Myoclonus-dystonia (DYT11, DYT-SGCE) — a channelopathy?

Introduction. Kaczyńska et al. reported a family with myoclonus-dystonia (M-D) caused by a truncating SGCE mutation, in which two members had epilepsy. Further, patients had mild psychiatric and developmental deficits.Clinical reflections. Characteristic motor features of M-D include myoclonus, dystonia and tremor. A wide range of additional disease manifestations are known. A few patients with M-D have seizures.Clinical implications. Altered neuronal excitability has been found in the pathogenesis of M-D. This may explain the partial effectiveness of antiepileptics and a lower seizure threshold, and could encourage trials of other membrane stabilisers. Careful clinical observations of seemingly well-known diseases remain important

Skogsvårdsstöd : växande eller igenväxande skogar?

Svensk skog täcker cirka 70 % av landytan och utgör en viktig del av landets sysselsättning, produktionsvärde och kompensation för global uppvärmning. Skogen erbjuder en mångfald av värden såsom klimatsmarta råvaror och produkter. Ett röjningsbehov råder primärt hos landets privata enskilda skogsägare. Föryngringsplikt har gällt sedan 1903 medan krav på röjning varade mellan 1979 – 1993. Skogspolitiken har varit mer reglerande men övergick år 1993 till frihet under ansvar. Sverige har som vision att bli fossilfritt till år 2050. En utökad efterfrågan predikteras av förnyelsebara råvaror och produkter. Syftet med denna uppsats är att undersöka privata enskilda skogsägares preferenser kring röjning och hur deras motivation och förmåga ter sig med eller utan olika politiska styrmedel. Studien fokuserar på medlemmar hos Skogsägarföreningarna Norra skogsägarna, Norrskog och Mellanskog. Enkätundersökningen skickades via e-post till 2 705 medlemmar med slumpmässig spridning och en svarsfrekvens på 20 %. Huvudsakligen behandlade enkäten historiska, aktuella och framtida frågor kring röjning. Skogsvårdsstöd antas omfatta både ekonomiska och informativa styrmedel, där hälften ansåg att det ekonomiska RÖJ-bidraget var det viktigaste förslaget. Skogsägarnas främsta mål enligt 89 % av de svarande var att förvalta skogen till kommande generationer, maximera värdetillväxt eller intäkter. Respondenternas associationer till röjning stämde till stor del med litteraturstudierna. Kvinnor bekräftades prioritera informativa styrmedel i större utsträckning än män. Äldre skogsägare bekräftades ha genomgått skogliga utbildningar i större skala jämfört med yngre. Samband uppvisades också vad gällde mer tilltro till den egna förmågan att fatta beslut om röjning om skogsägaren hade en skoglig utbildning. Slutsatsen i den här studien är att skogsägarna anser att röjning övergripande anses vara en investering snarare än en kostnad. Motivation och förmåga till att röja eller låta röja större andelar av sitt behov skulle öka för majoriteten av de privata enskilda skogsägarna via olika politiska styrmedel.The Swedish forest covers circa 70 % of the land area and represents an important part of the country’s employment, production output and resistance to the greenhouse effect. The forest offers a diversity of values such as climate smart raw materials and products. A need for pre-commercial thinning is primarily required among nonindustrial forest owners. A legal regeneration duty has been valid since 1903 while obligation for pre-commercial thinning lasted between 1979 and 1993. Forest policy has been more regulated until freedom under responsibility was initiated in 1993. Sweden has the vision of being fossil free until 2050. An increased demand for renewable raw material is predicted. The aim of this thesis was to investigate preferences of pre-commercial thinning among private individual forest owners and how different political instruments affect their motivation and ability of pre-commercial thinning. This study was carried out among members of the forest ownership associations Norra skogsägarna, Norrskog and Mellanskog. The survey was randomly sent by e-mail to 2 705 participants with a response rate of 20 %. Historical and future issues of pre-commercial thinning were covered in the survey. Support for forest tending assume to include both economic and informative policy instruments. Half of the respondents considered that the pre-commercial thinning subsidy was the most important proposition. The forest owners’ primary goal according to 89 % the respondants was to manage the forest for following generations, maximize value growth or income. The respondents associations of pre-commercial thinning corresponded mainly with literature studies. Women were confirmed to rank informative instruments higher than men. Older forest owners had studied forestry more than younger forest owners. Correlations were also confirmed among the trust in the forest owners’ abilities to make decisions about pre-commercial thinning if they had a forest education. This this study concludes that the forest owners consider pre-commercial thinning to be associated with an investment rather than a cost. Motivation and ability of pre-commercial thinning would increase among the majority of private non-industrial forest owners with different political instruments

Wind damage factors for Scots pine and lodgepole pine on SCA´s areas after the storm Dagmar

Dagmar är en av de mest förödande stormarna, som med sina 4-5 miljoner kubikmeter vindfälld skog präglat skogssverige det senaste årtiondet. Skogsbolaget SCA förlorade stora mängder skog den 26 december 2011 till följd av stormen. Två av trädslagen på SCA:s marker är tall och contortatall, med olika förutsättningar vad gäller förmåga att motstå stormvindar. Tillhandahållna data kom från SCA:s inventering före Dagmar, under åren 2007-2011, respektive efter stormen, i februari-mars 2012. Inventerat data har sammanställts, bearbetats och analyserats i Microsoft Office Excel, MiniTab 16 och ArcMap 10.1. Statistiskt signifikanta samband för insamlat data saknades mellan beståndsmedelhöjd och skadad volym skog. Samband erhölls däremot mellan skötselmetod, gallrat eller ogallrat, och skadade bestånd. Utifrån resultaten kan vi konstatera att trädslaget tall är att föredra i stormskadedrabbade områden. Vidare är gallrade bestånd känsligare än ogallrade inom en viss tidsperiod efter skötselingreppet. Tidpunkten före eller efter stormskada, ger en relativ ökning av skadetyperna ”liggande” och ”lutande” för tall och contortatall.Dagmar is one of the most devastating storms, with its 4-5 million cubic meters of wind damaged forest, that has struck Swedish forests since the ten last years. The forest product company SCA lost a lot of timber volume the 26th of December 2011 due to the storm. Two of the tree species on the areas of SCA, Scots pine and lodgepole pine, have different abilities of resisting wind damage. Provided data came from the inventory of SCA before Dagmar, years 2007-2011, and after the storm, February-Mars 2012. Inventoried data has been compiled, processed and analyzed in Microsoft Office Excel, MiniTab 16 and ArcMap 10.1. Statistically significant correlations of collected data, did not match between average stand height and damaged volume of forest. Correlations were received between treatment, thinned and un-thinned, damaged stands. From the results, we could confirm that Scots pine should be preferred in areas prone to wind damage. Furthermore, thinned stands were more susceptible than un-thinned in a certain period of time after treatment. There was a difference between types of damage for the two species studied. The moment before or after wind damage, provides an increase of “horizontal” and “tilting” trees of Scots pine and lodgepole pine

Development and testing of a self administered version of the Freezing of Gait Questionnaire

Background: The Freezing of Gait Questionnaire (FOGQ) was developed in response to the difficulties of observing and quantifying freezing of gait (FOG) clinically as well as in laboratory settings. However, as the FOGQ is a clinician-administered patient-reported rating scale it cannot be used in postal surveys. Here we report the development and measurement properties of a self-administered version of the FOGQ (FOGQsa). Methods: A clinical sample and a postal survey sample of non-demented people with Parkinson's disease (PD; total n = 225) completed the FOGQsa and questionnaires concerning physical functioning (PF) and fall-related self efficacy (FES). Additional questions (No/Yes) regarded previous falls and whether they were afraid of falling. The clinical sample was also assessed with the Unified PD Rating Scale (UPDRS). Thirty-five participants completed FOGQsa and were also assessed with the original version (FOGQ) in a clinical interview. Results: There were no differences (P = 0.12) between FOGQ (median, 10; q1-q3, 2-14) and FOGQsa (median, 8; 214) scores. The Spearman (r(s)) and intra-class correlations between the two were 0.92 and 0.91 (95% CI, 0.82-0.95), respectively. For FOGQsa, corrected item-total correlations ranged between 0.68-0.89. Reliability was 0.93 (95% CI, 0.91-0.94). FOGQsa scores correlated strongest with UPDRS Item 14 (Freezing; r(s), 0.76) and with FES (r(s), -0.74). The weakest correlation was found with age (r(s), 0.14). Fallers scored significantly (p < 0.001) higher on FOGQsa compared to non-fallers, median scores 8 (q1-q3, 4-14) versus 2 (0-7). Those expressing a fear of falling scored higher (p < 0.001) than those who did not, median scores 2 (0-7) versus 6 (2-14). Conclusions: The present findings indicate that the FOGQsa is as reliable and valid as the original interview administered FOGQ version. This has important clinical implications when investigating FOG in large scale studies

Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson's disease:A dose-finding study

In advanced stages of Parkinson's disease, serotonergic terminals take up l-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of l-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks l-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against l-DOPA-induced dyskinesias in patients with Parkinson's disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of l-DOPA (Sinemet®) in 22 patients with Parkinson's disease (16 male/six female; 66.6 ± 8.8 years old) with l-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson's Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of l-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [-1.02(1.49); P = 0.004] and Rush Dyskinesia Rating Scale [-0.15(0.23); P = 0.003]; and maximum Clinical Dyskinesia Rating Scale score [-1.14(1.59); P = 0.005]. The post hoc analysis confirmed these results and also showed an antidyskinetic effect of 7.5 mg eltoprazine. Unified Parkinson's Disease Rating Scale part III scores did not differ between the placebo and eltoprazine treatments. The most frequent adverse effects after eltoprazine were nausea and dizziness. It can be concluded that a single dose, oral treatment with eltoprazine has beneficial antidyskinetic effects without altering normal motor responses to l-DOPA. All doses of eltoprazine were well tolerated, with no major adverse effects. Eltoprazine has a favourable risk-benefit and pharmacokinetic profile in patients with Parkinson's disease. The data support further clinical studies with chronic oral eltoprazine to treat l-DOPA-induced-dyskinesias

Molecular mechanisms separating two axonal pathways during embryonic development of the avian optic tectum

During embryonic development of the avian optic tectum, retinal and tectobulbar axons form an orthogonal array of nerve processes. Growing axons of both tracts are transiently very closely apposed to each other. Despite this spatial proximity, axons from the two pathways do not intermix, but instead restrict their growth to defined areas, thus forming two separate plexiform layers, the stratum opticum and the stratum album centrale. In this study we present experimental evidence indicating that the following three mechanisms might play a role in segregating both axonal populations: Retinal and tectobulbar axons differ in their ability to use the extracellular matrix protein laminin as a substrate for axonal elongation; the environment in the optic tectum is generally permissive for retinal axons, but is specifically nonpermissive for tectobulbar axons, resulting in a strong fasciculation of the latter; and growth cones of temporal retinal axons are reversibly inhibited in their motility by direct contact with the tectobulbar axon's membrane

Roentgen cephalometric analysis of ridge resorption and changes in jaw and occlusal relationships in immediate complete denture wearers

In eighteen subjects assigned for immediate complete upper and lower dentures, roentgen cephalometric recordings were made before extraction of the residual anterior dentition and 3 weeks, 3 months, 6 months and 1 year after denture insertion. The cephalometric analysis was based on electronic measurements of linear and angular morphological variables and computer head plots generated from 177 reference points (Walker, 1967), derived for each subject for each of the five observation stages. The reduction of the alveolar ridges was most rapid during the first 3 months of denture wear and particularly during the post-extraction period of 3 weeks. The reduction in anterior height of the lower ridge was on average twice as great as that of the upper ridge. The ridge resorption and the accompanying settling of the dentures on the basal seats, measured from lead shots inserted in the dentures, brought about an upward rotation of the mandible with a resulting decrease in occlusal vertical dimension and reduction in overjet of the dentures. In accordance with the amount of ridge reduction, these changes showed great individual variation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73577/1/j.1365-2842.1980.tb01466.x.pd

Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord

BACKGROUND: Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC) transplants have shown either poor differentiation or a preferential choice of glial lineages. METHODS AND FINDINGS: In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. CONCLUSIONS: NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major challenges remain, especially with respect to the establishment of neuromuscular connections

Human embryonic stem cell-derived neurons establish region-specific, long-range projections in the adult brain

While the availability of pluripotent stem cells has opened new prospects for generating neural donor cells for nervous system repair, their capability to integrate with adult brain tissue in a structurally relevant way is still largely unresolved. We addressed the potential of human embryonic stem cell-derived long-term self-renewing neuroepithelial stem cells (lt-NES cells) to establish axonal projections after transplantation into the adult rodent brain. Transgenic and species-specific markers were used to trace the innervation pattern established by transplants in the hippocampus and motor cortex. In vitro, lt-NES cells formed a complex axonal network within several weeks after the initiation of differentiation and expressed a composition of surface receptors known to be instrumental in axonal growth and pathfinding. In vivo, these donor cells adopted projection patterns closely mimicking endogenous projections in two different regions of the adult rodent brain. Hippocampal grafts placed in the dentate gyrus projected to both the ipsilateral and contralateral pyramidal cell layers, while axons of donor neurons placed in the motor cortex extended via the external and internal capsule into the cervical spinal cord and via the corpus callosum into the contralateral cortex. Interestingly, acquisition of these region-specific projection profiles was not correlated with the adoption of a regional phenotype. Upon reaching their destination, human axons established ultrastructural correlates of synaptic connections with host neurons. Together, these data indicate that neurons derived from human pluripotent stem cells are endowed with a remarkable potential to establish orthotopic long-range projections in the adult mammalian brain