Tissue-specific effects of acetylcholine in the canine heart

Acetylcholine (ACh) release from the vagus nerve slows heart rate and atrioventricular conduction. ACh stimulates a variety of receptors and channels, including an inward rectifying current [ACh-dependent K(+) current (I(K,ACh))]. The effect of ACh in the ventricle is still debated. We compared the effect of ACh on action potentials in canine atria, Purkinje, and ventricular tissue as well as on ionic currents in isolated cells. Action potentials were recorded from ventricular slices, Purkinje fibers, and arterially perfused atrial preparations. Whole cell currents were recorded under voltage-clamp conditions, and unloaded cell shortening was determined on isolated cells. The effect of ACh (1–10 μM) as well as ACh plus tertiapin, an I(K,ACh)-specific toxin, was tested. In atrial tissue, ACh hyperpolarized the membrane potential and shortened the action potential duration (APD). In Purkinje and ventricular tissues, no significant effect of ACh was observed. Addition of ACh to atrial cells activated a large inward rectifying current (from −3.5 ± 0.7 to −23.7 ± 4.7 pA/pF) that was abolished by tertiapin. This current was not observed in other cell types. A small inhibition of Ca(2+) current (I(Ca)) was observed in the atria, endocardium, and epicardium after ACh. I(Ca) inhibition increased at faster pacing rates. At a basic cycle length of 400 ms, ACh (1 μM) reduced I(Ca) to 68% of control. In conclusion, I(K,ACh) is highly expressed in atria and is negligible/absent in Purkinje, endocardial, and epicardial cells. In all cardiac tissues, ACh caused rate-dependent inhibition of I(Ca.

Applications of long period gratings in solid core photonic bandgap fibers

Solid core photonic bandgap fibres are photonic crystal fibres with a solid core surrounded by high index inclusions. The guidance properties of these fibers are very sensitive to the refractive index of the inclusions, making them widely tunable and making them very promising for sensing applications. Combining these fibers with long period gratings unleashes their full potential, enabling narrow band notch filters tunable over hundreds of nm, refractive index sensors with sensitivity comparable to that of surface plasmon resonance sensors, but also the extraction of the full band diagrams of these bandgap fibres

Integration of paper microfluidic sensors into contact lenses for tear fluid analysis

In this article, using the integration of paper microfluidics within laser-inscribed commercial contact lenses, we demonstrate the multiplexed detection of clinically relevant analytes including hydrogen ions, proteins, glucose, nitrites and l-ascorbic acid, all sampled directly from model tears. In vitro measurements involved the optimization of colorimetric assays, with readouts collected, stored and analyzed using a bespoke Tears Diagnostics smartphone application prototype. We demonstrate the potential of the device to perform discrete measurements either for medical diagnosis or disease screening in the clinic or at the point-of-care (PoC), with future applications including monitoring of ocular infections, uveitis, diabetes, keratopathies and assessing oxidative stress

Identification of IKr Kinetics and Drug Binding in Native Myocytes

Determining the effect of a compound on IKr is a standard screen for drug safety. Often the effect is described using a single IC50 value, which is unable to capture complex effects of a drug. Using verapamil as an example, we present a method for using recordings from native myocytes at several drug doses along with qualitative features of IKr from published studies of HERG current to estimate parameters in a mathematical model of the drug effect on IKr. IKr was recorded from canine left ventricular myocytes using ruptured patch techniques. A voltage command protocol was used to record tail currents at voltages from −70 to −20 mV, following activating pulses over a wide range of voltages and pulse durations. Model equations were taken from a published IKr Markov model and the drug was modeled as binding to the open state. Parameters were estimated using a combined global and local optimization algorithm based on collected data with two additional constraints on IKrI–V relation and IKr inactivation. The method produced models that quantitatively reproduce both the control IKr kinetics and dose dependent changes in the current. In addition, the model exhibited use and rate dependence. The results suggest that: (1) the technique proposed here has the practical potential to develop data-driven models that quantitatively reproduce channel behavior in native myocytes; (2) the method can capture important drug effects that cannot be reproduced by the IC50 method. Although the method was developed for IKr, the same strategy can be applied to other ion channels, once appropriate channel-specific voltage protocols and qualitative features are identified

Resposta glicêmica de ratos submetidos ao treinamento de duas modalidades desportivas / Glycemic response of rats submitted to two sports modalities training

Introdução. O exercício físico é uma condição na qual ocorre uma elevação da exigência de diversos sistemas orgânicos com subsequente ativação de mecanismos de mobilização de substratos energéticos, através das vias aeróbias ou anaeróbias, resultando no aumento da disponibilidade de oxigênio, oxidação de gorduras, além do transporte e utilização de glicose. Objetivo: analisar resposta glicêmica de ratos antes e após o treinamento de duas modalidades esportivas. Métodos. A pesquisa foi aprovada pelo Comitê de Ética para o Uso de Animais (CEUA) da Universidade Estadual do Ceará (UECE), sob o protocolo nº 7007456/2015 de 04/03/2016. Foram utilizadas 14 ratas fêmeas albinas da linhagem Wistar com massa corporal entre 200 ± 15 g. Os animais foram distribuídos em dois grupos experimentais, cada grupo contendo (n = 07) animais, sendo: Corrida e Natação. O treino de corrida ocorreu em uma esteira adaptada para roedores. O treino de natação ocorreu em um recipiente de plástico com água aquecida e incrementos de carga na cauda do animal equivalente a 8% da massa corporal. Ambos os treinamentos iniciaram com 3 minutos e finalizaram com 30 minutos, seis vezes por semana durante quatro semanas. Os níveis de glicemia foram analisados por meio de um glicosímetro Accu-Chek Active®, antes e após os treinos, no qual foi coletado 10 µL de sangue da extremidade distal da cauda de cada animal para determinação da glicemia. Para a análise estatística utilizou-se o teste t de Student (p0,05). Os resultados foram expressos em média ± erro padrão da média. Resultados. Os valores obtidos foram: Corrida [antes] (61,71 mg/dL ± 5,42) e Corrida [depois] (111,14 mg/dL ± 5,06), p0,0003; Natação [antes] (71,42 mg/dL ± 5,96) e Natação [depois] (65,00 mg/dL ± 5,97), p=0,3068. Observou-se que houve um aumento estatisticamente significativo no grupo corrida após o treino, o que não ocorreu nos animais submetidos a natação. Conclusão. Verificou-se que o treino de corrida foi capaz de aumentar os níveis séricos de glicose, sugerindo maior mobilização desta durante a referida modalidade, o que não ocorreu durante a natação

TRACIONAMENTO ORTODÔNTICO DE ELEMENTOS DENTAIS COM PERDA DE ESPAÇO BIOLÓGICO

Para restaurações bem-sucedidas em dentes fraturados, onde a saúde dos tecidos periodontais é necessária, a extrusão ortodôntica radicular se tornou uma abordagem ortodôntica necessária. Esse procedimento oferece uma abordagem conservadora, mantendo o espaço biológico e protegendo o suporte periodontal. Para garantir resultados impressionantes, seja a extrusão lenta ou rápida, o tratamento requer uma avaliação específica de comprimento radicular, estética e idade do paciente. Embora apresente várias vantagens, como preservar o suporte ósseo e preservar a integridade periodontal, é importante levar em consideração suas limitações e possíveis complicações. Para evitar recidivas, o tratamento requer cuidados especiais durante e após. Assim, o tratamento radicular se destaca como uma ferramenta essencial na restauração de dentes fraturados, oferecendo não apenas melhorias estéticas, mas também melhorias na saúde do paciente

Developing a utility index for the Aberrant Behavior Checklist (ABC-C) for fragile X syndrome

Purpose This study aimed to develop a utility index (the ABC-UI) from the Aberrant Behavior Checklist-Community (ABC-C), for use in quantifying the benefit of emerging treatments for fragile X syndrome (FXS). Methods The ABC-C is a proxy-completed assessment of behaviour and is a widely used measure in FXS. A subset of ABC-C items across seven dimensions was identified to include in health state descriptions. This item reduction process was based on item performance, factor analysis and Rasch analysis performed on an observational study dataset, and consultation with five clinical experts and a methodological expert. Dimensions were combined into health states using an orthogonal design and valued using time trade-off (TTO), with lead-time TTO methods used where TTO indicated a state valued as worse than dead. Preference weights were estimated using mean, individual level, ordinary least squares and random-effects maximum likelihood estimation [RE (MLE)] regression models. Results A representative sample of the UK general public (n = 349; mean age 35.8 years, 58.2 % female) each valued 12 health states. Mean observed values ranged from 0.92 to 0.16 for best to worst health states. The RE (MLE) model performed best based on number of significant coefficients and mean absolute error of 0.018. Mean utilities predicted by the model covered a similar range to that observed. Conclusions The ABC-UI estimates a wide range of utilities from patient-level FXS ABC-C data, allowing estimation of FXS health-related quality of life impact for economic evaluation from an established FXS clinical trial instrument

The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK

OBJECTIVES: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy. METHODS: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them. RESULTS: In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases). CONCLUSIONS: A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease

ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe