Abstract
Objective
falls among older adults are common and can have devastating consequences. A novel task-specific exercise modality, gait adaptability training (GAT), has shown promising preventive ...effects. This systematic review and meta-analysis synthesise the evidence regarding GATs effect on falls and fall-related fractures in community-dwelling older adults.
Methods
electronic databases (PubMed, EMBASE, CINAHL, CENTRAL) were systematically searched from inception to 18 June 2020. Additional sources include searches of trial registrations, manual screening of reference lists and requests to experts. We included randomised controlled trials (RCTs) evaluating the effect of GAT on falls with at least 6-month follow-up among community-dwelling people aged 60+ years. Two reviewers independently screened studies against eligibility criteria, extracted relevant information and appraised studies for bias. Random-effects meta-analytic models were employed to pool effect estimates.
Results
eleven studies with 1,131 participants were included. A meta-analysis in which an outlier study was excluded showed that GAT reduces fall rates by 42% (incidence rate ratio 0.58, 95% confidence interval CI 0.39–0.81, I2 = 0.00%; moderate certainty; seven RCTs). Moreover, proportion with fall-related fractures and proportion of fallers was reduced by 81% (risk ratio RR 0.19, 95% CI 0.06–0.56, I2 = 0.00%; very low certainty; two RCTs) and 43% (RR 0.57, 95% CI 0.4–to 0.8, I2 = 47.08%; low certainty; 11 RCTs), respectively.
Conclusions
our results show that GAT significantly reduces the number of falls and prevents fall-related fractures in older community dwellers. GAT is a promising and feasible exercise modality; however, studies of high quality should be conducted to support a robust conclusion.
Protocol registration
PROSPERO; CRD42020191051.
Abstract High sugar consumption is associated with cardiovascular diseases and diabetes. Current sugar substitutes may cause taste sensations and gastrointestinal symptoms. ENSO 16 is a combination ...of 16 different sugar substitutes and plant fibers and has been designed as a sugar alternative. The impact on plasma glucose metabolism as well as on gastrointestinal tolerance has not been investigated yet. 17 healthy participants were enrolled in this randomized, double-blind trial. Participants received a single oral dose of 30 g glucose or 30 g ENSO 16 and crossed over to the alternate treatment after a 7 day wash out period. The study endpoint was the effect on plasma glucose, insulin, C-peptide concentrations and gastrointestinal disorders. A questionnaire regarding gastrointestinal symptoms was used for individual subjective scoring. The mean baseline adjusted plasma glucose AUC 0–180 min was significantly greater after glucose administration compared to ENSO 16 (n = 15, p = 0.0128, paired t-test). Maximum plasma glucose elevation over baseline was 117 mg*dl −1 and 20 mg*dl −1 after oral glucose or ENSO 16, respectively. Insulin and C-peptide AUC 0−180 min were significantly greater after glucose compared to ENSO 16 intake ( p < 0.01, Wilcoxon rank sum test). The mean maximal concentrations of plasma glucose, insulin and C-peptide after glucose intake were 1.5, 4.6 and 2.7-fold greater after glucose intake compared to ENSO 16 intake, respectively. Adverse reactions were mostly mild and not different between treatments. Conclusion. ENSO 16 has only a small impact on plasma glucose metabolism. This may be of interest in a dietary context and may help to reduce calory intake. Trail registration NCT05457400. First registration: 14/07/2022. https://clinicaltrials.gov/study/NCT05457400 .
Virtual reality (VR)-based simulation is being increasingly used to train medical students in emergency medicine. However, because the usefulness of VR may depend on various factors, the best ...practices for implementing this technology in the medical school curriculum are yet to be determined.
The overall objective of our study was to assess the perceptions of a large cohort of students toward VR-based training and to identify the associations between these attitudes and individual factors, such as gender and age.
The authors implemented a voluntary, VR-based teaching session in the emergency medicine course at the Medical Faculty in Tübingen, Germany. Fourth-year medical students were invited to participate on a voluntary basis. Afterward, we asked the students about their perceptions, collected data on individual factors, and assessed the test scores achieved by them in the VR-based assessment scenarios. We used ordinal regression analysis and linear mixed-effects analysis to detect the impact of individual factors on the questionnaire answers.
