RESUMEN
With wavelength tunability, free-electron lasers (FELs) are well-suited for generating orbital angular momentum (OAM) beams in a wide photon energy range. We report here the first experimental demonstration of OAM beam generation using an oscillator FEL with the tens of picosecond pulse duration. Lasing around 458 nm, we have produced the four lowest orders of superposed Laguerre-Gaussian beams using a very long FEL resonator of 53.73 m. The produced beams have good beam quality, excellent stability, and substantial average power. We have also developed a pulsed operation mode for these beams with a highly reproducible temporal structure for a range of repetition rate of 1-30 Hz. This development can be extended to short wavelengths, for example to x-rays using a future x-ray FEL oscillator. The OAM operation of such a storage-ring FEL also paves the way for the generation of OAM gamma-ray beams via inverse Compton scattering.
RESUMEN
The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.
Asunto(s)
Infecciones por Coronavirus/terapia , Sistemas de Apoyo a Decisiones Clínicas/normas , Técnicas de Apoyo para la Decisión , Servicio de Urgencia en Hospital/normas , Enfermedades Linfáticas/terapia , Neumonía Viral/terapia , Triaje/normas , Enfermedades Vasculares/terapia , COVID-19 , Toma de Decisiones Clínicas , Consenso , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Necesidades y Demandas de Servicios de Salud/normas , Humanos , Enfermedades Linfáticas/diagnóstico , Enfermedades Linfáticas/epidemiología , Pandemias , Selección de Paciente , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/epidemiologíaRESUMEN
The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semiurgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/nonurgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Enfermedades Linfáticas/terapia , Neumonía Viral/epidemiología , Triaje/organización & administración , Enfermedades Vasculares/terapia , Venas , COVID-19 , Consenso , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Humanos , Cooperación Internacional , Enfermedades Linfáticas/diagnóstico , Pandemias/prevención & control , Selección de Paciente , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , Reproducibilidad de los Resultados , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Sociedades Médicas , Enfermedades Vasculares/diagnóstico , Procedimientos Quirúrgicos VascularesRESUMEN
BACKGROUND: Few studies have directly compared the effects of different angiotensin receptor blockers (ARBs) on mechanisms involved in the pathogenesis of cardiovascular disease. METHODS: We studied the ability of different ARBs to inhibit the proliferation of vascular smooth muscle cells (VSMCs) and cardiac fibroblasts (CFs) in continuous culture and in quiescent cells stimulated to proliferate by platelet-derived growth factor (PDGF) and insulin. We also investigated whether the antiproliferative effects of ARBs depended on their ability to block angiotensin II receptors or activate the peroxisome proliferator-activated receptor gamma (PPAR gamma). RESULTS: Dose-response studies showed that candesartan, eprosartan, and irbesartan had little or no effect on the proliferation of VSMC or CF in continuous culture even when tested at concentrations as high as 10 mumol/l or when tested in cells stimulated with PDGF/insulin. In contrast, telmisartan inhibited VSMC and CF proliferation by 50-70% (P < 0.05) in a dose-dependent and reversible fashion and significantly inhibited the increases in cyclin D1 levels and cell proliferation induced by PDGF/insulin. Antiproliferative effects of telmisartan were also observed in Chinese hamster ovary (CHO-K1) cells that lack functional angiotensin II receptors and in human VSMCs treated with the PPAR gamma antagonist GW9662. CONCLUSION: Telmisartan, but not candesartan, irbesartan, or eprosartan, can significantly inhibit the proliferation of VSMC and CF in culture when tested at concentrations near those that can be achieved in plasma with usual oral dosing. Telmisartan can also inhibit the proliferation of cells that lack angiotensin II receptors and cells treated with a PPAR gamma antagonist suggesting that the antiproliferative effects of telmisartan may involve more than just angiotensin II receptor blockade or activation of PPAR gamma.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bencimidazoles/farmacología , Benzoatos/farmacología , Proliferación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Células Cultivadas , Ciclina D1/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Músculo Liso Vascular/citología , PPAR gamma/efectos de los fármacos , Ratas , Sistema Renina-Angiotensina/efectos de los fármacos , TelmisartánRESUMEN
A series of novel derivatives of potent antioxidant vitamin, alpha-lipoic acid, and related analogues were designed, synthesized, and evaluated for their PPARgamma agonist activities. Compounds 9a and the water soluble analogue11e were found to be potent PPARgamma agonists. Compound 9a appeared to have a significant role in improving insulin sensitivity and reducing triglyceride levels in fa/fa rats as well as inhibited proliferation of a variety of normal and neoplastic cultured human cell types. These novel compounds may prove efficacious not only in the treatment of Type 2 diabetes, but also atherosclerosis, prevention of vascular restenosis, and inflammatory skin diseases.
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Hipolipemiantes/síntesis química , PPAR gamma/agonistas , Fenilacetatos/síntesis química , Tiazolidinedionas/síntesis química , Ácido Tióctico/análogos & derivados , Ácido Tióctico/síntesis química , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Cristalografía por Rayos X , Diseño de Fármacos , Humanos , Hipolipemiantes/farmacología , Resistencia a la Insulina , Interleucinas/biosíntesis , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Modelos Moleculares , Estructura Molecular , PPAR gamma/química , Fenilacetatos/farmacología , Ratas , Ratas Zucker , Relación Estructura-Actividad , Tiazolidinedionas/farmacología , Ácido Tióctico/farmacologíaRESUMEN
OBJECTIVE: This prospective study assesses the roles of illness beliefs, emotion regulation factors, and sociodemographic characteristics in decisions to participate in a group support program for women recently diagnosed with breast cancer. METHOD: Women recruited during clinic visits 2 to 4 weeks after diagnosis completed measures of affective and cognitive factors identified by Leventhal's Common-Sense Model of illness self-regulation: cancer-related distress, avoidance tendencies, beliefs that the breast cancer was caused by stress and altered immunity, and personal control beliefs. Measures of general anxiety and depression, social support, and demographic characteristics were also completed; prognostic status information was obtained from medical records. All women were encouraged to participate in a free, 12-week program offering coping skills training and group support. Participation was recorded by program staff. RESULTS: Of the 110 women, 54 (49%) participated in the group support program and 56 (51%) did not. Logistic regression analyses revealed that participation was predicted by stronger beliefs that the cancer was caused by altered immunity, higher cancer-related distress, lower avoidance tendencies, and younger age. CONCLUSIONS: Participation in the group psychosocial support program appeared to be guided by cognitive and affective factors identified by the Common-Sense Model. Psychosocial support programs and informational materials promoting their use may attract more participants if they are tailored to focus on resolving cancer-related distress rather than on general anxiety or depression, appeal to those with high avoidance tendencies, address the role of immune function in cancer progression, and meet the needs of older participants.
Asunto(s)
Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Aceptación de la Atención de Salud , Apoyo Social , Estrés Psicológico/terapia , Adaptación Psicológica , Adulto , Actitud Frente a la Salud , Neoplasias de la Mama/complicaciones , Toma de Decisiones , Emociones , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Grupos de Autoayuda , Factores Socioeconómicos , Estrés Psicológico/etiología , Estrés Psicológico/psicologíaRESUMEN
PURPOSE: To determine the efficacy of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in inhibiting corneal neovascularization. METHODS: Twenty-six adult male Sprague-Dawley rats were randomly divided into three groups. Each group received intrastromal polymer micropellets containing one of the following: Group 1, no active ingredient (n=10); Group 2, vascular endothelial growth factor (VEGF) (n=7); Group 3, VEGF and pioglitazone (n=9). Neovascularization was evaluated 7 days after pellet implantation. After systemic India ink injection, digital photographs of the eyes were taken. The area and density of neovascularization were measured using imaging software. RESULTS: Mean area of neovascularization was 0.43+/-0.18 mm2 for Group 1, 2.87+/-0.48 mm2 for Group 2 and 2.10+/-0.22 mm2 for Group 3. Statistical analysis showed significant differences between Groups 1 and 2 and Groups 1 and 3. There was no significant difference between Groups 2 and 3. Mean density of neovascularization was 2.16+/-0.66 for Group 1, 27.14+/-2.93 for Group 2 and 12.02+/-2.24 for Group 3. All comparisons between groups were statistically significant (P<0.01). CONCLUSIONS: Pioglitazone is effective in decreasing the density of angiogenesis in a VEGF-induced neovascular rat cornea model. There is possibility of even greater effect with higher doses of the drug. Pioglitazone is a promising drug for the treatment of ocular neovascularization.
