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1.
J Endocrinol Invest ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38878126

RESUMEN

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

2.
Actas Dermosifiliogr ; 114(10): 850-857, 2023.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37482291

RESUMEN

BACKGROUND AND OBJECTIVES: There are no clinical guidelines on the management of dysplastic nevus (DN). The aims of this study were to determine the percentage of dermatologists in the center-Spain section of the Spanish Academy of Dermatology and Venereology (AEDV) who would manage a histologically confirmed DN with a watch-and-wait approach or with wider surgical margins and to investigate whether their attitudes would vary depending on whether or not the patient had a personal and/or family history of melanoma. MATERIAL AND METHODS: We collected data from an anonymous survey sent to 738 dermatologists between June 15 and July 31, 2022. The independent variables were degree of dysplasia (low vs. high), margin status (positive vs. negative), and a personal or family history of melanoma (yes vs. no in both cases). The dependent variables were attitude towards management (watch-and-wait vs. re-excision with a surgical margin of 1 to 4mm or re-excision with a surgical margin of 5 to 10mm). RESULTS: We obtained 86 responses to the questionnaire. When pathology indicated a low-grade DN, 60.5% of dermatologists stated they would obtain a surgical margin of 1 to 4mm if the first margins were positive, and 97.7% would watch and wait if the report described negative margins. For high-grade DNs, 1.2% of dermatologists would watch and wait to manage DN with positive margins; 68.8% would use this approach for negative margins. A family or personal history of melanoma had no influence on most of the dermatologists' attitudes. CONCLUSIONS: Management strategies for DN among dermatologists from the center-Spain section of the AEDV varied, particularly when faced with low-grade DN with positive margins and high-grade DN with negative margins. A family or personal history of melanoma did not influence clinical attitudes in most cases.


Asunto(s)
Dermatología , Síndrome del Nevo Displásico , Melanoma , Neoplasias Cutáneas , Venereología , Humanos , Síndrome del Nevo Displásico/cirugía , Síndrome del Nevo Displásico/patología , Márgenes de Escisión , España , Dermatólogos , Melanoma/cirugía , Melanoma/patología , Encuestas y Cuestionarios , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología
3.
Regul Toxicol Pharmacol ; 129: 105126, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35065094

RESUMEN

Asterarcys quadricellulare (AQ) is a microalgal species with potential applications in improving the quality of animal feed, and safety studies on this species are lacking. Therefore, this study presents safety data on an industrially cultivated strain of AQ tested using the following Organisation for Economic Co-operation and Development (OECD) guidelines: acute skin irritation in rabbits; skin sensitisation in guinea pigs; acute eye irritation in rabbits; acute oral fixed-dose procedure in rats; and bacterial reverse mutation using the B.N. Ames technique. Results showed that AQ is non-irritant and non-sensitising to skin. AQ caused transient conjunctival lacrimation and redness; however, the scores for these clinical signs translated into low ocular irritation indices and classification of AQ as non-irritant to the eyes. An acute oral dose of AQ (2000 mg/kg) did not cause mortality, change in body weight gain, or any general, functional, and neurobehavioral clinical signs. In five strains of Salmonella typhimurium bacteria, treatment with AQ did not cause biologically or statistically significant changes in the number of revertant colonies, indicating that AQ does not cause mutagenic toxicity. This study demonstrates the safety of a heterotrophically-produced strain of AQ and supports its use as a safe and non-toxic feed ingredient.


Asunto(s)
Alimentación Animal/microbiología , Crianza de Animales Domésticos , Chlorophyceae , Microalgas , Animales , Relación Dosis-Respuesta a Droga , Ojo/efectos de los fármacos , Cobayas , Pruebas de Mutagenicidad , Conejos , Ratas , Piel/efectos de los fármacos
4.
Regul Toxicol Pharmacol ; 123: 104924, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33831491

