Placebo Effects in Clinical Trials Evaluating Patients with Uncontrolled Persistent Asthma.

Patients with uncontrolled, persistent asthma can show substantial health improvements when administered placebo. We analyzed five randomized, placebo-controlled clinical trials that assessed subjects with uncontrolled, persistent asthma to determine the magnitudes of placebo effects across different clinical outcomes. Placebo effects for objective asthma-related outcomes, healthcare utilization outcomes, and patient-reported outcomes were estimated, with adjustments for regression to the mean.

Assessing Spatial Working Memory Using the Spontaneous Alternation Y-maze Test in Aged Male Mice.

The global population is aging and the prevalence of age-related diseases, such as Alzheimer's disease and vascular dementia is increasing. Understanding functional impairments and disease processes is of vital importance in order to develop effective therapeutics. Using the natural exploratory behavior of mice, the spontaneous alternation y-maze can assess short-term spatial working memory.

High-level artemisinin-resistance with quinine co-resistance emerges in P. falciparum malaria under in vivo artesunate pressure.

Background: Humanity has become largely dependent on artemisinin derivatives for both the treatment and control of malaria, with few alternatives available. A Plasmodium falciparum phenotype with delayed parasite clearance during artemisinin-based combination therapy has established in Southeast Asia, and is emerging elsewhere. Therefore, we must know how fast, and by how much, artemisinin-resistance can strengthen.

Evaluating Human Immune Responses for Vaccine Development in a Novel Human Spleen Cell-Engrafted NOD-SCID-IL2rγNull Mouse Model.

The lack of preclinical models able to faithfully predict the immune responses which are later obtained in the clinic is a major hurdle for vaccines development as it increases markedly the delays and the costs required to perform clinical studies. We developed and evaluated the relevance to human immune responses of a novel humanized mouse model, humanized-spleen cells-NOD-SCID-gamma null (Hu-SPL-NSG), in which we grafted human spleen cells in immunodeficient NOD-SCID-IL-2rγnull (NSG) mice. We selected the malaria vaccine candidate, Liver Stage Antigen 3-Full Length, because we had previously observed a major discrepancy between preclinical and clinical results, and compared its immunogenicity with that of a shorter form of the molecule, LSA3-729.

Reduced brain volume and impaired memory in betaine homocysteine S-methyltransferase knockout mice.

Using a mouse model, this study examined the impact of lack of betaine homocysteine S-methyltransferase (BHMT) on neurological function. Bhmt mice maintained on a control diet had elevated concentrations of homocysteine, reduced total brain magnetic resonance imaging (MRI) volume, as well as impaired reference and short-term memories. The results of this study indicate that the absence of BHMT may play a role in neurological function.

Malaria elimination in Haiti by the year 2020: an achievable goal?

Haiti and the Dominican Republic, which share the island of Hispaniola, are the last locations in the Caribbean where malaria still persists. Malaria is an important public health concern in Haiti with 17,094 reported cases in 2014. Further, on January 12, 2010, a record earthquake devastated densely populated areas in Haiti including many healthcare and laboratory facilities.

Pre-clinical assessment of novel multivalent MSP3 malaria vaccine constructs.

Background: MSP3 has been shown to induce protection against malaria in African children. The characterization of a family of Plasmodium falciparum merozoite surface protein 3 (MSP3) antigens sharing a similar structural organization, simultaneously expressed on the merozoite surface and targeted by a cross-reactive network of protective antibodies, is intriguing and offers new perspectives for the development of subunit vaccines against malaria.

Methods: Eight recombinant polyproteins containing carefully selected regions of this family covalently linked in different combinations were all efficiently produced in Escherichia coli.

A human Phase I/IIa malaria challenge trial of a polyprotein malaria vaccine.

We examined the safety, immunogenicity and efficacy of a prime-boost vaccination regime involving two poxvirus malaria subunit vaccines, FP9-PP and MVA-PP, expressing the same polyprotein consisting of six pre-erythrocytic antigens from Plasmodium falciparum. Following safety assessment of single doses, 15 volunteers received a heterologous prime-boost vaccination regime and underwent malaria sporozoite challenge. The vaccines were safe but interferon-γ ELISPOT responses were low compared to other poxvirus vectors, despite targeting multiple antigens.

