Dose-dependent von Willebrand Factor inhibition by aptamer BB-031 correlates with thrombolysis in a microfluidic model of arterial occlusion

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational thromboelastometry was used to assess changes in hemostasis. BB-031 induced maximal inhibition at the highest dose (3384 nM) in VWF:Ac, and demonstrated dose-dependent responses in all other assays. BB-031, but not vehicle, induced recanalization in the microfluidic model. Maximal lytic efficacy in the microfluidic model was seen at 1692 nM and not 3384 nM BB-031 when assessed by surface area. Minor changes in ROTEM parameters were seen at 3384 nM BB-031. Targeted VWF inhibition by BB-031 results in clinically measurable impairment of VWF function, and specifically VWF-GPIb function as measured by VWF:Ac. BB-031 also induced thrombolysis as measured in a microfluidic model of occlusion and reperfusion. Moderate correlation between inhibition and lysis was observed. Additional studies are required to further examine off-target effects of BB-031 at high doses, however, these are expected to be above the range of clinical targeted dosing

Optimal switching of a nanomagnet assisted by microwaves

We develop an efficient and general method for optimizing the microwave field that achieves magnetization switching with a smaller static field. This method is based on optimal control and renders an exact solution for the 3D microwave field that triggers the switching of a nanomagnet with a given anisotropy and in an oblique static field. Applying this technique to the particular case of uniaxial anisotropy, we show that the optimal microwave field, that achieves switching with minimal absorbed energy, is modulated both in frequency and in magnitude. Its role is to drive the magnetization from the metastable equilibrium position towards the saddle point and then damping induces the relaxation to the stable equilibrium position. For the pumping to be efficient, the microwave field frequency must match at the early stage of the switching process the proper precession frequency of the magnetization, which depends on the magnitude and direction of the static field. We investigate the effect of the static field (in amplitude and direction) and of damping on the characteristics of the microwave field. We have computed the switching curves in the presence of the optimal microwave field. The results are in qualitative agreement with micro-SQUID experiments on isolated nanoclusters. The strong dependence of the microwave field and that of the switching curve on the damping parameter may be useful in probing damping in various nanoclusters.Comment: 9 pages, 8 figure

Determinants of compliance with the World Health Organisation recommendations for pregnant women in an urban health centre in The Gambia

In 2001 the World Health Organization drew up recommendations for pregnant women in order to reduce maternal mortality: the first visit to the antenatal clinic to be in the first trimester, at least four visits in total and delivery with a trained birth attendant. This study reports the extent to which pregnant women attending a health centre in The Gambia complied with the recommendations. A cohort of 1611 consecutive pregnant women was recruited. Only 384 (23.9%) women first attended in the first trimester and 568 (41.6%) attended at least four times. Only 15.8% of the women complied with all recommendations. Following multivariate analysis the educational level of the partner was the sole factor associated with both recommendations regarding attendance. This level of compliance reflects widespread ignorance of the value of early antenatal care and frequent visits. Public health programmes require a basic level of education to be effective. (Afr J Reprod Health 2020; 24[3]: 24-32). Keywords: Maternal health, antenatal, first trimester, education, male partner, The Gambia   En 2001, l'Organisation mondiale de la santé a formulé des recommandations pour les femmes enceintes afin de réduire la mortalité maternelle: la première visite à la clinique prénatale doit avoir lieu au premier trimestre, au moins quatre visites au total et l'accouchement avec une accoucheuse qualifiée. Cette étude rapporte dans quelle mesure les femmes enceintes fréquentant un centre de santé en Gambie se sont conformées aux recommandations. Une cohorte de 1611 femmes enceintes consécutives a été recrutée. Seules 384 (23,9%) femmes y ont participé pour la première fois au cours du premier trimestre et 568 (41,6%) y ont assisté au moins quatre fois. Seulement 15,8% des femmes se sont conformées à toutes les recommandations. Suite à une analyse multivariée, le niveau d'éducation du partenaire était le seul facteur associé aux deux recommandations concernant la fréquentation. Ce niveau de conformité reflète l'ignorance généralisée de la valeur des soins prénatals précoces et des visites fréquentes. Les programmes de santé publique nécessitent un niveau d'éducation de base pour être efficaces. Mots-clés: Santé maternelle, prénatale, premier trimestre, éducation, partenaire masculin, Gambi

Fish hosts of the freshwater mussel Unio foucauldianus Pallary, 1936

The life cycle of Unio foucauldianus Pallary, 1936, a critically endangered freshwater mussel species (Bivalvia: Unionida), includes a parasitic phase using fish as hosts. Therefore, to develop more efficient conservation strategies it is essential to know which are the suitable fish hosts of U. foucauldianus. In this study, two approaches were used to assess the fish hosts of U. foucauldianus: the determination of infestation rates of fishes under natural conditions through monthly sampling (from January to June) in the Laabid River (Oum Rbia basin) and the N'Fis River (Tensift basin), and artificial infestation in laboratory trials using fish species from both rivers. The natural infestation of fish was detected from February to June, with a peak in May. Fully metamorphosed juveniles were only detected in native fish species, i.e. Luciobarbus ksibi (Boulenger, 1905), Carasobarbus fritschii (Gunther, 1874), Luciobarbus zayanensis Doadrio, Casal-lopez & Yahyaoui, 2016, Labeobarbus maroccanus (Gunther, 1874), and Luciobarbus magniatlantis (Pellegrin, 1919). The two non-native fish species used do not function as effective hosts. Given the increasing human pressure on native fish species in the Mediterranean biodiversity hotspot, including the increased number of non-native fish introductions, urgent conservation measures are discussed for this and other freshwater mussel species.The authors would like to express their thanks to the High Commission for Water and Forests (HCEFLCD) for granting permission to use electrofishing in the Moroccan basins. This study was conducted within the scope of the project ‘Biodiversity and conservation of the critically endangered freshwater mussels in Morocco: ecogeographic, genetic and physiological information’, funded by the Mohamed Bin Zayed Species Conservation Fund (ref. 15256799), and the project ‘Breeding the most endangered bivalve on Earth: argaritifera marocana’, funded by the IUCN SOS (Save our Species) fund (ref. 2015B‐015)

