RESUMO
BACKGROUND: Most pediatric patients present to general emergency departments, yet maintaining pediatric equipment, skilled staff, and resources remains a challenge for many hospitals. Pediatric readiness assessment is now a requirement for trauma center verification. OBJECTIVE: This study aims to assess the impact of a quality improvement initiative to improve emergency department pediatric readiness. METHODS: A pre- and poststudy design was used to evaluate a quality improvement initiative to improve the National Pediatric Readiness assessment survey results conducted at a Southwestern United States adult Level I trauma center from September 2022 to April 2023. The multicomponent initiative included implementing a pediatric emergency care coordinator, pediatric-specific policies and procedures, identifying pediatric-specific quality and performance indicators, and educating pediatric-specific staff. Study inclusion criteria were all patients younger than 18 years who presented to the emergency department. The primary outcome measure was the improvement in the weighted Pediatric Readiness Score. Secondary outcomes were throughput, nursing documentation of vital signs, and pain scores. RESULTS: A total of N = 2,356 patients met inclusion, of which n = 1,158 (49.2%) were in the preintervention group and n = 1,198 (50.8%) postintervention group. The weighted Pediatric Readiness Score improved by 45.4%. Transfers to a pediatric hospital increased from 4.1% to 8.6% (p = .016). Blood pressure documentation improved slightly from 88.3% to 88.6%. Pain score documentation decreased from 83.9% to 63.1% (p = .008). Pain medication and administration improved from 19.8% to 26.7% (p = .046). CONCLUSION: We found that participation in the quality improvement initiative was associated with emergency department pediatric readiness improvements.
Assuntos
Planejamento em Desastres , Centros de Traumatologia , Adulto , Humanos , Criança , Melhoria de Qualidade , Serviço Hospitalar de Emergência , DorRESUMO
Carbon fiber precursor materials, such as polyacrylonitrile, pitch, and cellulose/rayon, require thermal stabilization to maintain structural integrity during conversion into carbon fiber. Thermal stabilization mitigates undesirable decomposition and liquification of the fibers during the carbonization process. Generally, the thermal stabilization of mesophase pitch consists of the attachment of oxygen-containing functional groups onto the polymeric structure. In this study, the oxidation of mesophase pitch precursor fibers at various weight percentage increases (1, 3.5, 5, 7.5 wt%) and temperatures (260, 280, 290 °C) using in situ differential scanning calorimetry and thermogravimetric analysis is investigated. The results are analyzed to determine the effect of temperature and weight percentage increase on the stabilization process of the fibers, and the fibers are subsequently carbonized and tested for tensile mechanical performance. The findings provide insight into the relationship between stabilization conditions, fiber microstructure, and mechanical properties of the resulting carbon fibers.
RESUMO
BACKGROUND: Triage and neurological assessment of the 1.7 million traumatic brain injuries occurring annually is often done by nurse practitioners and physician assistants in the emergency department. Subjective assessments, such as the neurological examination that includes evaluation of the pupillary light reflex (PLR), can contain bias. Quantitative pupillometry (QP) standardizes and objectifies the PLR examination. Additional data are needed to determine whether QP can predict neurological changes in a traumatic brain injury (TBI) patient. PURPOSE: This study examines the effectiveness of QP in predicting neurological decline within 24 hours of admission following acute TBI. METHODOLOGY: This prospective, observational, clinical trial used pragmatic sampling to assess PLR in TBI patients using QP within 24 hours of ED admission. Chi-square analysis was used to determine change in patient status, through Glasgow Coma Scale (GCS), at baseline and within 24 hours of admission, to the QP. RESULTS: There were 95 participants included in the analysis; of whom 35 experienced neuroworsening, defined by change in GCS of >2 within the first 24 hours of admission. There was a significant association between an abnormal Neurological Pupil index (NPi), defined as NPi of <3, and neuroworsening (p < .0001). The sensitivity (51.43%) and specificity (91.67%) of abnormal NPi in predicting neuroworsening were varied. CONCLUSION: There is a strong association between abnormal NPi and neuroworsening in the sample of TBI patients with high specificity and moderate sensitivity. IMPLICATIONS: NPi may be an early indicator of neurological changes within 24 hours of ED admission in patients with TBI.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Humanos , Estudos Prospectivos , Reflexo , Lesões Encefálicas Traumáticas/diagnóstico , Escala de Coma de GlasgowRESUMO
