Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages.

New therapeutics are a priority for preventing and eliminating Plasmodium vivax (Pv) malaria because of its easy transmissibility and dormant stages in the liver. Relapses due to the dormant liver stages are the major contributor to reoccurring Pv. Therefore, therapies that reduce the establishment of dormant parasites and blood-stage infection are important for controlling this geographically widespread parasite. Here, we isolated 12 human monoclonal antibodies (humAbs) from the plasma of a Pv-exposed individual that recognized Pv apical membrane antigen 1 (PvAMA1). PvAMA1 is important for both sporozoite invasion of hepatocytes and merozoite invasion of reticulocytes. We identified one humAb, 826827, that blocked invasion of human erythrocytes using a transgenic P. falciparum line expressing PvAMA1 (IC 50 = 3 µg/mL) and all Pv clinical isolates in vitro . This humAb also inhibited sporozoite invasion of a human hepatocyte cell line and primary human hepatocytes (IC 50 of 0.3 - 3.7 µg/mL). The crystal structure of recombinant PvAMA1 with the antigen-binding fragment of 826827 at 2.4 Å resolution shows that the humAb partially occupies the highly conserved hydrophobic groove in PvAMA1 that binds its known receptor, RON2. HumAb 826827 binds to PvAMA1 with higher affinity than RON2, accounting for its potency. To our knowledge, this is the first reported humAb specific to PvAMA1, and the PvAMA1 residues it binds to are highly conserved across different isolates, explaining its strain-transcendent properties.

An Identical Twin Study on Human Achilles Tendon Adaptation: Regular Recreational Exercise at Comparatively Low Intensities Can Increase Tendon Stiffness.

Achilles tendon adaptation is a key aspect of exercise performance and injury risk prevention. However, much debate exists about the adaptation of the Achilles tendon in response to exercise activities. Most published research is currently limited to elite athletes and selected exercise activities. Also, existing studies on tendon adaptation do not control for genetic variation. Our explorative cross-sectional study investigated the effects of regular recreational exercise activities on Achilles tendon mechanical properties in 40 identical twin pairs. Using a handheld oscillation device to determine Achilles tendon mechanical properties, we found that the Achilles tendon appears to adapt to regular recreational exercise at comparatively low intensities by increasing its stiffness. Active twins showed a 28% greater Achilles tendon stiffness than their inactive twin (p < 0.05). Further, our research extends existing ideas on sport-specific adaptation by showing that tendon stiffness seemed to respond more to exercise activities that included an aerial phase such as running and jumping. Interestingly, the comparison of twin pairs revealed a high variation of Achilles tendon stiffness (305.4-889.8 N/m), and tendon adaptation was only revealed when we controlled for genetic variance. Those results offer new insights into the impact of genetic variation on individual Achilles tendon stiffness, which should be addressed more closely in future studies.

Phantom material testing indicates that the mechanical properties, geometrical dimensions, and tensional state of tendons affect oscillation-based measurements.

OBJECTIVE: There is an increasing interest in the application of oscillation-based measurement techniques to evaluate the mechanical stiffness of healthy and diseased tendons. These techniques measure the stiffness of a tendon indirectly by registering the oscillation response of a tendon to an external mechanical impulse. Although these measurement techniques seem to be comparatively easy and time-saving, their applicability is implicitly limited by their indirect measurement principle. APPROACH: In this study, we aim to find evidence that the oscillation response of a tendon to an external mechanical impulse is not only affected by the stiffness of a tendon but also by the tendons' cross-sectional area (CSA), length, and tension. Therefore, we reviewed the current literature on oscillation-based techniques that measure in vivo tendon properties. Further, a phantom material was used to mimic the nature of tendons and to test the impact of four factors on oscillation-based measurements. MAIN RESULTS: Our results indicate that the mechanical properties, geometrical dimensions (length and CSA), and tensional state affect oscillation-based measures. Surprisingly, most studies on tendon behavior often exclusively associate their oscillation-based measurements with the mechanical stiffness of a tendon. SIGNIFICANCE: While this narrow perspective bears the risk of misinterpretation or false implications, a broader understanding of oscillation-based measurements has the potential to shed new light on the interaction of muscles and tendons in vivo.

Role of Helicobacter pylori in conjunctival mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: Conjunctiva-associated lymphoid tissue is the conjunctival equivalent to mucosa-associated lymphoid tissue (MALT). Mucosa-associated lymphoid tissue lymphoma has been shown to be associated with Helicobacter pylori. In this study, the prevalence and possible role of H. pylori infection in conjunctival MALT lymphoma were evaluated. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirteen cases of conjunctival MALT lymphoma were investigated. Five samples of conjunctival lymphoid hyperplasia and 20 biopsies of normal conjunctiva served as controls. METHODS: The specimens were investigated for the presence of H. pylori with immunohistochemistry (IHC) and nested polymerase chain reaction (PCR) techniques. For each case of conjunctival MALT lymphoma, information regarding gender, age at presentation, conjunctival localization, and information of generalized MALT lymphoma were collected. MAIN OUTCOME MEASURES: Detection of H. pylori and patient characteristics. RESULTS: The 13 conjunctival MALT lymphomas originated from 8 women and 5 men with an average age of 62 years (range, 25-87). Only 1 patient had evidence of systemic MALT lymphoma. H. pylori could not be identified in any of the conjunctival MALT lymphomas, in conjunctival lymphoid hyperplasia, or in normal conjunctival biopsies using IHC and PCR techniques. CONCLUSIONS: An association between H. pylori and localized conjunctival MALT lymphoma could not be verified. Antigens other than H. pylori may take part in the development of conjunctival MALT lymphoma.

Dengue in the State of Rio de Janeiro, Brazil, 1986-1998.

This paper presents epidemiological, laboratory, and clinical data on 12 years of dengue virus activity in the State of Rio de Janeiro from the time the disease was first confirmed virologically in April 1986 through April 1998. DEN-1 and DEN-2 viruses are the serotypes circulating in the state and were responsible for the epidemics reported during the last 12 years. The results published here show both the impact of dengue virus infections on the population and laboratory advances that have improved dengue diagnosis.

Successfully developing biotech drugs in Europe--IBC biomedical conference. 19-20 November 1998, London, UK.

This conference gave an overview of developing business strategies to capitalize on opportunities in the biotech industry. Although the importance of the biotech sector is clear, it is faced with many and varied business and regulatory problems. Financing, timescales, manufacturing, drug development and drug registration, as well as analysis of the current biotech market were discussed.

Ventricular dysrhythmias in ischemic heart disease.

Ischemic heart disease remains a leading killer in industrialized nations. A significant cause of the morbidity and mortality in patients with ischemic heart disease is ventricular dysrhythmic events. There is a continued search for safe and effective treatment for patients with ventricular dysrhythmias. In this article, the author discusses current understanding of the mechanisms for dysrhythmias in the setting of acute ischemia and in the chronically infarcted ventricle. Therapy for patients with ventricular tachycardia and ventricular fibrillation is reviewed. Nurses caring for cardiac patients are continually involved in rhythm monitoring and dysrhythmia interpretation. The nurse is often the first responder present when a fatal dysrhythmia occurs. In addition, nurses can be involved at all levels of care, from prevention of heart disease to assisting the patient cope with a sudden cardiac death episode.

[Evaluation of speech therapy and rehabilitation exercises in mouth-breathers]. / Bilan logopédique et exercices de rééducation chez le respirateur buccal.

Mouth breathing induces a low rest posturing of the tongue and tongue thrusting in many cases. This disturbs the development of the oral functions. The first stage of the reeducation is nose breathing's rehabilitation in order to "liberate" the tongue. Nasal breathing cannot be taught exteriorly . It's a result of the physical well-being. It's important to observe the mouth breathers and understand their needs. The second stage of the reeducation concerns the tongue moving tonicity and suppleness. Every exercise relies on the proprioceptive control that makes the child aware of each motion of the tongue. The next stages will be the recovering of the different functions as the rest tongue posture, swallowing, chewing. The use of phonation (lingual alveolar speech sounds) will facilitate the automatism of the new functions, because the children feel the elevation of the tongue.