Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice

Introduction Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The proapoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis. Methods In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water. Results Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P less than 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell-or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group). Conclusion Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner

Tafoxiparin, a novel drug candidate for cervical ripening and labor augmentation : results from 2 randomized, placebo-controlled studies

Background: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. Objective: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. Study Design: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. Results: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2–8.5) hours with tafoxiparin and 7.03 (1.5–14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. Conclusion: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants.Peer reviewe

Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis

The polymeric immunoglobulin receptor (pIgR) is a key component of the mucosal immune system that mediates epithelial transcytosis of immunoglobulins. High pIgR expression has been reported to correlate with a less aggressive tumour phenotype and an improved prognosis in several human cancer types. Here, we examined the expression and prognostic significance of pIgR in pancreatic and periampullary adenocarcinoma. The study cohort encompasses a consecutive series of 175 patients surgically treated with pancreaticoduodenectomy for pancreatic and periampullary adenocarcinoma in Malmö and Lund University Hospitals, Sweden, between 2001-2011. Tissue microarrays were constructed from primary tumours (n = 175) and paired lymph node metastases (n = 105). A multiplied score was calculated from the fraction and intensity of pIgR staining. Classification and regression tree analysis was used to select the prognostic cut-off. Unadjusted and adjusted hazard ratios (HR) for death and recurrence within 5 years were calculated. pIgR expression could be evaluated in 172/175 (98.3%) primary tumours and in 96/105 (91.4%) lymph node metastases. pIgR expression was significantly down-regulated in lymph node metastases as compared with primary tumours (p = 0.018). Low pIgR expression was significantly associated with poor differentiation grade (p < 0.001), perineural growth (p = 0.027), lymphatic invasion (p = 0.016), vascular invasion (p = 0.033) and infiltration of the peripancreatic fat (p = 0.039). In the entire cohort, low pIgR expression was significantly associated with an impaired 5-year survival (HR = 2.99, 95% confidence interval (CI) 1.71-5.25) and early recurrence (HR = 2.89, 95% CI 1.67-4.98). This association remained significant for survival after adjustment for conventional clinicopathological factors, tumour origin and adjuvant treatment (HR = 1.98, 95% CI 1.10-3.57). These results demonstrate, for the first time, that high tumour-specific pIgR expression signifies a more favourable tumour phenotype and that low expression independently predicts a shorter survival in patients with pancreatic and periampullary cancer. The mechanistic basis for the putative tumour suppressing properties of pIgR in these cancers merits further study

Effekten av högintensiv aerob träning på kognitiva funktioner hos friska unga vuxna

Validerat; 20150112 (global_studentproject_submitter

Stressförekomst bland ungdomar i årskurs åtta : en studie baserad på skolpersonals uppfattningar

Stress är en riskfaktor för hälsan och blir allt vanligare i de yngre befolkningsgrupperna. Syftet med föreliggande arbete var att beskriva skolsköterskors, mentorers, lärare och kuratorers uppfattningar av stressförekomst bland ungdomar i årskurs åtta. Studien var baserad på en enkätundersökning. Resultatet som framkom var att deltagarna uppfattade att ungdomarna var stressade. Skolan tolkades som den största stressfaktorn. Huvudvärk ansågs vara det vanligaste symtomet. Åtgärder som föreslogs för att hantera stress var, att ungdomarna behövde hjälp att planera och prioritera sitt skolarbete. Ett ökat stöd hemifrån samt hjälp att begränsa fritidsaktiviteter och en ökad samverkan mellan lärare ansågs även vara viktigt. Slutsatsen blev att stress bland ungdomar i årskurs åtta förekom. Insatser inom skolans organisation angående stressprevention bör ge redskap och kunskap till ungdomar om stresshantering. För att kunna öka möjligheten till en bättre hälsa bland ungdomar ansåg vi att samverkan var ett område att studera närmare.Stress is a risk factor for the health and becomes all the more common in the younger groups of the population. The aim with the work in question was to describe school nurses’, mentors’, teachers’ and school welfare officers’ views of stress occurrence among youths in eighth grade. The study was based on an opinion poll. The result showed that the participants considered the young people as being stressed. School was looked upon as the largest stress factor. Headache was considered as the most common symptom. Measures proposed to handle stress were that the young people needed help to plan and prioritize their school work. An increased support from home and help to limit leisure-time activities and an increased cooperation between teachers were also regarded as important. The conclusion was that stress among youths in eighth grade occurred. Initiatives within the organization of school concerning stress prevention should give tools and knowledge to young people about stress handling. In order to increase the possibility for a better health among young people we were of the opinion that cooperation was one area to study closer

Vägledning på ett universitet - en jämförelse av studie- och yrkesvägledare med olika utbildningsbakgrund

I vår studie vill vi undersöka eventuella skillnader i arbetssätt mellan utbildade studie- och yrkesvägledare och vägledare med annan utbildningsbakgrund på ett universitet i södra Sverige, med fokus på det enskilda samtalet. Vår frågeställning har delats upp i följande frågor: vilka riktlinjer finns för vägledningsarbetet på universitetet, finns skillnader i arbetssätt mellan vägledare med studie- och yrkes-vägledarutbildning och vägledare med annan utbildningsbakgrund, i sådana fall vilka samt hur prioriteras det enskilda samtalet? Vi har använt oss av kvalitativa intervjuer för undersökningen. Vi har intervjuat fyra studievägledare verksamma inom universitet. Därefter har vi analyserat det resultat vi har fått, i förhållande till tidigare forskning inom området, samt kopplat till de teorier som vi ansett relevanta för studien. Vårt resultat visar att det finns skillnader i arbetssätt mellan studie- och yrkesvägledare och vägledare med annan utbildningsbakgrund. Vid en anställning som studievägledare på universitetet efterfrågas framförallt ämneskunskapen inom institutionen och fakulteten och inte en examen i studie- och yrkesvägledning. Vägledningssamtalet har hos våra intervjupersoner en hög prioritet men har olika innebörd för våra intervjupersoner beroende på vilken utbildningsbakgrund de har. Med hjälp av bland annat Bourdieus och Hodkinson & Sparkes teorier kan vi förstå att det finns skillnader i arbetssätt beroende på vilken utbildningsbakgrund studievägledarna har

Dynamic head loss in pilot- and full-scale wastewater sand filtration with phosphorus removal, denitrification, and associated bumping

Limitations of the operation of down-flow sand filters were investigated without and with dosages of methanol, ethanol, or acetate for denitrification and dosages of ferrous sulphate to remove phosphorous. The dynamic head loss was developed due to clogging by suspended solids (SS) that originated from the secondary sedimentation tanks including sludge overflow and from SS in primary settled wastewater that bypassed the biological step. The dynamic head loss was also developed from clogging by gas bubbles formed during denitrification, not by the SS produced from cell growth. The dynamic head loss in sand filters after 24 h operation without and with denitrification increased by 0.9–1.3 and 2.3–2.4 mH2O, respectively. The total time of operation was prolonged by 50% after one water bumping, by 75% after two bumpings, and by 85% after six or seven bumpings. Operational time for filter cycles was prolonged by 4–5 h by one bumping in the full-scale and pilot-scale filters. The time of operation depended on hydraulic loading. With a carbon source dosage, one filter cycle lasted 20–40 h at 10 m/h and 60 h at 5 m/h in pilot-scale filters, and 15–27 h at 3.3 m/h in full-scale filters. HIGHLIGHTS Head loss in the main filter bed in denitrification was similar to the total head loss in non-denitrifying filters after 24 h.; Pilot-scale study results were confirmed by full-scale studies.; The dynamic head loss was developed from SS or gas clogging.; Bumping could prolong the time of operation but was rejected due to increased filtrate SS concentration.; Operational time defined the functionality of abruptly gas-clogged filters.