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Hintergrund Rezidivierende mukokutane Infektionen durch PVL-positive Staphylococcus (S.) aureus-Stamme stellen in Deutschland ein zunehmendes Problem dar. In den letzten Jahren wurden Ausbruche in Kindertagesstatten und Kommunen beschrieben. Dennoch liegen zurzeit keine diagnostischen Algorithmen oder Therapieempfehlungen fur die entsprechenden Infektionen in Deutschland vor. Methode Eine Literaturrecherche in der Datenbank PubMed/MEDLINE erfolgte mit dem Ziel, einen diagnostischen und therapeutischen Algorithmus zu erarbeiten. Zudem wurden nationale und internationale Empfehlungen berucksichtigt. Ergebnisse Panton-Valentine Leukozidin (PVL) ist ein porenbildendes Protein, das von bestimmten S. aureus-Stammen produziert wird. Sowohl Methicillin-sensible (MSSA) als auch Methicillin-resistente S. aureus (MRSA)-Stamme konnen das fur die PVL-Produktion verantwortliche Gen lukS-lukF besitzen. Das klinische Bild der durch einen PVL-positiven S. aureus verursachten Infektionen erstreckt sich von einzelnen rezidivierenden Abszessen bis hin zu einer ausgedehnten Furunkulose. Bei etwa 40 % der Patienten kommt es zu Rezidiven der Beschwerden trotz einer konsequenten Behandlung der Erstinfektion. Die Therapie variiert je nach klinischem Bild der jeweiligen Infektion. Zudem wird in der Literatur eine Screeninguntersuchung der Patienten und ihrer engen Kontaktpersonen sowie eine bakterielle Dekolonisation der Betroffenen empfohlen. Schlussfolgerungen Diese Arbeit fokussiert auf die Pathogenese und Risikofaktoren der rezidivierenden mukokutanen Infektionen durch PVL-positive S. aureus-Stamme und versucht einen diagnostischen und therapeutischen Algorithmus zur optimalen Patientenversorgung vorzuschlagen.

Background Vital signs are usually recorded once every 8 h in patients at the hospital ward. Early signs of deterioration may therefore be missed. Wireless sensors have been developed that may capture patient deterioration earlier. The objective of this study was to determine whether two wearable patch sensors (SensiumVitals [Sensium Healthcare Ltd., United Kingdom] and HealthPatch [VitalConnect, USA]), a bed-based system (EarlySense [EarlySense Ltd., Israel]), and a patient-worn monitor (Masimo Radius-7 [Masimo Corporation, USA]) can reliably measure heart rate (HR) and respiratory rate (RR) continuously in patients recovering from major surgery. Methods In an observational method comparison study, HR and RR of high-risk surgical patients admitted to a step-down unit were simultaneously recorded with the devices under test and compared with an intensive care unit–grade monitoring system (XPREZZON [Spacelabs Healthcare, USA]) until transition to the ward. Outcome measures were 95% limits of agreement and bias. Clarke Error Grid analysis was performed to assess the ability to assist with correct treatment decisions. In addition, data loss and duration of data gaps were analyzed. Results Twenty-five high-risk surgical patients were included. More than 700 h of data were available for analysis. For HR, bias and limits of agreement were 1.0 (–6.3, 8.4), 1.3 (–0.5, 3.3), –1.4 (–5.1, 2.3), and –0.4 (–4.0, 3.1) for SensiumVitals, HealthPatch, EarlySense, and Masimo, respectively. For RR, these values were –0.8 (–7.4, 5.6), 0.4 (–3.9, 4.7), and 0.2 (–4.7, 4.4) respectively. HealthPatch overestimated RR, with a bias of 4.4 (limits: –4.4 to 13.3) breaths/minute. Data loss from wireless transmission varied from 13% (83 of 633 h) to 34% (122 of 360 h) for RR and 6% (47 of 727 h) to 27% (182 of 664 h) for HR. Conclusions All sensors were highly accurate for HR. For RR, the EarlySense, SensiumVitals sensor, and Masimo Radius-7 were reasonably accurate for RR. The accuracy for RR of the HealthPatch sensor was outside acceptable limits. Trend monitoring with wearable sensors could be valuable to timely detect patient deterioration. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Cultured meat is an emergent technology with the potential for significant environmental and animal welfare benefits. Accurate mimicry of traditional meat requires fat tissue; a key contributor to both the flavour and texture of meat. Here, we show that fibro-adipogenic progenitor cells (FAPs) are present in bovine muscle, and are transcriptionally and immunophenotypically distinct from satellite cells. These two cell types can be purified from a single muscle sample using a simple fluorescence-activated cell sorting (FACS) strategy. FAPs demonstrate high levels of adipogenic potential, as measured by gene expression changes and lipid accumulation, and can be proliferated for a large number of population doublings, demonstrating their suitability for a scalable cultured meat production process. Crucially, FAPs reach a mature level of adipogenic differentiation in three-dimensional, edible hydrogels. The resultant tissue accurately mimics traditional beef fat in terms of lipid profile and taste, and FAPs thus represent a promising candidate cell type for the production of cultured fat.

