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Optical generation of microwave signals using photonic techniques offers benefits of frequency agility, ease of frequency scaling, and reduced hardware complexity. We demonstrate the generation and detection of QPSK modulated with symbol rates up to 5 GBaud at carrier frequencies of 8-12 GHz through optical heterodyning of two-phase-locked lasers. The received data is demodulated through appropriate post-processing to correct for the phase noise and IQ imbalance. The approach is scalable to mmWave and THz communication.
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In view of the recent global pandemic caused by COVID-19 intense efforts have been devoted worldwide towards the development of an effective treatment for this disease. Recently, PDE4 inhibitors have been suggested to attenuate the cytokine storm in COVID-19 especially tumour necrosis factor alpha (TNF-α). In our effort we have explored the 2-substituted pyrrolo[2,3-b]quinoxalines for this purpose because of their potential inhibitory properties of PDE-4 / TNF-α. Moreover, several of these compounds appeared to be promising in silico when assessed for their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2. A rapid and one-pot synthesis of this class of molecules was achieved via the Cu-catalyzed coupling-cyclization-desulfinylation of 3-alkynyl-2-chloroquinoxalines with t-butyl sulfinamide as the ammonia surrogate under ultrasound irradiation. Most of these compounds showed good to significant inhibition of TNF-α in vitro establishing a SAR (Structure Activity Relationship) within the series. One compound e.g. 3i was identified as a promising hit for which the desirable ADME and acceptable toxicity profile was predicted in silico.
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AIM: There is uncertainty regarding the optimal sequence of surgery for patients with colorectal cancer (CRC) and synchronous liver metastases. This study was designed to describe temporal trends and inter-hospital variation in surgical strategy, and to compare long-term survival in a propensity score-matched analysis. METHOD: The National Bowel Cancer Audit dataset was used to identify patients diagnosed with primary CRC between 1 January 2010 and 31 December 2015 who underwent CRC resection in the English National Health Service. Hospital Episode Statistics data were used to identify those with synchronous liver-limited metastases who underwent liver resection. Survival outcomes of propensity score-matched groups were compared. RESULTS: Of 1830 patients, 270 (14.8%) underwent a liver-first approach, 259 (14.2%) a simultaneous approach and 1301 (71.1%) a bowel-first approach. The proportion of patients undergoing either a liver-first or simultaneous approach increased over the study period from 26.8% in 2010 to 35.6% in 2015 (P < 0.001). There was wide variation in surgical approach according to hospital trust of diagnosis. There was no evidence of a difference in 4-year survival between the propensity score-matched cohorts according to surgical strategy: bowel first vs simultaneous [hazard ratio (HR) 0.92 (95% CI: 0.80-1.06)] or bowel first vs liver first [HR 0.99 (95% CI: 0.82-1.19)]. CONCLUSION: There is evidence of wide variation in surgical strategy in dealing with CRC and synchronous liver metastases. In selected patients, the simultaneous and liver-first strategies have comparable long-term survival to the bowel-first approach.
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Neoplasias Colorrectales/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Hepatectomía/métodos , Hospitales , Neoplasias Hepáticas/cirugía , Metastasectomía/métodos , Pautas de la Práctica en Medicina , Anciano , Neoplasias Colorrectales/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Ablación por Radiofrecuencia/métodos , Tasa de Supervivencia , Factores de Tiempo , Reino UnidoRESUMEN
BACKGROUND: Left hepatic trisectionectomy (LHT) is a challenging major anatomical hepatectomy with a high complication rate and a worldwide experience that remains limited. The aim of this study was to describe changes in surgical practice over time, to analyse the outcomes of patients undergoing LHT for hepatobiliary malignancy, and to identify factors associated with morbidity and mortality. METHODS: A cohort study was undertaken of patients who underwent LHT at a single tertiary hepatobiliary referral centre between January 1993 and March 2013. Univariable and multivariable analysis was used to identify factors associated with short- and long-term outcomes following LHT. RESULT: Some 113 patients underwent LHT for colorectal liver metastasis (57), hilar cholangiocarcinoma (22), intrahepatic cholangiocarcinoma (12) and hepatocellular carcinoma (11); 11 patients had various other indications. Overall morbidity and 90-day mortality rates were 46.0 and 9.7 per cent respectively. Overall 1- and 3-year survival rates were 71.3 and 44.4 per cent respectively. Total hepatic vascular exclusion and intraoperative blood transfusion were independent predictors of postoperative morbidity, whereas blood transfusion was the only factor predictive of in-hospital mortality. Time period analysis revealed a decreasing trend in blood transfusion, duration of hospital stay, and postoperative morbidity and mortality in the last 5 years. CONCLUSION: Morbidity, mortality and long-term survival after LHT support its use in selected patients with a significant tumour burden.
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Neoplasias de los Conductos Biliares/cirugía , Carcinoma Hepatocelular/cirugía , Colangiocarcinoma/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Reino Unido/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a major cause of mortality and morbidity. The impact of inflammatory biomarkers (C-reactive protein etc.) on CRC is increasingly studied including systemic neutrophil-to-lymphocyte ratio (NLR) as they seem to predict outcome. METHODS: All patients who underwent curative resection for CRC from 2000 to 2004 at Leeds Teaching Hospitals NHS Trust had pre-operative NLR calculated. Demographic, histopathological and survival data were collected. Tissue microarrays were created and stained to determine the mismatch repair (MMR) protein status of each tumour. Local lymphocytic response to the tumour was assessed and graded. RESULTS: About 358 patients were eligible. Of these 88 had an NLR ⩾5, which predicted lower overall survival and greater disease recurrence. A high NLR is associated with higher pT- and pN-stage and a greater incidence of extramural venous invasion. MMR protein status was not associated with NLR. A pronounced lymphocytic reaction at the invasive margin (IM) indicated a better prognosis and was associated with a lower NLR. CONCLUSION: Neutrophil-to-lymphocyte ratio predicts disease-free and overall survival and is associated with a more aggressive tumour phenotype. The lymphocytic response to tumour at the IM is associated with NLR however dMMR is not. Neutrophil-to-lymphocyte ratio is a cheap, easy-to-access test that predicts outcome in CRC.
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Neoplasias Colorrectales/inmunología , Linfocitos/inmunología , Neutrófilos/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Reparación de la Incompatibilidad de ADN , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: This study was designed to determine the impact of positive margin and neoadjuvant chemotherapy (NAC) on recurrence and survival after resection of colorectal liver metastasis (CRLM). METHODS: Prospective analysis of 1,255 patients undergoing resection of CLRM was undertaken. The impact of NAC, site of recurrence, and survival between R0 and R1 groups was analysed. RESULTS: The R0 and R1 resection rates were 68.9 % (n = 865) and 31.1 % (390). The median OS for R0 group was 2.7 years (95 % CI 2.56-2.85) and R1 group 2.28 years (CI 2.06-2.52; P < 0.001). The median DFS for R0 group was 1.52 years (CI 1.38-1.66) and R1 group 1.04 years (CI 0.94-1.19; P < 0.001). The intrahepatic recurrence was higher in R1 group 132 (33.8 %) versus 142 (16.4 %) [P = 0.0001]. A total of 103 (11.9 %) patients in R0 group underwent redo liver resection for recurrence compared with 66 (16.9 %) patients in R1 group (P = 0.016). NAC did not impact recurrence rate (57.8 % vs. 61.5 %, P = 0.187) and redo liver surgery between R0 and R1 groups (13 % vs. 17 %, P = 0.092). Within the R1 group, the intrahepatic recurrence rates were similar with and without NAC (33.9 % vs. 33.7 %, P = 0.669). However, DFS was longer in the no chemotherapy group than the chemotherapy group. CONCLUSIONS: R1 resections increase the likelihood of recurrence in the liver and redo liver surgery. NAC does not seem to improve survival in margin positive patients or have an impact on recurrence or reduce need for redo liver surgery for recurrence. In patients with R1 resection, neoadjuvant chemotherapy may have adverse outcome on disease free survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/mortalidad , Hepatectomía/mortalidad , Neoplasias Hepáticas/mortalidad , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy). METHODS: Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost-utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting. RESULTS: Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P < 0·001). The operative strategy dominated non-operative treatments, being less costly (22,200 versus 32,800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario. CONCLUSION: Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly.
