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1.
J Gen Virol ; 105(1)2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38180085

RESUMEN

Host tissues represent diverse resources or barriers for pathogen replicative fitness. We tested whether viruses in specialist, generalist, and non-specialist interactions replicate differently in local entry tissue (fin), and systemic target tissue (kidney) using infectious hematopoietic necrosis virus (IHNV) and three salmonid fish hosts. Virus tissue replication was host specific, but one feature was shared by specialists and the generalist which was uncommon in the non-specialist interactions: high host entry and replication capacity in the local tissue after contact. Moreover, specialists showed increased replication in systemic target tissues early after host contact. By comparing ancestral and derived IHNV viruses, we also characterized replication tradeoffs associated with specialist and generalist evolution. Compared with the ancestral virus, a derived specialist gained early local replicative fitness in the new host but lost replicative fitness in the ancestral host. By contrast, a derived generalist showed small replication losses relative to the ancestral virus in the ancestral host but increased early replication in the local tissue of novel hosts. This study shows that the mechanisms of specialism and generalism are host specific and that local and systemic replication can contribute differently to overall within host replicative fitness for specialist and generalist viruses.


Asunto(s)
Salmonidae , Animales , Especialización , Riñón , Replicación Viral
2.
Br J Surg ; 111(3)2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38488528

RESUMEN

BACKGROUND: Histopathological and molecular features have been proposed to hold prognostic information, but few have been validated. The aim of this retrospective study was to validate the Genetic And Morphological Evaluation ('GAME') score and assess the impact of histological characteristics on the prognosis in patients with colorectal liver metastases. METHODS: Data were collected from 176 patients with metastatic colorectal cancer undergoing liver resection at Hospital de la Santa Creu i Sant Pau. Patients were classified into Genetic And Morphological Evaluation score groups and relapse-free survival and overall survival were calculated. Histopathological changes in colorectal liver metastases were documented and prognostic variables were selected to create a post-surgery score, called the Histopathological, Clinical, And Molecular ('HICAM') score. RESULTS: Regarding the Genetic And Morphological Evaluation score, the high-risk group had a median relapse-free survival of 8.8 months, compared with 20.5 months for the low-risk group (P = 0.005), and the high-risk group had a median overall survival of 37.8 months, compared with 67.0 months for the low-risk group (P = 0.005). Histological examination of 144 liver samples showed that the desertic immune phenotype was associated with worse overall survival in the multivariable analysis (P = 0.020). The Histopathological, Clinical, And Molecular score variables were age at diagnosis, tumour burden score, carcinoembryonic antigen levels greater than or equal to 20 ng/ml, primary tumour resection, TNM stage at diagnosis, molecular status, histopathological growth patterns, and immune phenotypes of the liver. The high-risk group had a median relapse-free survival of 8.4 months, compared with 20.4 months for the low-risk group (P < 0.001), and a median overall survival of 30.4 months, compared with 105.0 months for the low-risk group (P < 0.001). CONCLUSION: The Genetic And Morphological Evaluation score was validated as a preoperative prognostic tool to predict candidacy for liver resection. The Histopathological, Clinical, And Molecular score could be useful to assess adjuvant treatment after hepatic resection.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Estudios Retrospectivos , Neoplasias Colorrectales/patología , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Hepatectomía
3.
J Environ Manage ; 334: 117415, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36780814

RESUMEN

Much remains unknown about variation in pathogen transmission across the geographic range of a free-ranging fish or animal species and about the influence of movement (associated with husbandry practices or animal behavior) on pathogen transmission. Salmonid hatcheries are an ideal system in which to study these processes. Salmonid hatcheries are managed for endangered species recovery, supplementation of threatened or at-risk fish stocks, support of fisheries, and ecosystem stability. Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus of significant concern to salmon aquaculture. Landscape IHNV transmission dynamics previously had been estimated only for salmonid hatcheries in the Lower Columbia River Basin (LCRB). The objectives of this study were to estimate IHNV transmission dynamics in a unique geographic region, the Snake River Basin (SRB), and to quantitatively estimate the effect of model coproduction on inference because previous assessments of coproduction have been qualitative. In contrast to the LCRB, the SRB has hatchery complexes consisting of a main hatchery and ≥1 satellite facility. Knowledge about hatchery complexes was held by a subset of project researchers but would not have been available to project modelers without coproduction. Project modelers generated and tested multiple versions of Bayesian susceptible-exposedinfected models to realistically represent the SRB and estimate the effect of coproduction. Models estimated the frequency of transmission routes, route-specific infection probabilities, and infection probabilities for combinations of salmonid hosts and IHNV lineages. Model results indicated that in the SRB, avoiding exposure to IHNV-positive adult salmonids is the most important action to prevent juvenile infections. Migrating adult salmonids exposed juvenile cohort-sites most frequently, and the infection probability was greatest following exposure to migrating adults. Without coproduction, the frequency of exposure by migrating adults would have been overestimated by 70 cohort-sites, and the infection probability following exposure to migrating adults would have been underestimated by∼0.09. The coproduced model had less uncertainty in the infection probability if no transmission route could be identified (Bayesian credible interval (BCI) width = 0.12) compared to the model without coproduction (BCI width = 0.34). Evidence for virus lineage MD specialization on steelhead and rainbow trout (both Oncorhynchus mykiss) was apparent without model coproduction. In the SRB, we found a greater probability of virus lineage UC infection in Chinook salmon (Oncorhynchus tshawytscha) compared to in O. mykiss, whereas in the LCRB, UC more clearly exhibited a generalist approach. Coproduction influenced estimates that depended on transmission routes, which operated differently at main hatcheries and satellite sites within hatchery complexes. Hatchery complexes are found outside of the SRB and are not specific to salmonid hatcheries alone. There is great potential for coproduction and modeling spatial contact networks to advance understanding about infectious disease transmission in complex production systems and surrounding free-ranging animal populations.


Asunto(s)
Enfermedades de los Peces , Virus de la Necrosis Hematopoyética Infecciosa , Salmonidae , Animales , Ríos , Ecosistema , Teorema de Bayes , Salmón
4.
Br J Cancer ; 120(2): 190-195, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30585257

RESUMEN

BACKGROUND: Patients harbouring the UGT1A1*28/*28 genotype are at risk of severe toxicity with the standard irinotecan dose. However, this dose is considerably lower than the dose that can be tolerated by UGT1A1*1/*1 and *1/*28 patients. This randomised phase II trial evaluated the efficacy and safety of the FOLFIRI regimen with high-dose irinotecan (HD-FOLFIRI) in metastatic colorectal cancer patients. METHODS: Eighty-two patients with the UGT1A1*1/*1 or the *1/*28 genotype were randomised to receive HD-FOLFIRI versus FOLFIRI. Patients with the UGT1A1*28/*28 genotype were excluded. In the experimental group, the irinotecan dose was 300 mg/m2 for UGT1A1*1/*1 and 260 mg/m2 for *1/*28 patients. In the control group, the dose was 180 mg/m2. We analysed the overall response rate (ORR), toxicity, and survival. RESULTS: The ORR was significantly higher in the HD-FOLFIRI group (67.5 versus 43.6%; p = 0.001 OR: 1.73 [95% CI:1.03-2.93]). Neutropenia (17.7%), diarrhoea (5.1%), and asthenia (5.1%) were the most common grade 3-4 toxicity. No differences were observed in severe toxicity (22.5% versus 20.5%), dose reduction (22.5% versus 28.2%), or prophylactic G-CSF (17.5% versus 12.8%). No difference in survival was found. CONCLUSIONS: Patients with the UGT1A1*1/*1 and *1/*28 genotypes can receive high doses of irinotecan to achieve a more favourable ORR without significant adverse events.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Glucuronosiltransferasa/genética , Irinotecán/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Genotipo , Humanos , Irinotecán/efectos adversos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Pruebas de Farmacogenómica
5.
Pharmacogenomics J ; 18(4): 556-564, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29282362

