IgE-Mediated Hypersensitivity Reactions to Cannabis in Laboratory Personnel

Background: There have been sporadic reports of hypersensitivity reactions to plants of the Cannabinaceae family (hemp and hops), but it has remained unclear whether these reactions are immunologic or nonimmunologic in nature. Objective: We examined the IgE-binding and histamine-releasing properties of hashish and marijuana extracts by CAP-FEIA and a basophil histamine release test. Methods: Two workers at a forensic laboratory suffered from nasal congestion, rbinitis, sneezing and asthmatic symptoms upon occupational contact with hashish or marijuana, which they had handled frequently for 25 and 16 years, respectively. Neither patient had a history of atopic disease. Serum was analyzed for specific IgE antibodies to hashish or marijuana extract by research prototype ImmunoCAP, and histamine release from basophils upon exposure to hashish or marijuana extracts was assessed. Results were matched to those of 4 nonatopic and 10 atopic control subjects with no known history of recreational or occupational exposure to marijuana or hashish. Results: Patient 1 had specific IgE to both hashish and marijuana (CAP class 2), and patient 2 to marijuana only (CAP class 2). Controls proved negative for specific IgE except for 2 atopic individuals with CAP class 1 to marijuana and 1 other atopic individual with CAP class 1 to hashish. Stimulation of basophils with hashish or marijuana extracts elicited histamine release from basophils of both patients and 4 atopic control subjects. Conclusions: Our results suggest an IgE-related pathomechanism for hypersensitivity reactions to marijuana or hashish. Copyright (C) 2011 S. Karger AG, Base

Multi-tissue transcriptomic-informed in silico investigation of drugs for the treatment of dengue fever disease

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.Funding was provided by FEDER, Fundo Europeu de Desenvolvimento Regional funds, through the COMPETE 2020, Competitiveness and Internationalization Operational Programme (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Inovação, in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)

Absolutely stable proton and lowering the gauge unification scale

A unified model is constructed, based on flipped SU(5) in which the proton is absolutely stable. The model requires the existence of new leptons with masses of order the weak scale. The possibility that the unification scale could be extremely low is discussed

Estimation of PM10-bound As, Cd, Ni and Pb levels by means of statistical modelling: PLSR and ANN approaches

Air quality assessment regarding metals and metalloids using experimental measurements is expensive and time consuming due to the cost and time required for the analytical determination of the levels of these pollutants. According to the European Union (EU) Air Quality Framework Directive (Directive 2008/50/EC), other alternatives, such as objective estimation techniques, can be considered for ambient air quality assessment in zones and agglomerations where the level of pollutants is below a certain concentration value known as the lower assessment threshold. These conditions occur in urban areas in Cantabria (northern Spain). This work aims to estimate the levels of As, Cd, Ni and Pb in airborne PM10 at two urban sites in the Cantabria region (Castro Urdiales and Reinosa) using statistical models as objective estimation techniques. These models were developed based on three different approaches: partial least squares regression (PLSR), artificial neural networks (ANNs) and an alternative approach consisting of principal component analysis (PCA) coupled with ANNs (PCA-ANN). Additionally, these models were externally validated using previously unseen data. The results show that the models developed in this work based on PLSR and ANNs fulfil the EU uncertainty requirements for objective estimation techniques and provide an acceptable estimation of the mean values. As a consequence, they could be considered as an alternative to experimental measurements for air quality assessment regarding the aforementioned pollutants in the study areas while saving time and resources.The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the Project CMT2010-16068. The authors also thank the Regional Environment Ministry of the Cantabria Government for providing the PM10 samples at the Castro Urdiales and Reinosa sites

A Magnetically Driven Disk Wind in the Inner Disk of PDS 70

PDS 70 is so far the only young disk where multiple planets have been detected by direct imaging. The disk has a large cavity when seen at submillimeter and near-infrared wavelengths, which hosts two massive planets. This makes PDS 70 the ideal target to study the physical conditions in a strongly depleted inner disk shaped by two giant planets, and in particular to test whether disk winds can play a significant role in its evolution. Using X-Shooter and HARPS spectra, we detected for the first time the wind-tracing [O i] 6300 Å line, and confirm the low-moderate value of mass-accretion rate in the literature. The [O i] line luminosity is high with respect to the accretion luminosity when compared to a large sample of disks with cavities in nearby star-forming regions. The FWHM and blueshifted peak of the [O i] line suggest an emission in a region very close to the star, favoring a magnetically driven wind as the origin. We also detect wind emission and high variability in the He i 10830 Å line, which is unusual for low accretors. We discuss that, although the cavity of PDS 70 was clearly carved out by the giant planets, the substantial inner-disk wind could also have had a significant contribution to clearing the inner disk

Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season

<p>Abstract</p> <p>Background</p> <p>In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people. In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season. To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection was performed.</p> <p>Methods</p> <p>The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1) 2009 virus infection. Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season.</p> <p>Results</p> <p>A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1) 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011. During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years. In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years. During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season. Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02), and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005).</p> <p>Conclusions</p> <p>The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward seasonal patterns was seen, with a peak in mortality in the elderly, i.e. ≥ 75 years of age.</p

Is there an impact of public smoking bans on self-reported smoking status and exposure to secondhand smoke?