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Neoplasias Colorrectales , Neoplasias Hepáticas/economía , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Masculino , Cadenas de Markov , Metastasectomía/economía , Persona de Mediana Edad , Cuidados Paliativos/economía , Estudios Prospectivos , Años de Vida Ajustados por Calidad de Vida , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The most common sites of metastasis from colorectal cancer (CRC) are hepatic and pulmonary; they can present simultaneously (hepatic and pulmonary metastases) or sequentially (hepatic then pulmonary metastases, or vice versa). Simultaneous disease may be aggressive, and thus may be approached with caution by the clinician. The aim of this study was to determine the outcomes following hepatic and pulmonary resection for simultaneously presenting metastatic CRC. METHODS: A retrospective review was undertaken of a prospectively maintained database to identify patients presenting with simultaneous hepatopulmonary disease who underwent hepatic resection. Patients' electronic records were used to identify clinicopathological variables. The log rank test was used to determine survival, and χ(2) analysis to determine predictors of failure of intended treatment. RESULTS: Fifty-nine patients were identified and underwent hepatic resection; median survival was 45·4 months and the 5-year survival rate 38 per cent. Twenty-two patients (37 per cent) did not have the intended pulmonary intervention owing to progression or recurrence of disease. Thirty-seven patients who progressed to hepatopulmonary resection had a median survival of 54·2 months (5-year survival rate 43 per cent). Those who had hepatic resection alone had a median survival of 24·0 months (5-year survival rate 30 per cent). Failure to progress to pulmonary resection was predicted by heavy nodal burden of primary colorectal disease and bilobar hepatic metastases. Redo pulmonary surgery following pulmonary recurrence did not confer a survival benefit. CONCLUSION: Selected patients with simultaneous hepatopulmonary CRC metastases should be considered for attempted curative resection, but some patients may not receive the intended treatment owing to progression of pulmonary disease after hepatic resection.
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Neoplasias Colorrectales , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Quimioterapia Adyuvante/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Metastasectomía/métodos , Metastasectomía/mortalidad , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Half of patients with colorectal cancer develop liver metastases. There remains great variability between hospitals in rates of liver resection for colorectal cancer liver metastases (CLM). This study aimed to determine how many patients with potentially resectable CLM are not seen by specialist liver surgeons. METHODS: Patients presenting with new CLM in a cancer network consisting of a tertiary centre and seven attached hospitals were studied prospectively over 12 months. Data were collected retrospectively for patients who did not have a complete data set. Outcomes for patients referred to the liver tertiary centre were collated. The radiology of tumours deemed inoperable by the local colorectal specialist teams was reviewed by specialist liver surgeons and radiologists. RESULTS: In total, 631 patients with CLM were assessed. Prospective data were complete for 241 patients, and 64 (26.6 per cent) of these were referred to the specialist liver team for consideration of resection. No decision was documented for 16 patients (6.6 per cent). Of those not referred, 30 (18.6 per cent) were deemed unfit or refused and 131 (81.4 per cent) were thought inoperable. Referral rates varied between hospitals (13-43.6 per cent). Of 131 patients deemed fit but inoperable by the colorectal specialist teams, 38 (29.0 per cent) were deemed operable and 20 (15.3 per cent) had equivocal imaging when assessed retrospectively by liver specialists. In total, 142 of the 631 patients were referred to liver specialists for consideration of treatments, and 107 (75.4 per cent) treated with curative intent. CONCLUSION: A considerable number of patients with potentially resectable CLM are not assessed by specialist liver teams. Improved referral rates could greatly improve resection rates for CLM, which may improve outcomes for patients with colorectal cancer.
