How water-mediated hydrogen bonds affect chlorophyll a/b selectivity in Water-Soluble Chlorophyll Protein

The Water-Soluble Chlorophyll Protein (WSCP) of Brassicaceae is a remarkably stable tetrapyrrole- binding protein that, by virtue of its simple design, is an exceptional model to investigate the interactions taking place between pigments and their protein scaffold and how they affect the photophysical properties and the functionality of the complexes. We investigated variants of WSCP from Lepidium virginicum (Lv) and Brassica oleracea (Bo), reconstituted with Chlorophyll (Chl) b, to determine the mechanisms by which the different Chl binding sites control their Chl a/b specificities. A combined Raman and crystallographic investigation has been employed, aimed to characterize in detail the hydrogen-bond network involving the formyl group of Chl b. The study revealed a variable degree of conformational freedom of the hydrogen bond networks among the WSCP variants, and an unexpected mixed presence of hydrogen-bonded and not hydrogen-bonded Chls b in the case of the L91P mutant of Lv WSCP. These findings helped to refine the description of the mechanisms underlying the different Chl a/b specificities of WSCP versions, highlighting the importance of the structural rigidity of the Chl binding site in the vicinity of the Chl b formyl group in granting a strong selectivity to binding sites

Synthesis between clinical trials and patent families about leprosy

The aim of this study is Perform a comparative analysis between clinical trials and patent families about leprosy worldwide in the last 20 years, using three technological aspects: diagnosis, drug/treatment and vaccine. A prospecting search in patent bank was conducted in the ORBIT Intelligence system, from Questel company. The search strategies utilized were based on ORBIT system, for each of the technological aspects established in the study (diagnosis, drug/treatment and vaccine). Clinical trials prospecting process was performed using simulations by WHO International Clinical Trials Registry Platform (ICTRP). Searching was carried out following a step-by step provided by the platform. A twenty-year time cut was adopted to harmonize the comparative analysis between patent and clinical trials recovered. Seventy-one clinical trials (11 for diagnosis, 54 for drug and 6 for vaccine) and 3323 patent families (790 for diagnosis, 1515 for drug and 1018 for vaccine) were identified, both distributed into 58 institutions and 21 countries. Through quantitative and qualitative analysis, a pattern of similarity was observed between institutions sponsoring clinical trials and holders of patent families, mainly related to years of registration and unionist priority filing, countries where clinical trials were performed and countries of unionist priority for patent families, phases of clinical trials and legal status of filed patent families. In summary, it is suggested that new public policies should be created to encourage synergy between clinical trials and patents, in order to induce a safe path to technological independence and, accordingly, a better performance in the struggle against leprosy in Brazil

Quali-quantitative synthesis of the global panorama of clinical trials on leprosy

The work presents the analysis and synthesis of clinical trials about leprosy worldwide in the last 20 years. Three technological aspects for study were defined, namely: diagnosis, drug/treatment and vaccine. Seventy-one (71) clinical trials were identified (11 for diagnosis, 54 for drug and 6 for vaccine), distributed among 62 main sponsors, 70 secondary sponsors and 21 countries, with 14 countries participating in 7 international consortia. For the recovery of clinical trials, the ICTRP® platform of the World Health Organization was used. Through quantitative and qualitative analysis and synthesis, a pattern of similarity was observed between 6 types of indicators highlighted in the figurative elements of the article. Eighteen types of final results (3 genera and 18 species) and 9 phases of clinical development were mapped. The most significant participation of non-hegemonic nations was found, which corroborates and validates the state of the art on the investment dedicated to the diseases of neglected populations. A temporal prospecting of two decades was adopted, although records were only identified in 15 years. In this time cut, 9 inflection points were identified, which demonstrates an oscillating development agenda, which presupposes an inconstant interest of the hegemonic pharmaceutical industry in favor of the struggle against leprosy that devastate neglected populations. It is concluded that the clinical effort aimed at leprosy is "corrective", because "treatment" has the most significant amount of clinical trials, and in the background is the "preventive" clinical effort, which represent the subquantities related to the categories "vaccine” and “diagnosis”. Therefore, it appears that the quali-quantitative analysis and synthesis allows us to assert that the clinical development scenario dedicated to leprosy deserves special attention from the State and other real factors of power, in order to create more effective public policies in favor of the neglected populations affected by leprosy. In summary, it is suggested that new public policies shall be created to encourage synergy between clinical trials, both national and international, in order to induce a safe path to clinical-therapeutic independence and, consequently, better performance in the struggle against leprosy in Brazil

Patentometric synthesis of upcoming technologies against tuberculosis: recommendations for public policies

Background: Pharmaceutical technologies depend heavily on patent protection for their development and further access by people. Methods: To give insights about the upcoming technologies (pharmaceutical and non-pharmaceutical) to fight TB this study prospected the global portfolio on TB patents registered worldwide from 2001-2021. Results: In the last two decades were registered 12,283 anti-TB patent families globally, with a peak by 2015, but almost half are inactive. 70% of the portfolio is focused on TB treatment, the remaining for diagnose or vaccine technologies. Most top-30 countries in TB assets are high-income. Holders are spread mainly in USA (43 %) and China (10%). Half of them are universities and research centers. Conclusion: The market monopoly of TB drugs by the pharmaceutical industry from high-income nations may be sustaining the obsolete portfolio of TB technologies worldwide, what favors TB strain resistance. Public policies have an important role in counterbalance this scenario by promoting research in universities and research centers, especially in mid- to low-income countries. We suggest incentives towards diagnosis and vaccine-related technologies to build a solid and effective portfolio of anti-TB patents

Strategic patent benchmark actions against Tuberculosis

Tuberculosis (TB) is the second cause of death lead by infectious disease worldwide and with a growing incidence and death rates by 2022. United Nations preventive and treatment targets to fight TB were unmet and the upcoming TB patent portfolio is vulnerable what jeopardize global progress against TB. Funding for TB research is limited and strategical initiatives through intellectual property could be applied to optimize public and private efforts to fight TB epidemic. To stimulate the research and drug market aspects related with TB technologies, it was synthetized through searches in technological databases 15 strategic actions to enhance development and access of TB assets at regional, national and international level

Fatigue in laser shock peened open-hole thin aluminium specimens

An experimental study was performed in order to determine the influence of the sequence of operations on the effectiveness of Laser Shock Peening (LSP) treatment in increasing the fatigue performances of open-hole aluminium specimens. Residual stress measurements, fractographic analysis and FEM analysis were performed, indicating the presence of compressive residual stresses on the surface of the treated specimens and tensile residual stresses in the mid-section along the thickness of the specimens. Negative effects on fatigue lives were encountered on the specimens with the hole already present, while positive effect were observed in specimens in which the hole was drilled after LSP treatment. These results indicate that LSP can be a good solution for “in production” application, in which open holes are to be drilled after the LSP treatment. The application in which LSP is used “in service” on structures with pre-existing cut-outs, has proven to be impracticable in the investigated configuration

Acute kidney injury in a preterm infant homozygous for the C3435T polymorphism in the ABCB1 gene given oral morphine

A 34-week infant born from a mother with a history of drug abuse developed neonatal abstinence syndrome (NAS) in the first hours of life. Urine drug screening was positive for cocaine and heroin. The infant developed acute kidney injury and bilateral hydronephrosis while receiving oral morphine for control of NAS. Cessation of morphine therapy and urinary catheterization resulted in a rapid and complete resolution of the symptoms. Our patient was homozygous for the C3435T polymorphism in the ABCB1 gene, a polymorphism previously associated with impaired P-glycoprotein activity. We hypothesize that acute renal toxicity was related to accumulation of morphine within urothelial cells due to genetically determined impaired P-glycoprotein activity

Adultos com fraturas: das implicações funcionais e cirúrgicas à educação em saúde

Este estudo objetivou identificar as implicações funcionais e cirúrgicas relativas a pacientes adultos com fraturas, caracterizar o perfil sociodemográfico da amostra do estudo, avaliar a independência funcional das vítimas de fraturas e discutir as implicações relacionadas aos procedimentos cirúrgicos envolvidos no tratamento a esses pacientes. A pesquisa foi realizada entre novembro de 2006 e abril de 2007 com 74 pacientes internados em um hospital de São Paulo. Foram predominantes indivíduos do sexo masculino (91,9%), média de idade de 31,8 anos, brancos (51,3%), vítimas de acidentes de trabalho (51,4%). As fraturas de membros inferiores representaram 73,0% dos casos e membros superiores 13,5%. Os acidentes automobilísticos foram responsáveis por 58,1% das internações. Quanto à Medida de Independência Funcional (MIF), houve aumento nas médias dos valores no decorrer da avaliação. Por outro lado, há diminuição desses valores em casos de acidentes automobilísticos e atropelamentos e naqueles em que os membros inferiores são atingidos.Este estudio tuvo como objetivo identificar las implicaciones funcionales y quirúrgicas de adultos con fracturas, caracterizar el perfil demográfico de la muestra del estudio, evaluar la independencia funcional de las víctimas de fracturas y discutir las implicaciones relativas a los procedimientos quirúrgicos implicados en el tratamiento de estos pacientes. La encuesta fue realizada entre noviembre de 2006 y abril de 2007 con 74 pacientes ingresados en un hospital de Sao Paulo. Varones fueron predominantes (91,9%), edad promedio 31,8 años, blancos (51,3%), víctimas de accidentes (51,4%). Las fracturas de extremidades inferiores representaron el 73,0% de los casos y de extremidades superiores 13,5%. Los accidentes fueron responsables por 58,1% de los ingresos. Cuanto a la Medida de Independencia Funcional (MIF), hubo un aumento en los valores medios durante la evaluación. Por otra parte, hay una disminución de estos valores en casos de accidentes, atropellamientos y en aquellos cuyos miembros inferiores son lesionados.This study aimed to identify the functional and surgical implications for adult patients with fractures, characterizing the demographic profile of the study sample, to assess the functional independence of victims of fractures and discuss the implications related to surgical procedures involved in treating these patients. The survey was conducted between November 2006 and April 2007 with 74 patients admitted to a hospital in Sao Paulo. Male subjects were predominant (91.9%), mean age 31.8 years, whites (51.3%), victims of accidents (51.4%). Fractures of lower limbs accounted for 73.0% of cases and upper limbs 13.5%. The accidents were responsible for 58.1% of admissions. Regarding Functional Independence Measure (FIM), there was an increase in mean values of FIM during the evaluation. Moreover, there is a decrease of these values in cases of accidents and pedestrian accidents and in those whose limbs are affected