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BACKGROUND: The aim of this study was to demonstrate the biomechanical properties in different abdominal aortic aneurysm (AAA) presentations of real-life patients. We used the actual 3D geometry of the AAAs under analysis and a realistic, nonlinearly elastic biomechanical model. MATERIALS AND METHODS: Three patients with different clinical scenarios (R: rupture, S: symptomatic, and A: asymptomatic) with infrarenal aortic aneurysms were studied. Factors affecting aneurysm behavior such as morphology, wall shear stress (WSS), pressure, and velocities were studied and analyzed using steady state computer fluid dynamics using SolidWorks (Dassault Systems SolidWorksCorp., Waltham, Massachusetts). RESULTS: When analyzing the WSS, Patient R and Patient A had a decrease in the pressure in the bottom-back region compared with the body of the aneurysm. In contrast, WSS values appeared to be the most uniform across the entire aneurysm in Patient S. Furthermore, Patient A had focal small surface regions with high WSS values. The overall WSS in the unruptured aneurysms (Patient S and Patient A) were a lot higher than in the ruptured 1 (Patient R). All 3 patients showed a pressure gradient, being high at the top and low at the bottom. All patients had pressure values 20 times smaller in the iliac arteries compared with the neck of the aneurysm. The overall maximum pressure was similar between Patient R and Patient A, higher than the maximum pressure of Patient S. CONCLUSIONS: Computed fluid dynamics was implemented in anatomically accurate models of AAAs in different clinical scenarios for obtaining a broader understanding of the biomechanical properties that determine the behavior of AAA. Further analysis and the inclusion of new metrics and technological tools are needed to accurately determine the key factors that will compromise the integrity of the patient's aneurysms anatomy.
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Aneurisma da Aorta Abdominal , Hemodinâmica , Humanos , Resultado do Tratamento , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ruptura , Estresse MecânicoRESUMO
OBJECTIVE: The objective of Health Technology Assessment International's 6th Latin America Policy Form, held in 2021, was to explore the implementation of deliberative processes in the framework of health technology assessment (HTA) and how agencies in the region could involve stakeholders in this process. METHODS: This paper is based on a preparatory survey, a background document, and the deliberative work of participants at the virtual Forum conducted in 2021. There were ninety-one participants in the open session and fifty-two in the closed sessions, representing twelve countries and diverse areas of the health sector. RESULTS: While there are mechanisms in most countries in Latin America to consider stakeholder involvement to some degree, it remains reduced or limited to a consultative role, making true participative involvement rare. There are significant barriers and structural and contextual limitations that have impeded or slowed progress toward deliberative processes. Relatively low levels of institutionalization and knowledge about HTA, as well as the lack of trust among stakeholders are important challenges. This situation has impacted health systems by diminishing the legitimacy of decisions and the very structures and processes of HTA. CONCLUSION: The Forum's broad group of participants identified barriers, facilitators, and recommendations to improve the use of deliberative processes in Latin America to foster improved fairness and reasonableness in HTA and decision making.
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Tomada de Decisões , Avaliação da Tecnologia Biomédica , Humanos , América LatinaRESUMO
OBJECTIVE: To provide an update on the use of health technology assessment (HTA) in Asia and lessons for countries seeking to advance HTA. METHODS: Build upon the research by Chootipongchaivat and the World Health Organization identifying eighteen "factors conducive to the development of HTA in Asia." These factors were used to create a balanced scorecard to assess the progress of HTA, measuring progress against each factor in China, India, Indonesia, Malaysia, Philippines, South Korea, Taiwan, Thailand, and Vietnam. A scoring system was used wherein: 1, No progress; 2, milestone at early stages, ad hoc HTA use; 3, progress on milestone but limited impact; 4, significant progress but limited remit; and 5, significant progress on milestone, routine HTA informs decisions. Total scores indicated progress of HTA while milestone scores provided contextual insights within countries. Literature reviews and expert interviews were used to complete scorecards. RESULTS: South Korea and Thailand scored highest with seventy-three and seventy-one points, respectively, while Vietnam scored lowest at 28.5. Advanced HTA programs have independent HTA agencies with a broad remit, explicit process and methods, network of researchers, and routine use of HTA. Taiwan and Malaysia fall in a middle tier, with established HTA programs with limited remit. The final tier with China, India, Indonesia, Philippines, and Vietnam, emerging HTA processes. CONCLUSIONS: Universal Health Coverage goals have catalyzed expansion of HTA. Political will, technical expertise, and sustained financing remain challenges for sustainable HTA programs. Legislation supporting HTA is helpful but political will is key. Recommendations for regional collaboration are provided.
