Topiramate plus nortriptyline in the preventive treatment of migraine: a controlled study for nonresponders

A sizeable proportion of migraineurs in need of preventive therapy do not significantly benefit from monotherapy. The objective of the study is to conduct a randomized controlled trial testing whether combination therapy of topiramate and nortriptyline is useful in patients who had less than 50% decrease in headache frequency with the use of the single agents. Patients with episodic migraine were enrolled if they had less than 50% reduction in headache frequency after 8 weeks of using topiramate (TPM) (100 mg/day) or nortriptyline (NTP) (30 mg/day). They were randomized (blinded fashion) to have placebo added to their regimen, or to receive the second medication (combination therapy). Primary endpoint was decrease in number of headache days at 6 weeks, relative to baseline, comparing both groups. Secondary endpoint was proportion of patients with at least 50% reduction in headache frequency at 6 weeks relative to baseline. A total of 38 patients were randomized to receive combination therapy, while 30 continued on monotherapy (with placebo) (six drop outs in the combination group and three for each single drug group). For the primary endpoint, mean and standard deviation (SD) of reduction in headache frequency were 4.6 (1.9) for those in polytherapy, relative to 3.5 (2.3) for those in monotherapy. Differences were significant (p < 0.05]. Similarly, 78.3% of patients randomized to receive polytherapy had at least 50% headache reduction, as compared to 37% in monotherapy (p < 0.04). Finally we conclude that combination therapy (of TPM and NTP) is effective in patients with incomplete benefit using these agents in monotherapy

A concept for international societally relevant microbiology education and microbiology knowledge promulgation in society

Microbes are all pervasive in their distribution and influence on the functioning and well-being of humans, life in general and the planet. Microbially-based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision-makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative–the IMiLI–is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence-based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner-centric, not academic microbiology-centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators–learners. As such, they will collect and analyse feedback from the end-users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators–learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships–a global societally relevant microbiology education ecosystem–in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient. The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well-being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us–individuals/communities/nations/the human world–and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. HERE, WE PRESENT our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision-making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner-centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091–1111). Importantly, although the primary target of the freely available (CC BY-NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity-driven, web-based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.http://www.wileyonlinelibrary.com/journal/mbt2hj2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-01:No povertySDG-02:Zero HungerSDG-03:Good heatlh and well-beingSDG-04:Quality EducationSDG-06:Clean water and sanitationSDG-07:Affordable and clean energySDG-08:Decent work and economic growthSDG-12:Responsible consumption and productionSDG-13:Climate actionSDG-14:Life below wate

Freqüência de relatos de parafunções nos subgrupos diagnósticos de DTM de acordo com os critérios diagnósticos para pesquisa em disfunções temporomandibulares (RDC/TMD) Frequency of relates of parafunctions in the diagnostic subgroups of TMD according to research diagnostic criteria for temporomandibular disorders (RDC/TMD)

INTRODUÇÃO: as disfunções temporomandibulares (DTM) podem ser definidas como um conjunto de condições dolorosas e/ou disfuncionais, que envolvem os músculos da mastigação e/ou as articulações temporomandibulares (ATM). Um dos meios usados para o diagnóstico é o "Critério Diagnóstico para Pesquisa em Disfunções Temporomandibulares" (RDC/TMD). Hábitos parafuncionais são aqueles não relacionados à execução das funções normais do sistema estomatognático. O bruxismo é caracterizado por atividade parafuncional noturna involuntária dos músculos mastigatórios, enquanto o apertamento dentário é considerado uma parafunção diurna envolvendo esta musculatura, embora possa ocorrer também à noite. OBJETIVOS: o objetivo do presente estudo foi avaliar a freqüência do relato de parafunções orais diurna e/ou noturna em pacientes com DTM nos diferentes subgrupos diagnósticos do RDC/TMD. METODOLOGIA: foram utilizados dados provenientes de 217 pacientes que procuraram tratamento na Clínica de DTM e Dor Orofacial da Faculdade de Medicina de Petrópolis, sendo avaliados através do questionário e exame físico que compõem o RDC/TMD. RESULTADOS: dos 182 pacientes com DTM estudados, 76,9% relataram algum tipo de parafunção, podendo ser diurna, noturna ou a associação de ambas. A parafunção diurna foi a mais freqüentemente relatada entre os subgrupos de DTM, sendo encontrada em 64,8% dos casos contra 55,5% dos casos com relato de bruxismo. O relato de ambas as parafunções foi constatado em 43,4% dos pacientes com DTM. CONCLUSÕES: considerando cada subgrupo diagnóstico, os relatos de parafunções diurna e noturna foram mais freqüentes nos pacientes com dor miofascial.<br>INTRODUCTION: temporomandibular disorders (TMD) can be defined as a group of painful and/or dysfunctional conditions that involve masticatory muscles and/or the temporomandibular joints (TMJ). One of the methods used to the diagnostic is the "Research Diagnostic Criteria for Temporomandibular Disorders" (RDC/TMD). Parafunctional habits are those not related to the execution of normal functions of stomatognatic system. Bruxism is characterized by nocturnal involuntary parafunctional activity of masticatory muscles, while clenching is considered as a diurnal parafunction involving this musculature, although this may also occur at night. OBJECTIVE: the goal of the present study was to evaluate the frequency of relates of diurnal and/or nocturnal oral parafunctions in patients with TMD in different diagnostic subgroups of RDC/TMD. METHODOLOGY: it has been used data from 217 patients that seek for treatment at TMD and Orofacial Pain Clinic of Petropolis Medicine School, being evaluated through questionnaire and physical examination that compose RDC/TMD. RESULTS: from 182 TMD patients studied, 76.9% has related some kind of parafunction, that could be diurnal, nocturnal or both. Diurnal parafunction was the most frequent related among TMD subgroups, present in 64.8% of cases against 55.5% of cases with relates of bruxism. Relate of both parafunctions was verified in 43.4% of TMD patients. CONCLUSION: regarding each diagnostic subgroup, relates of diurnal and nocturnal parafunctions has been more frequent in patients of miofascial pain group

