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Within the XFLEX HYDRO project, the possibility of increasing the flexibility of hydro power plants to support the Electric Power System (EPS) is investigated. The flexibility of the pumped-storage power plant Frades 2, as the target, should increase by extending the operating range for each unit and by using the hydraulic short circuit (HSC) operation mode. Transient investigations of the additional plant conditions are performed to ensure the safety of the plant. With a 1D model of the entire hydro power plant including both pump-turbines, valves, surge tanks, and the water-bearing components, extensive calculations are carried out to verify the safety of the existing plant for extended operation conditions. In particular, the study focuses on the synchronous and asynchronous emergency shutdowns of the plant in the new operating conditions as well as other operation-related power plant transients regarding the HSC mode. With the results presented in this paper, the flexibility of the plant Frades 2 can be increased. Delayed emergency shutdowns are identified as particularly critical during the study and should always be given additional consideration in transient investigations.

This systematic review and meta-analysis is an update to prior research to evaluate the effects of yoga for managing prehypertension and hypertension. Medline/PubMed, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from their inception until April 5th 2024. Randomized-controlled trials (RCTs) that compared yoga to any control intervention in participants with diagnosed prehypertension (120-139/80-89 mmHg) or hypertension (≥140/ ≥ 90mmHg) were included. Mean differences (MD) and 95% confidence intervals (CI) were calculated. Risk of Bias was assessed using the Cochrane tool. 30 RCTs with 2283 participants were included. Very low quality of evidence was found for positive effects of yoga on systolic blood pressure (SBP, 26 RCTs, n = 2007; MD = -7.95 mmHg, 95% CI = -10.24 to -5.66, p < 0.01), diastolic blood pressure (DBP, 23 RCTs, n = 1836; MD = -4.93 mmHg, 95% CI = -6.25 to -3.60, p < 0.01) and heart rate (HR, 14 RCTs, n = 1118; MD = -4.43 mmHg, 95% CI = -7.36 to -1.50, p < 0.01) compared to waitlist control. Compared to active control, very low quality of evidence was found for positive effects yoga on SBP (5 RCTs, n = 306; MD = -4.16 mmHg, 95%CI = -10.76 to 2.44, p = 0.22), DBP (5 RCTs, n = 306; MD = -1.88 mmHg, 95%CI = -3.41 to -0.36, p = 0.02) and HR (2 RCT, n = 128; MD = -5.16 mmHg, 95% CI = -8.39 to -1.92, p < 0.01). Overall, the studies showed a high degree of heterogeneity. The effects found were robust against selection, detection and attrition bias. Yoga may be an option for lowering blood pressure in people with prehypertension to hypertension. More and larger high-quality studies are needed to substantiate our findings.

A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

Background Sarcoidosis is a systemic inflammatory disease that is characterized by non-caseating epithelioid-cell granulomas upon histology. However, similar histological findings may also be seen with certain infections. Thus, differentiation from infection is pivotal to ensure appropriate treatment. Here, we present a case of a disseminated infection with Mycobacterium genavense owing to an interleukin 12 receptor subunit beta 1 (IL-12Rβ1) associated immunodeficiency in a previously healthy female who was initially misdiagnosed with sarcoidosis. M. genavense is a nontuberculous mycobacterium which can cause lymphadenopathy, gastrointestinal and bone marrow infiltration in immunocompromised patients. With this case report we aim to highlight that an infection with M. genavense on the ground of a genetic defect of mycobacterial immune control may represent a rare differential diagnosis of sarcoidosis. Case presentation A 31-year-old female was referred to our hospital with progressive lymphadenopathy, hepatosplenomegaly, pancytopenia and systemic inflammation. She had previously been evaluated for generalized lymphadenopathy in another hospital. At that time, lymph node biopsies had revealed sarcoid-like lesions and a systemic corticosteroid treatment was initiated based on a putative diagnosis of sarcoidosis. When her condition worsened, she was transferred to our university clinic, where the diagnosis of disseminated M. genavense infection owing to an inborn interferonopathy was made. Her family history revealed that her brother had also suffered from IL-12Rβ1 deficiency and had died from a systemic infection with M. genavense at the age of 21. The patient received antimycobacterial treatment combined with subcutaneous type I interferon, which eventually led to a gradual improvement over the next months. Conclusions Differentiating between sarcoidosis and sarcoid-like lesions secondary to infections may be challenging, especially when pathogens are difficult to detect or not expected in an apparently immunocompetent patient. Patients with IL-12Rβ1 - associated immunodeficiency may be asymptomatic until adulthood, and disseminated M. genavense infection on the grounds of an IL-12Rβ1 - associated immunodeficiency may represent a rare differential diagnosis of sarcoidosis.

IntroductionThe effect of different anaesthetics on the incidence of postoperative delirium is still not entirely clear. Therefore, we will evaluate the effect of desflurane versus sevoflurane versus propofol for the maintenance of anaesthesia on the incidence of postoperative delirium in older adults undergoing moderate- to high-risk major non-cardiac surgery. We will further compare the incidences of delayed neurocognitive recovery, long-term postoperative neurocognitive disorder, postoperative nausea and vomiting between the groups.Methods and analysisIn this multicentre, prospective, observer-blinded, randomised controlled clinical trial, we will include 1332 patients ≥65 years of age undergoing moderate- to high-risk major non-cardiac surgery lasting at least 2 hours. Patients will be randomly 1:1:1 assigned to receive desflurane, sevoflurane or propofol for anaesthesia. Maintenance of anaesthesia will be performed in a goal-directed manner using processed electroencephalography with an intraoperative goal of bispectral index 40–60. Our primary outcome will be the incidence of postoperative delirium within the first five postoperative days. Postoperative delirium will be assessed using the three-dimensional-confusion assessment method (3D-CAM) or CAM-intensive care unit (ICU) in the morning and evening of the first five postoperative days by blinded study personnel. The primary outcome, the incidence of postoperative delirium, will be compared between the three study groups using a χ2 test. Furthermore, a logistic regression model for the incidence of postoperative delirium will be performed, accounting for randomised groups as well as other predefined confounding factors.Ethics and disseminationThis clinical trial has been approved by the ethics committee and the Federal Office for Safety in Healthcare as the competent authority for clinical trials in Austria. The results of this trial will be published in a peer-reviewed journal.Trial registration numberClinicalTrials.gov NCT05990790.

Arterial hypertension is a major public health issue. Non-pharmacological approaches like Mindfulness-Based Stress Reduction (MBSR) might be a promising addition to conventional therapy. This systematic review and meta-analysis aim to evaluate the effects of MBSR on systolic (SBP) and diastolic blood pressure (DBP) among individuals with prehypertension or hypertension. We searched Medline/PubMed, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) from their inception until August 1st 2021. RCTs were included that compared MBSR to any control intervention in participants with diagnosed prehypertension (120–139/80–89 mmHg) or hypertension (≥140/≥90 mmHg). Mean differences (MD) and 95% confidence intervals (CI) were calculated. Risk of Bias was assessed using the Cochrane tool. Seven RCTs with 429 participants were included. Very low quality of evidence was found for positive effects of MBSR on SBP (MD = −11.26 mmHg, 95%CI = −20.24 to −2.29, p = 0.01) but no evidence for effects on DBP levels (MD = −3.62 mmHg, 95%CI = −8.52 to 1.29, p = 0.15) compared to waitlist control. Compared to active control, very low quality of evidence was found for positive effects on DBP (MD = −5.51 mmHg, 95%CI = −10.93 to −0.09, p = 0.05) but no effects on SBP levels (MD = −4.33 mmHg, 95%CI = −12.04 to 3.38, p = 0.27). Overall, the studies showed a high degree of heterogeneity. The effects found were robust against selection, detection, and attrition bias. Only one RCT reported safety data. MBSR may be an option for lowering blood pressure in people with prehypertension to hypertension. More and larger high-quality studies are needed to substantiate our findings.