Asunto(s)
Neovascularización de la Córnea/prevención & control , Hipoglucemiantes/farmacología , PPAR gamma/farmacología , Tiazolidinedionas/farmacología , Animales , Western Blotting/métodos , Córnea/química , Córnea/efectos de los fármacos , Córnea/patología , Neovascularización de la Córnea/patología , Ligandos , Masculino , Microscopía de Contraste de Fase/métodos , PPAR gamma/análisis , Pioglitazona , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/farmacologíaAsunto(s)
Blastómeros/citología , Separación Celular/métodos , Embrión no Mamífero/citología , Embrión no Mamífero/embriología , Erizos de Mar/citología , Erizos de Mar/embriología , Animales , Blastómeros/fisiología , Técnicas de Cultivo de Célula/instrumentación , Técnicas de Cultivo de Célula/métodos , Separación Celular/instrumentación , Medios de Cultivo/química , Embrión no Mamífero/fisiología , Femenino , Mesodermo/citología , Mesodermo/fisiología , Modelos Animales , Erizos de Mar/fisiologíaRESUMEN
Novel thiazolidinedione derivatives of the potent antioxidant, alpha-lipoic (thioctic, 1,2-dithiolane) acid, were prepared. The prototype N-(2-[4-[2,4-dioxo(1,3-thiazolidin-5-yl)methyl]phenoxy]ethyl)-5-(1,2-dithiolan-3-yl)- N-methylpentanamide (designated BP-1003), and dithioester derivatives thereof were shown to be potent activators of peroxisome proliferator-activated receptor gamma (PPARgamma) (EC(50) range 15-101 nM) and modest activators of PPARalpha (EC(50) 5 microM). Both the relatively hydrophobic dithiolane prototype, BP-1003, and its water-soluble dithioglycinate derivative, BP-1017, were shown to inhibit the proliferation of human keratinocytes and suppress the production of interleukin-2 by human peripheral lymphocytes to a greater extent than the antidiabetic thiazolidinedione, rosiglitazone. Both oral and topical administration of BP-1017 showed significant antiinflammatory effects in the oxazolone-sensitized mouse model of allergic contact dermatitis (ACD). These findings suggest that water-soluble lipoic acid-based thiazolidinediones may be efficacious as oral and topical agents for treating inflammatory skin conditions such as contact dermatitis, atopic dermatitis, and psoriasis.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Dermatitis Alérgica por Contacto/tratamiento farmacológico , PPAR gamma/agonistas , Tiazoles/farmacología , Ácido Tióctico/análogos & derivados , Ácido Tióctico/farmacología , Células 3T3-L1 , Adipocitos/citología , Adipocitos/efectos de los fármacos , Animales , Antiinflamatorios/química , Antioxidantes/química , División Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Haplorrinos , Humanos , Interleucina-2/metabolismo , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Ratones , PPAR gamma/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Tiazoles/química , Ácido Tióctico/químicaRESUMEN
The metabolic syndrome is a common precursor of cardiovascular disease and type 2 diabetes that is characterized by the clustering of insulin resistance, dyslipidemia, and increased blood pressure. In humans, mutations in the peroxisome proliferator-activated receptor-gamma (PPARgamma) have been reported to cause the full-blown metabolic syndrome, and drugs that activate PPARgamma have proven to be effective agents for the prevention and treatment of insulin resistance and type 2 diabetes. Here we report that telmisartan, a structurally unique angiotensin II receptor antagonist used for the treatment of hypertension, can function as a partial agonist of PPARgamma; influence the expression of PPARgamma target genes involved in carbohydrate and lipid metabolism; and reduce glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet. None of the other commercially available angiotensin II receptor antagonists appeared to activate PPARgamma when tested at concentrations typically achieved in plasma with conventional oral dosing. In contrast to ordinary antihypertensive and antidiabetic agents, molecules that can simultaneously block the angiotensin II receptor and activate PPARgamma have the potential to treat both hemodynamic and biochemical features of the metabolic syndrome and could provide unique opportunities for the prevention and treatment of diabetes and cardiovascular disease in high-risk populations.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II , Bencimidazoles/farmacología , Benzoatos/farmacología , Receptores Citoplasmáticos y Nucleares/agonistas , Factores de Transcripción/agonistas , Adipocitos/efectos de los fármacos , Animales , Bencimidazoles/química , Benzoatos/química , Compuestos de Bifenilo/farmacología , Glucemia/análisis , Diferenciación Celular/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , Chlorocebus aethiops , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Imidazoles/farmacología , Insulina/sangre , Irbesartán , Losartán/farmacología , Masculino , Ratones , Modelos Moleculares , Mioblastos/efectos de los fármacos , Conformación Proteica/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores Citoplasmáticos y Nucleares/química , Receptores Citoplasmáticos y Nucleares/genética , Rosiglitazona , Relación Estructura-Actividad , Telmisartán , Tetrazoles/farmacología , Tiazoles/farmacología , Tiazolidinedionas/farmacología , Tiazolidinas , Factores de Transcripción/química , Factores de Transcripción/genética , Triglicéridos/sangre , Valina/análogos & derivados , Valina/farmacología , Valsartán , Aumento de Peso/efectos de los fármacosRESUMEN