Simple Summary Gastric cancer is characterized by poor survival rates despite surgery and chemotherapy. Current research focuses on biomarkers to improve diagnosis and prognosis, and to enable targeted treatment strategies. The aim of our review was to give an overview over the wide range of novel biomarkers in gastric cancer. These biomarkers are targets of a specific treatment, such as antibodies against human epidermal growth factor receptor 2. Other promising biomarkers for targeted therapies that have shown relevance in clinical trials are vascular endothelial growth factor, programmed cell death protein 1, and Claudin 18.2. There is a vast number of biomarkers based on DNA, RNA, and protein expression, as well as detection of circulating tumor cells and the immune tumor microenvironment. Abstract Overall survival of gastric cancer remains low, as patients are often diagnosed with advanced stage disease. In this review, we give an overview of current research on biomarkers in gastric cancer and their implementation in treatment strategies. The HER2-targeting trastuzumab is the first molecular targeted agent approved for gastric cancer treatment. Other promising biomarkers for targeted therapies that have shown relevance in clinical trials are VEGF and Claudin 18.2. Expression of MET has been shown to be a negative prognostic factor in gastric cancer. Targeting the PD-1/PD-L1 pathway with immune checkpoint inhibitors has proven efficacy in advanced gastric cancer. Recent technology advances allow the detection of circulating tumor cells that may be used as diagnostic and prognostic indicators and for therapy monitoring in gastric cancer patients. Prognostic molecular subtypes of gastric cancer have been identified using genomic data. In addition, transcriptome profiling has allowed a comprehensive characterization of the immune and stromal microenvironment in gastric cancer and development of novel risk scores. These prognostic and predictive markers highlight the rapidly evolving field of research in gastric cancer, promising improved treatment stratification and identification of molecular targets for individualized treatment in gastric cancer.

Bei geriatrischen Patienten ist ein mechanischer Ileus einer der haufigsten Grunde fur eine Vorstellung im Krankenhaus und in 50 % der Falle Grund fur eine notfallmasige Operation. Diagnostik und Therapie des mechanischen Ileus haben sich in den vergangenen Jahren verandert. Neue Therapiekonzepte sollten hinsichtlich des alternden Patientenkollektivs kritisch gepruft werden. Ziel der Arbeit ist das Herausarbeiten moglicher Verbesserungsansatze in der Therapie des mechanischen Ileus bei geriatrischen Patienten. Retrospektiv wurden die Daten von 132 Patienten untersucht, die am Universitatsklinikum Bonn aufgrund eines mechanischen Ileus operiert wurden. Es wurden 2 Kohorten gebildet (50- bis 70-jahrige oder >80-jahrige Patienten) und die Dauer von Triage bis zur Operation, die Atiologie des Ileus, die Notwendigkeit einer Darmresektion, Notwendigkeit einer Stomaanlage sowie postoperative Komplikationen verglichen. Die Datenanalyse erfolgte mit dem Fisher-Test oder einem Student-t-Test. Die Dauer von Triage im Notfallzentrum bis zum Schnitt im Operationssaal betrug bei Patienten zwischen 50 und 70 Jahren 18,23 ± 0,79 h vs. 43,38 ± 12,08 h bei >80-Jahrigen (p = 0,0111). Bei alteren Patienten war in 58,9 %, eine Darmresektion notwendig vs. 35,3 % bei den jungeren (p = 0,0401). Die Rate schwerwiegender Komplikationen (Dindo/Clavien >IIIB) war mit 50 % bei alteren Patienten im Vergleich zu 12,7 % bei jungeren erhoht (p = 0,0002). Die Dauer des Aufenthalts auf der Intensivstation war bei Patienten >80 Jahren langer, als bei Patienten zwischen 50 und 70 Jahren (93,97 ± 17,36 h vs. 26,11 ± 3,73 h; p

Aim: We investigated the significance of PD-L2 DNA methylation in gastric adenocarcinomas. Methods: We analyzed the methylation at different CpG sites within the PD-L2-encoding gene PDCD1LG2 with regard to correlations and associations with gene expression, clinicopathological parameters, molecular features and immune cell infiltrates in two publicly available cohorts (The Cancer Genome Atlas and Singapore cohorts) of a total of 594 gastric adenocarcinoma patients. Results: PD-L2 methylation is significantly associated with transcriptional activity, survival, Epstein–Barr virus infection, PD-L2 gene amplification, CD8+ T-cell infiltration, microsatellite instability and high mutational load (tumor mutational burden, hypermutation). Conclusion: PD-L2 methylation is associated with known predictive biomarkers of response to anti-PD-1 immunotherapies.

The Accelerate Pheno system is approved for rapid identification and phenotypic antimicrobial susceptibility testing (AST) of microorganisms grown from positive blood cultures inoculated with blood from septic patients. We evaluated the performance of the system for identification and AST from positive blood culture bottles inoculated with primary sterile nonblood specimens from patients with suspected severe infections. One hundred positive blood culture bottles with primary sterile specimens (63 cerebrospinal fluids, 16 ascites, 7 pleural fluids, 4 vitreous fluids, 5 joint aspirates, and 5 other aspirates) from 100 patients were included. Pathogen identification was in agreement with conventional methods for 72 of 100 cultures (72%) and for 81 of 112 (72%) pathogens when considering all pathogens and for 72 of 92 (78%) cultures and 81 of 104 (78%) pathogens when considering on-panel pathogens only. Eight of 31 isolates (26%) not identified by APS were pathogens not included in the APS panel. APS and conventional methods accordingly identified all pathogens from two of nine polymicrobial cultures (22%). APS generated antimicrobial resistance results for 57 pathogens of 57 cultures. The overall category agreement between APS and culture-based AST was 91.2%; and the rate for minor errors was 6.9%, for major was 1.7%, and for very major errors was 0.2%. APS may accelerate pathogen identification and phenotypic AST from positive blood culture bottles inoculated with primary sterile specimens from patients with serious infections, especially for hospitals without an on-site microbiology laboratory. However, the inclusion of nonblood specimens with a high likelihood of polymicrobial infections may result in an inferior performance.

Background Hospital stays after major surgery are shorter than ever before. Although enhanced recovery and early discharge have many benefits, some complications will now first manifest themselves in home settings. Remote patient monitoring with wearable sensors in the first days after hospital discharge may capture clinical deterioration earlier but is largely uncharted territory. Objective This study aimed to assess the technical feasibility of patients, discharged after esophagectomy, being remotely monitored at home with a wireless patch sensor and the experiences of these patients. In addition, we determined whether observing vital signs with a wireless patch sensor influences clinical decision making. Methods In an observational feasibility study, vital signs of patients were monitored with a wearable patch sensor (VitalPatch, VitalConnect Inc) during the first 7 days at home after esophagectomy and discharge from hospital. Vital signs trends were shared with the surgical team once a day, and they were asked to check the patient’s condition by phone each morning. Patient experiences were evaluated with a questionnaire, and technical feasibility was analyzed on a daily basis as the percentage of data loss and gap durations. In addition, the number of patients for whom a change in clinical decision was made based on the results of remote vital signs monitoring at home was assessed. Results Patients (N=20) completed 7 days each of home monitoring with the wearable patch sensor. Each of the patients had good recovery at home, and remotely observed vital signs trends did not alter clinical decision making. Patients appreciated that surgeons checked their vital signs daily (mean 4.4/5) and were happy to be called by the surgical team each day (mean 4.5/5). Wearability of the patch was high (mean 4.4/5), and no reports of skin irritation were mentioned. Overall data loss of vital signs measurements at home was 25%; both data loss and gap duration varied considerably among patients. Conclusions Remote monitoring of vital signs combined with telephone support from the surgical team was feasible and well perceived by all patients. Future studies need to evaluate the impact of home monitoring on patient outcome as well as the cost-effectiveness of this new approach.

BACKGROUND Hospital stays after major surgery are shorter than ever before. Although enhanced recovery and early discharge have many benefits, some complications will now first manifest themselves in home settings. Remote patient monitoring with wearable sensors in the first days after hospital discharge may capture clinical deterioration earlier but is largely uncharted territory. OBJECTIVE This study aimed to assess the technical feasibility of patients, discharged after esophagectomy, being remotely monitored at home with a wireless patch sensor and the experiences of these patients. In addition, we determined whether observing vital signs with a wireless patch sensor influences clinical decision making. METHODS In an observational feasibility study, vital signs of patients were monitored with a wearable patch sensor (VitalPatch, VitalConnect Inc) during the first 7 days at home after esophagectomy and discharge from hospital. Vital signs trends were shared with the surgical team once a day, and they were asked to check the patient’s condition by phone each morning. Patient experiences were evaluated with a questionnaire, and technical feasibility was analyzed on a daily basis as the percentage of data loss and gap durations. In addition, the number of patients for whom a change in clinical decision was made based on the results of remote vital signs monitoring at home was assessed. RESULTS Patients (N=20) completed 7 days each of home monitoring with the wearable patch sensor. Each of the patients had good recovery at home, and remotely observed vital signs trends did not alter clinical decision making. Patients appreciated that surgeons checked their vital signs daily (mean 4.4/5) and were happy to be called by the surgical team each day (mean 4.5/5). Wearability of the patch was high (mean 4.4/5), and no reports of skin irritation were mentioned. Overall data loss of vital signs measurements at home was 25%; both data loss and gap duration varied considerably among patients. CONCLUSIONS Remote monitoring of vital signs combined with telephone support from the surgical team was feasible and well perceived by all patients. Future studies need to evaluate the impact of home monitoring on patient outcome as well as the cost-effectiveness of this new approach.

Zusammenfassung Hintergrund Malignome des Ösophagus zählen zu den häufigsten krebsbedingten Todesursachen. Den einzigen kurativen Therapieansatz stellt die radikale Ösophagektomie, eingebettet in ein multimodales Therapiekonzept, dar. Ziel der Untersuchung war die Analyse von Langzeitentwicklungen in der operativen Therapie des Ösophaguskarzinoms und deren Einflüsse auf das kurz- (1-JÜR), mittel- (5-JÜR) und langfristige (10-JÜR) Überleben. Patienten und Methoden Es wurden retrospektiv 301 Patienten am Universitätsklinikum Bonn untersucht, bei denen zwischen 1989 und 2012 eine Ösophagusresektion durchgeführt wurde. Um mögliche Trends im Management und Veränderungen hinsichtlich der Prognose zu analysieren, wurden 2 Kohorten (Kohorte A: operiert 1989 – 2000, Kohorte B: operiert 2001 – 2012) gebildet und bez. demografischer Daten, Tumorentität, Stadium, Komplikationsrate und Überleben miteinander verglichen. Ergebnisse In der Kohorte B wurden signifikant ältere Patienten in niedrigeren Tumorstadien mit einer größeren Lymphknotenausbeute operiert, eine Zunahme des Adenokarzinoms (AC) war zu beobachten. Während sich die Gesamtmorbidität nicht signifikant veränderte, konnte eine geringere Rate an Anastomoseninsuffizienzen in Kohorte B (5,5%) verglichen mit Kohorte A (12,3%) bei gleichzeitigem Anstieg der kardialen Ereignisse (A: 3,6% vs. B: 12,3%) nachgewiesen werden. Die 30-Tage-Krankenhausmortalität lag bei insgesamt 2,7% und fiel von 5% (Kohorte A) signifikant (p = 0,05) auf 0,7% (Kohorte B). Das mittlere Überleben betrug in der Kohorte A 46 ± 6,5 Monate. In Kohorte B überlebten Patienten mit 53 ± 7,2 Monaten signifikant länger (p = 0,03). In der univariaten Analyse hatten das lokale Tumorstadium, der Resektionsgrad, die Anzahl der befallenen Lymphknoten (LK), der Lymphknotenquotient (LNR) sowie das Auftreten postoperativer Komplikationen einen Einfluss auf das Überleben, wohingegen in der multivariaten Analyse nur noch T-Stadium, R-Status und LNR als unabhängige Prognosefaktoren galten. Schlussfolgerung Patienten, die sich einer onkologischen Ösophagusresektion unterziehen, sind heutzutage älter als noch vor einigen Jahren. Die frühzeitigere Tumordiagnose, eine radikalere Operationstechnik mit radikalerer Lymphknotendissektion und weniger Anastomoseninsuffizienzen sowie eine verbesserte perioperative Medizin scheinen diesen demografischen Nachteil zu kompensieren. Die größte prognostische Bedeutung beim Ösophaguskarzinom hat die LNR.

Vital signs are usually recorded once every 8 h in patients at the hospital ward. Early signs of deterioration may therefore be missed. Wireless sensors have been developed that may capture patient deterioration earlier. The objective of this study was to determine whether two wearable patch sensors (SensiumVitals [Sensium Healthcare Ltd., United Kingdom] and HealthPatch [VitalConnect, USA]), a bed-based system (EarlySense [EarlySense Ltd., Israel]), and a patient-worn monitor (Masimo Radius-7 [Masimo Corporation, USA]) can reliably measure heart rate (HR) and respiratory rate (RR) continuously in patients recovering from major surgery.In an observational method comparison study, HR and RR of high-risk surgical patients admitted to a step-down unit were simultaneously recorded with the devices under test and compared with an intensive care unit-grade monitoring system (XPREZZON [Spacelabs Healthcare, USA]) until transition to the ward. Outcome measures were 95% limits of agreement and bias. Clarke Error Grid analysis was performed to assess the ability to assist with correct treatment decisions. In addition, data loss and duration of data gaps were analyzed.Twenty-five high-risk surgical patients were included. More than 700 h of data were available for analysis. For HR, bias and limits of agreement were 1.0 (-6.3, 8.4), 1.3 (-0.5, 3.3), -1.4 (-5.1, 2.3), and -0.4 (-4.0, 3.1) for SensiumVitals, HealthPatch, EarlySense, and Masimo, respectively. For RR, these values were -0.8 (-7.4, 5.6), 0.4 (-3.9, 4.7), and 0.2 (-4.7, 4.4) respectively. HealthPatch overestimated RR, with a bias of 4.4 (limits: -4.4 to 13.3) breaths/minute. Data loss from wireless transmission varied from 13% (83 of 633 h) to 34% (122 of 360 h) for RR and 6% (47 of 727 h) to 27% (182 of 664 h) for HR.All sensors were highly accurate for HR. For RR, the EarlySense, SensiumVitals sensor, and Masimo Radius-7 were reasonably accurate for RR. The accuracy for RR of the HealthPatch sensor was outside acceptable limits. Trend monitoring with wearable sensors could be valuable to timely detect patient deterioration.

Background Recurrent mucocutaneous infections caused by PVL-positive Staphylococcus (S.) aureus strains represent an increasing problem in Germany. Although there have been several outbreaks at day care centers and in urban communities in recent years, there are currently no diagnostic algorithms or treatment recommendations for these particular infections in Germany. Methods We performed a literature search in the PubMed/MEDLINE database with the goal of developing an algorithm for diagnosis and treatment of these infections. National and international recommendations were also considered. Results Panton-Valentine leukocidin (PVL) is a pore-forming protein produced by certain S. aureus strains. Both methicillin-susceptible (MSSA) and methicillin-resistant S. aureus (MRSA) strains may carry the lukS-lukF gene responsible for PVL production. The clinical presentation of infections caused by PVL-positive S. aureus ranges from isolated recurrent abscesses to extensive furunculosis. Despite adequate treatment of primary infections, approximately 40 % of patients develop recurrent disease. The choice of treatment regimen is guided by the clinical presentation of the infection. In addition, some scientific literature recommends bacteriological screening of patients and their contacts, followed by decolonization of affected individuals. Conclusions The present article focuses on the pathogenesis and risk factors of recurrent mucocutaneous infections caused by PVL-positive S. aureus strains and proposes a diagnostic and therapeutic algorithm for optimal patient care.

Mechanical bowel obstruction is a common condition in geriatric patients in the emergency department. It accounts for up to 50% of all emergency surgeries in the elderly. In recent years, diagnosis and treatment of mechanical bowel obstruction has improved, but little is known whether elderly patients benefit from modern treatment approaches.The aim of the work is to generate knowledge about possible improvement of diagnosis and treatment of mechanical bowel obstruction in the elderly.A retrospective review of 132 patients was performed comparing geriatric (80 years of age) and nongeriatric patients (50-70 years of age) admitted with mechanical bowel obstruction. Etiology, time from first contact to operation, bowel resection rate and morbidity/mortality were compared. Data analysis included Fisher's test and Student t‑test.In patients under 70 years of age it took 18.23 ± 0.79 h from first contact until laparotomy in the operating room (OR) vs. 43.38 ± 12.08 h in patients above 80 years of age (p = 0.0111). In 58.9% of geriatric patients, resection of bowel was necessary, while only 35.3% of70-year-old patients needed bowel resection (p = 0.0401). In all, 50% of geriatric patients experienced major complications (Dindo/ClavienIIIB) vs. only 12.7% of 50- to 70-year-old patients (p = 0.0002). Postoperative stay in the intensive care unit was significantly prolonged in geriatric patients compared to younger patients (93.97 ± 17.36 h vs. 26.11 ± 3.73 h, p 0.0001).Time from first contact in the emergency department until laparotomy in the OR is prolonged in geriatric patients, leading to a higher probability of bowel resection with greater morbidity and mortality. Diagnostics should be intensified and accelerated in geriatric patients. Emergency surgery should be considered earlier.

