Beliefs and preferences regarding biological treatments for severe asthma

Background: Severe asthma is a serious condition with a significant burden on patients' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers’ specialty and experience. Methods: We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared. Results: Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p < 0.05) and between OMA/IL5 and OMA groups (p < 0.05). Conclusions: Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber's specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice

Murine Models for Trypanosoma brucei gambiense Disease Progression—From Silent to Chronic Infections and Early Brain Tropism

Trypanosoma brucei gambiense is responsible for more than 90% of reported cases of human African trypanosomosis (HAT). Infection can last for months or even years without major signs or symptoms of infection, but if left untreated, sleeping sickness is always fatal. In the present study, different T. b. gambiense field isolates from the cerebrospinal fluid of patients with HAT were adapted to growth in vitro. These isolates belong to the homogeneous Group 1 of T. b. gambiense, which is known to induce a chronic infection in humans. In spite of this, these isolates induced infections ranging from chronic to silent in mice, with variations in parasitaemia, mouse lifespan, their ability to invade the CNS and to elicit specific immune responses. In addition, during infection, an unexpected early tropism for the brain as well as the spleen and lungs was observed using bioluminescence analysis. The murine models presented in this work provide new insights into our understanding of HAT and allow further studies of parasite tropism during infection, which will be very useful for the treatment and the diagnosis of the disease

Use of Full-Length Recombinant Calflagin and Its C Fragment for Improvement of Diagnosis of Trypanosoma cruzi Infection

Serological diagnosis of Trypanosoma cruzi infection is hampered by issues related to test specificity due to the cross-reactivity of most antigens with proteins of related parasites such as Leishmania spp. The recombinant calflagins are considered relevant antigens for the diagnosis of infection by Trypanosoma cruzi. In the present work, we describe two genes coding for putative calflagins in Leishmania major with the N-terminal moieties presenting high similarity with T. cruzi genes. This fact raised questions about their role in some cross-recognition of this antigen by sera from Leishmania spp.-infected individuals. The complete T. cruzi calflagin and two fragments of the protein, consisting of 146 amino acids of the N-terminal and 65 amino acids of the C-terminal regions, were expressed and evaluated against a panel of sera, which included well-characterized samples from T. cruzi, and Leishmania-infected patients. We were able to show that sera from Leishmania (Viannia) braziliensis-infected individuals recognized the recombinant full-length calflagin. Both the N-terminal and the complete protein presented the same high sensitivity (98.5% of sera from T. cruzi-infected patients was detected) but different specificities (94% and 98%, respectively, when evaluated against sera from people not infected by T. cruzi, including 15 sera from people infected with L. braziliensis). The C-terminal fragment presented low sensitivity (70%) but 100% specificity. We propose the use of these antigens in two sequential assays to optimize the serological diagnosis of T. cruzi infection in humans in geographic areas where Leishmania spp. infection is coendemic

Chagas disease reactivation in a patient non-Hodgkin's lymphoma

Chagas disease is a chronic infection caused by the protozoan Trypanosoma cruzi (T. cruzi). It has a worldwide distribution affecting at least 8---10 million people. In nonendemic countries, Chagas disease is an emerging illness and has become a public health problem. Most of the patients are asymptomatic, but about 30% of the individuals infected with T. cruzi develop clinically relevant syndromes involving the gastrointestinal tract and the heart. Actually, another important complication with poor prognosis is Chagas disease reactivation in relation with immunosuppressive states.Fil: Vicco, Miguel Hernán. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Cesar, L. I.. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Musacchio, Héctor Mario. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; ArgentinaFil: Bar, H. M.. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Bottasso, Oscar Adelmo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentin

An ionothermally prepared S=1/2 vanadium oxyfluoride kagome lattice

Frustrated magnetic lattices offer the possibility of many exotic ground states that are of great fundamental importance. Of particular significance is the hunt for frustrated spin-1/2 networks as candidates for quantum spin liquids, which would have exciting and unusual magnetic properties at low temperatures. The few reported candidate materials have all been based on d9 ions. Here, we report the ionothermal synthesis of [NH4]2[C7H14N][V7O6F18], an inorganic-organic hybrid solid that contains a S = 1/2 kagome network of d1 V4+ ions. The compound exhibits a high degree of magnetic frustration, with significant antiferromagnetic interactions but no long-range magnetic order or spin-freezing above 2 K, and appears to be an excellent candidate for realizing a quantum spin liquid ground state in a spin-1/2 kagome network.PreprintPostprintPeer reviewe

An improved approach to estimate the avidity index of immunoglobulins: Evaluation of the method using IgG anti-Toxoplasma gondii

The daily clinical practice frequently force physicians to make adecision of whether a patient is coursing an infectious disease at theacute or the chronic stage, since treatment may be different dependingon it. This is the case of toxoplasmosis, a worldwide disease caused bythe intracellular parasite Toxoplasma gondii. When a pregnant woman isinfected for the first time by T. gondii and is not treated, the parasite cancross the placenta and severely affect the fetus. In case of primary infection,the treatment protocol includes using antiparasitic drugs toprevent serious damages, including death of the unborn baby. However,antiparasitic chemicals have side effects that should be avoided, unlesstreatment is mandatory. That is why discrimination between long-termand primary T. gondii infection turns out to be critical in infectedpregnant women (Montoya and Remington, 2008).In this work we have used rP22a, an acute-phase recombinant protein werecently described (Costa et al., 2017), to assess anti-T. gondii IgG AI,calculated by two new easier approaches, one based on the area underthe avidity curve (AUAC) and the other one based on the E-P titrationmethod with minor variations. We compare our results with those obtainedwhen calculating the AI by the conventional methods abovementioned, and the performance to render a proper sample classificationas compared to that obtained having used a commercial kit asstandard.Fil: Garcia, Valeria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Peverengo, Luz María. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Peretti, Leandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: González, Verónica Doris Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Gugliotta, Luis Marcelino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Dalla Fontana, Maria L.. Laboratorio Central de la Provincia de Santa Fe; ArgentinaFil: Marcipar, Iván Sergio. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lagier, Claudia Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin

Decreased level of antibodies and cardiac involvement in patients with chronic Chagas heart disease vaccinated with BCG

Studies indicate that Trypanosoma cruzi is capable of inducing immunological disturbances such as decreased expression of molecules involved in T-cell survival and costimulation for antigen-driven T-cell responses. On the other hand, several reports have described that BCG vaccination induces a T-helper 1-type immune response with protective effects in different pathologies. In this regard, we evaluated whether BCG vaccination coexists with a better clinical and immunological profile of chronic Chagas heart disease (CCHD). We performed a cross-sectional study in T. cruzi seropositive patients categorized according the BCG vaccine background and to the well-established CCHD classification provided by Storino et al. All individuals were subjected to a complete clinical examination. All patients presented detectable levels of autoantibodies anti-p2β, anti-B13, anti-FRA and antiparasite homogenate immunoglobulins, which were unrelated to age and sex distribution or blood pressure values. Comparisons according to BCG vaccination revealed that individuals who had not been vaccinated presented higher values of antibodies, and patients without BCG vaccine had an OR of 6.1 (95 % CI 1.23?29.25, p = 0.02) for globally dilated cardiomyopathy with reduced ejection fraction (Hosmer and Lemeshow test of 5.2 p = 0.73). Our results suggest that BCG vaccination coexists with a better clinical and immunological profile of CCHD, associated with lower cardiac involvement.Fil: Vicco, Miguel Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Rodeles, Luz. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Yodice, Agustina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Marcipar, Iván Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin