Removal of proteinase K resistant alpha Syn species does not correlate with cell survival in a virus vector-based Parkinson's disease mouse model

Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neurons and accumu-lation of alpha-synuclein (alpha Syn) as Lewy bodies. Currently, there is no disease-modifying therapy available for PD. We have shown that a small molecular inhibitor for prolyl oligopeptidase (PREP), KYP-2047, relieves alpha Syn-induced toxicity in various PD models by inducing autophagy and preventing alpha Syn aggregation. In this study, we wanted to study the effects of PREP inhibition on different alpha Syn species by using cell culture and in vivo models.We used Neuro2A cells with transient alpha Syn overexpression and oxidative stress or proteasomal inhibition -induced alpha Syn aggregation to assess the effect of KYP-2047 on soluble alpha Syn oligomers and on cell viability. Here, the levels of soluble alpha Syn were measured by using ELISA, and the impact of KYP-2047 was compared to anle138b, nilotinib and deferiprone. To evaluate the effect of KYP-2047 on alpha Syn fibrillization in vivo, we used unilateral nigral AAV1/2-A53T-alpha Syn mouse model, where the KYP-2047 treatment was initiated two-or four -weeks post injection.KYP-2047 and anle138b protected cells from alpha Syn toxicity but interestingly, KYP-2047 did not reduce soluble alpha Syn oligomers. In AAV-A53T-alpha Syn mouse model, KYP-2047 reduced significantly proteinase K-resistant alpha Syn oligomers and oxidative damage related to alpha Syn aggregation. However, the KYP-2047 treatment that was initiated at the time of symptom onset, failed to protect the nigrostriatal dopaminergic neurons. Our results emphasize the importance of whole alpha Syn aggregation process in the pathology of PD and raise an important question about the forms of alpha Syn that are reasonable targets for PD drug therapy.Peer reviewe

Early and later timed cervical headgear treatment:a randomized controlled trial

Abstract Proper timing of orthodontic treatment is a continuous subject in orthodontic discussion. Particularly, it is debated whether early care is reasonable in Class II malocclusions. Cervical headgear (CH) is one of the commonly used orthodontic devices in early treatment of Class II malocclusion. Its dental and craniofacial effects are widely studied and well known. However, there are only a few longitudinal randomized controlled trials looking at the effect and timing of CH treatment in children with Class II malocclusion. The aim of this study was to investigate the dental, craniofacial and pharyngeal airway changes among children with a Class II malocclusion treated with CH when the timing of treatment is altered. A further aim was to study the effect of gender on the changes in outcomes. Sixty-seven seven-year-old children with Class II malocclusion were randomized in 1:1 ratio to two equal-sized groups. In the early group (EG), the CH treatment was started at the age of 7.8 years. In the late group (LG), the CH treatment was started at the age of 9.5 years. The active CH treatment was continued in both groups until normal Class I occlusion was achieved on permanent first molars. The data from participants were collected at the beginning of follow-up (T0), at the beginning of treatment of the LG (T1), and at the end of the treatment of the LG (T2). Fifty-six children completed the study. Changes in dental casts and cephalograms were considered as primary outcomes and changes in measurements were compared between groups and genders. There were timing and gender specific changes in dentofacial dimensions, but not in craniofacial structures. The dental arches were longer and wider after the early CH treatment, especially transversally among the EG males. This study supports the previous findings that CH treatment redirects the growth of the maxilla, and improves the sagittal relationship between the jaws. The mandible showed anterior growth rotation although the upper face height increased. In this study, the CH treatment did not cause adverse effects on pharyngeal airway structures.Tiivistelmä Oikomishoidon oikea ajoitus on jatkuva keskustelunaihe. Erityisesti keskustelua käydään siitä, onko varhainen oikomishoito perusteltua Angle II-luokan purentavirheiden hoidossa. Niskavetolaite on yksi yleisimmin käytetyistä oikomishoitolaitteista II-luokan purentavirheiden varhaishoidoissa. Niskavetohoidon vaikutukset hampaistoon ja kasvojen luustoon ovat laajalti tutkitut ja tunnetut. Kirjallisuudessa on kuitenkin vain muutamia pitkittäisiä, satunnaistettuja, kontrolloituja tutkimuksia, joissa tarkastellaan niskavetohoidon vaikutusta ja ajoitusta lapsilla, joilla on II-luokan purentavirhe. Tämän tutkimuksen tavoitteena oli tutkia hampaiston, kasvojen luuston ja nielun ilmateiden muutoksia niskavedolla hoidetuilla lapsilla, joilla oli II-luokan purentavirhe, kun hoidon ajoitusta muutetaan. Lisäksi tavoitteena oli tutkia sukupuolen vaikutusta hoitotuloksen muutoksiin. 67 7-vuotiasta lasta, joilla oli todettu II-luokan purentavirhe, satunnaistettiin suhteessa 1:1 kahteen samankokoiseen ryhmään. Varhaisemmassa hoitoryhmässä niskavetohoito aloitettiin 7,8 vuoden iässä. Myöhäisemmässä ryhmässä niskavetohoito aloitettiin 9,5-vuotiaana. Aktiivista niskavetohoitoa jatkettiin molemmissa ryhmissä, kunnes ensimmäiset pysyvät poskihampaat saatiin I-luokan purentasuhteeseen. Tiedot tutkimukseen osallistuneista kerättiin seurannan alussa (T0), myöhäisemmän ryhmän hoidon alussa (T1) ja myöhäisemmän ryhmän hoidon lopussa (T2). 56 lasta osallistui tutkimukseen loppuun asti. Kipsimalleista ja kefalometriakuvista todetut muutokset katsottiin ensisijaiseksi vasteeksi, ja mittausten muutoksia verrattiin ryhmien ja sukupuolten välillä. Hoidon ajoitus ja sukupuoli vaikuttivat hampaistollisiin muutoksiin, mutta eivät kasvojen luustollisiin muutoksiin. Hammaskaaret olivat varhaisen niskavetohoidon jälkeen pidempiä ja leveämpiä. Ero hammaskaarten leveydessä oli merkitsevä erityisesti varhain hoidetuilla pojilla. Tämä tutkimus tukee aikaisempia tutkimuksia, joiden mukaan niskavetohoito ohjaa yläleuan kasvua ja parantaa leukojen välistä sagittaalisuhdetta. Alaleuan kasvu noudatti sulkeutuvaa kasvusuuntaa, vaikka yläkasvokorkeus kasvoi. Tällä tutkimuksella ei voitu osoittaa, että niskavetohoidolla olisi haitallisia vaikutuksia nielun ilmateiden rakenteisiin

Airway and hard tissue dimensions in children treated with early and later timed cervical headgear:a randomized controlled trial

Abstract Background: A Kloehn-type cervical headgear (CH) aims to correct skeletal jaw discrepancy in Class II children. A few studies have reported CH treatment effects on airway dimensions, but none of them have been randomized according to timing. Objectives: To evaluate related craniofacial structures and pharyngeal airway dimensions in children with a Class II occlusion treated with CH and randomized into early and late treatment groups. Trial design: Randomized, parallel-group, prospective controlled trial. Methods: The material comprised 67 seven-year-old children with a Class II occlusion. Sealed-envelope randomization in 1:1 ratio was used to divide the children into two equal groups. In the early group (EG, n = 33), CH treatment was started immediately or after eruption of the first maxillary molars. In the second, late group (LG, n = 34), the active CH treatment was started about one and half year later. The active CH treatment was continued in both groups until normal Class I occlusion on first molars was achieved. Cephalometric radiographs were taken from both groups at the beginning of follow-up (T0), at the beginning of CH treatment of the second group (T1), and at the end of CH treatment of the second group (T2). Changes in cephalometric measurements were used as primary outcomes. Blinding was applicable for outcome assessment. Results: Fifty-six children completed the study. The posterior change in the position of the maxilla was significant for early treatment males at T0–T1 (SNA; P < 0.001, ANB; P = 0.009) and T0–T2 (SNA; P = 0.012). The palato-mandibular angle (PL-ML) decreased during T0–T1 in early treatment females (P = 0.018) and early treatment males (P = 0.037). The retroglossal airway increased (P = 0.010) in early treatment males at T0–T1. Highly significant positive correlations (P < 0.001) between skeletal and upper airway dimensions during early CH treatment were found in males. No harms were encountered. Conclusions: Despite the effective CH treatment, no harmful upper airway changes were found. Clinical registration: NCT02010346

