Paroxysmal Kinesigenic Dyskinesia

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition associated with heterozygous mutations in the PRRT2 gene. Phenomenology shown: In this letter we illustrate the phenomenology of PKD in a man previously misdiagnosed as Tourette’s syndrome. Educational value: Regardless of underlying phenotype, PKD is highly responsive to some antiepileptic drugs

IT-stöd för industriellt byggande i trä

Delar av den svenska träbyggnadsindustrin har stora möjligheter att utveckla det industriella byggandet. Villor har lång tradition av att prefabriceras i fabriker för senare transport och montage på byggplats. Volymbyggnadsteknik där prefabriceringen även innefattar ytskikt och installationer har ökat prefabriceringsgraden avsevärt. Fortfarande är dock tillverkningen hantverksbetonad och genomförs med samma dokumentation och styrning som råder på ett platsbygge. Ett industriellt angreppssätt kräver en metodutveckling inom tillverkningen med styrning och kvalitetskontroll som nyckelord för att dra nytta av den upprepningseffekt som troheten till ett byggsystem skapar. Om ett IT-verktyg skall stötta en process, måste processen utformas och beskrivas på ett entydigt sätt som är repeterbart. Införandet av IT-verktyg betyder nästan alltid att processen förändras. Träbyggindustrin har en situation som definierar deras dilemma: man tillhör bygg-branschen och har anammat deras metoder och IT-verktyg, men tillverkningen är en indu-striell process som inte stöds av byggbranschens arbetssätt utan liknar tillverkningsindustrins serietillverkning. Flera företag har implementerat affärssystem och börjat utnyttja dess material- och planeringsfunktioner, en metod som är vanlig i tillverkningsindustrin. Data som skapas i projekteringen vore till nytta för affärssystemet, t.ex. mängder och antal komponenter. Tyvärr är inte byggbranschens IT-verktyg uppbyggda för att kommunicera med affärssystem via databaser. Tillverkningsindustrin har löst detta problem genom att arbeta med PDM-system, där data kring själva produkten hanteras (CAD-ritningar, komponenter). Affärssystemet kan sedan tanka av önskat data från PDM-systemet. Idag saknar träbyggindustrin en effektiv hantering av den egna produkten, byggsystemet. De beskrivningar som finns består av ritningar och endast 50- 70% av den information som behövs för att beskriva byggsystemet kan hämtas från ritningar. Den resterande delen är regler för systemet som sällan dokumenteras, utan existerar som arbetsmetoder inom varje företag. Byggsystemet förvaltas idag genom ett kontinuerligt användande i projekt efter projekt. Det betyder att överblicken över själva byggsystemet försvinner och möjligheterna till strategisk produktutveckling inte tas till vara. Som förvaltningsverktyg av byggsystem vore ett PDM-system lämpligt. Där förvaras och uppdateras data kring själva byggsystemet, som därifrån appliceras i olika projekt. Produktutveckling som idag sker i projekten, sker istället med byggsystemet som bas och informationen blir direkt tillgänglig för nästa projekt. Projekterings- och produktutvecklingsprocessen måste ändras från projektbaserad, upprepande projektering till strukturerad hantering av byggkomponenter i databas som kombineras på nya sätt i projekten. Inom föreliggande projekt har process och byggsystem hos 6 företag inom träbyggindustrin kartlagts. Baserat på företagens tolkade behov som beskrivits ovan utvecklades tre demon-stratorer (mjukvaror) för att utröna applicerbarheten av ett PDM-system inom träbygg-industrin. Intelligenta GDL- objekt skapades som utgjorde stommen i data för en PLCS-struktur som kan användas som ett PDM-system och kompletteras med ytterligare data. En koppling på databasnivå mellan CAD-data från träbyggindustrin och ett PDM- system testades också. Demonstratorerna visade att det är möjligt att utveckla dagens IT-verktyg till att stödja en industriell träbyggnadsprocess. Det kommer dock att kräva ett förändrat arbetssätt hos företagen. För att starta förändringen krävs att företagen dokumenterar sina processer och byggsystem. Högskolorna kan stötta med framtagning av metoder för processkartläggningar och beskrivning av byggsystem

Bone Turnover Marker Profiling and Fracture Risk in Older Women: Fracture Risk from Age 75 to 90.

