Phase 1 clinical trial of apical membrane antigen 1: an asexual blood-stage vaccine for Plasmodium falciparum malaria

Apical membrane antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. A phase 1 trial was conducted with 30 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of recombinant proteins based on sequences from the FVO and 3D7 clones of Plasmodium falciparum. The proteins were expressed in Pichia pastoris and adsorbed on Alhydrogel. Ten volunteers in each of three dose groups (5 mug, 20 mug, and 80 mug) were vaccinated in an open-label study at 0, 28, and 180 days. The vaccine was well tolerated, with pain at the injection site being the most commonly observed reaction. Anti-AMA1 immunoglobulin G (IgG) was detected by enzyme-linked immunosorbent assay (ELISA) in 15/28 (54%) volunteers after the second immunization and in 23/25 (92%) after the third immunization, with equal reactivity to both AMA1-FVO and AMA1-3D7 vaccine components. A significant dose-response relationship between antigen dose and antibody response by ELISA was observed, and the antibodies were predominantly of the IgG1 isotype. Confocal microscopic evaluation of sera from vaccinated volunteers demonstrated reactivity with P. falciparum schizonts in a pattern similar to native parasite AMA1. Antigen-specific in vitro inhibition of both FVO and 3D7 parasites was achieved with IgG purified from sera of vaccinees, demonstrating biological activity of the antibodies. To our knowledge, this is the first AMA1 vaccine candidate to elicit functional immune responses in malaria-naive humans, and our results support the further development of this vaccine.     

Caring for survivors of torture in an urban, municipal hospital

Survivors of torture can present with multiple health consequences, both physical and psychological, which can persist even years after the abuse. The authors developed a multidisciplinary program in the primary care medical clinic of an urban municipal hospital in New York City serving an ethnically diverse population to provide multidisciplinary care to survivors of torture and their families.     

The Child Custody Protection Act: a "minor" issue at the top of the antiabortion agenda

By a 276/159 vote, the US House of Delegates approved a "Child Custody Protection Act" that would make it a federal crime to transport a minor across state lines to obtain an abortion unless the parental involvement requirements of her home state were met. This legislation was promoted by social conservatives within the Republican party and would only affect a small portion of abortion-seekers. The proposed legislation would criminalize anyone (grandparents, siblings, members of the clergy, or medical professionals) who helps a minor travel to another state to avoid parental involvement. Thus, young women will more likely be forced to deal with a crisis pregnancy on their own. The legislation also raises a number of constitutional and "federalism" issues beyond the abortion debate. In the US, teenagers account for 20% of all abortions, but minors for less than 10%. Parental involvement proponents argue that parents of minors have a right to decide what medical treatment their daughters can access, but no state requires parental consent before a minor obtains contraceptive services, prenatal care, sexually transmitted diseases services, or treatment for alcohol or drug abuse. Only a few services require parental permission for a minor to carry a pregnancy to term or to offer a baby for adoption. Also, many minors voluntarily involve their parents in abortion decisions. Opponents to the bill argue that it fails to strengthen families because it targets extended family members. The President will veto the bill as written.     

薄层色谱法检测恶性疟原虫乳酸脱氢酶的研究

目的建立一种敏感、简便、快速的恶性疟诊断方法.方法应用薄层色谱法检测体外培养的不同虫株恶性疟原虫感染红细胞中的恶性疟原虫乳酸脱氢酶(LDH-p).结果该方法的敏感度可达10个原虫/μl～20个原虫/μl血.检测感染期相同、原虫密度均为5%的恶性疟原虫FCC-1/HN株、FCC-1/AH株、FCC/YN株感染红细胞的最高阳性稀释度不同,提示不同虫株恶性疟原虫体内的LDH可能存在着差异.整个检测过程30min,不需特殊设备,费用低廉.结论薄层色谱法检测恶性疟原虫乳酸脱氢酶敏感、简便、快速.     

The promotion of axon extension in vitro using polymer-templated fibrin scaffolds

Biomaterial nerve cuffs are a clinical alternative to autografts and allografts as a means to repair segmental peripheral nerve defects. However, existing clinical biomaterial constructs lack true incorporation of physical guidance cues into their design. In both two- and three-dimensional systems, it is known that substrate geometry directly affects rates of axon migration. However, the ability to incorporate these cues into biomaterial scaffolds of sufficient porosity to promote robust nerve regeneration in three-dimensional systems is a challenge. We have developed fibrin constructs fabricated by a sacrificial templating approach, yielding scaffolds with multiple 10-250 μm diameter conduits depending on the diameter of the template fibers. The resulting scaffolds contained numerous, highly aligned conduits, had porosity of ～ 80%, and showed mechanical properties comparable to native nerve (150-300 kPa Young's modulus). We studied the effects of the conduit diameters on the rate of axon migration through the scaffold to investigate if manipulation of this geometry could be used to ultimately promote more rapid bridging of the scaffold. All diameters studied led to axon migration, but in contrast to effects of fiber diameters in other systems, the rate of axon migration was independent of conduit diameter in these templated scaffolds. However, aligned conduits did support more rapid axon migration than non-aligned, tortuous controls.     

Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress

Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS. We included a consecutive sample of 14 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations and 56 healthy control subjects of equal sex and age distribution. Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of –20 mmHg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04–0.15 Hz) and the high–frequency (HF) band (0.15–0.50 Hz), using an autoregressive algorithm. Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP, compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control. CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents.     

Health supervision for children with fragile X syndrome

Fragile X syndrome (an FMR1-related disorder) is the most commonly inherited form of mental retardation. Early physical recognition is difficult, so boys with developmental delay should be strongly considered for molecular testing. The characteristic adult phenotype usually does not develop until the second decade of life. Girls can also be affected with developmental delay. Because multiple family members can be affected with mental retardation and other conditions (premature ovarian failure and tremor/ataxia), family history information is of critical importance for the diagnosis and management of affected patients and their families. This report summarizes issues for fragile X syndrome regarding clinical diagnosis, laboratory diagnosis, genetic counseling, related health problems, behavior management, and age-related health supervision guidelines. The diagnosis of fragile X syndrome not only involves the affected children but also potentially has significant health consequences for multiple generations in each family.