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Aim. The aim of this review was to support nursing management in creating frameworks for the care of people requesting hastened death, based on the best available evidence on the experiences of nurses. Background. The legalisation of hastened death presents nurses with a complex set of ethical and moral risks. The largely unregulated role of nurses in the politics of hastened death can lead to moral distress and burnout. Evaluation. A systematic database search was conducted in CINAHL, LIVIVO, Medline, OVID, and Web of Science. The meta-aggregative approach was used to synthesise the findings. Quality appraisal was done using criteria of the Joanna Briggs Institute. Key Issues. Sixteen studies from four different countries were included. Interview data were from 200 nurses. Meta-aggregation resulted in ten synthesised findings including the need for guidelines; time resources; a supporting team; and professional, social, and personal skills. Conclusions. A working environment with clear guidelines, sufficient resources, structured professional adjustment programmes, and educational measures is supportive for nurses. Implications for Nursing Management. Nursing management should create a professional strategy, guidelines, promote good team culture, implement education, and training activities.

Zusammenfassung Ziel der Studie Zur Definition einer europaweit einheitlichen Mindestqualifikation von Gesundheits- und Krankenpfleger:innen in Palliative Care werden im Erasmus+-Projekt NurseEduPal@euro curriculare Empfehlungen für das Bachelorstudium erarbeitet. Ziel dieser Studie war die Erstellung einer Konsensliste zu pflegerischen Kernkompetenzen mit österreichischen Expert:innen. Methodik Im Mai 2021 wurden 8 Expert:innen nach der Nominalgruppentechnik befragt. Die Daten wurden sowohl quantitativ als auch qualitativ ausgewertet. Ergebnisse Insgesamt wurden 47 Ideen generiert. Zu den wichtigsten Kompetenzen zählten Ethik, Achtung und Haltung, rechtliche Grundlagen, Forschung, Selbstreflexion, der Umgang mit Sterbewunsch, Trauer, Sterben und Tod, Symptommanagement, Pflegediagnostik, Kommunikation und kulturelle Kompetenz. Schlussfolgerung Die gesammelten Ideen bilden einen Expert:innenkonsens und dienen als Anknüpfungspunkt für weitere Forschungsarbeiten.

Determinants of low bone turnover in type 2 diabetes (T2DM) are poorly understood. To investigate the relationship between markers of bone turnover, glycaemic control, disease duration and calciotropic hormones in T2DM we assessed baseline biochemical data from the DiabOS Study, a prospective multicenter observational cohort study. In a cross-sectional study-design data from 110 postmenopausal women and men aged 50–75 years diagnosed with T2DM for at least 3 years and 92 non-diabetic controls were evaluated. Biochemical markers of bone formation (N-terminal propeptide of type I procollagen [PINP]), bone-specific alkaline phosphatase [BAP]) and resorption (C-terminal cross-linking telopeptide of type I collagen [CTX]), measures of calcium homeostasis (intact parathormone [iPTH], 25-Hydroxyvitamin D, calcium, magnesium) and glycaemic control were assessed. After adjustment for age, gender and body mass index (BMI), patients with T2DM had lower serum levels of PINP (p p p = 0.03) and magnesium (p p = 0.02; CTX: p p

Aims To find out which variables may be associated with comfort of patients in an epilepsy monitoring unit. Design Exploratory, quantitative study design. Methods Data were collected from October 2018 to November 2019 in Austria and Southern Germany. A total of 267 patients of 10 epilepsy centres completed the Epilepsy Monitoring Unit Comfort Questionnaire which is based on Kolcaba's General Comfort Questionnaire. Secondary data analysis were conducted by using descriptive statistics and an exploratory model building approach, including different linear regression models and several sensitivity analyses. Results Total comfort scores ranged from 83 to 235 points. Gender, occupation and centre turned out to be possible influential variables. On average, women had a total comfort score 4.69 points higher than men, and retired persons 28.2 points higher than high school students ≥18 years. Comfort scores of younger patients were lower than those of older patients. However, age did not show a statistically significant effect. The same could be observed in marital status and educational levels. Conclusion When implementing comfort measures, nurses must be aware of variables which could influence the intervention negatively. Especially, high school students ≥18 years should be supported by epilepsy specialist nurses, in order to reduce uncertainty, anxiety and discomfort. But, since the identified variables account only for a small proportion of the inter-individual variability in comfort scores, further studies are needed to find out additional relevant aspects and to examine centre-specific effects more closely. Impact Nurses ensure patient comfort during a hospital stay. However, there are variables that may impair the effectiveness of the nursing measures. Our study showed that the experience of comfort was highly individual and could be explained by sociodemographic variables only to a limited extent. Nurses must be aware that additional factors, such as the situation in the individual setting, may be relevant.

Purpose The purpose of the study was to evaluate the psychometric properties of the newly developed Epilepsy Monitoring Unit Comfort Questionnaire (EMUCQ) according to the consensus-based standards for the selection of health measurements instruments (COSMIN). Moreover, we aimed to assess changes in comfort-levels. Methods From October 2018 to November 2019, a total of 267 patients participated in a quantitative study in ten epilepsy centers in Austria and southern Germany. For basic item analysis, descriptive analysis and correlational analysis were computed. An exploratory factor analysis (EFA) was undertaken to detect the factor structure. Reliability was checked through internal consistency (Cronbach's alpha) and the measurement error. In the validity domain, convergent validity and structural validity were estimated. t-Tests were used to detect changes in comfort-levels. Results Due to unfavorable statistical properties, two items were removed. Exploratory factor analysis showed a three-factorial solution. The EMUCQ was found to be a reliable instrument (Cronbach's alpha 0.77–0.81 for the subscales, 0.88 for the scale total comfort); convergent validity could be supported, too. Confirmatory factor analysis (CFA) supported the hypothesis that structural validity for the three subscales holds. The patients' comfort levels were lower at the end of the stay than at the beginning and lower in nonseizure-free patients compared with seizure-free patients. Conclusion Validity and reliability are supported for the 42-item EMUCQ in the three-factorial solution. Owing to the item reduction and modifications made in the CFA, a new test should be carried out on a different sample.

Zusammenfassung. Primärer Hyperparathyreoidismus (pHPT) wird meistens zufällig diagnostiziert, wenn bei einer routinemässigen Laboruntersuchung eine Hyperkalzämie auffällt. Die Patienten sind bei Diagnosestellung meistens klinisch asymptomatisch, können aber bereits skelettale und renale Folgeerkrankungen aufweisen. Dieser Beitrag geht insbesondere auf die Diagnosestellung des pHPT ein, sowie auf die nötigen Verlaufskontrollen, wenn noch keine Operationsindikation besteht. Da heute immer häufiger das Parathormon (PTH) ohne vorgängige Diagnose einer Hyperkalzämie gemessen wird, ist ein Abschnitt der isolierten PTH-Erhöhung und den häufigsten Ursachen des sekundären Hyperparathyreoidismus gewidmet.

Purpose The aim of this qualitative study was to determine which perception of personal comfort patients name in the context of their hospitalization in an Austrian Epilepsy Monitoring Unit (EMU). Methods Problem-centred interviews with twelve inpatients were conducted. Data analyses were done according to Mayring's qualitative content analyses following the technique of structuring-deductive category assignment. Results Patients experienced different kinds of comfort along with their hospitalization in the EMU. Comfort-decreasing factors were bed rest , boredom , and waiting for possible seizures . As comfort-increasing factors, hope for enhanced seizure control, support by family and staff, and intelligible information about the necessity of restrictive conditions were identified. Conclusions The study results should assist health care professionals, enabling them to design comfort enhancing interventions for patients undergoing video-electroencephalography (EEG) investigations in an EMU. Some of these seem to be simple and obtainable without high financial or technical effort. Others are more complex and have to be further assessed for their feasibility.

