Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target

Qualidade das anotações de enfermagem relacionadas à ressuscitação cardiopulmonar comparadas ao modelo Utstein Calidad de las anotaciones de enfermería relacionadas a la resucitación cardiopulmonar comparadas con el modelo Utstein Quality of nursing records related to cardiopulmonary resuscitation compared to the Utstein model

OBJETIVO: Analisar a qualidade das anotações de enfermagem relacionadas à ressuscitação cardiopulmonar, comparando-as ao protocolo validado Utstein, em um hospital universitário. MÉTODOS: Estudo retrospectivo, exploratório, descritivo, de abordagem quantitativa, realizado por meio de consulta a prontuários de pacientes que sofreram parada cardiorrespiratória (PCR) seguida de óbito. A coleta de dados foi realizada no período de 1° de maio a 30 de junho de 2009. RESULTADOS: Dos 144 prontuários consultados, 74 foram dispensados por não haver nenhuma informação registrada dos itens a serem estudados e, 70 constituíram a amostra do estudo. Nestes, não havia anotações referentes à causa imediata da PCR (92%), intervenções realizadas na tentativa de recuperação cardiorrespiratória (RCP) (71%), ritmo inicial de PCR (59%), hora dos eventos (16%), drogas utilizadas (50%) e profissionais envolvidos na RCP (88%). CONCLUSÕES: As anotações foram escassas e, frequentemente, não realizadas. A utilização do modelo Utstein favorece a anotação sequencial dos eventos, evitando a perda de dados.<br>OBJETIVO: Analizar la calidad de las anotaciones de enfermería relacionadas a la resucitación cardiopulmonar, comparándolas con el protocolo validado Utstein, en un hospital universitario. MÉTODOS: Estudio retrospectivo, exploratorio, descriptivo, de abordaje cuantitativo, realizado por medio de consulta a fichas de pacientes que sufrieron parada cardiorespiratoria (PCR) seguida de muerte. Los datos fueron recolectados en el período de 1° de mayo a 30 de junio de 2009. RESULTADOS: Entre las 144 fichas consultadas, 74 fueron liberadas por no haber ninguna información registrada de los ítems a ser estudiados y, 70 constituyeron la muestra del estudio. En estas, no habían anotaciones sobre la causa inmediata de la PCR (92%), intervenciones realizadas tratando de recuperar la parada cardiorespiratoria (RPC) (71%), ritmo inicial de PCR (59%), hora de los eventos (16%), drogas utilizadas (50%) y profesionales envueltos en la RPC (88%). CONCLUSIONES: Las anotaciones fueron escasas y, frecuentemente, no realizadas. La utilización del modelo Utstein favorece la anotación secuencial de los eventos, evitando la pérdida de datos.<br>OBJECTIVE: To assess the quality of nursing records related to cardiopulmonary resuscitation, comparing them to the validated Utstein protocol, in a university hospital. METHODS: Retrospective, exploratory and descriptive study, with quantitative approach, performed by means of consultation records of patients that suffered cardiorespiratory arrest (CRA) followed by death. The data collection was carried out in the period of May 1st to June 30th, in 2009. RESULTS: Of the 144 medical records surveyed, 74 were dismissed for not having any recorded information on the items to be studied and, 70 constituted the study sample. In these there were no entries on: the immediate cause of CRA (92%); the interventions seeking to recover the cardiorespiratoy arrest (RCA) (71%); on the initial rate of CRA (59%); on the time of events (16%); on drugs used (50%); and, on the professionals involved in RCA (88%). CONCLUSIONS: The notes were scarce and often not realized. The use of the Utstein model favors the annotation sequence of events, avoiding data loss

The impact of Helicobacter pylori resistance on the efficacy of a short course pantoprazole based triple therapy O impacto da resistência do Helicobacter pylori na eficácia de um esquema tríplice a curto prazo com pantoprazol

BACKGROUND: Many of the currently used Helicobacter pylori eradication regimens fail to cure the infection due to either antimicrobial resistance or poor patient compliance. Those patients will remain at risk of developing potentially severe complications of peptic ulcer disease. AIM: We studied the impact of the antimicrobial resistance on the efficacy of a short course pantoprazole based triple therapy in a single-center pilot study. METHODS: Forty previously untreated adult patients (age range 20 to 75 years, 14 males) infected with Helicobacter pylori and with inactive or healing duodenal ulcer disease were assigned in this open cohort study to 1 week twice daily treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and metronidazole 400 mg. Helicobacter pylori was assessed at entry and 50 ± 3 days after the end of treatment by rapid urease test, culture and histology of gastric biopsies. The criteria for eradication was a negative result in the tests. Susceptibility of Helicobacter pylori to clarithromycin and metronidazole was determined before treatment with the disk diffusion test. RESULTS: One week treatment and follow up were complete in all patients. Eradication of Helicobacter pylori was achieved in 35/40 patients (87.5%) and was higher in patients with nitroimidazole-susceptible strains [susceptible: 20/20 (100%), resistant: 10/15 (67%)]. There were six (15%) mild adverse events reports. CONCLUSIONS: A short course of pantoprazole-based triple therapy is well tolerated and effective in eradicating Helicobacter pylori. The baseline metronidazole resistance may be a significant limiting factor in treatment success.<br>OBJETIVO: Vários esquemas utilizados na erradicação do Helicobacter pylori falham por resistência ao antibiótico ou por pouca aderência ao tratamento pelo paciente. Esses pacientes permanecerão com alto risco de desenvolver complicações decorrentes da úlcera péptica. Assim, estudou-se o impacto da resistência antimicrobiana na eficácia de esquema tríplice em um único centro. MÉTODOS: Quarenta pacientes, virgens de tratamento para erradicação da bactéria (idade entre 20 e 75 anos, 14 homens) infectados pelo Helicobacter pylori e com úlcera duodenal ativa ou em cicatrização foram avaliados em um estudo aberto durante 1 semana com esquema de tratamento constituído por pantoprazol 40 mg, claritromicina 250 mg e metronidazol 400 mg, todos administrados duas vezes ao dia. A presença do Helicobacter pylori foi analisada no início e entre 50 ± 3 dias após o final do tratamento, pelo teste rápido da urease, cultura e histologia, obtidos através de biopsias gástricas. O critério de erradicação foi o resultado negativo em todos os testes. A susceptibilidade da claritromicina e metronidazol foi determinada antes do tratamento pelo teste de disco difusão em agar. RESULTADOS: O tratamento e o seguimento foi completo em todos os pacientes. A erradicação do Helicobacter pylori foi verificada em 35/40 pacientes (87,5%) e foi maior nos pacientes com cepas susceptíveis ao nitroimidazólico (susceptíveis 20/20 (100%), resistentes 10/15 (67%)). Seis pacientes (15%) referiram sintomas adversos leves. CONCLUSÕES: O esquema tríplice a curto prazo com pantoprazol é bem tolerado e efetivo na erradicação do Helicobacter pylori. A resistência ao metronidazol pode ser fator limitante significativo no sucesso terapêutico

The intertidal zone of the North-East Atlantic region: pattern and process.

The north-east Atlantic region is an area where clades originating in the north Pacific (fucoids, balanoids, littorinids, thaids, laminarians) collide with clades from further south in the Atlantic (e.g., patellids, trochids, chthamalids). At high latitudes in the north, seaweeds dominate the midshore zone of all but the most exposed shores. Further south, midshore space-occupying invertebrates (mussels and barnacles) win, facilitated by grazing by patellid limpets that controls algal recruitment; propagule pressure is much less as fucoids become rarer, and juvenile growth is slower due to environmental stress, thereby reducing the probability of escapes from grazing (Figure 2.4) (Ferreira et al., 2014, 2015a, 2015b). Low on the shore seaweeds dominate space by forming algal turfs or kelp or fucoid canopies. These algae outpace the ability of grazing limpets to control them in the low-intertidal zone. L. digitata canopies can lead to rock covered by encrusting algae and sponges, facilitating limpets. If canopy is removed, then colonising ephemeral algae and turf-forming algae swamp the limpets. There is usually too much water movement immediately either side of low water for effective foraging by sea urchins. Psammechinus miliaris and Echinus esculentus only appear in the subtidal, and Paracentrotus lividus is confined to refuges in burrows relying mainly on the drift of food (Benedetti-Cecchi and Cinelli, 1995;Boudouresque and Verlaque, 2007; Jacinto and Cruz, 2012). High on the shore, physical factors dominate. At high latitudes in the north of the Atlantic, ephemeral algae are present all year round. Further south they are only present in the winter, dying-off in the summer. Grazing has limited effects, only occurring around refuges that littorinids maintain (Stafford and Davies, 2005; Skov et al., 2010, 2011). Patterns are also strongly modified by mesoscale processes driven by upwelling that influences nutrient and larval supply (North Africa, Iberia) and coastal configuration, where embayed versus headlands also strongly influence larval supply (France northwards). In high-recruitment areas, interactions can be intense between spaceoccupying species, also driving predator abundance (e.g., dog whelks). Connell’s (1961a) classic paper on competition was possible on the Isle of Cumbrae because space was almost saturated; elsewhere lower larval supply would have created less intense interactions, as shown by Gordon and Knights (2017) in Plymouth. The north-east Atlantic has faster rates of warming than any other ocean, although the region south of Greenland and Iceland is undergoing cooling due to a climate-driven slowdown in the Atlantic meridional overturning circulation, causing a weakening in the Gulf Stream (Rahmstorf et al., 2015). Species are responding to rapid alterations in the marine climate by adapting or exhibiting range shifts, or by becoming locally extinct. There is a high degree of spatial and temporal heterogeneity in the resultant impacts on marine communities due to the idiosyncratic responses of individual species. Warming seas have resulted in biogeographic range shifts of intertidal and subtidal species in coastal waters of the northeast Atlantic. The leading range edges of Lusitanian species are expanding, while the trailing edges of boreal species are retracting to higher latitudes, but with some cold-water species showing surprising resilience (Southward et al., 1995; Mieszkowska et al., 2006, 2014b; Lima et al., 2007; Hawkins et al., 2008, 2009; Wethey and Woodin, 2008; Mieszkowska and Sugden, 2016). In addition to changes in the distribution ofspecies, community structure is also altering as species dominance and interactions change (Poloczanska et al., 2008; Hawkins et al., 2008, 2009; Mieszkowska et al., 2014b). In a warming world the midshore of France and the British Isles are likely to show much less cover by large canopy-forming fucoids as harsher warmer, drier and stormier conditions coupled with increased grazing pressure from more grazing species reduces the probability of fucoids recruiting to form adult populations. Lowshore kelp forests will likely change with less L. digitata and A. esculenta and more S. polyschides. The late autumn to early spring window of dense ephemeral algal growth high on the shore (Hawkins and Hartnoll, 1983a) will also constrict, except in the north and in extreme exposure. These changes will have consequences for biodiversity (Thompson et al., 1996; Smale et al., 2013; Teagle et al., 2017) and productivity (Hawkins et al., 1992) – particularly the decrease in export of algal detritus (Notman et al., 2016). More shores will become dominated by suspension-feeding barnacles and mussels. Thus, there will be switches on many mid-latitude shores as many become net importers rather than exporters of energy (Hawkins et al., 2008, 2009)