Outcomes of low-grade appendiceal mucinous neoplasms with remote acellular mucinous peritoneal deposits

Occasionally, low-grade appendiceal mucinous neoplasms (LAMN) present with mucinous peritoneal deposits (MPD) localized to periappendiceal tissue or diffused throughout the peritoneum. This study was aimed at evaluating the relevance of mucin cellularity for predicting outcomes of LAMN with remote MPD. The records of patients with LAMN and remote MPD who underwent initial assessment at a comprehensive cancer center from 1990 to 2015 were reviewed, and diagnostic procedures, treatments, and outcomes were analyzed. Of 48 patients included in the analysis, 19 had cellular MPD (CMPD) and 29 had acellular MPD. Of 33 patients who underwent cytoreductive surgery, 30 had a complete cytoreduction; the 3 patients with an incomplete cytoreduction had CMPD. In the follow-up period (median, 4 years), 6 patients died of the disease, all of whom had CMPD. Of 11 patients who had progression of disease, 10 had CMPD. Cellularity of remote MPD is an important determinant of disease outcome in LAMN. Approaches such as active surveillance may have a role in selected patients with LAMN and AMPD

Non-linear analysis of two-layer timber beams considering interlayer slip and uplift

A new mathematical model and its finite element formulation for the non-linear analysis of mechanical behaviour of a two-layer timber planar beam is presented. A modified principle of virtual work is employed in formulating the finite element method. The basic unknowns are strains. The following assumptions are adopted in the mathematical model: materials are taken to be non-linear and can differ from layer to layer; interacting shear and normal contact tractions between layers are derived from the non-linear shear contact traction-slip and the non-linear normal contact traction-uplift characteristics of the connectors; the geometrically linear and materially non-linear Bernoulli's beam theory is assumed for each layer. The formulation is found to be accurate, reliable and computationally effective. The suitability of the theory is validated by the comparison of the numerical solution and the experimental results of full-scale laboratory tests on a simply supported beam. An excellent agreement between measured and calculated results is observed for all load levels. The further objective of the paper is the analysis of the effect of different normal contact traction-uplift constitutive relationships on the kinematic and static quantities in a statically determined and undetermined structure. While the shear contact traction-slip constitutive relationship dictates the deformability of the composite beam and has a substantial influence on most of the static and kinematic quantities of the composite beam, a variable normal contact traction-uplift constitutive relationship is in most cases negligible

Balancing Clinical Objectives with Patient Centered Care

This poster is a reflection focuses on the challenges of balancing the medical needs of a patient and their preferences in an interdisciplinary health care setting. Students from UNE\u27s Physician Assistant, Osteopathic Medicine, Social Work, Dental Medicine, and Nursing programs collaborated with Allopathic Medicine and Podiatric Medicine students from Rosalind Franklin University Medical School as a virtual health care team to care for a patient with long-covid

Serum Cytokines Profiles and Some Salivary Parameters in Chronic Periodontitis Patients in Mosul - Iraq

The aim of study is to measure serum IL-1 ?, IL-6, IL-8, IFN-? and TNF-? levels, and some of salivary parameters like sIgA, total protein and peroxidase specific activity in patients with chronic periodontitis in Mosul and compared them with control group. The study population consisted of 91 patients suffering from chronic periodontitis, aging between ?18-73 years old and 18 control samples collected from healthy individuals ranged between 23-35 years old. Blood and saliva samples were collected from patients and control groups to measure serum IL-1?, IL-6, IL-8, IFN-? and TNF-? ,and salivary sIgA , total protein levels and peroxidase specific activity . In the present study most of patients were showed localized chronic periodontitis, ranging from severe 57% to moderate infection 43%.Salivary sIgA level showed significant increase in chronic periodontitis comparing with control group.Patients group showed significance correlation between serum TNF-? with serum IL-1?, IL-6 and IFN-? levels. Also serum IL-1? level showed significant correlation with salivary sIgA and total protein levels. Furthermore negative correlations were detected between salivary sIgA and serum IL-8, as well asbetween salivary total protein and peroxides specific activity. According to periodontal pocket depth, serum IL-1?, IFN-?, salivary sIgA levels and salivary peroxidase specific activity showed significance increase in patients with 7mm pocket depth. In the present study, most of patients showed localized chronic periodontitis. Salivary sIgA level showed significant increase in chronic periodontitis comparing with control group. Serum IL-1?, IFN-?, salivary sIgA levels and salivary peroxidase specific activitywere linked with 7mm periodontal pocket depth