RESUMEN

The aim of this paper was to provide a comprehensive toxicological and safety evaluation of a yeast cell wall preparation (YCWP) for use as an animal feed ingredient. The following toxicological assessments were carried out: the mutagenic activity was tested using the Ames' Test in five Salmonella typhimurium strains; clastogenic activity was investigated using the mammalian micronucleus test in Swiss ICO OF1 (IOPS Caw) mice; genotoxic activity was assessed using the in vitro mammalian chromosomal aberration test in human lymphocytes; acute oral toxicity was tested by administration of a single dose of 2000 mg/kg BW. Eye and skin irritation were assessed in rabbits according to OECD guidelines; skin sensitivity was established in guinea pigs by means of the Buehler test, while acute dermal and inhalation studies in rats were further completed, also according to OECD guidelines. All conducted tests were considered valid under the experimental conditions. No significant mutagenic activity or genotoxic activity was observed, and it was concluded that the test article did not induce any clastogenic effect. YCWP was found to be mildly irritating to the eye, slightly irritating to the skin but was found to be non-sensitizing in the guinea pig. The acute oral, dermal and inhalation studies did not yield any evidence of gross toxicity or pharmacological effects.


Asunto(s)
Polisacáridos/toxicidad , Saccharomyces cerevisiae , Pruebas de Toxicidad , Animales , Aberraciones Cromosómicas , Seguridad de Productos para el Consumidor , Cobayas , Hidrólisis , Irritantes , Ratones , Pruebas de Micronúcleos , Conejos , Ratas , Piel
5.
J Endocrinol Invest ; 43(6): 809-820, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31925754

RESUMEN

BACKGROUND: Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms. OBJECTIVE: To measure serum levels of markers related to adiposity, inflammation/angiogenesis and digestive metabolism and correlate them with body mass index (BMI), waist-to-hip ratio (WHR), metabolic parameters and menopausal symptoms (assessed with the 10-item Cervantes Scale [CS-10]). METHODS: Serum of perimenopausal women (n = 24), STRAW stages-2 and -1, was analyzed using the Bio-Plex 200 System technology to assess 30 proposed analytes. The MetS was defined by the American Heart Association criteria and women were divided as: normal BMI (NBMI), excessive BMI (EBMI), and EBMI with MetS (EBMI-MetS). RESULTS: Weight, BMI, abdominal circumference, WHR, systolic blood pressure, glucose and triglyceride levels were significantly higher and high-density lipoprotein cholesterol (HDL-C) was lower in EBMI-MetS women compared to NBMI ones. Insulin, C-peptide, resistin, adipsin, GIP, leptin, IL-6, FGF21 and PAI-1 levels were significantly higher and ghrelin and IGFBP-1 lower in EBMI-MetS women as compared to NBMI ones. Spearman's correlation of pooled data showed a significant positive correlation between abdominal perimeter and WHR and C-peptide, insulin, adipsin, resistin, leptin, PAI-1 and FGF21 and a negative correlation with IGFBP-1 levels. Total CS-10 scores and hot flush intensity did not differ between studied groups, yet positively correlated with anthropometric values but not with studied analytes. CONCLUSION: Perimenopausal women with EBMI and the MetS showed an altered metabolic profile, but no differences in menopausal symptoms which also did not correlate with changes in studied biomarkers.


Asunto(s)
Tejido Adiposo/metabolismo , Mediadores de Inflamación/sangre , Menopausia/sangre , Enfermedades Metabólicas/sangre , Síndrome Metabólico/sangre , Perimenopausia/sangre , Adiposidad/fisiología , Biomarcadores/sangre , Índice de Masa Corporal , Estudios Transversales , Digestión/fisiología , Femenino , Humanos , Enfermedades Metabólicas/diagnóstico , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Proyectos Piloto
6.
Ann Oncol ; 30(9): 1521-1530, 2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31282941

