Invalidisäätiö

During lucid dreaming (LD), dreamers are aware that they are dreaming and may be able to influence the oneiric content. There has been recent debate about the relative importance of the ability to influence the dream and having agency over the pure awareness of dreaming. To underline this, we examined the associations of lucid dreams without agency (LD-Ag) and lucid dreams with agency (LD + Ag) to sleep and mental health problems and long COVID during the pandemic. We collected data in 16 countries on four continents from May to December 2021 on 10,715 subjects. Logistic regression was performed to predict LD-Ag and LD + Ag, with a sample of 8133 participants. We found that 30% of the participants frequently knew they were dreaming during the pandemic. About half of those (17%) reported that they could influence their dreams. Female gender and anxiety symptoms were negatively associated with LD + Ag. Dream recall, nightmares, insomnia, dream enactment behaviour (DEB), sleep vocalisation, short and long COVID and PTSD were positively associated with LD + Ag. Old age, dream recall, nightmares and anxiety symptoms were positively associated with LD-Ag, while short sleep length, being an evening type, and short COVID were negatively associated with LD-Ag. The different associations for LD-Ag and LD + Ag suggest that they may be distinct sleep states. This is also the first study to show that both COVID-19 and long COVID are associated with LD.

Objective Antisense oligonucleotides (ASOs) have reached the clinic; however, they lack tissue specificity. Albumin is a plasma-abundant macromolecule that has been shown to accumulate in inflamed tissues. In this work, we have designed a recombinant human albumin (rHA)-based biomolecular assembly incorporating a DNase-resistant phosphorothioate-based complementary oligonucleotide (cODN) and an anti-ADAMTS5 ASO for potential delivery to inflamed sites. Ultrasound (US) was used to trigger ASO release from the assembly and enhance internalization into articular cartilage. Methods A phosphorothioate cODN was conjugated to rHA through a maleimide cross-linker after which, a therapeutic ADAMTS5-specific gapmer ASO was annealed to the cODN. ASO release was assessed after exposing the biomolecular assembly to different US conditions using an US-actuated medical needle operating at 32.2 kHz. Gene silencing efficiency of US-treated anti-ADAMTS5 ASO was assessed in human primary chondrocytes isolated from osteoarthritic patients. US-mediated ASO penetration into articular cartilage was assessed on ex vivo bovine articular cartilage. Results ASO release was observed after exposure to US waves in continuous mode conditions that did not compromise ASO gene silencing efficiency in human chondrocytes. Furthermore, US increased ASO internalization into bovine articular cartilage after 30 min of application without detrimental effects on chondrocyte viability. Conclusion A medical needle driven by continuous US waves at 32.2 kHz has the capability of disassembling a duplex oligonucleotide and enhancing released ASOs internalization into articular cartilage. This work offers the potential delivery and the local triggered release of ASOs at the surface of articular cartilage providing potential benefits for the treatment of diverse cartilage pathologies.

Evidence suggests that adolescents and adults with a later chronotype have poorer sleep habits and are more susceptible to unhealthy behaviors, but little is known about these associations in younger children. The objective of the study was to (1) identify and compare individual chronotype tendencies among preschool-aged children and (2) investigate associations of sleep dimensions and chronotype with diet. Participants were 636 3-6 years old (mean ± SD age: 4.74 ± 0.89 years, 49% girls) preschoolers from the cross-sectional Increased Health and Well-Being in Preschoolers (DAGIS) study in Finland. Sleep duration, sleep variability (in duration and midpoint), social jetlag, and midsleep on weekends adjusted for sleep debt (MSWEadj) were measured with 7-day actigraphy. Morning, intermediate, and evening chronotype tendencies were defined based on the lowest and highest 10th percentile cutoffs of MSWEadj. Food, energy, and macronutrient intake were assessed from 3-day records. Associations between sleep dimensions and diet were assessed with regression models. MSWEadj was 1:13 ± 14 minutes for morning (n = 64), 2:25 ± 28 minutes for intermediate (n = 560), and 3:38 ± 15 minutes for evening (n = 64) chronotype tendency. Children with an evening chronotype tendency had greater social jetlag and sleep variability. Having an evening chronotype tendency was associated with higher added sugar, higher sugary food consumption, and lower vegetable consumption compared to intermediate tendency types. A later chronotype (MSWEadj) was associated with higher sugary food consumption, as well as lower vegetable and fiber intake. Sleep duration, social jetlag, and sleep variability were not associated with diet. Several less healthy sleep and diet behaviors were observed among children with later chronotypes. Future public health interventions aimed towards children would benefit from taking into account chronotype.

BackgroundThe goal of all surgical and orthopaedic training is to ensure necessary education and surgical skills without compromising the quality of operations or patient safety. Anterior cruciate ligament reconstruction (ACLR) is a common multi-staged orthopaedic surgical procedure with a learning curve. Previous studies focus mainly on learning or the learning curve of one surgeon and tunnel placements. The aims of this study were to define the learning curve in arthroscopic ACLRs, define the number of procedures needed before the surgical “knifetime” plateaus, examine the effect of experience on complications, and identify possible individual differences in the surgical learning curve. MethodsThe study included the first 50 consecutive ACLR operations of five orthopaedic surgeons, thus, a total of 250 patients. For comparison and statistical analysis, patients were arranged into five groups, each comprising 50 patients (=order group). Order group 1 comprised the first 10 patients operated on by each of the five surgeons, group 2 patients 11–20, group 3 patients 21–30, group 4 patients 31–40, and group 5 the last 10 patients. The learning curve was defined with a LOESS curve. Surgical time and complications, including graft failure and postoperative knee instability, were analysed between order groups and between surgeons. ResultsMedian surgical time was 105 (interquartile range 82–124) min. The learning curve showed the first steep decline in surgical time and started to settle slowly after 20 reconstructions. Surgical time was significantly longer when order group 1 was compared with order group 2 (p = 0.031), and when order group 1 was compared separately with order groups 3, 4, and 5 (p < 0.001). Operation order alone explained only 17.1% of the alteration in surgical time. No significant difference emerged in graft failure rate between the order groups or the surgeons. Objective instability of the knee showed a significant difference when order group 1 was compared separately with order group 3 and with order group 4 (p = 0.004). Surgical time differed between surgeons (p < 0.001), and the shape of the learning curve showed great individual variability. ConclusionIn the first 10 to 20 ACLR operations, the surgical time was longer and the complication rate higher, but thereafter both started to settle down. We recommend that first 10–20 ACLR operations should be supervised.

Long-term outcome of small head (28 mm) metal-on-metal (MoM) total hip arthroplasty (THA) is available mainly for Metasul devices (Sulzer Medica, Winterthur, Switzerland). Biomet MoM THA was frequently used in Finland. Therefore, we assessed long-term survivorship of the M2a 28-mm RingLoc MoM THA (Biomet, Warsaw, IN, USA) and compared it with the metal-on-polyethylene (MoP) RingLoc THA from the same manufacturer. We conducted a register study based on THAs from the Finnish Arthroplasty Register performed between January 1, 2000 and December 31, 2007. 290 28-mm head M2a MoM THAs and 1,647 28-mm head MoP THAs (reference group) were included. The endpoint was revision for any reason, or revision for aseptic loosening, osteolysis, liner wear, or metallosis as one group. Kaplan-Meier survival estimates were calculated, and revision risks were assessed using a Cox multiple regression model, both with 95% confidence intervals (CI). No difference was found in the 15-year Kaplan-Meier survivorship between the 28-mm head M2a RingLoc MoM THA and the reference group for any reason for revision (87.7% [82.9-92.1] and 83.3% [81.0-85.3], respectively). The adjusted hazard ratio (HR) for any reason for revision for the MoM THA group compared with the reference group was at least equal or better (0.70 [0.48-1.02]). Both groups presented similar survival for revision for aseptic loosening of the cup, osteolysis, liner wear, or metallosis, at 96.2% (92.7-98.0) and 95.4% (93.9-96.5), respectively. In the long-term survival there was no difference between the M2a 28-mm RingLoc MoM THA and 28-mm MoP THA. Further follow-up regimens for M2a 28-mm RingLoc THA patients may be unnecessary, but long-term metal ion and radiological data is needed before any formal suggestions.