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Avaliação da Tecnologia Biomédica , Índia , Indonésia , Filipinas , TailândiaRESUMO
OBJECTIVE: This study aims to identify and codify the facilitators and barriers to help implementing partners institutionalize health technology assessment (HTA) successfully and navigate complex systems for health-related policy making. METHODS: We searched for peer-reviewed and gray literature articles examining HTA programs globally using six databases. Keywords used as a guide for capturing articles included "health technology assessment," "barrier," and "facilitator" and their synonyms. Search results were scrutinized for duplicates and screened through a review of titles and abstracts. A full-text review was conducted exploring articles' coverage of twenty-seven evaluation criteria across four primary areas of interest: barriers/facilitators, motivations, guidelines, and institutional frameworks. RESULTS: A total of 18,599 records were identified for duplication check, title, and abstract review. A total of 1,594 articles underwent full-text review, leading to a final synthesis of 262 studies. We found that ninety-seven articles discussed barriers/facilitators, with fifty-three of those discussing local capacity and unavailable human resources. Out of the sixty-six articles discussing motivations, forty-two cited the interest in supporting the decision-making process for, and promoting, appropriate resource allocation. Of the sixty-one articles that discussed guidelines and institutional framework, twenty-one articles described HTA as an independent national unit, and sixteen described their HTA unit as a unit within the Ministry of Health (MOH). CONCLUSIONS: This systematic review unpacks the dynamic and relevant contexts for understanding the HTA institutionalization process to help policy makers and practitioners achieve tangible progress in confronting the most critical issues facing priority setting and HTA institutionalization.
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Tomada de Decisões , Política de Saúde , Humanos , Avaliação da Tecnologia Biomédica/métodos , Formulação de Políticas , Tecnologia BiomédicaRESUMO
The over-enrichment of nitrogen (N) in the environment has contributed to severe and recurring harmful cyanobacterial blooms, especially by the non-N2 -fixing Microcystis spp. N chemical speciation influences cyanobacterial growth, persistence and the production of the hepatotoxin microcystin, but the physiological mechanisms to explain these observations remain unresolved. Stable-labelled isotopes and metabolomics were employed to address the influence of nitrate, ammonium, and urea on cellular physiology and production of microcystins in Microcystis aeruginosa NIES-843. Global metabolic changes were driven by both N speciation and diel cycling. Tracing 15 N-labelled nitrate, ammonium, and urea through the metabolome revealed N uptake, regardless of species, was linked to C assimilation. The production of amino acids, like arginine, and other N-rich compounds corresponded with greater turnover of microcystins in cells grown on urea compared to nitrate and ammonium. However, 15 N was incorporated into microcystins from all N sources. The differences in N flux were attributed to the energetic efficiency of growth on each N source. While N in general plays an important role in sustaining biomass, these data show that N-speciation induces physiological changes that culminate in differences in global metabolism, cellular microcystin quotas and congener composition.
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Compostos de Amônio/farmacologia , Microcistinas/metabolismo , Microcystis/efeitos dos fármacos , Nitrogênio/farmacologia , Ureia/farmacologia , Aminoácidos/metabolismo , Biomassa , Microcystis/crescimento & desenvolvimento , Microcystis/metabolismoRESUMO
Membrane lipids are key determinants in the regulation of voltage-gated ion channels. Phosphatidylinositol 4,5-bisphosphate (PIP2), a native membrane phospholipid, has been involved in the maintenance of the current amplitude and in the voltage-independent regulation of voltage-gated calcium channels (VGCC). However, the nature of the PIP2 regulation on VGCC has not been fully elucidated. This work aimed to investigate whether the interacting PIP2 electrostatic charges may account for maintaining the current amplitude of CaV2.2 channels. Furthermore, we tested whether charge shielding of PIP2 mimics the voltage-independent inhibition induced by M1 muscarinic acetylcholine receptor (M1R) activation. Therefore, neomycin, a polycation that has been shown to block electrostatic interactions of PIP2, was intracellularly dialyzed in superior cervical ganglion (SCG) neurons of the rat. Consistently, neomycin time-dependently diminished the calcium current amplitude letting the channel exhibit the hallmarks of the voltage-independent regulation. These results support that interacting PIP2 charges not only underly the maintenance of the channel-current but also that charge screening of PIP2 by itself unveils the voltage-independent features of CaV2.2 channels in SCG neurons.