This study was undertaken to evaluate the effects of thiazolidinediones (TZD) on keratinocyte proliferation, motility, and matrix metalloproteinase (MMP) production. Rosiglitazone (a potent TZD) inhibited both proliferation and motility as well as elaboration of MMP-1 and MMP-9. Inhibition was obtained with keratinocytes in monolayer culture and human skin in organ culture. There were significant concentration-response differences in sensitivity of the three keratinocyte responses to treatment with rosiglitazone. In contrast to keratinocytes, dermal fibroblasts were resistant to the effects of rosiglitazone. Treatment of keratinocytes with rosiglitazone did not suppress epidermal growth factor receptor autophosphorylation, but inhibited signaling through the extracellular regulated kinase mitogen-activated protein kinase pathway without a concomitant effect on pathways that lead to c-jun activation. Pioglitazone, another TZD, also suppressed keratinocyte proliferation, although it was less effective than rosiglitazone. An experimental TZD (BP-1107) inhibited keratinocyte proliferation at a much lower concentration than either rosiglitazone or pioglitazone. Because enhanced keratinocyte motility and increased MMP production as well as increased keratinocyte proliferation are thought to contribute to the phenotype of psoriatic lesional skin, we propose that interference with these keratinocyte responses contributes to the previously reported antipsoriatic activity of TZD.
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Hipoglucemiantes/farmacología , Queratinocitos/efectos de los fármacos , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Tiazolidinedionas/farmacología , Adulto , División Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Células Epidérmicas , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Queratinocitos/citología , Queratinocitos/enzimología , Técnicas de Cultivo de Órganos , Pioglitazona , Psoriasis/fisiopatología , Rosiglitazona , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: A reduction in acute rejection may reduce graft losses from chronic rejection, benefiting the recipient and helping ease the huge donor organ shortfall in the UK. The prediction of recipients at greater risk of acute rejection might justify the administration to them of more potent immunosuppression, but defining this group on clinical parameters has been largely unsuccessful. Events impacting on the kidney by the time of donation may, if detectable histologically, predict those kidneys more likely to undergo rejection. METHODS: A prospective immunohistochemical analysis was undertaken to detect P-Selectin (PS), E-Selectin (ES), platelets, leukocyte common antigen, macrophages, T cells, and neutrophils in the pretransplant biopsies of 77 adult renal transplant recipients. Twenty-nine (38%) of this group rejected. RESULTS: A significantly increased number of recipients rejected if the donor biopsy was PS positive (63 vs. 24%, P=0.0007), contained five or more leukocytes/glomerulus (48 vs. 21%, P=0.03), contained >9.3 leukocytes/high power field (46.5 vs. 10.5%, P=0.006) or was both PS positive and contained >9.3 leukocytes/high power field (61.9 vs. 0.0%, P=0.0001). The PS was mostly of platelet origin and the majority of leukocytes were macrophages. Only previous CMV or any current infection in the donor correlated with the immunohistochemical changes. CONCLUSIONS: These immuno-histochemical changes are present before transplantation, which allows the prediction of recipients at both a higher and a lower risk of acute rejection, enabling the administration of recipient tailored immunosuppression, and supports the use of additional therapeutic intervention to reduce the injury response both within the recipient and the donor.
Asunto(s)
Rechazo de Injerto/patología , Trasplante de Riñón/patología , Recuento de Leucocitos , Macrófagos/patología , Recuento de Plaquetas , Adulto , Factores de Edad , Análisis de Varianza , Plaquetas/patología , Moléculas de Adhesión Celular/análisis , Selectina E/análisis , Rechazo de Injerto/sangre , Rechazo de Injerto/epidemiología , Humanos , Inmunohistoquímica , Corteza Renal/patología , Glomérulos Renales/patología , Antígenos Comunes de Leucocito/análisis , Leucocitos/patología , Persona de Mediana Edad , Selectina-P/análisis , Valor Predictivo de las Pruebas , Factores de Riesgo , Trasplante HomólogoRESUMEN
Collagen fibrils with a main period banding of 610 Å and 220 Å in width were observed in the blastocoel of 72-h embryos of the sea urchin,Strongylocentrotus purpuratus. Non-striated fibrils of 50 Å diameter were also observed. The collagen is seen in highest concentration in the vicinity of mesenchyme cells which are richly endowed with endoplasmic reticulum and secretory vesicles. A role for collagen in cell attachment, orientation and spicule formation is discussed.