Electron microscopic and biochemical characterization of Fraction 1 protein

High resolution electron microscopy of Fraction I protein from plant leave

Impact of Tocilizumab Monotherapy on Clinical and Patient-Reported Quality-of-Life Outcomes in Patients with Rheumatoid Arthritis

INTRODUCTION: Tocilizumab (TCZ) monotherapy has been proven as an effective treatment for rheumatoid arthritis (RA) in clinical trials. However, there are limited data available regarding the effectiveness of TCZ monotherapy in real-world clinical settings in the United States. The objective of this study was to evaluate the impact of TCZ monotherapy on disease activity and patient-reported outcomes (PROs) in a US-based observational cohort of patients with RA seen in routine clinical practice. METHODS: Eligible patients had active RA, no prior use of TCZ, and initiated TCZ as monotherapy. Changes in disease activity and PROs were assessed 1 year after TCZ initiation for the overall cohort and stratified by number of prior tumor necrosis factor inhibitors (TNFis; 0, 1, or \u3e /=2). Primary outcomes were change in Clinical Disease Activity Index (CDAI); change in patient global disease activity, pain, fatigue; and the proportions of patients with improvement in modified Health Assessment Questionnaire (mHAQ), morning stiffness, and EQ-5D. RESULTS: Of 255 eligible TCZ monotherapy initiators, 9.4% were TNFi naive, 36.5% had one prior TNFi, and 54.1% had \u3e /=2 prior TNFis. Clinical and PRO measures indicated that patients were substantially impacted by their disease at baseline. The median decrease in CDAI from baseline to 1 year was 9.8 and median patient global and pain scores improved by 10 mm, indicative of clinically meaningful improvement; the median fatigue score improved by 5 mm. Approximately 26% of patients reported clinically meaningful improvement in mHAQ, 54% experienced improvement in morning stiffness, and 20% to 36% experienced improvement in EQ-5D domains (walking, self-care, usual activities, pain/discomfort, and anxiety/depression). Improvements were similar across TNFi groups. CONCLUSIONS: Patients with active, refractory RA who initiated TCZ monotherapy experienced improvements in both composite disease activity scores and PROs at 1 year, regardless of prior TNFi exposure. FUNDING: Corrona, LLC and Genentech

Assessment of asthma control and asthma exacerbations in the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) observational cohort

Patients with severe or difficult-to-treat asthma account for substantial asthma morbidity, mortality, and healthcare burden despite comprising only a small proportion of the total asthma population. TENOR, a multicenter, observational, prospective cohort study was initiated in 2001. It enrolled 4,756 adults, adolescents and children with severe or difficult-to-treat asthma who were followed semi-annually and annually for three years, enabling insight to be gained into this understudied population. A broad range of demographic, clinical, and patient self-reported assessments were completed during the follow-up period. Here, we present key findings from the TENOR registry in relation to asthma control and exacerbations, including the identification of specific subgroups found to be at particularly high-risk. Identification of the factors and subgroups associated with poor asthma control and increased risk of exacerbations can help physicians design individual asthma management, and improve asthma-related health outcomes for these patients

Mortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis

PURPOSE: Individuals with X-linked myotubular myopathy (XLMTM) who survive infancy require extensive supportive care, including ventilator assistance, wheelchairs and feeding tubes. Half die before 18 months of age. We explored respiratory support and associated mortality risk in RECENSUS, particularly among patients ≤5 years old who received respiratory support at birth; this subgroup closely matches patients in the ASPIRO trial of gene therapy for XLMTM. // DESIGN: RECENSUS is an international, retrospective study of patients with XLMTM. Descriptive and time-to-event analyses examined survival on the basis of age, respiratory support, tracheostomy use, predicted mutational effects and life-sustaining care. // RESULTS: Outcomes for 145 patients were evaluated. Among 126 patients with respiratory support at birth, mortality was 47% overall and 59% among those ≤5 years old. Median survival time was shorter for patients ≤5 years old than for those >5 years old (2.2 years (IQR 0.7-5.6) vs 30.2 years (IQR 19.4-30.2)). The most common cause of death was respiratory failure (66.7%). Median survival time was longer for patients with a tracheostomy than for those without (22.8 years (IQR 8.7-30.2) vs 1.8 years (IQR 0.2-not estimable)). The proportion of patients living without a tracheostomy was 50% at age 6 months and 28% at age 2 years. Median survival time was longer with provision of life-sustaining care than without (19.4 years (IQR 3.1-not estimable) vs 0.2 years (IQR 0.1-2.1)). CONCLUSIONS: High mortality, principally due to respiratory failure, among patients with XLMTM ≤5 years old despite respiratory support underscores the need for early diagnosis, informed decision-making and disease-modifying therapies

Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-to-Target Approach to Care of US Patients With Rheumatoid Arthritis

OBJECTIVE: To assess the feasibility and efficacy of implementing a treat-to-target approach versus usual care in a US-based cohort of rheumatoid arthritis patients. METHODS: In this behavioral intervention trial, rheumatology practices were cluster-randomized to provide treat-to-target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score \u3e 10) were followed for 12 months. Both treat-to-target and usual care patients were seen every 3 months. Treat-to-target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score \u3e 10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score \u3e 10, and achievement of low disease activity (LDA; CDAI score \u3c /=10) by an intent-to-treat analysis. RESULTS: A total of 14 practice sites per study arm were included (246 patients receiving treat-to-target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat-to-target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat-to-target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat-to-target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration. CONCLUSION: This study is the first to examine the feasibility and efficacy of a treat-to-target approach in typical US rheumatology practice. Treat-to-target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified

Variable Incidence of Spiroplasma Infections in Natural Populations of Drosophila Species

Spiroplasma is widespread as a heritable bacterial symbiont in insects and some other invertebrates, in which it sometimes acts as a male-killer and causes female-biased sex ratios in hosts. Besides Wolbachia, it is the only heritable bacterium known from Drosophila, having been found in 16 of over 200 Drosophila species screened, based on samples of one or few individuals per species. To assess the extent to which Spiroplasma infection varies within and among species of Drosophila, intensive sampling consisting of 50–281 individuals per species was conducted for natural populations of 19 Drosophila species. Infection rates varied among species and among populations of the same species, and 12 of 19 species tested negative for all individuals. Spiroplasma infection never was fixed, and the highest infection rates were 60% in certain populations of D. hydei and 85% in certain populations of D. mojavensis. In infected species, infection rates were similar for males and females, indicating that these Spiroplasma infections do not confer a strong male-killing effect. These findings suggest that Spiroplasma has other effects on hosts that allow it to persist, and that environmental or host variation affects transmission or persistence leading to differences among populations in infection frequencies

Diversity of Free-Living Environmental Bacteria and Their Interactions With a Bactivorous Amoeba

A small subset of bacteria in soil interact directly with eukaryotes. Which ones do so can reveal what is important to a eukaryote and how eukaryote defenses might be breached. Soil amoebae are simple eukaryotic organisms and as such could be particularly good for understanding how eukaryote microbiomes originate and are maintained. One such amoeba, Dictyostelium discoideum, has both permanent and temporary associations with bacteria. Here we focus on culturable bacterial associates in order to interrogate their relationship with D. discoideum. To do this, we isolated over 250 D. discoideum fruiting body samples from soil and deer feces at Mountain Lake Biological Station. In one-third of the wild D. discoideum we tested, one to six bacterial species were found per fruiting body sorus (spore mass) for a total of 174 bacterial isolates. The remaining two-thirds of D. discoideum fruiting body samples did not contain culturable bacteria, as is thought to be the norm. A majority (71.4%) of the unique bacterial haplotypes are in Proteobacteria. The rest are in either Actinobacteria, Bacteriodetes, or Firmicutes. The highest bacterial diversity was found in D. discoideum fruiting bodies originating from deer feces (27 OTUs), greater than either of those originating in shallow (11 OTUs) or in deep soil (4 OTUs). Rarefaction curves and the Chao1 estimator for species richness indicated the diversity in any substrate was not fully sampled, but for soil it came close. A majority of the D. discoideum-associated bacteria were edible by D. discoideum and supported its growth (75.2% for feces and 81.8% for soil habitats). However, we found several bacteria genera were able to evade phagocytosis and persist in D. discoideum cells through one or more social cycles. This study focuses not on the entire D. discoideum microbiome, but on the culturable subset of bacteria that have important eukaryote interactions as prey, symbionts, or pathogens. These eukaryote and bacteria interactions may provide fertile ground for investigations of bacteria using amoebas to gain an initial foothold in eukaryotes and of the origins of symbiosis and simple microbiomes

Intramucosal adenocarcinoma of the ileum originated 40 years after ileosigmoidostomy

<p>Abstract</p> <p>Background</p> <p>Small bowel adenocarcinomas (SBAs) are rare carcinomas. They are asymptomatic and usually neither endoscopy nor contrast studies are performed for screening</p> <p>Case presentation</p> <p>A 72-year-old Japanese male had a positive fecal occult blood test at a regular check-up in 2006. He suffered appendicitis and received an ileosigmoidostomy in 1966. A colonoscopy revealed an irregular mucosal lesion with an unclear margin at the ileum side of the anastomosis. A mucosal biopsy specimen showed adenocarcinoma histopathologically. Excision of the anastomosis was performed for this patient. The resected specimen showed a flat mucosal lesion with a slight depression at the ileum adjacent to the anastomosis. Histological examination revealed a well differentiated intramucosal adenocarcinoma (adenocarcinoma in situ). Immunohistological staining demonstrated the overexpression of p53 protein in the adenocarcinoma.</p> <p>Conclusion</p> <p>Adenocarcinoma of the ileum at such an early stage is a very rare event. In this case, there is a possibility that the ileosigmoidostomy resulted in a back flow of colonic stool to the ileum that caused the carcinogenesis of the small intestine.</p

Cyanobacterial Cell Lineage Analysis of the Spatiotemporal hetR Expression Profile during Heterocyst Pattern Formation in Anabaena sp. PCC 7120

Diazotrophic heterocyst formation in the filamentous cyanobacterium, Anabaena sp. PCC 7120, is one of the simplest pattern formations known to occur in cell differentiation. Most previous studies on heterocyst patterning were based on statistical analysis using cells collected or observed at different times from a liquid culture, which would mask stochastic fluctuations affecting the process of pattern formation dynamics in a single bacterial filament. In order to analyze the spatiotemporal dynamics of heterocyst formation at the single filament level, here we developed a culture system to monitor simultaneously bacterial development, gene expression, and phycobilisome fluorescence. We also developed micro-liquid chamber arrays to analyze multiple Anabaena filaments at the same time. Cell lineage analyses demonstrated that the initial distributions of hetR::gfp and phycobilisome fluorescence signals at nitrogen step-down were not correlated with the resulting distribution of developed heterocysts. Time-lapse observations also revealed a dynamic hetR expression profile at the single-filament level, including transient upregulation accompanying cell division, which did not always lead to heterocyst development. In addition, some cells differentiated into heterocysts without cell division after nitrogen step-down, suggesting that cell division in the mother cells is not an essential requirement for heterocyst differentiation