CME: Primary Hyperparathyroidism

Purpose It is recommended to perform a pilot testing before conducting a validation study of a novel questionnaire. Pilot studies may serve different purposes. The aim of this study was to assess the feasibility of a multicenter validation study, to recruit additional study centers, and to undertake orientating descriptive item analysis of the 44-item Epilepsy Monitoring Unit (EMU) Comfort Questionnaire (EMUCQ). Methods During a six-month sampling period, the EMUCQ was administered to eligible EMU patients. The patients filled out the questionnaire at two time points. Additional centers were recruited in Germany and Austria, and ethics votes obtained. In descriptive item analysis central tendency, variability, item distribution and item difficulty were calculated. Results A total of 44 EMU patients participated in the study. Eight additional EMUs agreed to join the planned validation study. Recruitment of the centers took four months. Another six months passed to obtain all the ethics votes. Floor and ceiling effects could be detected in 32 items. One item with the lowest median showed the low item difficulty. Another five items showed medians with the height of 6. In four items, high difficulty indices could be observed. Conclusion A good network has turned out to be very helpful while planning a multicenter study. Enough time must be scheduled, because obtaining an ethics vote may take quite a long time. No conclusive statements regarding item properties could be made as this was a feasibility study.

Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk. Sodium-glucose co-transporter 2 inhibitors may alter calcium and phosphate homeostasis as a result of secondary hyperparathyroidism induced by increased phosphate reabsorption. Although these changes may suggest detrimental effects of SGLT-2 inhibitors on skeletal integrity, treatment-related direct effects on bone metabolism seem unlikely. Observed changes in BMD, however, seem to result from increased bone turnover in the early phase of drug-induced weight loss. Fracture risk, which is observed in older patients with impaired renal function and elevated cardiovascular disease risk treated with SGLT2 inhibitors, seems to be independent of direct effects on bone but more likely to be associated with falls and changes in hydration status secondary to osmotic diuresis.

Frakturen sind bei alteren Menschen haufig und gehen mit einer Einbuse der Lebensqualitat und einer erhohten Mortalitat einher. Bei Typ-2-Diabetes (DM2) ist das Frakturrisiko zusatzlich erhoht, obwohl die hiervon Betroffenen eine hohere Knochendichte aufweisen konnen. Aufgrund der weiten Verbreitung des DM2 ist diese Tatsache klinisch relevant. Es wird auf die moglichen Grunde fur die Erhohung des Frakturrisikos bei DM2 eingegangen und es wird erortert, wie dem erhohten Frakturrisiko im klinischen Alltag Rechnung getragen werden kann. Der vorliegende Beitrag basiert auf den neuesten Ubersichtsartikeln zum Thema DM2 und Knochengesundheit. Zudem werden zu den einzelnen Themen die wichtigsten Originalartikel zitiert. Die Entwicklung einer diabetes-assoziierten Osteopathie ist eine nicht zu vernachlassigende Komplikation bei DM2. Vermehrte Sturze bei diabetischen Spatfolgen, eine langere Diabetesdauer und eine mangelnde Diabeteseinstellung erhohen das Frakturrisiko bei Patienten mit DM2. Bei normaler Knochendichte tragen die vermehrte Porositat des Knochens und Kollagenveranderungen zur schlechteren Knochenqualitat bei. Zur Risikoberechnung werden dieselben Tools empfohlen wie fur Patienten ohne Diabetes, wobei zu beachten bleibt, dass sowohl der mittels DXA ermittelte Knochenmineralgehalt als auch der FRAX-Score das Frakturrisiko unterschatzen. Bezuglich Kalzium- und Vitamin-D-Supplementierung konnen bei Patienten mit DM2 die generellen praventiven Empfehlungen befolgt werden. Es ist nicht bekannt, ob der DM2 einen Einfluss auf die Wirksamkeit von Osteoporosemedikamenten hat. Laut Post-hoc-Analysen scheint dies nicht der Fall zu sein, die Osteoporosetherapie erfolgt daher auch bei DM2 laut gangiger Leitlinien fur postmenopausale Frauen und fur Manner mit Osteoporose.

Background and Purpose:The Epilepsy Monitoring Unit Comfort Questionnaire (EMUCQ) is a self-assessment instrument to measure perceived patient comfort during hospitalization in an EMU. This study aimed at initially determining the content validity by rating the content validity index (CVI).Methods:Nine experts judged the 60-item EMUCQ-1 by filling out a content validation form. The CVI was computed on item (I-CVI) and at an average scale (S-CVI/Ave) level.Results:As many as 26 items remained unchanged and 12 items were reworded to prepare the 38-item EMUCQ-2 (I-CVI scores ≥ .78). Fourteen items were omitted and an additional eight items were put aside for further evaluation. The S-CVI/Ave reached .90.Conclusion:The first results indicate the EMUCQ-2 to be valid in terms of content. Further assessment by members of the target population is advisable.

Aims To identify problematic items, assess completeness and user-friendliness, and undertake modifications to enhance face validity of the newly developed Epilepsy Monitoring Unit Comfort Questionnaire. Design Qualitative-descriptive cross-sectional study. Methods Five iterative rounds of cognitive interviewing were conducted with members of the target population between July - November 2017. Think-aloud technique, verbal probing, and observation were used, to assess how respondents understood and answered questions. Data analysis was based on the framework method; an eight-column framework matrix was created for this purpose. Results In 25 interviews, problems regarding completeness of the item pool, comprehension of items, retrieval of information, judgment while finding answers and reporting the appropriate responses could be detected. According to the results, 27 items remained unchanged, 11 items were reworded, and six items were added. Instructions section of the questionnaire was reworked, too. Conclusion Although time-consuming, cognitive interviewing turned out to be a valuable approach for revealing problems in an instrument, which would, otherwise, remain undetected and threaten validity.

Aims/hypothesis: We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels. Methods: This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type 1 diabetes (mean ± SEM age 33.5 ± 2.4years, diabetes duration 20.1 ± 3.6years, HbA1c 6.7 ± 0.2% and peak oxygen uptake [ $$\mathop {\text{V}}\limits^{\text{.}} {\text{O}}_{2{\text{peak}}} $$ ] 50.3 ± 4.5ml min−1 kg−1). Men were studied twice while cycling for 120min at 55 to 60% of $$\mathop {\text{V}}\limits^{\text{.}} {\text{O}}_{{\text{2peak}}} $$ , with a blood glucose level randomly set either at 5 or 11mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism. Results: The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 ± 4.8 vs 30.6 ± 4.2%; p

Herr Muller kommt zur stationaren Aufnahme in die neurologische Abteilung. Seit Wochen verspurt er eine zunehmende Unsicherheit beim Gehen. Er hat das Gefuhl, „wie auf Watte zu gehen“. Und Frau Huber hat in den Beinen unangenehme Schmerzen. Diese werden ertraglicher, wenn sie sich bewegt. Auch sie wendet sich an die Arzte der Neurologie. Und diese stellen bei beiden Patienten rasch die Dia-gnose: Polyneuropathie.

The aim of this qualitative study was to determine which perception of personal comfort patients name in the context of their hospitalization in an Austrian Epilepsy Monitoring Unit (EMU).Problem-centred interviews with twelve inpatients were conducted. Data analyses were done according to Mayring's qualitative content analyses following the technique of structuring-deductive category assignment.Patients experienced different kinds of comfort along with their hospitalization in the EMU. Comfort-decreasing factors were bed rest, boredom, and waiting for possible seizures. As comfort-increasing factors, hope for enhanced seizure control, support by family and staff, and intelligible information about the necessity of restrictive conditions were identified.The study results should assist health care professionals, enabling them to design comfort enhancing interventions for patients undergoing video-electroencephalography (EEG) investigations in an EMU. Some of these seem to be simple and obtainable without high financial or technical effort. Others are more complex and have to be further assessed for their feasibility.