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Canais de Cálcio Tipo N/metabolismo , Cálcio/metabolismo , Neomicina/farmacologia , Neurônios/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Sistema Nervoso Simpático/citologia , Animais , Cátions , Masculino , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Fosfolipídeos/química , Ratos , Ratos Wistar , Receptores Muscarínicos/metabolismo , Transdução de Sinais , Eletricidade EstáticaRESUMO
AIMS: To evaluate the safety and pharmacokinetics of naringenin in healthy adults consuming whole-orange (Citrus sinensis) extract. METHODS AND METHODS: In a single-ascending-dose randomized crossover trial, 18 adults ingested doses of 150 mg (NAR150), 300 mg (NAR300), 600 mg (NAR600) and 900 mg (NAR900) naringenin or placebo. Each dose or placebo was followed by a wash-out period of at least 1 week. Blood safety markers were evaluated pre-dose and 24 hours post-dose. Adverse events (AEs) were recorded. Serum naringenin concentrations were measured before and over 24 hours following ingestion of placebo, NAR150 and NAR600. Four- and 24-hour serum measurements were obtained after placebo, NAR300 and NAR900 ingestion. Data were analysed using a mixed-effects linear model. RESULTS: There were no relevant AEs or changes in blood safety markers following ingestion of any of the naringenin doses. The pharmacokinetic variables were: maximal concentration: 15.76 ± 7.88 µM (NAR150) and 48.45 ± 7.88 µM (NAR600); time to peak: 3.17 ± 0.74 hours (NAR150) and 2.41 ± 0.74 hours (NAR600); area under the 24-hour concentration-time curve: 67.61 ± 24.36 µM × h (NAR150) and 199.05 ± 24.36 µM × h (NAR600); and apparent oral clearance: 10.21 ± 2.34 L/h (NAR150) and 13.70 ± 2.34 L/h (NAR600). Naringenin half-life was 3.0 hours (NAR150) and 2.65 hours (NAR600). After NAR300 ingestion, serum concentrations were 10.67 ± 5.74 µM (4 hours) and 0.35 ± 0.30 µM (24 hours). After NAR900 ingestion, serum concentrations were 43.11 ± 5.26 µM (4 hours) and 0.24 ± 0.30 µM (24 hours). CONCLUSIONS: Ingestion of 150 to 900 mg doses of naringenin is safe in healthy adults, and serum concentrations are proportional to the dose administered. Since naringenin (8 µM) is effective in primary human adipocytes, ingestion of 300 mg naringenin twice/d will likely elicit a physiological effect.
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Flavanonas/administração & dosagem , Flavanonas/farmacocinética , Administração Oral , Adulto , Área Sob a Curva , Citrus/química , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Flavanonas/efeitos adversos , Meia-Vida , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Extratos Vegetais/química , Adulto JovemRESUMO
[This corrects the article DOI: 10.1186/s12962-018-0127-6.].