Background: Remote monitoring of physical activity in patients with chronic conditions could be useful to offer care professionals real-time assessment of their patient's daily activity pattern to adjust appropriate treatment. However, the validity of commercially available activity trackers that can be used for telemonitoring purposes is limited. Objective: The purpose of this study was to test usability and determine the validity of 3 consumer-level activity trackers as a measure of free-living activity. Methods: A usability evaluation (study 1) and validation study (study 2) were conducted. In study 1, 10 individuals wore one activity tracker for a period of 30 days and filled in a questionnaire on ease of use and wearability. In study 2, we validated three selected activity trackers (Apple Watch, Misfit Shine, and iHealth Edge) and a fourth pedometer (Yamax Digiwalker) against the reference standard (Actigraph GT3X) in 30 healthy participants for 72 hours. Outcome measures were 95% limits of agreement (LoA) and bias (Bland-Altman analysis). Furthermore, median absolute differences (MAD) were calculated. Correction for bias was estimated and validated using leave-one-out cross validation. Results: Usability evaluation of study 1 showed that iHealth Edge and Apple Watch were more comfortable to wear as compared with the Misfit Flash. Therefore, the Misfit Flash was replaced by Misfit Shine in study 2. During study 2, the total number of steps of the reference standard was 21,527 (interquartile range, IQR 17,475-24,809). Bias and LoA for number of steps from the Apple Watch and iHealth Edge were 968 (IQR -5478 to 7414) and 2021 (IQR -4994 to 9036) steps. For Misfit Shine and Yamax Digiwalker, bias was -1874 and 2004, both with wide LoA of (13,869 to 10,121) and (-10,932 to 14,940) steps, respectively. The Apple Watch noted the smallest MAD of 7.7% with the Actigraph, whereas the Yamax Digiwalker noted the highest MAD (20.3%). After leave-one-out cross validation, accuracy estimates of MAD of the iHealth Edge and Misfit Shine were within acceptable limits with 10.7% and 11.3%, respectively. Conclusions: Overall, the Apple Watch and iHealth Edge were positively evaluated after wearing. Validity varied widely between devices, with the Apple Watch being the most accurate and Yamax Digiwalker the least accurate for step count in free-living conditions. The iHealth Edge underestimates number of steps but can be considered reliable for activity monitoring after correction for bias. Misfit Shine overestimated number of steps and cannot be considered suitable for step count because of the low agreement. Future studies should focus on the added value of remotely monitoring activity patterns over time in chronic patients.

Correction to: Chapter 26 in: Rubén Alcázar and Antonio F. Tiburcio (eds.), Polyamines: Methods and Protocols, Methods in Molecular Biology, vol. 1694, https://doi.org/10.1007/978-1-4939-7398-9_26.

Ornithine decarboxylase (ODC), a ubiquitin-independent substrate of the proteasome, is a homodimeric protein with a rate-limiting function in polyamine biosynthesis. Polyamines regulate ODC levels by a feedback mechanism mediated by ODC antizyme (OAZ). Higher cellular polyamine levels trigger the synthesis of OAZ and also inhibit its ubiquitin-dependent proteasomal degradation. OAZ binds ODC monomers and targets them to the proteasome. Here, we report that polyamines, aside from their role in the control of OAZ synthesis and stability, directly enhance OAZ-mediated ODC degradation by the proteasome. Using a stable mutant of OAZ, we show that polyamines promote ODC degradation in Saccharomyces cerevisiae cells even when OAZ levels are not changed. Furthermore, polyamines stimulated the in vitro degradation of ODC by the proteasome in a reconstituted system using purified components. In these assays, spermine shows a greater effect than spermidine. By contrast, polyamines do not have any stimulatory effect on the degradation of ubiquitin-dependent substrates.

Background and objectivesIntermittent vital signs measurements are the current standard on hospital wards, typically recorded once every 8 hours. Early signs of deterioration may therefore be missed. Recent innovations have resulted in ‘wearable’ sensors, which may capture patient deterioration at an earlier stage. The objective of this study was to determine whether a wireless ‘patch’ sensor is able to reliably measure respiratory and heart rate continuously in high-risk surgical patients. The secondary objective was to explore the potential of the wireless sensor to serve as a safety monitor.DesignIn an observational methods comparisons study, patients were measured with both the wireless sensor and bedside routine standard for at least 24 hours.SettingUniversity teaching hospital, single centre.ParticipantsTwenty-five postoperative surgical patients admitted to a step-down unit.Outcome measuresPrimary outcome measures were limits of agreement and bias of heart rate and respiratory rate. Secondary outcome measures were sensor reliability, defined as time until first occurrence of data loss.Results1568 hours of vital signs data were analysed. Bias and 95% limits of agreement for heart rate were −1.1 (−8.8 to 6.5) beats per minute. For respiration rate, bias was −2.3 breaths per minute with wide limits of agreement (−15.8 to 11.2 breaths per minute). Median filtering over a 15 min period improved limits of agreement of both respiration and heart rate. 63% of the measurements were performed without data loss greater than 2 min. Overall data loss was limited (6% of time).ConclusionsThe wireless sensor is capable of accurately measuring heart rate, but accuracy for respiratory rate was outside acceptable limits. Remote monitoring has the potential to contribute to early recognition of physiological decline in high-risk patients. Future studies should focus on the ability to detect patient deterioration on low care environments and at home after discharge.

Correction to: Chapter 26 in: Ruben Alcazar and Antonio F. Tiburcio (eds.), Polyamines: Methods and Protocols, Methods in Molecular Biology, vol. 1694, https://doi.org/10.1007/978-1-4939-7398-9_26.

Turbocharger (TC) bearing friction mostly affects the “low speed” operation of the turbocharger and is therefore relevant for the transient response and part load emissions of modern combustion engines. Further optimization of TC friction has to be supported by sophisticated simulation tools to shorten developmental time and reducing the costs for prototyping and testing.

