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Introduction Persistent psychosocial problems in people with lower-limb amputation due to vascular aetiology indicate a great need for long-lasting holistic rehabilitation. An in-depth understanding of the psychosocial problems is essential for the guidance of health professionals in meeting and normalising patients’ experiences and emotions. Furthermore, identifying the psychological problems may help develop effective rehabilitation and counselling programmes. This meta-aggregation study aims to explore the psychosocial perspectives of individuals who have undergone a major lower-limb amputation due to vascular aetiology during the post-discharge rehabilitation phase.Methods and analysis A systematic meta-aggregation study will be performed to identify full-text, peer-reviewed journal articles reporting on patients’ psychosocial perspectives on major lower-limb amputation due to vascular aetiology from post-discharge to several years afterward. The databases Embase, CINAHL Ultimate, APA PsycInfo, PubMed and Scopus will be searched with no limitations regarding the publication year. Studies that satisfy the eligibility criteria will be critically appraised using an acknowledged checklist and synthesised using the Joanna Briggs Institute three-phase approach for the synthesis of meta-aggregation studies. The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation- Confidence in Evidence from Reviews of Qualitative research) tool will be used to determine the level of confidence in the qualitative evidence, and the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) reporting guidelines will be followed throughout the review process.Ethics and dissemination Ethical approval is not required for the study, as the review is built on pre-existing available data in the literature. Findings from the review will be disseminated through publication in a peer-review journal.PROSPERO registration number CRD42022377114.

We present the discovery of TOI 762 A b and TIC 46432937 b, two giant planets transiting M-dwarf stars. Transits of both systems were first detected from observations by the NASA TESS mission, and the transiting objects are confirmed as planets through high-precision radial velocity observations carried out with Very Large Telescope/ESPRESSO. TOI 762 A b is a warm sub-Saturn with a mass of 0.251 ± 0.042 M _J , a radius of 0.744 ± 0.017 R _J , and an orbital period of 3.4717 days. It transits a mid-M-dwarf star with a mass of 0.442 ± 0.025 M _☉ and a radius of 0.4250 ± 0.0091 R _☉ . The star TOI 762 A has a resolved binary star companion, TOI 762 B, that is separated from TOI 762 A by 3.″2 (∼319 au) and has an estimated mass of 0.227 ± 0.010 M _☉ . The planet TIC 46432937 b is a warm super-Jupiter with a mass of 3.20 ± 0.11 M _J and radius of 1.188 ± 0.030 R _J . The planet’s orbital period is P = 1.4404 days, and it undergoes grazing transits of its early M-dwarf host star, which has a mass of 0.563 ± 0.029 M _☉ and a radius of 0.5299 ± 0.0091 R _☉ . TIC 46432937 b is one of the highest-mass planets found to date transiting an M-dwarf star. TIC 46432937 b is also a promising target for atmospheric observations, having the highest transmission spectroscopy metric or emission spectroscopy metric value of any known warm super-Jupiter (mass greater than 3.0 M _J , equilibrium temperature below 1000 K).

Background Regulatory assessment of anthroposophic medicinal products (AMPs) can be challenging due to their specific features. Objective The aim of this paper is therefore to provide adequate scientific information on AMPs for regulatory purposes. Methods A literature review was executed with database searches in PubMed, Cinahl, Merkurstab, Anthromedics, and https://iaap-pharma.org/ . Search terms were: anthroposophic medicinal products, anthroposophic medicines, anthroposophic pharmacy. There was no language restriction; searches were executed from onset until June 11, 2020. In addition, experts were invited to suggest relevant literature. Results Eighty-seven of 660 identified publications were included. The system of anthroposophic medicine (AM) with its conceptual background and various aspects of AMPs was described: definition, pharmaceutical properties, an example of AMP development, use in clinical practice, similarities with and differences to conventional medicinal products, societal aspects, scientific and regulatory assessment. Conclusion AMPs are part of the integrative whole medical system of AM. AMPs are manufactured according to Good Manufacturing Practice and national drug regulations and have an excellent safety status; the limited available evidence suggests clinical benefits. Current drug regulation of AMPs in the EU and most European countries does not take the special properties of AMPs into account. Future research should focus on appropriate methodologies for the evaluation of effects of AMPs as part of the AM whole medical system, the scientific quality of its non-atomistic holistic ontological position, and the integration of AM and conventional medicine in clinical practice. Future policies should focus on appropriate ways of addressing regulatory challenges to AMPs.

Objectives The aim of the study was to provide evidence for, at which vital and laboratory values, increased risk of 7-day mortality in acute adult patients on arrival to an emergency department (ED).Design A population-based cohort study.Setting ED at Odense University Hospital, Denmark.Participants All patients ≥18 years with a first-time contact within the study period, 1 April 2012 to 31 March 2015.Primary and secondary outcome measures Primary outcome was 7-day all-cause mortality.Variables were first recorded vital and laboratory values included in risk stratification scores; respiratory frequency, blood pressure, heart rate, Glasgow Coma Scale, temperature, saturation, creatinine, PaO2, platelet count and bilirubin. The association between values and mortality was described using a restricted cubic spline. A predefined 7-day mortality of 2.5% was chosen as a relevant threshold.Results We included 40 423 patients, 52.5% women, median age 57 (IQR 38–74) years and 7-day mortality 2.8%. Seven-day mortality of 2.5% had thresholds of respiratory frequency 18/min, systolic blood pressure 192 mm Hg, heart rate 102 beats/min, temperature 39.8°C, saturation 98 µmol/L for PaO2 12.3 kPa, platelet count 327×109/L and bilirubin >12 µmol/L.Conclusion Vital values on arrival, outside the normal ranges for the measures, are indicative of increased risk of short-term mortality, and most of the value thresholds are included in the lowest urgency level in triage and risk stratification scoring systems.

Abstract Background Acutely ill patients are a heterogeneous group, and some of these suffer from organ failure. As the prognosis of organ failure improves with early treatment, it is important to identify these patients as early as possible. Most studies on organ failure have been performed in intensive care settings, or on selected groups of patients, where a high prevalence and mortality have been reported. Before patients arrive to the intensive care unit, or the general ward, most of them have passed through the emergency department (ED), where diagnosis and treatment has been initiated. The prevalence and prognosis of acutely ill patients, with organ failure, at arrival have been studied in some selected groups, but methods and results differ. This systematic review aims to identify, summarize, and analyze studies of prevalence and prognosis of new onset organ failure in acutely ill undifferentiated patients, at arrival to hospital. The result of the review will assist physicians working in an ED, when assessing patients’ risk of organ failure and their associated prognosis. Methods The information sources used are electronic databases, PubMed, Cochrane Library, EMBASE, and CINAHL; references in included studies and review articles; and authors’ personal files. One author will perform the title and abstract screening and exclude obviously ineligible studies. By an independent full-text screening, two authors will decide on the eligibility for the remaining studies. Eligible studies will include an unselected group of acutely ill adult patients at arrival to hospital, with one or more organ failures (respiratory, renal, cerebral, circulatory, hepatic, or coagulation failure). Included studies will have assessed the prevalence or prognosis, defined as mortality or ICU transfer, of new onset organ failure. From included studies, bibliographical and study description data, patient characteristics, and data related to prevalence of organ failure and prognosis will be extracted. We will assess risk of bias in included studies using the Quality in Prognosis Studies tool for prognostic studies and the Newcastle-Ottawa Scale for observational studies. We expect heterogeneity and to conduct a qualitative synthesis of the results. If, however, heterogeneity is low, we will conduct a random effects meta-analysis stratified by basic study design. Discussion This review will summarize and analyze studies of prevalence and prognosis of acutely ill patients, with organ failure at arrival to hospital, assist ED physicians assessing the risk of organ failure in unselected patients, and guide recommendations for further research. Systematic review registration PROSPERO CRD42017060871

Abstract Background Firefighters have increased risk of cardiovascular disease and of sudden death from coronary heart disease on duty while suppressing fires. This study investigated the effect of firefighting activities, using appropriate personal protective equipment (PPE), on biomarkers of cardiovascular effects in young conscripts training to become firefighters. Methods Healthy conscripts (n = 43) who participated in a rescue educational course for firefighting were enrolled in the study. The exposure period consisted of a three-day training course where the conscripts participated in various firefighting exercises in a constructed firehouse and flashover container. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The exposure to particulate matter (PM) was assessed at various locations and personal exposure was assessed by portable PM samplers and urinary excretion of 1-hydroxypyrene. Cardiovascular measurements included microvascular function and heart rate variability (HRV). Results The subjects were primarily exposed to PM in bystander positions, whereas self-contained breathing apparatus effectively abolished pulmonary exposure. Firefighting training was associated with elevated urinary excretion of 1-hydroxypyrene (105%, 95% CI: 52; 157%), increased body temperature, decreased microvascular function (−18%, 95% CI: -26; −9%) and altered HRV. There was no difference in cardiovascular measurements for the two types of fires. Conclusion Observations from this fire extinction training show that PM exposure mainly occurs in situations where firefighters removed the self-contained breathing apparatus. Altered cardiovascular disease endpoints after the firefighting exercise period were most likely due to complex effects from PM exposure, physical exhaustion and increased core body temperature.

Abstract Background In order to dispatch ambulances with the correct level of urgency, the dispatch center has to balance the perceived urgency and traffic safety considerations with the available resources. As urgency is not clear in all clinical situations, some high urgency patients may end up with a suboptimal mode of transport. Patients with severe sepsis or septic shock suffer from highly time dependent conditions but they present with a wide range of symptoms, which might be difficult to identify in the dispatch system. The aim of the study is to investigate the modes of prehospital transport among acute admitted patients with sepsis, severe sepsis and septic shock. Methods We included all adult patients (≥15 years) presenting to an acute medical unit at Odense University Hospital with a first-time admission of community-acquired sepsis between September 2010-August 2011. Cases and prehospital ambulance transport were identified by structured manual chart review. In all cases it was registered, whether the ordinary ambulance was assisted by the mobile emergency care unit (MECU), manned by anesthesiologists. Results We included 1,713 patients median age 72 years (IQR 57–81), 793 (46.3%) male, 621 (36.3%) had sepsis, 1,071 (62.5%) severe sepsis, and 21 (1.2%) septic shock. In the group of sepsis patients, 390 (62.8%) arrived without public prehospital transport, 197 (31.7%) were transported by ambulance, and 34 (5.5%) were assisted by MECU. In the group of severe sepsis patients, the same percentage 62.8% arrived without public pre-hospital transport, a lower percentage 28.2% were transported by ambulance, and a larger percentage 9.0% were transported by MECU. Among 21 patients with septic shock, 10 arrived without public pre-hospital transport (47.7%), 7 (33.3%) were transported by ambulance, and 4 (19.0%) by MECU. The 30-day mortality hazard ratio was associated with mode of transport, with the adjusted highest hazard ratio found in the group of MECU transported patients 1.76 (95%Cl 1.16–2.66). Conclusions A substantial proportion of patients with severe sepsis and septic shock arrive to hospital without public prehospital transport or by unspecialized ambulances.

BackgroundVital signs, i.e. respiratory rate, oxygen saturation, pulse, blood pressure and temperature, are regarded as an essential part of monitoring hospitalized patients. Changes in vital signs prior to clinical deterioration are well documented and early detection of preventable outcomes is key to timely intervention. Despite their role in clinical practice, how to best monitor and interpret them is still unclear.ObjectiveTo evaluate the ability of vital sign trends to predict clinical deterioration in patients hospitalized with acute illness.Data sourcesPubMed, Embase, Cochrane Library and CINAHL were searched in December 2017.Study selectionStudies examining intermittently monitored vital sign trends in acutely ill adult patients on hospital wards and in emergency departments. Outcomes representing clinical deterioration were of interest.Data extractionPerformed separately by two authors using a preformed extraction sheet.ResultsOf 7,366 references screened, only two were eligible for inclusion. Both were retrospective cohort studies without controls. One examined the accuracy of different vital sign trend models using discrete-time survival analysis in 269,999 admissions. One included 44,531 medical admissions examining trend in Vitalpac Early Warning Score weighted vital signs. They stated that vital sign trends increased detection of clinical deterioration. Critical appraisal was performed using evaluation tools. The studies had moderate risk of bias, and a low certainty of evidence. Additionally, four studies examining trends in early warning scores, otherwise eligible for inclusion, were evaluated.ConclusionsThis review illustrates a lack of research in intermittently monitored vital sign trends. The included studies, although heterogeneous and imprecise, indicates an added value of trend analysis. This highlights the need for well-controlled trials to thoroughly assess the research question.

INTRODUCTION:Patients in an emergency department are diverse. Some are more seriously ill than others and some even arrive in multi-organ failure. Knowledge of the prevalence of organ failure and its prognosis in unselected patients is important from a diagnostic, hospital planning, and from a quality evaluation point of view, but is not reported systematically. OBJECTIVES:To analyse the prevalence and prognosis of new onset organ failure in unselected acute patients at arrival to hospital. METHODS:A systematic review of studies of prevalence and prognosis of acutely ill patients with organ failure at arrival to hospital. We searched PubMed, Cochrane Library, Embase and Cinahl, and read references in included studies. Two authors decided independently on study eligibility and extracted data. Results were summarised qualitatively. RESULTS:Four studies were included with a total of 678,960 patients. The number of different organ failures reported in the studies ranged from one to six, and the settings were emergency departments and wards. The definitions of organ failure varied between studies. The prevalence of organ failure was 7%, 14%, 14%, and 23%, and in-hospital mortality was 5%, 11% and 15% respectively. The relative risk of in-hospital mortality for patients with organ failure compared to patients without organ failure varied from 2.58 to 8.65. Numbers of organ failures per 1,000 visits varied from 71 to 256. CONCLUSION:The results of this review indicate that clinicians have good reasons to be alert when a patient arrives to the emergency department; as a state of organ failure seems both frequent and highly severe. However, most studies identified were performed in patients after a diagnosis was established, and only very few studies were performed in unselected patients. SYSTEMATIC REVIEW REGISTRATION NUMBER:PROSPERO: CRD42017060871.

This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the “Warburg” and “Crabtree” effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the “Warburg effect” and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the “Warburg effect”, i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as “multiple myeloma”. Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development.

Title: About pedagogues' social strategies in careers of change. Abstract: The work of social educators (pedagogues) in Denmark has undergone significant changes in recent decades. Under changing conditions, thousands of social educators lived through a working life and thereby helped to maintain and develop the profession of social educators. The article is about social educators' individual stories about how they have dealt with these changes. What kind of social strategies have the educators developed in relation to the shifting changes and changing social conditions? Are there signs of developing new kinds of professional standards under difficult conditions?