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OBJECTIVE: Recent years have witnessed an increased interest in the use of multicriteria decision analysis (MCDA) to support health technology assessment (HTA) agencies for setting healthcare priorities. However, its implementation to date has been criticized for being "entirely mechanistic," ignoring opportunity costs, and not following best practice guidelines. This article provides guidance on the use of MCDA in this context. METHODS: The present study was based on a systematic review and consensus development. We developed a typology of MCDA studies and good implementation practice. We reviewed 36 studies over the period 1990 to 2018 on their compliance with good practice and developed recommendations. We reached consensus among authors over the course of several review rounds. RESULTS: We identified 3 MCDA study types: qualitative MCDA, quantitative MCDA, and MCDA with decision rules. The types perform differently in terms of quality, consistency, and transparency of recommendations on healthcare priorities. We advise HTA agencies to always include a deliberative component. Agencies should, at a minimum, undertake qualitative MCDA. The use of quantitative MCDA has additional benefits but also poses design challenges. MCDA with decision rules, used by HTA agencies in The Netherlands and the United Kingdom and typically referred to as structured deliberation, has the potential to further improve the formulation of recommendations but has not yet been subjected to broad experimentation and evaluation. CONCLUSION: MCDA holds large potential to support HTA agencies in setting healthcare priorities, but its implementation needs to be improved.
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Tomada de Decisões , Avaliação da Tecnologia Biomédica/organização & administração , Técnicas de Apoio para a Decisão , Humanos , Avaliação das Necessidades , Anos de Vida Ajustados por Qualidade de Vida , Projetos de Pesquisa , Índice de Gravidade de Doença , Avaliação da Tecnologia Biomédica/normasRESUMO
BACKGROUND: All healthcare systems face problems of justice and efficiency related to setting priorities for allocating limited financial resources. Therefore, explicit decision-making in healthcare depicted as a continuum from evidence generation to deliberation and communication of the decision made, needs to be transparent and fair. Nevertheless, priority-setting in many parts of the world remains being implicit and ad-hoc process. Health Technology Assessment (HTA) and Multi-Criteria Decision Analysis (MCDA) have emerged as policy tools to assist informed decision-making. Both, MCDA and HTA have pros and cons. MAIN BODY: Colombia experienced an important institutional transformation after the establishment of the Health Technology Assessment Institute in 2012. This paper briefly presents the current challenges of the Colombian health system, the general features of the new health sector reform, the main characteristics of HTA in Colombia and the potential benefits and caveats of incorporating MCDA approaches into the decision-making process. CONCLUSION: Structured and objective consideration of the factors that are both measurable and value-based in an open and transparent manner may be feasible through combining HTA and MCDA in contexts like Colombia. Further testing and validation of HTA and MCDA solely or combined in LMICs are needed to advance these approaches into healthcare decision-making worldwide.
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Metabolomic profiling is becoming an increasingly important technique in the larger field of systems biology by allowing the simultaneous measurement of thousands of small molecules participating in and resulting from cellular reactions. In this way, metabolomics presents an opportunity to observe the physiological state of a system, which may provide the ability to monitor the whole of cellular metabolism as the technology progresses. The arbuscular mycorrhizal fungus Gigaspora margarita has not previously been explored with regard to metabolite composition. To develop a better understanding of G. margarita and the influences of its endosymbiont Candidatus Glomeribacter gigasporarum, a metabolomic analysis was applied to quiescent and germinated spores with and without endobacteria. Over 100 metabolites were identified and greater than 2600 unique unidentified spectral features were observed. Multivariate analysis of the metabolomes was performed, and a differentiation between all metabolic states of spores and spores hosting the endobacteria was observed. The known metabolites were recruited to many biochemical pathways, with many being involved in maintenance of the antioxidant potential, tyrosine metabolism, and melanin production. Each of the pathways had higher metabolite abundances in the presence of the endosymbiont. These metabolomics data also agree with previously reported transcriptomics results demonstrating the capability of this technique to confirm hypotheses and showing the feasibility of multi-omic approaches for the study of arbuscular mycorrhizal fungi and their endobacterial communities. Challenges still exist in metabolomic analysis, e.g., the identification of compounds is demanding due to incomplete libraries. A metabolomics technique to probe the effects of bacterial endosymbionts on fungal physiology is presented herein, and this method is useful for hypothesis generation as well as testing as noted above.
