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Air pollution accountability studies examine the relationship(s) between an intervention, regulation, or event and the resulting downstream impacts, if any, on emissions, exposure, and/or health. The sequence of events has been schematically described as an accountability chain. Here, we update the existing framework to capture real-life complexities and to highlight important factors that fall outside the linear chain. This new "accountability web" is intended to convey the intricacies associated with conducting an accountability study to various audiences, including researchers, policy makers, and stakeholders. We also identify data considerations for planning and completing a robust accountability study, including those relevant to novel and innovative air pollution and exposure data. Finally, we present a series of recommendations for the accountability research community that can serve as a guide for the next generation of accountability studies.
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PROBLEM: Experiencing a child's seizure can be challenging for parents. METHODS: We investigated parental experiences of their child's first seizure and how their perception and management of seizures changed over time. From September 2020 to March 2021, we invited parents who had witnessed at least two of their child's seizures to take part in a semi-structured interview. Parents whose children experienced solely absence seizures were excluded. RESULTS: Of the parents, 52/74 (70%) did not recognize their child's first epileptic seizure and assumed the event to be due to a different cause, for instance teething. Parents overwhelmingly reported fear (48/74; 65%) and surprise (13/74; 18%) as the predominant emotional responses to the first seizure. In response to the most recently observed seizure parents reported feelings related to fear (33/74; 45%) and happiness (16/74; 22%), with regard to the latter, especially "being calm" or "feeling safe". Asked for thoughts in response to the first seizure, 22/74 (30%) reported concerns about their child's future, with regard to the most recent seizure, 15/74 (20%) expressed such thoughts. Of the parents, 53/74 (72%) did not know how to respond to the first seizure. Concerning the most recent seizure, 48/74 (65%) said they felt confident in managing the seizure. CONCLUSION: Experiencing the child's first seizure was very challenging for parents. During the course of the epilepsy, changes were observed in both parental perception of and confidence in managing the seizures. Physicians should consider these changes when counselling parents in order to better target their evolving needs.
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Epilepsia Tipo Ausência , Convulsões , Humanos , Criança , Emoções , Relações Pais-Filho , Pais/psicologiaRESUMO
PURPOSE: Early clinical trials are the first step into clinical therapies for new drugs. Within the six Bavarian university-based hospitals (Augsburg, Erlangen, Regensburg, Munich (LMU and TU), Würzburg) we have enrolled a virtual network platform for patient discussion. METHODS: The virtual Early Clinical Trial Unit Tumor Board (ECTU Tumor Board) is a secured web-based meeting to evaluate early clinical trial options for patients, where representatives from local ECTUs participate. We retrospectively analyzed patient cases discussed between November 2021 and November 2022. RESULTS: From November 2021 to November 2022, a total of 43 patients were discussed in the ECTU Tumor Board. Median age at diagnosis was 44.6 years (range 10-76 years). The median number of previous lines of therapies was 3.7 (range 1-9 therapies) including systemic treatment, surgery, and radiation therapy. A total of 27 different tumor entities were presented and 83.7% (36/43) patients received at least one trial recommendation. In total, 21 different active or shortly recruiting clinical trials were recommended: ten antibody trials, four BiTE (bispecific T cell engager) trials, six CAR (chimeric antigen receptor) T-cell trials, and one chemotherapy trial. Only six trials (28.6%) were recommended on the basis of the previously performed comprehensive genetic profiling (CGP). CONCLUSION: The ECTU Tumor Board is a feasible and successful network, highlighting the force of virtual patient discussions for improving patient care as well as trial recruitment in advanced diseases. It can provide further treatment options after local MTB presentation, aiming to close the gap to access clinical trials.
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The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.
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Fótons , Radiografia , Raios XRESUMO
BACKGROUND AND PURPOSE: Prior research has shown substantial shifts in procedure shares between specialty groups providing lumbar punctures. Our aim was to analyze national trends in lumbar punctures among the Medicare population from 2010 to 2018. MATERIALS AND METHODS: Medicare Part B Physician/Supplier Procedure Summary Master Files from 2010 to 2018 were analyzed for all Current Procedural Terminology, Version 4 codes related to lumbar punctures (62270 and 62272). Lumbar puncture procedure volume and utilization rates were assessed and stratified by place of service and specialty background of the providers. RESULTS: From 2010 to 2018, the overall number of lumbar puncture procedures essentially has not changed (92,579 versus 92,533). Radiologists hold the largest and an increasing procedure share of diagnostic and overall lumbar punctures (overall share, 45.7% in 2010 [n = 42,296] versus 52.3% in 2018 [n = 48,414]). Advanced practice providers have increased their procedure share (3.7% in 2010 [n = 3388] versus 8.4% in 2018 [n = 7785], + 129.8% procedure volume). Emergency medicine physicians and neurologists have a decreasing procedure share (21.8% versus 15.3% and 12.5% versus 8.8%, respectively). The inpatient hospital setting remains the largest place of service for lumbar punctures, recording a 5.3% increase in procedure share. The emergency department lumbar puncture volume has declined, with a 7.4% decrease in the overall procedure share. Similarly, the hospital outpatient department procedure volume has increased (+4%), while the private office volume has decreased (-1.7%). CONCLUSIONS: During the past decade, lumbar puncture procedures among the Medicare population have remained stable, with a shift in procedure volume from the emergency department and private offices to the hospital setting, which has mainly affected radiologists and advanced practice providers.
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Radiologistas , Punção Espinal/tendências , Serviço Hospitalar de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/tendências , Feminino , Hospitais/estatística & dados numéricos , Hospitais/tendências , Humanos , Masculino , Medicare , Radiologistas/estatística & dados numéricos , Estados UnidosRESUMO
Background. Proper handwashing can reduce the burden of diseases related to hand hygiene (HH) and so contribute reducing under-5 mortality. Preschoolers can benefit from HH interventions by the burden of disease and absenteeism being reduced. Objective. To perform a scoping review of literature to assess the types and effectiveness of HH interventions at preschools, with a view to providing a guideline for appropriate interventions for South African facilities. Methods. A literature search was conducted through the PubMed database to identify relevant studies. An iterative screening process to focus the review allowed for information on the type and effectiveness of interventions to be collated. An updated PubMed search was conducted to determine whether any interventions related to COVID-19 at preschools could be included. Results. No additional studies relating to COVID-19 were found. Of the 305 studies identified during the initial search, only 12 fitted the specific search criteria. Of these, 10 studies showed improvements in HH-related indicators following the interventions. Only two studies used health education as an intervention, whereas the others included the supply of HH products (to varying extents) as part of the intervention. Conclusion. HH interventions appear successful in reducing diseases spread by poor HH, improving general HH practices and reducing absenteeism among preschoolers. Studies using innovative, entertaining methods of educating children have shown to be successful in improving handwashing techniques and decreasing microbial growth on children's hands. HH interventions are suggested as an effective measure to improve HH during the COVID-19 pandemic.
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Humanos , Pré-Escolar , Desinfecção das Mãos , Doenças Transmissíveis , Higiene das Mãos , COVID-19RESUMO
OBJECTIVE: We investigated whether ideal cardiovascular health (ICH), a metric proposed by the American Heart Association, predicts depression development. METHODS: Cohort analysis from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Adults with no current depression and other common mental disorders, cardiovascular diseases, and antidepressant drug use at baseline had their ICH (composite score of smoking, dietary habits, body mass index, blood pressure, fasting glucose, cholesterol, and physical activity) assessed and classified into poor, intermediate, and optimal. Depression was assessed using the Clinical Interview Schedule-Revised (CIS-R). Poisson regression models, adjusted for sociodemographic factors and alcohol consumption, were employed. Stratified analyses were performed for age and sex. RESULTS: We included 9214 participants (mean age 52 ± 9 years, 48.6% women). Overall depression incidence at 3.8-year follow-up was 1.5%. Intermediate and poor ICH significantly increased the risk rate (RR) of developing depression (2.48 [95%CI 1.06-5.78] and 3 [1.28-7.03], respectively) at a 3.8-year follow-up. Higher ICH scores decreased the rate of depression development (RR = 0.84 [0.73-0.96] per metric). Stratified analyses were significant for women and adults < 55 years old. CONCLUSIONS: Poor cardiovascular health tripled depression risk at follow-up in otherwise healthy adults. Ameliorating cardiovascular health might decrease depression risk development.
