Synthesis of (±)-3,4-dimethoxybenzyl- 4-methyloctanoate as a novel internal standard for capsinoid determination by HPLC-ESI-MS/MS(QTOF)

Capsinoids exhibit health-promoting properties and are therefore compounds of interest for medical and food sciences. They are minor compounds present in relatively high concentrations in only a few number of pepper cultivars. It is desirable to quantify capsinoids to provide selected cultivars with high capsinoid contents, which can then be employed as health food product. Quantifying low concentrations of capsinoids from pepper fruit requires a precise and selective analytical technique such as HPLC coupled to electrospray ionization - mass spectrometry, with development of an internal standard essential. In this work, the synthesis method of a novel compound analogue of capsinoids, the (±)-3,4-dimethoxybenzyl-4-methyloctanoate, which could be a suitable internal standard for capsinoid determination by electrospray ionization - mass spectrometry is described. (±)-3,4-dimethoxybenzyl-4-methyloctanoate was stable under the analysis conditions and exerted chemical and physical properties similar to those of capsinoids. This internal standard will provide an accurate capsinoid determination by electrospray ionization - mass spectrometry, thus facilitating the pepper breeding programs, screening pepper cultivars and a better understanding of capsinoid biosynthetic pathway

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières

BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed

Takayasu's arteritis presenting with temporary loss of vision in a 23-year-old woman with beta thalassemia trait: a case report

<p>Abstract</p> <p>Introduction</p> <p>The simultaneous presence of Takayasu's arteritis and beta thalassemia trait is a rare combination. To the best of our knowledge, this is the first case report on Takayasu's arteritis and beta thalassemia presenting together.</p> <p>Case presentation</p> <p>This is a case report of a 23-year-old Asian woman of Pakistani descent who presented with a headache, blurred vision and dizziness.</p> <p>Conclusion</p> <p>The correct diagnosis of our patient was based on clinical suspicion, appropriate imaging studies, and deliberation of the differential diagnosis. The management of our patient depended on the correct diagnosis of both the diseases.</p

Long-time Low-latency Quantum Memory by Dynamical Decoupling

Quantum memory is a central component for quantum information processing devices, and will be required to provide high-fidelity storage of arbitrary states, long storage times and small access latencies. Despite growing interest in applying physical-layer error-suppression strategies to boost fidelities, it has not previously been possible to meet such competing demands with a single approach. Here we use an experimentally validated theoretical framework to identify periodic repetition of a high-order dynamical decoupling sequence as a systematic strategy to meet these challenges. We provide analytic bounds-validated by numerical calculations-on the characteristics of the relevant control sequences and show that a "stroboscopic saturation" of coherence, or coherence plateau, can be engineered, even in the presence of experimental imperfection. This permits high-fidelity storage for times that can be exceptionally long, meaning that our device-independent results should prove instrumental in producing practically useful quantum technologies.Comment: abstract and authors list fixe

Treatment of reducible unstable fractures of the distal radius in adults: a randomised controlled trial of De Palma percutaneous pinning versus bridging external fixation

Background: At present, there is no conclusive evidence regarding the best treatment method for reducible unstable fractures of the distal radius. This study compared the effectiveness of two methods used in surgical treatment of such fractures: percutaneous pinning and external fixation.Methods: We randomly allocated 100 patients into two groups treated surgically with modified de Palma percutaneous pinning and bridging external fixation. Independent but not blinded evaluators administered the DASH quality-of-life questionnaire at postoperative months 6 and 24, performed functional assessment of pain, range of motion, and palm grip strength, and radiographic examinations (volar and radial angle, and height of the radius) before the operation, immediately afterwards, and at 6 and 24 months postoperative. Modified de Palma percutaneous pinning patients used an above-elbow cast whereas external fixation group had unrestricted elbow motion after surgery. Patients who for any reason demonstrated treatment failure or required additional interventions were followed up and their results were included in the group into which these patients had initially been randomised according to the intention-to-treat principle. A significance level of 5% (alpha = 0.05). was used for all statistical tests, such that tests presenting a p-value less than 0.05 were considered statistically significant.Results: Ninety one (58.8 mean age and 66 participants were female) were included in the final assessment at 24 months. the DASH questionnaire evaluation showed a statistically significant result favouring the de Palma group (mean difference = -7.1 p = 0.044) after six months, but this was not maintained at 24 months. There were no statistically differences between the groups with respect to palm grip strength. Analysis of the range-of-motion limitation index (uninjured side minus affected side motion of) showed a statistical difference (mean difference = 2.4 p = 0.043) favoring the external fixator group with regard to the supination movement 6 months after the operation; however, this was not maintained at 24 months. the final results of the radiographic evaluation were similar for the two groups. Overall, five patients developed complications: two with de Palma pinning and three with external fixation.Conclusion: There was a small statistically significant difference favouring the de Palma method in early functional at 6 months according to the DASH questionnaire, and for supination movement favouring the fixator group. However, both were not clinical relevant. By 24 months the groups were similar for all outcome

Two Distinct Coagulase-Dependent Barriers Protect Staphylococcus aureus from Neutrophils in a Three Dimensional in vitro Infection Model

Staphylococcus aureus is a pyogenic abscess-forming facultative pathogenic microorganism expressing a large set of virulence-associated factors. Among these, secreted proteins with binding capacity to plasma proteins (e.g. fibrinogen binding proteins Eap and Emp) and prothrombin activators such as Coagulase (Coa) and vWbp are involved in abscess formation. By using a three-dimensional collagen gel (3D-CoG) supplemented with fibrinogen (Fib) we studied the growth behavior of S. aureus strain Newman and a set of mutants as well as their interaction with mouse neutrophils by real-time confocal microscopy. In 3D-CoG/Fib, S. aureus forms microcolonies which are surrounded by an inner pseudocapsule and an extended outer dense microcolony-associated meshwork (MAM) containing fibrin. Coa is involved in formation of the pseudocapsule whereas MAM formation depends on vWbp. Moreover, agr-dependent dispersal of late stage microcolonies could be observed. Furthermore, we demonstrate that the pseudocapsule and the MAM act as mechanical barriers against neutrophils attracted to the microcolony. The thrombin inhibitor argatroban is able to prevent formation of both pseudocapsule and MAM and supports access of neutrophils to staphylococci. Taken together, this model can simulate specific stages of S. aureus abscess formation by temporal dissection of bacterial growth and recruitment of immune cells. It can complement established animal infection models in the development of new treatment options

Phylogenetic Relationships in Pterodroma Petrels Are Obscured by Recent Secondary Contact and Hybridization

The classification of petrels (Pterodroma spp.) from Round Island, near Mauritius in the Indian Ocean, has confounded researchers since their discovery in 1948. In this study we investigate the relationships between Round Island petrels and their closest relatives using evidence from mitochondrial DNA sequence data and ectoparasites. Far from providing clear delimitation of species boundaries, our results reveal that hybridization among species on Round Island has led to genetic leakage between populations from different ocean basins. The most common species on the island, Pterodroma arminjoniana, appears to be hybridizing with two rarer species (P. heraldica and P. neglecta), subverting the reproductive isolation of all three and allowing gene flow. P. heraldica and P. neglecta breed sympatrically in the Pacific Ocean, where P. arminjoniana is absent, but no record of hybridization between these two exists and they remain phenotypically distinct. The breakdown of species boundaries in Round Island petrels followed environmental change (deforestation and changes in species composition due to hunting) within their overlapping ranges. Such multi-species interactions have implications not only for conservation, but also for our understanding of the processes of evolutionary diversification and speciation

Role of 4-1BB Receptor in the Control Played by CD8+ T Cells on IFN-γ Production by Mycobacterium tuberculosis Antigen-Specific CD4+ T Cells

BACKGROUND: Antigen-specific IFN-gamma producing CD4(+) T cells are the main mediators of protection against Mycobacterium tuberculosis infection both under natural conditions and following vaccination. However these cells are responsible for lung damage and poor vaccine efficacy when not tightly controlled. Discovering new tools to control nonprotective antigen-specific IFN-gamma production without affecting protective IFN-gamma is a challenge in tuberculosis research. METHODS AND FINDINGS: Immunization with DNA encoding Ag85B, a candidate vaccine antigen of Mycobacterium tuberculosis, elicited in mice a low but protective CD4(+) T cell-mediated IFN-gamma response, while in mice primed with DNA and boosted with Ag85B protein a massive increase in IFN-gamma response was associated with loss of protection. Both protective and non-protective Ag85B-immunization generated antigen-specific CD8(+) T cells which suppressed IFN-gamma-secreting CD4(+) T cells. However, ex vivo ligation of 4-1BB, a member of TNF-receptor super-family, reduced the massive, non-protective IFN-gamma responses by CD4(+) T cells in protein-boosted mice without affecting the low protective IFN-gamma-secretion in mice immunized with DNA. This selective inhibition was due to the induction of 4-1BB exclusively on CD8(+) T cells of DNA-primed and protein-boosted mice following Ag85B protein stimulation. The 4-1BB-mediated IFN-gamma inhibition did not require soluble IL-10, TGF-beta, XCL-1 and MIP-1beta. In vivo Ag85B stimulation induced 4-1BB expression on CD8(+) T cells and in vivo 4-1BB ligation reduced the activation, IFN-gamma production and expansion of Ag85B-specific CD4(+) T cells of DNA-primed and protein-boosted mice. CONCLUSION/SIGNIFICANCE: Antigen-specific suppressor CD8(+) T cells are elicited through immunization with the mycobacterial antigen Ag85B. Ligation of 4-1BB receptor further enhanced their suppressive activity on IFN-gamma-secreting CD4(+) T cells. The selective expression of 4-1BB only on CD8(+) T cells in mice developing a massive, non-protective IFN-gamma response opens novel strategies for intervention in tuberculosis pathology and vaccination through T-cell co-stimulatory-based molecular targeting

A Kinetic Study of Acrylamide/ Acrylic Acid Copolymerization

Homo- and co-polymers of acrylamide (AAm) and acrylic acid (or acrylate salt) (AA) or methacrylic acid (MAA)) are important classes of water-soluble polymers due to their numerous applications in fields such as super absorbents, additives in cosmetics, membrane technology, waste-water treatment and oil field operations. These polymers are generally made by free radical polymerization. For copolymerization reactions it is extremely important to know the details of reaction kinetics in order to ascertain the kinetic effects of different reaction parameters, which ultimately dictate final copolymer composition, microstructure and properties. The reactivity ratios for copolymerization of AAm and AA have been shown to be dependent on pH and they also change with reaction solvent. The present experimental investigation has been performed to study the kinetics of copolymerization of these monomers in aqueous and alcoholic media by considering factors such as type of initiator and solvent, and pH, in order to determine how they affect the reactivity ratios of these monomers. Reactivity ratios were determined by non-linear least squares (NLLS) and the error-in-variables-model (EVM) techniques and full conversion range kinetic investigations were carried out to confirm these values

IgE Mediated Autoallergy against Thyroid Peroxidase – A Novel Pathomechanism of Chronic Spontaneous Urticaria?

Chronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation.We developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n = 478) and healthy control subjects (n = 127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences. ( = 61%, IgE-anti-TPO: median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels.Our findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause “autoallergic” mast cell activation, a novel pathomechanism of chronic spontaneous urticaria