The kinetics of ER fusion protein activation in vivo.

Reversibly switchable proteins are powerful tools with which to explore protein function in vitro and in vivo. For example, the activity of many proteins fused to the hormone-binding domain of the modified oestrogen receptor (ER(TAM)) can be regulated by provision or removal of 4-hydroxytamoxifen (4-OHT). Despite the widespread use of ER(TAM) fusions in vivo, inadequate data are available as to the most efficacious routes for systemic tamoxifen delivery. In this study, we have used two well-characterized ER(TAM) fusion proteins, both reversibly activated by 4-OHT, to compare the effectiveness and kinetics of 4-OHT delivery in mice in vivo by either tamoxifen in food or by intraperitoneal injection. Our data indicate that dietary tamoxifen offers an effective, facile and ethically preferable means for long-term activation of ER(TAM) fusion proteins in vivo.This is the final published version. It's also available from the publishers at: http://www.nature.com/onc/journal/vaop/ncurrent/full/onc201478a.html

Using patient experience in optimizing the total knee arthroplasty patient journey

Information was used to improve the patient journey and to achieve patient-centered care. Patients (\u3e18 years, purposive sampling) were interviewed once at one point of their total knee arthrosis journey within the hospital setting. Patients were accompanied and observed during their hospital visit by one of the 19 healthcare professionals which were trained as interviewers. A qualitative research approach with in-depth and semi-structured interviews using a standardized interview guide were used to gather an in-depth understanding of the perceptions of patients. Interviews were written out with the emphasis on positive and negative feedback, quotes and observations that were made. The audio recordings were verbatim transcribed and coded using selective and open coding. Thirty-five semi-structured interviews were conducted. Five different themes were identified: overall experience, waiting, communication, information and facilities. Several easy fixes were dealt with immediately to improve service quality, productivity and the organization of the healthcare service. Other improvements were discussed with the stakeholders and were resolved directly or were planned for the long-term. Involving patients and let them collaborate with healthcare professionals is essential in optimizing patient-centered care. Most feedback was related to clarification and comprehensibility of the patient journey, to improve autonomy and to remove uncertainty of the patients. Continuity of care with medical personnel, personal attention and recognition of the problem are fundamental during the knee arthrosis patient journey. Experience Framework This article is associated with the Quality & Clinical Excellence lens of The Beryl Institute Experience Framework. (http://bit.ly/ExperienceFramework) Access other PXJ articles related to this lens. Access other resources related to this lens

Okkultes Basalzellkarzinom vermischt mit seborrhoischer Keratose am Lid

Purpose!#!To objectively determine whether there is potential thermal tissue damage during Tm:YAG laser-based LUTS treatment.!##!Methods!#!Our experimental model was comprised of a prostatic resection trainer placed in a 37 °C water bath. In a hollowed-out central area simulating the urethral lumen, we placed a RigiFib 800 fibre, irrigation inflow regulated with a digital pump, and a type K thermocouple. A second thermocouple was inserted 0.5/1 cm adjacently and protected with an aluminum barrier to prevent it from urethral fluid. We investigated continuous and intermittent 120 W and 80 W laser application with various irrigation rates in eight measurement sessions lasting up to 14 min. Thermal measurements were recorded continuously and in real-time using MatLab. All experiments were repeated five times to balance out variations.!##!Results!#!Continuous laser application at 120 W and 125 ml/min caused a urethral ∆T of ~ 15 K and a parenchymal temperature increase of up to 7 K. With 50 ml/min irrigation, a urethral and parenchymal ∆T of 30 K and 15 K were reached, respectively. Subsequently and in absence of laser application, prostatic parenchyma needed over 16 min to reach baseline body temperature. At 80 W lower temperature increases were reached compared to similar irrigation but higher power.!##!Conclusions!#!We showed that potentially harming temperatures can be reached, especially during high laser power and low irrigation. The heat generation can also be conveyed to the prostate parenchyma and deeper structures, potentially affecting the neurovascular bundles. Further clinical studies with intracorporal temperature measurement are necessary to further investigate this potentially harming surgical adverse effect

Chinese version of the recovery self-assessment scale : psychometric evidence from Rasch analysis and reliability estimates

202206 bcchAccepted ManuscriptSelf-fundedPublishe

Osteoarthritis treatment using autologous conditioned serum after placebo

Background and purpose - Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients from that RCT would now opt for ACS treatment, which would result in a greater clinical improvement than placebo. Methods - Of 74 patients treated with placebo in the previous trial, 20 opted for ACS treatment. Patients who did not choose further treatment were interviewed about their reasons. Clinical improvement of the 20 ACS-treated patients was measured using knee-specific clinical scores, as was "response shift" at 3 and 12 months. Results - In the 20 patients who did opt for ACS, the visual analog scale (VAS) score for pain improved; but after 12 months, clinical results were similar to those after placebo treatment. Response shift measurement demonstrated that the 20 patients had adapted to their disabilities during treatment. Interpretation - Placebo-treated patients from an earlier trial were reluctant to undergo ACS treatment, in part due to the laborious nature of the therapy. In a subset of patients who opted for treatment, ACS treatment after placebo did not result in greater clinical improvement than placebo treatment only. However, due to the limited power of the current study and possible selection bias, definite advice on using or refraining from ACS cannot be given

Analysis of pigmented polymers in red wine by reverse phase HPLC

A reverse phase HPLC method has been developed for the quantitative analysis of pigmented polyphenolic polymers in red wines. Pigmented polymers were well separated from anthocyanins and other simple wine pigments and eluted last as a single peak. The polymeric and polyphenolic nature of this peak was confirmed by its precipitation with gelatine and its behaviour during ultrafiltration and chromatography on Sephadex LH20. This method correlates well with spectrophotometric measures of total pigmented polymers and indices of wine age. The proportion of the pigmented material incorporated into polymers increased with increasing wine age