Single umbilical incision laparoscopic cholecystectomy: initial experience of the Coelio Club.

Aim: To assess the initial results of single umbilical incision laparoscopic cholecystectomies (SUILC) performed by the members of the Club Coelio.

Patients And Methods: This multicenter study involved 65 consecutive patients undergoing SUILC between September 2008 and December 2009. The operation was performed with a 0° scope in 35 and with a 30° scope in 30 patients.

Toward the rational design of a malaria vaccine construct using the MSP3 family as an example: contribution of antigenicity studies in humans.

Plasmodium falciparum merozoite surface protein (MSP3) is a main target of protective immunity against malaria that is currently undergoing vaccine development. It was shown recently to belong, together with MSP6, to a new multigene family whose C-terminal regions have a similar organization, contain both homologous and divergent regions, and are highly conserved across isolates. In an attempt to rationally design novel vaccine constructs, we extended the analysis of antigenicity and function of region-specific antibodies, previously performed with MSP3 and MSP6, to the remaining four proteins of the MSP3 family using four recombinant proteins and 24 synthetic peptides.

The malaria candidate vaccine liver stage antigen-3 is highly conserved in Plasmodium falciparum isolates from diverse geographical areas.

Background: A high level of genetic stability has been formerly identified in segments of the gene coding for the liver stage antigen-3 (LSA-3), a subunit vaccine candidate against Plasmodium falciparum. The exploration of lsa-3 polymorphisms was extended to the whole sequence of this large antigen in 20 clinical isolates from four geographical areas; Senegal, Comoro islands, Brazil and Thailand.

Methods: The whole 4680 bp genomic sequence of lsa-3 was amplified by polymerase chain reaction and sequenced.

Toward the rational design of a malaria vaccine construct using the MSP3 family as an example: contribution of immunogenicity studies in models.

Plasmodium falciparum merozoite surface protein 3 (MSP3), the target of antibodies that mediate parasite killing in cooperation with blood monocytes and are associated with protection in exposed populations, is a vaccine candidate under development. It belongs to a family of six structurally related genes. To optimize immunogenicity, we attempted to improve its design based on knowledge of antigenicity of various regions from the conserved C terminus of the six proteins and an analysis of the immunogenicity of "tailored" constructs.

[Technique of pancreatic procurement for pancreatic islet isolation].

Aim Of The Study: The allograft of pancreatic islets represents a potential alternative to insulin therapy in patients suffering from the most severe forms of Type 1 diabetes. Here we report our experience of pancreatic procurement for isolation and islet allograft.

Materials And Methods: Pancreata were procured in brain-dead donors.

A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses.

To generate broadly protective T cell responses more similar to those acquired after vaccination with radiation-attenuated Plasmodium falciparum sporozoites, we have constructed candidate subunit malaria vaccines expressing six preerythrocytic antigens linked together to produce a 3240-aa-long polyprotein (L3SEPTL). This polyprotein was expressed by a plasmid DNA vaccine vector (DNA) and by two attenuated poxvirus vectors, modified vaccinia virus Ankara (MVA) and fowlpox virus of the FP9 strain. MVAL3SEPTL boosted anti-thrombospondin-related adhesive protein (anti-TRAP) and anti-liver stage antigen 1 (anti-LSA1) CD8(+) T cell responses when primed by single antigen TRAP- or LSA1-expressing DNAs, respectively, but not by DNA-L3SEPTL.

Biphasic culture of rat lung slices for pharmacotoxicological evaluation of complex atmospheres.

The relevance to the in vivo situation of in vitro toxicity studies of complex atmospheres has frequently been limited by the procedures used for the exposure of the biological samples. We have evaluated from on-road measurements the size distribution pattern and the subsequent respiratory tract deposition rates of particulate matter from urban atmospheric aerosols, which are in the range of 110 and 3 pg/cm2 per min for tracheobronchial and alveolar areas, respectively. Continuous flow-through rotating chambers and a specific design for exhaust sampling and dilution with controlled adjustment of pO2 and pCO2 to 20% and 5%, respectively, have been developed to expose biphasic air/liquid organotypic cultures of rat lung slices to continuous flows of diluted exhausts from diesel engines with preservation of the physicochemical properties of the exhaust.