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Bactérias/crescimento & desenvolvimento , Metabolômica/métodos , Micorrizas/fisiologia , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Redes e Vias Metabólicas , Metaboloma , Micorrizas/metabolismo , Esporos Fúngicos/metabolismo , Esporos Fúngicos/fisiologia , SimbioseRESUMO
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the first causes of skin and soft tissue infections, and can also produce severe diseases such as osteomyelitis and pneumonia. The aim of this descriptive study was to determine the SCCmec type and virulence profile and to study the genetic diversity by MLVA analysis of 21 CA-MRSA isolates that infected Paraguayan children in 2010. The SCCmec type and virulence factors were performed by PCR and genetic diversity by MLVA (multiple locus variable analysis). All the isolates carried SCCmec cassette iv. hla, hlb and sea genes were detected in 28,6%, 9,5% and 4,8% respectively. The MLVA analysis showed high genetic diversity with congruent antibiotic resistance and virulence profiles. This study revealed the presence of CA-MRSA harbouring SCCmeciv with high genetic diversity, providing information not available in our country.
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Staphylococcus aureus Resistente à Meticilina , Meticilina , Infecções Estafilocócicas , Antibacterianos , Criança , Infecções Comunitárias Adquiridas , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Paraguai/epidemiologia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Virulência , Fatores de VirulênciaRESUMO
Vessel diameter is objectively measured by a lead ruler positioned in the fluoroscopic field and software calibration during angioplasty. We conducted a prospective study to evaluate the accuracy of lead ruler determination of vessel diameter. Chronic hemodialysis patients undergoing an angioplasty procedure were included in this study (n = 37). Vessel diameter was determined by calibrating the fluoroscopy machine to a ruler with lead markers placed in the fluoroscopic field. The same calibration was used to measure the fully effaced angioplasty balloon in its intravascular location. We compared the measured balloon diameter with the actual (manufacturer's) diameter. The approximate depth of the ruler from the measured vessel was also determined. Angioplasty balloons appeared 13.75-40.83% (mean 25.8% ± 7.015) smaller than the actual size of the balloon (p < 0.0001) when measured using a calibrated fluoroscopic machine. There was a tendency toward the fact that the bigger the distance between the ruler and the vessel (that contained the angioplasty balloon), the more likely the technique underestimated the size of the angioplasty balloon. Lead ruler method underestimates the diameter of the vessel. Recognizing such a discrepancy is important when determining the size of an angioplasty balloon or endovascular stent.
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Angioplastia Coronária com Balão/métodos , Angiografia Coronária/métodos , Doença das Coronárias/diagnóstico por imagem , Vasos Coronários/cirurgia , Fluoroscopia/métodos , Stents , Doença das Coronárias/cirurgia , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Percutaneous transluminal balloon angioplasty (PTA) is a commonly performed procedure for hemodialysis vascular access dysfunction including thrombosis. While PTA is generally safe, balloon rupture during the procedure is a potential complication. Because such a rupture can cause damage to the blood vessel, indication of an imminent balloon rupture might help avoid such a complication. This analysis reports on six PTA procedures that were complicated by balloon rupture. All cases demonstrated terminal (caudal/cranial) cinch deformation. There was a loss of sharp terminal tapering and its replacement with banana silhouette before the balloon rupture. Importantly, the contour deformation and balloon rupture occurred at a pressure that was lower than the rated burst pressure. The cinch deformity can be used as an indication for impending balloon rupture. We suggest deflation of balloons that demonstrate shape deformations to avoid vascular injury.
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Angioplastia com Balão/instrumentação , Falha de Equipamento , Adulto , Idoso , Feminino , Humanos , Complicações Intraoperatórias/prevenção & controle , Masculino , Pessoa de Meia-IdadeRESUMO
Cow's milk allergy (CMA) is an immune-based disease that has become an increasing problem. The diagnosis and management of CMA varies from one clinical setting to another and represents a challenge in pediatric practice. In addition, because nonallergic food reactions can be confused with CMA symptoms, there is an overdiagnosis of the disease. In response to these situations, pediatric specialties from recognized institutions throughout Latin America decided to develop a clinical guideline for diagnosis and management of cow's milk allergy. These guidelines include definitions, epidemiology, pathophysiology overview, clinical and evidencebased recommendations for the diagnosis and treatment of CMA. They also include prevention and prognosis sections and identify gaps in the current knowledge to be addressed through future research.
