ABSTRACT
BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Reproducibility of Results , Neoplasm Recurrence, Local/genetics , RNA/analysis , RNA, Messenger/geneticsABSTRACT
The global area cultivated with oil palm has doubled in the past two decades, causing deforestation, land-use change, freshwater pollution, and species loss in tropical ecosystems worldwide. Despite the palm-oil industry been linked to severe deterioration of freshwater ecosystems, most studies have focused on terrestrial environments, while freshwaters have been significantly less studied. We evaluated these impacts by contrasting freshwater macroinvertebrate communities and habitat conditions in 19 streams from primary forests (7), grazing lands (6), and oil palm plantations (6). In each stream, we measured environmental characteristics, e.g., habitat composition, canopy cover, substrate, water temperature, and water quality; and we identified and quantified the assemblage of macroinvertebrates. Streams in oil palm plantations lacking riparian forest strips showed warmer and more variable temperatures, higher turbidity, lower silica content, and poorer macroinvertebrate taxon richness than primary forests. Grazing lands showed higher conductivity and temperature, and lower dissolved oxygen and macroinvertebrate taxon richness than primary forests. In contrast, streams in oil palm plantations that conserved a riparian forest, showed a substrate composition, temperature, and canopy cover more similar to the ones in primary forests. These habitat improvements by riparian forests in the plantations increased macroinvertebrate taxon richness and maintained a community resembling more the one in primary forests. Therefore, the conversion of grazing lands (instead of primary forests) to oil palm plantations can increase freshwater taxon richness only if riparian native forests are safeguarded.
Subject(s)
Ecosystem , Rivers , Rivers/chemistry , Forests , Fresh Water , Water Quality , AgricultureSubject(s)
Humans , Altitude Sickness/epidemiology , Chronic Disease , Acute Disease , Spain/epidemiology , PrevalenceABSTRACT
KEY MESSAGES: Visual acuity is the most used method to assess visual function in children. Contrast sensitivity complements the information provided for visual acuity, but it is not commonly used in clinical practice. Digital devices are increasingly used as a method to evaluate visual function, due to multiple advantages. Testing with these devices can improve the evaluation of visual development in children from a few months of age. Visual acuity and contrast sensitivity tests, using eye tracking technology, are able to measure visual function in children across a wide range of ages, objectively, quickly and without need of an experienced examiner. PURPOSE: To report age-normative values for grating visual acuity and contrast sensitivity in healthy children using a digital device with eye tracking technology and to validate the grating acuity test. METHODS: In the first project of the study, we examined healthy children aged between 6 months and 7 years with normal ophthalmological assessment. Grating visual acuity (VA) and contrast sensitivity (CS) were assessed using a preferential gaze paradigm with a DIVE (Device for an Integral Visual Examination) assisted with eye tracking technology to provide age norms. For the validation project, we compared LEA grating test (LGT) with DIVE VA in a group of children aged between 6 months and 4 years with normal and abnormal visual development. RESULTS: Fifty-seven children (2.86 ± 1.55 years) were examined with DIVE VA test and 44 successfully completed DIVE CS test (3.06 ± 1.41 years). Both, VA and CS values increased with age, mainly along the first two years of life. Sixty-nine patients (1.34 ± 0.61 years) were included in the DIVE VA test validation. The mean difference between LGT and DIVE VA was - 1.05 ± 4.54 cpd with 95% limits of agreement (LoA) of - 9.95-7.84 cpd. Agreement between the two tests was higher in children younger than 1 year with a mean difference of - 0.19 ± 4.02 cpd. CONCLUSIONS: DIVE is an automatic, objective and reliable tool to assess several visual function parameters in children, and it has good agreement with classical VA tests, especially for the first stage of life.
Subject(s)
Contrast Sensitivity , Ophthalmology , Child , Eye-Tracking Technology , Humans , Infant , Vision Tests/methods , Visual AcuityABSTRACT
Más de 100 millones de personas ascienden cada año a áreas montañosas elevadas en todo el planeta y en altitudes no extremas (< 5.500 m) entre el 10 y el 85% se ven afectados por el denominado mal agudo de montaña, la enfermedad más frecuentemente inducida por una hipoxia hipobárica ligera-moderada. Asimismo, unos 140 millones de seres humanos viven de forma permanente en cotas comprendidas entre 2.500-5.500 m y hasta un 10% de ellos padecen la forma subaguda del mal de montaña (hipertensión pulmonar de la gran altitud) o la forma crónica (enfermedad de Monge), esta última especialmente frecuente en etnias andinas. La presente revisión expone los conceptos generales más relevantes en torno a estas 3variantes clínicas, las cuales pueden ser incapacitantes, llegar a complicarse y ser potencialmente mortales, siendo esencial realizar una correcta prevención, diagnóstico, terapéutica y manejo de las mismas en un entorno hostil como es la alta montaña (AU)
More than 100 million people ascend to high mountainous areas worldwide every year. At nonextreme altitudes (<5500 m), 1085% of these individuals are affected by acute mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia. Approximately 140 million individuals live permanently at heights of 25005500 m, and up to 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary hypertension) or the chronic form (Monge's disease), the latter of which is especially common in Andean ethnicities. This review presents the most relevant general concepts of these 3 clinical variants, which can be incapacitating and can result in complications and become life-threatening. Proper prevention, diagnosis, treatment and management of these conditions in a hostile environment such as high mountains are therefore essential (AU)
Subject(s)
Humans , Altitude Sickness/diagnosis , Altitude Sickness/therapy , Diagnosis, Differential , Chronic Disease , Acute DiseaseABSTRACT
More than 100 million people ascend to high mountainous areas worldwide every year. At nonextreme altitudes (<5500m), 10-85% of these individuals are affected by acute mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia. Approximately 140 million individuals live permanently at heights of 2500-5500m, and up to 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary hypertension) or the chronic form (Monge's disease), the latter of which is especially common in Andean ethnicities. This review presents the most relevant general concepts of these 3 clinical variants, which can be incapacitating and can result in complications and become life-threatening. Proper prevention, diagnosis, treatment and management of these conditions in a hostile environment such as high mountains are therefore essential.
Subject(s)
Altitude Sickness , Hypertension, Pulmonary , Acute Disease , Altitude , Altitude Sickness/diagnosis , Altitude Sickness/epidemiology , Altitude Sickness/therapy , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/etiology , HypoxiaABSTRACT
The direct reaction between Cu(CH3COO)2 and uracil-1-acetic acid in water gives rise to the formation of a hydrogel consisting of entangled nanometric ribbons of a crystalline antiferromagnetic 1D Cu(ii) coordination polymer (CP) decorated with biocompatible uracil nucleobases. This hydrogel is the precursor for the preparation of a meso/macroporous ultralight aerogel that shows a remarkable Young's modulus. As a proof-of-concept of the molecular recognition capability of the terminal uracil moieties anchored at Cu(ii) CP chains, this material has been tested as the selective stationary phase for the separation of nucleobase derivatives in HPLC columns.
Subject(s)
Nanofibers , Copper , Hydrogels , Metals , PolymersABSTRACT
More than 100 million people ascend to high mountainous areas worldwide every year. At nonextreme altitudes (<5500 m), 10-85% of these individuals are affected by acute mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia. Approximately 140 million individuals live permanently at heights of 2500-5500 m, and up to 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary hypertension) or the chronic form (Monge's disease), the latter of which is especially common in Andean ethnicities. This review presents the most relevant general concepts of these 3 clinical variants, which can be incapacitating and can result in complications and become life-threatening. Proper prevention, diagnosis, treatment and management of these conditions in a hostile environment such as high mountains are therefore essential.
ABSTRACT
Objetivo: Evaluar la estructura retiniana mediante tomografía de coherencia óptica (OCT) en niños con antecedentes de exposición prenatal a tóxicos. Métodos: Se exploraron 49niños expuestos a tóxicos prenatalmente, de edades comprendidas entre 5 y 18años. De ellos, 25 tenían antecedentes de exposición prenatal a tabaco, 20 fueron expuestos durante el embarazo a alcohol y 4 a otras drogas de abuso. Todos los niños fueron sometidos a una exploración oftalmológica completa incluyendo la realización de una OCT. Se realizó una comparación frente a un grupo control, pareado por edad, de 25niños con embarazos controlados sin exposición a tóxicos. Resultados: Los niños expuestos prenatalmente a tóxicos presentan una reducción significativa del espesor medio de la capa de fibras nerviosas de la retina (CFNR) en comparación con los no expuestos (81,5 vs. 99,7; p < 0,005), así como de sus cuatro cuadrantes (CFNR superior: 97,5 vs. 127,5; p < 0,005; CFNR nasal: 61,5 vs. 72,3; p = 0,005; CFNR inferior: 99,8 vs. 128,6; p < 0,005, CFNR temporal: 58,3 vs. 68,2; p<0,005). También se objetivó una disminución significativa en el espesor medio de la capa de células ganglionares (72,9 vs. 85,9; p < 0,005). De las diferentes exposiciones prenatales estudiadas, en los niños expuestos a drogas de abuso se encontró la mayor disminución en el grosor de CFNR (CFNR espesor medio = 72), seguidos de los expuestos a alcohol (CFNR espesor medio = 72,9) y, en tercer lugar, el grupo de expuestos a tabaco durante el embarazo (CFNR espesor medio = 94,6). Conclusiones: La exposición a tóxicos durante la gestación interfiere en el desarrollo de la retina. Estos resultados refuerzan la evidencia de las recomendaciones acerca de evitar el consumo de cualquier tipo de tóxicos durante el embarazo
Purpose: To assess structural changes in the retina using optical coherence tomography (OCT) in children prenatally exposed to toxic substances. Methods: The study included a total of 49 infants, aged between 5 and 18 years, exposed to toxic substances during pregnancy. Among the exposed children, 25 were exposed to tobacco, 20 were exposed to alcohol, and 4 children were exposed to other drugs of abuse. All children underwent a complete ophthalmology examination, including an OCT. The results were compared against a control group composed of 25 infants, age matched with controlled pregnancy, and not exposed to toxic substances. Results: Children prenatally exposed to toxic substances showed significantly thinner average retinal nerve fibre layer (RNFL) compared with control children (81.5 vs. 99.7μm; P < .005), as well as RNFL thinning in its four quadrants (superior RNFL: 97.5 vs. 127.5μm; P < .005; nasal RNFL: 61.5 vs. 72.3μm; P < .005; inferior RNFL: 99.8 vs. 128.6μm; P < .005, temporal RNFL: 58.3 vs. 68.2μm; P < .005). Exposed children also exhibited a thinner ganglion cell layer (72.9 vs. 85.9; P < .005). Greater RNFL thinning was observed in children exposed to drugs of abuse (RNFL thinner average = 72), followed by children exposed to alcohol (RNFL thinner average = 72.9), and finally the least affected were those children exposed to tobacco during pregnancy (RNFL = 94.6). Conclusion: Toxic substances during pregnancy interfere in retinal development. These results strengthen the evidence about the avoidance of any toxic substance during pregnancy
Subject(s)
Humans , Male , Female , Pregnancy , Child, Preschool , Child , Adolescent , Prenatal Exposure Delayed Effects/diagnostic imaging , Tobacco Use/adverse effects , Alcoholism/complications , Illicit Drugs/adverse effects , Substance-Related Disorders/complications , Refractive Errors/diagnostic imaging , Refractive Errors/etiology , Strabismus/diagnostic imaging , Strabismus/etiology , Optic Nerve/diagnostic imaging , Tomography, Optical Coherence , Case-Control Studies , Cross-Sectional Studies , Observational Study , Visual AcuityABSTRACT
PURPOSE: To assess structural changes in the retina using optical coherence tomography (OCT) in children prenatally exposed to toxic substances. METHODS: The study included a total of 49 infants, aged between 5 and 18years, exposed to toxic substances during pregnancy. Among the exposed children, 25 were exposed to tobacco, 20 were exposed to alcohol, and 4 children were exposed to other drugs of abuse. All children underwent a complete ophthalmology examination, including an OCT. The results were compared against a control group composed of 25 infants, age matched with controlled pregnancy, and not exposed to toxic substances. RESULTS: Children prenatally exposed to toxic substances showed significantly thinner average retinal nerve fibre layer (RNFL) compared with control children (81.5 vs. 99.7µm; P<.005), as well as RNFL thinning in its four quadrants (superior RNFL: 97.5 vs. 127.5µm; P<.005; nasal RNFL: 61.5 vs. 72.3µm; P<.005; inferior RNFL: 99.8 vs. 128.6µm; P<.005, temporal RNFL: 58.3 vs. 68.2µm; P<.005). Exposed children also exhibited a thinner ganglion cell layer (72.9 vs. 85.9; P<.005). Greater RNFL thinning was observed in children exposed to drugs of abuse (RNFL thinner average=72), followed by children exposed to alcohol (RNFL thinner average=72.9), and finally the least affected were those children exposed to tobacco during pregnancy (RNFL=94.6). CONCLUSION: Toxic substances during pregnancy interfere in retinal development. These results strengthen the evidence about the avoidance of any toxic substance during pregnancy.
Subject(s)
Central Nervous System Depressants , Ethanol , Illicit Drugs , Nicotiana , Prenatal Exposure Delayed Effects , Retina/growth & development , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Matched-Pair Analysis , Organ Size , Pregnancy , Regression Analysis , Retina/drug effects , Retina/pathology , Tomography, Optical Coherence , Visual AcuityABSTRACT
BACKGROUND: Among malignancies, lung cancer is a leading cause of death. Platinum-based therapeutic compounds used to treat lung cancer have not been able to increase the survival of patients and such compounds have a high incidence of adverse and toxic effects. It has been proposed that flavonoids such as catechins may significantly reduce the risk of developing cancer, alongside with other health benefits. The aim of this work was to determine the effect of (-)-epicatechin, the main flavanol found in cocoa, on the proliferation of the lung non-small cell adenocarcinoma cancer cell line A549, and to determine its effects when added simultaneously with cisplatin. MATERIALS AND METHODS: Concentration-response curves for cisplatin and epicatechin were obtained, inhibitory concentrations calculated and an isobolographic analysis was then performed. RESULTS: We found that epicatechin has a concentration-dependent inhibitory effect on proliferation of tumor cells and the isobolographic analysis reveals that the effect of its combination with cisplatin is synergistic. It was also observed that epicatechin promotes cell death by apoptosis. CONCLUSIONS: Epicatechin might be considered for future studies to explore its possible use as coadjuvant in cisplatin-based treatments.
Subject(s)
Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Lung Neoplasms/pathology , A549 Cells , Adenocarcinoma of Lung , Catechin/pharmacology , Cell Survival/drug effects , Cisplatin/pharmacology , Drug Synergism , HumansABSTRACT
Myiasis is an infestation of tissues and organs of humans and animals by Diptera larvae (flies, horseflies, mosquitoes). They are located at different body sites, and classified clinically as cutaneous, visceral and cavitary. We report a 26-year-old woman with a history of seborrheic dermatitis and recent trip to Brazil. She presented with a seven days history of suppurating wounds in the parieto-occipital area of the scalp. At physical examination we found three ulcers of approximately 1.5 cm each, with multiple mobile larvae inside. The obtained larvae were analyzed, identifying Cochliomyia hominivorax larvae at L2 and L3 stages. The patient was managed successfully with oral antimicrobials and local cleansing. The screwworm Cochliomyia hominivorax in our country is rare. Known risk factors are wounds, poor personal hygiene, extreme ages, psychiatric disorders, presence of specific dermatosis such as psoriasis and seborrheic dermatitis, among others.
Subject(s)
Dermatitis, Seborrheic/complications , Diptera/growth & development , Larva/growth & development , Myiasis/complications , Myiasis/diagnosis , Adult , Animals , Antiparasitic Agents/therapeutic use , Diptera/classification , Female , Humans , Ivermectin/therapeutic use , Larva/classification , Myiasis/drug therapy , TravelABSTRACT
Resumen La linfohistiocitosis hemofagocítica es un síndrome hiperinflamatorio y no una enfermedad independiente. Representa una reacción hiperinflamatoria terminal que puede ocurrir en diferentes condiciones. Las formas genéticas de la linfohistiocitosis hemofagocítica se deben a un defecto en el transporte y el funcionamiento de los gránulos citotóxicos de las células NK y de los linfocitos T citotóxicos y no sólo están restringidas durante la niñez. Las formas adquiridas de esta enfermedad se encuentran en infecciones, enfermedades autoinflamatorias y autoinmunitarias, neoplasias malignas e insuficiencias inmunológicas adquiridas. El tratamiento está dirigido a suprimir la actividad de las citocinas y eliminar las células activadas e infectadas.
Abstract Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome and not an independent disease. Hemophagocytic lymphohistiocytosis is a terminal hyperinflammatory reaction that can occur in different conditions. The hemophagocytic lymphohistiocytosis genetic forms are due to a defect in the transport and operation of the cytotoxic granules of NK cells and cytotoxic T lymphocytes and are not only restricted in childhood. Acquired forms of hemophagocytic lymphohistiocytosis are found in infections, auto-inflammatory and autoimmune diseases, cancers and acquired immune deficiencies. The treatment is aimed at suppressing the activity of cytokines and eliminate infected and activated cells.
ABSTRACT
Myiasis is an infestation of tissues and organs of humans and animals by Diptera larvae (flies, horseflies, mosquitoes). They are located at different body sites, and classified clinically as cutaneous, visceral and cavitary. We report a 26-year-old woman with a history of seborrheic dermatitis and recent trip to Brazil. She presented with a seven days history of suppurating wounds in the parieto-occipital area of the scalp. At physical examination we found three ulcers of approximately 1.5 cm each, with multiple mobile larvae inside. The obtained larvae were analyzed, identifying Cochliomyia hominivorax larvae at L2 and L3 stages. The patient was managed successfully with oral antimicrobials and local cleansing. The screwworm Cochliomyia hominivorax in our country is rare. Known risk factors are wounds, poor personal hygiene, extreme ages, psychiatric disorders, presence of specific dermatosis such as psoriasis and seborrheic dermatitis, among others.
Subject(s)
Humans , Animals , Female , Adult , Dermatitis, Seborrheic/complications , Diptera/growth & development , Larva/growth & development , Myiasis/complications , Myiasis/diagnosis , Travel , Ivermectin/therapeutic use , Diptera/classification , Larva/classification , Myiasis/drug therapy , Antiparasitic Agents/therapeutic useABSTRACT
BACKGROUND: Prematurity and low birth weight are known risk factors for cognitive and developmental impairments, and school failure. Visual perceptual and visual motor skills seem to be among the most affected cognitive domains in these children. AIMS: To assess the influence of prematurity and low birth weight in visual cognitive skills and school performance. METHODS: We performed a prospective cohort study, which included 80 boys and girls in an age range from 5 to 13. Subjects were grouped by gestational age at birth (preterm, <37 weeks; term, 37-42 weeks) and birth weight (small for gestational age (SGA), <10th centile; appropriate weight for gestational age (AGA), ≥10th centile). Each child underwent full ophthalmologic assessment and standardized testing of visual cognitive abilities (Test of Visual Perceptual Skills and Test of Visual Analysis Skills). Parents completed a questionnaire on school performance in children. RESULTS: Figure-ground skill and visual motor integration were significantly decreased in the preterm birth group, compared with term control subjects (figure-ground: 45.7 vs 66.5, p=0.012; visual motor integration, TVAS: (9.9 vs 11.8, p=0.018), while outcomes of visual memory (29.0 vs 47.7, p=0.012), form constancy (33.3 vs 52.8, p=0.019), figure-ground (37.4 vs 65.6, p=0.001), and visual closure (43.7 vs 62.6 p=0.016) testing were lower in the SGA (vs AGA) group. Visual cognitive difficulties corresponded with worse performance in mathematics (r=0.414, p=0.004) and reading (r=0.343, p=0.018). CONCLUSION: Specific patterns of visual perceptual and visual motor deficits are displayed by children born preterm or SGA, which hinder mathematics and reading performance.
Subject(s)
Achievement , Child Development , Cognition , Psychomotor Performance , Reading , Visual Perception , Adolescent , Birth Weight , Child , Child, Preschool , Cohort Studies , Female , Gestational Age , Humans , Infant, Low Birth Weight , Infant, Premature , Infant, Small for Gestational Age , Male , Mathematics , Motor Skills , Prospective Studies , SchoolsABSTRACT
OBJECTIVE: To evaluate whether menopausal status and symptoms among female gynecologists would influence their clinical behavior related to menopausal hormone therapy (MHT). METHODS: Female gynecologists of 11 Latin American countries were requested to fill out the Menopause Rating Scale and a questionnaire containing personal information and that related to MHT use. RESULTS: A total of 818 gynecologists accepted to participate (86.4%). Overall, the mean age was 45.0 ± 10.7 years, 32.2% were postmenopausal, and 17.6% worked in an academic position; 81.8% reported that they would use MHT if they have symptoms, regardless of menopausal status. Academic gynecologists favor personal MHT use at a higher rate (p = 0.04) and have a higher MHT prescription rate as compared to non-academic ones (p = 0.0001). The same trend was observed among post- as compared to premenopausal ones (p = 0.01) and among those who had hysterectomy alone as compared to those experiencing natural menopause (p = 0.002). The presence of menopausal symptoms did not influence their MHT prescription. Current use of MHT and alternative therapy was higher among post- than premenopausal gynecologists (both, p = 0.0001) and among those who had undergone hysterectomy than those experiencing natural menopause. A 38.5% perceived breast cancer as the main risk related to MHT, and a high proportion prescribed non-hormonal drugs (86.4%) or alternative therapies (84.5%). CONCLUSION: Most female gynecologists in this survey would use MHT if menopausal symptoms were present. Postmenopausal physicians use MHT and prescribe it to their symptomatic patients at a higher rate than premenopausal physicians.
