Expression of Growth Factors and Growth Factor Receptor in Non-healing and Healing Ischaemic Ulceration

AbstractObjectivesTo characterise the histological and cytokinetic characteristics of purely ischaemic ulcers and the processes that underpin healing following successful revascularisation.DesignProspective observational study.Materials and methodsBiopsies were taken immediately pre- and 6 weeks following successful revascularisation of solely ischaemic ulceration. They were evaluated for morphological differences using H&E staining for the platelet derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), TGFβreceptorIII (TGFβRIII), transforming growth factor beta 1 and 3 (TGFβ1 and TGFβ3) and von Willebrand factor (vWF) expression using immunohistochemistry. Localisation and quantification of these growth factors and receptors was assessed systematically by three independent investigators who were blinded to the timing of biopsy.ResultsPre-operatively, small vessel vasculitis, necrosis and infection with a profuse neutrophil and macrophage infiltrate was observed in all samples. Post-operative biopsies revealed a proliferation of new capillaries in and around the ulcer edge and base. vWF staining confirmed an endothelial layer within these new vessels. Following successful revascularisation there was less infection and inflammation with minimal vasculitis. These newly formed capillaries had increased staining for TGFβ3, PDGFR and TGFβRIII with staining for PDGFR also localised to dermal fibroblasts which were larger and more numerous. Accelerated epithelial cell proliferation was observed with detachment from the underlying dermis.ConclusionsHealing of purely ischaemic ulcers is characterised by vasculogenesis associated with increased presence of the proangiogenic cytokines PDGF and TGFβ3. These findings show promise for the use of growth factor manipulation to aid healing in ischaemic ulcers

Сучасний стан бджільництва в Україні та перспективи розвитку апі-туризму в Рівненській області

The article examines the current state and problems of beekeeping products market development in the Rivne region and Ukraine. The prospects for the development of apiturism in the Rivne region have been assessed. It has been established that Ukraine has sufficient resources for the intensification of the development of tourist and recreational activities, the use of which will contribute to the development of infrastructure and the solution of a number of social and economic issues of the activities of territorial communities, the development of environmental education, the dissemination of knowledge about the history and culture of our people, and the improvement of the population. Apitourism, as a component of rural green tourism of the Rivne region, will contribute to the preservation of jobs in rural areas and is a way to ensure the development of the infrastructure of non-urbanized rural areas with minimal technogenic load. The further development of apitourism will contribute to the growth of a positive image of Ukraine in the international arena as a producer and exporter of high-quality beekeeping products. The territory of the Rivne region is sufficiently equipped with natural objects for the development of beekeeping and apitourism in particular. In the presence of significant areas of the objects of the nature reserve fund, the territory of which is not subject to significant anthropogenic load, it is possible to increase the production of beekeeping products from ecologically clean territories and the implementation of state and regional programs for the development of this type of activity. On the example of one of the personal peasant households, it was established that the apitherapy of the private estate of Malih Sadiv is a young direction of modern medicine in the Rivne region. It consists in the use of healing products produced by bees. They are used to improve the health of the human body to strengthen immunity. The air inside the api-inhalation room is saturated with biologically active substances of propolis, which has antimicrobial properties.У статті розглянуто сучасний стан та проблеми розвитку ринку продукції бджільництва в Рівненській області та Україні. Оцінено перспективи розвитку апітуризму в Рівненській області. Встановлено, що Україна володіє достатніми для інтенсифікації розвитку туристично-рекреаційної діяльності ресурсами, використання яких сприятиме розвитку інфраструктури та вирішенню ряду соціальних та економічних питань діяльності територіальних громад, розвитку екологічної освіти, поширенню знань про історію та культуру нашого народу, оздоровлення населення. Апітуризм як складова сільського зеленого туризму Рівненщини, сприятиме збереженню робочих місць в сільській місцевості та є способом забезпечення розвитку інфраструктури неурбанізованих сільських територій при мінімальному техногенному навантаженні. Подальший розвиток апітуризму сприятиме зростанню позитивного іміджу України на міжнародній арені, як виробника і експортера якісної продукції бджільництва. Територія Рівненської області достатньо забезпечена природними об’єктами для розвитку бджільництва та апітуризму зокрема. За наявності значних площ об’єктів природно-заповідного фонду, територія яких не зазнає значного антропогенного навантаження, можливе збільшення обсягів виробництва продукції бджільництва з екологічно чистих територій та впровадження державних і регіональних програм розвитку даного виду діяльності. На прикладі одного з особистих селянських господарств встановлено, що апітерапія приватної садиби с. Малих Садів є молодим напрямком сучасної медицини Рівненської області. Вона полягає у використанні цілющих продуктів, вироблених бджолами. Їх застосовують для оздоровлення організму людини та зміцнення імунітету. Повітря апі-інгаляційної кімнати всередині насичене біологічно активними речовинами прополісу, який має антимікробні властивості

Rapid sea level rise and ice sheet response to 8,200-year climate event

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 34 (2007): L20603, doi:10.1029/2007GL031318.The largest abrupt climatic reversal of the Holocene interglacial, the cooling event 8.6–8.2 thousand years ago (ka), was probably caused by catastrophic release of glacial Lake Agassiz-Ojibway, which slowed Atlantic meridional overturning circulation (AMOC) and cooled global climate. Geophysical surveys and sediment cores from Chesapeake Bay reveal the pattern of sea level rise during this event. Sea level rose ~14 m between 9.5 to 7.5 ka, a pattern consistent with coral records and the ICE-5G glacio-isostatic adjustment model. There were two distinct periods at ~8.9–8.8 and ~8.2–7.6 ka when Chesapeake marshes were drown as sea level rose rapidly at least ~12 mm yr−1. The latter event occurred after the 8.6–8.2 ka cooling event, coincided with extreme warming and vigorous AMOC centered on 7.9 ka, and may have been due to Antarctic Ice Sheet decay.Cronin, Willard, Thunell, Berke supported by USGS Earth Surface Dynamics Program; Vogt and Pohlman by Office of Naval Research; Halka by MGS

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Rates of abiotic Mn^(II) oxidation by O₂: Influence of various multidentate ligands at high pH

Oxidn. of manganous manganese (Mn^(II)) is an important process driving manganese cycles in natural aquatic systems and leading to the formation of solid-phase Mn^(III,IV) (hydr)oxide products. Previous research has shown that some simple ligands (e.g., phosphate, sulfate, chloride, fluoride) can bind with Mn^(II) to make it unreactive to oxidn. by dissolved oxygen. However, there is little to no understanding of the role played by strong, complex-forming ligands in Mn^(II) oxidn. reactions. The objective of this study was to evaluate the rates of abiotic Mn^(II) oxidn. by O₂ in the presence of several strong complex-forming ligands (pyrophosphate, tripolyphosphate, EDTA, oxalate) in bicarbonate-carbonate buffered lab. solns. of pH 9.42, 9.65 and 10.19. The influence of increasing ligand concns. on obsd. autocatalytic patterns of Mn^(II) oxidn. was investigated, and initial oxidn. rates have been tentatively linked to the initial Mn^(II) speciation in exptl. solns. Obsd. rates of Mn^(II) oxidn. decreased with increasing ligand concn. for all four ligands tested. However, the profiles obsd. and the magnitudes of decrease in initial oxidn. rates were different for the different ligands. Likely explanations for these observations include the denticity of the tested ligands, the relative strength of the ligands to complex Mn^(II) vs. Mn^(III), and the ability of some ligands to act as an electron donor and thereby enhance the back reaction