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1.
Proc Natl Acad Sci U S A ; 120(52): e2313999120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38079564

RESUMO

Brine shrimp (Artemia) are the only animals to thrive at sodium concentrations above 4 M. Salt excretion is powered by the Na+,K+-ATPase (NKA), a heterodimeric (αß) pump that usually exports 3Na+ in exchange for 2 K+ per hydrolyzed ATP. Artemia express several NKA catalytic α-subunit subtypes. High-salinity adaptation increases abundance of α2KK, an isoform that contains two lysines (Lys308 and Lys758 in transmembrane segments TM4 and TM5, respectively) at positions where canonical NKAs have asparagines (Xenopus α1's Asn333 and Asn785). Using de novo transcriptome assembly and qPCR, we found that Artemia express two salinity-independent canonical α subunits (α1NN and α3NN), as well as two ß variants, in addition to the salinity-controlled α2KK. These ß subunits permitted heterologous expression of the α2KK pump and determination of its CryoEM structure in a closed, ion-free conformation, showing Lys758 residing within the ion-binding cavity. We used electrophysiology to characterize the function of α2KK pumps and compared it to that of Xenopus α1 (and its α2KK-mimicking single- and double-lysine substitutions). The double substitution N333K/N785K confers α2KK-like characteristics to Xenopus α1, and mutant cycle analysis reveals energetic coupling between these two residues, illustrating how α2KK's Lys308 helps to maintain high affinity for external K+ when Lys758 occupies an ion-binding site. By measuring uptake under voltage clamp of the K+-congener 86Rb+, we prove that double-lysine-substituted pumps transport 2Na+ and 1 K+ per catalytic cycle. Our results show how the two lysines contribute to generate a pump with reduced stoichiometry allowing Artemia to maintain steeper Na+ gradients in hypersaline environments.


Assuntos
Artemia , Salinidade , Animais , Artemia/genética , Lisina , Sódio/metabolismo , Cloreto de Sódio/metabolismo , Íons/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
2.
J Am Soc Nephrol ; 35(2): 135-148, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38044490

RESUMO

SIGNIFICANCE STATEMENT: In this study, we demonstrate that a common, low-cost compound known as octanedioic acid (DC 8 ) can protect mice from kidney damage typically caused by ischemia-reperfusion injury or the chemotherapy drug cisplatin. This compound seems to enhance peroxisomal activity, which is responsible for breaking down fats, without adversely affecting mitochondrial function. DC 8 is not only affordable and easy to administer but also effective. These encouraging findings suggest that DC 8 could potentially be used to assist patients who are at risk of experiencing this type of kidney damage. BACKGROUND: Proximal tubules are rich in peroxisomes, which are damaged during AKI. Previous studies demonstrated that increasing peroxisomal fatty acid oxidation (FAO) is renoprotective, but no therapy has emerged to leverage this mechanism. METHODS: Mice were fed with either a control diet or a diet enriched with dicarboxylic acids, which are peroxisome-specific FAO substrates, then subjected to either ischemia-reperfusion injury-AKI or cisplatin-AKI models. Biochemical, histologic, genetic, and proteomic analyses were performed. RESULTS: Both octanedioic acid (DC 8 ) and dodecanedioic acid (DC 12 ) prevented the rise of AKI markers in mice that were exposed to renal injury. Proteomics analysis demonstrated that DC 8 preserved the peroxisomal and mitochondrial proteomes while inducing extensive remodeling of the lysine succinylome. This latter finding indicates that DC 8 is chain shortened to the anaplerotic substrate succinate and that peroxisomal FAO was increased by DC 8 . CONCLUSIONS: DC 8 supplementation protects kidney mitochondria and peroxisomes and increases peroxisomal FAO, thereby protecting against AKI.


Assuntos
Injúria Renal Aguda , Ácidos Dicarboxílicos , Suplementos Nutricionais , Traumatismo por Reperfusão , Animais , Humanos , Camundongos , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/patologia , Cisplatino , Ácidos Dicarboxílicos/administração & dosagem , Ácidos Graxos , Proteômica , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/patologia
3.
Am J Physiol Renal Physiol ; 327(1): F128-F136, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38695076

RESUMO

Acute kidney injury (AKI) is extremely prevalent among hospitalizations and presents a significant risk for the development of chronic kidney disease and increased mortality. Ischemia caused by shock, trauma, and transplant are common causes of AKI. To attenuate ischemic AKI therapeutically, we need a better understanding of the physiological and cellular mechanisms underlying damage. Instances of ischemia are most damaging in proximal tubule epithelial cells (PTECs) where hypoxic signaling cascades, and perhaps more rapidly, posttranslational modifications (PTMs), act in concert to change cellular metabolism. Here, we focus on the effects of the understudied PTM, lysine succinylation. We have previously shown a protective effect of protein hypersuccinylation on PTECs after depletion of the desuccinylase sirtuin5. General trends in the results suggested that hypersuccinylation led to upregulation of peroxisomal activity and was protective against kidney injury. Included in the list of changes was the Parkinson's-related deglycase Park7. There is little known about any links between peroxisome activity and Park7. In this study, we show in vitro and in vivo that Park7 has a crucial role in protection from AKI and upregulated peroxisome activity. These data in combination with published results of Park7's protective role in cardiovascular damage and chronic kidney disease lead us to hypothesize that succinylation of Park7 may ameliorate oxidative damage resulting from AKI and prevent disease progression. This novel mechanism provides a potential therapeutic mechanism that can be targeted.NEW & NOTEWORTHY Succinylation is an understudied posttranslational modification that has been shown to increase peroxisomal activity. Furthermore, increased peroxisomal activity has been shown to reduce oxidative stress and protect proximal tubules after acute kidney injury. Analysis of mass spectrometry succinylomic and proteomic data reveals a novel role for Parkinson's related Park7 in mediating Nrf2 antioxidant response after kidney injury. This novel protection pathway provides new insights for kidney injury prevention and development of novel therapeutics.


Assuntos
Injúria Renal Aguda , Túbulos Renais Proximais , Proteína Desglicase DJ-1 , Animais , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/patologia , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Proteína Desglicase DJ-1/metabolismo , Proteína Desglicase DJ-1/genética , Processamento de Proteína Pós-Traducional , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Masculino , Sirtuínas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Camundongos , Estresse Oxidativo , Lisina/metabolismo
4.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33597302

RESUMO

Cellular survival requires the ion gradients built by the Na+/K+ pump, an ATPase that alternates between two major conformations (E1 and E2). Here we use state-specific engineered-disulfide cross-linking to demonstrate that transmembrane segment 2 (M2) of the pump's α-subunit moves in directions that are inconsistent with distances observed in existing crystal structures of the Na+/K+ pump in E1 and E2. We characterize this movement with voltage-clamp fluorometry in single-cysteine mutants. Most mutants in the M1-M2 loop produced state-dependent fluorescence changes upon labeling with tetramethylrhodamine-6-maleimide (TMRM), which were due to quenching by multiple endogenous tryptophans. To avoid complications arising from multiple potential quenchers, we analyzed quenching of TMRM conjugated to R977C (in the static M9-M10 loop) by tryptophans introduced, one at a time, in M1-M2. This approach showed that tryptophans introduced in M2 quench TMRM only in E2, with D126W and L130W on the same helix producing the largest fluorescence changes. These observations indicate that M2 moves outward as Na+ is deoccluded from the E1 conformation, a mechanism consistent with cross-linking results and with proposals for other P-type 2 ATPases.


Assuntos
Cisteína/química , Oócitos/fisiologia , ATPase Trocadora de Sódio-Potássio/química , ATPase Trocadora de Sódio-Potássio/metabolismo , Sódio/metabolismo , Animais , Cisteína/genética , Cisteína/metabolismo , Fluorometria , Oócitos/citologia , Conformação Proteica , Domínios Proteicos , ATPase Trocadora de Sódio-Potássio/genética , Xenopus laevis
5.
Pediatr Radiol ; 53(11): 2167-2179, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37710037

RESUMO

The use of magnetic resonance imaging (MRI) in the evaluation of the central extracranial nervous system, namely the brachial and lumbosacral plexuses, is well established and has been performed for many years. Only recently after numerous advances in MRI, has image quality been sufficient to properly visualize small structures, such as nerves in the extremities. Despite the advances, peripheral MR Neurography remains a complex and difficult examination to perform, especially in the pediatric patient population, in which the risk for motion artifact and compliance is always of concern. Thus, technical aspects of the MR imaging protocol must be flexible but robust, to balance image quality with scan time, in a patient population of varying sizes. An additional important step for reliably performing a successful MR Neurography examination is the non-technical pre-imaging preparation, which includes patient/family education and open communication with referring teams. This paper will discuss in detail the individual technical and non-technical/operational aspects of peripheral MR Neurography, to help guide in building a successful program in the pediatric population.

6.
J Couns Psychol ; 70(3): 276-292, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37023277

RESUMO

Anti-Black racism (ABR) contributes to racial trauma and to the disproportionate negative mental, physical, and social outcomes faced by Black populations (Hargons et al., 2017; Wun, 2016a). The previous literature demonstrates that storytelling and other narrative interventions are often used to promote collective healing among Black people (Banks-Wallace, 2002; Moors, 2019). Storying survival (i.e., the utilization of stories to promote liberation from racial trauma) is one such narrative intervention (Mosley et al., 2021); however, little is known about the processes by which Black people utilize storying survival to promote radical healing. Using an intersectional framework and thematic analysis from a phenomenological perspective (Braun & Clarke, 2006), the present study analyzed interviews from 12 racial justice activists in order to understand how these activists engage in storying survival to foster Black survival and healing. Results show that storying survival includes five interconnected components: storying influences, mechanisms of storying survival, content of storying survival, context of storying survival, and impact of storying survival. Each of these categories and subcategories are detailed herein and are supported with quotations. The findings and related discussion explore the concept of storying survival and its contributions to critical consciousness, radical hope, strength and resistance, cultural self-knowledge, and collectivism among participants and their communities. This study therefore provides important and practical information about how Black people and the counseling psychologists who aim to serve them can utilize storying survival to resist and heal from ABR. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Narração , Racismo , Humanos , Comunicação , Autoimagem , Racismo/psicologia
7.
Radiographics ; 42(6): 1580-1597, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36190845

RESUMO

The field of pediatric interventional radiology encompasses the treatment of a broad range of patients. Whether treating a premature infant who weighs less than 1 kg or treating an adult-sized teenager who weighs more than 100 kg, the innovative skills of the interventional radiologist are required to adapt equipment designed for adult patients, to meet the needs of children. Moreover, children cannot be treated simply as small adults owing to a number of factors, including differences in physiology, disease processes, and treatment techniques between pediatric and adult patients. In this article, the unique medical needs of children are highlighted, noting specific areas the interventional radiologist should be aware of when treating patients of all ages. Specific focus is placed on the unique considerations related to children in terms of their periprocedural needs and the procedural modifications required for routine pediatric procedures, with specific diseases of the liver, chest, and musculoskeletal system highlighted. The broader topic of vascular anomalies, although an important part of pediatric interventional radiology, was intentionally excluded to highlight some of the lesser-known procedures performed. ©RSNA, 2022.


Assuntos
Radiologia Intervencionista , Adolescente , Criança , Humanos , Lactente , Radiologia Intervencionista/métodos
8.
Pediatr Radiol ; 52(3): 570-586, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34713322

RESUMO

In pediatric liver transplantation, bile duct complications occur with a greater incidence than vascular anastomotic dysfunction and represent a major source of morbidity and mortality. While surgical re-anastomosis can reduce the need for retransplantation, interventional radiology offers minimally invasive and graft-saving therapies. The combination of small patient size and prevailing Roux-en-Y biliary enteric anastomotic techniques makes endoscopic retrograde cholangiopancreatography difficult if not impossible. Expertise in percutaneous management is therefore imperative. This article describes post-surgical anatomy, pathophysiology and noninvasive imaging of biliary complications. We review percutaneous techniques, focusing heavily on biliary access and interventions for reduced liver grafts. Subsequently we review the results and adverse events of these procedures and describe conditions that masquerade as biliary obstruction.


Assuntos
Sistema Biliar , Colestase , Transplante de Fígado , Criança , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Radiologia Intervencionista , Reoperação , Estudos Retrospectivos
9.
J Magn Reson Imaging ; 53(2): 504-513, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32815203

RESUMO

BACKGROUND: Diffusion-weighted imaging (DWI) is common for evaluating pediatric musculoskeletal lesions, but suffers from geometric distortion and intense acoustic noise. PURPOSE: To investigate the performance of a near-silent and distortion-free DWI sequence (DW-SD) relative to standard echo-planar DWI (DW-EPI) in pediatric extremity MRI. STUDY TYPE: Prospective validation study. SUBJECTS: Thirty-nine children referred for extremity MRI. FIELD STRENGTH/SEQUENCE: DW-EPI and DW-SD, based on a rotating ultrafast sequence modified with sinusoidal diffusion preparation gradients, at 3T. ASSESSMENT: DW-SD image quality (Sanat ) was assessed from 0 (nondiagnostic) to 5 (outstanding) and comparative image quality (Scomp ) (from -2 = DW-EPI more delineated to +2 = DW-SD more delineated, 0 = same). ADC measured by DW-SD and DW-EPI were compared in bone marrow, muscle, and lesions. STATISTICAL TESTS: Wilcoxon rank-sum test and confidence interval of proportions (CIOP) were calculated for Scomp , Student's t-test, coefficient of variation (COV), and Bland-Altman analysis for ADC values, and intraclass correlation coefficient (ICC) for interreader agreement. RESULTS: DW-SD and DW-EPI ADC values for bone marrow, muscle, and lesions were not significantly different (P = 0.3, P = 0.2, and P = 0.27, respectively) and had an overall ADC COV of 14.8% (95% confidence interval: 12.3%, 16.9%) and no significant proportional bias on Bland-Altman analysis. Sanat CIOP was rated diagnostic or better (score of 3, 4, or 5) in 72-98% of cases for bone marrow, muscle, and soft tissues. DW-SD was equivalent to or preferred over DW-EPI in muscles and soft tissues, with CIOP 86-93% and 93%, respectively. Lesions were equally visualized on DW-SD and DW-EPI in 40-51%, with DW-SD preferred in 44-56% of cases. DW-SD was rated significantly better than DW-EPI across all comparative variables that included bone marrow, muscle, soft tissue, cartilage, and lesions (P < 0.05). Readers had moderate to near-perfect (ICC range = 0.45-0.85). DATA CONCLUSION: DW-SD of the extremities provided similar ADC values and improved image quality compared with conventional DW-EPI. Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:504-513.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Interpretação de Imagem Assistida por Computador/métodos , Doenças Musculoesqueléticas/diagnóstico por imagem , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
10.
Pediatr Radiol ; 51(13): 2549-2560, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34156504