RESUMEN

The role of vascular endothelial growth factor (VEGF) gene polymorphisms in the prognosis of colon cancer prognosis remains unclear. We evaluated the influence of 28 single-nucleotide polymorphisms in 12 genes in the VEGF pathway on the prognosis of 347 patients with stage II-III colon cancer. We found that rs9513070 (VEGFR1) and rs1137282 (KRAS) were associated with overall survival in stage II colon cancer patients (p = 0.025 and p = 0.001, respectively). When primary tumor location was considered, rs9513070 was also associated with relapse-free and overall survival (p = 0.033 and p = 0.031, respectively) in left colon cancer patients. Additionally, rs35251833 in the ITGAV gene correlated with relapse-free survival (p = 0.032). This study provides evidence that germline polymorphisms in VEGFR1, KRAS and ITGAV genes are associated with prognosis in stages II-III colon cancer patients. As stage and tumor location are correlated with prognosis, future genetic studies should stratify colon cancer patients according to these parameters.


Asunto(s)
Neoplasias del Colon/genética , Integrina alfaV/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Neoplasias del Colon/epidemiología , Neoplasias del Colon/patología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Polimorfismo de Nucleótido Simple/genética , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos
6.
Br J Clin Pharmacol ; 84(6): 1389-1392, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29504153

RESUMEN

Severe irinotecan-induced toxicity is associated with UGT1A1 polymorphisms. However, some patients develop side-effects despite harbouring a normal UGT1A1 genotype. As CYP3A4 is also an irinotecan-metabolizing enzyme, our study aimed to elucidate the influence of the CYP3A4*20 loss-of-function allele in the toxicity profile of these patients. Three-hundred and eight metastatic colorectal cancer patients treated with an irinotecan-containing chemotherapy were studied. The presence of CYP3A4*20, UGT1A1*37 and UGT1A1*28 alleles was tested. Associations between these genetic variants and toxicity were evaluated. UGT1A1*28 was significantly associated with severe diarrhoea, neutropenia and asthenia (P = 0.002, P = 0.037 and P = 0.041, respectively). One patient with the UGT1A1*28/*37 genotype presented with grade IV neutropenia and lethal septic shock. One heterozygous UGT1A1 (*1/*28) patient also carried the CYP3A4*20 allele but did not develop toxicity. We confirm that UGT1A1*37 and UGT1A1*28 are associated with severe toxicity and suggest that the CYP3A4*20 allele does not play a role in irinotecan-induced toxicity.


Asunto(s)
Astenia/inducido químicamente , Neoplasias Colorrectales/tratamiento farmacológico , Citocromo P-450 CYP3A/genética , Diarrea/inducido químicamente , Glucuronosiltransferasa/genética , Irinotecán/efectos adversos , Neutropenia/inducido químicamente , Variantes Farmacogenómicas , Inhibidores de Topoisomerasa I/efectos adversos , Anciano , Astenia/diagnóstico , Astenia/genética , Neoplasias Colorrectales/patología , Citocromo P-450 CYP3A/metabolismo , Diarrea/diagnóstico , Diarrea/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Glucuronosiltransferasa/metabolismo , Heterocigoto , Humanos , Masculino , Neutropenia/diagnóstico , Neutropenia/genética , Fenotipo , Factores de Riesgo , Índice de Severidad de la Enfermedad
7.
Ecol Lett ; 20(10): 1325-1336, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28871636

RESUMEN

Superspreading, the phenomenon where a small proportion of individuals contribute disproportionately to new infections, has profound effects on disease dynamics. Superspreading can arise through variation in contacts, infectiousness or infectious periods. The latter has received little attention, yet it drives the dynamics of many diseases of critical public health, livestock health and conservation concern. Here, we present rare evidence of variation in infectious periods underlying a superspreading phenomenon in a free-ranging wildlife system. We detected persistent infections of Mycoplasma ovipneumoniae, the primary causative agent of pneumonia in bighorn sheep (Ovis canadensis), in a small number of older individuals that were homozygous at an immunologically relevant genetic locus. Interactions among age-structure, genetic composition and infectious periods may drive feedbacks in disease dynamics that determine the magnitude of population response to infection. Accordingly, variation in initial conditions may explain divergent population responses to infection that range from recovery to catastrophic decline and extirpation.


