| 41. |
- Ombrello, MJ, et al.
(författare)
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Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications
- 2017
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:5, s. 906-913
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Tidskriftsartikel (refereegranskat)abstract
- Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA.MethodsWe performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes.ResultsThe major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes.ConclusionsThe lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.
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| 42. |
- Schwager, Evelyn E., et al.
(författare)
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The house spider genome reveals an ancient whole-genome duplication during arachnid evolution
- 2017
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Ingår i: BMC Biology. - : BIOMED CENTRAL LTD. - 1741-7007. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some chelicerate lineages including two rounds of whole genome duplication (WGD) in horseshoe crabs. To investigate this further, we sequenced and analyzed the genome of the common house spider Parasteatoda tepidariorum.Results: We found pervasive duplication of both coding and non-coding genes in this spider, including two clusters of Hox genes. Analysis of synteny conservation across the P. tepidariorum genome suggests that there has been an ancient WGD in spiders. Comparison with the genomes of other chelicerates, including that of the newly sequenced bark scorpion Centruroides sculpturatus, suggests that this event occurred in the common ancestor of spiders and scorpions, and is probably independent of the WGDs in horseshoe crabs. Furthermore, characterization of the sequence and expression of the Hox paralogs in P. tepidariorum suggests that many have been subject to neo-functionalization and/or sub-functionalization since their duplication.Conclusions: Our results reveal that spiders and scorpions are likely the descendants of a polyploid ancestor that lived more than 450 MYA. Given the extensive morphological diversity and ecological adaptations found among these animals, rivaling those of vertebrates, our study of the ancient WGD event in Arachnopulmonata provides a new comparative platform to explore common and divergent evolutionary outcomes of polyploidization events across eukaryotes.
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| 43. |
- Villa, A., et al.
(författare)
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World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction
- 2016
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Ingår i: Oral Diseases. - : Wiley. - 1354-523X. ; 22:5, s. 365-382
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper was to perform a systematic review of the pathogenesis of medication-induced salivary gland dysfunction (MISGD). Review of the identified papers was based on the standards regarding the methodology for systematic reviews set forth by the World Workshop on Oral Medicine IV and the PRISMA statement. Eligible papers were assessed for both the degree and strength of relevance to the pathogenesis of MISGD as well as on the appropriateness of the study design and sample size. A total of 99 papers were retained for the final analysis. MISGD in human studies was generally reported as xerostomia (the sensation of oral dryness) without measurements of salivary secretion rate. Medications may act on the central nervous system (CNS) and/or at the neuroglandular junction on muscarinic, α-and β-adrenergic receptors and certain peptidergic receptors. The types of medications that were most commonly implicated for inducing salivary gland dysfunction were those acting onthe nervous, cardiovascular, genitourinary, musculoskeletal, respiratory, and alimentary systems. Although many medications may affect the salivary flow rate and composition, most of the studies considered only xerostomia. Thus, further human studies are necessary to improve our understanding of the association between MISGD and the underlying pathophysiology. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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| 44. |
- Villa, A., et al.
(författare)
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World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment
- 2015
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Ingår i: Clinical Oral Investigations. - : Springer Science and Business Media LLC. - 1432-6981 .- 1436-3771. ; 19:7, s. 1563-1580
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Medication-induced salivary gland dysfunction (MISGD) causes significant morbidity resulting in decreased quality of life. This systematic review assessed the literature on the prevalence, diagnosis, treatment, and prevention of MISGD. Materials and methods Electronic databases were searched for articles related to MISGD through June 2013. Four independent reviewers extracted information regarding study design, study population, interventions, outcomes, and conclusions for each article. Only papers with acceptable degree of relevance, quality of methodology, and strength of evidence were retained for further analysis. Results There were limited data on the epidemiology of MISGD. Furthermore, various methods were used to assess salivary flow rate or xerostomia. Preventive and therapeutic strategies included substitution of medications, oral, or systemic therapy with sialogogues, use of saliva substitutes or of electro-stimulating devices. Although there are promising approaches to improve salivary gland function, most studies are characterized by small numbers and heterogeneous methods. Conclusions Physicians and dentists should identify the medications associated with xerostomia and salivary gland dysfunction through a thorough medical history. Preferably, health care providers should measure the unstimulated and stimulated whole salivary flow rates of all their patients so that these values can be used as a baseline to rate the complaints of patients who subsequently claim to experience xerostomia or salivary gland dysfunction as well as the possibilities of effectively treating this condition. Clinical relevance MISGD remains a major burden for the population. This systematic review provides a contemporary in-depth description of the diagnosis and treatment of MISGD.
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| 45. |
- Wolff, A., et al.
(författare)
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A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI
- 2017
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Ingår i: Drugs in R&D. - : Springer Science and Business Media LLC. - 1174-5886 .- 1179-6901. ; 17:1, s. 1-28
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Tidskriftsartikel (refereegranskat)abstract
- Background Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist. Objective Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. Data Sources Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the abovementioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. Limitations While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search. Conclusions We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.
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| 46. |
- Wolff, A., et al.
(författare)
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Electrostimulation of the lingual nerve by an intraoral device may lead to salivary gland regeneration: A case series study
- 2018
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Ingår i: Medicina Oral Patologia Oral Y Cirugia Bucal. - : Medicina Oral, S.L.. - 1698-6946. ; 23:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Salivary gland function is controlled by the salivary reflex, whose efferent arm is composed by the parasympathetic and the sympathetic divisions of the autonomic nervous system. Parenchymal injury is the main salivary gland involvement of Sjögren’s syndrome and head and neck radiotherapy, but neural damage has been reported as well. Recently an intraoral device for electrostimulation of the lingual nerve in vicinity to the lower third molar has been introduced. At this point this nerve carries efferent fibers for the innervation of the submandibular, sublingual and several minor salivary glands and afferent fibers of the salivary reflex. Therefore, excitation of these fibers potentially leads to increased secretion of all salivary glands. Thus, the study objective was to assess whether comprehensive neural activation by electrostimulation of the lingual nerve carries the potential to induce the regeneration of damaged salivary glands. Material and Methods: The device was tested on three patients with no collectable resting and stimulated secretion of saliva during a double blind, sham controlled period of two months and nine open-label months. Results: All three subjects developed the capacity to spit saliva, not only in direct response to the electrostimulation but also after free intervals without electrostimulation. In addition, their symptoms of dry mouth severity and frequency improved. Conclusions: This recovery is probably due to the combined effect of increase in secretory functional gland mass and regain of nervous control of the secretory elements and blood vessels. Both are phenomena that would contribute to gland regeneration.
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| 47. |
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| 48. |
- Wolff, Ellen, 1987, et al.
(författare)
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Cost-effectiveness of sex-neutral HPV-vaccination in Sweden, accounting for herd-immunity and sexual behaviour
- 2018
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 36:34, s. 5160-5165
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim was to assess cost-effectiveness of expanding the Swedish HPV-vaccination program to include preadolescent boys, by comparing health-effects and costs of HPV-related disease, with a sex-neutral vaccination program versus only vaccinating girls. Methods: We used a dynamic compartmental model to simulate the burden of HPV16/18-related disease in Sweden, accounting for indirect effects of vaccination through herd-immunity. The model accounted for sexual behaviour, such as age preferences and men who have sex with men. The main outcome was number of individuals with HPV-related cancers (cervical, genital, anal and oropharyngeal cancer) and cervical intraepithelial neoplasia (CIN). Costs included in the analysis were those incurred when treating HPV-related cancer and CIN, production losses during sick-leave, and acquisition and administration of vaccine. Health effects were measured as quality-adjusted life years (QALY). The time horizon was set to 100 years, and both effects and costs were discounted by 3% annually. Health effects and costs were accumulated over the time horizon and used to create an incremental cost-effectiveness ratio. Results: A sex-neutral vaccination program would reduce HPV-related cancer and CIN, both due to direct effects among vaccinated as well as through herd-immunity, further decreasing HPV-related cancer burden annually by around 60 cases among men and women respectively in steady-state. The cost per gained QALY was estimated to 40,000 euro. Applying the procurement price of 2017, sex-neutral vaccination was dominant. Conclusion: Introducing a sex-neutral HPV-vaccination program would be good value for money also in Sweden where there this 80% coverage in the current HPV-vaccination program for preadolescent girls. The cost-effectiveness of a sex-neutral program is highly dependent on the price of the vaccine, the lower the price the more favourable it is to also vaccinate boys. (C) 2018 The Author(s). Published by Elsevier Ltd.
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