Purpose: A major challenge in osteoporosis is to identify individuals at high fracture risk. We investigated six bone turnover markers (BTMs) to determine association with specific fracture types; the time-frame for risk prediction and whether these are influenced by age at assessment.Methods: Population-based OPRA cohort (n = 1044) was assessed at ages 75, 80, 85 and fractures documented for up to 15 years. Six BTMs were analyzed at each time-point (N-terminal propeptide of type I collagen, PINP; total osteocalcin, OC; bone-specific alkaline phosphatase, BALP; C-terminal telopeptide of type I collagen, CTX; tartrate-resistant acid phosphatase 5b, TRAcP5b; urinary osteocalcin). Hazard ratios (HR) for any, major osteoporotic, vertebral and hip fractures were calculated as short (1, 2, 3 years) and long-term risk (5, 10, 15 years).Results: At 75 year, high CTX levels were associated with an increased risk of all fractures, including major osteoporotic fractures, across most time-frames (HRs ranging: 1.28 to 2.28). PINP was not consistently associated. Urinary osteocalcin was consistently associated with elevated short-term risk (HRs ranging: 1.83-2.72). Other BTMs were directionally in accordance, though not all statistically significant. BTMs were not predictive for hip fractures. Association of all BTMs attenuated over time; at 80 year none were associated with an increased fracture risk.Conclusion: CTX, urinary OC and TRAcP5b are predictive for fracture in a 1 to 3 year, perspective, whereas in the long-term or above age 80 years, BTMs appear less valuable. Resorption markers, particularly CTX, were more consistently associated with fracture risk than formation markers in the very elderly.</p

The complexity of kidney disease and diagnosing it – cystatin C, selective glomerular hypofiltration syndromes and proteome regulation

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5–30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.publishedVersio

De Novo Loss-of-Function Mutations in USP9X Cause a Female-Specific Recognizable Syndrome with Developmental Delay and Congenital Malformations

Mutations in more than a hundred genes have been reported to cause X-linked recessive intellectual disability (ID) mainly in males. In contrast, the number of identified X-linked genes in which de novo mutations specifically cause ID in females is limited. Here, we report 17 females with de novo loss-of-function mutations in USP9X, encoding a highly conserved deubiquitinating enzyme. The females in our study have a specific phenotype that includes ID/developmental delay (DD), characteristic facial features, short stature, and distinct congenital malformations comprising choanal atresia, anal abnormalities, post-axial polydactyly, heart defects, hypomastia, cleft palate/bifid uvula, progressive scoliosis, and structural brain abnormalities. Four females from our cohort were identified by targeted genetic testing because their phenotype was suggestive for USP9X mutations. In several females, pigment changes along Blaschko lines and body asymmetry were observed, which is probably related to differential (escape from) X-inactivation between tissues. Expression studies on both mRNA and protein level in affected-female-derived fibroblasts showed significant reduction of USP9X level, confirming the loss-of-function effect of the identified mutations. Given that some features of affected females are also reported in known ciliopathy syndromes, we examined the role of USP9X in the primary cilium and found that endogenous USP9X localizes along the length of the ciliary axoneme, indicating that its loss of function could indeed disrupt cilium-regulated processes. Absence of dysregulated ciliary parameters in affected female-derived fibroblasts, however, points toward spatiotemporal specificity of ciliary USP9X (dys-)function

Patients’ experiences of Preimplantation Genetic Diagnosis (PGD)

The aim of the present study was to investigate the experiences and attitudes concerningpreimplantation genetic diagnosis (PGD) among the couples that have undergone PGD in Sweden.PGD is an alternative to conventional prenatal diagnosis for couples with a high risk of having a childwith genetic disease. Couples opting for PGD have to perform in vitro fertilisation, generatedembryos are subjected to biopsy and diagnosis, and healthy embryos can be transferred to the femaleuterus. Hopefully a pregnancy will be established. However, PGD is a strategy that implies bothphysical and psychological stress, and it is not obvious that this is an easier alternative than prenataldiagnosis. A questionnaire was sent to 116 couples that had carried out at least one PGD treatmentcycle. The response rate was 89%, thus almost all couples treated in Sweden since the start in 1995was represented. Results: The stress, both psychologically and physically, caused by the PGD treatment was evaluatedsomewhere between “As expected” and “More stressful than expected”. The stress experienced duringthe PGD treatments was not associated with the couples’ previous reproductive experiences. The mostphysical stressful event was the oocyte retrieval and the most psychologically stressful period was“waiting for a possibly/ hopefully embryo transfer”.The majority of couples that had performed prenatal diagnosis on a spontaneous pregnancy andexperienced a PGD treatment reported that PGD was more physically stressful (54%), but that prenataldiagnosis was more psychologically stressful (51%). The couples reported the reproductivealternatives chosen after PGD closure, and couples performing PGD at the present rated futurereproductive alternatives. Results indicated that ocyte- and sperm donations were a less attractivealternative than for example adoption. Participants in the study also had the opportunity to state forwhom /which indications PGD should be an option. Conclusion: The stress associated with performing PGD or prenatal diagnosis is extensive and noneof the alternatives is an obvious choice. PGD was reported as more physical stressful, but prenataldiagnosis was more psychologically stressful. The reproductive pathways chosen after PGD closurewas reported, and surprisingly sperm and oocyte donations were not attractive alternatives. The choiceof reproductive alternatives might be influenced by the information and support provided by thehealthcare personal. Knowledge about the experience of PGD treatments is of great importance forthose that meet these couples for genetic and reproductive counselling, in order to give them propercare and to better meet their demand of information and support

