The IUIS Allergen Nomenclature Sub‐Committee, under the auspices of the World Health Organization and the International Union of Immunological Societies, maintains the systematic nomenclature of ...allergenic proteins and publishes a database of approved allergen names on its Web site, www.allergen.org. In this paper, we summarize updates of allergen names approved at the meetings of the committee in 2011 through 2013. These changes reflect recent progress in identification, cloning, and sequencing of allergens. The goals of this update were to increase consistency in the classification of allergens, isoallergens, and variants and in the incorporation of the evolutionary classification of proteins into allergen nomenclature, while keeping changes of established names to a minimum in the interest of continuity. Allergens for which names have been updated include respiratory allergens from birch and ragweed pollen, midge larvae, and horse dander; food allergens from peanut, cow's milk, and tomato; and cereal grain allergens. The IUIS Allergen Nomenclature Sub‐Committee encourages researchers to use these updated allergen names in future publications.
Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to ...another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.
Although habituation is one of the most ancient and fundamental forms of learning, its regulators and its relevance for human disease are poorly understood.
We manipulated the orthologs of 286 genes ...implicated in intellectual disability (ID) with or without comorbid autism spectrum disorder (ASD) specifically in Drosophila neurons, and we tested these models in light-off jump habituation. We dissected neuronal substrates underlying the identified habituation deficits and integrated genotype–phenotype annotations, gene ontologies, and interaction networks to determine the clinical features and molecular processes that are associated with habituation deficits.
We identified >100 genes required for habituation learning. For 93 of these genes, a role in habituation learning was previously unknown. These genes characterize ID disorders with macrocephaly and/or overgrowth and comorbid ASD. Moreover, individuals with ASD from the Simons Simplex Collection carrying damaging de novo mutations in these genes exhibit increased aberrant behaviors associated with inappropriate, stereotypic speech. At the molecular level, ID genes required for normal habituation are enriched in synaptic function and converge on Ras/mitogen-activated protein kinase (Ras/MAPK) signaling. Both increased Ras/MAPK signaling in gamma-aminobutyric acidergic (GABAergic) neurons and decreased Ras/MAPK signaling in cholinergic neurons specifically inhibit the adaptive habituation response.
Our work supports the relevance of habituation learning to ASD, identifies an unprecedented number of novel habituation players, supports an emerging role for inhibitory neurons in habituation, and reveals an opposing, circuit-level-based mechanism for Ras/MAPK signaling. These findings establish habituation as a possible, widely applicable functional readout and target for pharmacologic intervention in ID/ASD.
Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an ...allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15‐fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop.
Summary
Glutaryl‐CoA dehydrogenase (GCDH) deficiency is an autosomal recessive disease with an estimated overall prevalence of 1 in 100 000 newborns. Biochemically, the disease is characterized by ...accumulation of glutaric acid, 3‐hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine, which can be detected by gas chromatography–mass spectrometry of organic acids or tandem mass spectrometry of acylcarnitines. Clinically, the disease course is usually determined by acute encephalopathic crises precipitated by infectious diseases, immunizations, and surgery during infancy or childhood. The characteristic neurological sequel is acute striatal injury and, subsequently, dystonia. During the last three decades attempts have been made to establish and optimize therapy for GCDH deficiency. Maintenance treatment consisting of a diet combined with oral supplementation of L‐carnitine, and an intensified emergency treatment during acute episodes of intercurrent illness have been applied to the majority of patients. This treatment strategy has significantly reduced the frequency of acute encephalopathic crises in early‐diagnosed patients. Therefore, GCDH deficiency is now considered to be a treatable condition. However, significant differences exist in the diagnostic procedure and management of affected patients so that there is a wide variation of the outcome, in particular of pre‐symptomatically diagnosed patients. At this time of rapid expansion of neonatal screening for GCDH deficiency, the major aim of this guideline is to re‐assess the common practice and to formulate recommendations for diagnosis and management of GCDH deficiency based on the best available evidence.