Nuclear factor κ light-chain enhancer of activated B cells (NF-κB) family of evolutionarily conserved transcription factors are involved in key cellular signaling pathways. Previously, hypogammaglobulinemia and common variable immunodeficiency (CVID)-like phenotypes have been associated with NFKB1 variants and loss-of-function NFKB1 variants have been reported as the most common monogenic cause for CVID among Europeans. Here, we describe a Finnish cohort of NFKB1 carriers consisting of 31 living subjects in six different families carrying five distinct heterozygous variants. In contrast to previous reports, the clinical penetrance was not complete even with advancing age and the prevalence of CVID/hypogammaglobulinemia was significantly lower, whereas (auto)inflammatory manifestations were more common (42% of the total cohort). At current stage of knowledge, routine genetic screening of asymptomatic individuals is not recommended, but counseling of potential adult carriers seems necessary.

ABSTRACT Introduction The etiology and pathogenesis of osteoarthritis (OA) have been intensely investigated; however, the disease course and progression are not completely understood. A prominent role for interstitial collagenases is recognized in this degenerative process; hence, strategies to target them are of major interest. Areas covered The pathogenesis of OA, the role of interstitial collagenases (MMP-1, −8, and −13), and collagenase modifying drugs are examined and discussed. We reviewed relevant papers from PubMed and Google Scholar. Expert opinion There is strong evidence for the therapeutic potential of MMP inhibitors in OA; however, they are not expected to impact the inflammatory process. Therefore, there is a need for a relative inhibitor of MMP-13 collagenase, which possesses anti-inflammatory properties. The identification of novel broad-spectrum relative to multiple peptidase inhibitors could provide desirable tools for the prophylaxis, cure, or treatment of diseases involving articular cartilage (AC) degradation, in particular OA.

We report the use of a three-dimensional virtual surgical planning technique including both fusion and superimposition to obtain harmony and symmetry of the face in an 18-year-old woman suffering from cherubism. The treatment contained several threedimensional techniques that allowed precise planning and a predictable surgical outcome. The reduction plasty was successful, and the postoperative healing was uneventful. No relapse of the disease occurred after the surgical treatment and the sensation of the mentalis area recovered. The patient was satisfied with the aesthetic result and no additional surgery was needed. The surgical planning techniques described, and the CAD/CAM patient-specific resection guides seems to be safe and reliable in a one-step surgical treatment of cherubism patients after the disease has clearly ceased based on radiological findings. A systematic review of the literature on surgical correction of deformities due to cherubism was conducted. The systematic review of the existing literature was performed on the available studies from PubMed and Ovid Medline published before June 9, 2020. The search term was ''Cherubism.'' The inclusion criteria were: 1) full article published in English and 2) the patient had surgical treatment. We excluded the cases that included only minor surgery as biopsy or only treatment of unerupted teeth. The database identified 638 citations of which 50 met the eligibility criteria. The systematic review revealed no earlier use of surgical 3D planning in the treatment of cherubism.

The Ikaros family transcription factors regulate lymphocyte development. Loss-of-function variants in IKZF1 cause primary immunodeficiency, but Ikaros family members IKZF2 and IKZF3 have not yet been associated with immunodeficiency. Here, we describe a pedigree with a heterozygous truncating variant in IKZF2, encoding the transcriptional activator and repressor Helios, which is highly expressed in regulatory T cells and effector T cells, particularly of the CD8+ T cell lineage. Protein-protein interaction analysis revealed that the variant abolished heterodimerization of Helios with Ikaros and Aiolos and also prevented Helios binding to members of the Mi-2/NuRD chromatin remodeling complex. Patients carrying the IKZF2 variant presented with a combined immunodeficiency phenotype characterized by recurrent upper respiratory infections, thrush and mucosal ulcers, and chronic lymphadenopathy. With extensive immunophenotyping, functional assays, and transcriptional analysis, we show that reduced Helios expression was associated with chronic T cell activation and increased production of proinflammatory cytokines both in effector and regulatory T cells. Lymph node histology from patients indicated dysregulated germinal center reactions. Moreover, affected individuals displayed a profound reduction in circulating MAIT cell numbers. In summary, we show that this previously undescribed loss-of-function variant in Helios leads to an immunodeficiency with signs of immune overactivation.