RESUMO

BACKGROUND: Projection radiography (XR) is often supplemented by both CT (to evaluate osseous structures with ionizing radiation) and MRI (for marrow and soft-tissue assessment). Zero echo time (ZTE) MR imaging produces a "CT-like" osseous contrast that might obviate CT. OBJECTIVE: This study investigated our institution's initial experience in implementing an isotropic ZTE MR imaging sequence for pediatric musculoskeletal examinations. MATERIALS AND METHODS: Pediatric patients referred for extremity MRI at 3 tesla (T) underwent ZTE MR imaging to yield images with contrast similar to that of CT. A radiograph-like image was also created with ray-sum image processing. We assessed ZTE-CT/XR anatomical image quality (Sanat) from 0 (nondiagnostic) to 5 (outstanding). Further, we made image comparisons on a 5-point scale (Scomp) (range of -2 = conventional CT/XR greater anatomical delineation to +2 = ZTE-CT/XR greater anatomical delineation; 0=same) for three cohorts: (1) ZTE-XR to conventional radiography, (2) ZTE-CT to conventional CT and (3) pathological lesion assessment on ZTE-XR to conventional radiography. We measured cortical thickness of ZTE-XR and ZTE-CT and compared these with conventional imaging. We calculated confidence interval of proportions, Wilcoxon rank sum test and intraclass correlation coefficients for inter-reader agreement. RESULTS: Cohorts 1, 2 and 3 consisted of 40, 20 and 35 cases, respectively (age range 0.6-23.0 years). ZTE-CT versus CT and ZTE-XR versus radiography of cortical thicknesses were not significantly different (P=0.55 and P=0.31, respectively). Cortical delineation was rated diagnostic or better (score of 3, 4 or 5) in all cases (confidence interval of proportions = 100%) for ZTE-CT/XR. Similarly, intramedullary cavity delineation was rated diagnostic or better in all cases for ZTE-CT, and ZTE-XR was at least diagnostic in 58-63% of cases. For cohort 2, cortex and intramedullary cavity Scomp for ZTE-CT was comparable to those of conventional CT, with confidence interval of proportion (sum of score of -1 to +2) of 93-100% and 95%, respectively. Pathology visualized on ZTE-CT/XR was comparable; Scomp confidence interval of proportions was 95%/97-100%, with improved delineation of non-displaced fractures on ZTE-XR. Readers had moderate to near-perfect intraclass correlation coefficient (range=0.60-0.93). CONCLUSION: Implementation of a diagnostic-quality ZTE MRI sequence in the pediatric population is feasible and can be performed as a complementary pulse sequence to enhance musculoskeletal MRI studies. Compared to conventional CT, ZTE has comparable cortical delineation, intramedullary cavity and pathology visualization. While not intended as a replacement for conventional radiography, ZTE-XR provides similar visualization of pathology.


Assuntos
Imageamento por Ressonância Magnética , Sistema Musculoesquelético , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Espectroscopia de Ressonância Magnética , Sistema Musculoesquelético/diagnóstico por imagem , Adulto Jovem
11.
J Vasc Interv Radiol ; 30(10): 1549-1554, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31526576

RESUMO

PURPOSE: To identify factors independently associated with disease recurrence after venoplasty and stent placement for May-Thurner syndrome (MTS). MATERIALS AND METHODS: Fifty-nine consecutive patients (age, 47 y ± 15; 93% female) were identified who had undergone endovascular stent placement for MTS. Patient charts were reviewed for demographic data, risk factors for venous thrombosis, comorbidities, and venous inflow or outflow at first follow-up (3 wk to 6 mo after treatment). Logistic regression was used to identify independent predictors of symptom recurrence or repeat intervention, and multivariate analysis of variance and receiver operator characteristic curve analysis were used to assess relationships between degrees of in-stent stenosis and other variables in the 73% of patients with available cross-sectional imaging. Median follow up was 20.7 months (interquartile range, 4.7-49.5 mo). RESULTS: All procedures were technically successful. Disease recurrence, defined as symptom recurrence following initial postprocedural resolution, was observed in 38% of patients. No preprocedural variable was found to be independently predictive of disease recurrence; however, poor venous inflow or outflow were both strongly associated with recurrent disease, with adjusted odds ratios and 95% confidence intervals of 38.02 (3.76-384.20; P = .002) and 7.00 (1.15-42.71; P = .04), respectively. Higher degrees of in-stent stenosis were also associated with symptom recurrence, with an area under the curve of 0.93 (P = .000002) and 39%-41% stenosis being 78%-83% sensitive and 88%-92% specific for symptom recurrence. CONCLUSIONS: These results suggest that cross-sectional imaging can help differentiate patients in whom closer follow-up may be warranted after venoplasty and stent placement for MTS and also guide counseling regarding prognosis.


Assuntos
Procedimentos Endovasculares/instrumentação , Veia Ilíaca , Síndrome de May-Thurner/terapia , Stents , Adulto , Chicago , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/fisiopatologia , Masculino , Síndrome de May-Thurner/diagnóstico por imagem , Síndrome de May-Thurner/fisiopatologia , Pessoa de Meia-Idade , Flebografia/métodos , Recidiva , Retratamento , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
12.
J Zoo Wildl Med ; 50(1): 266-269, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120689

RESUMO

Livingstone's fruit bats (Pteropus livingstonii) are critically endangered and a captive population has been established as part of the International Union for Conservation of Nature Species Action Plan. The largest colony, in Jersey Zoo, was sampled for staphylococcal carriage and at infection sites, as disease associated with staphylococci had previously been found. Staphylococci were cultured from swabs from 44 bats (skin, oropharynx, mouth ejecta, skin lesions) and from their enclosure. The isolates were identified by matrix-assisted laser desorption-ionization time of flight mass spectrometry; antimicrobial susceptibility testing was performed by disc diffusion and screening for mecA and mecC. Seventeen species of coagulase-negative staphylococci including Staphylococcus xylosus, S. kloosii, S. nepalensis, and S. simiae were isolated. Staphylococcus aureus was identified from both carriage and lesional sites. These findings suggest S. nepalensis may be part of the normal carriage flora of bats. Antimicrobial resistance rates were low and methicillin-resistant Staphylococcus aureus (MRSA) was not identified. Sampling of mouth ejecta for staphylococci may provide results representative for carriage sites.


Assuntos
Quirópteros , Farmacorresistência Bacteriana , Microbiologia Ambiental , Infecções Estafilocócicas/veterinária , Staphylococcus/isolamento & purificação , Animais , Animais de Zoológico , Anti-Infecciosos/farmacologia , Ilhas Anglo-Normandas , Microbiota , Infecções Estafilocócicas/microbiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/fisiologia
13.
Biophys J ; 115(2): 361-374, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-30021111

RESUMO

Na/K pumps build essential ion gradients across the plasmalemma of animal cells by coupling the extrusion of three Na+, with the import of two K+ and the hydrolysis of one ATP molecule. The mechanisms of selectivity and competition between Na+, K+, and inhibitory amines remain unclear. We measured the effects of external tetrapropylammonium (TPA+) and ethylenediamine (EDA2+) on three different Na/K pump transport modes in voltage-clamped Xenopus oocytes: 1) outward pump current (IP), 2) passive inward H+ current at negative voltages without Na+ or K+ (IH), and 3) transient charge movement reporting the voltage-dependent extracellular binding/release of Na+ (QNa). Both amines competed with K+ to inhibit IP. TPA+ inhibited IH without competing with H+, whereas EDA2+ did not alter IH at pH 7.6. TPA+ competed with Na+ in QNa measurements, reducing Na+-apparent affinity, evidenced by a ∼-75 mV shift in the charge-voltage curve (at 20 mM TPA+) without reduction of the total charge moved (Qtot). In contrast, EDA2+ and K+ did not compete with Na+ to inhibit QNa; both reduced Qtot without decreasing Na+-apparent affinity. EDA2+ (15 mM) right-shifted the charge-voltage curve by ∼+50 mV. Simultaneous occlusion of EDA2+ and Na+ by an E2P conformation unable to reach E1P was demonstrated by voltage-clamp fluorometry. Trypsinolysis experiments showed that EDA2+-bound pumps are much more proteolysis-resistant than Na+-, K+-, or TPA+-bound pumps, therefore uncovering unique EDA2+-bound conformations. K+ effects on QNa and IH were also evaluated in pumps inhibited with beryllium fluoride, a phosphate mimic. K+ reduced Qtot without shifting the charge-voltage curve, indicating noncompetitive effects, and partially inhibited IH to the same extent as TPA+ in non-beryllium-fluorinated pumps. These results demonstrate that K+ interacts with beryllium-fluorinated pumps inducing conformational changes that alter QNa and IH, suggesting that there are two external access pathways for proton transport by IH.


Assuntos
Aminas/metabolismo , Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Sódio/metabolismo , Aminas/farmacologia , Animais , Transporte de Íons/efeitos dos fármacos , Cinética , Modelos Moleculares , Ligação Proteica , Conformação Proteica , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/química , Xenopus laevis
14.
Neuroradiology ; 60(7): 745, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29766237

RESUMO

In the original version of this article one author name was published incorrectly: Tanja Ddjurdjevic has been corrected to Tanja Djurdjevic.