Simple phenotypic tests to improve accuracy in screening chromosomal and plasmid-mediated colistin resistance in gram-negative bacilli

Fil: Pasteran, Fernando. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Danze, Diego. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Menocal, Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Cabrera, Carla. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Castillo, Ignacio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Albornoz, Ezequiel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Lucero, Celeste. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Rapoport, Melina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Ceriana, Paola. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Corso, Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.CLSI and EUCAST recommends that only broth microdilution (BMD) should be used for routine colistin susceptibility testing, however, it could be difficult to perform in resource-poor settings. The purpose of this study was to evaluate the accuracy of an agar spot test (COL-AS) and a colistin drop test (COL-DT) as compared to BMD. COL-AS and COL-DT were challenged with a collection of 271 Gram-negative bacilli clinical isolates: 195 Enterobacterales (including 63 mcr-1 positive strains), 37 Acinetobacter spp. and 39 Pseudomonas aeruginosa For COL-AS, 3.0μg/ml (final concentration) of colistin was added to a Mueller-Hinton agar plate and subsequently swabbed with a 0.5 McFarland suspension of tested strain within 1cm2 spot. For COL-DT, 10μl of a 16μg/ml colistin solution was dripped on the surface of a Mueller-Hinton agar plate, previously inoculated with a lawn of tested strain (0.5 McFarland). Colistin solution was made either, by dissolving powder or by disk elution in CA-MHB. Overall, 141/271 (52%) isolates were categorized as colistin resistant by reference BMD. COL-AS yielded a categorical agreement (CA) of 95.5% compared to BMD, with 0.7% very major errors and 3.8% major errors. COL-DT yielded a CA of 96.2% compared to BMD, with 0.7% and 0% very major errors and 3.1% and 3.8% major errors, for colistin powder and disk elution solutions, respectively. Most major errors occurred for mcr-1 producing strains with MICs that fluctuated from 2 to 4 μg/ml according to the method used. In conclusion, we developed and validated methods suited to the systematic screening of resistance to colistin in gram negative bacilli.Clinical relevance: colistin continues to be one of the last-line therapeutic options to treat carbapenemase-producing gram negative bacilli. The BMD reference methodology, recommended by current standards for evaluating colistin sensitivity, is difficult to implement in laboratories from low-resource countries. Recently CLSI endorsed two MIC-based alternative methods for testing colistin in Enterobacterales and P. aeruginosa, a colistin broth disk elution (CBDE) and a colistin agar test (CAT).In this work, we propose two simple methodologies, related to CLSI methods, to screen for colistin resistance, with a performance equivalent to the reference method in detecting resistance to colistin, both of plasmid (mcr) and chromosomal nature. Furthermore, the methods validated here allowed a better identification of those producers of mcr producer with borderline MICs. These screening tests can be routinely performed in addition to the tests currently in use, showed long stability during storage and some of them do not require colistin powder as the source of antibiotic, an important limitation in low-resource countries