RESUMEN

BACKGROUND: The tumor immune microenvironment (TIME) of lung cancer brain metastasis is largely unexplored. We carried out immune profiling and sequencing analysis of paired resected primary tumors and brain metastases of non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: TIME profiling of archival formalin-fixed and paraffin-embedded specimens of paired primary tumors and brain metastases from 39 patients with surgically resected NSCLCs was carried out using a 770 immune gene expression panel and by T-cell receptor beta repertoire (TCRß) sequencing. Immunohistochemistry was carried out for validation. Targeted sequencing was carried out to catalog hot spot mutations in cancer genes. RESULTS: Somatic hot spot mutations were mostly shared between both tumor sites (28/39 patients; 71%). We identified 161 differentially expressed genes, indicating inhibition of dendritic cell maturation, Th1, and leukocyte extravasation signaling pathways, in brain metastases compared with primary tumors (P < 0.01). The proinflammatory cell adhesion molecule vascular cell adhesion protein 1 was significantly suppressed in brain metastases compared with primary tumors. Brain metastases exhibited lower T cell and elevated macrophage infiltration compared with primary tumors (P < 0.001). T-cell clones were expanded in 64% of brain metastases compared with their corresponding primary tumors. Furthermore, while TCR repertoires were largely shared between paired brain metastases and primary tumors, T-cell densities were sparse in the metastases. CONCLUSION: We present findings that suggest that the TIME in brain metastases from NSCLC is immunosuppressed and comprises immune phenotypes (e.g. immunosuppressive tumor-associated macrophages) that may help guide immunotherapeutic strategies for NSCLC brain metastases.


Asunto(s)
Biomarcadores de Tumor/inmunología , Neoplasias Encefálicas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Proteínas de Neoplasias/inmunología , Microambiente Tumoral/inmunología , Adulto , Anciano , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Células Dendríticas/inmunología , Femenino , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Mutación/genética , Proteínas de Neoplasias/genética , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Microambiente Tumoral/genética
7.
Br Poult Sci ; 60(4): 414-422, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30955350

RESUMEN

1. The consumption of sufficient quantities of long chain omega-3 fatty acids (n-3 LCPUFA) from meat and other animal products can lead to a variety of health benefits in humans. The fatty acid content of poultry meat can be increased by feeding birds ingredients that are rich in n-3 LCFUFA 2. The effect of feeding a docosahexaenoic acid (DHA) rich Aurantiochytrium limacinum biomass (AURA) on the fatty acid content of breast and thigh tissues was investigated in a feeding trial with 2880 male Ross 308 broilers. The broiler diets were supplemented with either 0, 0.25, 0.5 or 1% AURA from day 21 to 42 of age. 3. Supplementation significantly increased the DHA content of both breast and thigh meat at an inclusion rate of 1% in the diet, leading to a total of 42 and 46 mg DHA/100 g of fresh breast or thigh tissue respectively. Significant increases in the tissue eicosapentaenoic acid (EPA) concentration were seen alongside a reduced omega-6/omega-3 ratio, improving the nutritional value of the meat for consumers and identifying supplementation of broiler diets with A. limacinum as an effective and sustainable method to increase n-3 LCPUFA consumption in the human population.


Asunto(s)
Pollos/fisiología , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Estramenopilos/química , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Animales , Dieta/veterinaria , Suplementos Dietéticos/análisis , Ácidos Docosahexaenoicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Ácidos Grasos Omega-3/metabolismo , Masculino , Distribución Aleatoria
8.
Br Poult Sci ; 60(5): 570-578, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31124696

RESUMEN

1. The consumption of adequate amounts of the long-chain polyunsaturated omega-3 fatty acids (n-3 LC-PUFA) has been associated with beneficial effects on human health. Eggs are commonly consumed worldwide, and their omega-3 content can be easily altered by changing the diets of laying hens and so represent an important target for enrichment. 2. In this study, the effect of supplementing laying hens with DHA-rich, Aurantiochytrium limacinum at three different inclusion levels was investigated over a 24-week period. 3. Significant increases in egg DHA concentrations were observed after four weeks and were maintained for the duration of the 24-week study. The supplemented eggs in the current study had a DHA content of 82, 101, and 129 mg/yolk when supplemented with 0.25%, 0.5% and 1% treatments, respectively, which meets the EU criteria to be considered 'high in omega-3'. 4. Using the sustainably grown protist Aurantiochytrium limacinum to supplement layer diets increased the egg DHA concentration and decreased the n-6/n-3 ratio, improving the nutritional value of the eggs for human consumers.


Asunto(s)
Pollos/metabolismo , Ácidos Grasos Omega-3/metabolismo , Valor Nutritivo , Óvulo/química , Estramenopilos/química , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Suplementos Dietéticos/análisis , Huevos/análisis , Femenino , Humanos
9.
Clin Radiol ; 73(6): 509-516, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29395224

RESUMEN

Blast injuries are complex, severe, and outside of our everyday clinical practice, but every radiologist needs to understand them. By their nature, bomb blasts are unpredictable and affect multiple victims, yet require an immediate, coordinated, and whole-hearted response from all members of the clinical team, including all radiology staff. This article will help you gain the requisite expertise in blast imaging including recognising primary, secondary, and tertiary blast injuries. It will also help you understand the fundamental role that imaging plays during mass casualty attacks and how to avoid radiology becoming a bottleneck to the forward flow of severely injured patients as they are triaged and treated.


Asunto(s)
Traumatismos por Explosión/diagnóstico , Bombas (Dispositivos Explosivos) , Traumatismos por Explosión/clasificación , Traumatismos por Explosión/etiología , Servicios Médicos de Urgencia/métodos , Explosiones , Hospitalización , Humanos , Imagen por Resonancia Magnética/métodos , Incidentes con Víctimas en Masa , Imagen Multimodal/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Triaje/métodos
10.
J Anim Physiol Anim Nutr (Berl) ; 102(2): 576-590, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29024131

RESUMEN

The aim of this study was to investigate the effect of dietary supplementation with the docosahexaenoic acid (DHA)-rich microalgae, Aurantiochytrium limacinum (AURA), on a variety of health and productivity parameters in lactating cows. Twenty-four cows were blocked by parity and number of days in milk and then randomly assigned to a control (CON; n = 12) group with no algal supplementation, or a treatment group (AURA; n = 12) provided with 100 g AURA cow-1  day-1 or 16 g DHA cow-1  day-1 . A variety of health and productivity measurements were taken, and results indicated that supplementation had no negative effects on animal health in terms of somatic cell count, haematological and biochemical blood parameters, while body condition was marginally improved by algal supplementation. No differences were found for the various production parameters measured; however, a tendency towards increased milk production was observed for the AURA group during the final stage of the study (+4.5 kg cow-1  day-1 , day 78-84). The fatty acid profile of milk was improved by supplementation, with significantly lower saturated fatty acids, significantly higher omega-3 fatty acids and an improved omega-3/omega-6 ratio observed when compared to the control group. The amount of DHA in the milk of cows provided 105 g AURA head-1  day-1 was 4.7 mg/100 g milk with a peak transfer efficiency from feed to milk at day 49 of 8.3%. These results indicate that supplementation with 105 g AURA head-1  day-1 resulted in the successful enrichment of milk with DHA without negatively impacting the health or productivity of the animals.


Asunto(s)
Alimentación Animal/análisis , Bovinos , Lactancia/efectos de los fármacos , Microalgas , Leche/química , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Femenino
11.
J Anim Physiol Anim Nutr (Berl) ; 102(4): 1026-1038, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29671902

RESUMEN

Two 125-day experiments of the same design were conducted to evaluate the effects of a heterotrophically grown microalgae (AURA) containing docosahexaenoic acid (DHA) on pig performance, carcass traits and the fatty acid composition of lean and adipose tissue. In each experiment, 144 Hypor pigs were blocked by sex, allocated to three treatment groups, and fed 0, 0.25% or 0.50% AURA in isonutritive, isocaloric diets. Pigs were weighed on days 0, 28, 56, 84 and 112. Feed and water intakes were measured every 28 days. Pigs were slaughtered on day 125. Data from the two studies were analysed as a single data set. Performance and carcass traits did not differ between treatments. Both microalgae treatment levels enriched (p < .05) Longissimus lumborum (LL) and backfat in DHA and improved (p < .05) their ratios of n-6 to n-3 fatty acids.


Asunto(s)
Dieta , Ácidos Docosahexaenoicos/farmacología , Carne/normas , Microalgas/química , Porcinos/crecimiento & desarrollo , Tejido Adiposo , Alimentación Animal , Animales , Composición Corporal , Dieta/veterinaria , Suplementos Dietéticos , Ácidos Grasos , Distribución Aleatoria , Porcinos/metabolismo
13.
Ann Oncol ; 28(1): 75-82, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-27687306