Asunto(s)
Neumonía por Mycoplasma/veterinaria , Enfermedades de las Ovejas/epidemiología , Borrego Cimarrón , Animales , Animales Salvajes , Mycoplasma ovipneumoniae , Neumonía , Ovinos
8.
Am Nat ; 189(6): 616-629, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28514636

RESUMEN

Eco-evolutionary theory argues that population cycles in consumer-resource interactions are partly driven by natural selection, such that changes in densities and changes in trait values are mutually reinforcing. Evidence that the theory explains cycles in nature, however, is almost nonexistent. Experimental tests of model assumptions are logistically impractical for most organisms, while for others, evidence that population cycles occur in nature is lacking. For insect baculoviruses in contrast, tests of model assumptions are straightforward, and there is strong evidence that baculoviruses help drive population cycles in many insects, including the gypsy moth that we study here. We therefore used field experiments with the gypsy moth baculovirus to test two key assumptions of eco-evolutionary models of host-pathogen population cycles: that reduced host infection risk is heritable and that it is costly. Our experiments confirm both assumptions, and inserting parameters estimated from our data into eco-evolutionary insect-outbreak models gives cycles closely resembling gypsy moth outbreak cycles in North America, whereas standard models predict unrealistic stable equilibria. Our work shows that eco-evolutionary models are useful for explaining outbreaks of forest insect defoliators, while widespread observations of intense selection on defoliators in nature and of heritable and costly resistance in defoliators in the lab together suggest that eco-evolutionary dynamics may play a general role in defoliator outbreaks.


Asunto(s)
Evolución Biológica , Mariposas Nocturnas , Animales , Bosques , América del Norte , Hojas de la Planta , Dinámica Poblacional
9.
Gut ; 64(6): 921-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25011934

RESUMEN

OBJECTIVE: We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled. DESIGN: To show a HR advantage of 0.6 in progression-free survival (PFS) for FCGR2A-HH versus the rest and FCGR3A-VV versus the rest, with an 80% power, 80 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type (KRAS-WT) and 52 KRAS-WT patients are required, respectively. This leads to a total sample size of 952 and 619 patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated with cetuximab alone or in combination with chemotherapy. Fc gamma receptor (FCGR) status was centrally genotyped. Two additional externally genotyped series were included. RESULTS: Incidences of FCGR2A-HH and FCGR3A-VV in KRAS-WT patients were 220/660 (33%) and 109/676 (16.1%) respectively. There was no difference in median PFS (mPFS) for KRAS-WT patients with FCGR2A-HH (22.0 weeks; 95% CI18.8 to 25.2) versus non-HH (22.0 weeks; 95% CI 19.4 to 24.6) or for FCGR3A-VV (16.4 weeks; 95% CI 13.0 to 19.8) versus non-VV (23 weeks; 95% CI 21.1 to 24.9) (p=0.06). Median overall survival, response rate and disease control rate assessments showed no benefit for either HH or VV. CONCLUSIONS: No differences in mPFS were found between the FCGR polymorphisms HH and the others and VV versus the others in KRAS-WT mCRC patients refractory to irinotecan, oxaliplatin and 5-fluorouracil treated with cetuximab. We cannot confirm the effects of other IgG1 antibodies, which may be weaker than previously suggested. Other markers may be needed to study the actual host antibody response to cetuximab.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Receptores ErbB/antagonistas & inhibidores , Mutación de Línea Germinal , Polimorfismo Genético , Receptores de IgG/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Cetuximab , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Técnicas de Genotipaje/normas , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tasa de Supervivencia , Adulto Joven
10.
Proc Biol Sci ; 281(1779): 20132567, 2014 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-24478295

RESUMEN

Hosts have evolved two distinct defence strategies against parasites: resistance (which prevents infection or limit parasite growth) and tolerance (which alleviates the fitness consequences of infection). However, heritable variation in resistance and tolerance and the genetic correlation between these two traits have rarely been characterized in wild host populations. Here, we estimate these parameters for both traits in Leuciscus burdigalensis, a freshwater fish parasitized by Tracheliastes polycolpus. We used a genetic database to construct a full-sib pedigree in a wild L. burdigalensis population. We then used univariate animal models to estimate inclusive heritability (i.e. all forms of genetic and non-genetic inheritance) in resistance and tolerance. Finally, we assessed the genetic correlation between these two traits using a bivariate animal model. We found significant heritability for resistance (H = 17.6%; 95% CI: 7.2-32.2%) and tolerance (H = 18.8%; 95% CI: 4.4-36.1%), whereas we found no evidence for the existence of a genetic correlation between these traits. Furthermore, we confirm that resistance and tolerance are strongly affected by environmental effects. Our results demonstrate that (i) heritable variation exists for parasite resistance and tolerance in wild host populations, and (ii) these traits can evolve independently in populations.


Asunto(s)
Cyprinidae/parasitología , Resistencia a la Enfermedad/genética , Variación Genética , Interacciones Huésped-Parásitos/genética , Animales , Genotipo
12.
Med Sci Monit ; 20: 268-73, 2014 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-24535068

RESUMEN

BACKGROUND: Atrial fibrillation is a relatively common arrhythmia often seen in patients with permanent pacemakers. In this study we aimed to assess the incidence of atrial fibrillation in patients whose pacemakers were programmed to pace in the right ventricle (VVI) and compared it with patients whose pacemakers were programmed in non-VVI mode(i.e. AAI or DDD). MATERIAL AND METHODS: Records of the patients with permanent pacemaker or implantable-cardioverter-defibrillator were evaluated and analyzed. These patients had regular periodic follow-up evaluation over the last 10 years. (January 1, 2002 to December 31, 2012). Patient demographic, pacemaker data, pacing mode, review and analysis of arrhythmia log for occurrence of new atrial fibrillation and echocardiographic findings for left atrial size, mitral regurgitation, were analyzed and recorded. Left atrial size was classified as mild, moderate or severe enlargement, depending on the left atrial dimension. RESULTS: Average age was 68 years. There was no gender predominance (51% male). Mean follow-up duration was 6 years and 3 months. Hispanic population represented the majority of the patients (65.4%). Majority of the devices (80.0%) were programmed as DDD pacing mode. Fifty-five patients (52.8%) did not develop atrial fibrillation. 85.7% of the patients paced in VVI-mode had atrial fibrillation while atrial fibrillation occurred in 37.4% among patients paced in non-VVI-mode. This difference was statistically significant (P<0.0001). CONCLUSIONS: Right ventricular pacing in a VVI mode was associated with higher incidence of atrial fibrillation, mitral regurgitation and left atrial enlargement. Non-VVI based pacing demonstrated lower incidence of new onset atrial fibrillation.


Asunto(s)
Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Estimulación Cardíaca Artificial/métodos , Desfibriladores Implantables/efectos adversos , Marcapaso Artificial/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Atrios Cardíacos/patología , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Texas/epidemiología
13.
Clin Transl Oncol ; 26(1): 98-108, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37316754

RESUMEN

PURPOSE: Growing complexity and demand for cancer care entail increased challenges for Medical Oncology (MO). The Spanish Society of Medical Oncology (SEOM) has promoted studies to provide updated data to estimate the need for medical oncologists in 2040 and to analyse current professional standing of young medical oncologists. METHODS: Two national, online surveys were conducted. The first (2021) targeted 146 Heads of MO Departments, and the second (2022), 775 young medical oncologists who had completed their MO residency between 2014 and 2021. Participants were contacted individually, and data were processed anonymously. RESULTS: Participation rates reached 78.8% and 48.8%, respectively. The updated data suggest that 87-110 new medical oncologist full-time equivalents (FTEs) should be recruited each year to achieve an optimal ratio of 110-130 new cases per medical oncologist FTE by 2040. The professional standing analysis reveals that 9.1% of medical oncologists trained in Spain do not work in clinical care in the country, with tremendous employment instability (only 15.2% have a permanent contract). A high percentage of young medical oncologists have contemplated career paths other than clinical care (64.5%) or working in other countries (51.7%). CONCLUSIONS: Optimal ratios of medical oncologists must be achieved to tackle the evolution of MO workloads and challenges in comprehensive cancer care. However, the incorporation and permanence of medical oncologists in the national healthcare system in Spain could be compromised by their current sub-optimal professional standing.