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Hipersensibilidade a Leite/diagnóstico , Proteínas do Leite/efeitos adversos , Guias de Prática Clínica como Assunto , Medicina Baseada em Evidências , Humanos , América Latina , Hipersensibilidade a Leite/epidemiologia , Hipersensibilidade a Leite/terapia , Proteínas do Leite/imunologia , PrognósticoRESUMO
Cervical cancer is a global health concern and ranks fourth among the most prevalent cancers in women worldwide. Human papillomavirus (HPV) infection is a known precursor of cervical cancer and preventive measures include prophylactic vaccines. This study focused on sexually active Paraguayan women aged 18-25 years, exploring the intersection of HPV vaccination and sexual behavior. Among 254 participants, 40.9% received the Gardasil-4 vaccine, with no significant differences in sexual behavior between the vaccinated and unvaccinated sexually active groups. However, a notable decrease in the prevalence of HPV among the vaccinated women highlights the efficacy of this vaccine in reducing infections. The prevalence of any HPV type was 37.5% in vaccinated participants compared to 56.7% in unvaccinated participants (p = 0.0026). High-risk HPV types showed a significant difference, with a prevalence of 26.0% in vaccinated women compared with 52.7% in unvaccinated women (p < 0.001). Although a potential decline in genital warts was observed among the vaccinated individuals, statistical significance (p = 0.0564) was not reached. Despite the challenges in achieving high vaccination coverage, the observed reduction in HPV prevalence underscores the importance of ongoing monitoring, healthcare professional recommendations, and comprehensive risk management. These findings contribute to dispelling concerns about HPV vaccination influencing sexual behavior, advocating further large-scale research to explore the impact of vaccines on various HPV types and potential cross-protection.
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OBJECTIVE: The objective of this study was to investigate the flow effects in different degrees of thoracic aortic stent graft protrusion extension by creating bird beak effect simulations using accurate 3D geometry and a realistic, nonlinear, elastic biomechanical model using computer-aided software SolidWorks. METHODS: Segmentation in 3D of an aortic arch from a computed tomography (CT) scan of a real-life patient was performed using SolidWorks. A parametric analysis of three models was performed: (A) Aortic arch with no stent, (B) 3 mm bird-beak configuration, and (C) 6.5 mm bird-beak configuration. Flow velocity, pressure, vorticity, wall shear stress (WSS), and time average WSS were assessed. RESULTS: The flow velocity in Model A remained relatively constant and low in the area of the ostium of the brachiocephalic artery and doubled in the left subclavian artery. On the contrary, Models B and C showed a decrease in velocity of 52.3 % in the left subclavian artery. Furthermore, Model B showed a drop in velocity of 82.7% below the bird-beak area, whereas Model C showed a decline of 80.9% in this area. The pressure inside the supra-aortic branches was higher in Model B and C compared with Model A. In Model A, vorticity only appeared at the level of the descending aorta, with low to non-vorticity in the aortic arch. In contrast, Models B and C had an average vorticity of 241.4 Hz within the bird beak area. Regarding WSS, Model A, and Model B shared similar WSS in the peak systolic phase, in the aortic arch, and the bird beak area, whereas Model C had an increased WSS by 5 Pa on average at these zones. CONCLUSION: In the present simulations' lower velocities, higher pressures, vortices, and WSS were observed around the bird beak zone, the aortic arch, and the supra-aortic vessels.
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Aorta Torácica , Aortografia , Prótese Vascular , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Hemodinâmica , Modelos Cardiovasculares , Stents , Estresse Mecânico , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aorta Torácica/fisiologia , Humanos , Velocidade do Fluxo Sanguíneo , Procedimentos Endovasculares/instrumentação , Implante de Prótese Vascular/instrumentação , Simulação por Computador , Fluxo Sanguíneo Regional , Modelagem Computacional Específica para o Paciente , Desenho de Prótese , Pressão Arterial , Dinâmica não Linear , Fenômenos Biomecânicos , Interpretação de Imagem Radiográfica Assistida por ComputadorRESUMO
GPCRs regulate Ca(V)2.2 channels through both voltage dependent and independent inhibition pathways. The aim of the present work was to assess the phosphatidylinositol-4,5-bisphosphate (PIP2) as the molecule underlying the voltage independent inhibition of Ca(V)2.2 channels in SCG neurons. We used a double pulse protocol to study the voltage independent inhibition and changed the PIP(2) concentration by means of blocking the enzyme PLC, filling the cell with a PIP(2) analogue and preventing the PIP(2) resynthesis with wortmannin. We found that voltage independent inhibition requires the activation of PLC and can be hampered by internal dialysis of exogenous PIP(2). In addition, the recovery from voltage independent inhibition is blocked by inhibition of the enzymes involved in the resynthesis of PIP(2). These results support that the hydrolysis of PIP(2) is responsible for the voltage independent inhibition of Ca(V)2.2 channels.