[Hemorrhagic digestive metastases from testicular choriocarcinoma].

The metastasis of testicular choriocarcinoma are often hemorrhagic, primarily of cerebral or pulmonary seat. The secondary digestive localizations are rare and of bad forecast when they bleed. The surgical operation by laparotomy allows the topographic diagnosis and the treatment, but was made responsible for hemorrhagic decompensation of other metastatic localizations engaging the vital forecast.

[Progressive correction of an ulnar clubhand secondary to post-traumatic epiphysiodesis of the distal ulna].

The authors report the correction of an ulnar club-hand in a 16 year-old boy who complained of recurrent wrist pain after a fracture of both bones of his left forearm treated by internal fixation at the age of nine years. Correction was achieved by progressive ulnar lengthening, using Ilizarov's method, without radius osteotomy or bone grafting. Union was achieved 2 months post-operatively.

DNA-based vaccines for malaria: a heterologous prime-boost immunisation strategy.

A generic approach to inducing high level CD8+ T cell responses would be of value for prophylactic and therapeutic immunisation against several infectious diseases. However, it has been very difficult to achieve such immune responses using available vaccination strategies. Malaria is one of several diseases against which a new generation of better CD8+ T cell-inducing vaccines might be useful and is unusual in that it allows assessment of vaccine efficacy in small numbers of volunteers in carefully controlled challenge studies.

Toxicity of diesel engine exhausts in an in vitro model of lung slices in biphasic organotypic culture: induction of a proinflammatory and apoptotic response.

Precision-cut rat lung slices in organotypic culture placed in a biphasic air/liquid system were used for this study. This model allowed pathological as well as cellular and molecular biology investigations to be carried out. Slices were exposed to a continuous flow of diluted diesel exhaust, with a pO2 adjusted to 20% to avoid hypoxia-induced effects.

Development of a new in vitro system for continuous in vitro exposure of lung tissue to complex atmospheres: application to diesel exhaust toxicology.

The purpose of this study was the development of a new incubation system that can allow continuous exposure of lung tissue to complex atmospheres as a tool for the assessment of aerial environmental lung toxicology. To assess the pertinence of this new exposure system, we studied the impact of diesel engine exhausts as a complex atmosphere containing both gaseous and particulate fractions and have been able to discriminate between the toxicological impacts of the gaseous phase and particulate matter from diesel exhausts. Continuous flow-through rotating chambers with controlled PO2, pCO2, and hygrometry have been designed in which lung slices are positioned in rolling inserts that allow free access of atmosphere to the exposed lung tissue.

Induction of CD8+ T cells using heterologous prime-boost immunisation strategies.

One of the current challenges in vaccine design is the development of antigen delivery systems or vaccination strategies that induce high protective levels of CD8+ T cells. These cells are crucial for protection against certain tumours and intracellular pathogens such as the liver-stage parasite of malaria. A liver-stage malaria vaccine should therefore include CD8+ T-cell-inducing components.

Acrolein toxicity: comparative in vitro study with lung slices and pneumocytes type II cell line from rats.

Toxicological effects of acrolein have been studied in precision-cut rat lung slices and in L2 cells, a rat pneumocyte II cell line. These two models were cultured for 24 h with or without acrolein (0-100 microM in L2 cells; 0-200 microM in lung slices). Treatment with this pneumotoxicant produced a concentration dependent decrease in intracellular ATP levels.

Characterization of Precision-cut Rat Lung Slices in a Biphasic Gas/Liquid Exposure System: Effect of O(2).

Influence of oxygen on lung cell differentiation has been studied in precision-cut rat lung slice cultures. Rat lung slices were positioned on rolling inserts placed into vials with opened caps to allow free access to the gaseous phase. This system was placed into a continuous-flow rotating chamber with controlled pO(2), pCO(2) and hygrometry.