Long-term feasibility of the new sutureless excimer laser-assisted non-occlusive anastomosis clip in a pig model

Background: High flow bypass surgery can be a last resort procedure for patients suffering from complex neurovascular pathology. Temporary occlusion of a recipient artery in these patients could result in debilitating neurological deficits. We developed a sutureless, mechanical anastomotic connection device, the SELANA clip (Sutureless Excimer Laser-Assisted Non-occlusive Anastomosis clip: SEcl). In the present study, we aim to determine the long-term non-inferiority of the SEcl technique compared with historical data of the conventional ELANA anastomosis technique. Methods: A total of 18 SEcl bypasses were created on the carotid artery in a porcine model in 6 different survival groups. Mean application times, flap retrieval rates, hemostasis, patency, flow, endothelialization, and remodeling were assessed. Results: The mean application time of the SEcl anastomoses was 15.2 ± 9.6 min, which was faster compared with the conventional ELANA anastomoses. The flap retrieval rate of the SEcl anastomoses was 86% (32/37). Direct hemostasis was achieved in 89% (33/37) SEcl anastomoses. Patency in all surviving animals was 94% (17/18). Bypass flow after six months was 156.5 ± 24.7 mL/min. Full endothelialization of the SEcl pins was observed after 3 weeks. Conclusion: The SEcl technique is not inferior to the ELANA technique regarding patency, flap retrieval rate, flow, and endothelialization. On the basis of a significantly shorter application time and superior hemostasis, the SEcl technique could be preferable over the ELANA technique. A pilot study in patients is a logical next step based on our current results

UPDATE trial: investigating the effects of ultra-processed versus minimally processed diets following UK dietary guidance on health outcomes: a protocol for an 8-week community-based cross-over randomised controlled trial in people with overweight or obesity, followed by a 6-month behavioural intervention

INTRODUCTION: Obesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy source. The UK Eatwell Guide (EWG) provides public guidance for a healthy balanced diet but offers no UPF guidance. Whether a healthy diet can largely consist of UPFs is unclear. No study has assessed whether the health impact of adhering to dietary guidelines depends on food processing. Furthermore, our study will assess the impact of a 6-month behavioural support programme aimed at reducing UPF intake in people with overweight/obesity and high UPF intakes. METHODS AND ANALYSIS: UPDATE is a 2×2 cross-over randomised controlled trial with a 6-month behavioural intervention. Fifty-five adults aged ≥18, with overweight/obesity (≥25 to <40 kg/m2), and ≥50% of habitual energy intake from UPFs will receive an 8-week UPF diet and an 8-week minimally processed food (MPF) diet delivered to their home, both following EWG recommendations, in a random order, with a 4-week washout period. All food/drink will be provided. Participants will then receive 6 months of behavioural support to reduce UPF intake. The primary outcome is the difference in weight change between UPF and MPF diets from baseline to week 8. Secondary outcomes include changes in diet, waist circumference, body composition, heart rate, blood pressure, cardiometabolic risk factors, appetite regulation, sleep quality, physical activity levels, physical function/strength, well-being and aspects of behaviour change/eating behaviour at 8 weeks between UPF/MPF diets, and at 6-month follow-up. Quantitative assessment of changes in brain MRI functional resting-state connectivity between UPF/MPF diets, and qualitative analysis of the behavioural intervention for feasibility and acceptability will be undertaken. ETHICS AND DISSEMINATION: Sheffield Research Ethics Committee approved the trial (22/YH/0281). Peer-reviewed journals, conferences, PhD thesis and lay media will report results. TRIAL REGISTRATION NUMBER: NCT05627570

Psychological distress among frontline workers during the COVID-19 pandemic:A mixed-methods study

BACKGROUND: Novel virus outbreaks, such as the COVID-19 pandemic, may increase psychological distress among frontline workers. Psychological distress may lead to reduced performance, reduced employability or even burnout. In the present study, we assessed experienced psychological distress during the COVID-19 pandemic from a self-determination theory perspective. METHODS: This mixed-methods study, with repeated measures, used surveys (quantitative data) combined with audio diaries (qualitative data) to assess work-related COVID-19 experiences, psychological need satisfaction and frustration, and psychological distress over time. Forty-six participants (nurses, junior doctors, and consultants) completed 259 surveys and shared 60 audio diaries. Surveys and audio diaries were analysed separately. RESULTS: Quantitative results indicated that perceived psychological distress during COVID-19 was higher than pre-COVID-19 and fluctuated over time. Need frustration, specifically autonomy and competence, was positively associated with psychological distress, while need satisfaction, especially relatedness, was negatively associated with psychological distress. In the qualitative, thematic analysis, we observed that especially organisational logistics (rostering, work-life balance, and internal communication) frustrated autonomy, and unfamiliarity with COVID-19 frustrated competence. Despite many need frustrating experiences, a strong connection with colleagues and patients were important sources of relatedness support (i.e. need satisfaction) that seemed to mitigate psychological distress. CONCLUSION: The COVID-19 pandemic resulted in an increase of psychological distress among frontline workers. Both need frustration and need satisfaction explained unique variance of psychological distress, but seemed to originate from different sources. Challenging times require healthcare organisations to better support their professionals by tailored formal and informal support. We propose to address both indirect (e.g. organisation) and direct (e.g. colleagues) elements of the clinical and social environment in order to reduce need frustration and enhance need satisfaction

Clinical pharmacology of exogenously administered alkaline phosphatase

Purpose: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). Methods: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg-124 h-1) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. Results: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. Conclusions: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis

Physiological responses during ascent to high altitude and the incidence of acute mountain sickness.

Acute mountain sickness (AMS) occurs when there is failure of acclimatisation to high altitude. The aim of this study was to describe the relationship between physiological variables and the incidence of AMS during ascent to 5300 m. A total of 332 lowland-dwelling volunteers followed an identical ascent profile on staggered treks. Self-reported symptoms of AMS were recorded daily using the Lake Louise score (mild 3-4; moderate-severe ≥5), alongside measurements of physiological variables (heart rate, respiratory rate (RR), peripheral oxygen saturation (SpO2 ) and blood pressure) before and after a standardised Xtreme Everest Step-Test (XEST). The overall occurrence of AMS among participants was 73.5% (23.2% mild, 50.3% moderate-severe). There was no difference in gender, age, previous AMS, weight or body mass index between participants who developed AMS and those who did not. Participants who had not previously ascended >5000 m were more likely to get moderate-to-severe AMS. Participants who suffered moderate-to-severe AMS had a lower resting SpO2 at 3500 m (88.5 vs. 89.6%, p = 0.02), while participants who suffered mild or moderate-to-severe AMS had a lower end-exercise SpO2 at 3500 m (82.2 vs. 83.8%, p = 0.027; 81.5 vs. 83.8%, p 5000 m (OR 2.740, p-value 0.003) predicted the development of moderate-to-severe AMS. The Xtreme Everest Step-Test offers a simple, reproducible field test to help predict AMS, albeit with relatively limited predictive precision

Supplementation of diet with krill oil protects against experimental rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Although the efficacy of standard fish oil has been the subject of research in arthritis, the effect of krill oil in this disease has yet to be investigated. The objective of the present study was to evaluate a standardised preparation of krill oil and fish oil in an animal model for arthritis.</p> <p>Methods</p> <p>Collagen-induced arthritis susceptible DBA/1 mice were provided <it>ad libitum </it>access to a control diet or diets supplemented with either krill oil or fish oil throughout the study. There were 14 mice in each of the 3 treatment groups. The level of EPA + DHA was 0.44 g/100 g in the krill oil diet and 0.47 g/100 g in the fish oil diet. Severity of arthritis was determined using a clinical scoring system. Arthritis joints were analysed by histopathology and graded. Serum samples were obtained at the end of the study and the levels of IL-1α, IL-1β, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17 and TGF-β were determined by a Luminex™ assay system.</p> <p>Results</p> <p>Consumption of krill oil and supplemented diet significantly reduced the arthritis scores and hind paw swelling when compared to a control diet not supplemented with EPA and DHA. However, the arthritis score during the late phase of the study was only significantly reduced after krill oil administration. Furthermore, mice fed the krill oil diet demonstrated lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia, when compared to control. Inclusion of fish oil and krill oil in the diets led to a significant reduction in hyperplasia and total histology score. Krill oil did not modulate the levels of serum cytokines whereas consumption of fish oil increased the levels of IL-1α and IL-13.</p> <p>Conclusions</p> <p>The study suggests that krill oil may be a useful intervention strategy against the clinical and histopathological signs of inflammatory arthritis.</p