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BACKGROUND: Patients with Epstein-Barr virus-positive gastric cancers or those with microsatellite instability appear to have a favourable prognosis. However, the prognostic value of the chromosomal status (chromosome-stable (CS) versus chromosomal instable (CIN)) remains unclear in gastric cancer. METHODS: Gene copy number aberrations (CNAs) were determined in 16 CIN-associated genes in a retrospective study including test and validation cohorts of patients with gastric cancer. Patients were stratified into CS (no CNA), CINlow (1-2 CNAs) or CINhigh (3 or more CNAs). The relationship between chromosomal status, clinicopathological variables, and overall survival (OS) was analysed. The relationship between chromosomal status, p53 expression, and tumour infiltrating immune cells was also assessed and validated externally. RESULTS: The test and validation cohorts included 206 and 748 patients, respectively. CINlow and CINhigh were seen in 35.0 and 15.0 per cent of patients, respectively, in the test cohort, and 48.5 and 20.7 per cent in the validation cohort. Patients with CINhigh gastric cancer had the poorest OS in the test and validation cohorts. In multivariable analysis, CINlow, CINhigh and pTNM stage III-IV (P < 0.001) were independently associated with poor OS. CIN was associated with high p53 expression and low immune cell infiltration. CONCLUSION: CIN may be a potential new prognostic biomarker independent of pTNM stage in gastric cancer. Patients with gastric cancer demonstrating CIN appear to be immunosuppressed, which might represent one of the underlying mechanisms explaining the poor survival and may help guide future therapeutic decisions.
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Adenocarcinoma/genética , Adenocarcinoma/inmunología , Inestabilidad Cromosómica , Dosificación de Gen , Huésped Inmunocomprometido , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Adenocarcinoma/patología , Adenocarcinoma/virología , Anciano , Biomarcadores de Tumor/genética , Femenino , Genes p53/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/virologíaRESUMEN
BACKGROUND: The purpose of this study is to determine whether there are radiographic and systemic clinical characteristics that can predict final visual outcomes in patients with indirect traumatic optic neuropathy (iTON). METHODS: This study is a retrospective, multicenter case series of adult patients with iTON treated initially at large, urban, and/or academic trauma centers with follow-up at an affiliated ophthalmology clinic. In addition to detailed cranial computed tomography characteristics, demographics, systemic comorbidities, coinjuries, blood products administered, and intracranial pressure, along with other factors, were gathered. LogMAR visual acuity (VA) at the initial presentation to the hospital and up to 12 months follow-up was collected. RESULTS: Twenty patients met inclusion criteria; 16 (80%) were men with a mean age of 40.9 years (±20.9). Mean initial VA was 1.61 logMAR (â¼20/800, ± 0.95), and final VA was 1.31 logMAR (â¼20/400, ± 1.06). Three patients (4 eyes) had no light perception (NLP) VA at presentation and remained NLP at final follow-up. Of the predictors analyzed, only the initial VA was found to be a significant predictor of visual outcome. The presence of orbital fractures, intraconal and/or extraconal hemorrhage, as well as systemic comorbidities, were not found to significantly affect visual outcome. CONCLUSIONS: After evaluating multiple factors, initial VA was the only factor associated with visual prognosis in iTON. This knowledge may better enable clinicians to predict visual prognosis and set reasonable expectations with patients and families at the time of injury.
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Traumatismos del Nervio Óptico , Adulto , Ojo , Femenino , Humanos , Masculino , Traumatismos del Nervio Óptico/diagnóstico , Pronóstico , Estudios Retrospectivos , Agudeza VisualRESUMEN
INTRODUCTION: The success of the WHO Framework Convention on Tobacco Control (FCTC) depends on parties' active participation in its governance and implementation, particularly via biennial Conference of the Parties (COP) meetings. The COP's efficacy is threatened by declining attendance and reductions in travel support for low-income and middle-income countries, and there are growing concerns about transparency and representation in country delegations amid industry efforts to shape their composition. METHODS: We examined parties' participation in the COP based on official meeting records, and the relationship between attendance and strength of tobacco control based on national global tobacco control reports. RESULTS: Attendance at the COP has decreased over time, and at several meetings would have fallen below 66% (the threshold for decision-making) if it was not for high levels of participation among low-income and lower-middle-income countries. Despite their higher attendance at COP meetings, these countries represent a smaller share of meeting attendees due to the smaller size of their delegations. Additionally, there has been a decline in the proportion of delegates from ministries of health and tobacco control focal points. Nationally, COP participation is correlated with stronger tobacco control policies; attendance by low-income countries has a strong correlation with implementation of advertising bans, while attendance among high-income and lower-middle-income countries shows a moderate correlation with implementation of tobacco taxes. CONCLUSIONS: Supporting states to actively engage in the COP is crucial for ongoing FCTC implementation, strengthening national capacity for tobacco control, and protecting the legitimacy and efficacy of global health governance.
