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- Antonini, Angelo, et al.
(författare)
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Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson’s disease : a multi-country Delphi-panel approach
- 2018
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Ingår i: Current Medical Research and Opinion. - : Informa UK Limited. - 0300-7995 .- 1473-4877. ; 34:12, s. 2063-2073
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lack of a global consensus on the definition of advanced Parkinson’s disease (APD) and considerations for timing of device-aided therapies may result in heterogeneity in care. Objectives: To reach consensus among movement disorder specialists regarding key patient characteristics indicating transition to APD and guiding appropriate use of device-aided therapies in the management of PD symptoms. Methods: A Delphi-panel approach was utilized to synthesize opinions of movement disorder specialists and build consensus. Results: A panel was comprised of movement disorder specialists from 10 European countries with extensive experience of treating PD patients (mean =24.8 ± 7.2 years). Consensus on indicators of suspected APD and eligibility for device-aided therapies were based on motor symptoms, non-motor symptoms, and functional impairments. Key indicators of APD included: (i) motor—moderate troublesome motor fluctuations, ≥1 h of troublesome dyskinesia/day, ≥2 h “off” symptoms/day, and ≥5-times oral levodopa doses/day; (ii) non-motor—mild dementia, and non-transitory troublesome hallucinations; (iii) functional impairment—repeated falls despite optimal treatment, and difficulty with activities of daily living. Patients with good levodopa response, good cognition, and <70 years of age were deemed as good candidates for all three device-aided therapies. Patients with troublesome dyskinesia were considered good candidates for both levodopa-carbidopa intestinal gel and Deep Brain Stimulation (DBS). PD patients with levodopa-resistant tremor were considered good candidates for DBS. Conclusion: Identifying patients progressing to APD and suitable for device-aided therapies will enable general neurologists to assess the need for referral to movement disorder specialists and improve the quality of care and patient outcomes.
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- Haschka, J, et al.
(författare)
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Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis
- 2023
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 62:10, s. 3448-3458
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivemiRNAs are small non-coding RNAs that control gene expression. Specific intra- and extracellular miRNA signatures have been identified in various diseases. Whether certain miRNA signatures are associated with psoriasis (PsO) and PsA is currently unknown. We aimed to search for circulating miRNA signatures associated with PsO and PsA patients.MethodsExpression of miRNAs was analysed by reverse transcription quantitative real-time PCR (RT-qPCR) in the serum of PsA, PsO patients and healthy controls. Demographic and disease-specific characteristics and imaging data from hand MRI were recorded. In the discovery phase, 192 miRNA assays were analysed in 48 samples (PsA, PsO, controls: each N = 16). For validation, 17 selected miRNAs were measured in the total population.ResultsA total of 141 patients and controls were analysed (51 PsA, 40 PsO, 50 controls). In the discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared with controls, with 33 miRNAs being changed in both (adj. P < 0.05). The 17 top candidates from discovery were assessed in the validation phase, 9 of them discriminated PsA and PsO from controls [area under the curve (AUC) ≥0.70, all P < 0.05]. Four miRNAs (miR-19b-3p, miR-21-5p, miR-92a-3p and let-7b-5p) were significantly differently regulated between PsO and PsA. A combination of these miRNAs increased the AUC to 0.92 in multivariate regression model to discriminate PsO and PsA.ConclusionmiRNA signatures in PsA and PsO patients differ from controls. Nine miRNAs were differentially regulated in PsA and PsO patients, five of them previously reported to be involved in bone and cartilage metabolism, indicating an intimate association of psoriatic inflammation and bone/cartilage changes.
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- Cavallin, I, et al.
(författare)
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HITS-CLIP analysis of human ALKBH8 reveals interactions with fully processed substrate tRNAs and with specific noncoding RNAs
- 2022
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Ingår i: RNA (New York, N.Y.). - : Cold Spring Harbor Laboratory. - 1469-9001 .- 1355-8382. ; 28:12, s. 1568-1581
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Tidskriftsartikel (refereegranskat)abstract
- Transfer RNAs acquire a large plethora of chemical modifications. Among those, modifications of the anticodon loop play important roles in translational fidelity and tRNA stability. Four human wobble U containing tRNAs obtain 5-methoxycarbonylmethyluridine (mcm5U34) or 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U34), which play a role in decoding. This mark involves a cascade of enzymatic activities. The last step is mediated by Alkylation Repair Homolog 8 (ALKBH8). In this study, we performed a transcriptome-wide analysis of the repertoire of ALKBH8 RNA targets. Using a combination of HITS-CLIP and RIP-seq analyses, we uncover ALKBH8-bound RNAs. We show that ALKBH8 targets fully processed and CCA modified tRNAs. Our analyses uncovered the previously known set of wobble-U containing tRNAs. In addition, our both approaches revealed ALKBH8 binding to several other types of non-coding RNAs, in particular C/D box snoRNAs.
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