To bite or not to bite! A questionnaire-based survey assessing why some people are bitten more than others by midges

BACKGROUND: The Scottish biting midge, Culicoides impunctatus, responsible for more than 90% of biting attacks on human beings in Scotland, is known to demonstrate a preference for certain human hosts over others. METHODS: In this study we used a questionnaire-based survey to assess the association between people's perception of how badly they get bitten by midges and their demographic, lifestyle and health related characteristics. RESULTS: Most people (85.8%) reported being bitten sometimes, often or always with only 14.2% reporting never being bitten by midges when in Scotland. There was no association between level of bites received and age, smoking, diet, exercise, medication, eating strongly flavoured foods or alcohol consumption. However, there was a strong association between the probability of being bitten and increasing height (in men) and BMI (in women). A large proportion of participants (33.8%) reported experiencing a bad/severe reaction to midge bites while 53.1% reported a minor reaction and 13.1% no reaction at all. Also, women tend to react more than men to midge bites. Additionally, the results indicated that the susceptibility to being bitten by midges is hereditary. CONCLUSIONS: This study suggests that midges prefer to bite men that are tall and women that have a large BMI, and that the tendency for a child to be bitten or not could be inherited from their parent. The study is questionnaire-based; therefore, the interpretation of the results may be limited by the subjectivity of the answers given by the respondents. Although the results are relevant only to the Scottish biting midge, the approach used here could be useful for investigating human-insect interactions for other insects, particularly those which transmit pathogens that cause disease

A new primary dental care service compared with standard care for child and family to reduce the re-occurrence of childhood dental caries (Dental RECUR): study protocol for a randomised controlled trial

Background: In England and Scotland, dental extraction is the single highest cause of planned admission to the hospital for children under 11 years. Traditional dental services have had limited success in reducing this disease burden. Interventions based on motivational interviewing have been shown to impact positively dental health behaviours and could facilitate the prevention of re-occurrence of dental caries in this high-risk population. The objective of the study is to evaluate whether a new, dental nurse-led service, delivered using a brief negotiated interview based on motivational interviewing, is a more cost-effective service than treatment as usual, in reducing the re-occurrence of dental decay in young children with previous dental extractions. Methods/Design: This 2-year, two-arm, multicentre, randomised controlled trial will include 224 child participants, initially aged 5 to 7 years, who are scheduled to have one or more primary teeth extracted for dental caries under general anaesthesia (GA), relative analgesia (RA: inhalation sedation) or local anaesthesia (LA). The trial will be conducted in University Dental Hospitals, Secondary Care Centres or other providers of dental extraction services across the United Kingdom. The intervention will include a brief negotiated interview (based on the principles of motivational interviewing) delivered between enrolment and 6 weeks post-extraction, followed by directed prevention in primary dental care. Participants will be followed up for 2 years. The main outcome measure will be the dental caries experienced by 2 years post-enrolment at the level of dentine involvement on any tooth in either dentition, which had been caries-free at the baseline assessment. Discussion: The participants are a hard-to-reach group in which secondary prevention is a challenge. Lack of engagement with dental care makes the children and their families scheduled for extraction particularly difficult to recruit to an RCT. Variations in service delivery between sites have also added to the challenges in implementing the Dental RECUR protocol during the recruitment phase. Trial registration: ISRCTN24958829 (date of registration: 27 September 2013), Current protocol version: 5.0

Nuclear and Chloroplast Microsatellites Show Multiple Introductions in the Worldwide Invasion History of Common Ragweed, Ambrosia artemisiifolia

BACKGROUND: Ambrosia artemisiifolia is a North American native that has become one of the most problematic invasive plants in Europe and Asia. We studied its worldwide population genetic structure, using both nuclear and chloroplast microsatellite markers and an unprecedented large population sampling. Our goals were (i) to identify the sources of the invasive populations; (ii) to assess whether all invasive populations were founded by multiple introductions, as previously found in France; (iii) to examine how the introductions have affected the amount and structure of genetic variation in Europe; (iv) to document how the colonization of Europe proceeded; (v) to check whether populations exhibit significant heterozygote deficiencies, as previously observed. PRINCIPAL FINDINGS: We found evidence for multiple introductions of A. artemisiifolia, within regions but also within populations in most parts of its invasive range, leading to high levels of diversity. In Europe, introductions probably stem from two different regions of the native area: populations established in Central Europe appear to have originated from eastern North America, and Eastern European populations from more western North America. This may result from differential commercial exchanges between these geographic regions. Our results indicate that the expansion in Europe mostly occurred through long-distance dispersal, explaining the absence of isolation by distance and the weak influence of geography on the genetic structure in this area in contrast to the native range. Last, we detected significant heterozygote deficiencies in most populations. This may be explained by partial selfing, biparental inbreeding and/or a Wahlund effect and further investigation is warranted. CONCLUSIONS: This insight into the sources and pathways of common ragweed expansion may help to better understand its invasion success and provides baseline data for future studies on the evolutionary processes involved during range expansion in novel environments