Currently, there is a multitude of methods for evaluating the costs and benefits of programs, tools, etc. While cost-benefit analysis (CBA) is commonly used, cost-effectiveness analysis (CEA) is a more appropriate method of evaluation in clinical contexts, such as radiology practices, as CEAs use units such as life years gained as opposed to money (as is the case for CBAs). This review examines CEAs performed within the past 15 years to highlight their applications and key findings in the context of medical imaging. In total, 20 articles published between 2006 and 2022 were identified using a PubMed search for keywords including "cost-effectiveness analysis," "breast cancer," and "medical imaging," with studies lacking a substantial discussion of CEA or a related topic being excluded. CEAs have traditionally been criticized for lack of a standard methodology, despite their utility in the detection and treatment of various pathologies. Although mammography and magnetic resonance imaging (MRI) are the preferred and cost-effective imaging modalities for breast cancer, other imaging modalities, such as contrast-enhanced mammography and digital breast tomosynthesis, may be more cost-effective in the appropriate clinical context. Different combinations of mammography and MRI screenings for certain breast cancers may also prove to be more cost-effective compared to current mammography/MRI screening schedules. While CEA has shown potential utility in estimating the costs (per unit of health gained) of different imaging tools, CEA risks ignoring important outcomes not included in the analysis and cannot address if the benefits of the imaging tool exceed its costs, as a CBA would, suggesting the need for combining several economic evaluations for a more complete understanding.
RESUMO
Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system. The study aims to assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM. Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study. Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.
Assuntos
Glioblastoma , Omento , Glioblastoma/cirurgia , Humanos , Recidiva Local de Neoplasia/cirurgia , Omento/irrigação sanguínea , Omento/transplante , Retalhos Cirúrgicos , Transplante AutólogoRESUMO
The increase in risk for acute ischemic stroke (AIS) with age is well established. If not treated properly and promptly, AIS can result in permanent neurological damage and even death. This literature review assesses the clinical outcomes of AIS patients treated with both intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT) compared to those treated solely with mechanical thrombectomy. Randomized controlled trials (RCTs) and meta-analyses published from 2015 to 2020 and available on PubMed were selected for review, and their quantitative and qualitative findings were extrapolated and summarized. Post-hoc analyses from ASTER and ETIS trials were reviewed as well as the impact of combined therapy and monotherapy on large vessel occlusions (LVO). Clinical outcomes in all examined trials demonstrated significant successful reperfusion as well as a higher rate of functional independence at 90 days for IVT prior to MT. Concerns of thrombus fragility, safety and cost effectiveness of dual therapy are also addressed. Based on these findings, we recommend the use of IVT as a pretreatment procedure to MT for AIS when eligible for IVT. Recent articles further strengthen this recommendation and provide new insights that IVT prior to MT is especially beneficial for patients presenting with multiple LVOs localized to the anterior intracranial circulation. Additional multi-center RCTs are necessary for further analysis of statistical outcomes demonstrating mixed effects.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/terapia , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica , Resultado do TratamentoRESUMO
BACKGROUND: Anatomic compression of the optic nerve secondary to a dolichoectatic cerebrovascular compression is a rare clinical entity. Because of the limited number of published cases and variable clinical presentation, the natural history remains ambiguous and no consensus exists regarding management. In addition, there is an ongoing debate regarding whether a dolichoectatic cerebral blood vessel can actually cause optic neuropathy, or it merely represents an incidental finding. As a result, it is thought that a diagnosis of compressive optic neuropathy from an adjacent dolichoectatic internal carotid artery (ICA) should be considered only after other possible etiologies are excluded. Although this might seem straightforward, the clinical scenario becomes complex if the patient is also found to have additional incidental pituitary lesions. Such coexistence has not been reported previously in the literature. CASE DESCRIPTION: A 52-year-old left-handed man presented to us with intermittent headache and painless progressive visual deterioration in the right eye for 1 month. Screening magnetic resonance imaging (MRI) scan revealed a 9-mm eccentrically placed pituitary adenoma with right optic nerve compression because of dolichoectatic ICA. He underwent microvascular decompression of the right optic nerve. On follow-up, significant vision improvement was noticed and MRI scan revealed no change in the size of the pituitary adenoma. CONCLUSIONS: The compression of the optic nerve by dolichoectatic ICA is commonly thought to be a diagnosis of exclusion. However, the presence of a coexisting pathology should not prompt the exclusion in every case and a case-based approach is highly recommended to correctly manage this rare clinical condition.