Nowadays, hydro power plants are demanded to operate in a highly flexible manner to support the electric power system, providing flexibility services. Such plant operation often results in operational transients in the hydro power plant. Extensive investigations must be performed to ensure safe operation of the plant. Transient model tests provide an opportunity to analyze these power plant condition changes. This paper demonstrates the successful reproduction of a pump-turbine transition from pump to turbine mode in an existing hydro power plant on a closed-loop test rig. The plant boundary conditions are transferred to the model size through similarity laws. The time scale is adapted considering the Strouhal similarity. To set the boundary conditions at the model machine, the transient process in the test rig is simulated, and the rotational speed of a service pump is adjusted using an optimizer. Based on these results, the transient model measurement is carried out.

Sarcoidosis is a systemic inflammatory disease that is characterized by non-caseating epithelioid-cell granulomas upon histology. However, similar histological findings may also be seen with certain infections. Thus, differentiation from infection is pivotal to ensure appropriate treatment. Here, we present a case of a disseminated infection with Mycobacterium genavense owing to an interleukin 12 receptor subunit beta 1 (IL-12R[beta]1) associated immunodeficiency in a previously healthy female who was initially misdiagnosed with sarcoidosis. M. genavense is a nontuberculous mycobacterium which can cause lymphadenopathy, gastrointestinal and bone marrow infiltration in immunocompromised patients. With this case report we aim to highlight that an infection with M. genavense on the ground of a genetic defect of mycobacterial immune control may represent a rare differential diagnosis of sarcoidosis. Differentiating between sarcoidosis and sarcoid-like lesions secondary to infections may be challenging, especially when pathogens are difficult to detect or not expected in an apparently immunocompetent patient. Patients with IL-12R[beta]1-associated immunodeficiency may be asymptomatic until adulthood, and disseminated M. genavense infection on the grounds of an IL-12R[beta]1-associated immunodeficiency may represent a rare differential diagnosis of sarcoidosis.

Metabolic syndrome often accompanies obesity and hyperglycemia and is associated with a breakdown in the integrity of the intestinal barrier and increased risk of systemic infection. Thaiss et al. found that mice with systemic infection of a Salmonella analog, Citrobacter rodentium , also exhibited hyperglycemia. Deletion of the glucose transporter GLUT2 altered sensitivity to chemically induced epithelial permeability and protected mice from pathogen invasion. The authors also found a correlation in humans between glycated hemoglobin (an indicator of hyperglycemia) and serum levels of pathogen recognition receptor ligands. Science , this issue p. 1376 High blood sugar levels cause epithelial reprogramming, compromising gut barrier integrity and increasing susceptibility to pathogens. Obesity, diabetes, and related manifestations are associated with an enhanced, but poorly understood, risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia, intestinal epithelial–specific GLUT2 deletion, or inhibition of glucose metabolism restores barrier function and bacterial containment. In humans, systemic influx of intestinal microbiome products correlates with individualized glycemic control, indicated by glycated hemoglobin levels. Together, our results mechanistically link hyperglycemia and intestinal barrier function with systemic infectious and inflammatory consequences of obesity and diabetes.

Background: Brown adipose tissue (BAT) is abundant in small mammals and in newborns and helps them to survive cold temperatures. In adults, it had long been considered to be absent or at least of no relevance. Recent investigations, however, have fuelled interest in adult BAT. Objective: We aimed at (1) summarizing structural and physiological characteristics of BAT versus white adipose tissue (WAT); (2) discussing the development of the two adipose tissue types; (3) reviewing the data available from human studies on BAT, and (4) discussing the impact of aging. Methods: We summarize recent descriptions of BAT and WAT based on the original literature and reviews in the field, with emphasis on human BAT. Results: WAT and BAT have essentially antagonistic functions: WAT stores excess energy as triglycerides and BAT is specialized in the dissipation of energy through the production of heat. Considerable amounts of BAT are present in a substantial proportion of adult humans and relatively high quantities of BAT are associated with lower body weight. With increasing age, BAT decreases and body weight increases. Conclusions: Although the available cross-sectional data do not allow definite conclusions to be drawn concerning a causal relationship between loss of BAT and increasing body weight with advancing age or obesity-related metabolic disorders of older age, stimulation of BAT appears to be an attractive novel candidate target for the treatment of age-related obesity.