Muscarinic Modulation of High Frequency Oscillations in Pedunculopontine Neurons

We previously reported that persistent application of the non-specific cholinergic agonist carbachol (CAR) increased the frequency of calcium channel-mediated oscillatory activity in pedunculopontine nucleus (PPN) neurons, which we identified as dependent on voltage-gated, high-threshold P/Q-type channels. Here, we tested the hypothesis that M2 muscarinic receptors and G-proteins associated with M2 receptors mediate the increase in oscillatory frequency in PPN neurons. We found, using depolarizing ramps, that patch clamped 9–12 day old rat PPN neurons (n = 189) reached their peak oscillatory activity around −20 mV membrane potential. Acute (short duration) application of CAR blocked the oscillatory activity through M2 muscarinic receptors, an effect blocked by atropine. However, persistent (long duration) application of CAR significantly increased the frequency of oscillatory activity in PPN neurons through M2 receptors [40 ± 1 Hz (with CAR) vs. 23 ± 1 Hz (without CAR); p < 0.001]. We then tested the effects of the G-protein antagonist guanosine 5′-[β-thio] diphosphate trilithium salt (GDP-β-S), and the G-protein agonist 5′-[γ-thio] triphosphate trilithium salt (GTP-γ-S). We found, using a three-step protocol in voltage-clamp mode, that the increase in the frequency of oscillations induced by M2 cholinergic receptors was linked to a voltage-dependent G-protein mechanism. In summary, these results suggest that persistent cholinergic input creates a permissive activation state in the PPN that allows high frequency P/Q-type calcium channel-mediated gamma oscillations to occur

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Aguas del Iténez o Guaporé

Bolivia y Brasil comparten una de las cuencas más atractivas y preservadas de la te-giuri amazônica: la cuenca del rio llénez o Guaporé, que escurre tanto sobre el lecho rocoso del Escudo Precámbrico Brasilefto como sobre las Hanuras del Beni. Estas influencias hacen que la cuenca del iténez tenga una elevada heterogeneidad de habitats, una fauna acuálica peculiar y un alto valor de conservation. Este patrimo­nio binacional posée un potencial importante para la conservación de la diversidad regional y cl dcsar rollo sostcniblc participativo de las comunidades locales. El libro contiene un resumen del conotimìento de la cuenca y sus recursos, generado en los últimos 10 anos por un equipo de investigadores bolivianos, brasilefios y de otras nacionalidades. Se presenta una descripeión del medio fisico, así como resultados relevantes sobre la biodiversidad acuática, con énfasis en algas, peces, reptiles y mamíferos. El aporte más notable del libro, adernas de la descripeión ecológica del ecosistema, son las lecciones aprendidas que surgieron de experiências locales sobre la élaboration participativa de herramientas para la gestion de los recursos hidrobiológicos.A Bolívia e o Brasil compartilham uma das bacias hidrográficas mais atrativas e preservadas da região amazônica: a bacia do Rio Iténez ou Guaporé. A combinação das influências do escudo pré-cambriano brasileiro e da planícies do Beni é uma das razões pela qual existem na região elevada heterogeneidade de habitats, fauna aquática peculiar e alto grau valor dc conservação. Eslc patrimônio binacional possui potencial significativo para a conservação da diversidade regional e desenvolvimento sustentável participativo das comunidades locais. O livro contém um resumo do conhecimento da bacia e seus recursos, gerado nos últimos dez anos por uma equipe de pesquisadores bolivianos, brasileiros e de outras nacionalidades. Apresentamos uma descrição do meio físico, bem como resultados relevantes da biodiversidade aquática, com ênfase em algas, peixes, répteis e mamíferos. A contribuição mais notável do livro, além da descrição ecológica do ecossistema, é a descrição das lições aprendidas que surgiram a partir de experiências locais sobre elaboração participativa de ferramentas para a gestão dos recursos aquáticos presentes nesta bacia

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Estudio del incremento volumétrico del Cupressus lusitanica Mill. en relación a la edad y al sitio

Tesis (M. Sc) -- IICA, Turrialba (Costa Rica), 195