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Neoplasias Colorrectales , Neoplasias Hepáticas/cirugía , Derivación y Consulta/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Inglaterra , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente , Estudios Prospectivos , Radiografía , Derivación y Consulta/normas , Estudios RetrospectivosRESUMEN
BACKGROUND: Obesity and tissue adiposity constitute a risk factor for several cancers. Whether tissue adiposity increases the risk of cancer recurrence after curative resection is not clear. The present study analysed the influence of hepatic steatosis on recurrence following resection of colorectal liver metastases. METHODS: A prospective cohort of patients who had primary resection of colorectal liver metastases in two major hepatobiliary units between 1987 and 2010 was studied. Hepatic steatosis was assessed in non-cancerous resected liver tissue. Patients were divided into two groups based on the presence of hepatic steatosis. The association between hepatic steatosis and local recurrence was analysed, adjusting for relevant patient, pathological and surgical factors using Cox regression and propensity score case-match analysis. RESULTS: A total of 2715 patients were included. The cumulative local (liver) disease-free survival rate was significantly better in the group without steatosis (hazard ratio (HR) 1·32, 95 per cent confidence interval 1·16 to 1·51; P < 0·001). On multivariable analysis, hepatic steatosis was an independent risk factor for local liver recurrence (HR 1·28, 1·11 to 1·47; P = 0·005). After one-to-one matching of cases (steatotic, 902) with controls (non-steatotic, 902), local (liver) disease-free survival remained significantly better in the group without steatosis (HR 1·27, 1·09 to 1·48; P = 0·002). Patients with steatosis had a greater risk of developing postoperative liver failure (P = 0·001). CONCLUSION: Hepatic steatosis was an independent predictor of local hepatic recurrence following resection with curative intent of colorectal liver metastases.
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Neoplasias Colorrectales , Hígado Graso/complicaciones , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/etiología , Anciano , Métodos Epidemiológicos , Femenino , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: Some 75-80 per cent of patients undergoing liver resection for colorectal liver metastases develop intrahepatic recurrence. A significant number of these can be considered for repeat liver surgery. This study examined the outcomes of repeat liver resection for the treatment of recurrent colorectal metastases confined to the liver. METHODS: Patients who underwent repeat liver resection in a single tertiary referral hepatobiliary centre were identified from a database. Clinicopathological variables were analysed to assess factors predictive of survival. RESULTS: A total of 195 patients underwent repeat resection between 1993 and 2010. Median age was 63 years, and the median interval between first and repeat resection was 13·8 months. Thirty-three patients (16·9 per cent) underwent completion hemihepatectomy or extended hemihepatectomy and the remainder had non-anatomical or segmental resection. The 30-day mortality rate was 1·5 per cent, and the overall 30-day morbidity rate was 20·0 per cent. Overall 1-, 3- and 5-year survival rates were 91·2, 44·3 and 29·4 per cent respectively. Tumour size 5 cm or greater was the only independent predictor of overall survival (relative risk 1·71, 95 per cent confidence interval 1·08 to 2·70; P = 0·021). Neoadjuvant chemotherapy before resection, perioperative blood transfusion, bilobar disease, R1 resection margin and multiple metastases were among factors that did not significantly influence survival. CONCLUSION: Repeat hepatic resection remains the only curative option for patients presenting with recurrent colorectal liver metastases.
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Neoplasias Colorrectales , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transfusión de Sangre Autóloga , Ablación por Catéter/estadística & datos numéricos , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Reoperación , Adulto JovenRESUMEN
Molecular iodine facilitated the reaction of 5,5-dimethyl-1,3-cyclohexanedione with aromatic aldehydes in iso-propanol affording a variety of 1,8-dioxo-octahydroxanthenes in high yields. Most of the compounds synthesized showed good anti-proliferative properties in vitro against three cancer cell lines and 9-(2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione possessing a 2-hydroxy phenyl group at C-9 position was found to be promising. Further structure elaboration of the same compound and the crystal structure analysis and hydrogen bonding patterns of another compound that is, 9-(4-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione prepared by using this methodology is presented.
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Antineoplásicos/síntesis química , Yodo/química , Xantenos/síntesis química , Aldehídos/química , Antineoplásicos/farmacología , Catálisis , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Ciclohexanos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Enlace de Hidrógeno , Concentración 50 Inhibidora , Estructura Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Xantenos/farmacologíaRESUMEN
AIM: The optimal management of patients presenting with colorectal cancer and synchronous liver metastases is controversial. This survey was intended to summarize the opinions of UK colorectal and liver surgeons on the specific issues pertaining to synchronous resection. METHOD: A validated electronic survey was sent to the consultant members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the Association of Upper Gastrointestinal Surgeons (AUGIS). The questions were structured to allow direct comparison between the two groups of the responses obtained. RESULTS: Four hundred and twenty-four specialist colorectal surgeons and 52 specialist hepatobiliary surgeons were identified from the register of their respective associations. Responses were obtained from 133 (31%) colorectal and 22 (42%) liver surgeons. A majority of both groups of surgeons felt that synchronous resection was a valid therapeutic option. A majority of both groups believed that synchronous resection was justified despite the options of laparoscopic surgery and enhanced recovery programmes for each discipline. Agreed possible advantages of synchronous resections were: a decrease in the overall length of hospital stay, cost and patient anxiety. The major concern about synchronous resections was an excessive overall physiological insult. Specific scenarios indicated that synchronous resection was favoured for major/complex major colorectal resection with minor liver resection or most colorectal resections not involving an anastomosis with either a minor or major liver resection. CONCLUSION: Although significant concerns relating to synchronous resection remain amongst colorectal and liver surgeons, a majority of them felt that synchronous resections could be offered to appropriately selected patients.
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Actitud del Personal de Salud , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Pautas de la Práctica en Medicina/estadística & datos numéricos , Humanos , Encuestas y Cuestionarios , Resultado del Tratamiento , Reino UnidoRESUMEN
The paper describes the synthesis and characterization of copper oxide nanoparticles (CuO NPs) using the mixture of plant rhizome extracts Ocimum sanctum and Saussurea lappa as a reducing agent. The prepared CuO nanoparticles are characterized and confirmed their formation based on data obtained from powder X-ray diffraction spectroscopy, Fourier Transmission Infrared, Ultraviolet-Visible spectra, Field Emission Scanning Electron Microscopy images, Energy Dispersive X-ray analysis and Dynamic light scattering techniques and data reveal that the average size of CuO Nps was 103.4 nm. The result of antibacterial and antifungal activities for concentrations 50, 100, and 170 ppm indicate that NPs may exhibit appreciable activity at higher (170 ppm) concentrations. The MTT cytotoxic assay studies of Chinese Hamster Ovary (CHO) cell lines showed a Half-maximal inhibitory concentration (IC50) value of 4.14 âµg/mL.
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The total synthesis of Benzannulated macrolide, (+)-Xestodecalactone A was accomplished starting from commercially available enantiomerically pure propylene oxide and 3,5-dihydroxyphenylacetic acid using Grignard reaction, alkylation of 1,3-dithiane and Yamaguchi macrolactonisation as key steps.
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Lactonas , Macrólidos , Estereoisomerismo , AlquilaciónRESUMEN
Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec-associated side effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.
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Neoplasias Hepáticas , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Leucocitos Mononucleares , Neoplasias Hepáticas/terapia , Terapia Neoadyuvante , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , Virus Vaccinia/genéticaRESUMEN
The plant extracts are known for their anti-inflammatory, antifungal, antiviral and antibacterial properties. The use of plant extracts in the preparation of bio-materials increases their biological application. In this concern, herein reporting an eco-friendly procedure which is also a simple and cost effective, for the synthesis of Zinc Oxide nanoparticles (ZnONPs) using Saussurea lappa plant root (rhizome) extract as a fuel. The prepared nanoparticles were confirmed using various characterization techniques. The Dynamic light scattering data showed 123.5 nm particle size with -99.9 mv zeta potential which indicates excellent stability of the particles. The peak at 541 cm-1 in the IR spectrum is assigned to the stretching frequency of the zinc-binding to oxygen. The X-ray diffraction peaks confirm the close association with JCPDS Data Card No: 36-1451. The FESEM data revealed a hexagonal wurtzite structure with a hexagonal shape of synthesized ZnO nanoparticles. The antibacterial studies indicate the gram-negative strains showed better inhibition activity than gram-positive strains. Among Fungal strains, Aspergillus niger and flavus, Fusarium oxysporum, and Rhizopus oryzae showed good inhibition activity at higher concentrations. The cytotoxic data indicates the 5 µg/mL of the ZnO particles showed cytotoxicity on the CHO cell line and with IC50 value 3.164 ± 0.8956 µg/mL.
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BACKGROUND: The impact of computed tomography (CT)-based follow-up for the detection of resectable disease recurrence following surgery for colorectal liver metastases (CRLM) was evaluated. METHODS: Some 705 patients undergoing resection of CRLM between January 1993 and March 2007 were included. Surveillance comprised 3-monthly CT (thorax, abdomen and pelvis) in the first 2 years after surgery, 6 monthly for 3 years and annually from years 6 to 10. Survival differences following recurrence between patients managed surgically and palliatively were determined, and the cost was calculated. RESULTS: Five-year disease-free and overall survival rates were 28.3 and 32.3 per cent respectively. Of 402 patients who developed recurrence within 2 years, 88 were treated with liver resection alone and 36 with lung and/or liver resection. Their 5-year overall survival rates were 31 and 30 per cent respectively, compared with 3.9 per cent in 278 patients managed palliatively (P < 0.001). For each 3-month interval during the first year of follow-up, patients with recurrence treated surgically had better overall survival than those treated palliatively. The cost of surveillance that identified 124 patients amenable to further resection was 12,338 pounds per operated recurrence. Assuming that patients with recurrence gained 5 years' survival, the mean survival gain was 4.28 years per resection and the cost per life-year gained was 2883 pounds. CONCLUSION: Intensive 3-monthly CT surveillance after liver resection for CRLM detects recurrence that is amenable to further resection in a considerable number of patients. These patients have significantly better survival with a reasonable cost per life-year gained.
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Neoplasias Colorrectales , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Femenino , Hepatectomía/economía , Hepatectomía/métodos , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Tomografía Computarizada por Rayos X/economía , Resultado del Tratamiento , Adulto JovenAsunto(s)
Neoplasias Colorrectales/sangre , Hiponatremia/sangre , Sodio/sangre , Femenino , Humanos , MasculinoRESUMEN
Grafts from donation after cardiac death (DCD) donors are used to increase the number of organs available for liver transplantation. There is concern that warm ischemia may impair graft function. We compared our DCD recipients with a case-matched group of donation after brain death (DBD) recipients. Between January 2002 and April 2008, 39 DCD grafts were transplanted. These were matched with 39 DBD recipients on the basis of identified variables that had a significant impact on mortality. These were used to individually match DCD and DBD patients with similar predictive mortality. We compared patient/graft survival, primary non-function (PNF), and rates of complications. Of all liver transplants, 6.1% were DCD grafts. PNF occurred twice in the DCD group. The incidence of nonanastomotic biliary strictures (NABS; 20.5% versus 0%, P = 0.005) and hepatic artery stenosis (HAS; 12.8% versus 0%, P = 0.027) in the DCD group was higher. One-year (79.5% versus 97.4%, P = 0.029) and 3-year (63.6% versus 97.4%, P = 0.001) graft survival was lower in the DCD group. Three-year patient survival was also lower (68.2% versus 100%, P < 0.0001). Our study is the first to use case-matched patients and compare groups with similar predictive mortality. There was a higher incidence of NABS and HAS in the DCD group. NABS were likely a result of warm ischemia. HAS may have been due to ischemia or arterial injury during retrieval. The DCD group had significantly poorer outcomes, but DCD grafts remain a valuable resource. With careful donor/recipient selection, minimization of ischemia, and good postoperative care, acceptable results can be achieved.