Blood flow in microvascular networks

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Simulation of blood presents a very complex haemodynamics problem especially in relation to the understanding of atherogenesis. In many simulations, blood has been treated as a single-phase homogeneous fluid, a classical approach that does not account for the presence of red blood cells (RBCs). Although this approach provides satisfactory tools to describe certain aspects of blood flow in large arteries, it fails to give an adequate representation of the flow field in the vessels of smaller diameter where the size of the RBC becomes significant relative to vessel diameter. So, this article is concerned with the study of non-Newtonian blood flow in microvascular networks with the intention of developing a new cell depletion layer model to represent the behaviour of RBCs through bifurcating networks. The model is tested in a microvascular network constructed possessing realistic bifurcation features, with controlled dimensions and angles. The RBC depletion model treats blood as two continuum layers, with a central, non-Newtonian core region of concentrated red cell suspension that is surrounded by a layer of plasma (Newtonian fluid) adjacent to the vessel wall. In the central core region, blood is described by Quemada's non-Newtonian rheological model. Geometry differences are shown to significantly affect flow rates, haematocrit distributions and the corresponding cell depletion layers

Effect of Foot Refelexology on Preeclampsia

Purpose: This study was conducted to investigate the effect of foot reflexology on mean arterial blood pressure, Serum Cortisol level, proteinuria and quality of life in pregnant women suffering from mild preeclampsia. Subjects and Methods: Sixty mild preeclamptic pregnant women were selected randomly from Out Patient Clinic of Obstetrics Department in Minia University Hospital in Minia to participate in this study. Their ages were between 20-36 years old. Their body mass index less than 35 kg/m2. They were divided randomly into two equal groups (A & B); Group A (control group): It comprised thirty pregnant women with mild preeclampsia who were treated by antihypertensive drugs only while group B (study group): It comprised thirty pregnant women with mild preeclampsia who were treated by antihypertensive drugs and foot reflexology sessions (25 minutes, 2 sessions weekly for 8 weeks). Assessment: Mean arterial blood pressure (MABP), Serum Cortisol level and proteinuria were assessed before and after treatment for all patients in both groups (A&B), as well as quality of life was evaluated through World Health Organization quality of Life Questionnaire (WHOQOL). Results: revealed that, between groups; pretreatment, there was insignificant difference between both groups A & B in MABP, serum cortisol level, proteinuria and WHOQOL questionnaire scores. While post treatment, there was significant difference between both groups A &B in MABP, serum cortisol level, proteinuria and WHOQOL questionnaire scores [in favor of group B (more decrease in MABP, serum cortisol level and proteinuria; and more increase in WHOQOL questionnaire scores)]. Conclusion: Foot reflexology is an effective modality in decreasing MABP, serum cortisol level and proteinuria, as well as enhancing the quality of life of mild preeclamptic pregnant women

Orally active antischistosomal early leads identified from the open access malaria box.

BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development

Duodenal enteroglucagonoma revealed by differential comparison of serum and tissue glucagon reactivity with Siemens' Double Glucagon Antibody and DakoCytomation's Polyclonal Rabbit Anti-Human Glucagon: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case report demonstrates that the differential immunohistochemical reactivities of Siemens' <it>Double Antibody Glucagon </it>compared to DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon </it>allow for pathologic distinction of enteral versus pancreatic glucagonoma.</p> <p>Case presentation</p> <p>A 64-year-old Caucasian man was diagnosed with a duodenal enteroglucagonoma following presentation with obstructive jaundice. He had a low serum glucagon level using Siemens' <it>Double Antibody Glucagon</it>, a clinical syndrome consistent with glucagon hypersecretion. A periampullary mass biopsy proved to be a neuroendocrine tumor, with positive immunohistochemical reactivity to DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon</it>.</p> <p>Conclusions</p> <p>Differential comparison of the immunohistochemical reactivities of Siemens' <it>Double Antibody Glucagon </it>and DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon </it>discerns enteroglucagon from pancreatic glucagon.</p

Correction: Metal complexes as a promising source for new antibiotics

Correction for ‘Metal complexes as a promising source for new antibiotics’ by Angelo Frei et al., Chem. Sci., 2020, 11, 2627–2639

Primary liposarcoma of the ascending colon: a rare case of mixed type presenting as hemoperitoneum combined with other type of retroperitoneal liposarcoma

<p>Abstract</p> <p>Background</p> <p>Liposarcoma occurs most commonly in the extremities and retroperitoneum, however, it has been rarely observed in the colon.</p> <p>Case Presentation</p> <p>A case is reported a 41-year-old man with liposarcoma of ascending colon which was presented as hemoperitoneum and combined with a different histological type of retroperitoneal liposarcoma. He visited hospital with right lower abdominal pain and palpable mass. Laboratory data including tumor markers were within normal limits, and computed tomography revealed a 15 × 10 cm sized enhancing soft mass. Right hemicolectomy was performed, and after that, a further large retroperitoneal mass was revealed and this was also radically excised. Mixed-type colon liposarcoma and well differentiated type of retroperitoneal liposarcoma were diagnosed in pathologic report. The patient has remained free of disease for 24 months.</p> <p>Conclusions</p> <p>No standardized guidelines have been established for its treatment because too small a number of cases have been reported, but surgical resection was considered the treatment of choice.</p

Comparison of Microscopy and Alamar Blue Reduction in a Larval Based Assay for Schistosome Drug Screening

Only one drug, praziquantel, is widely available for treating schistosomiasis, a disease affecting an estimated 200 million people. Because of increasing usage there is concern about development of praziquantel drug resistance and a perceived need to develop new schistosomicides. Possible sources of these are large collections of compounds held by pharmaceutical companies and academic institutions. Anti-schistosome activity can be detected in vitro by visually assessing damage to cultured adult schistosome worms, but these are large and are recovered from mice which somewhat limits screening throughput. By contrast, schistosomula can be produced in vitro and used for screening in microwell plates, thus allowing medium throughput screening. High throughput screening (HTS) would require automated readout of schistosomulicidal action rather than manual microscopy. Here we report on the use of Alamar blue (AB), a fluorescent indicator of cell viability which can be measured rapidly and automatically. The AB assay was readily able to detect compounds causing death or severe damage to the larvae but was less reliable than microscopy for more subtle morphological changes including those induced by some known schistosome drugs. It is concluded that an automated HTS would benefit from integrated use of both AB and automatic image-based morphology assays

Saccharomyces cerevisiae-based system for studying clustered DNA damages

DNA-damaging agents can induce clustered lesions or multiply damaged sites (MDSs) on the same or opposing DNA strands. In the latter, attempts to repair MDS can generate closely opposed single-strand break intermediates that may convert non-lethal or mutagenic base damage into double-strand breaks (DSBs). We constructed a diploid S. cerevisiae yeast strain with a chromosomal context targeted by integrative DNA fragments carrying different damages to determine whether closely opposed base damages are converted to DSBs following the outcomes of the homologous recombination repair pathway. As a model of MDS, we studied clustered uracil DNA damages with a known location and a defined distance separating the lesions. The system we describe might well be extended to assessing the repair of MDSs with different compositions, and to most of the complex DNA lesions induced by physical and chemical agents

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats

Anxiety and Depression in Adults with Autism Spectrum Disorder: A Systematic Review and Meta-analysis

Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations