Botulinum toxin type A versus botulinum toxin type B for cervical dystonia

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2016Background This is an update of a Cochrane review first published in 2003, and previously updated in 2009 (no change in conclusions). Cervical dystonia is the most common form of focal dystonia and is a disabling disorder characterized by painful involuntary head posturing. Botulinum toxin type A (BtA) is usually considered the first line therapy for this condition, although botulinum toxin type B (BtB) is an alternative option, with no compelling theoretical reason as to why it might not be as, or even more effective, than BtA. Objectives To compare the efficacy, safety, and tolerability of botulinum toxin type A versus botulinum toxin type B in cervical dystonia. Search methods We identified studies for inclusion in the review using the Cochrane Movement Disorders Group trials register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and conference proceedings, last run in October 2015. Search was unrestricted by language. Selection criteria Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus BtB in adult patients with cervical dystonia. Data collection and analysis Two independent authors assessed records, selected included studies, extracted data using a paper pro forma and evaluated the risk of bias. Disagreements were solved by consensus or by a third author. We performed one meta-analysis for the comparison BtA versus BtB. We used random-effects models in the presence of considerable heterogeneity and fixed-effect models when there was no heterogeneity. We performed no subgroup analyses. The primary efficacy outcome was overall improvement on any validated symptomatic rating scale. The primary safety outcome was the proportion of participants with any adverse event.Main results Three RCTs of low-to-moderate overall methodological quality including 270 participants with cervical dystonia were included. Two studies exclusively enrolled patients known to have a positive response to BtA treatment, therefore including an enriched population with higher probability of benefit from BtA treatment. None of the trials were independently funded. All RCTs evaluated the effect of a single Bt treatment session using doses between 100 and 250U of BtA and 5000 to 10000U of BtB. We found no difference between the two types of botulinum toxin in terms of overall efficacy and safety, as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the number of adverse events, respectively. However, when compared to BtA, treatment with BtB was associated with an improvement of 0.99 points (95% CI: 0.12 to 1.85; I2=0%) on the TWSTRS pain sub-scale at weeks 2-4 after injection, as well as with an increased risk of treatment-related dysphagia with a risk ratio (RR) of 0.49, favouring the BtA group (95% CI: 0.32 to 0.75, I2=27%) and sore throat/dry mouth, with a RR of 0.42 favouring the BtA group (95% CI: 0.31 to 0.57, I2=77%). The two types of botulinum toxin were otherwise shown to be clinically non-distinguishable in all the remaining outcomes. Authors' conclusions A single treatment session of BtA and a single treatment session of BtB are equally effective and well tolerated in the treatment of adults with certain types of cervical dystonia. Treatment with BtB causes a greater decrease disease-associated pain whilst also increasing the rate of dysphagia and sore throat/dry mouth when compared to treatment with BtA. Overall, there is no clinical evidence to support or not support the preferential use of one form of botulinum toxin over another. There is no evidence from RCTs neither regarding comparative development of secondary non-responsiveness to botulinum toxin nor regarding quality of life domains with either treatment.A distonia cervical compreende uma patologia neurológica pouco frequente com impacto negativo na qualidade de vida dos doentes. O tratamento de primeira linha é com efetuado com recuro a injecções intramusculares de toxina botulínica, que está disponível comercialmente em dois tipos: a toxina botulínica tipo A e a toxina botulínica tipo B. Esta revisão sistemática Cochrane visa comparar estes dois compostos em relação à sua eficácia e segurança no tratamento da distonia cervical. Após um processo de pesquisa sistemática para ensaios aleatorizados sobre o tema, extração de dados e combinação dos mesmos com recurso a técnicas de combinação por meta-análise, demonstrou-se que não existem diferenças nos perfis de eficácia e segurança entre ambas as formulações de toxina botulínica, com as exepções de uma subescala de doença (avaliador dor) e a proporção de doentes com efeitos adversos específicos

Heart rate variability behavior in athletes after a sports concussion: A systematic review

Objective This systematic review aims to investigate the adaptations of the autonomic nervous system (ANS) after a concussion by measuring HRV in athletes over the age of 16 after injury. Methods This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Web of Science, Pubmed, SCOPUS, and Sport Discus were searched using predefined search terms to identify relevant original cross-sectional, longitudinal, and cohort epidemiological studies published before December 2021. Results After screening 1737 potential articles, four studies met the inclusion criteria. Studies included participants with concussion (n = 63) and healthy control athletes (n = 140) who practised different sports. Two studies describe a decrease in HRV following a sports concussion, and one proposed that the resolution of symptoms does not necessarily reflect ANS recovery. Lastly, one study concluded that submaximal exercise induces alteration in ANS, not seen in rest after an injury. Conclusions In the frequency domain, a decrease in high frequency power and an increase of low frequency/high frequency ratio is expected, as the activity of the sympathetic nervous system increases, and the parasympathetic nervous system decreases after injury. In the frequency domain, heart rate variability (HRV) may help monitor the activity of ANS evaluating signals of somatic tissue distress and early identification of other types of musculoskeletal injuries. Further research should investigate the relationship between HRV and other musculoskeletal injuries.info:eu-repo/semantics/publishedVersio

O efeito dos extractos de cereja em células humanas do cancro da próstata: Do cultivo à clínica?

A proliferação descontrolada das células da próstata é uma condição observada normalmente na população masculina à medida que esta envelhece, e está associada com o desenvolvimento do cancro da próstata. Assim, estratégias que visem diminuir a proliferação dos tecidos prostáticos durante o seu envelhecimento deverão diminuir a prevalêcia desta condição médica. As cerejas são ricas em compostos fenólicos como as antocianinas, com efeitos antioxidantes e anti-proliferativos bem estudados em células cancerígenas como as MCF-7 (cancro da mama) e HCT116 (cancro colo-rectal). O estudo elaborado para esta dissertação pretendeu avaliar o efeito de extractos da cereja Saco, uma variedade local da região do Fundão, na viabilidade, apoptose, e metabolismo glicolítico das células não-neoplásicas do epitélio da próstata PNT1A, nas células neoplásicas androgeno-dependentes LNCap, e nas células neoplásicas androgeno-independentes PC3. As cerejas foram descaroçadas, liofilizadas, e a sua extracção efectuada recorrendo a ultrassons e utilizando metanol acidificado com 0,1% HCl como solvente. O extracto obtido foi então dissolvido em meio de cultura celular a várias concentrações (0, 2, 20, 200 e 2000 µg/mL) e utilizado para tratar as células não-neoplásicas e neoplásicas durante 48, 72 e 96 horas. A viabilidade celular nas diferentes condições experimentais foi determinada por ensaios MTT. Globalmente, a viabilidade celular mais baixa foi observada às 72 horas e com 20 µg/mL de extracto de cereja, e estas condições foram utilizadas para avaliar os efeitos dos extractos de cereja na proliferação,apoptose e metabolismo glicolítico das células PNT1A, LNCaP e PC3. A análise à expressão génica e a actividade dos reguladores-alvo destes processos biológicos foram efectuadas através da metodologia de Western Blots e kits de análises bioquimicas, respectivamente. O consumo de glucose e a produção de lactato foram ambos medidos por análise espectofotométrica. Os resultados obtidos demonstraram que a administração dos extractos metanólicos de cereja aumentou a apoptose das células LNCaP, um efeito não-confirmado nas células não-neoplásicas PNT1A. Curiosamente, as células PC3 mostraram uma diminuição da actividade apoptótica na presença dos extractos de cereja, apesar da proliferação diminuída. Quanto ao metabolismo glicolítico, foi observado que as células PNT1A tratadas com extractos de cereja apresentaram uma diminuição parcial deste, enquanto que as células LNCaP demonstraram uma supressão da metabolização da glucose em resposta aos extractos de cereja, com consumo de glucose e produção de lactato ambos diminuídos, acompanhados por alterações da expressão/actividade de transportadores e enzimas glicolíticas. Analogamente aos resultados da apoptose, as células PC3 apresentaram um comportamento distinto das LNCaP relativamente ao metabolismo glicolítico; os extractos de cereja induziram um aumento da glicólise e da produção de lactato. Os presentes resultados indicam que os extractos metanólicos de cereja podem ter efeitos benéficos nas células do cancro da próstata, tanto neoplásicas como não-neoplásicas, diminuindo a sua proliferação e controlando as vias apoptóticas e glicolíticas, produzindo efeitos mais visíveis no caso das células sensíveis à ação dos androgénios, LNCaP.The uncontrolled proliferation of prostate cells is a condition commonly observed in the ageing male population, which is associated with the development of prostate cancer. Thus, strategies to counteract the proliferative feature of aging prostatic tissues should prove beneficial by diminishing the widespread prevalence of this condition. Sweet cherries are rich in phenolic compounds such as anthocyanins, with widely studied anti-proliferative and antioxidant effects in different types of cancer cells such as MCF-7 (human breast) and HCT116 (human colorectal). The present study aimed to evaluate the effect of crude extracts of Saco sweet cherry, a local cultivar from the Fundão region (Portugal), on the viability, apoptosis and glycolytic metabolism of non-neoplastic PNT1A prostate epithelial cells, and androgen-sensitive LNCaP cells and androgen-insensitive PC3 prostate cancer cells. Sweet cherries were seeded, freeze-dried, and underwent ultrasound-assisted extraction with methanol acidified with HCl 0.1%. The extract was then dissolved in cell culture medium at several concentrations (0, 2, 20, 200 and 2000 µg/mL) and used to treat non-neoplastic and neoplastic prostate cells for 48, 72 and 96 hours. Cell viability at different experimental conditions was determined by MTT assay. Overall, the lowest viability was observed at 72 hours of culture with 20 µg/mL of cherry extract, and these conditions were used to evaluate the effect of cherry extracts on the cell proliferation, apoptosis and glycolytic metabolism of PNT1A, LNCaP and PC3 cells. Gene expression analysis and activity of target regulators of the aforementioned biological processes was assessed by means of Western blot and biochemical assays, respectively. Glucose consumption and lactate production were measured spectrophotometrically. The obtained results demonstrated that the administration of methanolic cherry extracts increased the apoptotic rate of LNCaP cells, an effect not confirmed in the non-neoplastic PNT1A cells. Curiously, PC3 cells had an overall down-regulation of apoptotic activity in the presence of cherry extracts, in spite of its decreased proliferation. Concerning metabolism, it was found that treated PNT1A cells had a partial down-regulation of glycolytic metabolism, while LNCaP cells markedly displayed a suppression of this process with decreased glucose consumption and lactate production, which was accompanied by altered expression/activity of glycolytic transporters and enzymes. Analogously with the results of apoptosis, PC3 cells had a distinct behavior relatively to LNCaP in what concerns glycolytic metabolism; cherry extracts induced an up-regulation of glycolysis and lactate production. The present findings indicate that cherry methanolic extracts may have beneficial effects on prostate cells, both neoplastic and non-neoplastic, diminishing proliferation and controlling the apoptotic and glycolytic pathways, producing more visible effects in the case of the androgen-sensitive LNCaP cells

A igreja matriz de Monchique

Dissertação de mest., História da Arte, Faculdade de Ciências Humanas e Sociais, Univ. do Algarve, 2012O tema deste trabalho, que incide sobre a Igreja matriz de Monchique, apresenta um carácter monográfico, descritivo e interpretativo. O objectivo é fazer uma análise do monumento e saber as suas origens, encomendantes, autores e cronologias. A partir do trabalho de seminário Dando Logar a Monchique realizado para a licenciatura em Património Cultural, na parte que à igreja matriz diz respeito, aprofundou-se a observação, investigou-se e compilou-se bibliografia, foi sistematizada e relacionada a informação obtida. Surgiram ideias e colocaram-se hipóteses sobre algumas premissas como a contextualização no espaço, a influência da história nacional e regional, a intervenção directa ou indirecta de pessoas e entidades colectivas, a religião e a arte. Esta dissertação de mestrado é o resultado desse esforço no sentido de avançar no conhecimento deste templo quinhentista

Half Friend, Half Enemy? Comparative Phytophagy between Two Dicyphini Species (Hemiptera: Miridae)

Despite their importance as biological control agents, zoophytophagous dicyphine mirids can produce economically important damage. We evaluated the phytophagy and potential impact on tomato plants of Dicyphus cerastii and Nesidiocoris tenuis. We developed a study in three parts: (i) a semi-field trial to characterize the type of plant damage produced by these species on caged tomato plants; (ii) a laboratory experiment to assess the effect of fruit ripeness, mirid age, and prey availability on feeding injuries on fruit; and (iii) a laboratory assay to compare the position of both species on either fruit or plants, over time. Both species produced plant damage, however, although both species produced scar punctures on leaves and necrotic patches on petioles, only N. tenuis produced necrotic rings. Both species caused flower abortion at a similar level. Overall, N. tenuis females produced more damage to tomato fruit than D. cerastii. There was an increased frequency of D. cerastii females found on the plants over time, which did not happen with N. tenuis. Our results suggested that, although D. cerastii caused less damage to fruit than N. tenuis, it still fed on them and could cause floral abortion, which requires field evaluation and caution in its use in biological control strategiesinfo:eu-repo/semantics/publishedVersio

Changes in Vessel Traffic Disrupt Tidal Flats and Saltmarshes in the Tagus Estuary, Portugal

The Tagus Estuary is one of the largest in Europe with 320 km2 , and it has been, for centuries, a gateway to Lisbon. This study focuses on the Moita-Montijo Bay and on the recent dynamics of its tidal flats and saltmarshes. Aerial photographs, orthomosaics, and very high-resolution satellite imagery were used to analyze landcover and shoreline changes. Tidal flats have shown expansion from 1977 to 1995, but since then, contraction dominated, with a change of position of the tidal flat edge of−2.8 m/year in the north bank and−4.2 m/year in the south bank of the Montijo channel. Most contraction occurred along the route of the fast transport catamarans that started operating in 1995, while in the sector without catamaran navigation, expansion was observed. Saltmarshes have been suffering contraction since 1958, with increased rates after 1995 (−0.38 to−0.44 m/year), especially along the catamaran route (−0.57 to−1.27 m/year). The analysis of the wake generated by different vessel types shows a wake increase with the catamarans, in agreement with the increase in contraction along the Montijo channel. Inside abandoned salt pans, saltmarshes expanded. Since 1995, major changes are also observed along the tidal flat margin, with the formation of coarse lag deposits of coarse sands and shells. Given the contraction increase associated with catamaran traffic and the resulting degradation of the tidal flat and the saltmarshes, it is important to introduce measures for containing contraction.info:eu-repo/semantics/acceptedVersio

Tetrabenazine versus deutetrabenazine for Huntington's disease : twins or distant cousins?

© 2017 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: Tetrabenazine is the only US Food and Drug Administration‐approved drug for Huntington's disease, and deutetrabenazine was recently tested against placebo. A switching‐trial from tetrabenazine to deutetrabenazine is underway, but no head‐to‐head, blinded, randomized controlled trial is planned. Using meta‐analytical methodology, the authors compared these molecules. Methods: RCTs comparing tetrabenazine or deutetrabenazine with placebo in Huntington's disease were searched. The authors assessed the Cochrane risk‐of‐bias tool, calculated indirect treatment comparisons, and applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: The evidence network for this report comprised 1 tetrabenazine trial and 1 deutetrabenazine trial, both against placebo. Risk of bias was moderate in both. Participants in the tetrabenazine and deutetrabenazine trials did not differ significantly on motor scores or adverse events. Depression and somnolence scales significantly favored deutetrabenazine. Conclusion: There is low‐quality evidence that tetrabenazine and deutetrabenazine do not differ in efficacy or safety. It is important to note that these results are likely to remain the only head‐to‐head comparison between these 2 compounds in Huntington's disease.info:eu-repo/semantics/publishedVersio

Analysis of the Cochrane review : topical treatments for scalp psoriasis : Cochrane Database Syst Rev. 2016;2:CD009687

Copyright © Ordem dos Médicos 2017Regardless the psoriasis subtype, up to 79% of people with this skin condition present scalp involvement, which is often the first site to show symptoms of the disease. In addition to being itchy, the red and scaly lesions are usually easy to see, and may be embarrassing. Topical therapy is usually the first line of treatment; however the wide array of available interventions can make the choice difficult, and may even lead to an inadequate treatment. The objective of this review was to evaluate the efficacy and safety of topical treatments for scalp psoriasis. A systematic review was performed according to the methodology recommended by Cochrane in order to evaluate the clinical severity of psoriasis, quality of life, and adverse events that led to treatment discontinuation. To evaluate this, 59 studies were included, with a total of 11 561 participants, and 15 comparisons were made between the various drugs and application vehicles tested. The principal conclusion is that corticosteroids of high or very high potency are more effective than vitamin D. The combination of a corticosteroid with vitamin D has only a marginal benefit over corticosteroid monotherapy, but is superior to vitamin D alone. Given the similar safety profile and only marginal benefit of the combination of corticosteroid with vitamin D over the corticosteroid alone, topical corticosteroid monotherapy appears to be fully acceptable for short-term therapy of scalp psoriasis.Independentemente do tipo de psoríase, até 79% dos doentes com esta patologia apresentam atingimento do couro cabeludo, sendo este frequentemente o primeiro local a mostrar sintomas da doença. Para além do prurido, as lesões avermelhadas e escamosas são visíveis e muitas vezes embaraçosas. A terapêutica tópica é geralmente a primeira opção para estes doentes, no entanto a ampla gama de tratamentos disponíveis pode muitas vezes dificultar a escolha e levar a um tratamento potencialmente desadequado. O objetivo desta revisão foi avaliar a eficácia e a segurança dos tratamentos tópicos para a psoríase do couro cabeludo. Foi efetuada uma revisão sistemática de acordo com a metodologia preconizada pela Cochrane, com vista à avaliação da redução da gravidade clínica da psoríase, melhoria da qualidade de vida e efeitos adversos que motivassem a suspensão do tratamento. Para tal, foram incluídos 59 estudos, com um total de 11 561 participantes, tendo sido efetuadas 15 comparações entre os vários fármacos e veículos de aplicação testados. Os resultados obtidos sugerem que os corticosteroides de potência elevada ou muito elevada são mais eficazes que a vitamina D. A combinação de um corticosteroide com a vitamina D tem apenas um benefício marginal em relação à monoterapia com corticosteroide, mas é superior à vitamina D isolada. Dado o perfil de segurança semelhante e o benefício apenas marginal da combinação corticosteroide com vitamina D sobre o corticosteroide isolado, a monoterapia com corticosteroide tópico parece ser aceitável para a terapia a curto prazo da psoríase do couro cabeludo.info:eu-repo/semantics/publishedVersio