Polyamines are essential poly-cations with vital functions in all cellular systems. Their levels are controlled by intricate regulatory feedback mechanisms. Abnormally high levels of polyamines have been linked to cancer. A rate-limiting enzyme in the biosynthesis of polyamines in fungi and higher eukaryotes is ornithine-decarboxylase (ODC). Its levels are largely controlled posttranslationally via ubiquitin-independent degradation mediated by ODC antizyme (OAZ). The latter is a critical polyamine sensor in a feedback control mechanism that adjusts cellular polyamine levels. Here, we describe an approach employing quantitative western blot analyses that provides in vivo evidence for cotranslational polyamine-sensing by nascent OAZ in yeast. In addition, we describe an in vitro method to detect polyamine binding by antizyme.

Polyamines are essential poly-cations with vital functions in all cellular systems. Their levels are controlled by intricate regulatory feedback mechanisms. Abnormally high levels of polyamines have been linked to cancer. A rate-limiting enzyme in the biosynthesis of polyamines in fungi and higher eukaryotes is ornithine-decarboxylase (ODC). Its levels are largely controlled posttranslationally via ubiquitin-independent degradation mediated by ODC antizyme (OAZ). The latter is a critical polyamine sensor in a feedback control mechanism that adjusts cellular polyamine levels. Here, we describe an approach employing quantitative western blot analyses that provides in vivo evidence for cotranslational polyamine-sensing by nascent OAZ in yeast. In addition, we describe an in vitro method to detect polyamine binding by antizyme.

Die Reduktion der Reibungsverluste von Verbrennungsmotoren stellt auch weiterhin ein kosteneffizientes Mittel zur Erreichung zukunftiger CO2-Grenzwerte dar. Wie ein Ver-gleich mit der bei der FEV GmbH verfugbaren weltweit grosten Reibungsdatenbank auf-zeigt, offenbaren selbst moderne Motoren, die erst vor kurzem in die Serie eingefuhrt wurden, noch Potentiale zur CO2-Reduzierung von bis zu 8 % allein durch reibungsreduzierende Masnahmen.

Of all pathogenic mitochondrial DNA (mtDNA) mutations in humans, ∼25% is de novo, although the occurrence in oocytes has never been directly assessed. We used next-generation sequencing to detect point mutations directly in the mtDNA of 3–15 individual mature oocytes and three somatic tissues from eight zebrafish females. Various statistical and biological filters allowed reliable detection of de novo variants with heteroplasmy ≥1.5%. In total, we detected 38 de novo base substitutions, but no insertions or deletions. These 38 de novo mutations were present in 19 of 103 mature oocytes, indicating that ∼20% of the mature oocytes carry at least one de novo mutation with heteroplasmy ≥1.5%. This frequency of de novo mutations is close to that deducted from the reported error rate of polymerase gamma, the mitochondrial replication enzyme, implying that mtDNA replication errors made during oogenesis are a likely explanation. Substantial variation in the mutation prevalence among mature oocytes can be explained by the highly variable mtDNA copy number, since we previously reported that ∼20% of the primordial germ cells have a mtDNA copy number of ≤73 and would lead to detectable mutation loads. In conclusion, replication errors made during oogenesis are an important source of de novo mtDNA base substitutions and their location and heteroplasmy level determine their significance.

Purpose To explore the possibilities for IT interventions in care of older persons with dementia. Method Inventory of international and national studies on implemented technology interventions for the care of persons with dementia and their caregivers. Three categories of technology are distinguished: (1) help with symptoms of dementia (2) social contact and company for the patient, and (3) health monitoring and safety. Results Eighteen international and eight national studies are included. The first results of the effects of technology interventions for patients with dementia look promising. Evidence exists for significant improvements as to the quality of life and effects on behaviour (such as less falling). The caregivers and healthcare professionals are satisfied with the usability of the technology. The purchase and user costs, however, are often too high. The labour satisfaction of healthcare professionals in relation to the use of technology has rarely been studied. Conclusion Although technology can improve the ability to cope with certain consequences of dementia, the effects of technology for dementia patients, caregivers and healthcare professionals has not yet been extensively studied. Further research may focus on effects of technology for people with dementia and their caregivers as to their quality of life, feeling of safety and work satisfaction, respectively.

The hydrodynamic radius, rh, of low molar mass polyethylene glycol, MPEG = (200 to 1000) g·mol-1, in a homologous series of primary alcohols, acetone, and toluene has been determined from viscosity measurements. The viscosity data have been collected using a fast one-point method as well as a more generally used multipoint method. The results for both approaches are in good agreement. For a given average molar mass of PEG, rh is the largest in acetone, methanol, and toluene and shows a decrease with the chain length of the alcohol. For the solvents studied, rh shows an increase with MPEG that can be described adequately by the two-parameter Mark-Houwink equation for MPEG = (400 to 1000) g·mol-1. In the range T = (298.2 to 323.2) K, the influence of the temperature is not significant. © 2008 American Chemical Society

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In the yeast Saccharomyces cerevisiae, substrates of the N-end rule pathway are targeted for degradation by a complex that includes the 225-kDa N-recognin, encoded by UBR1, and the 20-kDa ubiquitin-conjugating enzyme encoded by UBC2. We report that both physical stability and functional activity of the N-recognin.Ubc2 complex require the presence of a highly acidic 23-residue region at the C terminus of Ubc2. Ubc2-C88A, an inactive variant of Ubc2 in which the active-site Cys-88 has been replaced by Ala, is shown to retain the affinity for N-recognin. Expression of Ubc2-C88A inhibits the N-end rule pathway, apparently as a result of competition between Ubc2 and Ubc2-C88A for binding to N-recognin. The two-hybrid (interaction cloning) technique was used to identify a approximately 170-residue C-terminal fragment of the 1,950-residue N-recognin as a Ubc2-interacting domain. We also show that the level of UBR1 mRNA decreases upon overexpression of UBC2. This effect of UBC2 is observed with cells whose UBR1 is expressed from an unrelated promoter but is not observed if UBR1 contains a frameshift mutation, or if the Ubc2 protein lacks its C-terminal acidic region. The N-recognin.Ubc2 complex appears to regulate the expression of N-recognin through changes in the metabolic stability of its mRNA.

To explore the possibilities for IT interventions in care of older persons with dementia.Inventory of international and national studies on implemented technology interventions for the care of persons with dementia and their caregivers. Three categories of technology are distinguished: (1) help with symptoms of dementia (2) social contact and company for the patient, and (3) health monitoring and safety.Eighteen international and eight national studies are included. The first results of the effects of technology interventions for patients with dementia look promising. Evidence exists for significant improvements as to the quality of life and effects on behaviour (such as less falling). The caregivers and healthcare professionals are satisfied with the usability of the technology. The purchase and user costs, however, are often too high. The labour satisfaction of healthcare professionals in relation to the use of technology has rarely been studied.Although technology can improve the ability to cope with certain consequences of dementia, the effects of technology for dementia patients, caregivers and healthcare professionals has not yet been extensively studied. Further research may focus on effects of technology for people with dementia and their caregivers as to their quality of life, feeling of safety and work satisfaction, respectively.

Micro structures of coating surfaces lead to new industrial applications. They allow to steer the wetting and dewetting behaviour of surfaces and in particular to enhance hydrophobicity. Here, we discuss the formation of micro structures in the drying process of a coating. Furthermore, for a given micro structured surface we show how to predict the effective contact angle of drops on the surface. At first, we derive a new approach for the simulation of micro structure evolution based on a gradient flow perspective for thin liquid films. This formulation includes a solvent dependent surface tension, viscosity and evaporation rate. In each time step of the resulting algorithm a semi implicit Rayleigh functional is minimized. The functional itself depends on the solution of a transport problem. We apply a finite difference discretization both for the functional and the transport process. As in PDE optimization a duality argument allows the efficient computation of descent directions. Next, given a certain micro structured coating we mathematically describe effective contact angles in different configurations and their impact on the macroscopic hydrophilic or hydrophobic surface properties. On periodic surfaces we aim at the computation of effective contact angles. This involves a geometric free boundary problem on the fundamental cell. Its solution describes vapor inclusions on the wetted surface. The free boundary problem is solved by a suitable composite finite element approach.

We adapt the Mextram 504 compact model for Si and SiGe bipolar transistors to make it suitable for compact modeling of GaAs HBT's. We discuss the different physics included in the new model, Mextram 3500, and demonstrate the capabilities of the new model on GaAs HBT characteristic simulations. We also show an example of advanced GaAs PA-circuit simulations that have been performed with our model.

20S proteasomes constitute the proteolytic core of large protease complexes found in all branches of life. Among these, the eukaryotic 26S proteasome ubiquitously poses as a vital final entity in regulated degradation of intracellular proteins. The composition of 20S core particles has been disclosed in detail, facilitated by groundbreaking studies on ancestral prokaryotic 20S proteasomes of low complexity and culminated in the crystal structure determination of the much more complex eukaryotic particles. This article first summarizes insights into the structural organization of the 20S core followed by characterization of its proteolytic activities, which are confined to the central cavity of the particle. In eukaryotes they reside in three different subunit types differing in their preference for cleavage sites in substrates as well as in their importance for the proteasome's cellular function. The second part reviews current knowledge on the biogenesis pathways of 20S core particles, which have to ensure not only the fixed subunit arrangement but also activation of proteolytic subunits in a late assembly state.