Assuntos
Adenoma/epidemiologia , Doenças das Artérias Carótidas/complicações , Doenças do Nervo Óptico/etiologia , Neoplasias Hipofisárias/epidemiologia , Insuficiência Vertebrobasilar/complicações , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/etiologiaRESUMO
Whole-grain wheat, in particular coloured varieties, may have health benefits in adults with chronic metabolic disease risk factors. Twenty-nine overweight and obese adults with chronic inflammation (high-sensitivity C-reactive protein) > 1·0 mg/l) replaced four daily servings of refined grain food products with bran-enriched purple or regular whole-wheat convenience bars (approximately 41-45 g fibre, daily) for 8 weeks in a randomised, single-blind parallel-arm study where body weight was maintained. Anthropometrics, blood markers of inflammation, oxidative stress, and lipaemia and metabolites of anthocyanins and phenolic acids were compared at days 1, 29 and 57 using repeated-measures ANOVA within groups and ANCOVA between groups at day 57, with day 1 as a covariate. A significant reduction in IL-6 and increase in adiponectin were observed within the purple wheat (PW) group. TNF-α was lowered in both groups and ferulic acid concentration increased in the regular wheat (RW) group. Comparing between wheats, only plasma TNF-α and glucose differed significantly (P < 0·05), that is, TNF-α and glucose decreased with RW and PW, respectively. Consumption of PW or RW products showed potential to improve plasma markers of inflammation and oxidative stress in participants with evidence of chronic inflammation, with modest differences observed based on type of wheat.
Assuntos
Proteína C-Reativa/metabolismo , Ingestão de Alimentos/fisiologia , Obesidade/sangue , Sobrepeso/sangue , Triticum , Grãos Integrais , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Fatores de Risco Cardiometabólico , Dieta/métodos , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: Spontaneous spinal cerebrospinal fluid (CSF) leak is an increasingly recognized condition responsible for spontaneous intracranial hypotension. A host of connective tissue disorders and mechanical factors may precipitate the condition. Conservative treatment has limited efficacy, and many patients with persistent symptoms ultimately require epidural blood patch (EBP). However, about 23%-44% of patients experience recurrence of symptoms after EBP. Unidentified or multiple sites of CSF leaks are thought to be responsible for the failure of EBP. Using our previously published technique, we treated a patient who developed a large spontaneous CSF leak in her cervicothoracic spine after a boxing class, offering further evidence of the utility of the technique for select patients. CASE DESCRIPTION: A 28-year-old woman was referred to our center with recurrent, severe headaches and associated nausea and vomiting. She underwent EBP 3 times with no resolution of her symptoms. A right-side partial C7-T1 hemilaminotomy was performed to identify a large meningocele filled with CSF. After dissection, dural sealant was applied using an angled needle with a syringe to buttress the meningocele to allow for normalization of the hydrostatic pressure. At 5-month follow-up, her symptoms have resolved with no headaches and paresthesias in upper limbs. CONCLUSIONS: Commonplace events, such as a boxing/sparring class, may precipitate a spontaneous spinal CSF leak. Our minimally invasive surgical approach can be safely used in patients with spontaneous intracranial hypotension with recurrent symptoms, no identified leak site, and prior failed attempts of EBP.
Assuntos
Placa de Sangue Epidural/métodos , Boxe/lesões , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Vazamento de Líquido Cefalorraquidiano/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Falha de Tratamento , Adulto , Vazamento de Líquido Cefalorraquidiano/etiologia , Feminino , HumanosRESUMO
OBJECTIVE. Multiple studies suggest CT should be a primary diagnostic tool for coronavirus disease (COVID-19) because they reported sensitivities with CT far superior to that of reverse transcriptase polymerase chain reaction (RT-PCR) testing. This review aimed to assess these reports and found chest CT to have a clinical utility that is limited, particularly for patients who show no symptoms and patients who are screened early in disease progression. CONCLUSION. CT has limited sensitivity for COVID-19 and a lower specificity than RT-PCR testing, and it carries a risk of exposing providers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chest CT should be considered a supplemental diagnostic tool, particularly for patients who show symptoms.
Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios X , Betacoronavirus , COVID-19 , Teste para COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Sensibilidade e EspecificidadeAssuntos
Infarto do Miocárdio/terapia , Near Miss , Alta do Paciente , Readmissão do Paciente , Nível de Saúde , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Equipe de Assistência ao Paciente , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The glycaemic response of millet foods and the effect of processing are not known. Therefore, decorticated proso millet was used to produce four types of common food products (biscuits, couscous, porridge and an extruded snack). Postprandial blood glucose response of these products (all containing 50 g of total starch) was compared to the same foods produced with refined corn, in a crossover human study with 12 healthy male participants (age 26.3 ± 3.8 yr; BMI 23.3 ± 2.8 kg/m2). Capillary blood samples were collected and glycaemic response was determined; differences were assessed using repeat measures ANOVA. Overall, the mean (±SEM) incremental area under the blood glucose response curve (mmol min/l) of the proso millet products was different from the corn products, but individual products (couscous = 66.7 ± 11.6, biscuit = 82.6 ± 13.7, extrudate = 198.7 ± 20.9, porridge = 40.1 ± 5.8) were not significantly lower (couscous = 43.5 ± 5.8, biscuit = 102.0 ± 10.3, extrudate = 198.7 ± 20.9, porridge = 52.2 ± 8.1) (p > .05). Glycaemic response of the products was not dependent on the grain type, but rather product matrix.
Assuntos
Glicemia/efeitos dos fármacos , Panicum/química , Adulto , Estudos Cross-Over , Alimentos Especializados , Humanos , Masculino , Período Pós-Prandial , Lanches , Adulto Jovem , Zea maysRESUMO
Reproducibility and validity testing of appetite ratings and energy intakes are needed in experimental and natural settings. Eighteen healthy young women ate a standardized breakfast for 8 days. Days 1 and 8, they rated their appetite (Hunger, Fullness, Desire to Eat, Prospective Food Consumption (PFC)) over a 3.5 h period using visual analogue scales, consumed an ad libitum lunch, left the research center and recorded food intake for the remainder of the day. Days 2-7, participants rated their at-home Hunger at 0 and 30 min post-breakfast and recorded food intake for the day. Total area under the curve (AUC) over the 180 min period before lunch, and energy intakes were calculated. Reproducibility of satiety measures between days was evaluated using coefficients of repeatability (CR), coefficients of variation (CV) and intra-class coefficients (ri). Correlation analysis was used to examine validity between satiety measures. AUCs for Hunger, Desire to Eat and PFC (ri = 0.73-0.78), ad libitum energy intakes (ri = 0.81) and total day energy intakes (riâ = 0.48) were reproducible; fasted ratings were not. Average AUCs for Hunger, Desire to Eat and PFC, Desire to Eat at nadir and PFC at fasting, nadir and 180 min were correlated to total day energy intakes (r = 0.50-0.77, P < 0.05), but no ratings were correlated to lunch consumption. At-home Hunger ratings were weakly reproducible but not correlated to reported total energy intakes. Satiety ratings did not concur with next meal intake but PFC ratings may be useful predictors of intake. Overall, this study adds to the limited satiety research on women and challenges the accepted measures of satiety in an experimental setting.
Assuntos
Apetite , Ingestão de Energia , Período Pós-Prandial , Adulto , Índice de Massa Corporal , Peso Corporal , Desjejum , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Jejum , Feminino , Seguimentos , Humanos , Fome , Almoço , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Saciação , Adulto JovemRESUMO
Increasing feelings of satiety may reduce appetite and energy intake. The role of inulin consumption in impacting satiety is unclear. A randomised double-blind controlled crossover trial aimed to determine the effects of inulin+yogurt on satiety after 1 and 8-d consumption. The preload breakfast included 100 g vanilla yogurt with (yogurt-inulin (YI)) and without (yogurt-control (YC)) 6 g inulin. A total of nineteen healthy females (22·8 (sd 2·7) years) with non-restrained eating behaviour and taking hormonal contraceptives participated in the study. Day 1 and 8 visual analogue scale (VAS) ratings of Hunger, Fullness, Desire to Eat and Prospective Food Consumption (PFC) were collected at fasting and every 30 min for 180 min. Energy intake was calculated from a weighed ad libitum lunch and remainder of day food records. Total AUC was calculated for each VAS. Day 1 (VAS only) and 8 (VAS and energy intakes) data were compared between YI and YC using ANCOVA, and ANOVA was used to compare energy intakes on Day 1. There were no significant differences between Day 1 YI and YC AUC appetite ratings or energy intakes. However, 8-d consumption of YI v. YC was associated with lower Desire to Eat and PFC ratings but similar lunch and total day energy intakes. Therefore, the addition of 6 g inulin to a commercially available yogurt affected feelings of appetite, but not energy intake, after repeated consumption. These results suggest that inulin may be a suitable ingredient to increase dietary fibre consumption, with potential to impact appetite.
Assuntos
Apetite/efeitos dos fármacos , Desjejum , Ingestão de Energia , Inulina/administração & dosagem , Iogurte , Anticoncepcionais Orais Hormonais , Estudos Cross-Over , Fibras na Dieta/administração & dosagem , Método Duplo-Cego , Comportamento Alimentar , Feminino , Humanos , Fome , Inulina/efeitos adversos , Período Pós-Prandial , Saciação/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: With no cure or effective treatments for osteoarthritis (OA), the need to identify modifiable factors to decrease pain and increase physical function is well recognized. OBJECTIVE: To examine factors that characterize OA patients at different levels of pain, and to investigate the relationships among these factors and pain. METHODS: Details of OA characteristics and lifestyle factors were collected from interviews with healthy adults with knee OA (n=197). The Western Ontario and McMaster Universities Osteoarthritis Index was used to assess pain. Factors were summarized across three pain score categories, and χ(2) and Kruskal-Wallis tests were used to examine differences. Multiple linear regression analysis using a stepwise selection procedure was used to examine associations between lifestyle factors and pain. RESULTS: Multiple linear regression analysis indicated that pain was significantly higher with the use of OA medications and higher body mass index category, and significantly lower with the use of supplements and meeting physical activity guidelines (≥ 150 min/week). Stiffness and physical function scores, bilateral knee OA, body mass index category and OA medication use were significantly higher with increasing pain, whereas self-reported health, servings of fruit, supplement use and meeting physical activity guidelines significantly lower. No significant differences across pain categories were found for sex, age, number of diseases, duration of OA, ever smoked, alcoholic drinks/week, over-the-counter pain medication use, OA supplement use, physical therapy use, servings of vegetables or minutes walked/week. CONCLUSIONS: Healthy weight maintenance, exercise for at least 150 min/week and appropriate use of medications and supplements represent important modifiable factors related to lower knee OA pain.
Assuntos
Estilo de Vida , Osteoartrite do Joelho/complicações , Dor/etiologia , Dor/psicologia , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Autorrelato , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
In order to design P. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (CS) T and B cell epitopes displayed on the woodchuck hepatitis virus core antigen (WHcAg) VLP platform was produced. To test the protective efficacy of the WHcAg-CS VLPs, hybrid CS P. berghei/P. falciparum (Pb/Pf) sporozoites were used to challenge immunized mice. VLPs carrying 1 or 2 different CS repeat B cell epitopes and 3 VLPs carrying different CS non-repeat B cell epitopes elicited high levels of anti-insert antibodies (Abs). Whereas, VLPs carrying CS repeat B cell epitopes conferred 98% protection of the liver against a 10,000 Pb/Pf sporozoite challenge, VLPs carrying the CS non-repeat B cell eptiopes were minimally-to-non-protective. One-to-three CS-specific CD4/CD8 T cell sites were also fused to VLPs, which primed CS-specific as well as WHcAg-specific T cells. However, a VLP carrying only the 3 T cell domains failed to protect against a sporozoite challenge, indicating a requirement for anti-CS repeat Abs. A VLP carrying 2 CS repeat B cell epitopes and 3 CS T cell sites in alum adjuvant elicited high titer anti-CS Abs (endpoint dilution titer >1x10(6)) and provided 80-100% protection against blood stage malaria. Using a similar strategy, VLPs were constructed carrying P. vivax CS repeat B cell epitopes (WHc-Pv-78), which elicited high levels of anti-CS Abs and conferred 99% protection of the liver against a 10,000 Pb/Pv sporozoite challenge and elicited sterile immunity to blood stage infection. These results indicate that immunization with epitope-focused VLPs carrying selected B and T cell epitopes from the P. falciparum and P. vivax CS proteins can elicit sterile immunity against blood stage malaria. Hybrid WHcAg-CS VLPs could provide the basis for a bivalent P. falciparum/P. vivax malaria vaccine.
Assuntos
Imunidade , Estágios do Ciclo de Vida , Malária Falciparum/imunologia , Malária Vivax/imunologia , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologia , Vírion/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Vírus da Hepatite B da Marmota/imunologia , Imunização , Malária Falciparum/parasitologia , Malária Falciparum/prevenção & controle , Malária Vivax/parasitologia , Malária Vivax/prevenção & controle , Camundongos Endogâmicos C57BL , Proteínas de Protozoários/imunologia , Coelhos , Sequências Repetitivas de Aminoácidos , Reprodutibilidade dos TestesRESUMO
We evaluated whether phospholemman (PLM) regulates L-type Ca(2+) current (ICa) in mouse ventricular myocytes. Expression of α1-subunit of L-type Ca(2+) channels between wild-type (WT) and PLM knockout (KO) hearts was similar. Compared to WT myocytes, peak ICa (at -10 mV) from KO myocytes was ~41% larger, the inactivation time constant (τ(inact)) of ICa was ~39% longer, but deactivation time constant (τ(deact)) was similar. In the presence of isoproterenol (1 µM), peak ICa was ~48% larger and τ(inact) was ~144% higher in KO myocytes. With Ba(2+) as the permeant ion, PLM enhanced voltage-dependent inactivation but had no effect on τ(deact). To dissect the molecular determinants by which PLM regulated ICa, we expressed PLM mutants by adenovirus-mediated gene transfer in cultured KO myocytes. After 24h in culture, KO myocytes expressing green fluorescent protein (GFP) had significantly larger peak ICa and longer τ(inact) than KO myocytes expressing WT PLM; thereby independently confirming the observations in freshly isolated myocytes. Compared to KO myocytes expressing GFP, KO myocytes expressing the cytoplasmic domain truncation mutant (TM43), the non-phosphorylatable S68A mutant, the phosphomimetic S68E mutant, and the signature PFXYD to alanine (ALL5) mutant all resulted in lower peak ICa. Expressing PLM mutants did not alter expression of α1-subunit of L-type Ca(2+) channels in cultured KO myocytes. Our results suggested that both the extracellular PFXYD motif and the transmembrane domain of PLM but not the cytoplasmic tail were necessary for regulation of peak ICa amplitude. We conclude that PLM limits Ca(2+) influx in cardiac myocytes by reducing maximal ICa and accelerating voltage-dependent inactivation.
Assuntos
Canais de Cálcio Tipo L/metabolismo , Proteínas de Membrana/metabolismo , Miócitos Cardíacos/metabolismo , Fosfoproteínas/metabolismo , Adenoviridae/metabolismo , Motivos de Aminoácidos , Animais , Células Cultivadas , Citoplasma/química , Cães , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ativação do Canal Iônico/efeitos dos fármacos , Isoproterenol/farmacologia , Proteínas de Membrana/química , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Mutantes/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Fosfoproteínas/química , Fosfosserina/metabolismo , Estrutura Terciária de Proteína , Relação Estrutura-AtividadeRESUMO
UNLABELLED: Individuals with medically diagnosed knee osteoarthritis (OA) participated in a randomized, double-blind study to investigate the effects of a high-rosmarinic acid (rosA) spearmint tea. Sixty-two participants were randomized by sex and screening pain score to consume tea brewed from a high-rosA spearmint variety or a commercially available spearmint twice daily for 16 weeks. Pain, quality of life (QoL), and physical function at baseline and week 16 were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short-Form 36-item Health Survey (SF-36), 6-minute walk test (6MWT), and stair climb test (SCT). Data from 46 participants (mean age=60.7; BMI=32.9 kg/m(2)) were analyzed. Pain score significantly decreased from week 0 to 16 for the high-rosA group but not for the control group and scores for stiffness and physical disability significantly decreased from week 0 to 16 for both groups. Increased QoL score on the bodily pain index in the SF-36 was observed at week 16 within the high-rosA group only, although no significant differences were observed between the groups. A nonsignificant improvement was observed in the 6MWT at week 16 in the high-rosA group only. There were no changes in the SCT for either group. Therefore, 16-week daily consumption of the high-rosA and commercial spearmint teas significantly improved stiffness and physical disability scores in adults with knee OA, but only the high-rosA tea significantly decreased pain. Consumption of high-rosA tea warrants further consideration as a potential complementary therapy to reduce pain in OA. CLINICAL TRIAL REGISTRATION NUMBER: NCT01380015.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Cinamatos/uso terapêutico , Depsídeos/uso terapêutico , Mentha spicata/química , Osteoartrite do Joelho/tratamento farmacológico , Fitoterapia , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Medição da Dor/efeitos dos fármacos , Qualidade de Vida , Chá , Ácido RosmarínicoRESUMO
PROBLEM: Cardiovascular disease (CVD) is clinically unique in women and is often underdiagnosed and undertreated. Chronic diseases account for 75% of healthcare expenditures in the United States, of which 70% are preventable through lifestyle changes and active medical management. Lifestyle modification is difficult in the context of the traditional medical visit. DESIGN: The Club Red Clinic uses a novel approach to enhance the care of women at risk for or with CVD. Through shared medical appointments (SMAs) and a multidisciplinary team approach, Club Red provides lifestyle training in addition to evidence-based practice to reduce CVD risk factors in women. In Club Red, nurse practitioners function independently and effectively in delivering lifestyle intervention for the management and prevention of CVD. SETTING: The clinic functions within an academic medical school at the University of Virginia. KEY MEASURES FOR IMPROVEMENT: Patient access, patient satisfaction, provider efficiency, and frequency of cardiovascular visits. EFFECTS OF CHANGE: Process improvements include reduced appointment wait times, improved provider efficiency (more patients seen with the SMAs), high patient satisfaction (96%), and improved adherence to recommended medical monitoring (3.8 visits/year). LESSONS LEARNED: Club Red improved patient access, patient satisfaction, medical and behavioral management, and health promotion education for women with or at risk for CVD.