The use of etoricoxib to treat an idiopathic stabbing headache: a case report

According to the International Headache Society, idiopathic stabbing headache (ISH), an indomethacin-responsive headache syndrome, is a paroxysmal disorder of short duration manifested as head pain occurring as a single stab or a series of stabs involving the area supplied in the distribution of the first division of the trigeminal nerve. Stabs last for approximately a few seconds, occurring and recurring from once to multiple times per day in an irregular frequency, with no underlying attributable disorder

Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention

Glycogen synthase kinase-3 (GSK-3) is well documented to participate in a complex array of critical cellular processes. It was initially identified in rat skeletal muscle as a serine/threonine kinase that phosphorylated and inactivated glycogen synthase. This versatile protein is involved in numerous signaling pathways that influence metabolism, embryogenesis, differentiation, migration, cell cycle progression and survival. Recently, GSK-3 has been implicated in leukemia stem cell pathophysiology and may be an appropriate target for its eradication. In this review, we will discuss the roles that GSK-3 plays in hematopoiesis and leukemogenesis as how this pivotal kinase can interact with multiple signaling pathways such as: Wnt/β-catenin, phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR), Ras/Raf/MEK/extracellular signal-regulated kinase (ERK), Notch and others. Moreover, we will discuss how targeting GSK-3 and these other pathways can improve leukemia therapy and may overcome therapeutic resistance. In summary, GSK-3 is a crucial regulatory kinase interacting with multiple pathways to control various physiological processes, as well as leukemia stem cells, leukemia progression and therapeutic resistance. GSK-3 and Wnt are clearly intriguing therapeutic targets

Predicting SARS-CoV-2 variant spread in a completely seropositive population using semi-quantitative antibody measurements in blood donors

SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021–November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants

Global, regional, and national levels of maternal mortality, 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015. Methods We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Findings Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68% in 1990 to more than 80% in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91% coverage of one antenatal care visit, 78% of four antenatal care visits, 81% of in-facility delivery, and 87% of skilled birth attendance. Interpretation Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care-including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population.Peer reviewe

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Tatiana G Ribeiro,1 Juçara R Franca,1 Leonardo L Fuscaldi,1 Mara L Santos,2 Mariana C Duarte,3 Paula S Lage,3 Vivian T Martins,4 Lourena E Costa,3 Simone OA Fernandes,1,5 Valbert N Cardoso,1,5 Rachel O Castilho,1,6 Manuel Soto,7 Carlos AP Tavares,4 André AG Faraco,1,6 Eduardo AF Coelho,3,8,* Miguel A Chávez-Fumagalli3,* 1Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, 2Departamento de Morfologia, Instituto de Ciências Biológicas, 3Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, 4Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, 5Departamento de Análises Clínicas e Toxicológicas, 6Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 7Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain; 8Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil *These authors contributed equally to this work Abstract: Amphotericin B (AmpB) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. In this study, a nanoparticles-delivery system for AmpB (NQC-AmpB), containing chitosan and chondroitin sulfate molecules, was evaluated in BALB/c mice against Leishmania amazonensis. An in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of AmpB. Nanoparticles were radiolabeled with technetium-99m and injected in mice. The products presented a similar biodistribution in the liver, spleen, and kidneys of the animals. Free AmpB induced alterations in the body weight of the mice, which, in the biochemical analysis, indicated hepatic and renal injury, as well as morphological damage to the kidneys of the animals. In general, no significant organic alteration was observed in the animals treated with NQC-AmpB. Mice were infected with L. amazonensis and treated with the nanoparticles or free AmpB; then, parasitological and immunological analyses were performed. The NQC-AmpB group, as compared to the control groups, presented significant reductions in the lesion size and in the parasite burden in all evaluated organs. These animals presented significantly higher levels of IFN-γ and IL-12, and low levels of IL-4 and IL-10, when compared to the control groups. The NQC-AmpB system was effective in reducing the infection in the animals, and proved to be effective in diminishing the toxicity evoked by AmpB, which was observed when it was administered alone. In conclusion, NQC-AmpB could be considered a viable possibility for future studies in the treatment of leishmaniasis. Keywords: in vivo treatment, Leishmania amazonensis, nanoparticles, chitosan, chondroitin sulfat

Spirituality in palliative home care: a framework for the clinician

Item does not contain fulltextPURPOSE: Spiritual care at the end of life remains poorly understood despite its promotion by the World Health Organisation. The purpose of this paper was to develop a consensus-based framework of the main elements of spiritual care in palliative home care. METHODS: Expert meeting using the nominal group technique, followed by a two-stage web-based Delphi process, was used. Experts from three stakeholder groups (physicians, professional spiritual care givers and researchers) representing two countries (Belgium and the Netherlands) participated in this study. RESULTS: Fourteen elements of spiritual care were retained: (1) being sensitive to patient's fear of the dying process; (2) listening to the patient's expectations and wishes about the end of life; (3) giving attention to patient's wishes about the design of the farewell; (4) offering rituals if the patient experiences them as meaningful; (5) listening to the stories, dreams and passions of the patient; (6) helping the patient find strength in inner resources; (7) connecting with the patient in truth, openness and honesty; (8) supporting communication and quality of relationships; (9) making sure the patient feels comfortable and safe; (10) seeing spirituality as an interwoven, though specific dimension; (11) caring for your own spirituality; (12) knowing and accepting your vulnerability; (13) being able to learn from your patient; and (14) having an interdisciplinary team that is there when needed. CONCLUSIONS: The experts agreed to the 14 main elements of spiritual care in palliative home care. There were no differences in this regard between the stakeholder groups. This study provides a first step towards the development of an interdisciplinary spiritual care model in palliative home care