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Background/Objectives The Protein Screener 55 + (Pro55 + ) is a brief food questionnaire to screen older community-dwelling adults for low protein intake. The result is the predicted probability of protein intake Subjects/Methods After translation and pilot-testing, the Pro55+ and the reference standard (3-day dietary record) were completed by 144 participants (81.6 ± 3.9 years, 61.8% female). Discriminative properties were tested by receiver operating characteristic curves and by calculating sensitivity and specificity for different cut-offs of predicted probability (>0.3/>0.5/>0.7) using Results Protein intake was Conclusion The overall discriminative accuracy of the German Pro55+ to identify older community-dwelling people with low protein intake was poor. However, applying different probability cut-offs allows increasing specificity and sensitivity for 0.8 g/kg aBW/d to levels justifying the use for certain purposes e.g. excluding individuals with adequate protein intake. Further validation is needed.

A longitudinal alteration in health-related quality of life (HRQoL) over a two-year period and its association with early-stage chronic kidney disease (CKD) progression was investigated among 1748 older adults (>75 years). HRQoL was measured by the Euro-Quality of Life Visual Analog Scale (EQ-VAS) at baseline and at one and two years after recruitment. A full comprehensive geriatric assessment was performed, including sociodemographic and clinical characteristics, the Geriatric Depression Scale-Short Form (GDS-SF), Short Physical Performance Battery (SPPB), and estimated glomerular filtration rate (eGFR). The association between EQ-VAS decline and covariates was investigated by multivariable analyses. A total of 41% of the participants showed EQ-VAS decline, and 16.3% showed kidney function decline over the two-year follow-up period. Participants with EQ-VAS decline showed an increase in GDS-SF scores and a greater decline in SPPB scores. The logistic regression analyses showed no contribution of a decrease in kidney function on EQ-VAS decline in the early stages of CKD. However, older adults with a greater GDS-SF score were more likely to present EQ-VAS decline over time, whereas an increase in the SPPB scores was associated with less EQ-VAS decline. This finding should be considered in clinical practice and when HRQoL is used to evaluate health interventions among older adults.

Background Older cyclists are in great risk of being injured or killed in a traffic-related accident and their needs should find more consideration in safety guidelines, urban planning, and future intervention programs. Objective The aim for this cross-sectional analysis was to comprehensively explore characteristics of community-dwelling cyclists aged 65 years and older with a self-perceived need to increase cycle competence. Methods 118 older adults (mean age 73.3 ± 5.2 years, 61% women) performed a standardized cycle course representing specific cycling skills. Additionally, health and functional assessments were carried out and characteristics regarding demographic, health, falls, bicycle equipment/type and cycling biography/behavior were obtained. Results The majority (67.8%) of this community-dwelling adults reported being unsafe when cycling and 41.3% had a bicycle fall in the past year. More than half of the participants showed at least one limitation in each of the measured cycling skills. Women significantly had more frequent limitations in four of the cycling skills measured (p ≤ 0.001) compared to men. While no significant differences were found for falls, health and functional characteristics, women and men differed significantly in terms of bicycle type, equipment, and perceived safety (p 0.001). Conclusion Limitations in cycling should be compensated by preventive bicycle training and a safe cycling infrastructure. Bicycle fit, the wearing of bicycle helmets and promotion of a sense of security while cycling can further reduce accident risk and must find recognition in safety guidelines. In addition, educational initiatives have to dismantle gender-related bicycle stereotypes.

Aging is associated with reduced appetite as well as a slight increase in pro-inflammatory status, which both might contribute to the development of malnutrition. We aimed to evaluate the association between inflammation based on serum C-reactive protein (CRP), and appetite in healthy community-dwelling older adults. In this cross-sectional study of 158 healthy and non-smoking persons (aged 75-85 years), appetite was assessed in personal interviews by a single question with five answer categories. As nobody reported (very) poor appetite, the remaining three categories were dichotomised into "(very) good" and "moderate" appetite. Fasting serum CRP was analysed according to standard procedures, values ≥ 5.0 mg/L were considered as inflammation. The association between inflammation and appetite was examined by binary logistic regression, unadjusted and adjusted for age, sex, waist circumference, leptin, depressive mood, number of medications, interleukin-6 and tumor necrosis factor-α. Appetite was very good in 27.8%, good in 58.9%, and moderate in 13.3% of participants. Inflammation was present in 10.8% overall, in 8.8% of those with (very) good and in 23.8% of those with moderate appetite (

Background Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). Methods Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR 2) and low EQoL-VAS was investigated by multivariable logistic regression models. Results CKD was found to be significantly associated with low EQoL-VAS in crude analysis (OR = 1.47, 95%CI = 1.16–1.85 for eGFR Conclusions CKD may significantly affect QoL in community-dwelling older adults. Physical performance, polypharmacy, diabetes, hypertension and COPD may affect such association, which suggests that the impact of CKD on QoL is likely multifactorial and partly mediated by co-occurrent conditions/risk factors.

