Clinical, anthropometric, radiological and molecular characteristics of Egyptian achondroplasia patients

Background: Achondroplasia is the most common form of non lethal skeletal dysplasia. It is a fully penetrant autosomal dominant disorder and the majority of cases are sporadic resulting from de novo mutations associated with advanced paternal age. The phenotype of achondroplasia is related to disturbance in endochondral bone formation due to mutations in the fi broblast growth factor receptor-3 (FGFR3) gene. Aim of the Work: Evaluation of the cardinal phenotypic features in achondroplasia, the body physique using anthropometric measurements, the characteristic radiological signs in the patients as a main tool for diagnosis and detection of the most common mutations in achondroplasia patients in the studied sample.Subjects and Methods: From 42 cases referred to us as achondroplasia, we selected 20 cases where clinical manifestations were consistent with achondroplasia. Cases were subjected to full clinical examination, detailed anthropometric measurements, whole body skeletal survey and molecular studies of the most common mutations of the FGFR3 gene using PCR amplifi cation technique. Results: Nineteen cases were sporadic (95%) and one case had an affected father (5%). A paternal age above 35 years at the time of child’s birth was present in 7 cases (35%). Paternal exposure to occupational heat was noted in 6 cases (30%) and parental exposure to chemicals in 3 cases (15%). All cases showed typical clinical and radiological manifestations of achondroplasia. Anthropometricmeasurements quantitatively confi rmed the body physique in thestudied cases. G380R common mutations of the FGFR3 gene were detected in 15/18 cases (83%) with the G to A transition at nucleotide 1138 in 14 cases (77%). Agenesis of corpus callosum, not previously reported in association with achondroplasia, was present in the only case with the G-C transversio nmutation at nucleotide 1138 (5%).Conclusions: Awareness of the cardinal features of achondroplasia, properanthropometric measurements and detailed skeletal survey are the key foraccurate diagnosis, genetic counseling and avoidance of over diagnosis. The majority of studied Egyptian achondroplasia patients have the same common mutation that has been most often defi ned in patients with achondroplasia from other countries.Keywords: Achondroplasia, fi broblast growth factor receptor3,skeletal dysplasia, paternal heat exposure

Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy

Histological evidence for a supraspinous ligament in sauropod dinosaurs

Supraspinous ossified rods have been reported in the sacra of some derived sauropod dinosaurs. Although different hypotheses have been proposed to explain the origin ofthis structure, histological evidence has never been provided to support or reject any of them. In order to establish its origin, we analyse and characterize the microstructure of thesupraspinous rod of two sauropod dinosaurs from the Upper Cretaceous of Argentina. The supraspinous ossified rod is almost entirely formed by dense Haversian bone. Remains ofprimary bone consist entirely of an avascular tissue composed of two types of fibre-like structures, which are coarse and longitudinally (parallel to the main axis of the element) oriented. These structures are differentiated on the basis of their optical properties under polarized light. Very thin fibrous strands are also observed in some regions. These small fibres are all oriented parallel to one another but perpendicular to the element main axis. Histological features of the primary bone tissue indicate that the sacral supraspinous rod corresponds to an ossified supraspinous ligament. The formation of this structure appears to have been a non-pathological metaplastic ossification, possibly induced by the continuous tensile forces applied to the element.Fil: Cerda, Ignacio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Casal, Gabriel. Universidad Nacional de la Patagonia; ArgentinaFil: Martínez, Rubén Darío. Universidad Nacional de la Patagonia ; ArgentinaFil: Ibiricu, Lucio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentin

Immune-phenotyping and transcriptomic profiling of peripheral blood mononuclear cells from patients with breast cancer: identification of a 3 gene signature which predicts relapse of triple negative breast cancer

Background: Interactions between the immune system and tumors are highly reciprocal in nature, leading to speculation that tumor recurrence or therapeutic resistance could be influenced or predicted by immune events that manifest locally, but can be detected systemically. Methods: Multi-parameter flow cytometry was used to examine the percentage and phenotype of natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), monocyte subsets and regulatory T (Treg) cells in the peripheral blood of of 85 patients with breast cancer (50 of whom were assessed before and after one cycle of anthracycline-based chemotherapy), and 23 controls. Transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) in 23 patients were generated using a NanoString gene profiling platform. Results: An increased percentage of immunosuppressive cells such as granulocytic MDSCs, intermediate CD14++CD16+ monocytes and CD127negCD25highFoxP3+ Treg cells was observed in patients with breast cancer, especially patients with stage 3 and 4 disease, regardless of ER status. Following neoadjuvant chemotherapy, B cell numbers decreased significantly, whereas monocyte numbers increased. Although chemotherapy had no effect on the percentage of Treg, MDSC and NK cells, the expression of inhibitory receptors CD85j, LIAR and NKG2A and activating receptors NKp30 and NKp44 on NK cells increased, concomitant with a decreased expression of NKp46 and DNAM-1 activating receptors. Transcriptomic profiling revealed a distinct group of 3 patients in the triple negative breast cancer (TNBC) cohort who expressed high levels of mRNA encoding genes predominantly involved in inflammation. The analysis of a large transcriptomic dataset derived from the tumors of patients with TNBC revealed that the expression of CD163, CXCR4, THBS1 predicted relapse-free survival. Conclusions: The peripheral blood immunome of patients with breast cancer is influenced by the presence and stage of cancer, but not by molecular subtypes. Furthermore, immune profiling coupled with transcriptomic analyses of peripheral blood cells may identify patients with TNBC that are at risk of relapse after chemotherapy

Simultaneous voltammetric determination of antihypertensive drugs nifedipine and atenolol utilizing MgO nanoplatelet modified screen-printed electrodes in pharmaceuticals and human fluids

© 2017 The Authors. Nifedipine and atenolol dugs are conjugated in several anti-hypertensive pharmaceutical formulations. Herein, a reproducible and sensitive voltammetric procedure has been developed for the simultaneous analysis of nifedipine and atenolol for the first time using MgO − nanoplatelets modified screen-printed electrodes (MgO − SPEs) via differential pulse voltammetry (DPV). Two very well-resolved and reproducible signals/oxidation peaks with a voltammetric separation of 0.35 V were obtained in Britton–Robinson (BR) buffer (pH 9). The MgO NPLs are found to exhibit a high electrocatalytic activity and improved voltammetric response compared to unmodified (bare) SPEs. Under optimum pH conditions (pH 9), the DPV curves exhibit linear responses to nifedipine and atenolol over the concentration ranges of 0.2–104.41 μM and 6.66–909.09 μM with detection limits of 0.032 μM and 1.76 μM, respectively. The applicability of the MgO-SPEs is successfully utilized for simultaneous determination of nifedipine and atenolol in pharmaceutical tablets and human urine samples with good accuracy and precision, these results agreeing with independent high-performance liquid chromatography (HPLC)

Bleeding from ruptured hepatic metastases as a cause of syncope in an octogenarian: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acute hemoperitoneum as a result of hemorrhage from liver metastases is an uncommon but serious condition. The use of appropriate imaging is important in the diagnosis and can have a profound impact on subsequent management. This case is important because the presentation was of recurrent syncopal episodes with an unusual underlying cause. This case highlights the need to consider this diagnosis in the differential in patients presenting with collapse in the acute setting.</p> <p>Case presentation</p> <p>We present the case of an 85-year-old Caucasian man who was admitted following a collapse episode and was found to be persistently hypotensive despite aggressive resuscitation. An acute intra-peritoneal bleed originating from hepatic metastases from an unknown primary was identified promptly with computed tomography imaging and was subsequently managed conservatively.</p> <p>Conclusions</p> <p>This case aims to convey key teaching points: (A) the need to consider intra-abdominal hemorrhage in the differential diagnosis when assessing patients with collapse; and (B) the use of appropriate imaging such as computed tomography can facilitate a prompt diagnosis and appropriate management steps can then be taken accordingly.</p

Simulation of Single and Twin Impinging Jets in Cross-flow of VTOL Aircrafts (Review)

When operating near the ground beneath a Vertical/Short Take-Off and Landing (VSTOL) aircraft a complex turbulent 3D flow is generated. This flow field can be represented by the configuration of twin impinging jets in a cross-flow. Studying these jets is a significant parameter for the design of VTOL aircraft. This flowfield during very low speed or hover flight operations is very complex and time dependent. An important number of experimental researches and simulations have been carried out to be able to understand much better these flows related with powered lift vehicles. Computational Fluid Dynamics (CFD) approach will be used in this paper work for simulation purposes of a single and twin impinging jet through and without crossflow

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

Vaccination with Plasmodium knowlesi AMA1 Formulated in the Novel Adjuvant Co-Vaccine HT™ Protects against Blood-Stage Challenge in Rhesus Macaques

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC50 values correlated with estimated in vivo growth rates