Deep brain stimulation:hoito ja hoidon tarkkuuteen vaikuttavat tekijät

Tiivistelmä. Syväaivostimulaatio on jo pitkään ollut tehokas tapa lukuisten neurologisten sairauksien pysyvään hoitoon mahdollistaen esimerkiksi Parkinsonin taudissa parhaimmillaan potilaan täyden itsenäisyyden palauttamisen ja lääkityksestä luopumisen. Syväaivostimulaatiota voidaan pitääkin eräänlaisena ”aivojen sydämentahdistimena”. Stimulaatiossa johdetaan elektrodien välityksellä korkeataajuista virtaa potilaan aivoihin halutulle kohdealueelle, joka saa aikaan toivotun vasteen. Vaste esimerkiksi Parkinsonin taudin kohdalla on vapinan merkittävä väheneminen tai loppuminen. DBS-hoidolla pyritään usein säätelemään tai hillitsemään hyperaktiivista, synkronoitua tai liian vähäistä neurosignalointia. Yleisimpiä syväaivostimulaation hoitokohteita ovat Parkinsonin tauti, epilepsia sekä Dystonia. DBS-hoidon tehokkuutta on kuitenkin tutkittu myös masennuksen, syömishäiriön, Touretten syndrooman sekä esimerkiksi pakko-oireisen häiriön (OCD) hoidossa. Yhteistä kaikille hoitomuodoille on pyrkimys säädellä välittäjäaineen, esimerkiksi dopamiinin määrää, siitä johtuvaa neuronien välistä signalointia ja sen aktiivisuutta potilaalla

Diversity and transmission of Aleutian mink disease virus in feral and farmed American mink and native mustelids

Aleutian mink disease virus (AMDV), which causes Aleutian disease, is widely spread both in farmed mink and wild mustelids. However, only limited data are available on the role of wild animals in AMDV transmission and spread. Our aim was to shed light on AMDV transmission among wild mustelids and estimate the effect of intense farming practices on the virus circulation by studying AMDV prevalence and genetic diversity among wild mustelids in Poland. We compared AMDV seroprevalence and proportion of PCR-positive individuals in American mink, polecats, otters, stone martens, and pine martens and used the phylogenetic analysis of the NS1 region to study transmission. In addition, we used a metagenomic approach to sequence complete AMDV genomes from tissue samples. In eastern Poland, AMDV seroprevalence in wild mustelids varied from 22 per cent in otters to 62 per cent and 64 per cent in stone martens and feral mink, respectively. All studied antibody-positive mink were also PCR positive, whereas only 10, 15, and 18 per cent of antibody-positive polecats, pine martens, and stone martens, respectively, were PCR positive, suggesting lower virus persistence among these animal species as compared to feral mink. In phylogenetic analysis, most sequences from feral mink formed region-specific clusters that have most likely emerged through multiple introductions of AMDV to feral mink population over decades. However, virus spread between regions was also observed. Virus sequences derived from farmed and wild animals formed separate subclusters in the phylogenetic tree, and no signs of recent virus transmission between farmed and wild animals were observed despite the frequent inflow of farmed mink escapees to wild populations. These results provide new information about the role of different mustelid species in AMDV transmission and about virus circulation among the wild mustelids. In addition, we pinpoint gaps of knowledge, where more studies are needed to achieve a comprehensive picture of AMDV transmission.Peer reviewe

RydIQule: A Graph-based Paradigm for Modelling Rydberg and Atomic Systems

We describe a numerical technique and accompanying open-source Python software package called RydIQule. RydIQule uses a directional graph, relying on adjacency matrices and path-finding to generate a Hamiltonian for multi-level atomic systems. RydIQule then constructs semi-classical equations of motion (Bloch equations) into a tensor which can store an entire simulation consisting of varied system parameters. Using this framework, RydIQule returns solutions significantly faster than typical for interpreted programming languages. RydIQule extends beyond the capabilities of currently-available tools, facilitating rapid development in atomic and Rydberg spectroscopy. To demonstrate its utility, we use RydIQule to simulate a Doppler-broadened Rydberg atomic sensor that simultaneously demodulates five rf tones spanning from 1.7 to 116 GHz. Using RydIQule, this simulation can be solved in several hours on a commercial off-the-shelf desktop computer.Comment: 5 pages, 3 figure

Co-circulation of highly diverse Aleutian mink disease virus strains in Finland

Aleutian mink disease virus (AMDV) is the causative agent of Aleutian disease (AD), which affects mink of all genotypes and also infects other mustelids such as ferrets, martens and badgers. Previous studies have investigated diversity in Finnish AMDV strains, but these studies have been restricted to small parts of the virus genome, and mostly from newly infected farms and free-ranging mustelids. Here, we investigated the diversity and evolution of Finnish AMDV strains by sequencing the complete coding sequences of 31 strains from mink originating from farms differing in their virus history, as well as from free-ranging mink. The data set was supplemented with partial genomes obtained from 26 strains. The sequences demonstrate that the Finnish AMDV strains have considerable diversity, and that the virus has been introduced to Finland in multiple events. Frequent recombination events were observed, as well as variation in the evolutionary rate in different parts of the genome and between different branches of the phylogenetic tree. Mink in the wild carry viruses with high intra-host diversity and are occasionally even co-infected by two different strains, suggesting that free-ranging mink tolerate chronic infections for extended periods of time. These findings highlight the need for further sampling to understand the mechanisms playing a role in the evolution and pathogenesis of AMDV.Peer reviewe

Differences in JAK Isoform Selectivity Among Different Types of JAK Inhibitors Evaluated for Rheumatic Diseases Through In Vitro Profiling

Objective: The selectivity of JAK inhibitors (Jakinibs) forms the basis for understanding their clinical characteristics; however, evaluation of selectivity is hampered by the lack of comprehensive head-to-head studies. Our objective was to profile in parallel Jakinibs indicated or evaluated for rheumatic diseases for their JAK and cytokine selectivity in vitro. Methods: We analyzed 10 Jakinibs for JAK isoform selectivity by assaying their inhibition of JAK kinase activity, binding to kinase and pseudokinase domains, and inhibition of cytokine signaling using blood samples from healthy volunteers and using isolated peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis and from healthy donors. Results: Pan-Jakinibs effectively suppressed kinase activity of 2 to 3 JAK family members, whereas isoform-targeted Jakinibs possessed varying degrees of selectivity for 1 or 2 JAK family members. In human leukocytes, Jakinibs predominantly inhibited the JAK1-dependent cytokines interleukin-2 (IL-2), IL-6, and interferons (IFNs). In PBMCs from patients with rheumatoid arthritis compared with healthy controls, inhibition of these cytokines was more pronounced, and some cell-type and STAT isoform differences were observed. Novel Jakinibs demonstrated high selectivity: the covalent Jakinib ritlecitinib showed 900- to 2,500-fold selectivity for JAK3 over other JAKs and specific suppression of IL-2-signaling, whereas the allosteric TYK2 inhibitor deucravacitinib inhibited IFNα signaling with high specificity. Interestingly, deucravacitinib targeted the regulatory pseudokinase domain and did not affect JAK in vitro kinase activity. Conclusion: Inhibition of JAK kinase activity did not directly translate into cellular inhibition of JAK/STAT signaling. Despite differences in JAK selectivity, the cytokine inhibition profiles of currently approved Jakinibs were highly similar, with preference for JAK1-mediated cytokines. Novel types of Jakinibs showed narrow cytokine inhibition profile specific for JAK3- or TYK2-mediated signaling. (Figure presented.).Peer reviewe

Upscaling field-measured seasonal ground vegetation patterns with Sentinel-2 images in boreal ecosystems

Aboveground biomass (AGB) and leaf area index (LAI) are key variables of ecosystem processes and functioning. Knowledge is lacking on how well the seasonal patterns of ground vegetation AGB and LAI can be detected by satellite images in boreal ecosystems. We conducted field measurements between May and September during one growing season to investigate the seasonal development of ground vegetation AGB and LAI of seven plant functional types (PFTs) across seven vegetation types (VTs) within three peatland and forest study areas in northern Finland. We upscaled field-measured AGB and LAI with Sentinel-2 (S2) imagery by applying random forest (RF) regressions. Field-measured AGB peaked around the first week of August and, in most cases, one to two weeks later than LAI. Regarding PFTs, deciduous vascular plants had clear unimodal seasonal patterns, while the AGB and LAI of evergreen vegetation and mosses remained steady over the season. Remote sensing regression models explained 24.2–50.2% of the AGB (RMSE: 78.8–198.7 g m−2) and 48.5–56.1% of the LAI (RMSE: 0.207–0.497 m2 m−2) across sites. Peatland-dominant sites and VTs had a higher prediction accuracy. S2-predicted peak dates of AGB and LAI were one to three weeks earlier than the field-based ones. Our findings suggest that boreal ground vegetation seasonality varies among PFTs and VTs and that S2 time series data can be applied to monitor its spatiotemporal patterns, especially in treeless regions

Associations Between Brain Gray Matter Volumes and Adipose Tissue Metabolism in Healthy Adults

Objective Gray matter (GM) volume in different brain loci has been shown to vary in obesity and diabetes, and elevated fasting plasma nonesterified fatty acid (NEFA) levels have been suggested as one potential mechanism. The hypothesis presented in this study is that brown adipose tissue (BAT) activity may correlate with GM volume in areas negatively associated with obesity and diabetes.Methods A total of 36 healthy patients (M/F: 12/24, age 39.7 +/- 9.4 years, BMI 27.5 +/- 5.6 kg/m(2)) were imaged with positron emission tomography using fatty acid analog [F-18]FTHA to measure NEFA uptake and with [O-15]H2O to measure perfusion during cold exposure, at room temperature during fasting, or during a postprandial state. A 2-hour hyperinsulinemic euglycemic clamp was performed to measure whole-body insulin sensitivity (M value, mean 7.6 +/- 3.9 mg/kg/min). T1-weighted magnetic resonance imaging at 1.5 T was performed on all patients.Results BAT NEFA uptake was associated directly with GM volume in anterior cerebellum and occipital lobe (P <= 0.04) when adjusted for age, gender, and intra-abdominal fat volume and with anterior cerebellum, limbic lobe, and temporal lobe GM volumes when adjusted for M value.Conclusions BAT NEFA metabolism may participate in protection from cognitive degeneration associated with cardiometabolic risk factors, such as central obesity and insulin resistance. Potential causal relationships between BAT activity and GM volumes remain to be examined