Purpose Whole-body electromyostimulation (WB-EMS) especially in combination with a high-protein supplementation has been established as an efficient treatment against sarcopenia. However, there are several case reports of rhabdomyolysis after WB-EMS application. Thus, we asked if this training could potentially lead to deteriorations of the cardiac as well as the renal function. Materials and Methods One hundred sarcopenic obese men aged 70 years and older were randomly balanced (1-1-1) and allocated to one of the three study arms. During 16 weeks of intervention, these groups either performed WB-EMS and took a protein supplement (WB-EMS&P), solely received the protein supplement (Protein) or served as control group (CG). WB-EMS consisted of 1.5×20 min (85 Hz, 350 μs, 4 s of strain to 4 s of rest) applied with moderate-to-high intensity while moving. We further generated a daily protein intake of 1.7–1.8 g/kg/body mass per day. At baseline and 8–10 days after completion of the intervention, blood was drawn and biomarkers of muscle, cardiac and renal health were assessed. Results Hereby, we found slight but significant elevations of creatine kinase (CK) levels in the WB-EMS group pointing to minor damages of the skeletal muscle (140 U/l [81–210], p < 0.001). This was accompanied by a significant, low-grade increase of creatine kinase–muscle brain (CK-MB, 0.43 ng/mL [−0.29–0.96], p < 0.01) and high-sensitivity troponin T (hsTnT, 0.001 ng/mL. [0.000–0.003], p < 0.001) but without a higher risk of developing heart failure according to N-terminal prohormone of brain natriuretic peptide (NT-proBNP, −5.7 pg/mL [−38.8–24.6], p = 0.17). Estimated glomerular filtration rate (eGFR) was impaired neither by the high-protein supplementation alone nor in combination with WB-EMS (CG 76.0 mL/min/1.73 m2 [71.9–82.2] vs Protein 73.2 mL/min/1.73 m2 [63.0–78.9] vs WB-EMS&P 74.6 mL/min/1.73 m2 [62.8–84.1], p = 0.478). Conclusion In conclusion, even in the vulnerable group of sarcopenic obese seniors, the combination of WB-EMS with a high-protein intake revealed no short-term, negative impact on the eGFR, but potential consequences for the cardiovascular system need to be addressed in future studies.

Background Reduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls. Methods The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving community-dwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment. The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUTS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects. Results Our series consisted of 2256 SCOPE participants (median age = 79.5 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment. CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79–1.14 for eGFROR = 1.02, 95%CI = 0.81–1.28 for eGFROR = 1.08, 95%CI = 0.74–1.57 for eGFROR = 0.91, 95%CI = 0.67–1.24 for eGFROR = 0.93, 95%CI = 0.63–1.37 for eGFROR = 1.19, 95%CI = 0.62–2.29 for eGFROR = 1.56, 95%CI = 1.29–1.89) and injurious falls (OR = 1.58, 95%CI = 1.14–2.19), and such associations were confirmed in all multivariable models. Conclusions Cross-sectional data suggest that CKD may not be associated with history of falls or injurious falls, whereas LUTS is significantly associated with the outcomes. Trial registration This study was registered on 25th February 2016 at clinicaltrials.gov (NCT02691546).

Objectives Translation, adaptation, and validation of the German version of the SARC-F for community-dwelling older adults in Germany. Design Cross-sectional. Setting and Participants 117 community-dwelling outpatients with a mean age of 79.1 ± 5.2 years were included in the study; 94 (80.4%) of them were female. Sixty-three (53.8%) had a positive SARC-F score of ≥4 points. According to the definition of sarcopenia from the European Working Group on Sarcopenia in Older People (EWGSOP2), 8 patients (6.8%) were identified as sarcopenic and 57 (48.7%) as probable sarcopenic. Methods According to EWGSOP2, probable sarcopenia was defined for patients with reduced hand grip strength (women: 15 seconds). Patients with additional low skeletal muscle index were classified as sarcopenic (women: Results The translated and culturally adapted version of the SARC-F for the German language has shown excellent inter-rater reliability and good test-retest reliability. The internal consistency is acceptable. Sensitivity (63%) and specificity (47%) for sarcopenia is low. For detecting patients with probable sarcopenia, the SARC-F in the German version has shown 75% sensitivity and 67% specificity. Conclusions and Implications Because of a low sensitivity for detecting sarcopenia but an acceptable sensitivity for identifying probable sarcopenia, the German version of the SARC-F is a suitable tool for case finding of probable sarcopenia.

Background Sarcopenia is linked to functional impairments, loss of independence, and mortality. In the past few years, obesity has been established as being a risk factor for a decline in muscle mass and function. There are several molecular pathological mechanisms, which have been under discussion that might explain this relationship. However, most studies were conducted using male animals and for a short period of time. Methods In this study, the gender-specific effect of long-term, high-fat content feeding in Sprague–Dawley rats was examined. Development of the quadriceps muscle of the animals was monitored in vivo using magnetic resonance. The results of these measurements and of the biochemical analysis of the aged muscle were compared. Results Surprisingly, only male but not female rats showed a decline in muscle cross-sectional area at 16 months of age as a result of a chronic oversupply of dietary fats. This loss of muscle mass could not be explained by either de-regulation of the anabolic Akt pathway or by up-regulation of the main ubiquitin ligases of muscle, MAFbx and MuRF-1. However, fusion of satellite cells to myotubes was induced by the high-fat diet in male rats, possibly as a result of an increased need for compensatory regeneration processes. Caspase-3-dependent apoptosis induction, irrespective of diet, seems to be the major determinant of muscle decline during ageing in male but not female rats. Conclusion Taken together, activation of the apoptosis-inducing Caspase-3 seems to be the most important trigger for the age-related muscle loss. Male rats were more prone to the decline of muscle during ageing than female animals, which was further enforced by a long-term, high fat diet.

To maintain muscle mass in older age, several aspects regarding the amount and distribution of protein intake have been suggested. Our objective was to investigate single and combined associations of daily protein intake, evenness of protein distribution across the three main meals, number of meals providing ≥0.4 g protein/kg body weight (BW), and number of meals providing ≥2.5 g leucine, with muscle mass, strength, and power in successful agers. In this cross-sectional study in 97 healthy community-dwelling adults without functional limitations aged 75–85 years, protein intake was assessed using 7-day food records. Muscle mass, leg muscle strength, leg muscle power, and handgrip strength were measured according to standardized protocols. Mean daily protein intake was 0.97 ± 0.28 g/kg BW and the coefficient of variance between main meals was 0.53 ± 0.19. Per day, 0.72 ± 0.50 meals providing ≥0.4 g protein/kg BW and 1.11 ± 0.76 meals providing ≥2.5 g leucine were consumed. No correlations between single or combined aspects of protein intake and skeletal muscle index, leg muscle power, leg muscle strength, or handgrip strength were observed (Spearman’s r of −0.280 to 0.291). In this sample of healthy older adults without functional limitations, aspects of protein intake were not associated with muscle mass, strength, or power.

Hintergrund: Ziel dieser Studie war es, mogliche Zusammenhange zwischen dem Patientenalter, der Notaufnahme-Aufenthaltsdauer, der dem Patienten zugeordneten Fachdisziplin sowie der stationaren Aufnahmewahrscheinlichkeit in einer deutschen, interdisziplinaren Notaufnahme zu untersuchen. Patienten und Methodik: In einer retrospektiven Kohortenanalyse wurden 7937 Patienten einer interdisziplinaren Notaufnahme bezuglich ihres Alters, Geschlechts, der Aufenthaltsdauer in der Notaufnahme und einer stationaren Krankenhausaufnahme evaluiert. Anhand der Berechnung von Rangkorrelationskoeffizienten fur die einzelnen Fachdisziplinen sowie der Testung explorativer Hypothesen wurde der Einfluss des Patientenalters auf die oben genannten Parameter analysiert. Ergebnisse: Die Altersstruktur der Notfallpatienten unterscheidet sich deutlich zwischen den einzelnen Fachdisziplinen. Patientenalter und Aufenthaltsdauer korrelieren besonders bei unfallchirurgischen, allgemeinchirurgischen und ophthalmologischen Patienten. Korrelationen zwischen Patientenalter und stationarer Aufnahmewahrscheinlichkeit sind besonders ausgepragt bei internistischen, unfallchirurgischen und neurologischen Patienten. Schlussfolgerung: Bei Patienten in der Notaufnahme bestehen Zusammenhange zwischen Patientenalter, Aufenthaltsdauer in der Notaufnahme und stationarer Aufnahmewahrscheinlichkeit.

The COP9 complex (signalosome) is a known regulator of the proteasome/ubiquitin pathway. Furthermore it regulates the activity of the cullin-RING ligase (CRL) families of ubiquitin E3-complexes. Besides the CRL family, the anaphase-promoting complex (APC/C) is a major regulator of the cell cycle. To investigate a possible connection between both complexes we assessed interacting partners of COP9 using an in vivo protein-protein interaction assay. Hereby, we were able to show for the first time that CSN2, a subunit of the COP9 signalosome, interacts physically with APC/C. Furthermore, we detected a functional influence of the COP9 complex regarding the stability of several targets of the APC/C. Consistent with these data we showed a genetic instability of cells overexpressing CSN2.

Annexin A5 is a Ca(2+)-binding protein which is involved in membrane organization and dynamics. As recent data suggest a role of annexin A5 in cancer we aimed to gain more insight into the biological function of endogenous annexin A5 and assessed its possible influence on proliferation and invasion capacity. We downregulated annexin A5 by RNA interference in HaCaT keratinocytes, squamous carcinoma cell line A431 as well as in a primary cell culture of a human oral carcinoma. Hereby, we detected reduced migration and invasion capacity of HaCaT cells which was even stronger in the oral carcinoma. To determine target genes of annexin A5 we used a metastasis specific microarray. Thereby, genes implicated in cell motility including S100A4, TIMP-3 and RHOC were observed to be regulated. These deregulations were confirmed by RT-PCR or western blots, respectively. These observations suggest that the invasion capacity, a main characteristic of tumors, is at least partially regulated by annexin A5 in oral carcinoma.

The tumor suppressor p33ING1 is involved in DNA repair and cell cycle regulation. Furthermore, p33ING1 is a transcriptional silencer that recognizes the histone mark for trimethylated lysine 4 at histone H3. Interestingly, expression of p33ING1 and p33ING2 is able to induce premature senescence in primary human fibroblasts. The corepressor Alien is involved in gene silencing mediated by selected members of nuclear hormone receptors. In addition, Alien acts as a corepressor for E2F1, a member of the E2F cell cycle regulatory family. Furthermore, recent findings suggest that Alien is complexed with transcription factors participating in DNA repair and chromatin. Here, using a proteomic approach by surface-enhanced laser desorption ionization and mass spectrometry (SELDI-MS) combined with immunological techniques, we show that Alien interacts in vivo with the tumor suppressor p33ING1 as well as with the related tumor suppressor candidate p33ING2. The interaction of Alien with p33ING1 and p33ING2 was confirmed in vitro with GST-pull-down, suggesting a direct binding of Alien to these factors. The binding domain was mapped to a central region of Alien. Functionally, the expression of p33ING1 or p33ING2 enhances the Alien-mediated silencing, suggesting that the interaction plays a role in transcriptional regulation. Thus, the findings suggest that the identified interaction between Alien and the tumor suppressors p33ING1 and p33ING2 reveals a novel cellular protein network.

Interacting proteins are often involved in the same cellular processes, and thus the identification of interacting partners of a given protein with unknown function may give insight into the physiological role of this protein. For the detection of protein-protein interactions of the corepressor Alien we used a proteomic approach comprising mass spectrometry and immunological techniques. We assessed solely endogenously expressed proteins. In this study we present for the first time that Alien is interacting within a network of proteins involved in transcriptional regulation, DNA repair, and cell cycle in vivo. In this way we detected protein interactions of Alien involving nucleophosmin, ERCC3, TRIP11, as well as CRSP3.

