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To investigate molecular biomarkers of a-synuclein and tau aggregation, autophagy, and inflammation in the saliva of de novo Parkinson's disease (PD) patients in comparison to healthy subjects (HS), and to correlate molecular data with clinical features of PD patients, in order to establish whether abnormalities of these parameters are associated with specific clusters of de novo PD patients, and their potential diagnostic power in differentiating PD patients from HS.We measured total and oligomeric a-synuclein, total-tau and phosphorylated-tau, MAP-LC3beta, and TNFalpha in the saliva of 80 de novo PD patients and 62 HS, using quantitative Enzyme-Linked Immunosorbent Assay analysis.Oligomeric a-synuclein, total-tau, MAP-LC3beta, and TNFalpha levels resulted significantly higher in patients with respect to HS, while no significant differences were detected for total a-synuclein or phosphorylated-tau. Phosphorylated-tau directly correlated with MAP-LC3beta, whereas it inversely correlated with TNFalpha in PD patients. An inverse correlation was detected between MAP-LC3beta and non-motor symptoms severity. Principal Component Analysis showed that molecular and clinical parameters were independent of each other in de novo PD patients. Receiver Operating Characteristic curve analysis reported an accurate diagnostic performance of oligomeric a-synuclein and MAP-LC3beta. The diagnostic accuracy of total a-synuclein increased when it was combined with other salivary biomarkers targeting different molecular pathways.Our study proposes a novel biomarker panel using saliva, a non-invasive biofluid, in de novo PD patients, with implications in understanding the molecular pathways involved in PD pathogenesis and the relevance of different molecular pathways in determining clinical PD subtypes. This article is protected by copyright. All rights reserved.

Introduction Cervical dystonia (CD) is a heterogeneous condition. However, while motor subtypes of CD have recently been identified, it is still unknown whether and how non-motor symptoms contribute to CD heterogeneity. In the present cross-sectional study, we aimed to identify clinical CD subtypes on the basis of motor and non-motor symptoms by using a hypothesis-free data-driven approach. Methods Fifty-seven patients with CD participated in the study. Patients underwent a clinical evaluation that assessed motor and non-motor features of CD with standardized clinical scales. We investigated five clinical domains, including motor symptoms, psychiatric disturbances, sleep disorders, cognitive impairment and pain. These domains were used as variables in a k-means cluster analysis with two-, three-, and four-cluster solutions. Results The two-cluster solution best fits our sample. Cluster I (n = 32) included patients who were younger and had less severe non-motor symptoms and a lower disability level than patients included in Cluster II (n = 25). The two clusters showed similar sex distribution and disease duration. Similarly, the type of motor pattern and the occurrence of tremor and sensory trick were equally distributed in the two subtypes. Conclusions We identified two clinical subtypes of CD. The two subtypes shared similar motor features but were characterized by different non-motor symptom severity. These findings suggest that motor network dysfunction is a common pathophysiological feature of CD, whereas the extent of non-motor network involvement may differ in CD, with age acting as a possible modulating factor.

Climate change will affect many human activities and sectors. Among those, the built environment will face several challenges with respect to the varying climate conditions. The present study investigated the global warming impacts on energy demand and indoor climate comfort for an office building in Stockholm. Considering a service life of 50 years, the future climate conditions were investigated for the only air temperature increase in 2070, in accordance with the medium forecasted greenhouse gas emissions scenario provided by the International Panel on Climate Change (IPCC). Another climate morphing approach was adopted to develop the climate file for the year 2080 considering the variation of all the weather parameters. Three different passive cooling solutions, such as external roller shade, electrochromic glazing, and internally ventilated shading, have been implemented in the case study building to decrease the cooling demand. The characteristics of the strategies were preliminarily assessed and then implemented into the building energy simulation software IDA-ICE to evaluate the energy performances with respect to the different climates. The results indicated that an increment of the cooling demand and a reduction of the heating usage will be experienced in the future. The different morphing approaches displayed the inherent uncertainties when future evaluations are performed, although similar weather patterns were found. The improvement of the solar and optical properties, such as the introduction of the exhaust air extraction and the electrochromic technology, implied a lower cooling and ventilation usage. The EC technology reported the lowest cooling demand, while the internally ventilated shading option outperformed the others in terms of annual energy consumption. Klimatförändringar kommer att påverka många mänskliga aktiviteter och sektorer. Bland dem kommer den byggda miljön att möta flera utmaningar med avseende på de olika klimatförhållandena. Denna studie undersökte effekterna av den globala uppvärmningen på energibehovet och inomhusklimatkomforten för en kontorsbyggnad i Stockholm. Med hänsyn till en livslängd på 50 år undersöktes de framtida klimatförhållandena för ökningen av lufttemperaturen utomhus till 2070, i enlighet med det medelprognoserade växthusgasutsläppsscenariot som tillhandahålls av International Panel on Climate Change (IPCC). En annan klimatförändringsmetod antogs för att utveckla klimatfilen för år 2080 med tanke på variationen i alla väderparametrar. Tre olika passiva kyllösningar, såsom utvändigt solskydd (vertikalmarkis med screenväv), elektrokromt glas och invändigt ventilerat solskydd, har implementerats i fallstudiebyggnaden för att minska kylbehovet. Karaktären av strategierna utvärderades preliminärt och implementerades sedan i programvaran för byggenergisimulering IDA-ICE för att utvärdera energiprestanda med avseende på de olika klimaten. Resultaten indikerade att en ökning av kylbehovet och en minskning av värmeanvändningen kommer att ske i framtiden. De olika klimatförändringsmetoderna visade de inneboende/medföljande osäkerheterna när framtida utvärderingar utförs, även om liknande vädermönster hittades. De passiva kyllösningarnas reducering av total solenergitransmission, såsom införandet av frånluftsutsug och den elektrokroma tekniken, innebar en lägre kyl- och ventilationsanvändning. EC-tekniken rapporterade det lägsta kylbehovet, medan det invändiga ventilerade solskyddet överträffade de andra när det gäller årlig energiförbrukning.