<p>Abstract</p> <p>Background</p> <p>Implementation of smoke free policies has potentially substantial effects on health by reducing secondhand smoke exposure. However little is known about whether the introduction of anti-smoking legislation translates into decreased secondhand smoke exposure. We examined whether smoking bans impact rates of secondhand smoke exposure in public places and rates of complete workplace smoking restriction.</p> <p>Methods</p> <p>Canadian Community Health Survey was used to obtain secondhand smoking exposure rates in 15 Ontario municipalities. Data analysis included descriptive summaries and 95% confidence intervals were calculated and compared across groups</p> <p>Results</p> <p>Across all studied municipalities, secondhand smoke exposure in public places decreased by 4.7% and workplace exposure decreased by 2.3% between the 2003 and 2005 survey years. The only jurisdiction to implement a full ban from no previous ban was also the only setting that experienced significant decreases in both individual exposure to secondhand smoke in a public place (-17.3%, 95% CI -22.8, -11.8) and workplace exposure (-18.1%, 95% CI -24.9, -11.3). Exposures in vehicles and homes declined in almost all settings over time.</p> <p>Conclusions</p> <p>Implementation of a full smoking ban was associated with the largest decreases in secondhand smoke exposure while partial bans and changes in existing bans had inconsistent effects. In addition to decreasing exposure in public places as would be expected from legislation, bans may have additional benefits by decreasing rates of current smokers and decreasing exposures to secondhand smoke in private settings.</p

Origin and Epidemiological History of HIV-1 CRF14_BG

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Users must also make clear the license terms under which the work was published. CC BY Licence: http://creativecommons.org/licenses/by/4.0/Background: CRF14_BG isolates, originally found in Spain, are characterized by CXCR4 tropism and rapid disease progression. This study aimed to identify the origin of CRF14_BG and reconstruct its epidemiological history based on new isolates from Portugal.Methodology/Principal Findings: C2V3C3 env gene sequences were obtained from 62 samples collected in 1993–1998 from Portuguese HIV-1 patients. Full-length genomic sequences were obtained from three patients. Viral subtypes, diversity, divergence rate and positive selection were investigated by phylogenetic analysis. The molecular structure of the genomes was determined by bootscanning. A relaxed molecular clock model was used to date the origin of CRF14_BG. Geno2pheno was used to predict viral tropism. Subtype B was the most prevalent subtype (45 sequences; 73%) followed by CRF14_BG (8; 13%), G (4; 6%), F1 (2; 3%), C (2; 3%) and CRF02_AG (1; 2%). Three CRF14_BG sequences were derived from 1993 samples. Near full-length genomic sequences were strongly related to the CRF14_BG isolates from Spain. Genetic diversity of the Portuguese isolates was significantly higher than the Spanish isolates (0.044 vs 0.014, P,0.0001). The mean date of origin of the CRF14_BG cluster was estimated to be 1992 (range, 1989 and 1996) based on the subtype G genomic region and 1989 (range, 1984–1993) based on the subtype B genomic region. Most CRF14_BG strains (78.9%) were predicted to be CXCR4. Finally, up to five amino acids were under selective pressure in subtype B V3 loop whereas only one was found in the CRF14_BG cluster.Conclusions: CRF14_BG emerged in Portugal in the early 1990 s soon after the beginning of the HIV-1 epidemics, spread to Spain in late 1990 s as a consequence of IVDUs migration and then to the rest of Europe. CXCR4 tropism is a general characteristic of this CRF that may have been selected for by escape from neutralizing antibody response

Chemotherapy-Induced Late Transgenerational Effects in Mice

To our knowledge, there is no report on long-term reproductive and developmental side effects in the offspring of mothers treated with a widely used chemotherapeutic drug such as doxorubicin (DXR), and neither is there information on transmission of any detrimental effects to several filial generations. Therefore, the purpose of the present paper was to examine the long-term effects of a single intraperitoneal injection of DXR on the reproductive and behavioral performance of adult female mice and their progeny. C57BL/6 female mice (generation zero; G0) were treated with either a single intraperitoneal injection of DXR (G0-DXR) or saline (G0-CON). Data were collected on multiple reproductive parameters and behavioral analysis for anxiety, despair and depression. In addition, the reproductive capacity and health of the subsequent six generations were evaluated. G0-DXR females developed despair-like behaviors; delivery complications; decreased primordial follicle pool; and early lost of reproductive capacity. Surprisingly, the DXR-induced effects in oocytes were transmitted transgenerationally; the most striking effects being observed in G4 and G6, constituting: increased rates of neonatal death; physical malformations; chromosomal abnormalities (particularly deletions on chromosome 10); and death of mothers due to delivery complications. None of these effects were seen in control females of the same generations. Long-term effects of DXR in female mice and their offspring can be attributed to genetic alterations or cell-killing events in oocytes or, presumably, to toxicosis in non-ovarian tissues. Results from the rodent model emphasize the need for retrospective and long-term prospective studies of survivors of cancer treatment and their offspring

Are firms exporting to China and India different from other exporters?

This chapter asks if and why advanced countries differ in their ability to export to China and India. To this end we exploit a newly collected, comparable cross-country dataset (EFIGE) obtained from a survey of 15,000 manufacturing firms in Austria, France, Germany, Hungary, Italy, Spain and the United Kingdom. The EFIGE dataset contains detailed information on firms’ international activities as well as firm characteristics such as size and productivity, governance and management structure, workforce, innovation and research activity. We study both the extensive and intensive margins of exports and identify firm characteristics that are positively or negatively correlated wiThexporting activity tout court and wiThexporting to China and India conditional on being an exporter. We confirm previous rich evidence and show that larger, more productive, and more innovative firms are more likely to become exporters and export more. We also provide some new evidence on the role of governance and management: while there does not seem to be a strong negative effect of family ownership, we find that a higher percentage of family management reduces a firm’s export propensity and export volumes. When we turn to exports to China and India, we find that firms exporting there must be on average larger, more productive, and more innovative than firms exporting elsewhere