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1.
Midwifery ; 132: 103961, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479151

RESUMO

BACKGROUND: There is currently a gap in the evidence on how working practices, such as the ability to take rest breaks, finish on time or intershift recovery influence outcomes. AIM: The aim of this study was to explore the association of individual characteristics, work-related factors and working practices on emotional wellbeing outcomes of UK midwives. METHODS: An online cross-sectional survey collated data between September and October 2020. Outcomes explored were work-related stress, burnout, being pleased with their standard of care, job satisfaction and thoughts about leaving midwifery. Univariate analysis identified the explanatory variables to be investigated using multivariable logistic regression. FINDINGS: A total of 2347 midwives from the four UK nations completed the survey. No standard approach in monitoring safe staffing or in-shift or intershift recovery was found. There were high levels of work-related stress, burnout and thoughts about leaving midwifery, and low levels of job satisfaction, with just half of midwives reporting they were satisfied with the standard of care they could provide. Multivariable regression revealed that working practices variables, generally related to impeded recovery or compounded by staffing issues, had a significant association with poorer emotional wellbeing outcomes. CONCLUSION: This research has demonstrated an association between impeded recovery, including a lack of formal methods to monitor this, and poorer emotional wellbeing outcomes, and that staffing levels are highly influential in determining outcomes. There is a need to re-evaluate current approaches to job design and how midwives are expected to work.


Assuntos
Satisfação no Emprego , Enfermeiros Obstétricos , Admissão e Escalonamento de Pessoal , Humanos , Reino Unido , Estudos Transversais , Adulto , Inquéritos e Questionários , Feminino , Pessoa de Meia-Idade , Enfermeiros Obstétricos/psicologia , Enfermeiros Obstétricos/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/normas , Esgotamento Profissional/psicologia , Tocologia/métodos , Tocologia/estatística & dados numéricos
2.
Neurology ; 100(20): e2093-e2102, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-36977597

RESUMO

BACKGROUND AND OBJECTIVES: Urgent transient ischemic attack (TIA) management to reduce stroke recurrence is challenging, particularly in rural and remote areas. In Alberta, Canada, despite an organized stroke system, data from 1999 to 2000 suggested that stroke recurrence after TIA was as high as 9.5% at 90 days. Our objective was to determine whether a multifaceted population-based intervention resulted in a reduction in recurrent stroke after TIA. METHODS: In this quasi-experimental health services research intervention study, we implemented a TIA management algorithm across the entire province, centered around a 24-hour physician's TIA hotline and public and health provider education on TIA. From administrative databases, we linked emergency department discharge abstracts to hospital discharge abstracts to identify incident TIAs and recurrent strokes at 90 days across a single payer system with validation of recurrent stroke events. The primary outcome was recurrent stroke; with a secondary composite outcome of recurrent stroke, acute coronary syndrome, and all-cause death. We used an interrupted time series regression analysis of age-adjusted and sex-adjusted stroke recurrence rates after TIA, incorporating a 2-year preimplementation period (2007-2009), a 15-month implementation period, and a 2-year postimplementation period (2010-2012). Logistic regression was used to examine outcomes that did not fit the time series model. RESULTS: We assessed 6,715 patients preimplementation and 6,956 patients postimplementation. The 90-day stroke recurrence rate in the pre-Alberta Stroke Prevention in TIA and mild Strokes (ASPIRE) period was 4.5% compared with 5.3% during the post-ASPIRE period. There was neither a step change (estimate 0.38; p = 0.65) nor slope change (parameter estimate 0.30; p = 0.12) in recurrent stroke rates associated with the ASPIRE intervention implementation period. Adjusted all-cause mortality (odds ratio 0.71, 95% CI 0.56-0.89) was significantly lower after the ASPIRE intervention. DISCUSSION: The ASPIRE TIA triaging and management interventions did not further reduce stroke recurrence in the context of an organized stroke system. The apparent lower mortality postintervention may be related to improved surveillance after events identified as TIAs, but secular trends cannot be excluded. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a standardized population-wide algorithmic triage system for patients with TIA did not reduce recurrent stroke rate.


Assuntos
Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/terapia , Ataque Isquêmico Transitório/complicações , Triagem , Recidiva Local de Neoplasia/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Educação em Saúde , Infarto Cerebral/complicações , Recidiva
3.
J Pharm Sci ; 112(8): 2069-2078, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36638959

RESUMO

These proceedings contain presentation summaries and discussion highlights from the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) Workshop on Co-processed API, held on July 13 and 14, 2022. This workshop examined recent advances in the use of co-processed active pharmaceutical ingredients as a technology to improve drug substance physicochemical properties and drug product manufacturing process robustness, and explored proposals for enabling commercialization of these transformative technologies. Regulatory considerations were discussed with a focus on the classification, CMC strategies, and CMC documentation supporting the use of this class of materials from clinical studies through commercialization. The workshop format was split between presentations from industry, academia and the FDA, followed by breakout sessions structured to facilitate discussion. Given co-processed API is a relatively new concept, the authors felt it prudent to compile these proceedings to gain further visibility to topics discussed and perspectives raised during the workshop, particularly during breakout discussions. Disclaimer: This paper reflects discussions that occurred among stakeholder groups, including FDA, on various topics. The topics covered in the paper, including recommendations, therefore, are intended to capture key discussion points. The paper should not be interpreted to reflect alignment on the different topics by the participants, and the recommendations provided should not be used in lieu of FDA published guidance or direct conversations with the Agency about a specific development program. This paper should not be construed to represent FDA's views or policies.

4.
Trials ; 23(1): 873, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36242050

RESUMO

BACKGROUND: Neuromuscular electrical stimulation (NMES) is an established therapy that has been widely used for many decades to improve circulation in the legs. However, studies using NMES devices in an elderly, ambulant, and otherwise apparently healthy population are lacking; this is despite the use of such devices being indicated for lower leg symptoms (such as aches, pain, and cramps) that are frequently seen in older individuals. The main purpose of this study is to evaluate the effect of non-invasive foot NMES (administered using Revitive Medic©) on such symptoms compared to a sham in a 12-week period. METHODS: This is a single-center, single (participant)-blind, parallel-group, randomized, placebo-controlled (sham group), interventional study. Participants will be randomized to 1 of 3 groups (1:1:1) with each study group receiving a different type of foot NMES: Revitive sham; Revitive Medic© Program 1; or Revitive® Program 2. Each participant will be instructed to self-administer the foot NMES device for 30 min twice daily for 8 weeks. During the study, all participants will continue with their normal life, activities, medications, and diet with no restrictions. Following the 8-week NMES treatment program participants will be assessed for Canadian Occupational Performance Measure performance (COPM-P) and satisfaction (COPM-S) scores, lower leg pain, lower leg symptoms (heaviness, tiredness, aching and cramps), and blood flow volume and intensity. DISCUSSION: Revitive® foot NMES has been proven to increase blood circulation in the legs during use, which may help to relieve symptoms such as pain, heaviness, cramps, and tiredness. When NMES is applied to the plantar surface of the feet it indirectly induces contraction of the calf muscle, activating the musculo-venous pump and thus improving circulation. This study aims to provide data informing on the applicability of foot NMES for the management of leg symptoms that are likely to be indicative of poor circulation in an elderly (> 65 years) community population. TRIAL REGISTRATION: ISRCTN10576209.


Assuntos
Terapia por Estimulação Elétrica , Perna (Membro) , Idoso , Canadá , Terapia por Estimulação Elétrica/efeitos adversos , Humanos , Vida Independente , Perna (Membro)/irrigação sanguínea , Cãibra Muscular , Dor/diagnóstico , Dor/etiologia , Dor/prevenção & controle
5.
Phys Rev E ; 104(4-2): 045003, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34781470

RESUMO

A rotational sliceform (RS) forms a stiff, ringlike array of intersecting planar slices. Removing a few slices and disconnecting the ends of an RS enables the incomplete array to be collapsed scissorlike into a compact stack; it can be expanded smoothly as far as the original incomplete configuration, but not beyond. Its structured architecture, coupled to apparent mechanistic motion and a natural self-locking ability, expresses equivalently a novel deployable metamaterial, and we set out to determine its natural limits of motion for symmetrical and asymmetrical RS architectures. We first reconceptualize the RS as an array of plane-faced pyramidal cells bounded by rigid slices of zero thickness. The minimum articulation range from all cells is shown to set an upper bound on the range of motion of an incomplete RS, specifically, that symmetrical architectures can collapse fully while asymmetrical cannot and that expansion always stops at the design configuration. We also find that planar rotation of slices is not possible without distorting the original intersections. Each slice is then permitted to kink out-of-plane while preserving the initial geometry of each cell, in order to marshal compatible rotations of now compliant slices. Our analysis then reliably captures the deployment features: the minimum collapsed state, the degree of slice deformation as they rotate, and the limit of expansion.