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Doenças Cardiovasculares/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Indicadores Básicos de Saúde , Adulto , Idoso , Brasil/epidemiologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
Extensively malted cereals counteract enterotoxic diarrhea and inflammatory bowel diseases. This effect depends on a protein called antisecretory factor (AF), which is secreted into the blood as a larger complex known as the compleasome. In this study, we identified anti-inflammatory substances in malt and assayed their capacity to induce AF. Guaiacol and quercetin inhibited inflammation in a mouse footpad model, while catechin, sinapic acid, ferulic acid, and quercetin inhibited nitric oxide formation in RAW 264.7 cells. The proteasome activity in these cells was inhibited by vanillic acid and quercetin but not by the other tested phenols. As the transient receptor potential vanilloid 1 (TRPV1) might be involved in AF induction, the TRPV1 antagonist capsazepine was tested and shown to inhibit inflammation in mouse paw and nitric oxide formation. Catechin, ferulic acid, and sinapic acid induced AF in rat blood, and these substances were all increased in malt compared to control wheat. These phenols might therefore be of particular importance for the beneficial effect of malted cereals on inflammatory diseases. Our results further suggest that TRPV1 might play a role in the anti-inflammatory activity of phenols via the induction of AF.
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Neuropeptídeos , Triticum , Animais , Anti-Inflamatórios , Grão Comestível , Camundongos , RatosRESUMO
AIM: To determine the willingness of women with extremely dense breasts to undergo breast cancer screening with magnetic resonance imaging (MRI) in a research setting, and to examine reasons for women to participate or not. MATERIALS AND METHODS: Between 2011 and 2015, 8,061 women (50-75 years) were invited for supplemental MRI as part of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial (ClinicalTrials.gov Identifier: NCT01315015), after a negative screening mammography in the national population-based mammography screening programme. Demographics of participants and non-participants were compared. All invitees were asked to report reasons for (non)participation. Ethical approval was obtained. Participants provided written informed consent. RESULTS: Of the 8,061 invitees, 66% answered that they were interested, and 59% eventually participated. Participants were on average 54-years old (interquartile range: 51-59 years), comparable to women with extremely dense breasts in the population-based screening programme (55 years). Women with higher socio-economic status (SES) were more often interested in participation than women with lower SES (68% versus 59%, p<0.001). The most frequently stated reasons for non-participation were "MRI-related inconveniences and/or self-reported contraindications to MRI" (27%) and "anxiety regarding the result of supplemental screening" (21%). "Expected personal health benefit" (68%) and "contribution to science" (43%) were the most frequent reasons for participation. CONCLUSION: Of women invited for MRI because of extremely dense breasts, 59% participated. Common reasons for non-participation were "MRI-related inconveniences" and "anxiety regarding the result of supplemental screening". In case of future implementation, availability of precise evidence on benefits and harms might reduce this anxiety.
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Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cooperação do Paciente , Idoso , Neoplasias da Mama/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Programas de Rastreamento , Pessoa de Meia-Idade , Países Baixos , Fatores de RiscoRESUMO
The antisecretory factor is an endogenous protein found in all mammalian tissues investigated so far. It acts by counteracting intestinal hypersecretion and various forms of inflammation, but the detailed mechanism of antisecretory factor (AF) action is unknown. We tested neuronal GABAA receptors by means of AF-16, a potent AF peptide derived from amino acids 36-51 from the NH2 part of AF. Cultured rat cerebellar granule cells were used, and the effects on the GABA-mediated chloride currents were determined by whole-cell patch clamp. Both the neurotransmitter GABA and AF-16 were added by perfusion of the experimental system. A 3-min AF-16 preincubation was more efficacious than 30 s in significantly elevating the rapidly desensitizing GABA-activated chloride current. No effect was found on the tonic, slowly desensitizing current. The GABA-activated current increase by AF-16 demonstrated a low k of 41 pM with a maximal increase of 37% persisting for some minutes after AF washout, independent from GABA concentration. This indicates an effect on the maximal stimulation (E%Max) excluding an altered affinity between GABA and its receptor. An immunocytochemical fluorescence approach with anti γ2 subunit antibodies demonstrated an increased expression of GABAA receptors. Thus, both the electrophysiological and the immunofluorescence approach indicate an increased appearance of GABAA receptors on the neuronal membrane. The rationale of the experiments was to test the effect of AF on a defined neuronal population of GABAA receptors. The implications of the results on the impact of AF on the enteric nervous system or on brain function are discussed.
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Neurônios/efeitos dos fármacos , Peptídeos/farmacologia , Receptores de GABA-A/metabolismo , Animais , Células Cultivadas , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Acute myocardial infarction (AMI) is the main cause of global and in-hospital mortality in patients with cardiovascular diseases. We aimed to examine the association between the coronary artery involved and the in-hospital mortality in patients who underwent primary percutaneous coronary intervention (pPCI) after ST segment elevation myocardial infarction (STEMI). METHODS: The in-hospital mortality of STEMI patients who underwent pPCI was assessed at the Department of Cardiology, Harzklinik Goslar, Germany, which has no access to immediate mechanical circulatory support (MCS), between 2013 and 2017. RESULTS: We enrolled 312 STEMI patients, with a mean age of 67.1 ± 13.4 years, of whom 211 (68%) were male. In-hospital mortality was documented in 31 patients (10%). In-hospital mortality was associated with pre-hospital cardiopulmonary resuscitation (CPR; n = 39/12.5%), older age, lower systolic blood pressure, Killip class > 1, triple-vessel disease (each p < 0.0001), female gender (p = 0.0158), and with the localization of the treated culprit lesion in the left main coronary artery (LMCA; p = 0.0083) and in the ramus circumflexus (RCX; p = 0.0141). CONCLUSION: In this monocentric cohort, all-cause in-hospital mortality of STEMI patients after pPCI was significantly higher in those patients with culprit lesions in the LMCA and in the RCX, which may prove to be a substantial novel risk factor for STEMI-related mortality. Increasing age and female gender may be interdependent risk factors for mortality in this patient population. Furthermore, our data highlight the importance of the availability of MCS options in pPCI centers for patients after CPR.
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Mortalidade Hospitalar , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Resultado do TratamentoRESUMO
The data in this article shows the effect of isopropyl myristate (IPM) on a 2D Stratum Corneum lipid model. In the first part, the analytical characterization of the synthesized deuterated isopropyl myristate is given. Then a BAM image of the pure Stratum Corneum model used is shown and a dataset of surface-pressure - area isotherms considering various ratios of deuterated and non-deuterated IPM and the Stratum Corneum model mixture is provided. Assuming that after the plateau in the isotherm the area per molecule corresponds only to the Stratum Corneum model (squeezing out of IPM), the value of the area will correspond to the percentage of these lipids in the mixture when considering the pure SC model. The comparison of the real and the calculated areas per molecule is also done.
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BACKGROUND AND PURPOSE: T2*-weighted imaging provides sharp contrast between spinal cord GM and WM, allowing their segmentation and cross-sectional area measurement. Injured WM demonstrates T2*WI hyperintensity but requires normalization for quantitative use. We introduce T2*WI WM/GM signal-intensity ratio and compare it against cross-sectional area, the DTI metric fractional anisotropy, and magnetization transfer ratio in degenerative cervical myelopathy. MATERIALS AND METHODS: Fifty-eight patients with degenerative cervical myelopathy and 40 healthy subjects underwent 3T MR imaging, covering C1-C7. Metrics were automatically extracted at maximally compressed and uncompressed rostral/caudal levels. Normalized metrics were compared with t tests, area under the curve, and logistic regression. Relationships with clinical measures were analyzed by using Pearson correlation and multiple linear regression. RESULTS: The maximally compressed level cross-sectional area demonstrated superior differences (P = 1 × 10-13), diagnostic accuracy (area under the curve = 0.890), and univariate correlation with the modified Japanese Orthopedic Association score (0.66). T2*WI WM/GM showed strong differences (rostral: P = 8 × 10-7; maximally compressed level: P = 1 × 10-11; caudal: P = 1 × 10-4), correlations (modified Japanese Orthopedic Association score; rostral: -0.52; maximally compressed level: -0.59; caudal: -0.36), and diagnostic accuracy (rostral: 0.775; maximally compressed level: 0.860; caudal: 0.721), outperforming fractional anisotropy and magnetization transfer ratio in most comparisons and cross-sectional area at rostral/caudal levels. Rostral T2*WI WM/GM showed the strongest correlations with focal motor (-0.45) and sensory (-0.49) deficits and was the strongest independent predictor of the modified Japanese Orthopedic Association score (P = .01) and diagnosis (P = .02) in multivariate models (R2 = 0.59, P = 8 × 10-13; area under the curve = 0.954, respectively). CONCLUSIONS: T2*WI WM/GM shows promise as a novel biomarker of WM injury. It detects damage in compressed and uncompressed regions and contributes substantially to multivariate models for diagnosis and correlation with impairment. Our multiparametric approach overcomes limitations of individual measures, having the potential to improve diagnostics, monitor progression, and predict outcomes.