RESUMEN

Background: Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. Methods: We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry (IHC) in a subset of LUADs (n = 92). Associations among mutations, immune markers and clinicopathological variables were analyzed using ANOVA and Fisher's exact test. Cox proportional hazards regression models were used for multivariate analysis of clinical outcome. Results: LUADs in this cohort exhibited an average of 243 coding mutations. We identified 28 genes with significant enrichment for mutation. SETD2-mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant tumors. EGFR, KEAP1 and PIK3CA mutations were predictive of poor response to adjuvant therapy. Immune marker analysis revealed that LUADs in smokers and with relatively high mutation burdens exhibited increased levels of immune markers. Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited relatively low levels of infiltrating CD4+/CD8+ T-cells indicative of a muted immune response. Tumoral PD-L1 was significantly elevated in TP53 mutant LUADs whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression. LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration. Conclusion(s): Our study highlights molecular and immune phenotypes that warrant further analysis for their roles in clinical outcomes and personalized immune-based therapy of LUAD.


Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Adenocarcinoma/mortalidad , Adenocarcinoma del Pulmón , Biomarcadores de Tumor/análisis , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Exoma , Femenino , Estudios de Seguimiento , Estudio de Asociación del Genoma Completo , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Mutación , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales
14.
Ann Oncol ; 28(1): 83-89, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-28177435

RESUMEN

Background: Lung squamous cell carcinoma (LUSC) accounts for 20­30% of non-small cell lung cancers (NSCLCs). There are limited treatment strategies for LUSC in part due to our inadequate understanding of the molecular underpinnings of the disease. We performed whole-exome sequencing (WES) and comprehensive immune profiling of a unique set of clinically annotated early-stage LUSCs to increase our understanding of the pathobiology of this malignancy. Methods: Matched pairs of surgically resected stage I-III LUSCs and normal lung tissues (n = 108) were analyzed by WES. Immunohistochemistry and image analysis-based profiling of 10 immune markers were done on a subset of LUSCs (n = 91). Associations among mutations, immune markers and clinicopathological variables were statistically examined using analysis of variance and Fisher's exact test. Cox proportional hazards regression models were used for statistical analysis of clinical outcome. Results: This early-stage LUSC cohort displayed an average of 209 exonic mutations per tumor. Fourteen genes exhibited significant enrichment for somatic mutation: TP53, MLL2, PIK3CA, NFE2L2, CDH8, KEAP1, PTEN, ADCY8, PTPRT, CALCR, GRM8, FBXW7, RB1 and CDKN2A. Among mutated genes associated with poor recurrence-free survival, MLL2 mutations predicted poor prognosis in both TP53 mutant and wild-type LUSCs. We also found that in treated patients, FBXW7 and KEAP1 mutations were associated with poor response to adjuvant therapy, particularly in TP53-mutant tumors. Analysis of mutations with immune markers revealed that ADCY8 and PIK3CA mutations were associated with markedly decreased tumoral PD-L1 expression, LUSCs with PIK3CA mutations exhibited elevated CD45ro levels and CDKN2A-mutant tumors displayed an up-regulated immune response. Conclusion(s): Our findings pinpoint mutated genes that may impact clinical outcome as well as personalized strategies for targeted immunotherapies in early-stage LUSC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Mutación , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Inmunofenotipificación , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Medicina de Precisión , Secuenciación del Exoma
15.
Haemophilia ; 23(1): 135-143, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27486060

RESUMEN

INTRODUCTION AND OBJECTIVES: Intra-articular corticosteroid injections are standard of care for managing joint pain secondary to osteoarthritis or rheumatoid arthritis but are rarely used in haemophilic arthropathy. We have introduced and evaluated the efficacy and safety of ultrasound-guided corticosteroid injections for pain relief in patients with haemophilic arthropathy. PATIENTS AND METHODS: Ultrasound-guided intra-articular injections performed on haemophilia patients at UCSD between March 2012 and January 2016 were analysed. Needle placement and injection (40 mg triamcinolone; 3-5 mL lidocaine) were performed with musculoskeletal ultrasound and Power Doppler. Analysis included patient demographics, joint-specific parameters such as tissue hypervascularity and effusions, pain relief, and procedure-associated complications. RESULTS: Forty-five injections (14 ankles, 13 elbows, 18 knees) were administered in 25 patients. Advanced arthropathy with hypervascularity and/or effusions was present in 91% and 61% of joints, respectively. Ninety-one per cent of injections resulted in pain relief which was significant in 84% (>30% reduction). Median pain score was reduced from 7 of 10 to 1 of 10 (P < 0.001), usually within 24 h. Median duration of pain relief was 8 weeks (range 1-16 weeks). Haemophilia B patients experienced longer periods of relief, and high Pettersson scores were associated with shorter duration of relief. There were no procedure-associated complications. Repeat ultrasound of eight joints within 4 weeks of injection demonstrated nearly complete resolution of hypervascularity. CONCLUSIONS: Point-of-care ultrasound enabled intra-articular corticosteroid injections that provided highly effective, safe, and relatively long-lasting pain relief in haemophilic arthropathy. This approach should be used to improve pain management in haemophilic arthropathy.


Asunto(s)
Corticoesteroides/uso terapéutico , Hemofilia A/diagnóstico por imagen , Artropatías/tratamiento farmacológico , Ultrasonografía/métodos , Corticoesteroides/administración & dosificación , Adulto , Femenino , Humanos , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Resultado del Tratamiento
16.
Regul Toxicol Pharmacol ; 88: 106-117, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28583667

RESUMEN

Animal feed is routinely supplemented with exogenous enzymes to improve nutrient utilization, such as proteases to enhance protein hydrolysis in vivo and xylanases to alleviate feed related anti-nutritional factors. The present studies were conducted to evaluate the potential oral toxicity and genotoxicity of a dual-enzyme preparation, Vegpro® concentrate (VPr-C). Acute oral toxicity studies were conducted in adult male and female Sprague-Dawley Crl CD rats and CHS Swiss ICO:OFI (IOPS Caw) mice. Thirteen week preliminary and final subchronic oral toxicity studies were conducted in male and female rats. Genotoxicity was evaluated through a bacterial reverse mutation test (Ames test), an in-vitro mammalian chromosomal aberration test, and a mammalian micronucleus test. The LD50 was >2000 mg/kg of BW in mice and rats. In the 13-week oral toxicity study, the No Observed Adverse Effects Level (NOAEL) was 1000 mg/kg BW per day for females and 300 mg/kg BW per day for males. VPr-C showed no mutagenic activity in Salmonella typhimurium, did not induce significant chromosomal aberrations in cultured human lymphocytes, and did not increase the frequency or proportion of micronucleated immature erythrocytes in mice. There was no evidence of acute or subchronic toxicity or genotoxicity associated with the test article at these test dosages.


Asunto(s)
Alimentación Animal/toxicidad , Enzimas/toxicidad , Animales , Aberraciones Cromosómicas , Femenino , Humanos , Linfocitos/efectos de los fármacos , Masculino , Ratones , Pruebas de Micronúcleos , Nivel sin Efectos Adversos Observados , Ratas , Ratas Sprague-Dawley , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subcrónica
17.
J Fish Biol ; 91(1): 302-316, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28589694

RESUMEN

The goal for this project was to re-examine key morphological characters hypothesized to differentiate Gila intermedia, Gila robusta and Gila nigra and outline methods better suited for making species designations based on morphology. Using a combination of meristic counts, morphological measurements and geometric morphometrics, morphological dissimilarities were quantified among these three putative species. Traditional meristic counts and morphological measurements (i.e. distances between landmarks) were not useful for species identification. Geometric morphometrics, however, identified differences among species, while also suggesting an effect of geographic location on morphological variation. Using canonical variate analysis for the 441 fish sampled in this study, geometric morphometrics accurately predicted true group membership 100% of the time for G. nigra, 97% of the time for G. intermedia and 91% of the time for G. robusta. These results suggest that geometric morphometric analysis is necessary to identify morphological differences among the three species. Geometric morphometric analysis used in this study can be adopted by management officials as a tool to classify unidentified individuals.


Asunto(s)
Cyprinidae/anatomía & histología , Cyprinidae/clasificación , Animales , Arizona , Fenotipo , Ríos , Movimientos del Agua
18.
Eur J Orthop Surg Traumatol ; 27(2): 267-272, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27928639

RESUMEN

Proximal femoral fractures in adults under 50 years are not as common as in the elderly, but may have just as significant an impact. There is little in the literature describing the functional outcomes of fixation in this age group. Our aim was to assess the clinical and functional outcomes of operative management of extracapsular proximal femoral fractures (AO 31-A) in the young adult (<50 years). Consecutive skeletally mature patients <50 years undergoing operative fixation of these fractures were obtained from a prospective database over a 12-year period. Complications and mortality data were obtained from this database and case note review. Outcome scores were obtained via postal questionnaires. Eighty-eight patients were included in the study of which 74 (84%) had fixation with the dynamic hip screw. The mean age was 39 years (range 17-50) with a male preponderance (73.8%). Mean hospital stay was 14 days (range 2-94). Seventeen (19.3%) patients had died at a mean of 40 months from their operation date. The 1-year mortality was 4.5%. There were five complications (5.7%). SF-36 and EuroQol 5D scores showed that 5-10% had severe problems with a 20% decrease in quality of life compared to population norms. The biggest differences were in the physical function modalities. One-third had fair to poor hip function as assessed by the Oxford Hip Score. Though these injuries are relatively rare in this age group, they do have significant mortality and functional impairment reflecting a higher energy of injury rather than the frailty seen in the elderly.


Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas de Cadera/cirugía , Adolescente , Adulto , Tornillos Óseos , Inglaterra/epidemiología , Ejercicio Físico/fisiología , Femenino , Fijación Interna de Fracturas/mortalidad , Fijación Interna de Fracturas/estadística & datos numéricos , Estado de Salud , Fracturas de Cadera/mortalidad , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Adulto Joven
19.
Am J Physiol Renal Physiol ; 310(10): F1065-73, 2016 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-26936873

RESUMEN

The aim of the present study was to use a model of simulated human childbirth in rats to determine the damage to genitourinary structures and behavioral signs of urinary dysfunction induced by vaginal distension (VD) in female rats. In experiment 1, the length of the genitourinary tract and the nerves associated with it were measured immediately after simulated human delivery induced by VD or sham (SH) procedures. Electroneurograms of the dorsal nerve of the clitoris (DNC) were also recorded. In experiment 2, histological characteristics of the bladder and major pelvic ganglion of VD and SH rats were evaluated. In experiment 3, urinary parameters were determined in conscious animals during 6 h of dark and 6 h of light before and 3 days after VD or SH procedures. VD significantly increased distal vagina width (P < 0.001) and the length of the motor branch of the sacral plexus (P < 0.05), DNC (P < 0.05), and vesical nerves (P < 0.01) and decreased DNC frequency and amplitude of firing. VD occluded the pelvic urethra, inducing urinary retention, hematomas in the bladder, and thinness of the epithelial (P < 0.05) and detrusor (P < 0.01) layers of the bladder. Major pelvic ganglion parameters were not modified after VD. Rats dripped urine in unusual places to void, without the stereotyped behavior of micturition after VD. The neuroanatomic injuries after VD occur alongside behavioral signs of urinary incontinence as determined by a new behavioral tool for assessing micturition in conscious animals.


Asunto(s)
Modelos Animales de Enfermedad , Trastornos Puerperales/etiología , Incontinencia Urinaria/etiología , Animales , Femenino , Ganglión/patología , Compresión Nerviosa/efectos adversos , Parto , Trastornos Puerperales/patología , Distribución Aleatoria , Ratas Wistar , Vejiga Urinaria/patología , Incontinencia Urinaria/patología , Micción
20.
Knee Surg Sports Traumatol Arthrosc ; 24(5): 1510-8, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26231150

RESUMEN

The science and surgery of the meniscus have evolved significantly over time. Surgeons and scientists always enjoy looking forward to novel therapies. However, as part of the ongoing effort at optimizing interventions and outcomes, it may also be useful to reflect on important milestones from the past. The aim of the present manuscript was to explore the history of meniscal surgery across the ages, from ancient times to the twenty-first century. Herein, some of the investigations of the pioneers in orthopaedics are described, to underline how their work has influenced the management of the injured meniscus in modern times. Level of evidence V.


Asunto(s)
Meniscos Tibiales/cirugía , Procedimientos Ortopédicos/historia , Procedimientos Ortopédicos/métodos , Lesiones de Menisco Tibial/cirugía , Historia del Siglo XV , Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Historia Antigua , Historia Medieval , Humanos , Ortopedia
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