Análise da revisão Cochrane : antihistamínicos para a constipação : Cochrane Database Syst Rev. 2015;11:CD009345

Copyright © Ordem dos Médicos 2016The common cold is an acute, self-limiting inflammation of the mucosa of the upper airways, which may involve one or all the sinuses, nasopharynx, oropharynx and larynx. It is common to have at least one episode per year. Common cold symptoms, which may include sore throat, sneezing, nasal congestion, runny nose, headache, malaise and mild fever usually disappear within a few days without treatment. The causative agent of most colds is rhinovirus. Although not associated with mortality, common cold is associated with significant morbidity. There is no vaccine or cure for common cold and, therefore, their treatment is centered on relieving the symptoms. This Cochrane review aimed to synthesize the existing evidence about the clinical benefit of antihistamines, used as monotherapy, compared with placebo or no treatment in children and adult patients with common cold. A total of 18 randomized clinical trials with 4342 participants were included. Main results were: 1) Antihistamines have a small (days one and two) beneficial effect in the short term on the severity of overall symptoms in adult patients, although this effect is not present in the medium to long term; 2) antihistamines were not associated with a clinically significant beneficial effect on the individual symptoms (nasal congestion, rhinorrhea, and sneezing); 3) Antihistamines are not associated with an increased risk of adverse effects; 4) No conclusion can be made about the effectiveness of antihistamines in pediatric populations. Our interpretation of the results is that the available evidence is insufficient to support the prescription or buying OTC antihistamines to relieve the symptoms of common cold without allergic component.A constipação representa uma inflamação aguda e autolimitada da mucosa das vias aéreas superiores, que pode envolver uma ou todas de entre os seios perinasais, rinofaringe, orofaringe e laringe. É comum ter-se pelo menos um episódio por ano. Os sintomas da constipação, que podem incluir dor de garganta, crises esternutatórias, congestão nasal, rinorreia, cefaleias, mal-estar e febre baixa geralmente desaparecem dentro de alguns dias sem tratamento. O agente etiológico da maioria das constipações é o rinovírus. Embora não esteja associado letalidade, a constipação é associada com morbidade significativa. Não existe vacina ou cura para a constipação e, portanto, o seu tratamento está centrado em aliviar os sintomas. Esta revisão Cochrane teve como objetivo sintetizar a evidência existente sobre o benefício clínico de anti-histamínicos, utilizados em monoterapia, em comparação com placebo ou nenhum tratamento, em crianças e em doentes adultos com constipação. Foram incluídos um total de 18 ensaios clínicos aleatorizados, com um total de 4 342 participantes. Os principais resultados foram: 1) Anti-histamínicos têm um pequeno (dias um e dois de tratamento) efeito benéfico a curto-prazo sobre a gravidade dos sintomas globais em doentes adultos, embora este efeito não esteja presente no médio a longo prazo; 2) Os anti-histamínicos foram associados com um efeito benéfico não clinicamente relevante sobre os sintomas individuais (congestão nasal, rinorreia e esternutos); 3) Os anti-histamínicos não estão associados com um risco aumentado de efeitos adversos; 4) Nenhuma conclusão pode ser feita sobre a eficácia dos anti-histamínicos em populações pediátricas. A nossa interpretação dos resultados é que a evidência disponível é insuficiente para apoiar a prescrição ou a compra de anti-histamínicos de venda-livre para aliviar os sintomas da constipação sem componente alérgico.info:eu-repo/semantics/publishedVersio