Molecular and immunological characterization of profilin from mugwort pollen

In late summer in Europe, pollen of mugwort is one of the major sources of atopic allergens. No information about the complete molecular structure of any mugwort allergen has been published so far. Here we report the isolation and characterization of mugwort pollen cDNA clones coding for two isoforms of the panallergen profilin. Thirtysix percent of the mugwort allergic patients tested displayed IgE antibodies against natural and recombinant profilin, and no significant differences were observed in the IgEbinding properties of the isoforms. One profilin isoform was purified to homogeneity and detailed structural analysis indicated that the protein exists in solution as dimers and tetramers stabilized by sulfydryl and/or ionic interactions. Profilin monomers were detectable only after exposure of multimers to harsh denaturing conditions. Dimers and tetramers did not significantly differ in their ability to bind serum IgE from mugwort pollenallergic patients. However, oligomeric forms might have a higher allergenic potential than monomers because larger molecules would have additional epitopes for IgEmediated histamine release. Profilin isolated from mugwort pollen also formed multimers. Thus, oligomerization is not an artifact resulting from the recombinant production of the allergen. Inhibition experiments showed extensive IgE crossreactivity of recombinant mugwort profilin and profilin from various pollen and food extracts

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases

PURPOSE: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT) in patients with brain metastases treated with stereotactic radiosurgery (SRS) as their initial radiotherapy approach. MATERIALS AND METHODS: Patients with brain metastases treated with SRS from 2001 to 2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky performance status \u3e /=70, and life expectancy \u3e /=3 months. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with \u3e /=1-year WBRT-free survival (N = 104), and those who died or required salvage WBRT within 3 months of SRS (N = 56). Differences between these groups were assessed by univariate and multivariate analyses. RESULTS: Median survival for all patients was 11 months. Among patients with \u3e /=1-year WBRT-free survival, median survival was 33 months (12-107 months) with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p \u3c 0.05) included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden ( \u3c /=5 metastatic lesions). After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival. CONCLUSION: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone

Efficacy of Personal Protective Equipment to Prevent Environmental Infection of COVID-19 among Healthcare Workers: A Systematic Review

Background: Healthcare workers (HCWs) employed personal protective equipment (PPE) during the COVID-19 pandemic, crucial to protecting themselves from infection. To highlight the efficacy of PPE in preventing environmental infection among HCWs, a systematic review was conducted in line with PRISMA guidance. Methods: A search of the PubMed and Web of Science databases was conducted from January 2019 to April 2021 using pre-defined search terms. Articles were screened by three researchers. The approved papers were read in full and included in this review if relevance was mutually agreed upon. Data were extracted by study design and types of PPEs. Results: 47 of 108 identified studies met the inclusion criteria, with seven reviews and meta-analyses, seven cohort, nine case-control, fifteen cross-sectional studies, four before and after, four case series, and one modeling studies. Wearing PPE offered COVID-19 protection in HCWs but required adequate training. Wearing surgical masks provided improved protection over cloth masks, while the benefit of powered air-purifying respirators is less clear, as are individual gowns, gloves, and/or face shields. Conclusions: Wearing PPE, especially facial masks, is necessary among HCWs, while training in proper use of PPE is also important to prevent COVID-19 infection

Lifestyle-related diseases following the evacuation after the Fukushima Daiichi nuclear power plant accident: a retrospective study of Kawauchi Village with long-term follow-up

Objectives: Kawauchi Village lies 20 km west of the Fukushima Daiichi nuclear power plant. On 16 March 2011, evacuation was ordered due to the threat of radiological exposure, and was lifted in April 2012. In this study, we aimed to evaluate the predisaster and postdisaster health status of the Kawauchi Villagers, measured by routine yearly physical examinations. Methods: We analysed the annual health examination data of residents of Kawauchi Village from 2008 to 2013, as available from the Japanese National Health Insurance system. Data from 2011 were not available due to the disaster. Since the health data included the same participants repeatedly from year to year, the sample was non-independent and generalised estimated equation modelling was used. A predisaster time period (2008–2010) was categorised for comparison with postdisaster 2012 and 2013. The outcome examined was the prevalence of metabolic disease, and was adjusted for confounding factors. Results: Data for 20.6%–25.9% of the total residents were available in this period. In 2013, the prevalence of metabolic syndrome (from 17.0% to 25.2%, p<0.001), diabetes (from 11.3% to 17.0%, p<0.001), dyslipidaemia (from 43.2% to 56.7%, p<0.0001), hyperuricaemia (from 5.2% to 8.4%, p=0.006) and chronic kidney disease (from 16.1% to 26.7%, p<0.001) was found to be elevated significantly compared to predisaster years, while that of obesity or hypertension did not change. Conclusions: The present follow-up study for Kawauchi Village revealed an increase in lifestyle-related disease following the March 2011 disaster and subsequent evacuation, and this trend still continues 2 years later