BACKGROUND One of the main causes of acute kidney injury (AKI) in patients treated on an intensive care unit (ICU) is sepsis. The identification of new biomarkers indicating the early development and future course of AKI are of utmost medical interest. The C-terminal agrin fragment (CAF) is measurable in blood serum and might reflect kidney function. Therefore, this study evaluates CAF in patients presenting to an internal ICU with severe sepsis or septic shock. Serum levels of CAF are correlated with biomarkers of kidney function, markers of systemic inflammation, and the presence of AKI and renal replacement therapy (RRT). METHODS 61 patients suffering from severe sepsis or septic shock were included during the first 24 hours of ICU treatment and blood samples for biomarker measurements, i.e., CAF, creatinine, cystatin C, procalcitonin (PCT), interleukin 6, C reactive protein (CRP), and white blood cells (WBC) were collected on the first day of intensive care treatment. The number of RRT days and the incidence of AKI were documented. RESULTS 13% of the patients (8/61) suffered from SIRS/sepsis, 20% (12/61) from severe sepsis, and 67% (41/61) from septic shock. Serum levels of CAF significantly correlated with creatinine (r = 0.623, p < 0.001) and cystatin C (r = 0.578, p < 0.001). Multiple linear regression analyses adjusting CAF for inflammatory parameters (i.e., WBC, CRP, interleukin 6, PCT), age, and gender showed a strong correlation between CAF and creatinine (r = 0.643, p < 0.001). Serum levels of CAF were significantly associated with the need of RRT (area under the curve (AUC) = 0.772, 95% CI: 0.641-0.903, p = 0.002) and the incidence of AKI (AUC = 0.721, 95% CI: 591-0.850, p = 0.004) as indicated by ROC analysis. CONCLUSIONS In patients suffering from severe sepsis and septic shock, serum levels of CAF were significantly associated with kidney function and RRT and were not influenced by severe septic conditions.

An age-dependent decline in skeletal muscle mass, strength, and endurance during the aging process is a physiological development, but several factors may exacerbate this process, leading to the threatening state of sarcopenia, frailty, and eventually higher mortality rates. Obesity appears to be such a promoting factor and has been linked in several studies to sarcopenia. The reason for this causal association remains poorly understood. Notwithstanding the fact that a higher body mass might simply lead to diminished physical activity and therefore contribute to a decline in skeletal muscle, several molecular mechanisms have been hypothesized. There could be an obesity derived intracellular lipotoxicity (i.e., elevated intramuscular levels of lipids and their derivatives), which induces apoptosis by means of an elevated oxidative stress. Paracrine mechanisms and inflammatory cytokines, such as CRP and IL-6 could be confounders of the actual underlying pathological mechanism. Due to a cross-talk of the hypothalamo-pituitary axis with nutritional status, obese subjects are more in a catabolic state of metabolism, with a higher susceptibility to muscle wasting under energy restriction. Obesity induces insulin resistance in the skeletal muscle, which consequently leads to perturbed metabolism, and misrouted signaling in the muscle cells. In obesity, muscle progenitor cells could differentiate to an adipocyte-like phenotype as a result of paracrine signals from (adipo)cytokines leading to a reduced muscular renewal capacity. The present review outlines current knowledge concerning possible pathways, which might be involved in the molecular pathogenesis of sarcopenic obesity.

Background: Knowledge about the molecular pathomechanisms of sarcopenia is still sparse, especially with regard to nutritional risk factors and the subtype of sarcopenic obesity. Objective: The aim of this study was to characterize diet-induced and age-related changes on the quality and quantity of the quadriceps muscle in a rat model of sarcopenia by different magnetic resonance (MR) techniques. Methods: A total of 36 6-month-old male Sprague-Dawley rats were randomly subdivided into 2 groups and received either a high-fat diet (HFD) or a control diet (CD). At the age of 16 months, 15 HFD and 18 CD rats underwent MR at 1.5 T. T1-weighted images as well as T2 relaxation time maps were acquired perpendicular to the long axis of the quadriceps muscles. Maximum cross-sectional area (CSA) of the quadriceps muscle was measured on T1-weighted images, and T2 relaxation times of muscle were assessed in a region without visible intramuscular fat (T2lean muscle) and across the complete CSA (T2muscle). Furthermore, 1H-MR spectroscopy was performed to evaluate the relative lipid content of the quadriceps muscles. These measurements were repeated 5 months later in the surviving 8 HFD and 14 CD rats. Results: HFD rats revealed significantly decreased CSA and CSA per body weight (BW) as well as prolonged T2 relaxation times of muscle. A higher weight gain (upper tertile during the first 6 months of diet in CD rats) resulted in a significant change of T2muscle, but had no relevant impact on CSA. Advancing age up to 21 months led to significantly decreased BW, CSA and CSA/BW, significantly prolonged T2muscle and T2lean muscle and enlarged lipid content in the quadriceps muscle. Conclusions: In an experimental setting a chronically fat-enriched diet was shown to have a relevant and age-associated influence on both muscle quantity and quality. By translational means the employed MR techniques give rise to the possibility of an early detection and noninvasive quantification of sarcopenia in humans, which is highly relevant for the field of geriatrics., OA-Komponente aus Allianzlizenz