Asunto(s)
Oncólogos , Carga de Trabajo , Humanos , España , Censos , Oncología Médica , Recursos Humanos , Encuestas y Cuestionarios
14.
Clin Transl Oncol ; 26(4): 864-871, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37651021

RESUMEN

PURPOSE: Clinical practice guidelines recommend that all patients with metastatic colorectal cancer (mCRC) should be tested for mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). We aimed to describe the dMMR/MSI-H testing practice in patients with mCRC in Spanish centers. METHODS: Multicenter, observational retrospective study that included patients newly diagnosed with mCRC or who progressed to a metastatic stage from early/localized stages. RESULTS: Three hundred patients were included in the study from May 2020 through May 2021, with a median age of 68 years, and two hundred twenty-five (75%) had stage IV disease at initial diagnosis; two hundred eighty-four patients received first-line treatment, and dMMR/MSI-H testing was performed in two hundred fifty-one (84%) patients. The results of the dMMR/MSI-H tests were available in 61 (24%) of 251 patients before the diagnosis of metastatic disease and in 191 (81%) of 236 evaluable patients for this outcome before the initiation of first-line treatment. Among the 244 patients who were tested for dMMR/MSI-H with IHC or PCR, 14 (6%) were MMR deficient. The most frequent type of first-line treatment was the combination of chemotherapy and biological agent, that was received by 71% and 50% of patients with MMR proficient and deficient tumors, respectively, followed by chemotherapy alone, received in over 20% of patients in each subgroup. Only 29% of dMMR/MSI-H tumors received first-line immunotherapy. CONCLUSION: Our study suggests that a high proportion of patients with mCRC are currently tested for dMMR/MSI-H in tertiary hospitals across Spain. However, there is still room for improvement until universal testing is achieved. TRIAL REGISTRATION: Not applicable.


Asunto(s)
Neoplasias Encefálicas , Neoplasias del Colon , Neoplasias Colorrectales , Síndromes Neoplásicos Hereditarios , Neoplasias del Recto , Anciano , Humanos , Neoplasias del Colon/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , Inestabilidad de Microsatélites , Estudios Retrospectivos , España
15.
Pharmacogenet Genomics ; 23(3): 142-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23324806

RESUMEN

OBJECTIVE: Although KRAS mutation status has been identified as a strong predictor of response to anti-epidermal growth factor receptor (EGFR) therapies, not all wild-type patients respond. The lethal-7 (let-7) family of microRNAs regulates KRAS activity. A functional polymorphism (rs61764370) has been described in the let-7 complementary site (LCS6). We hypothesized a possible association between this KRAS let-7 LCS6 polymorphism and the response to anti-EGFR treatments in KRAS and BRAF wild-type metastatic colorectal cancer patients (mCRC). MATERIALS AND METHODS: We studied the association of the KRAS let-7 LCS6 polymorphism with the response in 100 refractory mCRC patients treated with anti-EGFR antibodies. To assess the real effect of this polymorphism in relation to the treatment administered, we also studied this association in an independent cohort of patients treated exclusively with chemotherapy. The KRAS let-7 LCS6 polymorphism was genotyped using the BioMark system in blood and tumor DNA samples. The BRAF V600E mutation was analyzed in tumor samples. RESULTS: The KRAS let-7 LCS6 G-allele showed a statistically significant association with nonresponse to anti-EGFR-based treatment: 31.9% of patients with the T/T genotype presented a complete or a partial response versus no patients with T/G or G/G genotypes (P=0.004). No statistically significant differences were observed in the patients who received chemotherapy only. CONCLUSION: These data support the pharmacogenetic role of the KRAS let-7 LCS6 polymorphism in predicting the efficacy of anti-EGFR-based therapy in mCRC patients with the KRAS and the BRAF wild-type genotype.


