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Objective: Investigation of the feasibility and preliminary effect of a short-term intensive preoperative exercise programme for elderly patients scheduled for elective abdominal oncological surgery. Design: Single-blind randomized controlled pilot study. Setting: Ordinary hospital in the Netherlands. Subjects: Forty-two elderly patients (>60 years). Interventions: Patients were randomly assigned to receive a short-term intensive therapeutic exercise programme to improve muscle strength, aerobic capacity, and functional activities, given in the outpatient department (intervention group; n =22), or home-based exercise advice (control group; n=20). Main measures: Parameters of feasibility, preoperative functional capacity and postoperative course. Results: The intensive training programme was feasible, with a high compliance and no adverse events. Respiratory muscle endurance increased in the preoperative period from 259 ± 273 to 404 ± 349 J in the intervention group and differed significantly from that in the control group (350 ± 299 to 305 ± 323 J; P<0.01). Timed-Up-and-Go, chair rise time, LASA Physical Activity Questionnaire, Physical Work Capacity and Quality of Life (EORTC-C30) did not reveal significant differences between the two groups. There was no significant difference in postoperative complications and length of hospital stay between the two groups. Conclusion: The intensive therapeutic exercise programme was feasible and improved the respiratory function of patients due to undergo elective abdominal surgery compared with home-based exercise advice.

A critical step in profitable post-harvest potato storage management is to cure tubers at appropriate temperatures long enough for rapid wound-healing to prevent disease and defect development, but not too long to jeopardize storage quality. A two-year storage study was conducted in macro-storage totes at the University of Wisconsin Hancock storage research facility to evaluate the effects of higher wound-healing temperatures (15.6 °C, 18.3 °C) imposed for different durations, and compare them to the U.S. potato industry’s standard practice (12.8 °C), on weight loss and frying quality of multiple processing potato varieties during long-term storage. It was found that in the experimental setting of this study, warmer wound-healing temperatures resulted in (1) less weight loss, particularly during the early storage season across varieties; (2) ameliorated senescent sweetening of the Snowden variety; (3) improved fry quality of the Russet Burbank variety; (4) and no apparent disease spread during long-term storage if tubers were harvested healthy out of fields. Overall, no significant difference was found between 15.6 °C and 18.3 °C regarding their treatment effects. Our conclusion is that compared to the current standard practice, higher wound-healing temperatures may have the potential benefits of improving potato storage quality while reducing the economic penalty associated with weight loss for specific varieties, but tubers should be healthy at harvest in order to gain the benefits. Further research is needed to test if those benefits of higher wound-healing temperatures hold true in large-scale commercial storage facilities.

BackgroundAlthough promising results have been reported for Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, this treatment is not yet widely implemented in clinical practice. During the implementation of a new technology, lessons are learned and an institutional learning-curve often has to be completed. The primary aim of our prospective cohort study was to characterize our learning-curve based on our clinical outcomes. Secondary aims included identifying our lessons learned during implementation of MR-HIFU on a technical, patient selection, patient counseling, medical specialists and organizational level.ResultsOur first seventy patients showed significant symptom reduction and improvement of quality of life at 3, 6 and 12 months after MR-HIFU treatment compared to baseline. After the first 25 cases, a clear plateau phase was reached in terms of failed treatments. The median non-perfused volume percentage of these first 25 treatments was 44.6% (range: 0–99.7), compared to a median of 74.7% (range: 0–120.6) for the subsequent treatments.ConclusionsOur findings describe the learning-curve during the implementation of MR-HIFU and include straightforward suggestions to shorten learning-curves for future users. Moreover, the lessons we learned on technique, patient selection, patient counseling, medical specialists and organization, together with the provided supplements, may be of benefit to other institutions aiming to implement MR-HIFU treatment of uterine fibroids.Trial registration ISRCTN14634593. Registered January 12, 2021—Retrospectively registered, https://www.isrctn.com/ISRCTN14634593.

Abstract Background: Understanding the relationship between dose, lung exposure, and drug efficacy continues to be a challenging aspect of inhaled drug development. An experimental inhalation platform was developed using mometasone furoate to link rodent lung exposure to its in vivo pharmacodynamic (PD) effects. Methods: We assessed the effect of mometasone delivered directly to the lung in two different rodent PD models of lung inflammation. The data obtained were used to develop and evaluate a mathematical model to estimate drug dissolution, transport, distribution, and efficacy, following inhaled delivery in rodents and humans. Results: Mometasone directly delivered to the lung, in both LPS and Alternaria alternata rat models, resulted in dose dependent inhibition of BALf cellular inflammation. The parameters for our mathematical model were calibrated to describe the observed lung and systemic exposure profiles of mometasone in humans and in animal models. We found that physicochemical properties, such as lung fluid solubility and lipophilicity, strongly influenced compound distribution and lung retention. Conclusions: Presently, we report on a novel and sophisticated mathematical model leading to improvements in a current inhaled drug development practices by providing a quantitative understanding of the relationship between PD effects and drug concentration in lungs.

For almost a quarter of a century 1 , the origin of γ-ray bursts— brief, energetic bursts of high-energy photons—has remained unknown. The detection of a counterpart at another wavelength has long been thought to be a key to understanding the nature of these bursts (see, for example, ref. 2), but intensive searches have not revealed such a counterpart. The distribution and properties of the bursts 3 are explained naturally if they lie at cosmological distances (a few Gpc) 4 , but there is a countervailing view that they are relatively local objects 5 , perhaps distributed in a very large halo around our Galaxy. Here we report the detection of a transient and fading optical source in the error box associated with the burst GRB970228, less than 21 hours after the burst 6,7 . The optical transient appears to be associated with a faint galaxy 7,8 , suggesting that the burst occurred in that galaxy and thus that γ-ray bursts in general lie at cosmological distance.

Filgotinib is a preferential Janus kinase 1 (JAK-1) inhibitor registered for the treatment of ulcerative colitis (UC). Real-world effectiveness of filgotinib, especially for difficult-to-treat (DTT, failure of ≥ 2 prior advanced therapies) patients, has been scarcely reported. This study aimed to assess the effectiveness and safety of filgotinib for UC patients in routine care. The Dutch ICC registry enrolled UC patients initiating filgotinib and prospectively evaluated outcomes up to 52 weeks. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤ 2 without steroid use) at week 52. Secondary outcomes included clinical remission (SCCAI ≤ 2), biochemical remission (C-reactive protein serum concentration < 5 mg/L and/or faecal calprotectin level < 250 μg/g), treatment persistence and safety. A total of 96 UC patients were included. At 52 weeks, 39.5% (34/76) of patients with disease activity at baseline were in CSFR. Out of the patients that met the criteria for DTT disease (n = 68; 71%), 36.4% achieved CSFR. Treatment persistence at 52 weeks was 71.4% (CI 56.5-90.3) and 53.4% (CI 42.6-67.0) for non-DTT and DTT patients, respectively. The main reasons for discontinuation of filgotinib were primary non-response (n = 21, 54%) or secondary loss of response (n = 8, 23%). No severe infections were documented. Most reported adverse events included headache (n = 5), nausea (n = 3) and hypercholesterolemia (n = 3). Filgotinib is an effective and well-tolerated treatment option for UC, including DTT disease. No new safety signals were found.

This study tested whether inattentive–impulsive–overactive (I/O) and oppositional-defiant (O/D) behaviors were associated with peer problems and whether these associations were moderated by callous–unemotional (CU) traits in clinically referred children with disruptive behaviors. Parents of 135 children aged 6–12 years ( M  = 9.09, SD  = 1.62) completed measures to assess their child’s I/O, O/D, and CU behaviors, and peer functioning problems. Findings showed that I/O and O/D behaviors were associated with greater peer problems, and CU traits significantly moderated the I/O behaviors and peer problems association. Children with relatively more CU traits and I/O behaviors showed greater peer problems. However, those with more CU traits and fewer I/O behaviors showed less peer problems. I/O behaviors and CU traits have an important influence on peer functioning that varies according to the severities of each.