Objective: we examined the diagnostic accuracy of different methods of body temperature measurement to diagnose infection in geriatric patients presenting to the emergency department (ED). Methods: this observational study was done in consecutive patients ≥75 years old presenting to the ED. Body temperature was determined by tympanal thermometry, temporal artery thermometry and rectal temperature measurement. Adjudicated final diagnosis of infection was done by two experts including patient history, clinical and laboratory findings as well as radiographic studies. Results: a total of 427 patients were included in the data analysis (age: 82.7 ± 5.1 years). Infection was present in 105 patients (24.6%). Respiratory rate, heart rate and body temperature were significantly higher in patients with infection, blood pressure was lower (P< 0.01). Body temperature measured by tympanal and temporal artery thermometry was correlated with rectal thermometry. Body temperature was significantly higher in patients with infection compared with those without infection independent of the method of body temperature measurement (P< 0.001). The diagnostic accuracy for infection quantified by the area under curve (AUC) was comparable among rectal [AUC: 0.72 (95% CI: 0.65–0.80)] and tympanal thermometry [AUC: 0.73 (95% CI: 0.66–0.81)], but significantly lower in temporal artery thermometry [AUC: 0.65 (95% CI: 0.57–0.73; P< 0.001)]. Compared with rectal measurement tympanal thermometry showed a higher bias than temporal artery thermometry (0.54 versus 0.03°C), while its limits of agreement were more narrow (−0.14 to 1.21°C versus −0.94–1.01°C). Conclusion: diagnostic accuracy for the identification of infection was comparable among tympanal and rectal thermometry and lower for temporal artery thermometry. Different cut-off points should be used to identify infection using tympanal (37.3° C) or rectal (37.9°C) thermometry. In general, temperature measurement is an insensitive method to identify geriatric patients with infection. Registration number clinicaltrials.com: KSMC-tempger-1.

It is indefinite whether nonalcoholic steatohepatitis (NASH) results as by-product from general metabolic perturbations and adipokine dysregulations or whether defined dietary factors also play a pathogenetic role. Here, we examine the effects of a modification of dietary lipids in a NASH inducing diet on metabolic changes as well as hepatic steatosis, inflammation, and fibrosis in rats. Male Wistar rats were fed with variations of the atherogenic diet (AD), which induces pathophysiological changes resembling human NASH. Dietary variants (AD without cholesterol, cholate, or choline; change of neutral fat to olive oil or coconut oil) were fed for 8 weeks. Insulin resistance, adipokine profile, liver histology, and lipid content as well as expression of proinflammatory and profibrogenic genes were examined. AD led to clear signs of hepatic steatosis and inflammation together with an increase in TNF and collagen type 1 expression. AD without cholesterol showed markedly less liver damage without changes of insulin action and adipokine profile. AD with olive oil and AD without cholate clearly attenuated hepatic inflammation, whereas fat deposition and features of the metabolic syndrome were increased in these animals. Insulin resistance and hepatic fat deposition per se do not cause significant hepatic inflammation in this rodent model. However, dietary cholesterol is an important causal agent for the development of NASH. Olive oil plays a protective role in this respect, which might be due to the high content of monounsaturated fatty acids.

The regulation of gene repression by corepressors is a controlled process. Surface-enhanced laser desorption ionization MS proteomic analysis and a yeast two-hybrid screen showed independently that the corepressor Alien interacts with the CREB-binding protein (CBP) coactivator. This interaction was further confirmed by coimmunoprecipitation and glutathione S-transferase pull-down experiments, suggesting that Alien interacts in vivo and in vitro with the histone acetyltransferase (HAT) coactivators CBP and its paralog p300. Acetylation detection experiments indicated that Alien is acetylated in vivo. Furthermore, Alien interacts with the central region of CBP/p300 containing the HAT domain and becomes acetylated in vitro. When an inhibitor of CBP/p300 HAT activity was employed, the Alien-mediated silencing was enhanced. Thus, these findings suggest crosstalk between corepressors and coactivators, and indicate fine-tuning of corepressor function by post-translational modification through corepressor acetylation. Structured digital abstract p300 binds to Alien α by pull down (View interaction) Alien α physically interacts with CBP by two hybrid (View interaction) Alien α physically interacts with MLK2 by two hybrid (View interaction) p300 acetylates Alien α by acetylation assay (View interaction) Alien α physically interacts with NAP1 by two hybrid (View interaction) Alien α physically interacts with TAFI68 by two hybrid (View interaction) Alien α physically interacts with CBP by anti bait coimmunoprecipitation (View Interaction: 1, 2, 3) Alien α binds to CBP by pull down (View interaction)