Comparison of effects of cervical headgear treatment on skeletal facial changes when the treatment time is altered:a randomized controlled trial

Summary Background: There is a lack of evidence based on longitudinal information in the field of Class II malocclusion management with cervical headgear (CH), especially in a randomized setting. Objectives: The main objective of this study was to evaluate skeletal facial changes, particularly in vertical dimensions, after Kloehn-type CH treatment in children when the timing of treatment is altered. Trial design: Prospective, parallel-group, randomized controlled trial. Methods: Screened children with Class II malocclusion were randomized in 1:1 ratio to two groups of equal size by sealed-envelope randomization: the early group (EG), where active CH treatment was started at the age of 7.8 years, and the late group (LG), where CH treatment was started at the age of 9.5 years. The active treatment was continued until normal Class I occlusion on first molars was achieved. Cephalograms were taken at three different time points. Changes in cephalometric measurements were compared between groups and genders. Blinding was applicable for outcome evaluation. Results: Of 67 randomized children, 56 completed the study. Upper face height increased during the CH treatment phase, as the parameter N–ANS increased significantly during the active treatments of EG (P < 0.05) and LG (P < 0.05). Also, the parameter NSL–PL increased significantly during the treatment of EG (P < 0.01) and during the treatment of LG (P < 0.01). The Gonial angle decreased significantly in the early CH treatment group compared to the later treatment group (T₀–T₂: P < 0.01). CH improved the antero-posterior jaw relationship. No harms were encountered. Conclusions: Although the upper face height increased, the mandible showed anterior rotation after CH treatment. The Gonial angle was significantly decreased in the EG compared to the LG. There were gender-specific differences in both sagittal and vertical dimensions when examining interrelations in dimensional changes. The differences found between the early and later treatment groups were not clinically important when the cephalometric results are considered. Clinical registration: ClinicalTrials.gov (NCT02010346)

Scientific thinking and decision-making in everyday life

Scientific reasoning plays an important role in science literacy and science capital, i.e. who in society can access, understand, engage with, and use scientific knowledge and resources that have social and economic value (Archer, 2015; Howell and Brossell, 2021). Education and scientific content knowledge provide the necessary framework to understand scientific concepts. However, education may not give a straightforward protective effect against naïve theories, heuristic thinking, and bias, which tend to persist even when people are aware that they are active (Zmigrod et al., 2021; Morsanyi et al., 2009). Cognitive flexibility, the capacity to adjust one’s thinking to different situations, has been linked to perceptual processing, creativity, and ideological attitudes, suggesting that it also plays an important role in engaging with new ideas, reasoning, and decision-making (Blake & Palmisano, 2021; Zmigrod et al., 2019). Recent research suggests that reasoning and decision-making are also driven by how people engage with information on a social and emotional level. Trait-like individual qualities such as curiosity, openness and motivation to seek answers, and willingness to consider alternative viewpoints also contribute to how and why people seek, filter, and integrate new information (Zedelius et al., 2021; FitzGibbon et al., 2020). Moreover, understanding how people engage with information to update or maintain knowledge and beliefs is essential to addressing the issues of misinformation and disinformation in a “post-truth” society (Scheufele & Krause, 2019). This study will employ exploratory factor analysis on a battery of surveys and cognitive tasks to identify relationships between personality traits related to information-seeking, science-related attitudes and experiences, and cognitive skills and styles. The goals for this study are to: 1. Identify the factors underlying engagement with scientific thinking and reasoning. 2. Understand how the factors are related to each other in order to develop a framework of people's engagement with science. The factors identified from this exploratory phase feed into a second study phase which focuses on the citizen’s initiative task, a realistic science-related decision-making task. In the citizen’s initiative task, participants are presented with a petition related to reclassifying peat as a renewable resource, a recent subject of debate in Finland. Participants are asked about their likelihood of supporting the petition and their familiarity, curiosity and interest in the topic. Then, they are presented with a series of six news and information sources on the subject representing different levels of authority and credibility and asked to evaluate the quality of the sources, and again asked about their opinions on the petition. The outcome variables from this task represent realistic behavior when encountering a science-related decision in everyday life: e.g. time spent information seeking, source evaluation, and self-reported shifts in interest and familiarity with a topic. We are interested in which factors from the first phase predict behavior in the citizen’s initiative task. In the first phase, we identify the relationships between cognitive, personality, attitudinal, and behavioural factors and create profiles that describe how people engage with scientific concepts in general. In the second phase, we examine how the different profiles behave when presented with the realistic citizen’s initiative task. Plans for the second study phase will be reported in a subsequent preregistration and the citizen’s initiative data are not further described here