Carnosine (β-alanyl-L-histidine) is found in high concentrations in skeletal muscle and chronic β-alanine (BA) supplementation can increase carnosine content. This placebo-controlled, double-blind study compared two different 8-week BA dosing regimens on the time course of muscle carnosine loading and 8-week washout, leading to a BA dose-response study with serial muscle carnosine assessments throughout. Thirty-one young males were randomized into three BA dosing groups: (1) high-low: 3.2 g BA/day for 4 weeks, followed by 1.6 g BA/day for 4 weeks; (2) low-low: 1.6 g BA/day for 8 weeks; and (3) placebo. Muscle carnosine in tibialis-anterior (TA) and gastrocnemius (GA) muscles was measured by 1H-MRS at weeks 0, 2, 4, 8, 12 and 16. Flushing symptoms and blood clinical chemistry were trivial in all three groups and there were no muscle carnosine changes in the placebo group. During the first 4 weeks, the increase for high-low (TA 2.04 mmol/kgww, GA 1.75 mmol/kgww) was ~twofold greater than low-low (TA 1.12 mmol/kgww, GA 0.80 mmol/kgww). 1.6 g BA/day significantly increased muscle carnosine within 2 weeks and induced continual rises in already augmented muscle carnosine stores (week 4-8, high-low regime). The dose-response showed a carnosine increase of 2.01 mmol/kgww per 100 g of consumed BA, which was only dependent upon the total accumulated BA consumed (within a daily intake range of 1.6-3.2 g BA/day). Washout rates were gradual (0.18 mmol/kgww and 0.43 mmol/kgww/week; ~2%/week). In summary, the absolute increase in muscle carnosine is only dependent upon the total BA consumed and is not dependent upon baseline muscle carnosine, the muscle type, or the daily amount of supplemented BA.

ObjectivePatients with GH deficiency (GHD) are insulin resistant with an increase in visceral fat mass (FM). Whether this holds true when sedentary control subjects (CS) are matched for waist has not been documented.GH replacement therapy (GHRT) results in a decrease in FM. Whether the decrease in FM is mainly related to a reduction in visceral FM remains to be proven. The aim was to separately assess visceral and subcutaneous FM in relation to insulin resistance (IR) in GHD patients before and after GHRT and in sedentary CS.MethodsTen patients with GHD were investigated before and 6 months after GHRT. Sedentary CS matched for age, gender, body mass index, and waist were assessed. Exercise capacity was measured as VO2maxusing an incremental work load on a treadmill. Visceral and subcutaneous FM were measured using whole-body magnetic resonance imaging and IR by the homeostasis model assessment of IR (HOMA-IR) index.ResultsGHD patients had a non-significantly lower VO2maxbut did not have increased subcutaneous and visceral FM compared with CS. GHRT resulted in a similar relative decrease in subcutaneous and visceral FM. Compared with CS, GHD patients showed a lower HOMA-IR. GHRT tended to increase HOMA-IR.ConclusionMatching for waist and separate assessment of visceral and subcutaneous FM may be critical in the evaluation of body composition and IR in GHD patients before and after GHRT.

Intramyocellular lipids (IMCL) are flexible fuel stores that are depleted by physical exercise and replenished by fat intake. IMCL or their degradation products are thought to interfere with insulin signaling thereby contributing to insulin resistance. From a practical point of view it is desirable to deplete IMCL prior to replenishing them. So far, it is not clear for how long and at which intensity subjects have to exercise in order to deplete IMCL. We therefore aimed at developing a standardized exercise protocol that is applicable to subjects over a broad range of exercise capacity and insulin sensitivity and allows measuring reliably reduced IMCL levels.Twelve male subjects, including four diabetes type 2 patients, with wide ranges of exercise capacity (VO(2)peak per total body weight 27.9-55.8 ml x kg(-1) x min(-1)), insulin sensitivity (glucose infusion rate per lean body mass 4.7-15.3 mg x min(-1) x kg(-1)), and BMI (21.7-31.5 kg x m(-2)), respectively, were enrolled. Using (1)H magnetic resonance spectroscopy ((1)H-MRS), IMCL was measured in m.tibialis anterior and m.vastus intermedius before and during a depletion protocol of a week, consisting of a moderate additional physical activity (1 h daily at 60% VO(2)peak) and modest low-fat (10-15%) diet.Absolute IMCL-levels were significantly reduced in both muscles during the first 3 days and stayed constant for the next 3 days of an identical diet/exercise-scheme. These reduced IMCL levels were independent of insulin sensitivity, yet a tendency to lower depleted IMCL levels has been observed in subjects with higher VO(2)peak.The proposed protocol is feasible in subjects with large differences in exercise capacity, insulin sensitivity, and BMI, leading to reduced IMCL levels that neither depend on the exact duration of the depletion protocol nor on insulin sensitivity. This allows for a standardized preparation of IMCL levels either for correlation with other physiological parameters or for replenishment studies.

Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50–60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn’t significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.

Type 2 diabetes is associated with increased fracture risk and the mechanisms underlying the detrimental effects of diabetes on skeletal health are only partially understood. Antidiabetic drugs are indispensable for glycemic control in most type 2 diabetics, however, they may, at least in part, modulate fracture risk in exposed patients. Preclinical and clinical data clearly demonstrate an unfavorable effect of thiazolidinediones on the skeleton with impaired osteoblast function and activated osteoclastogenesis. The negative effect of thiazolidinediones on osteoblastogenesis includes decreased activity of osteoblast-specific transcription factors (e.g. Runx2, Dlx5, osterix) and decreased activity of osteoblast-specific signaling pathways (e.g. Wnt, TGF-β/BMP, IGF-1). In contrast, metformin has a positive effect on osteoblast differentiation due to increased activity of Runx2 via the AMPK/USF-1/SHP regulatory cascade resulting in a neutral or potentially protective effect on bone. Recently marketed antidiabetic drugs include incretin-based therapies (GLP-1 receptor agonists, DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2)-inhibitors. Preclinical studies indicate that incretins (GIP, GLP-1, and GLP-2) play an important role in the regulation of bone turnover. Clinical safety data are limited, however, meta-analyses of trials investigating the glycemic-lowering effect of both, GLP-1 receptor agonists and DPP4-inhibitors, suggest a neutral effect of incretin-based therapies on fracture risk. For SGLT2-inhibitors recent data indicate that due to their mode of action they may alter calcium and phosphate homeostasis (secondary hyperparathyroidism induced by increased phosphate reabsorption) and thereby potentially affect bone mass and fracture risk. Clinical studies are needed to elucidate the effect of SGLT2-inhibitors on bone metabolism. Meanwhile SGLT2-inhibitors should be used with caution in patients with high fracture risk, which is specifically true for the use of thiazolidinediones.

A questionnaire was used to investigate the crying behavior of medical personnel and medical students in Austrian hospitals. The results from 275 respondents show that shedding tears occurs relatively frequently. Main reasons were dying patients and having to give bad news. Explicitly negative reactions are rare. Attitudes towards crying are generally tolerant, although physicians tend to be more restrictive/(reserved?).

BACKGROUND Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass). AIM To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy. METHODS Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO(2max)) using ¹H-MR-spectroscopy. RESULTS Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO(2max), 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (-22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity. CONCLUSIONS IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions. TRIAL REGISTRATION ClinicalTrial.gov NCT00491582.