We previously identified transthyretin (TTR) and its posttranslational modifications as a down-regulated marker in mycosis fungoides (MF), a benign subtype of cutaneous T-cell lymphoma (CTCL). In order to more precisely understand the biological role of TTR in the etiology of MF, it is essential to clarify the pathways of progression by identifying further interacting proteins. This study is the first to combine blue native polyacrylamide gel electrophoresis (BN-PAGE) with surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to detect new TTR interaction partners and to determine whether these TTR interaction partners can themselves be used as biomarkers. By this procedure, apolipoprotein A1, which was additionally found to be down-regulated in the serum of MF patients, apolipoprotein A4, retinol binding protein 4 (RBP-4), and retinoid X receptor β (RXR-β) were identified as interaction partners of TTR. The RXR family plays a role in cell differentiation and proliferation and is known to be the target of bexarotene, which is used in the treatment of CTCL. In conclusion, the combination of BN-PAGE and SELDI-TOF-MS used in this study allowed for the detection of protein interaction partners, which, in the case of RBP-4 and RXR, indicated a connection between the common tumor marker TTR and tumor progression in CTCL.

Proteins perform their activities in cells by the cooperation within protein complexes. For this reason, it is important to investigate protein−protein interactions to receive insights in physiological processes. A multitude of proteins are involved in the regulation of the cell cycle. Specific key factors participating here are members of the E2F transcription factors. Using an in vivo protein−protein complex detection assay, which comprises mass spectrometric and immunological techniques, we detected a number of known as well as new protein−protein interactions. We describe here for the first time protein complexes containing the corepressor Alien and members of the E2F transcription factor family. Furthermore, we assessed the functional relevance and show a repression of the transcriptional activity of E2F by Alien. Additionally, we detected new interactions that link endogenously expressed Alien with the tumor suppressor retinoblastoma protein (pRB) and with proteins involved in cell cycle regulation....

Background The immune system undergoes several alterations of innate and adaptive immunity during ageing. The main features of the aged immune system are a reduced diversity of T cell receptors and a reduced activity of innate immune cells with subsequent changes in adaptive immunity resulting in a less effective, less specific, and dys-regulated immune response and in an increased susceptibility towards infection, malignancy, and autoimmunity. The process is referred to as immunosenescence and is also modulated by environmental modifiers, such as dietary factors. High fat diet (HFD), via direct modulation of immune cell function by fatty acids and/or increased body fat mass, influences immune function. However, it is not clear whether HFD is beneficial or detrimental for the functioning of the ageing immune system. Methods Male Wistar rats fed with either a high fat diet (HFD 43 en% of fat) or control diet (SD, 25 en% of fat) over up to 24 month and were analyzed for plasma IL-1β, IL-6, TNF, IgM, IgG1, IgA, IgG2a, IgG2b, IgG2c, light chains lambda and kappa, testosterone, prolactin and percentage of splenic B cells and apoptosis rate, respectively. Results In general, all analyzed immunoglobuline isotypes increased with age, except for IgA. This increase was attenuated by HFD. In HFD and SD rats the percentage of B cells in the spleen and also their apoptotic rate was lower in aged as compared to young animals with no additional diet-induced effect. Testosterone and prolactin levels were lower in old animals, as expected. There was a statistical trend towards an increased prolactin/testosterone ratio in middle aged (6–12 monthsnth) HFD rats as compared to SD. IL-6 was neither affected by HFD nor age. On the other hand, HFD rats showed a decrease in IL-1β as compared to SD, which correlated with the above-mentioned suppressive effect on immunoglobulin isotypes, especially IgM. Conclusion In Wistar rats, HFD reveals an immunosuppressive effect in ageing animals by decreasing immunoglobulins, especially IgM, and IL-1β when compared to SD.