Patient-reported treatment response in chronic graft-versus-host disease

Chronic graft-versus-host disease (GvHD) treatment response is assessed using National Institutes of Health (NIH) Consensus Criteria in clinical trials, and by clinician assessment in routine practice. Patient-reported treatment response is central to the experience of chronic GvHD manifestations as well as treatment benefit and toxicity, but how they correlate with clinician- or NIH-responses has not been well-studied. We aimed to characterize 6-month patientreported response, determine associated chronic GvHD baseline organ features and changes, and evaluate which patientreported quality of life and chronic GvHD symptom burden measures correlated with patient-reported response. From two nationally representative Chronic GVHD Consortium prospective observational studies, 382 subjects were included in this analysis. Patient and clinician responses were categorized as improved (completely gone, very much better, moderately better, a little better) versus not improved (about the same, a little worse, moderately worse, very much worse). At six months, 270 (71%) patients perceived chronic GvHD improvement, while 112 (29%) perceived no improvement. Patient-reported response had limited correlation with either clinician-reported (kappa 0.37) or NIH chronic GvHD response criteria (kappa 0.18). Notably, patient-reported response at six months was significantly associated with subsequent failure-free survival. In multivariate analysis, NIH responses in eye, mouth, and lung had significant association with 6-month patient-reported response, as well as a change in Short Form 36 general health and role physical domains and Lee Symptom Score skin and eye changes. Based on these findings, patient-reported responses should be considered as an important complementary endpoint in chronic GvHD clinical trials and drug development

Measuring fitness of Kenyan children with polyparasitic infections using the 20-meter shuttle run test as a morbidity metric.

BACKGROUND: To date, there has been no standardized approach to the assessment of aerobic fitness among children who harbor parasites. In quantifying the disability associated with individual or multiple chronic infections, accurate measures of physical fitness are important metrics. This is because exercise intolerance, as seen with anemia and many other chronic disorders, reflects the body's inability to maintain adequate oxygen supply (VO(2) max) to the motor tissues, which is frequently linked to reduced quality-of-life in terms of physical and job performance. The objective of our study was to examine the associations between polyparasitism, anemia, and reduced fitness in a high risk Kenyan population using novel implementation of the 20-meter shuttle run test (20mSRT), a well-standardized, low-technology physical fitness test. METHODOLOGY/PRINCIPAL FINDINGS: Four villages in coastal Kenya were surveyed during 2009-2010. Children 5-18 years were tested for infection with Schistosoma haematobium (Sh), malaria, filaria, and geohelminth infections by standard methods. After anthropometric and hemoglobin testing, fitness was assessed with the 20 mSRT. The 20 mSRT proved easy to perform, requiring only minimal staff training. Parasitology revealed high prevalence of single and multiple parasitic infections in all villages, with Sh being the most common (25-62%). Anemia prevalence was 45-58%. Using multiply-adjusted linear modeling that accounted for household clustering, decreased aerobic capacity was significantly associated with anemia, stunting, and wasting, with some gender differences. CONCLUSIONS/SIGNIFICANCE: The 20 mSRT, which has excellent correlation with VO(2), is a highly feasible fitness test for low-resource settings. Our results indicate impaired fitness is common in areas endemic for parasites, where, at least in part, low fitness scores are likely to result from anemia and stunting associated with chronic infection. The 20 mSRT should be used as a common metric to quantify physical fitness and compare sub-clinical disability across many different disorders and community settings

Using molecular techniques for rapid detection of Salmonella serovars in frozen chicken and chicken products collected from Riyadh, Saudi Arabia

The current study was aimed to investigate the incidence of different Salmonella serovars in chicken products either from local or imported source. A total of 152 samples of chicken and chicken productswere collected from different retail establishment markets in Riyadh, KSA including 38 local whole frozen chickens, 62 imported whole frozen chickens, 22 whole poultry eggs and 30 local chicken cuts samples and examined by standard microbiological techniques (SMT). Salmonella isolation revealed a total percentage of 5.92%; chicken cuts revealed a high incidence among the examined samples (10%), followed by local frozen chickens and imported frozen chicken samples with incidence of 7.89 and 4.83%, respectively. For this experiment, the whole chicken eggs were negative for Salmonella species by SMT. Salmonella enteritidis was dominating among the recovered Salmonella serovars, followed bySalmonella typhimurium, while only two strains of Salmonella agona and Salmonella newport were isolated. The PCR assay combined with Rappaport- Vassiliadis (RV) selective broth (PCR-RV) for the detection of Salmonella species in the collected field samples revealed the same positive samples directly from the imported frozen chickens and whole chicken eggs which gave negative results by SMT. Thus PCR-RV technique is rapid, time saving and applicable to detect Salmonella serovarsdirectly from chicken samples

Multiplex polymerase chain reaction for detection and characterization of shiga toxigenic Escherichia coli (STEC)

