Morphometric analysis of muscularis proper and myenteric plexus of the normal human oesophagus. Age related changes

Background: Oesophagus is a muscular tube that transports food and liquidsby coordinated contraction of its muscular lining led by stimuli from the nerveplexus. Its muscularis proper layer consists of muscle cells, connective tissue andmyenteric plexus. The aim of our histomorphometric study was to reveal detailedcharacteristics of this layer, cell number, volume, orientation, properties of myentericplexus as well as changes related to aging.Materials and methods: Oesophagus tissue samples from 17 male cadavers weretaken from the cranial and thoracic parts. Samples were divided in 2 groups: younger(ages 21–45) and older (ages 66–78). The tissue was routinely processed,embedded and serially sectioned. Sections were stained with Masson-Goldner andCresyl-violet dyes. Digital images were analysed with the image analysis software.Statistics were performed with SPSS software.Results: The average thickness of the cranial part of the oesophageal wall andmuscularis proper was 2590 μm and 1197 μm, respectively in the younger and2453 μm and 1144 μm in the older group. Overall volume of the muscle tissuewas slightly larger in the thoracic part, and in the younger group comparedto the cranial part and the older group. The average number of the striatedmuscle cells per 100 μm in the cranial part was 771.5 and 749.7 in the youngerand the older group, respectively. Striated cells were significantly lesspresent only in the lower thoracic part of the oesophagus. In the older group,smaller striated muscle cells dominated over the larger ones. In the youngergroup, majority of the striated muscle cells were mid-sized. The thickness ofthe circular layer of muscularis proper was more affected by aging than thelongitudinal one. Ganglion cells number was lower in the older group, butplexus area was unchanged.Conclusions: Aging affects muscularis proper and myenteric plexus of the oesophagus.Major differences can be observed in the striated muscle cells size, volumeof the circular layer and number of the ganglionic cells in the myenteric plexus

ARTreat Project: Three-Dimensional Numerical Simulation of Plaque Formation and Development in the Arteries

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in arteries. It is characterized by dysfunction of endothelium and vasculitis, and accumulation of lipid, cholesterol, and cell elements inside blood vessel wall. In this study, a continuum-based approach for plaque formation and development in 3-D is presented. The blood flow is simulated by the 3-D Navier-Stokes equations, together with the continuity equation while low-density lipoprotein (LDL) transport in lumen of the vessel is coupled with Kedem-Katchalsky equations. The inflammatory process was solved using three additional reaction-diffusion partial differential equations. Transport of labeled LDL was fitted with our experiment on the rabbit animal model. Matching with histological data for LDL localization was achieved. Also, 3-D model of the straight artery with initial mild constriction of 30% plaque for formation and development is presented

Proportions of CD4+ memory T cells are altered in individuals chronically infected with Schistosoma haematobium

Characterisation of protective helminth acquired immunity in humans or experimental models has focused on effector responses with little work conducted on memory responses. Here we show for the first time, that human helminth infection is associated with altered proportions of the CD4+ memory T cells, with an associated alteration of TH1 responses. The reduced CD4+ memory T cell proportions are associated with a significantly lower ratio of schistosome-specific IgE/IgG4 (marker for resistance to infection/re-infection) in uninfected older people. Helminth infection does not affect the CD8+ memory T cell pool. Furthermore, we show for the first time in a helminth infection that the CD4+ memory T cell proportions decline following curative anti-helminthic treatment despite increased CD4+ memory cell replication. Reduced accumulation of the CD4+ memory T cells in schistosome-infected people has implications for the development of natural or vaccine induced schistosome-specific protective immunity as well as for unrelated pathogens

Drosophila Evolution over Space and Time (DEST): A New Population Genomics Resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.We thank four reviewers and the handling editor for helpful comments on previous versions of our manuscript. We are grateful to the members of the DrosEU and DrosRTEC consortia for their long-standing support, collaboration, and for discussion. DrosEU was funded by a Special Topic Networks (STN) grant from the European Society for Evolutionary Biology (ESEB). M.K. was supported by the Austrian Science Foundation (grant no. FWF P32275); J.G. by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2014-CoG-647900) and by the Spanish Ministry of Science and Innovation (BFU-2011-24397); T.F. by the Swiss National Science Foundation (SNSF grants PP00P3_133641, PP00P3_165836, and 31003A_182262) and a Mercator Fellowship from the German Research Foundation (DFG), held as a EvoPAD Visiting Professor at the Institute for Evolution and Biodiversity, University of Münster; AOB by the National Institutes of Health (R35 GM119686); M.K. by Academy of Finland grant 322980; V.L. by Danish Natural Science Research Council (FNU) (grant no. 4002-00113B); FS Deutsche Forschungsgemeinschaft (DFG) (grant no. STA1154/4-1), Project 408908608; J.P. by the Deutsche Forschungsgemeinschaft Projects 274388701 and 347368302; A.U. by FPI fellowship (BES-2012-052999); ET Israel Science Foundation (ISF) (grant no. 1737/17); M.S.V., M.S.R. and M.J. by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200178); A.P., K.E. and M.T. by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200007); and TM NSERC grant RGPIN-2018-05551. The authors acknowledge Research Computing at The University of Virginia for providing computational resources and technical support that have contributed to the results reported within this publication (https://rc.virginia.edu, last accessed September 6, 2021)

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Computational and experimental model of electroporation for human aorta

Purpose: In this study the computational and experimental electroporation model with human aorta tissue is made in order to examine the reduction of smooth muscle cells. Methods. The segments in native state of the aorta are treated by electroporation method through a series of electrical impulses from 50 V/cm to 2500 V/cm. For each patient we analyzed one sample with and one sample without electroporation as a control. In the computational study, electrical field distribution is solved by the Laplace equation. The Pennes Bioheat equation without metabolism and blood perfusion heating is used to solve heat transfer problems. Different conductivity values are used in order to fit the experimental results. Results: Experimental histology has shown us that there are a smaller number of vascular smooth muscle cells (VSMC) nuclei at the tunica media, while the elastic fibre morphology is maintained 24 h after electroporation. In the computational model, heat generation coupled with electrical field is included. The fitting procedure is applied for conductivity values in order to make material properties of the aorta tissue. The fitting procedure gives tissue conductivity of 0.44 [S/m] for applied electrical field of 2500 V/cm. Conclusions: Future studies are necessary for investigation of a new device for in-vivo ablation with electroporation of plaque stenosis. It will open up a new avenue for stenosis treatment without stent implantation

Predictors of potential drug-drug interactions in patients at intensive care unit

© 2019 Sciendo. All rights reserved. Drug-drug interactions (DDIs) with serious adverse consequences for patients at intensive care unit (ICU) occur with the prevalence of 5.3%. The aim of our study was to reveal the risk factors for potential DDIs among the ICU patients. This retrospective cohort analysis took place in the ICU of the Clinical Center Podgorica, Montenegro, between June 1, 2017 and September 30, 2018. The study was conducted as a chart review of the ICU patients (n = 99) who spent ≥ 2 days in the ICU. The main outcome measure was the number of DDIs per patient. Ninety-four percent of patients had at least one potential DDI, while 20% of patients had at least one potential DDI which required a change of therapy. The number of potential DDIs per patient according to the Medscape was 6.6 ± 9.1 and 3.8 ± 4.9 according to the Epocrates. A higher number of drugs (or therapeutic groups) prescribed per patient increased the number of potential DDIs, including those which required a change of therapy. The patients who were prescribed antiarrhythmics, anticoagulants or two antiplatelet drugs experienced more DDIs than patients without these therapeutic groups, while delirium, dementia and drug allergy were protective factors. The main limitation of our study was its uni-centerdness, which allowed for certain degree of bias. Routine screening of the ICU patients with high number of prescribed drugs who receive antiarrhythmics, anticoagulants or double antiplatelet therapy for potential DDIs may prevent a great deal of DDIs with potentially deleterious effects

A novel semi-quantitative method for measuring tissue bleeding

In this study, we describe a new semiquantitative method for measuring the extent of bleeding in pathohistological tissue samples. To test our novel method, we recruited 120 female patients in their first trimester of pregnancy and divided them into three groups of 40. Group I was the control group, in which no dilation was applied. Group II was an experimental group, in which dilation was performed using classical mechanical dilators. Group III was also an experimental group, in which dilation was performed using a hydraulic dilator. Tissue samples were taken from the patients’ cervical canals using a Novak’s probe via energetic single-step curettage prior to any dilation in Group I and after dilation in Groups II and III. After the tissue samples were prepared, light microscopy was used to obtain microphotographs at 100x magnification. The surfaces affected by bleeding were measured in the microphotographs using the Autodesk AutoCAD 2009 program and its “polylines” function. The lines were used to mark the area around the entire sample (marked A) and to create “polyline” areas around each bleeding area on the sample (marked B). The percentage of the total area affected by bleeding was calculated using the formula: N=Bt x 100 / At where N is the percentage (%) of the tissue sample surface affected by bleeding, At (A total) is the sum of the surfaces of all of the tissue samples and Bt (B total) is the sum of all the surfaces affected by bleeding in all of the tissue samples. This novel semi-quantitative method utilizes the Autodesk AutoCAD 2009 program, which is simple to use and widely available, thereby offering a new, objective and precise approach to estimate the extent of bleeding in tissue samples