Subject(s)
Estrogen Replacement Therapy/psychology , Gynecology , Menopause/psychology , Physicians, Women/psychology , Practice Patterns, Physicians'/statistics & numerical data , Adult , Female , Humans , Latin America , Middle Aged , Premenopause/psychology , Surveys and QuestionnairesABSTRACT
BACKGROUND: Fibrin provides a temporary matrix at the site of vascular injury. The aims of the present work were (1) to follow fibrin formation and lysis onto the surface of human dermal microvascular endothelial cells (HMEC-1), and (2) to quantify the secretion of fibrinolytic components in the presence of fibrin. METHODS: Fibrin clots at different fibrinogen concentrations were formed on top of (model 1) or beneath (model 2) the endothelial cells. Fibrin formation or lysis onto the surface of HMEC-1 cells, was followed by turbidity. Clot structure was visualized by laser scanning confocal microscopy (LSCM). The secretion of uPA and PAI-1 by HMEC-1 cells was quantified by ELISA. RESULTS: The rate of fibrin formation increased approximately 1.5-fold at low fibrinogen content (0.5 and 1 mg/mL; p < 0.05) compared to the condition without cells; however, it was decreased at 2 mg/mL fibrinogen (p < 0.05) and no differences were found at higher fibrinogen concentrations (3 and 5 mg/mL). HMEC-1 retarded dissolution of clots formed onto their surface at 0.5 to 3 mg/mL fibrinogen (p < 0.05). Secretion of uPA was 13 × 10(-6) ng/mL per cell in the absence of RGD and 8 × 10(-6) ng/mL per cell in the presence of RGD, when clots were formed on the top of HMEC-1. However, the opposite was found when cells were grown over fibrin: 6 × 10(-6) ng/mL per cell without RGD vs. 17 × 10(-6) ng/mL per cell with RGD. The secretion of PAI-1 by HMEC-1 cells was unrelated to the presence of fibrin or RGD, 7 × 10(-6) µg/mL per cell and 5 × 10(-6) µg/mL per cell, for the apical (model 1) and basal clots (model 2), respectively. CONCLUSIONS: HMEC-1 cells influence fibrin formation and dissolution as a function of the fibrin content of clots. Clot degradation was accentuated at high fibrin concentrations. The secretion of fibrinolytic components by HMEC-1 cells seemed to be modulated by integrins that bind RGD ligands.
ABSTRACT
BACKGROUND: We present the oncological and functional results from a series of 43 patients with renal tumours, treated consecutively with robot-assisted partial nephrectomy (RPN). MATERIALS AND METHOD: Between 2010 and 2014, we performed 95 RPNs. To assess the results, we included only those patients (n=43) who had a minimum follow-up of 2 years. A descriptive analysis was conducted of the demographic characteristics and perioperative variables. We employed Kaplan-Meier curves to assess overall survival, cancer-specific survival and recurrence-free survival. RESULTS: The patients' mean age was 53.1±13.5 years. The mean preoperative tumour size was 3.7±2.3cm. The mean surgical time was 102.2±37.1min. The mean ischemia time was 21.27±7.74minutes, with a median intraoperative bleeding volume of 150mL (IQR, 87.5-425). There was a 7% rate of postoperative complications (Clavien≥III). There was no mortality. The average Fürhman grade was 2.5±0.56. There were no positive surgical margins or local recurrences. The median follow-up was 38±8 months, with an overal survival, recurrence-free survival and cancer-specific survival of 100% at 3 years of follow-up. The recurrence-free survival was 92,3% at 48 months of follow-up. The mean preoperative glomerular filtration rate was 91.04±28.17mL/min/1.73m(2), and the postoperative rate was 89.9±27.69mL/min/1.73m(2), with a nonsignificant reduction (P=.74). CONCLUSIONS: The functional and oncological results of our series confirm the safety and efficacy of RPN. RPN offers optimal preservation of renal function and oncological control in the medium term.
Subject(s)
Kidney Neoplasms/surgery , Nephrectomy/methods , Robotic Surgical Procedures , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recovery of Function , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Los países de América Latina y El Caribe avanzan hacia una mayor urbanización, pero la población rural no desaparecerá. Se estima que, en 2030, algunos países tendrán una población rural superior al 30%. A su vez, el conjunto de cambios sociales, económicos y políticos están diseñando lo que se ha denominado "la nueva ruralidad".El acceso a agua y saneamiento es un derecho humano. Pese a los avances logrados en las dos últimas décadas, se mantienen las brechas de cobertura entre áreas rurales y urbanas y entre acceso a agua y a saneamiento. Sin embargo, se tienen experiencias exitosas validadas en programas con un amplio componente de participación comunitaria, tales como los de Ecuador, Bolivia, Honduras, Nicaragua y Perú; en varios casos, se cuenta con estrategias de intervención en las que las comunidades rurales implementan la contratación de servicios de los proveedores para acceder a la rehabilitación o construcción de sus sistemas de agua potable y saneamiento básico