Piperine has been shown to bind to myosin and shift the distribution of conformational states of myosin molecules from the super-relaxed state to the disordered relaxed state. However, little is known about the implications for muscle force production and potential underlying mechanisms. Muscle contractility experiments were performed using isolated muscles and single fibres from rats and mice. The dose-response effect of piperine on muscle force was assessed at several stimulation frequencies. The potentiation of muscle force was also tested in muscles fatigued by eccentric contractions. Potential mechanisms of force potentiation were assessed by measuring Ca 2+ levels during stimulation in enzymatically dissociated muscle fibres, while myofibrillar Ca 2+ sensitivity was assessed in chemically skinned muscle fibres. Piperine caused a dose-dependent increase in low-frequency force with no effect on high-frequency force in both slow- and fast-twitch muscle, with similar relative increases in twitch force, rate of force development and relaxation rate. The potentiating effect of piperine on low-frequency force was reversible, and piperine partially recovered low-frequency force in fatigued muscle. Piperine had no effect on myoplasmic free [Ca 2+ ] levels in mouse muscle fibres, whereas piperine substantially augmented the force response to submaximal levels of [Ca 2+ ] in rat MyHCII fibres and MyHCI fibres along with a minor increase in maximum Ca 2+ -activated force. Piperine enhances low-frequency force production in both fast- and slow-twitch muscle. The effects are reversible and can counteract muscle fatigue. The primary underlying mechanism appears to be an increase in Ca 2+ sensitivity. KEY POINTS: Piperine is a plant alkaloid derived from black pepper. It is known to bind to skeletal muscle myosin and enhance resting ATP turnover but its effects on contractility are not well known. We showed for the first time a piperine-induced force potentiation that was pronounced during low-frequency electrical stimulation of isolated muscles. The effect of piperine was observed in both slow and fast muscle types, was reversible, and could counteract the force decrements observed after fatiguing muscle contractions. Piperine treatment caused an increase in myofibrillar Ca 2+ sensitivity in chemically skinned muscle fibres, while we observed no effect on intracellular Ca 2+ concentrations during electrical stimulation in enzymatically dissociated muscle fibres., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Currently no single proteomics technology has sufficient analytical power to allow for the detection of an entire proteome of an organelle, cell, or tissue. One approach that can be used to expand proteome coverage is the use of multiple separation technologies especially if there is minimal overlap in the proteins observed by the different methods. Using the inner mitochondrial membrane subproteome as a model proteome, we compared for the first time the ability of three protein separation methods (two-dimensional liquid chromatography using the ProteomeLab PF 2D Protein Fractionation System from Beckman Coulter, one-dimensional reversed phase high performance liquid chromatography, and two-dimensional gel electrophoresis) to determine the relative overlap in protein separation for these technologies. Data from these different methods indicated that a strikingly low number of proteins overlapped with less than 24% of proteins common between any two technologies and only 7% common among all three methods. Utilizing the three technologies allowed the creation of a composite database totaling 348 non-redundant proteins. 82% of these proteins had not been observed previously in proteomics studies of this subproteome, whereas 44% had not been identified in proteomics studies of intact mitochondria. Each protein separation method was found to successfully resolve a unique subset of proteins with the liquid chromatography methods being more suited for the analysis of transmembrane domain proteins and novel protein discovery. We also demonstrated that both the one- and two-dimensional LC allowed for the separation of the alpha-subunit of F1F0 ATP synthase that differed due to a change in pI or hydrophobicity.

The purpose of this study was to investigate the effect of large single doses of radiation on the function of a cochlear implant. A cochlear implant (Nucleus 24 k, Cochlear Ltd., Sydney, Australia) was implanted into a cadaver head and tested for functional changes following irradiation. Within 2 h, the device was given single fractions of 16.3 Gy, 6.2 Gy and 20 Gy with 6 MV photons. The size of the fractions was derived from maximum doses registered in linear accelerator-based radiosurgery of more than 300 patients treated for benign or malignant tumors at the Department of Radiation Therapy of the University Hospital of Freiburg. After each treatment an integrity test was performed testing the impedance and current output of the CI system. The total dose of 42.5 Gy caused no changes with regard to the tested parameters. The risk of implant failure seems to be low for Nucleus 24 k cochlear implants exposed to large single doses of radiation as used in radiosurgery.