15.
Neuroradiology ; 60(7): 735-744, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29644398

RESUMO

PURPOSE: Endovascular stents are widely used for the elective treatment of cerebral aneurysms. Acute stenting is performed in the management of dissections, pseudo-aneurysms, broad-based aneurysms or as a 'bail out' measure after coil migration. The purpose of this study is to review the safety of using stents in acute subarachnoid haemorrhage. METHODS: The stent registry of our institution was reviewed for procedures in patients with acute subarachnoid haemorrhage. Imaging studies were reviewed on the hospital's PACS system and the patients' notes were retrieved to assess complications and clinical outcomes. Procedures were analysed according to the type of stent, treatment indication, antiplatelet regime, complications and outcomes. RESULTS: Between 2008 and 2016, 51 stents were placed during 50 stenting procedures in 49 patients with acute subarachnoid haemorrhage. This included 24 patients with saccular aneurysms, 10 with blister aneurysms, 10 dissections and five fusiform aneurysms. Stents were deployed in 'bail out' situations on eight occasions. In six cases, flow-diverting stents were used. Eighteen patients (37%) in the cohort suffered a stroke. Nine patients (18%) suffered persistent clinical deficits as a result of the stenting procedure, all but one of which occurred within 24 h. Two patients had a transient ischaemic episode, and there was evidence of asymptomatic ischaemia on imaging in four cases (8%). Five patients died, three (6%) as a result of procedural complications. Twelve patients (25%) required a further embolisation procedure. CONCLUSION: The use of stents in acute subarachnoid haemorrhage incurs a considerable complication risk and should be reserved for exceptional circumstances.


Assuntos
Stents , Hemorragia Subaracnóidea/cirurgia , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Complicações Pós-Operatórias , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento
16.
Eur Radiol ; 27(7): 2828-2834, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27957642

RESUMO

OBJECTIVES: To describe the use of radiology in the emergency department (ED) in a trauma centre during a mass casualty incident, using a minimum acceptable care (MAC) strategy in which CT was restricted to potentially severe head injuries. METHODS: We retrospectively studied the initial use of imaging on patients triaged to the trauma centre following the twin terrorist attacks in Norway on 22 July 2011. RESULTS: Nine patients from the explosion and 15 from the shooting were included. Fourteen patients had an Injury Severity Score >15. During the first 15 h, 22/24 patients underwent imaging in the ED. All 15 gunshot patients had plain films taken in the ED, compared to three from the explosion. A CT was performed in 18/24 patients; ten of these were completed in the ED and included five non-head CTs, the latter representing deviations from the MAC strategy. No CT referrals were delayed or declined. Mobilisation of radiology personnel resulted in a tripling of the staff. CONCLUSIONS: Plain film and CT capacity was never exceeded despite deviations from the MAC strategy. An updated disaster management plan will require the radiologist to cancel non-head CTs performed in the ED until no additional MCI patients are expected. KEY POINTS: • Minimum acceptable care (MAC) should replace normal routines in mass casualty incidents. • MAC implied reduced use of imaging in the emergency department (ED). • CT in ED was restricted to suspected severe head injuries during MAC. • The radiologist should cancel all non-head CTs in the ED during MAC.


Assuntos
Planejamento em Desastres/métodos , Serviço Hospitalar de Emergência , Incidentes com Feridos em Massa/estatística & dados numéricos , Terrorismo/estatística & dados numéricos , Centros de Traumatologia , Triagem/organização & administração , Ferimentos por Arma de Fogo/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Noruega/epidemiologia , Estudos Retrospectivos , Ferimentos por Arma de Fogo/epidemiologia , Adulto Jovem
17.
J Neuroeng Rehabil ; 13(1): 97, 2016 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-27842598

RESUMO

BACKGROUND: The purpose of this study was to derive data from real, recorded, personal emergency response call conversations to help improve the artificial intelligence and decision making capability of a spoken dialogue system in a smart personal emergency response system. The main study objectives were to: develop a model of personal emergency response; determine categories for the model's features; identify and calculate measures from call conversations (verbal ability, conversational structure, timing); and examine conversational patterns and relationships between measures and model features applicable for improving the system's ability to automatically identify call model categories and predict a target response. METHODS: This study was exploratory and used mixed methods. Personal emergency response calls were pre-classified according to call model categories identified qualitatively from response call transcripts. The relationships between six verbal ability measures, three conversational structure measures, two timing measures and three independent factors: caller type, risk level, and speaker type, were examined statistically. RESULTS: Emergency medical response services were the preferred response for the majority of medium and high risk calls for both caller types. Older adult callers mainly requested non-emergency medical service responders during medium risk situations. By measuring the number of spoken words-per-minute and turn-length-in-words for the first spoken utterance of a call, older adult and care provider callers could be identified with moderate accuracy. Average call taker response time was calculated using the number-of-speaker-turns and time-in-seconds measures. Care providers and older adults used different conversational strategies when responding to call takers. The words 'ambulance' and 'paramedic' may hold different latent connotations for different callers. CONCLUSIONS: The data derived from the real personal emergency response recordings may help a spoken dialogue system classify incoming calls by caller type with moderate probability shortly after the initial caller utterance. Knowing the caller type, the target response for the call may be predicted with some degree of probability and the output dialogue could be tailored to this caller type. The average call taker response time measured from real calls may be used to limit the conversation length in a spoken dialogue system before defaulting to a live call taker.


Assuntos
Serviços Médicos de Emergência/métodos , Idioma , Reconhecimento Automatizado de Padrão/métodos , Adulto , Idoso , Comunicação , Feminino , Humanos , Masculino
19.
Tidsskr Nor Laegeforen ; 140(7)2020 05 05.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-32378864

RESUMO

A woman with acute abdominal pain was admitted to hospital with suspected cholecystitis. In addition to abdominal pain, she had vomiting, loss of appetite, diarrhoea and symptoms of pyrexia. She had no symptoms from the respiratory tract, but was later found to have COVID-19. A number of patients have presented with similar symptoms at our hospital. This has led to temporary changes in our procedures for handling and investigating patients with acute abdominal pain.


Assuntos
Abdome Agudo , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Abdome Agudo/etiologia , Betacoronavirus , COVID-19 , Infecções por Coronavirus/complicações , Humanos , Pneumonia Viral/complicações , SARS-CoV-2
20.
J Magn Reson Imaging ; 39(1): 85-93, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24339366

RESUMO

PURPOSE: To use a simplified hemodynamic model and Fourier-encoded velocity data to measure pulse pressure (PP) in the descending aorta. MATERIALS AND METHODS: A one-dimensional, cylindrically localized pulse sequence with Fourier velocity encoding (FVE) was used to obtain time-dependent velocity distributions along the descending aorta. Numerical evaluation of a simplified hemodynamic model, based on a cross-sectionally averaged form of the mass conservation equation, allowed estimation of the average pressure waveform and PP along 6-cm-long segments located within the descending aorta. Magnetic resonance (MR)-derived pressures were compared against applanation tonometry (AT) performed in healthy subjects (n = 18) and intravascular pressure measurements (IVPM) obtained in patients (n = 4) undergoing diagnostic cardiac angiography and then found to be either normal or with clinically insignificant coronary artery disease. RESULTS: The root mean square (RMS) error between MR- and AP-derived pressure waveforms was 11.7 ± 5.8%. With respect to IVPM, the RMS error ranged from 4.2% to 14.7%. In terms of pulse pressures, there was good agreement with both AT (bias = 0.99 mmHg; 95% limits of agreement (LOA) = [-5.0 to 7.0 mmHg]; range = 12.0 mmHg) and IVPM (bias = -1.82 mmHg; 95% LOA = [-7.2 to 3.5 mmHg]; range = 10.7 mmHg). CONCLUSION: FVE M-mode and numerical evaluation of a simplified flow model can be used to estimate central pulse pressures noninvasively and accurately with respect to well-established gold standards.


Assuntos
Pressão Arterial , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Algoritmos , Cateterismo Cardíaco , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/patologia , Análise de Fourier , Voluntários Saudáveis , Hemodinâmica , Humanos , Processamento de Imagem Assistida por Computador , Manometria , Pessoa de Meia-Idade , Pressão
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