The transcription factor ELF5 is responsible for gene expression patterning underlying molecular subtypes of breast cancer and may mediate acquired resistance to anti-estrogen therapy., We have previously shown that during pregnancy the E-twenty-six (ETS) transcription factor ELF5 directs the differentiation of mammary progenitor cells toward the estrogen receptor (ER)-negative and milk producing cell lineage, raising the possibility that ELF5 may suppress the estrogen sensitivity of breast cancers. To test this we constructed inducible models of ELF5 expression in ER positive luminal breast cancer cells and interrogated them using transcript profiling and chromatin immunoprecipitation of DNA followed by DNA sequencing (ChIP-Seq). ELF5 suppressed ER and FOXA1 expression and broadly suppressed ER-driven patterns of gene expression including sets of genes distinguishing the luminal molecular subtype. Direct transcriptional targets of ELF5, which included FOXA1, EGFR, and MYC, accurately classified a large cohort of breast cancers into their intrinsic molecular subtypes, predicted ER status with high precision, and defined groups with differential prognosis. Knockdown of ELF5 in basal breast cancer cell lines suppressed basal patterns of gene expression and produced a shift in molecular subtype toward the claudin-low and normal-like groups. Luminal breast cancer cells that acquired resistance to the antiestrogen Tamoxifen showed greatly elevated levels of ELF5 and its transcriptional signature, and became dependent on ELF5 for proliferation, compared to the parental cells. Thus ELF5 provides a key transcriptional determinant of breast cancer molecular subtype by suppression of estrogen sensitivity in luminal breast cancer cells and promotion of basal characteristics in basal breast cancer cells, an action that may be utilised to acquire antiestrogen resistance., Author Summary The molecular subtypes of breast cancer are distinguished by their intrinsic patterns of gene expression and can be used to group patients with different prognoses and treatment options. Although molecular subtyping tests are currently under evaluation, some of them are already in use to better tailor therapy for patients; however, the molecular events that are responsible for these different patterns of gene expression in breast cancer are largely undefined. The elucidation of their mechanistic basis would improve our understanding of the disease process and enhance the chances of developing better predictive and prognostic markers, new therapies, and interventions to overcome resistance to existing therapies. Here, we show that the transcription factor ELF5 is responsible for much of the patterning of gene expression that distinguishes the breast cancer subtypes. Additionally, our data suggest that ELF5 may also be involved in the development of resistance to therapies designed to stop estrogen stimulation of breast cancer. These effects of ELF5 appear to represent a partial carryover into breast cancer of its normal role in the mammary gland, where it is responsible for the development of milk-producing structures during pregnancy.

Aim: To investigate whether a decrease in physical working capacity occurs during the first year of unemployment and if this is accompanied by a deterioration in mental health. Methods: In a longitudinal study, 71 unemployed individuals were investigated for 1, 6 months and 1 year after becoming unemployed. An additional 102 individuals who have been unemployed for more than 1 year were included in the cross-sectional part of the study. Possible decrease of physical working capacity was tested by bicycle ergometry. Psycho-emotional stress was tested by serum cortisol concentrations and by the Giessen symptom questionnaire. Results: In short-term unemployed (STU) individuals, a significant decrease (P=0.001) of physical working capacity (16.3%) and a significant increase (P=0.004) of cortisol levels (17.6 μg/dl) was found. The Giessen symptom questionnaire score showed an increased emotional disturbance (P=0.035) during unemployment. The comparison of long-term unemployed and STU revealed a significant decrease (P=0.012) in physical working capacity (18.2%), a significant increase in cortisol levels (P=0.001) and a significant worsening of the Giessen symptom questionnaire score (P=0.001). Conclusion: Unemployment has a negative effect on physical working capacity and mental health, depending on the duration of unemployment. Factors that facilitate or impede physical and mental health during unemployment should be identified in future studies.

A questionnaire was used to investigate the crying behavior of medical personnel and medical students in Austrian hospitals. The results from 275 respondents show that shedding tears occurs relatively frequently. Main reasons were dying patients and having to give bad news. Explicitly negative reactions are rare. Attitudes towards crying are generally tolerant, although physicians tend to be more restrictive/(reserved?).