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Canais de Cálcio Tipo N/metabolismo , Neurônios/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Sistema Nervoso Simpático/citologia , Androstadienos/farmacologia , Animais , Fenômenos Eletrofisiológicos , Ativação Enzimática , Hidrólise , Masculino , Fosfoinositídeo Fosfolipase C/biossíntese , Inibidores de Fosfoinositídeo-3 Quinase , Ratos , Ratos Wistar , WortmaninaRESUMO
Cardiac implantable electronic device (CIED) leads can cause central venous stenosis (CVS). In addition, these devices can get infected. Both are critically important considerations in patients with chronic kidney disease (CKD) for at least two reasons: (i) central veins serve as the final pathway should these patients need an arteriovenous access to provide dialysis therapy; and (ii) the presence of renal failure increases the risk of CIED infection. In this analysis, we investigated the prevalence as well as the degree of chronic kidney disease in patients harboring a CIED. Patients undergoing CIED removal were evaluated from 2001 to 2011. The patients were categorized into CKD stage I-V based on National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines. A total of 503 patients underwent CIED removal. Demographic characteristics revealed that 30% had hypertension, 44% were diabetics, 77% had coronary artery disease, and 84% suffered from congestive heart failure. Ninety percent (452/503) of the patients had CKD (stage I = I9 [4.2%], stage II = 189 [41.8%], stage III A = 96 [21.2%], stage III B = 59 [13.0%], stage IV = 45 [9.9%], and stage V = 44 [9.7%]). Overall, 148 (32.7%) patients (stage III B, stage IV, and stage V) of 452 had advanced renal failure. The results of this study reveal that one-third of CIED patients undergoing device removal have advanced chronic kidney disease.
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Arritmias Cardíacas/terapia , Remoção de Dispositivo , Marca-Passo Artificial/efeitos adversos , Insuficiência Renal Crônica/epidemiologia , Trombose Venosa Profunda de Membros Superiores/complicações , Idoso , Feminino , Humanos , Masculino , Prevalência , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Trombose Venosa Profunda de Membros Superiores/cirurgiaRESUMO
A retrospective study evaluating the pattern of blood pressure and its related complications before, during, and after percutaneous hemodialysis interventions was performed in patients presenting with asymptomatic hypertension. Hemodialysis patients undergoing percutaneous interventions including tunneled hemodialysis catheter insertion, percutaneous balloon angioplasty and thrombectomy procedure, and stage II hypertension (systolic blood pressure ≥160 mmHg) were included in this analysis. Blood pressure medications were not used while midazolam and fentanyl were routinely administered. Patients were followed for up to 4 weeks to monitor any complications. The mean blood pressure before, during, and after the procedures were 185 ± 18/96 ± 14, 172 ± 22/92 ± 15, and 153 ± 25/87 ± 14, respectively. There was a statistically significant difference between the blood pressure readings before and after the procedure (before = 185 ± 18/96 ± 14, after = 153 ± 25/87 ± 14; p = 0.001). None of the patients had a stroke, myocardial infarction, or acute pulmonary edema before, during, or after the procedure or during the 4-week follow-up period. A significant reduction in blood pressure was observed after the procedure without the administration of any antihypertensive medication. These results suggest that the reduction in blood pressure observed after percutaneous dialysis access interventions (particularly in the presence of midazolam and fentanyl) may make it unnecessary to treat asymptomatic hypertension prior to these procedures.