Abstract Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the development of multi-organ neoplasms. Among the manifestations of VHL are pancreatic neuroendocrine neoplasms (panNENs). In order to detect these lesions in a timely manner, patients are enrolled in a surveillance program, in accordance with the several existing VHL guidelines. However, these guidelines remain unclear about the role of biomarkers in diagnosing panNENs, despite the benefits a biomarker may offer regarding early detection of new lesions, thereby possibly limiting radiation exposure, and improving quality of life. The aim is to determine which biomarkers might be available in VHL patients and to assess their clinical relevance in diagnosing panNENs in VHL patients. We searched the databases of PubMed/Medline, Embase, and Web of Science to identify relevant articles. Seven studies assessing the diagnostic or prognostic value of biomarkers were included. The results from these studies were conflicting. Since no evident association between VHL-related panNENs and biomarkers was established in studies with larger study populations, currently biomarkers do not play a significant role in early detection or follow-up for panNENs in VHL patients. The absence of evidence underscores the need for specific research to address this unmet need.

There have been significant increases in stream flow in many rivers of the Upper Midwestern United States since 1980. Increased summer flows may negatively impact ecological processes, including aquatic organisms’ life cycles. The smooth softshell (Apalone mutica) and wood turtle (Glyptemys insculpta) are threatened by alteration of stream flow regime and other changes to river ecosystems in the Upper Midwest. We hypothesized that prolonged duration of high summer flows would reduce time available for nesting. We assessed hydrologic change using the Indicators of Hydrologic Alteration program and stream gauge data, characterized physical properties of sandbars, surveyed turtle nesting sites and assessed historical channel change using aerial photos in GIS on five Upper Midwest rivers. A river stage-sandbar area relationship was developed to determine the effect of prolonged summer flow duration on turtle nesting opportunity for the 1940–2009 time period. Suitable water levels have declined since 1980 in the agricultural watersheds of southern Minnesota likely delaying hatching and reducing survival, particularly for aquatic turtles such as A. mutica. In contrast to the agricultural watersheds, there was no significant change in the northern forested rivers’ stream flow and sandbar availability during the nesting season. Management to reduce summer stream flow in agricultural watersheds and protection of known nest sites could benefit threatened aquatic turtle populations.

A critical step in profitable post-harvest potato storage management is to cure tubers at appropriate temperatures long enough for rapid wound-healing to prevent disease and defect development, but not too long to jeopardize storage quality. A two-year storage study was conducted in macro-storage totes at the University of Wisconsin Hancock storage research facility to evaluate the effects of higher wound-healing temperatures (15.6 [degrees]C, 18.3 [degrees]C) imposed for different durations, and compare them to the U.S. potato industry's standard practice (12.8 [degrees]C), on weight loss and frying quality of multiple processing potato varieties during long-term storage. It was found that in the experimental setting of this study, warmer wound-healing temperatures resulted in (1) less weight loss, particularly during the early storage season across varieties; (2) ameliorated senescent sweetening of the Snowden variety; (3) improved fry quality of the Russet Burbank variety; (4) and no apparent disease spread during long-term storage if tubers were harvested healthy out of fields. Overall, no significant difference was found between 15.6 [degrees]C and 18.3 [degrees]C regarding their treatment effects. Our conclusion is that compared to the current standard practice, higher wound-healing temperatures may have the potential benefits of improving potato storage quality while reducing the economic penalty associated with weight loss for specific varieties, but tubers should be healthy at harvest in order to gain the benefits. Further research is needed to test if those benefits of higher wound-healing temperatures hold true in large-scale commercial storage facilities.