6.
Electromagn Biol Med ; 40(1): 210-221, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33174467

RESUMO

This study investigated the effect of 448 kHz capacitive resistive monopolar radiofrequency (CRMRF) on the superficial and deep physiological responses of patients with osteoarthritis (OA) of the knee(s). Forty-five patients diagnosed with OA in their knee(s) were enrolled into a three-group randomised controlled study, from the waiting list of a local hospital. They received localized treatment with either CRMRF, CRMRF placebo or a control (no treatment) to the knee for 15 minutes. Pre, post, and 20 min follow-up measurements of skin temperature (SKT) and skin blood flow (SBF) were obtained from the knee using the FlexComp Infiniti (SA7550) physiological measurement system. Pre and post-treatment deep blood flow were recorded using Doppler ultrasound. Core temperature, blood pressure (BP) and pulse rate (PR) were concurrently monitored. Group data were compared using the ANOVA model. Statistical significance was set at p ≤ 0.05, 0.8 power, and 95% CI. Significant increases and sustenance of SKT and SBF, and significant increases in volume and intensity of deep blood flow were demonstrated with CRMRF over the placebo and control interventions in all comparisons (p< .001). No meaningful changes in blood flow velocity, core temperature, BP, or PR were noted for any condition. The findings were markedly more pronounced than those previously reported in asymptomatic adults. However, the patients had received a higher average dose of CRMRF (mean (SD): 46.87 (4.08) W) compared to the asymptomatic sample (mean (SD): 42.37 (4.64) W); therefore, further research is needed to better understand the differences in physiological responses between patients and asymptomatic people.


Assuntos
Articulação do Joelho/fisiopatologia , Articulação do Joelho/efeitos da radiação , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/terapia , Ondas de Rádio , Temperatura , Adulto , Capacitância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Clin Med ; 9(7)2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32635158

RESUMO

BACKGROUND: The aim of this longitudinal, one-year cohort study was to explore the hypothesis that fluorescence sampling of the root canal space prior to obturation could predict the outcome of root canal treatment (RCT). METHODS: Sixty-five teeth underwent primary RCT and were followed up clinically and radiographically. The outcome was determined radiographically with periapical radiographs (PR) and cone beam computed tomography (CBCT) scans. RESULTS: Success at 12 months was predictable based on the fluorescence score. When the fluorescence score (defined as the percentage of signal over total signal including background) was lower than 67, there was a 4.5 times (Odds ratio (OR) = 0.028; 95% confidence interval (CI): 0.003, 0.291, p = 0.001) greater chance of success (90% overall). When the readings were above this threshold, the success rate was 20%. CONCLUSION: A chairside sampling method is able to predict the outcome of RCT, through the use of paper point sampling and fluorescence staining. This has reduced the prevalence of persistent infections by guiding the optimum time for obturation. ClinicalTrials.gov trial NCT03660163.

8.
Arch Dis Child ; 104(8): 755-760, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30910816

RESUMO

OBJECTIVE: To develop paediatric gait standards in healthy children and young people. METHODS: This observational study aims to address the lack of population standards for gait measurements in children. Analysing gait in children affected by neurological or musculoskeletal conditions is an important component of paediatric assessment but is often confounded by developmental changes. The standards presented here do not require clinician expertise to interpret and offer an alternative to developmental tables of normalised gait data. Healthy children aged 1-19 years were recruited from community settings in London and Hertfordshire, UK. The GAITRite walkway was used to record measurements for each child for velocity, cadence, step length, base of support and stance, single and double support (as percentage of gait cycle). We fitted generalised linear additive models for location, scale and shape (gamlss). RESULTS: We constructed percentile charts for seven gait variables measured on 624 (321 males) contemporary healthy children using a gamlss package in R. A clinical application of gait standards was explored. CONCLUSION: Age-related, gender-specific standards for seven gait variables were developed and are presented here. They have a familiar format and can be used clinically to aid diagnoses and to monitor change over time for both medical therapy and natural history of the condition. The clinical example demonstrates the potential of the Great Ormond Street Institute of Child Health Paediatric Gait Centiles to enable meaningful interpretation of change in an individual's performance and describes characteristic features of gait from a specific population throughout childhood.


Assuntos
Serviços de Saúde da Criança , Marcha/fisiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Inglaterra , Feminino , Humanos , Lactente , Masculino , Padrões de Referência , Medicina Estatal , Adulto Jovem
9.
Physiotherapy ; 105(1): 98-107, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30269963

RESUMO

OBJECTIVE: This study investigated whether capacitive resistive monopolar radiofrequency (CRMRF)-based treatment improves pain and function among patients with osteoarthritis of the knee. DESIGN AND SETTING: Three-group randomised controlled trial with concealed allocation, participant blinding and intention-to-treat analysis. Forty-five patients diagnosed with osteoarthritis, from the waiting list for physiotherapy at a local hospital were enrolled. INTERVENTION: Participants in the active and sham groups received eight sessions of CRMRF and sham-CRMRF respectively over four weeks, along with standard care. The control group received standard care only. ASSESSMENT: Pain and function were measured at four time points: week zero (baseline), week four (post intervention), week eight and week 16 (two follow-ups) using visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, timed up and go (TUG) test and knee range of motion (ROM). RESULTS: For pain (VAS), there were clinically significant changes in the active group at post treatment compared to sham (Mean difference: 0.79 (95% CI: 0.29 to 1.3), effect size: 1.3) and control (Mean difference: 0.82 (95% CI: 0.32 to 1.3), effect size: 1.5), and at one-month follow-up compared to control (Mean difference: 0.68 (95% CI: 0.10 to 1.3), effect size: 1.1). For function (WOMAC), there was clinically significant change in the active group at post treatment compared to control (Mean difference: 1.3 (95% CI: 0.02 to 2.6), effect size: 0.94), but not compared to sham. No meaningful differences were noted for TUG or knee ROM. No differences were noted at three-month follow-up for any outcomes. CONCLUSION: CRMRF treatment can improve pain and function in patients with knee osteoarthritis in the short term. TRIAL REGISTRATION: NIHR-CRN study ID: 20264.


Assuntos
Osteoartrite do Joelho/terapia , Terapia por Radiofrequência/métodos , Idoso , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Modalidades de Fisioterapia , Pulso Arterial , Qualidade de Vida , Amplitude de Movimento Articular , Método Simples-Cego , Teste de Caminhada
10.
Electromagn Biol Med ; 37(1): 1-12, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29308927

RESUMO

Radiofrequency-based electrophysical agents (EPA) have been used in therapy practice over several decades (e.g., shortwave therapies). Currently, there is insufficient evidence supporting such devices operating below shortwave frequencies. This laboratory-based study investigated the skin physiological effects of 448 kHz capacitive resistive monopolar radiofrequency (CRMRF) and compared them to pulsed shortwave therapy (PSWT). In a randomised crossover study, seventeen healthy volunteers received four treatment conditions - High, Low and Placebo dose conditions receiving 15-min CRMRF treatment and a Control condition receiving no intervention. Fifteen participants also received high dose PSWT for comparison. Treatment was applied to the right lower medial thigh. Pre, post and 20-min follow-up measurements of skin temperature (SKT), skin blood flow (SBF) and nerve conduction velocity (NCV) were obtained using Biopac MP150 system. Group data were compared using the ANOVA model. Statistical significance was set at p ≤ 0.05 (0.8P, 95%CI). Significant increase and sustenance of SKT with both high and low dose CRMRF was demonstrated over the other groups (p < 0.001). PSWT increased SKT significantly (p < 0.001) but failed to sustain it over the follow-up. However, among the five conditions, only high dose CRMRF significantly increased and sustained SBF (p < 0.001). Overall, the CRMRF physiological responses were significantly more pronounced than that of PSWT. No significant changes in NCV were noted for any condition. Physiological changes associated with CRMRF were more pronounced when compared to PSWT, placebo or control. Any potential stronger therapeutic benefits of CRMRF need to be confirmed by comparative clinical studies.


Assuntos
Capacitância Elétrica , Voluntários Saudáveis , Ondas de Rádio , Terapia por Ondas Curtas , Fenômenos Fisiológicos da Pele/efeitos da radiação , Pele/efeitos da radiação , Temperatura , Adulto , Estudos Cross-Over , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/efeitos da radiação , Fluxo Sanguíneo Regional/efeitos da radiação , Pele/irrigação sanguínea , Pele/inervação
11.
J Sports Sci Med ; 16(3): 311-317, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28912647

RESUMO

The physical demands of fast-medium bowling are increasingly being recognised, yet comparative exploration of the differing demands between competitive formats (i.e. one-day [OD] versus multi-day [MD] matches) remain minimal. The aim of this study was to describe in-match physiological profiles of professional fast-medium bowlers from England across different versions of competitive matches using a multivariable wearable monitoring device. Seven professional cricket fast-medium bowlers wore the BioharnessTM monitoring device during matches, over three seasons (>80 hours in-match). Heart Rate (HR) and Acceleromety (ACC) was compared across match types (OD, MD) and different in-match activity states (Bowling, Between over bowling, Fielding). Peak acceleration during OD bowling was significantly higher in comparison to MD cricket ([OD vs. MD] 234.1 ± 57.9 vs 226.6 ± 32.9 ct·episode-1, p < 0.05, ES = 0.11-0.30). Data for ACC were also higher during OD than MD fielding activities (p < 0.01, ES = 0.11-.30). OD bowling stimulated higher mean HR responses (143 ± 14 vs 137 ± 16 beats·min-1, p < 0.05, ES = 0.21) when compared to MD matches. This increase in OD cricket was evident for both between over (129 ± 9 vs 120 ± 13 beats·min-1,p < 0.01, ES = 0.11-0.50) and during fielding (115 ± 12 vs 106 ± 12 beats·min-1, p < 0.01, ES = 0.36) activity. The increased HR and ACC evident in OD matches suggest greater acute physical loads than MD formats. Therefore, use of wearable technology and the findings provided give a valuable appreciation of the differences in match loads, and thus required physiological preparation and recovery in fast-medium bowlers.

12.
Int J Hyperthermia ; 31(8): 883-95, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26524223

RESUMO

PURPOSE: Radiofrequency-based electrophysical agents are widely used in therapy-related clinical practice for their thermal effects, mainly relieving pain and inflammation and improving tissue extensibility. The most commonly used and researched are shortwave therapies that operate at 27.12 MHz. Although relatively new, electrophysical agents employing much lower frequencies have also emerged. Capacitive resistive monopolar radiofrequency employing 448 kHz is one such therapy. This laboratory-based study was aimed to investigate the skin thermal responses to 448 kHz radiofrequency-based therapy in healthy adults. METHODS: In a two-group randomised crossover study, 15 volunteers attended two modes (capacitive and resistive) of 448 kHz radiofrequency-based therapy (using 'Indiba Activ 902') administered locally to the lower thigh region. Starting at minimum, the intensity was increased incrementally until thermal discomfort was felt. Participants reported three time points: thermal onset, definite thermal sensation, and onset of thermal discomfort. Local skin temperature was measured before, immediately post-treatment and up to 45 min post-treatment. RESULTS: Both capacitive and resistive modes of therapy significantly increased the skin temperature and sustained it over the 45-min follow-up. There was statistically significant difference between the thermal response patterns produced by the two modes. Peak post-treatment temperatures attained were not significantly different between the two; however, the retention rate at follow-up was significantly higher for the resistive mode. CONCLUSIONS: This study confirms that radiofrequency-based therapy at 448 kHz can significantly increase and sustain skin temperature. The study also provides useful baseline data for further research in the low frequency ranges of radiofrequency-based therapy that remain largely unexplored.


Assuntos
Hipertermia Induzida , Ondas de Rádio , Adulto , Estudos Cross-Over , Eletrodos , Feminino , Voluntários Saudáveis , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Temperatura Cutânea , Sensação Térmica
13.
EuroIntervention ; 11(3): 257-63, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26196752

RESUMO

AIMS: FFR measurements have been limited by the handling characteristics of pressure wire (PW) systems, and by signal drift. This first-in-human study evaluated the safety and efficacy of a new monorail catheter (Navvus) to assess coronary FFR, compared to a PW system. METHODS AND RESULTS: Resting measurements were acquired with both systems. After initiating IV adenosine, FFR was measured with the PW alone, simultaneously using both systems, and again with PW alone. Any zero offset of PW or Navvus was then recorded. Navvus measured FFR in all patients in whom a PW recording was obtained (50 of 58 patients); there were no complications related to Navvus. Navvus FFR correlated well with PW FFR (r=0.87, slope 1.0, intercept -0.02). Within PW measurement accuracy, in no cases did Navvus FFR classify lesion significance differently from PW FFR. PW signal drift was significantly greater than Navvus (0.06±0.12 vs. 0.02±0.02, p=0.014). CONCLUSIONS: Navvus and PW FFR correlated well. Navvus had less sensor drift. This new catheter-based system offers an alternative method for measuring FFR, with some potential advantages over PW.


Assuntos
Estenose Coronária/cirurgia , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Cateteres Cardíacos , Angiografia Coronária/métodos , Circulação Coronária/fisiologia , Estenose Coronária/diagnóstico , Estenose Coronária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
14.
J Gen Physiol ; 145(5): 405-18, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25918359

RESUMO

The regulation of arterial tone is critical in the spatial and temporal control of cerebral blood flow. Voltage-gated Ca(2+) (CaV) channels are key regulators of excitation-contraction coupling in arterial smooth muscle, and thereby of arterial tone. Although L- and T-type CaV channels have been identified in rodent smooth muscle, little is known about the expression and function of specific CaV subtypes in human arteries. Here, we determined which CaV subtypes are present in human cerebral arteries and defined their roles in determining arterial tone. Quantitative polymerase chain reaction and Western blot analysis, respectively, identified mRNA and protein for L- and T-type channels in smooth muscle of cerebral arteries harvested from patients undergoing resection surgery. Analogous to rodents, CaV1.2 (L-type) and CaV3.2 (T-type) α1 subunits were expressed in human cerebral arterial smooth muscle; intriguingly, the CaV3.1 (T-type) subtype present in rodents was replaced with a different T-type isoform, CaV3.3, in humans. Using established pharmacological and electrophysiological tools, we separated and characterized the unique profiles of Ca(2+) channel subtypes. Pressurized vessel myography identified a key role for CaV1.2 and CaV3.3 channels in mediating cerebral arterial constriction, with the former and latter predominating at higher and lower intraluminal pressures, respectively. In contrast, CaV3.2 antagonized arterial tone through downstream regulation of the large-conductance Ca(2+)-activated K(+) channel. Computational analysis indicated that each Ca(2+) channel subtype will uniquely contribute to the dynamic regulation of cerebral blood flow. In conclusion, this study documents the expression of three distinct Ca(2+) channel subtypes in human cerebral arteries and further shows how they act together to orchestrate arterial tone.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Artérias Cerebrais/metabolismo , Vasoconstrição , Potenciais de Ação , Animais , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo T/genética , Células Cultivadas , Artérias Cerebrais/fisiologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie
16.
Circ Res ; 115(7): 650-61, 2014 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-25085940

RESUMO

RATIONALE: T-type (CaV3.1/CaV3.2) Ca(2+) channels are expressed in rat cerebral arterial smooth muscle. Although present, their functional significance remains uncertain with findings pointing to a variety of roles. OBJECTIVE: This study tested whether CaV3.2 channels mediate a negative feedback response by triggering Ca(2+) sparks, discrete events that initiate arterial hyperpolarization by activating large-conductance Ca(2+)-activated K(+) channels. METHODS AND RESULTS: Micromolar Ni(2+), an agent that selectively blocks CaV3.2 but not CaV1.2/CaV3.1, was first shown to depolarize/constrict pressurized rat cerebral arteries; no effect was observed in CaV3.2(-/-) arteries. Structural analysis using 3-dimensional tomography, immunolabeling, and a proximity ligation assay next revealed the existence of microdomains in cerebral arterial smooth muscle which comprised sarcoplasmic reticulum and caveolae. Within these discrete structures, CaV3.2 and ryanodine receptor resided in close apposition to one another. Computational modeling revealed that Ca(2+) influx through CaV3.2 could repetitively activate ryanodine receptor, inducing discrete Ca(2+)-induced Ca(2+) release events in a voltage-dependent manner. In keeping with theoretical observations, rapid Ca(2+) imaging and perforated patch clamp electrophysiology demonstrated that Ni(2+) suppressed Ca(2+) sparks and consequently spontaneous transient outward K(+) currents, large-conductance Ca(2+)-activated K(+) channel mediated events. Additional functional work on pressurized arteries noted that paxilline, a large-conductance Ca(2+)-activated K(+) channel inhibitor, elicited arterial constriction equivalent, and not additive, to Ni(2+). Key experiments on human cerebral arteries indicate that CaV3.2 is present and drives a comparable response to moderate constriction. CONCLUSIONS: These findings indicate for the first time that CaV3.2 channels localize to discrete microdomains and drive ryanodine receptor-mediated Ca(2+) sparks, enabling large-conductance Ca(2+)-activated K(+) channel activation, hyperpolarization, and attenuation of cerebral arterial constriction.


Assuntos
Canais de Cálcio Tipo T/metabolismo , Sinalização do Cálcio , Artérias Cerebrais/metabolismo , Músculo Liso Vascular/metabolismo , Animais , Artérias Cerebrais/citologia , Retroalimentação Fisiológica , Feminino , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Potenciais da Membrana , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Ratos , Ratos Sprague-Dawley , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo
17.
J Endod ; 40(11): 1840-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25129025

RESUMO

INTRODUCTION: Matrix metalloproteinase (MMP) inhibition may improve endodontic treatment prognosis. The purpose of this study was to determine if zinc incorporation into experimental resin cements containing bioactive fillers may modulate MMP-mediated collagen degradation of dentin. METHODS: Human dentin samples untreated and demineralized using 10% phosphoric acid or 0.5 mol/L EDTA were infiltrated with the following experimental resins: (1) unfilled resin, (2) resin with Bioglass 45S5 particles (OSspray, London, UK), (3) resin with beta-tricalcium silicate particles (ßTCS), (4) resin with zinc-doped Bioglass 45S5, and (5) resin with zinc-doped ßTCS particles. The specimens were stored in artificial saliva (for 24 hours, 1 week, and 4 weeks) and submitted to radioimmunoassay to quantify C-terminal telopeptide. Scanning electron microscopy analysis was also undertaken on dentin samples after 4 weeks of storage. RESULTS: Collagen degradation was prominent both in phosphoric acid and EDTA-treated dentin. Resin infiltration strongly reduced MMP activity in demineralized dentin. Resin containing Bioglass 45S5 particles exerted higher and stable protection of collagen. The presence of zinc in ßTCS particles increases MMP inhibition. Different mineral precipitation was attained in dentin infiltrated with the resin cements containing bioactive fillers. CONCLUSIONS: MMP degradation of dentin collagen is strongly reduced after resin infiltration of dentin. Zinc incorporation in ßTCS particles exerted an additional protection against MMP-mediated collagen degradation. However, it did not occur in resin containing Bioglass 45S5 particles, probably because of the formation of phosphate-zinc compounds.


Assuntos
Materiais Biocompatíveis/química , Fosfatos de Cálcio/química , Substâncias Protetoras/química , Cimentos de Resina/química , Óxido de Zinco/química , Condicionamento Ácido do Dente/métodos , Bis-Fenol A-Glicidil Metacrilato/química , Compostos de Cálcio/química , Cerâmica/química , Colágeno/ultraestrutura , Colágeno Tipo I/análise , Resinas Compostas/química , Dentina/enzimologia , Dentina/ultraestrutura , Ácido Edético/química , Microanálise por Sonda Eletrônica , Vidro/química , Humanos , Teste de Materiais , Inibidores de Metaloproteinases de Matriz/química , Metacrilatos/química , Microscopia Eletrônica de Varredura , Peptídeos/análise , Ácidos Fosfóricos/química , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Poliuretanos/química , Saliva Artificial/química , Silicatos/química , Fatores de Tempo
18.
Int J Stroke ; 9(8): 974-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23013039

RESUMO

BACKGROUND: There is an increasing trend to treating proximal vessel occlusions with intravenous-inter-arterial (IV-IA) thrombolysis. The best dose of IV tissue plasminogen activator (tPA) remains undetermined. We compared the combination of full-dose IV recombinant tissue plasminogen activator (rtPA) and IA thrombolytic therapy to IA therapy. METHODS: Between 2002 and 2009, we reviewed our computed tomographic angiography database for patients who received full-dose intravenous rtPA and endovascular therapy or endovascular therapy alone for acute ischaemic stroke treatment. Details of demographics, risk factors, endovascular procedure, and symptomatic intracranial haemorrhage were noted. Modified Rankin Scale ≤2 at three-months was used as good outcome. Recanalization was defined as Thrombolysis in Myocardial Ischaemia 2-3 flow on angiography. RESULTS: Among 157 patients, 104 patients received IV-IA treatment and 53 patients underwent direct IA therapy. There was a higher recanalization rate with IV-IA therapy compared with IA alone (71% vs. 60%, P < 0·21) which was driven by early recanalization after IV rtPA. Mortality and independent outcome were comparable between the two groups. Symptomatic intracranial haemorrhage occurred in 8% of patients (12% in the IA group, 7% in the IV-IA group) but was more frequent as the intensity of intervention increased from device alone to thrombolytic drug alone to device plus thrombolytic drug(s). Recanalization was a strong predictor of reduced mortality risk ratio (RR) 0·48 confidence interval95 0·27-0·84) and favourable outcome (RR 2·14 confidence interval95 1·3-3·5). CONCLUSIONS: Combined IV-IA therapy with full-dose intravenous rtPA was safe and results in good recanalization rates without excess symptomatic intracranial haemorrhage. Testing of full-dose IV tPA followed by endovascular treatment in the IMS3 trial is justified.