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Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Traumatismos da Medula Espinal/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Anatomia Transversal , Anisotropia , Imagem de Tensor de Difusão , Avaliação da Deficiência , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Compressão da Medula Espinal/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability. MATERIALS AND METHODS: Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects. RESULTS: T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation. CONCLUSIONS: Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.
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Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/ultraestrutura , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Traumatismos da Medula Espinal/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Medula Espinal/ultraestrutura , Adulto , Idoso , Anatomia Transversal , Anisotropia , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Coração/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Isopropyl myristate (IPM) is a widely used penetration enhancer in pharmaceutical formulations, however, its mechanism of action on a molecular scale is still not completely understood. Previous work using a quaternary Stratum Corneum (SC) lipid model in bulk suggested the incorporation of isopropyl myristate into the SC lipid matrix, phase separation, and perturbation of the multilamellar lipid assembly. Here, we used 2D Langmuir monolayers of a ternary SC lipid model, containing ceramide AP C18:18, stearic acid and cholesterol in a molar ratio of [1:1:0.7], respectively, to shed light on the mechanism of action of this important lipophilic penetration enhancer. To do so, the synthesis of chain deuterated isopropyl myristate was successfully performed in order to study the different coupling possibilities between the hydrogenated and deuterated IPM and the alkyl chains of the SC molecules. Our results indicate that only a small portion of IPM is able to mix with our SC model leading to a limited fluidizing effect (small increase of the wavenumber of CH2 stretching vibration, increase of the SC layer flexibility), but will be squeezed out at higher lateral pressures. Furthermore, the deuteration of IPM enhances the miscibility with this SC model, probably due to a different coupling between the alkyl chains or the alkyl and deuterated chains. Additionally, using the pure D-form of CER[AP] in the SC model amplifies the obtained results.
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Ceramidas/química , Miristatos/química , Pele/química , Termodinâmica , Humanos , Lipídeos/química , Modelos Moleculares , Estrutura MolecularRESUMO
We recently reported that skeletal muscle fibers of obscurin knockout (KO) mice present altered distribution of ankyrin B (ankB), disorganization of the subsarcolemmal microtubules, and reduced localization of dystrophin at costameres. In addition, these mice have impaired running endurance and increased exercise-induced sarcolemmal damage compared with wild-type animals. Here, we report results from a combined approach of physiological, morphological, and structural studies in which we further characterize the skeletal muscles of obscurin KO mice. A detailed examination of exercise performance, using different running protocols, revealed that the reduced endurance of obscurin KO animals on the treadmill depends on exercise intensity and age. Indeed, a mild running protocol did not evidence significant differences between control and obscurin KO mice, whereas comparison of running abilities of 2-, 6-, and 11-mo-old mice exercised at exhaustion revealed a progressive age-dependent reduction of the exercise tolerance in KO mice. Histological analysis indicated that heavy exercise induced leukocyte infiltration, fibrotic connective tissue deposition, and hypercontractures in the diaphragm of KO mice. On the same line, electron microscopy revealed that, in the diaphragm of exercised obscurin KO mice, but not in the hindlimb muscles, both M-line and H-zone of sarcomeres appeared wavy and less defined. Altogether, these results suggest that obscurin is required for the maintenance of morphological and ultrastructural integrity of skeletal muscle fibers against damage induced by intense mechanical stress and point to the diaphragm as the skeletal muscle most severely affected in obscurin-deficient mice.
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Diafragma/fisiologia , Diafragma/ultraestrutura , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas Musculares/metabolismo , Condicionamento Físico Animal/métodos , Sarcômeros/fisiologia , Sarcômeros/ultraestrutura , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Anquirinas/metabolismo , Tolerância ao Exercício/fisiologia , Fatores de Troca do Nucleotídeo Guanina/genética , Masculino , Camundongos , Camundongos Knockout , Contração Muscular/fisiologia , Proteínas Musculares/genética , Proteínas Serina-Treonina Quinases , Fatores de Troca de Nucleotídeo Guanina RhoRESUMO
OBJECTIVE: A retrospective chart review was performed to determine patient outcomes before and after partnership by gynecologic oncologists (GYN/ONC) with a sarcoma center (SC) for patients with recurrent unresectable/metastatic (RM) uterine leiomyosarcoma (uLMS). METHODS: 58 RM patients, identified from medical records of uLMS patients cared for by either GYN/ONC service and/or the SC between 1/1/2000-4/1/2014, were audited for patient and tumor characteristics, outcomes, and clinical trials enrollments. RESULTS: Of the 58 patients, 26 patients (48%) were treated by GYN/ONC alone and 32 were treated by a combination of GYN/ONC and SC (52%). Age, race, tumor size, grade, presence of lymphovascular invasion, cervical involvement, and FIGO stage at diagnosis were not statistically different between the two groups. There was a significant difference between the number of clinical trial enrollments (0.07 vs 0.84 trials/patient, p<0.001) and the number of chemotherapy regimens prescribed (2.67 vs 4.29/patient, p=0.03) by GYN/ONC vs SC; the latter was driven by the number of clinical trial enrollments by the SC. Sixty-nine percent of patients referred to the SC were enrolled in at least one clinical trial, while just 8% of patients in the GYN/ONC group were enrolled in at least one clinical trial, a difference that is significant (p<0.0001). CONCLUSIONS: Referral of RM uLMS patients by GYN/ONC to a dedicated clinical trials-based SC resulted in an increase in the number of chemotherapy regimens prescribed and clinical trial enrollments. Partnership between GYN/ONC and a dedicated SC with access to clinical trials should be encouraged for all RM uLMS patients.
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Ensaios Clínicos como Assunto/métodos , Ginecologia/organização & administração , Leiomiossarcoma/tratamento farmacológico , Oncologia/organização & administração , Seleção de Pacientes , Neoplasias Uterinas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto/estatística & dados numéricos , Feminino , Humanos , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Uterinas/patologiaRESUMO
BACKGROUND: Antibiotic resistence is increasing worldwide. AIM: A longitudinal analysis of the influence of the density of antibiotic use on the development of resistance in surgical units was undertaken. MATERIAL AND METHODS: Over five years the incidence of pathogens and the resistance rates of isolates from patients of normal surgical units and those of a surgical ICU at a university hospital were examined. The resistence rates were correlated with the density of antibiotic use - calculated from the antibiotic consumption (in DDD) and the number of patient-days. RESULTS: At both units, Enterobacteriaceae and Enterococci were mostly cultured. Among the Enterobacteriaceae, E. coli, Klebsiella spp., Proteus mirabilis and Enterobacter predominated. In the group of Enterococci, E. faecalis predominated at wards whereas at ICU E. faecium was the most frequent. Anaerobes ranked third at normal wards and Candida spp. at ICU. From 2007 to 2011, there was an increasing resistance against ciprofloxacin in P. mirabilis (r = 0.87; p = 0.054) and against imipenem (r = 0.86; p = 0.06) and piperacillin (r = 0.81; p = 0.09) in P. aeruginosa at normal wards. At ICU, the resistance rates of imipenem in P. aeruginosa rose (r = 0.88; p = 0.049). Resistance against ciprofloxacin in E. coli increased (r = 0.65; p = 0.23). Due to the increasing use of ciprofloxacin and meropenem at normal wards, the density of antibiotic usage rose 1.4â%/year (r = 0.94; p = 0.02). Despite the increase of meropenem use at ICU (r = 0.9; p = 0.035), the total antibiotic uptake rate remained almost constant. The antibiotic usage density was 3-fold higher at ICU than at normal wards. At normal wards, the ciprofloxacin usage correlated with the rate of resistance against ciprofloxacin in P. mirabilis P. m. At ICU, an association was detected between the uptake rate of ceftazidime and the rate of resistance against cefotaxime in the CES group. In P. aeruginosa, the use of piperacillin and the rate of resistance against piperacillin correlated. CONCLUSION: The high uptake rates of fluoroquinolones and carbapenems were accompanied by increases in resistances. The resistance rates are influenced by hygiene management and microbiological diagnostics. The extensive use of carbapenems should be reassessed on both units to counter further development of antibiotic resistance.