The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a widely used measure for assessing the presence and severity of obsessive-compulsive disorder symptoms. The Yale-Brown Obsessive-Compulsive ...Scale-Second Edition (Y-BOCS-II) was developed, in part, to more comprehensively evaluate symptom severity, especially in extremely ill patients, and improve consistency in detecting and incorporating avoidance behaviors. We present 3 case studies that demonstrate the enhanced ability of the Y-BOCS-II to: (1) detect fluctuations in symptom severity among extremely ill patients, (2) systematically incorporate avoidance variables for more accurate ratings, and (3) maintain strong convergence with the Y-BOCS in assessing patients presenting with mild to moderate symptoms. In addition, we outline how to obtain both Y-BOCS and Y-BOCS-II scores within 1 administration by adding Y-BOCS item 4 to the Y-BOCS-II assessment, then "back-coding" the Y-BOCS-II ratings to Y-BOCS ratings and using Y-BOCS item 4 in place of Y-BOCS-II item 2. The use of this method allows for more robust data collection while providing comparability across the literature.
Chronic hepatitis C infection is now recognized as an important health care problem.
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Nearly 4 million Americans are estimated to be infected, and cirrhosis will eventually develop in at least 15 to ...20 percent of them.
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In the United States, infection with hepatitis C virus (HCV) is a leading cause of chronic liver disease and the most common indication for liver transplantation.
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Until recently, interferon alfa was the only therapy available for patients with chronic hepatitis C. However, after 48 weeks of treatment, serum HCV RNA levels are undetectable in only 15 to 20 percent of patients.
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The purpose of our study was to determine radiation dose to the fetus at early gestation when contemporary MDCT scanners are used for common clinical indications.
Anthropomorphic phantoms were ...constructed to reflect a pregnant woman. Thermoluminescence dosimeters (TLDs) and metal oxide semiconductor field effect transistor (MOSFET) detectors were placed in appropriate locations to determine real-time radiation exposure to the fetus at 0 and 3 months' gestation. Imaging was performed on a 16-MDCT scanner using current institutional CT protocols: renal stone (140 kVp, 160 mA, rotation time of 0.5 sec, 16 x 0.625 mm), appendix (140 kVp, 340 mA, rotation time of 0.5 sec, 16 x 0.625 mm), and pulmonary embolus (140 kVp, 380 mA, rotation time of 0.8 sec, 16 x 1.25 mm).
The radiation dose to the fetus at 0 and 3 months, respectively, was as follows: renal stone protocol, 0.8-1.2 and 0.4-0.7 cGy; appendix protocol, 1.52-1.68 and 2-4 cGy; and pulmonary embolus protocol, 0.024-0.047 and 0.061-0.066 cGy.
Radiation doses to the fetus from institutional MDCT protocols that may be used during pregnancy (for pulmonary embolus, appendicitis, and renal colic) are below the level thought to induce neurologic detriment to the fetus. Imaging the mother for appendicitis theoretically may double the fetal risk for developing a childhood cancer. Radiation doses to the fetus from pulmonary embolus chest CT angiography are of the same magnitude as ventilation-perfusion (V/Q) scanning.
Abstract
Long-term care homes play an essential role within health and social care. Successful measures to support older people at home for longer have led to increased prevalence of disability, ...frailty and cognitive impairment in those who live in care homes over the last two decades. The need for care home places is projected to increase for the next two decades. Modern care homes provide care for people who are predominantly over 80, have multiple long-term conditions, take multiple medicines, are physically dependent and live with cognitive impairment. Residents do better when services recognise the contributions of staff and care home providers rather than treating residents as individual patients living in a communal setting. There is a strong case given residents’ frailty, multimorbidity and disability, that care should be structured around Comprehensive Geriatric Assessment (CGA). Care should be designed to allow opportunities for multiprofessional teams to come together for CGA, particularly if healthcare professionals are based outside care homes. Good data about care homes and residents are central to efforts to deliver high quality care—in some countries, these data are collected but not collated. Collating such data is a priority. Care home staff are under-recognised and underpaid—parity of pay and opportunity with NHS staff is the bare minimum to ensure that the best are recruited and retained in the sector. During the COVID-19 pandemic, residents and relatives have frequently been left out of decisions about policies that affect them, and better consultation is needed to deliver high quality care.
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