Escherichia coli is ubiquitous in the cow's environment that is contaminated by feces, and it is also a frequent cause of bovine mastitis. Thus, the present study was targeted at the rapid detection and characterization of shiga toxigenic E. coli (STEC) in bovine fecal and milk samples. Twenty two strains of E. coli (39.29%) were isolated from 56 diarrheic calves, while only 5 strains (20.83%) were isolated from apparently normal contact calves. Moreover, 20 strains of E. coli (25%) were isolated from milk samples collected from 80 animals suffering from mastitis and subclinical mastitis. E. coli serovars yielded from bacteriological examination of milk samples were similar to that of fecal samples. Serogroup-specific multiplex polymerase chain reaction (PCR) assay could detect all the bacteriologically positive samples as well as 4 strains (7.98%), O157:H7 and 3 strains (5.36%), O111 from diarrheic calves and 2 strains (8.33%), O111 from normal calves. Such samples were proved to be negative by bacteriological examination. Multiplex PCR for detection of genes encoding accessorySTEC virulence factors, such as shiga toxin type-2 (stx2) and intimin gene (eaeA) revealed the specificity of such gene to O157:H7 serovars and small number of other sero-groups

The estrogen-induced miR-19 downregulates secretory leucoprotease inhibitor expression in monocytes

Compared to females, males are more susceptible to acute viral and other respiratory tract infections that display greater severity and higher mortality. In contrast, females tend to fare worse with chronic inflammatory diseases. Circulating 17β-estradiol (E2) is a female-specific factor that may influence the progression of human lung diseases. Here we hypothesize that E2 modulates the inflammatory response of monocytes through microRNA (miRNA)-based modulation of secretory leucoprotease inhibitor (SLPI), an antiprotease with immunomodulatory effects. Monocytic cells were treated ± E2, and differentially expressed miRNAs were identified using PCR profiling. Cells were transfected with miRNA mimics or antimiRs and SLPI mRNA and protein levels were quantified. Luciferase activity assay using wildtype and ΔmiR-19a/b-SLPI3'UTR reporter constructs and chromatin immunoprecipitation on E2-treated monocytes were performed. E2 downregulated SLPI and upregulated miR-19 expression in monocytes. Transfection with premiR-19b reduced SLPI mRNA and protein levels and this effect was abrogated using antimiRs against miR-19b. miR-19b directly binds the SLPI 3'UTR. The mechanism responsible for E2-mediated upregulation of miR-19 occurs via increased MIR17HG promoter activity mediated by c-MYC. Overall E2 decreases SLPI expression in human monocytic cells, via changes in miRNA expression and highlights the potential for estrogen to modulate the innate immune system

Carbon Sequestration in Biogenic Magnesite and Other Magnesium Carbonate Minerals

The stability and longevity of carbonate minerals make them an ideal sink for surplus atmospheric carbon dioxide. Biogenic magnesium carbonate mineral precipitation from the magnesium-rich tailings generated by many mining operations could offset net mining greenhouse gas emissions, while simultaneously giving value to mine waste products. In this investigation, cyanobacteria in a wetland bioreactor enabled the precipitation of magnesite (MgCO3), hydromagnesite [Mg5(CO3)4(OH)2·4H2O], and dypingite [Mg5(CO3)4(OH)2·5H2O] from a synthetic wastewater comparable in chemistry to what is produced by acid leaching of ultramafic mine tailings. These precipitates occurred as micrometer-scale mineral grains and microcrystalline carbonate coatings that entombed filamentous cyanobacteria. This provides the first laboratory demonstration of low temperature, biogenic magnesite precipitation for carbon sequestration purposes. These findings demonstrate the importance of extracellular polymeric substances in microbially enabled carbonate mineral nucleation. Fluid composition was monitored to determine carbon sequestration rates. The results demonstrate that up to 238 t of CO2 could be stored per hectare of wetland/year if this method of carbon dioxide sequestration was implemented at an ultramafic mine tailing storage facility. The abundance of tailings available for carbonation and the anticipated global implementation of carbon pricing make this method of mineral carbonation worth further investigation

Carboxylate Adsorption on Rutile TiO2(100): Role of Coulomb Repulsion, Relaxation, and Steric Hindrance

Understanding the adsorption and photoactivity of acetic acid and trimethyl acetic acid on TiO2 surfaces is important for improving the performance of photocatalysts and dye-sensitized solar cells. Here we present a structural study of adsorption on rutile TiO2(100)-1 × 1 and -1 × 3 using Scanning Tunnelling Microscopy and Density Functional Theory calculations. Exposure of both terminations to acetic acid gives rise to a ×2 periodicity in the [001] direction (i.e., along Ti rows), with a majority ordered c(2 × 2) phase in the case of the 1 × 1 termination. The DFT calculations suggest that the preference of c(2 × 2) over the 2 × 1 periodicity found for TiO2(110)-1 × 1 can be attributed to an increase in interadsorbate Coulomb repulsion. Exposure of TiO2(100)-1 × 1 and -1 × 3 to trimethyl acetic acid gives rise to largely disordered structures due to steric effects, with quasi-order occurring in small areas and near step edges where these effects are reduced