Malignant mesothelioma

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis

Biallelic variants in the ectonucleotidase ENTPD1 cause a complex neurodevelopmental disorder with intellectual disability, distinct white matter abnormalities, and spastic paraplegia.

OBJECTIVE: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia (HSP) is associated with over 80 genes with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (MIM# 615683). METHODS: Individuals with biallelic ENTPD1 variants were recruited worldwide. Deep phenotyping and molecular characterizations were performed. RESULTS: A total of 27 individuals from 17 unrelated families were studied; additional phenotypic information was collected from published cases. Twelve novel pathogenic ENTPD1 variants are described: c.398_399delinsAA; p.(Gly133Glu), c.540del; p.(Thr181Leufs* 18), c.640del; p.(Gly216Glufs* 75), c.185T>G; p.(Leu62*), c.1531T>C; p.(*511Glnext* 100), c.967C>T; p.(Gln323*), c.414-2_414-1del, and c.146 A>G; p.(Tyr49Cys) including four recurrent variants c.1109T>A; p.(Leu370* ), c.574-6_574-3del, c.770_771del; p.(Gly257Glufs*18), and c.1041del; p.(Ile348Phefs*19). Shared disease traits include: childhood-onset, progressive spastic paraplegia, intellectual disability (ID), dysarthria, and white matter abnormalities. In vitro assays demonstrate that ENTPD1 expression and function are impaired and that c.574-6_574-3del causes exon skipping. Global metabolomics demonstrates ENTPD1 deficiency leads to impaired nucleotide, lipid, and energy metabolism. INTERPRETATION: The ENTPD1 locus trait consists of childhood disease-onset, ID, progressive spastic paraparesis, dysarthria, dysmorphisms, and white matter abnormalities with some individuals showing neurocognitive regression. Investigation of an allelic series of ENTPD1: i) expands previously described features of ENTPD1-related neurological disease, ii) highlights the importance of genotype-driven deep phenotyping, iii) documents the need for global collaborative efforts to characterize rare AR disease traits, and iv) provides insights into the disease trait neurobiology. This article is protected by copyright. All rights reserved

The Synthesis of 5-Fluorokynurenine and 6-Fluorokynurenic Acid as Metabolic Probes

(2S)-5-Fluorokynurenine 9 and 6-fluorokynurenic acid 14 were synthesised as fluorinated probes to enable the metabolism of kynurenine to be monitored in vivo by F-19 NMR spectroscopy. The ( 2S)-5-fluorokynurenine 9 was prepared using a Friedel-Crafts acylation of N-((t)butoxycarbonyl)-4-fluoroaniline with a chiral oxazolidine derivative 6, derived from 2S-aspartic acid. This represents a novel, and simple, method for the synthesis of kynurenine derivatives. The 6-fluorokynurenic acid 14 was synthesised using a Conrad-Limpach type synthesis. Preliminary biological studies are described.</p

A Comparative Study on The Inhibition of Human and Bacterial Kynureninase by Novel Bicyclic Kynurenine Analogues

A series of novel bicyclic analogues of kynurenine were synthesised as inhibitors of kynureninase. The tryptophan-induced bacterial enzyme from Pseudomonas fluorescens,ls was compared to the constitutive recombinant human enzyme expressed in a baculovirus/insect cell system. with regard to their inhibition by these compounds. All the compound studied were found to be simple competitive. reversible inhibitors of kynureninase. It was found that altering the size of the second ring of the inhibitor affected the observed K-i values for both enzymes. The addition of an oxygen atom into the secund ring had little effect on binding to the bacterial enzyme but gave a more potent inhibitor of human kynureninase. Of the compounds tasted, a naphthyl analogue of desaminokynurenine was found to be the most potent inhibitor for both enzymes with k(i) values of 5 and 21 CIM For bacterial and human enzyme respectively. This report also describes an alternative system for the expression of recombinant human kynureninase which is more convenient for expression in mammalian cells and produces a relatively greater quantity of enzyme. (C) 2001 Elsevier Science Ltd. All rights reserved.</p