Patients’ experiences of Preimplantation Genetic Diagnosis (PGD)

The aim of the present study was to investigate the experiences and attitudes concerningpreimplantation genetic diagnosis (PGD) among the couples that have undergone PGD in Sweden.PGD is an alternative to conventional prenatal diagnosis for couples with a high risk of having a childwith genetic disease. Couples opting for PGD have to perform in vitro fertilisation, generatedembryos are subjected to biopsy and diagnosis, and healthy embryos can be transferred to the femaleuterus. Hopefully a pregnancy will be established. However, PGD is a strategy that implies bothphysical and psychological stress, and it is not obvious that this is an easier alternative than prenataldiagnosis. A questionnaire was sent to 116 couples that had carried out at least one PGD treatmentcycle. The response rate was 89%, thus almost all couples treated in Sweden since the start in 1995was represented. Results: The stress, both psychologically and physically, caused by the PGD treatment was evaluatedsomewhere between “As expected” and “More stressful than expected”. The stress experienced duringthe PGD treatments was not associated with the couples’ previous reproductive experiences. The mostphysical stressful event was the oocyte retrieval and the most psychologically stressful period was“waiting for a possibly/ hopefully embryo transfer”.The majority of couples that had performed prenatal diagnosis on a spontaneous pregnancy andexperienced a PGD treatment reported that PGD was more physically stressful (54%), but that prenataldiagnosis was more psychologically stressful (51%). The couples reported the reproductivealternatives chosen after PGD closure, and couples performing PGD at the present rated futurereproductive alternatives. Results indicated that ocyte- and sperm donations were a less attractivealternative than for example adoption. Participants in the study also had the opportunity to state forwhom /which indications PGD should be an option. Conclusion: The stress associated with performing PGD or prenatal diagnosis is extensive and noneof the alternatives is an obvious choice. PGD was reported as more physical stressful, but prenataldiagnosis was more psychologically stressful. The reproductive pathways chosen after PGD closurewas reported, and surprisingly sperm and oocyte donations were not attractive alternatives. The choiceof reproductive alternatives might be influenced by the information and support provided by thehealthcare personal. Knowledge about the experience of PGD treatments is of great importance forthose that meet these couples for genetic and reproductive counselling, in order to give them propercare and to better meet their demand of information and support

Palliativ vård - Sjuksköterskans upplevelse av omvårdnad och stöd till patienter och dess närstående.

Syftet med denna systematiska litteraturstudie var att beskriva sjuksköterskans upplevelser av omvårdnadsarbetet med palliativa patienter samt sjuksköterskans upplevelser att stödja dess närstående. Litteraturen söktes på databasen Elin@Dalarna. Valet av vetenskapliga artiklar gjordes med hjälp av titel och abstrakt för att se om innehållet var relevant för studien. Till resultatet användes totalt 17 vetenskapliga artiklar som var skrivna på engelska. Artiklarna granskades med hjälp av granskningsmallar som bedömde artiklarnas tillförlitlighet med hjälp av ett poängsystem. I resultatet kom uppsatsförfattarna fram till att sjuksköterskorna hade både positiva och negativa upplevelser av omvårdnaden av palliativa patienter och stödjandet av närstående. Det som sjuksköterskor upplevde som positivt i omvårdnaden var att de hade ett tillfredställande och betydelsefullt arbete. Sjuksköterskorna upplevde att det underlättade om de hade ett bra samarbete inom teamen. Negativa upplevelser var att det samtidigt kunde vara stressigt och känslomässigt svårt. I flera artiklar framkom att sjuksköterskan upplevde att stöd och information var viktiga uppgifter