Assuntos
Procedimentos Endovasculares/métodos , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Isquemia Encefálica/complicações , Angiografia Cerebral/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
19.
Int J Stroke ; 9 Suppl A100: 135-43, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23088263

RESUMO

RATIONALE: Stroke risk after transient ischaemic attack is high and, it is a challenge worldwide to provide urgent assessment and preventive services to entire populations. AIMS: To determine whether a province-wide transient ischaemic attack Triaging algorithm and transient ischaemic attack hotline (the Alberta Stroke Prevention in transient ischaemic attacks and mild strokes intervention) can reduce the rate of stroke recurrence following transient ischaemic attack across the population of Alberta, Canada (population 3·7 million, 90-day rate of post-stroke transient ischaemic attack currently 9·5%). It also seeks to improve upon current transient ischaemic attack triaging rules by incorporating time from symptom onset as a predictive variable. DESIGN: The transient ischaemic attack algorithm and hotline were developed with a broad consensus of clinicians, patients, policy-makers, and researchers and based on local adaptation of the work of others and research and insights developed within the province. Because neither patient-level nor region-level randomization was possible, we conducted a quasi-experimental design examining changes in the post-transient ischaemic attack rate of stroke recurrence before and after the 15-month implementation period using an interrupted time-series regression analysis. The design controls for changes in case-mix, co-interventions, and secular trends. A prospective transient ischaemic attack cohort will also be concurrently created with telephone follow-up at seven-days and 90 days as well as passive follow-up over the longer term using linkages to provincial healthcare administrative databases. STUDY OUTCOMES: The primary outcome measure is the change in recurrence rate of stroke following transient ischaemic attack at seven-days and 90 days, comparing a period of two-years before vs. two-years after the intervention is implemented. All cases of recurrent stroke will be validated. Secondary outcomes include functional status, hospitalizations, morbidity, and mortality. CONCLUSIONS: We are undertaking a rigorous evaluation of a population-based approach to improving quality of transient ischaemic attack care. Whether positive or negative, our work should provide important insights for all potential stakeholders.


Assuntos
Ataque Isquêmico Transitório/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Triagem/estatística & dados numéricos , Alberta/epidemiologia , Algoritmos , Estudos de Coortes , Planejamento em Saúde Comunitária , Feminino , Linhas Diretas , Humanos , Ataque Isquêmico Transitório/epidemiologia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Qualidade da Assistência à Saúde , Fatores de Risco , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia
20.
J Strength Cond Res ; 28(5): 1465-73, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23897016

RESUMO

Cricket is a global sport played in over 100 countries with elite performers attracting multimillion dollar contracts. Therefore, performers maintaining optimum physical fitness and remaining injury free is important. Fast bowlers have a vital position in a cricket team, and there is an increasing body of scientific literature that has reviewed this role over the past decade. Previous research on fast bowlers has tended to focus on biomechanical analysis and injury prevention in performers. However, this review aims to critically analyze the emerging contribution of physiological-based literature linked to fast bowling in cricket, highlight the current evidence related to simulated and competitive in-match performance, and relate this practically to the conditioning coach. Furthermore, the review considers limitations with past research and possible avenues for future investigation. It is clear with the advent of new applied mobile monitoring technology that there is scope for more ecologically valid and longitudinal exploration capturing in-match data, providing quantification of physiological workloads, and analysis of the physical demands across the differing formats of the game. Currently, strength and conditioning specialists do not have a critical academic resource with which to shape professional practice, and this review aims to provide a starting point for evidence in the specific area.


Assuntos
Desempenho Atlético/fisiologia , Condicionamento Físico Humano/fisiologia , Aptidão Física/fisiologia , Esportes/fisiologia , Antropometria , Fenômenos Biomecânicos , Humanos , Esforço Físico/fisiologia
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