FOURIER trial population. Methods and results A retrospective population-based cohort study was conducted using Swedish national registers from 1 July 2001 to 31 December 2015. Patients in the atherosclerotic cardiovascular disease (ASCVD) prevalent cohort met the FOURIER-like inclusion criteria, including treatment with high/moderate-intensity statins, on 1 July 2006. Additionally, two cohorts defined by diagnosis of incident ischaemic stroke (IS) and incident myocardial infarction (MI), meeting the FOURIER-like inclusion criteria were followed from date of diagnosis. Event rates were calculated for the hard major adverse cardiovascular events (MACE) composite: MI, IS, and CV death; and the ASCVD composite: MI, IS, unstable angina, coronary revascularization, and CV death. Approximately half of patients experienced a CV event (ASCVD composite) during follow-up. The MACE composite rates/100 person-years were 6.3, 11.9, and 12.3 in the ASCVD prevalent (n = 54 992), MI incident (n = 45 895), and IS incident (n = 36 134) cohorts, respectively. The ASCVD composite rates/100 person-years were 7.0, 21.7, and 12.9 in the ASCVD prevalent, MI incident, and IS incident cohorts, respectively. The multiple-event MACE composite rates/100 person-years were 8.5 (ASCVD prevalent cohort), 15.4 (MI incident cohort), and 14.4 (IS incident cohort). Conclusion In this real-world setting, CV event rates were high in all studied cohorts. In particular, the MACE composite rates were two to three times higher than in the FOURIER clinical trial, indicating a substantial disease burden despite treatment with moderate or high-intensity statins.

We have recently isolated an interleukin-1 (IL-1)-like factor from the rat testis, which originates from the seminiferous tubules and is a protein with an MW of 17,000 and a pI of 5-6. This paper reports on the appearance of the IL-1-like factor during postnatal development and investigates its cellular origin further. IL-1 activity was measured by a murine thymocyte proliferation assay. Very low IL-1 activity was present in culture medium conditioned by seminiferous tubules from rats aged 10 or 20 days. From 30 days of age, increasing amounts were detected, reaching a maximum level in adult animals (60-90 days). No IL-1 activity was found in medium conditioned by peritubular cells. Sertoli cell-enriched seminiferous tubules obtained from experimentally cryptorchid or from prenatally irradiated rats produced much higher levels of IL-1 activity than did those obtained from intact testes. IL-1 activity was detected in efferent duct fluid after ligation of the efferent ducts for 24 h, indicating that the IL-1-like factor was secreted into the tubular lumen. Low levels of IL-1 activity were detected in extracts of epididymal tissue and epididymal sperm, whereas ejaculated seminal plasma, seminal vesicle fluid and extracts of seminal vesicles (together with the coagulating glands) and ventral and dorsolateral prostate lacked IL-1 activity. Instead, seminal plasma inhibited testicular IL-1 activity dose-dependently without affecting cell viability in the thymocyte cultures. Although its biological function remains to be defined, our results indicate that the testicular IL-1-like factor is produced by Sertoli cells and that its appearance during development coincides with the initiation of active spermatogenesis in the rat testis.