A 30-Year Clinical and Magnetic Resonance Imaging Observational Study of Multiple Sclerosis and Clinically Isolated Syndromes

OBJECTIVE: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes. METHODS: One hundred thirty-two people presenting with a clinically isolated syndrome were prospectively recruited between 1984 and 1987, and followed up clinically and radiologically 1, 5, 10, 14, 20, and now 30 years later. All available notes and magnetic resonance imaging scans were reviewed, and MS was defined according to the 2010 McDonald criteria. RESULTS: Clinical outcome data were obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded Disability Status Scale (EDSS) scores were available in 107 participants, of whom 77 had MS; 32 (42%) remained fully ambulatory (EDSS scores ≤3.5), all of whom had relapsing-remitting MS (RRMS), 3 (4%) had RRMS and EDSS scores >3.5, 26 (34%) had secondary progressive MS (all had EDSS scores >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 received disease-modifying therapy. The strongest early predictors (within 5 years of presentation) of secondary progressive MS at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at 1 year. INTERPRETATION: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, whereas others ran a more favorable long-term course. These outcomes could, in part, be predicted by radiological findings from within 1 year of first presentation. ANN NEUROL 2020;87:63-74

Assessment of bladder filling during prostate cancer radiation therapy with ultrasound and cone-beam CT

Prostate cancer patients undergoing external beam radiation therapy (EBRT) benefit from a full bladder to decrease bowel and bladder toxicity. Ultrasound may offer a proxy metric for evaluation, sparing CBCT dosing. Patients were prospectively enrolled pre-simulation from January 2017 to February 2018. Bladder volume was evaluated prior to RT using US daily and CBCT for three daily treatments and then weekly unless otherwise indicated. 29 patients completed median 40 days of RT, resulting in 478 CBCT and 1,099 US bladder volumes. 21 patients were treated to intact glands and 8 to the post-prostatectomy bed. Median patient age was 70 years. Bladder volume on CBCT and US positively correlated (r = 0.85), with average bladder volume for all patients of 162 mL versus 149 mL, respectively. Bladder volume during treatment was consistently lower than the volume at CT simulation (153 mL vs 194 mL, p&lt;0.01) and progressively declined during treatment. Patients older than 70 years presented with lower average bladder volumes than those &lt; 70 years (122 mL vs 208 mL, respectively, p&lt;0.01). Patients with the highest agreement between CBCT and US (&lt;10% variability) had higher average bladder volumes (192 mL vs 120 mL, p=0.01). US was found to be an accurate measure of bladder volume and may be used to monitor daily bladder volumes in patients being treated with radiation for prostate cancer

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae

Automated Force Volume Image Processing for Biological Samples

Atomic force microscopy (AFM) has now become a powerful technique for investigating on a molecular level, surface forces, nanomechanical properties of deformable particles, biomolecular interactions, kinetics, and dynamic processes. This paper specifically focuses on the analysis of AFM force curves collected on biological systems, in particular, bacteria. The goal is to provide fully automated tools to achieve theoretical interpretation of force curves on the basis of adequate, available physical models. In this respect, we propose two algorithms, one for the processing of approach force curves and another for the quantitative analysis of retraction force curves. In the former, electrostatic interactions prior to contact between AFM probe and bacterium are accounted for and mechanical interactions operating after contact are described in terms of Hertz-Hooke formalism. Retraction force curves are analyzed on the basis of the Freely Jointed Chain model. For both algorithms, the quantitative reconstruction of force curves is based on the robust detection of critical points (jumps, changes of slope or changes of curvature) which mark the transitions between the various relevant interactions taking place between the AFM tip and the studied sample during approach and retraction. Once the key regions of separation distance and indentation are detected, the physical parameters describing the relevant interactions operating in these regions are extracted making use of regression procedure for fitting experiments to theory. The flexibility, accuracy and strength of the algorithms are illustrated with the processing of two force-volume images, which collect a large set of approach and retraction curves measured on a single biological surface. For each force-volume image, several maps are generated, representing the spatial distribution of the searched physical parameters as estimated for each pixel of the force-volume image