Dental arch effects after early and later timed cervical headgear treatment—a randomized controlled trial

Summary Background: Cervical headgear (CH) is a commonly used orthodontic appliance and its dentoalveolar changes are known. However, the effects related to gender and timing have gained less attention. Objectives: To examine dimensions of dental arches among children with Class II occlusion without posterior mandibular rotation according to timing of Kloehn-type CH treatment. Trial design: Prospective, randomized, parallel-group controlled trial. Methods: Sixty-seven seven-year-old children with a Class II occlusion were included in the study. The children were randomized into two equal-size groups in 1:1 ratio by sealed-envelope randomization. The early group (EG, n = 33) was treated between T₀ and T₁ (26 months), right after eruption of the first maxillary molars. The late group (LG, n = 34) was treated between T₁ and T₂ (24 months). The children were treated with CH until normal Class I occlusion on first molars was achieved. Impressions for dental casts were taken from all participants at T₀, T₁, and T₂. Blinding was applicable for outcome assessors. Changes in dental cast measurements were compared between the groups and genders using t-test, Mann-Whitney U-test, and repeated measures analysis of variance. Results: Of the children, 56 completed the study. The maxillary arch length and the transversal changes between the upper canines and upper first molars were significantly increased in EG at T₀−T₁ (P < 0.001). At T₂, the transversal dimension between the upper first molars was larger (P < 0.05), and in the lower arch the mandibular arch length (P < 0.05) and the transversal dimension between the lower first molars (P < 0.01) were increased in EG males compared to LG males. No harms were encountered. Conclusions: The male gender benefits most from early timing of the CH treatment, showing larger dimensions at the end of the follow-up. The results clearly indicated a wider and longer upper dental arch and spontaneous expansion of the lower dental arch after treatment. Clinical registration: NCT02010346

Effects of headgear timing on dental arch changes from 7 to 18 years of age:a follow-up study

Abstract Background: Dental arch effects after cervical headgear (CHG) treatment have been researched from several different perspectives. However, the long-term effects of CHG timing are still unknown. Objectives: To analyse the long-term effects of CHG timing on dental arches. Material and methods: A total of 67 children with Angle Class II malocclusion comprised the study group in this trial. The participants were randomized into two equal-sized groups. In the early group (EG, n = 33), treatment was started after the eruption of the first upper molars. In the later-timed group (LG, n = 34), treatment was started 18 months later compared with the early group. Long-term effects were measured from dental casts taken at five time points between 7 and 18 years of age. Results: The total maxillary dental arch length was achieved earlier, the gained length persisted better in the long term, and significantly more space was achieved in EG compared with LG (P = .048). The intermolar width in the maxillary dental arch was more stable and was reached earlier in EG compared with LG (P = .002). The results showed that in terms of total mandibular arch length increases, EG males benefited the most and LG females the least from CHG treatment (P = .031). Conclusions: Both genders benefited from earlier CHG treatment. The maxillary dental arches remained longer, and the final width was gained earlier in EG compared with LG

Reduced evoked activity and cortical oscillations are correlated with anisometric amblyopia and impairment of visual acuity

Amblyopia is a developmental disorder associated with abnormal visual experience during early childhood commonly arising from strabismus and/or anisometropia and leading to dysfunctions in visual cortex and to various visual deficits. The different forms of neuronal activity that are attenuated in amblyopia have been only partially characterized. In electrophysiological recordings of healthy human brain, the presentation of visual stimuli is associated with event-related activity and oscillatory responses. It has remained poorly understood whether these forms of activity are reduced in amblyopia and whether possible dysfunctions would arise from lower- or higher-order visual areas. We recorded neuronal activity with magnetoencephalography (MEG) from anisometropic amblyopic patients and control participants during two visual tasks presented separately for each eye and estimated neuronal activity from source-reconstructed MEG data. We investigated whether event-related and oscillatory responses would be reduced for amblyopia and localized their cortical sources. Oscillation amplitudes and evoked responses were reduced for stimuli presented to the amblyopic eye in higher-order visual areas and in parietal and prefrontal cortices. Importantly, the reduction of oscillation amplitudes but not that of evoked responses was correlated with decreased visual acuity in amblyopia. These results show that attenuated oscillatory responses are correlated with visual deficits in anisometric amblyopia.Peer reviewe

Occlusal characteristics and oral health-related quality of life in adults operated due to sagittal synostosis in childhood:a case–control study with 26 years of follow-up

Abstract Purpose: The aim of this case–control study was to investigate occlusal characteristics, received orthodontic treatment, oral health-related quality of life (OHRQoL), and satisfaction with dental esthetics in adults operated due to sagittal synostosis. Methods: The study group consisted of 40 adults (25 males, 15 females, mean age 27.4 years, range 18–41) who were operated due to isolated sagittal synostosis in childhood. The control group comprised 40 age and gender-matched adults. Occlusal characteristics were evaluated clinically during study visits. Information on the previous orthodontic treatment was collected from dental records. OHRQoL was measured using the 14-item Oral Health Impact Profile (OHIP-14), and satisfaction with dental esthetics was evaluated using a visual analogue scale. Results: No statistically significant differences were found between the patient group and the controls in malocclusion traits (overjet, overbite, molar relationships, crossbite, scissor bite), previous orthodontic treatment, pre-treatment malocclusion diagnoses, OHIP variables, or satisfaction with dental esthetics. However, there was a tendency toward increased overjet and overbite in scaphocephalic patients. Conclusions: It seems that adults with scaphocephaly operated in childhood do not differ from the average population in terms of occlusion, received orthodontic treatment, or oral health-related well-being

Dental age assessment on panoramic radiographs:comparison between two generations of young Finnish subjects

Abstract Objective: To analyse the accuracy of a meta-analysis-based dental age assessment (DAA) method in Finnish paediatric patients and to compare the dental development between two generations of Finnish children. Methods: Panoramic radiographs of Finnish Caucasian healthy children from two generations (early: born 1981–1984; subsequent: born 1996–2008) were analysed. All developing teeth on the left maxilla and mandible as well as the third permanent molars were analysed following Demirjian’s classification. For each patient, dental age was calculated and compared with chronological age. Dental maturation patterns between the two groups were compared. Results: The study included 200 Finnish Caucasian healthy children from two generations (early: aged 7–13 years; subsequent: aged 6–15 years). In the early generation, DAA underestimated the chronological age by a mean of 3.15 years. The underestimation was only 0.11 years in patients < 10 years, but 3.86 years in patients ≥ 10 years. In the subsequent generation, the dental age was overestimated by a mean of 0.34 years; by 0.40 years in patients < 10 years and by 0.08 years in patients ≥ 10 years. Conclusions: The present DAA method is applicable to current Finnish children. Differences in dental development between two generations of Finnish children were detected