A total of 129 students participated in our study (mean age 24.7, SD 2.9 years; n=51, 39.8% male; n=77, 60.2% female). No student had previously used VR for learning, and only 4.7% (n=6) of the students had prior experience with VR. Most of the students agreed that VR can convey complex issues quickly (n=117, 91%), that VR is a useful addition to mannequin-based courses (n=114, 88%) or could even replace them (n=93, 72%), and that VR simulations should also be used for examinations (n=103, 80%). However, female students showed significantly less agreement with these statements. Most students perceived the VR scenario as realistic (n=69, 53%) and intuitive (n=62, 48%), with a relatively lower agreement for the latter among female respondents. We found high agreement among all participants (n=88, 69%) for immersion but strong disagreement (n=69, 54%) for empathy with the virtual patient. Only 3% (n=4) of the students felt confident regarding the medical content. Responses for the linguistic aspects of the scenario were largely mixed; however, most of the students were confident with the English language (not native) scenarios and disagreed that the scenario should be offered in their native language (female students agreed more strongly than male students). Most of the students would not have felt confident with the scenarios in a real-world context (n=69, 53%). Although physical symptoms during VR sessions were reported by 16% (n=21) of the respondents, this did not lead to the termination of the simulation. The regression analysis revealed that the final test scores were not influenced by gender, age, or prior experience in emergency medicine or with virtual reality.
In this study, we observed a strong positive attitude in medical students toward VR-based teaching and assessment. However, this positivity was comparatively lower among female students, potentially indicating that gender differences need to be addressed when VR is implemented in the curriculum. Interestingly, gender, age, or prior experience did not influence the final test scores. Furthermore, confidence regarding the medical content was low, which suggests that the students may need further training in emergency medicine.
Abstract The risk of venous thromboembolism (VTE) increases with age. However, the risk of VTE in the setting of long-term care hospitals is understudied. Our objective was to provide data on the ...prevalence and incidence of VTE in older adults admitted to long-term care hospitals. In this retrospective cohort study, we collected data about chronically ill and multimorbid patients aged 65 years and older from two long-term care hospitals. The primary endpoint of this study was the lifetime prevalence of VTE, and the secondary endpoint was VTE incidence during residency in long-term care hospitals. We analysed data from 1148 patients with a mean age of 84.1 ± 7.9 years, of whom 74.2% were women. The lifetime prevalence of VTE at baseline was 9.6% (95% CI 7.9–11.4). Cumulative incidence of VTE at 1, 2, and 3 years from baseline was estimated at 3.5% (95% CI 2.5–4.7), 4.2% (95% CI 3.1–5.5), and 5.4% (95% CI 4.1–7.0), respectively. Overall, the incidence rate of VTE in our study was 2.82 (95% CI 2.18–3.66) per 100 person-years. The study indicated a considerably high lifetime prevalence and incidence of VTE during residence in long-term care hospital settings, requiring further evaluation in larger prospective studies.
Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for ...antibody detection tools has proven particularly acute in the COVID-19 era. We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. We find that the array is readily able to distinguish uninfected from convalescent COVID-19 subjects, and provides quantitative information about total Ig, as well as IgG- and IgM-specific responses.
•Antibody detection is key to addressing COVID-19 and other upper respiratory diseases.•We describe an arrayed sensor for COVID-19, other coronaviruses, and influenza.•The sensor can quantify antibody responses in convalescent COVID-19 patients.•Quantitative results are consistent with gold-standard ELISA assays.
Bitumen ageing – Impact of reactive oxygen species Hofko, Bernhard; Maschauer, Daniel; Steiner, Daniel ...
Case Studies in Construction Materials,
December 2020, 2020-12-00, 2020-12-01, Letnik:
13
Journal Article
Recenzirano
Odprti dostop
•Lab ageing methods for asphalt consider molecular oxygen (O2) as an oxidant. Its reactivity is low at ambient temperatures.•Atmospheric chemistry shows that other reactive oxygen species (ROS) with ...high reactivity interact with asphalt in the field.•Ageing experiments with different gaseous atmospheres were conducted.•The results show that a combination of O3 and NOx induce significant oxidative ageing at ambient temperatures and pressures.
Bitumen from crude oil refinery is an important construction material as the binding component for asphalt mixes in road construction. Due to its organic composition, it is susceptible to oxidation when being exposed to reactive oxygen species (ROS). Oxidation is the main factor driving long-term ageing of the bitumen, which leads to an increase of brittleness and stiffness at lower temperatures and thus, makes road constructions more prone to cracking. Ageing is therefore a limiting factor for the service life of road infrastructure.
In the presented study, the impact of different ROS on oxidative ageing of bitumen is studied. Asphalt mix specimens are aged in a specially designed device (VAPro) by leading different gases through the specimen, i.e. pressurized air, O2, O3 enriched O2 and dried air enriched with O3 and NOx. The flow rate is 1.0 L/min and the conditioning time is set to 7 days for air and 3 days for all other gases, respectively. Temperature (+60 °C) and pressure are set to simulate realistic field conditions. Bitumen is extracted and recovered from the specimens after ageing and assessed rheologically by DSR analysis. It was found that neither ambient atmosphere, nor pure O2 or O3 enriched O2 by themselves induce relevant oxidative ageing. By combining air, O3 and NOx, high oxidative ageing levels comparable to RTFOT + PAV can be achieved. Thus, realistic, yet efficient laboratory ageing methods for bitumen and asphalt mixtures need to take all ROS, especially NOx, into account.
Abstract
A long systemic half-life is key for therapeutic proteins. To that end we have generated serum albumin-binding designed ankyrin repeat domains. These domains bind serum albumin of different ...species with nanomolar affinities, and have significantly improved pharmacokinetic properties both in mouse and cynomolgus monkey compared to non-serum albumin-binding DARPin® domains. In addition, they exhibit high thermal stability and long storage stability, which is an essential feature for their use in drug development. Covalently linking a serum albumin-binding DARPin® domain to domains with other target specificities results in improvements of multiple orders of magnitude in exposure and terminal half-life, both in mouse and cynomolgus monkey. Pharmacokinetic assessment of such constructs revealed terminal half-life values ranging from 27 h to 80 h in mouse, and from 2.6 days to 20 days in cynomolgus monkey. Extrapolation by allometric scaling on these findings suggests terminal half-life values of 5-50 days in human, indicating that pharmacokinetic properties in the range of monoclonal antibodies can be achieved with DARPin® drug candidates. Such serum albumin-binding DARPin® domains are thus valuable tools for the generation of multi-functional drugs with an extended in vivo half-life.
The EGF receptor (EGFR) has been implicated in the development and progression of many tumors. Although monoclonal antibodies directed against EGFR have been approved for the treatment of cancer in ...combination with chemotherapy, there are limitations in their clinical efficacy, necessitating the search for robust targeting molecules that can be equipped with new effector functions or show a new mechanism of action. Designed ankyrin repeat proteins (DARPins) may provide the targeting component for such novel reagents. Previously, four DARPins were selected against EGFR with (sub)nanomolar affinity. As any targeting module should preferably be able to inhibit EGFR-mediated signaling, their effect on A431 cells overexpressing EGFR was examined: three of them were shown to inhibit proliferation by inducing G1 arrest, as seen for the Food and Drug Administration-approved antibody cetuximab. To understand this inhibitory mechanism, we mapped the epitopes of the DARPins using yeast surface display. The epitopes for the biologically active DARPins overlapped with the EGF-binding site, whereas the fourth DARPin bound to a different domain, explaining the lack of a biological effect. To optimize the biological activity of the DARPins, we combined two DARPins binding to different epitopes with a flexible linker or with a leucine zipper, leading to a homodimer. The latter DARPin was able to reduce surface EGFR by inhibiting receptor recycling, leading to a dramatic decrease in cell viability. These results indicate that multispecific EGFR-specific DARPins are superior to cetuximab and may form the basis of new opportunities in tumor targeting and tumor therapy.
Background: The EGF receptor (EGFR) is an important therapeutic target.
Results: Bispecific anti-EGFR designed ankyrin repeat proteins (DARPins), alternative targeting molecules efficiently produced in bacteria, were shown to inhibit A431 cell proliferation and receptor recycling.
Conclusion: One bispecific construct containing four DARPins showed a biological activity superior to that of the registered antibody cetuximab.
Significance: Bispecific DARPins may form building blocks for tomorrow's cancer therapeutics.
Anthracnose (
Elsinöe ampelina
) is a major fungal disease in humid regions, causing damage to grapevine berries and decreasing fruit quality. Studies concerning enzymatic and biochemical changes ...caused by infection and tissue colonization of
E. ampelina
in berries are scarce, but they are fundamental to gaining insights about the defense response to the pathogen. Thus, this study aims to quantify biochemical and enzymatic alterations in different varieties of grapevine berries attacked by
E. ampelina
, and their association with anthracnose symptoms. Must quality, carbohydrate production, and enzymatic activity were assessed in berries with and without anthracnose symptoms, from five varieties that presented different degrees of anthracnose symptoms. Berries with anthracnose symptoms showed higher must acidity, while berries without anthracnose symptoms produced more proteins and higher polyphenol oxidase activity. The varieties manifesting the highest anthracnose symptoms showed higher sugar and hydrogen peroxide concentrations on berry skins. On the other hand, the varieties with the lowest anthracnose symptoms showed the highest catalase, polyphenol oxidase, and phenylalanine ammonia-lyase activities on berry skins. In conclusion, the varieties presented different severities of anthracnose on berries with higher anthracnose severities correlated with high hydrogen peroxide production and carbohydrate concentration on grape skins.
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