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Salud Global , Política Pública , Productos de Tabaco/legislación & jurisprudencia , Uso de Tabaco/legislación & jurisprudencia , Publicidad/legislación & jurisprudencia , Toma de Decisiones , Países en Desarrollo , Humanos , Impuestos , Industria del Tabaco/legislación & jurisprudencia , Productos de Tabaco/economía , Organización Mundial de la SaludRESUMEN
It is established that radiation forces can be used to transport ultrasound contrast agents, particularly for molecular imaging applications. However, the ability to model and control this process in the context of therapeutic ultrasound is limited by a paucity of data on the translational dynamics of encapsulated microbubbles under the influence of longer pulses. In this work, the translation of individual microbubbles, isolated with optical tweezers, was experimentally investigated over a range of diameters (1.8-8.8 µm, n = 187) and pressures (25, 50, 100, 150, and 200 kPa) with millisecond pulses. Data were compared with theoretical predictions of the translational dynamics, assessing the role of shell and history force effects. A pronounced feature of the displacement curves was an effective threshold size, below which there was only minimal translation. At higher pressures (≥150 kPa) a noticeable structure emerged where multiple local maxima occurred as a function of bubble size. The ability to accurately capture these salient features depended on the encapsulation model employed. In low Reynolds number conditions (i.e., low pressures, or high pressures, off-resonance) the inclusion of history force more accurately fit the data. After pulse cessation, bubbles exhibited substantial displacements consistent with the influence of history effects.
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Pérdida Auditiva , Acúfeno , Cefalea , Pérdida Auditiva/etiología , Humanos , Síndrome , Vértigo/etiologíaRESUMEN
The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in proinflammatory signaling, and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short-term secondhand smoke (SHS) exposure in RAGE knockout and control mice compared with identical animals exposed to room air only. Quantitative PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after 4 wk of SHS exposure and an anticipated absence of RAGE expression in RAGE knockout mice regardless of smoke exposure. Ras activation, NF-κB activity, and cytokine elaboration were assessed to characterize the molecular basis of SHS-induced inflammation in the mouse lung. Furthermore, bronchoalveolar lavage fluid was procured from RAGE knockout and control animals for the assessment of inflammatory cells and molecules. As a general theme, inflammation coincident with leukocyte recruitment was induced by SHS exposure and significantly influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to SHS. However, ongoing research is still warranted to fully explain roles for RAGE and other receptors in cells coping with involuntary smoke exposure for prolonged periods of time.
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Neumonía/metabolismo , Receptores Inmunológicos/metabolismo , Transducción de Señal , Contaminación por Humo de Tabaco/efectos adversos , Enfermedad Aguda , Animales , Regulación de la Expresión Génica/genética , Ratones , Ratones Noqueados , FN-kappa B/genética , FN-kappa B/metabolismo , Neumonía/etiología , Neumonía/genética , Neumonía/patología , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/genética , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
OBJECTIVE: As inspired oxygen availability falls with ascent to altitude, some individuals develop high-altitude headache (HAH). We postulated that HAH results when hypoxia-associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies. METHODS: In high-altitude studies, retinal venous distension (RVD) was ophthalmoscopically assessed in 24 subjects (6 female) and sea-level cranial magnetic resonance imaging was performed in 12 subjects ascending to 5,300m. Correlation of headache burden (summed severity scores [0-4]≤24 hours from arrival at each altitude) with RVD, and with cerebral/cerebrospinal fluid (CSF)/venous compartment volumes, was sought. In a sea-level hypoxic study, 11 subjects underwent gadolinium-enhanced magnetic resonance venography before and during hypoxic challenge (fraction of inspired oxygen=0.11, 1 hour). RESULTS: In the high-altitude studies, headache burden correlated with both RVD (Spearman rho=0.55, p=0.005) and with the degree of narrowing of 1 or both transverse venous sinuses (r=-0.56, p=0.03). It also related inversely to both the lateral+third ventricle summed volumes (Spearman rho=-0.5, p=0.05) and pericerebellar CSF volume (r=-0.56, p=0.03). In the hypoxic study, cerebral and retinal vein engorgement were correlated, and rose as the combined conduit score fell (a measure of venous outflow restriction; r=-0.66, p<0.05 and r=-0.75, p<0.05, respectively). INTERPRETATION: Arterial hypoxemia is associated with cerebral and retinal venous distension, whose magnitude correlates with HAH burden. Restriction in cerebral venous outflow is associated with retinal distension and HAH. Limitations in cerebral venous efferent flow may predispose to headache when hypoxia-related increases in cerebral arterial flow occur.
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Altitud , Venas Cerebrales/patología , Venas Cerebrales/fisiopatología , Circulación Cerebrovascular/fisiología , Cefalea/etiología , Cefalea/patología , Adulto , Anciano , Causalidad , Estudios de Cohortes , Femenino , Humanos , Hipoxia/metabolismo , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Retina/patología , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. METHODS AND RESULTS: We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), interleukin 7 (IL-7), and interleukin 14 (IL-14) in whole lung homogenates compared to controls. CONCLUSIONS: These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.
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Células Epiteliales Alveolares/metabolismo , Neumonía/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Células Epiteliales Alveolares/inmunología , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Genotipo , Mediadores de Inflamación/metabolismo , Interleucina-7/metabolismo , Interleucinas/metabolismo , Ratones Transgénicos , Infiltración Neutrófila , Fenotipo , Neumonía/genética , Neumonía/inmunología , Regiones Promotoras Genéticas , Receptor para Productos Finales de Glicación Avanzada/genética , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba , Uteroglobina/genética , Proteínas de Transporte VesicularRESUMEN
BACKGROUND: Receptors for advanced glycation end-products (RAGE) are immunoglobulin-like pattern recognition receptors abundantly localized to lung epithelium. Our research demonstrated that primary tobacco smoke exposure increases RAGE expression and that RAGE partly mediates pro-inflammatory signaling during exposure. However, the degree to which RAGE influences developing lungs when gestating mice are exposed to secondhand smoke (SHS) has not been determined to date. METHODS: Timed pregnant RAGE null and wild type control mice were exposed to 4 consecutive days of SHS from embryonic day (E) 14.5 through E18.5 using a state of the art nose-only smoke exposure system (Scireq, Montreal, Canada). RAGE expression was assessed using immunofluorescence, immunoblotting, and quantitative RT-PCR. TUNEL immunostaining and blotting for caspase-3 were performed to evaluate effects on cell turnover. Matrix abnormalities were discerned by quantifying collagen IV and MMP-9, a matrix metalloprotease capable of degrading basement membranes. Lastly, TNF-α and IL-1ß levels were assessed in order to determine inflammatory status in the developing lung. RESULTS: Pulmonary RAGE expression was elevated in both dams exposed to SHS and in fetuses gestating within mothers exposed to SHS. Fetal weight, a measure of organismal health, was decreased in SHS-exposed pups, but unchanged in SHS-exposed RAGE null mice. TUNEL assessments suggested a shift toward pulmonary cell apoptosis and matrix in SHS-exposed pups was diminished as revealed by decreased collagen IV and increased MMP-9 expression. Furthermore, SHS-exposed RAGE null mice expressed less TNF-α and IL-1ß when compared to SHS-exposed controls. CONCLUSIONS: RAGE augmentation in developing pups exposed to maternal SHS weakens matrix deposition and influences lung inflammation.
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Feto/metabolismo , Pulmón/metabolismo , Neumonía/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Receptores Inmunológicos/biosíntesis , Contaminación por Humo de Tabaco/efectos adversos , Animales , Femenino , Feto/patología , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Neumonía/patología , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Receptor para Productos Finales de Glicación AvanzadaRESUMEN
OBJECTIVE: Ascent to high altitude leads to a reduction in ambient pressure and a subsequent fall in available oxygen. The resulting hypoxia can lead to elevated pulmonary artery (PA) pressure, capillary stress, and an increase in interstitial fluid. This fluid can be assessed on lung ultrasound (LUS) by the presence of B-lines. We undertook a chamber and field study to assess the impact of high-intensity exercise in hypoxia on the development of pulmonary interstitial edema in healthy lowlanders. METHODS: Thirteen volunteers completed a high-intensity intermittent exercise (HIIE) test at sea level, in acute normobaric hypoxia (12% O2, approximately 4090 m equivalent altitude), and in hypobaric hypoxia during a field study at 4090 m after 6 days of acclimatization. Pulmonary interstitial edema was assessed by the evaluation of LUS B-lines. RESULTS: After HIIE, no increase in B-lines was seen in normoxia, and a small increase was seen in acute normobaric hypoxia (2 ± 2; P < .05). During the field study at 4090 m, 12 participants (92%) demonstrated 7 ± 4 B-lines at rest, which increased to 17 ± 5 immediately after the exercise test (P < .001). An increase was evident in all participants. There was a reciprocal fall in peripheral arterial oxygen saturations (Spo2) after exercise from 88% ± 4% to 80% ± 8% (P < .01). B-lines and Spo2 in all participants returned to baseline levels within 4 hours. CONCLUSIONS: HIIE led to an increase in B-lines at altitude after subacute exposure but not during acute exposure at equivalent simulated altitude. This may indicate pulmonary interstitial edema.
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Mal de Altura/fisiopatología , Ejercicio Físico/fisiología , Hipoxia/fisiopatología , Edema Pulmonar/fisiopatología , Adulto , Altitud , Prueba de Esfuerzo , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Edema Pulmonar/diagnóstico por imagen , Perfil de Impacto de Enfermedad , UltrasonografíaRESUMEN
OBJECTIVE: To assess the effect of acetazolamide (Az) on exercise performance during early acclimatization to altitude. METHODS: Az (250 mg twice daily) or placebo was administered for 3 days in a double-blind, randomized manner followed by a rapid ascent to 3459 m in the Italian Alps. Twenty healthy adults (age range, 18-67 years) were tested at 60% of sea-level peak power output for 15 minutes on a bicycle ergometer after 16 to 27 hours of altitude exposure. Exercise performance was measured in relation to peripheral oxygen saturations measured from pulse oximetry (Spo2), Lake Louise acute mountain sickness (AMS) score, and perceived difficulty. RESULTS: At altitude, resting Spo2 was higher in the Az group compared with placebo (P < .001). The highest AMS scores were in 4 of the placebo individuals with the lowest resting Spo2 (P < .05). During the exercise test, Spo2 fell in all but 1 subject (P < .001) and was reduced more in the Az group (P < .01). Four Az and 1 placebo subject were unable to complete the exercise test; 4 of these 5 had the largest fall in Spo2. The perception of exercise difficulty was higher in the Az subjects compared with those taking the placebo (P < .01). There was an age relationship with exercise limitation; 4 of the 9 older than 50 years failed to complete the test whereas only 1 of 11 younger than 50 years failed, and there were no failures in the 6 younger than 30 years (P < .05). CONCLUSIONS: In this study group, and despite higher resting Spo2, Az may have compromised exercise at 3459 m altitude during early acclimatization, particularly in older subjects.
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Acetazolamida/uso terapéutico , Mal de Altura/tratamiento farmacológico , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Ejercicio Físico , Aclimatación , Enfermedad Aguda , Adolescente , Adulto , Anciano , Altitud , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oximetría , Adulto JovenRESUMEN
Thrombotic occlusions of large blood vessels are increasingly treated with catheter based mechanical approaches, one of the most prominent being to employ aspiration to extract clots through a hollow catheter lumen. A central technical challenge for aspiration catheters is to achieve sufficient suction force to overcome the resistance of clot material entering into the distal tip. In this study, we examine the feasibility of inducing cavitation within hollow cylindrical transducers with a view to ultimately using them to degrade the mechanical integrity of thrombus within the tip of an aspiration catheter. Hollow cylindrical radially polarized PZT transducers with 3.3/2.5 mm outer/inner diameters were assessed. Finite element simulations and hydrophone experiments were used to investigate the pressure field distribution as a function of element length and resonant mode (thickness, length). Operating in thickness mode (â¼5 MHz) was found to be associated with the highest internal pressures, estimated to exceed 23 MPa. Cavitation was demonstrated to be achievable within the transducer under degassed water (10 %) conditions using hydrophone detection and high-frequency ultrasound imaging (40 MHz). Cavitation clouds occupied a substantial portion of the transducer lumen, in a manner that was dependent on the pulsing scheme employed (10 and 100 µs pulse lengths; 1.1, 11, and 110 ms pulse intervals). Collectively the results support the feasibility of achieving cavitation within a transducer compatible with mounting in the tip of an aspiration format catheter.
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Ultrasonido Enfocado de Alta Intensidad de Ablación , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Transductores , Succión , Catéteres , AguaRESUMEN
BACKGROUND: Receptors for advanced glycation end-products (RAGE) are cell surface receptors prominently expressed by lung epithelium. Previous research demonstrated that over-expression of RAGE by murine alveolar epithelial cells during embryogenesis caused severe lung hypoplasia and neonatal lethality. However, the effects of RAGE over-expression on adjacent matrix and endothelial cells remained unknown. METHODS: RAGE transgenic (TG) mice were generated that conditionally over-expressed RAGE in alveolar type II cells when fed doxycycline (dox) from conception to E18.5. To evaluate effects on the basement membrane, immunostaining and immunoblotting were performed for collagen IV and MMP-9, a matrix metalloprotease capable of degrading basement membranes. To assess changes in vasculature, immunostaining, immunoblotting and qRT-PCR were performed for Pecam-1, a platelet endothelial cell adhesion marker also known as CD31. Lastly, to characterize potential regulatory mechanisms of endothelial cell differentiation, immunoblotting and qRT-PCR for FoxM1, a key endothelium-specific transcription factor of the Forkhead Box (Fox) family, were completed. RESULTS: Qualitative immunostaining for collagen IV was less in RAGE TG mice compared to controls and immunoblotting revealed decreased collagen IV in the RAGE TG mouse lung. Additionally, elevated MMP-9 detected via immunostaining and immunoblotting implicated MMP-9 as a possible down stream effector in matrix destabilization mediated by RAGE signaling. Lastly, Pecam-1 assessment revealed a decrease in the prevalence of microvascular endothelial cells coincident with FoxM1 abrogation in RAGE TG mice compared to controls. CONCLUSIONS: RAGE over-expression by alveolar epithelium weakened the basement membrane and associated matrix via increased MMP-9 activity. Furthermore, over-expression of RAGE inhibited FoxM1, suggesting that anomalous transcriptional control contributes to decreased endothelial cell prevalence in the TG mouse lung.
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Membrana Basal/metabolismo , Endotelio/patología , Alveolos Pulmonares/embriología , Alveolos Pulmonares/metabolismo , Receptores Inmunológicos/metabolismo , Animales , Diferenciación Celular/fisiología , Colágeno/metabolismo , Endotelio/metabolismo , Epitelio/embriología , Epitelio/metabolismo , Factores de Transcripción Forkhead/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Modelos Animales , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/genéticaRESUMEN
Therapeutic focused ultrasound in combination with encapsulated microbubbles is being widely investigated for its ability to elicit bioeffects in the microvasculature, such as transient permeabilization for drug delivery or at higher pressures to achieve 'antivascular' effects. While it is well established that the behaviors of microbubbles are altered when they are situated within sufficiently small vessels, there is a paucity of data examining how the bubble population dynamics and emissions change as a function of channel (vessel) diameter over a size range relevant to therapeutic ultrasound, particularly at pressures relevant to antivascular ultrasound. Here we use acoustic emissions detection and high-speed microscopy (10 kframes/s) to examine the behavior of a polydisperse clinically employed agent (Definity®) in wall-less channels as their diameters are scaled from 1200 to 15 µm. Pressures are varied from 0.1 to 3 MPa using either a 5 ms pulse or a sequence of 0.1 ms pulses spaced at 1 ms, both of which have been previously employed in an in vivo context. With increasing pressure, the 1200 µm channel - on the order of small arteries and veins - exhibited inertial cavitation, 1/2 subharmonics and 3/2 ultraharmonics, consistent with numerous previous reports. The 200 and 100 µm channels - in the size range of larger microvessels less affected by therapeutic focused ultrasound - exhibited a distinctly different behavior, having muted development of 1/2 subharmonics and 3/2 ultraharmonics and reduced persistence. These were associated with radiation forces displacing bubbles to the distal wall and inducing clusters that then rapidly dissipated along with emissions. As the diameter transitioned to 50 and then 15 µm - a size regime that is most relevant to therapeutic focused ultrasound - there was a higher threshold for the onset of inertial cavitation as well as subharmonics and ultraharmonics, which importantly had more complex orders that are not normally reported. Clusters also occurred in these channels (e.g. at 3 MPa, the mean lateral and axial sizes were 23 and 72 µm in the 15 µm channel; 50 and 90 µm in the 50 µm channel), however in this case they occupied the entire lumens and displaced the wall boundaries. Damage to the 15 µm channel was observed for both pulse types, but at a lower pressure for the long pulse. Experiments conducted with a 'nanobubble' (<0.45 µm) subpopulation of Definity followed broadly similar features to 'native' Definity, albeit at a higher pressure threshold for inertial cavitation. These results provide new insights into the behavior of microbubbles in small vessels at higher pressures and have implications for therapeutic focused ultrasound cavitation monitoring and control.
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Sonicación , Terapia por Ultrasonido , Sonicación/métodos , Microburbujas , Acústica , Terapia por Ultrasonido/métodosRESUMEN
INTRODUCTION: Scotland implemented a minimum price per unit of alcohol (MUP) of £0.50 in May 2018 (1 UK unit = 10 mL/8 g ethanol). Some stakeholders expressed concerns about the policy having potential negative consequences for people with alcohol dependence. This study aimed to investigate anticipated impacts of MUP on people presenting to alcohol treatment services in Scotland before policy implementation. METHODS: Qualitative interviews were conducted with 21 people with alcohol dependence accessing alcohol treatment services in Scotland between November 2017 and April 2018. Interviews examined respondents' current and anticipated patterns of drinking and spending, effects on their personal life, and their views on potential policy impact. Interview data were thematically analysed using a constant comparison method. RESULTS: Three key themes were identified: (i) strategies used to manage the cost of alcohol and anticipated responses to MUP; (ii) broader effects of MUP; and (iii) awareness and preparedness for MUP. Respondents expected to be impacted by MUP, particularly those on low incomes and those with more severe dependence symptoms. They anticipated using familiar strategies including borrowing and reprioritising spending to keep alcohol affordable. Some respondents anticipated negative consequences. Respondents were sceptical about the short-term benefits of MUP for current drinkers but felt it might prevent harm for future generations. Respondents had concerns about the capacity of treatment services to meet support needs. DISCUSSION AND CONCLUSIONS: People with alcohol dependence identified immediate concerns alongside potential long-term benefits of MUP before its introduction. They also had concerns over the preparedness of service providers.
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Bebidas Alcohólicas , Alcoholismo , Humanos , Alcoholismo/terapia , Etanol , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/prevención & control , Escocia , Costos y Análisis de Costo , Investigación Cualitativa , ComercioRESUMEN
Purpose Compare postoperative outcomes in cataract surgery between eyes with standard drop regimen versus dropless protocol by residents. Design Retrospective cohort study between April 1, 2018 and March 31, 2020. Methods The study was performed at Lyndon B. Johnson General Hospital in Houston, Harris County, Texas. A total of 547 eyes (234 dropless vs. 313 standard) with phacoemulsification cataract surgery and minimum of 1-month follow-up with best-corrected visual acuity (BCVA) were included. Dropless received 40 mg sub-Tenon's triamcinolone and intracameral moxifloxacin. Patients were followed at postoperative day 1 (POD1), week 1 (POW1), and month 1 (POM1). Postoperative rate of BCVA better than 20/40 (Good vision) and rate of complications were compared between groups. Results Good vision on POM1 in dropless (77.8%) was noninferior to standard (75.1%, p = 0.80). Complication rate in dropless (28.6%) was noninferior to standard (24.0%, p = 0.13). Intraocular pressure (IOP) elevation on POD1 ( p = 0.041) and anterior chamber (AC) cells on POW1 and POM1 ( p < 0.001) were more frequent in dropless. Mean spherical equivalent at POM1 was better in dropless (-0.37 D [±0.81 D]) compared with standard (-0.61D [±0.77 D], p = 0.001). Early posterior capsular opacification (early PCO) was more frequent in dropless ( p = 0.042). Conclusions Postoperative rate of BCVA better than 20/40 and rate of postoperative complications were noninferior, although dropless had higher rates of AC inflammation, IOP elevation, and early PCO.
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Objectives: The h-index is a measure of research output and contribution that shows strong correlation with academic promotion in medicine. The purpose of this article is to clearly explain how h-index scores are calculated and how otolaryngologists can effectively and advantageously use these scores for their career development. Data Sources: PubMed. Review Methods: We performed an up-to-date PubMed literature review describing the design of the h-index and how to use it effectively along with its role in academic medicine, including otolaryngology. Conclusions: H-index scores are used as a metric for scientific output that considers the number of publications and the number of times each is cited. Search engines can automatically calculate h-index scores for one's work. Studies also revealed significant positive correlations that the h-index has from fellowship involvement, which could be beneficial for career advancement in academic medicine. Implications for Practice: Aspiring academic otolaryngologists should create a research profile to link and calculate the h-index for publications, submit to well-read high-impact journals for increased viewership and citations, and expand on foundational and personal research topics. Future studies should evaluate faculty and resident awareness of h-indices in the otolaryngology department to see how we can further address any underlying barriers. Otolaryngologists with the knowledge and tools necessary to maximize h-index scores and produce high-quality research in modern-day medicine not only provide potential advantages in career development but also bring significant contribution to the field of otolaryngology and patient care.
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BACKGROUND: Scholarly productivity and research output vary among different subspecialties. The h-index was developed as a more wholesome metric that measures an author's contribution to literature. OBJECTIVE: Through a web-based cross-sectional analysis, we investigated the differences in scholarly impact and influence of both fellowship and nonfellowship-trained academic otolaryngologists in the United States. A secondary objective was to further understand the output among the larger fellowship fields. METHODS: A cross-sectional analysis was performed for active faculty otolaryngologists. A total of 1704 otolaryngologists were identified as faculty in residency training programs across the United States. Their h-index and publication data were gathered using the Scopus database. The data were obtained in August 2019 and analysis occurred in January 2020. RESULTS: Head and neck surgical faculty (25.5%) had the highest representation with fellowship experience. Among all faculty, there was no statistical difference in the overall average h-index scores when comparing faculty that had fellowship training with those who did not (12.6 and 12.1, respectively, P = .498). Rhinologists had the highest publication output per year at 3.90. Among fellowship-trained faculty, the highest average h-index and total publications were seen in head & neck surgery, while facial plastics had the lowest averages (P < .001). CONCLUSIONS: In this study, fellowship-trained faculty had a greater but not significant scholarly impact than nonfellowship faculty. Furthermore, there were significant variations in output among the various subspecialties of otolaryngology. Growing fields, as academic rhinology, are continuing to flourish in robust research productivity and output. This study further demonstrates the potential, growing influence of fellowship training on research involvement and academic advancement within the otolaryngology subspecialties.
Asunto(s)
Éxito Académico , Internado y Residencia , Otolaringología , Estudios Transversales , Eficiencia , Becas , Humanos , Otolaringología/educación , Estados Unidos/epidemiologíaRESUMEN
The IEEE and ICNIRP had specified a maximum permissible exposure for instantaneous peak electric field of 100 kV/m. However, no rationale was given for this limit. A novel exposure system was designed through a detailed process of analytical analysis, numerical modelling and prototype testing. The system consists of a cylindrical re-entrant resonant cavity that can achieve an electric field strength of more than 100 kV/m with an input power of 200 W. The working of the system was evaluated in simulation and experiment in terms of scattering parameters, electric field distributions and specific absorption rate. The system was then used to carry out in-vitro exposures of a human lymphoid cell line (GG0257) to a 1195 MHz signal at 53 dBm peak power and a pulse width of 550 ns at a range of interpulse intervals to identify heating-induced changes in cell viability. The proposed system offers high Q value of 5920 in unloaded condition which was reduced to 57 when loaded with 12 ml of cell culture but still offering 67 kV/m of the field intensity. Using the system for the exposure of GG0257 cells lasting 18 min, interpulse intervals of 11 µs or less caused a reduction in the number of viable cells and a corresponding increase in necrotic cells. For a shorter exposure duration of 6 min, the reduction in cell viability was seen at interpulse intervals of 5.5 µs or less. The designed exposure system is well capable of handling high intensity electric fields. Temperature measurements with a fibre optic probe and temperature sensitive labels showed that changes in viability were associated with temperature increases above 46 °C. This novel exposure system is an efficient means to investigate the possible relationship between peak field intensity and biological effects to provide a rationale behind the maximum exposure limit of 100 kV/m.