Asunto(s)
Regiones no Traducidas 3' , Neoplasias Colorrectales/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Genes ras , Polimorfismo de Nucleótido Simple , Sitios de Unión , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Metástasis de la Neoplasia
16.
J Invertebr Pathol ; 112(2): 184-91, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23232473

RESUMEN

The Guatemala potato tuber moth Tecia solanivora (Povolny) (Lep. Gelechiidae) is an invasive species from Mesoamerica that has considerably extended its distribution area in recent decades. While this species is considered to be a major potato pest in Venezuela, Colombia, and Ecuador, currently no specific control methods are available for farmers. To address this issue we developed a biopesticide formulation to be used in integrated pest management of T. solanivora, following three steps. First, search for entomopathogenic viruses were carried out through extensive bioprospections in 12 countries worldwide. As a result, new Phthorimaea operculella granulovirus (PhopGV) isolates were found in T. solanivora and five other gelechid species. Second, twenty PhopGV isolates, including both previously known and newly found isolates, were genetically and/or biologically characterized in order to choose the best candidate for a biopesticide formulation. Sequence data were obtained for the ecdysteroid UDP-glucosyltransferase (egt) gene, a single copy gene known to play a role in pathogenicity. Three different sizes (1086, 1305 and 1353 bp) of egt were found among the virus isolates analyzed. Unexpectedly, no obvious correlation between egt size and pathogenicity was found. Bioassays on T. solanivora neonates showed a maximum of a 14-fold difference in pathogenicity among the eight PhopGV isolates tested. The most pathogenic PhopGV isolate, JLZ9f, had a medium lethal concentration (LC(50)) of 10 viral occlusion bodies per square mm of consumed tuber skin. Third, we tested biopesticide dust formulations by mixing a dry carrier (calcium carbonate) with different adjuvants (magnesium chloride or an optical brightener or soya lecithin) and different specific amounts of JLZ9f. During laboratory experiments, satisfactory control of the pest (>98% larva mortality compared to untreated control) was achieved with a formulation containing 10 macerated JLZ9f-dead T. solanivora larvae per kg of calcium carbonate mixed with 50 mL/kg of soya lecithin. The final product provides an interesting alternative to chemical pesticides for Andean farmers affected by this potato pest.


Asunto(s)
Granulovirus/patogenicidad , Insecticidas , Mariposas Nocturnas/virología , Control Biológico de Vectores/métodos , Solanum tuberosum/parasitología , Animales , Bioensayo , Glucosiltransferasas/genética , Granulovirus/enzimología , Granulovirus/genética , Mariposas Nocturnas/fisiología
17.
Eur J Popul ; 39(1): 10, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-36976350

RESUMEN

Subnational differences in male fertility within sub-Saharan African countries have not been explored, nor the differences in male fertility according to migration status been sufficiently probed. We study divergences in rural and urban male fertility and investigate the relationship between male fertility and migration across 30 sub-Saharan African countries. We employ 67 Demographic and Health Surveys to estimate completed cohort fertility among men aged 50-64 according to migration status. Overall, we find that urban male fertility has declined faster than rural male fertility, widening the gap between the sectors. Rural-urban migrant men have lower fertility than their rural non-migrant counterparts. Men migrating within the rural sector have similarly high fertility as rural non-migrants, while urban-urban migrant men have even lower fertility than non-migrant urban men. Using country-fixed effects models, we find that among men with at least secondary education, differences in completed cohort fertility by migration status are widest. When we consider the timing of migration in relation to the timing of the birth of the last child, we observe that migrant men are a select group, having around two children less than non-migrant rural men. There is also evidence of adaptation to destination, though to a lesser extent. Furthermore, migration within the rural sector does not seem to be disruptive to fathering. These results indicate that rural-to-urban migration has the potential to delay rural fertility decline, and that urban male fertility is likely to decline further, especially as the proportion of urban-to-urban migration increases.

18.
Environ Sci Pollut Res Int ; 30(51): 110089-110103, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37783992

RESUMEN

The reduction of nitric oxide (NO) emissions to atmosphere has been recently addressed using biological technologies. However, NO removal through bioprocesses is quite challenging due to the low solubility of NO in water. Therefore, the abatement of NO emissions might be improved by adding a chelating agent or a mass transfer vector (MTV) to increase the solubility of this pollutant into the aqueous phase where the bioprocess takes place. This research seeks to assess the performance of different non-aqueous phase liquids (NAPs): n-hexadecane (HEX), diethyl sebacate (DSE), 1,1,1,3,5,5,5-heptamethyl-trisiloxane (HTX), 2,2,4,4,6,8,8-heptamethylnonane (HNO), and high temperature silicone oil (SO) in chemical absorption-biological reduction (CABR) integrated systems. The results showed that HNO and HTX had the maximum gas-liquid mass transfer capacity, being 0.32 mol NO/kmol NAP and 0.29 mol NO/kmol NAP, respectively. When an aqueous phase was added to the system, the mass transfer gas-liquid of NO was increased, with HTX reaching a removal efficiency of 82 ± 3% NO with water, and 88 ± 6% with a phosphate buffer solution. All NAPs were tested for short-term toxicity assessment and resulted neither toxic nor inhibitory for the biological activity (denitrification). DSE was found to be biodegradable, which could limit its applicability in biological processes for gas treatment. Finally, in the CABR system tests, it was shown that NO elimination improved in a short time (30 min) when the three mass transfer vectors (HEX, HTX, HNO) were added to enriched denitrifying bacteria.


Asunto(s)
Reactores Biológicos , Óxido Nítrico , Reactores Biológicos/microbiología , Agua
19.
BMJ Open ; 13(11): e071791, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37977863

RESUMEN

OBJECTIVES: This study aims to assess sample selection bias in mobile phone survey estimates of fertility and under-5 mortality. DESIGN: With data from the Demographic and Health Surveys, we use logistic regressions to identify sociodemographic correlates of mobile phone ownership and access, and Poisson regressions to estimate the association between mobile phone ownership (or access) and fertility and under-5 mortality estimates. We evaluate the potential reasons why estimates by mobile phone ownership differ using a set of behavioural characteristics. SETTING: 34 low-income and middle-income countries, mostly in sub-Saharan Africa. PARTICIPANTS: 534 536 women between the ages of 15 and 49. OUTCOME MEASURES: Under-5 mortality rate (U5MR) and total fertility rate (TFR). RESULTS: Mobile phone ownership ranges from 23.6% in Burundi to 96.7% in Armenia. The median TFR ratio and U5MR ratio between the non-owners and the owners of a mobile phone are 1.48 and 1.29, respectively. Fertility and mortality rates would be biased downwards if estimates are only based on women who own or have access to mobile phones. Estimates of U5MR can be adjusted through poststratification using age, educational level, area of residence, wealth and marital status as weights. However, estimates of TFR remain biased even after adjusting for these covariates. This difference is associated with behavioural factors (eg, contraceptive use) that are not captured by the poststratification variables, but for which there are also differences between mobile phone owners and non-owners. CONCLUSIONS: Mobile phone surveys need to collect data on sociodemographic background characteristics to be able to weight and adjust mortality estimates ex post facto. Fertility estimates from mobile phone surveys will be biased unless further research uncovers the mechanisms driving the bias.


Asunto(s)
Teléfono Celular , Países en Desarrollo , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Sesgo de Selección , Encuestas y Cuestionarios , Fertilidad
20.
Clin Transl Oncol ; 25(3): 796-802, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36418642

RESUMEN

BACKGROUND: There is a lack of knowledge about the career paths and employment situation of young medical oncologists. The aim of our study was to evaluate the current professional standing of these professionals in Spain. METHODS: The Spanish Society of Medical Oncology + MIR section conducted a national online survey in May 2021 of young medical oncology consultants (< 6 years of expertise) and final year medical oncology residents. RESULTS: A total of 162 responses were eligible for analysis and included participants from 16 autonomous communities; 64% were women, 80% were consultants, and 20% were residents. More than half of the participants performed routine healthcare activity and only 7% research activity. Almost three quarters (73%) were subspecialized in a main area of interest and almost half of these chose this area because it was the only option available after residency. Half of the respondents (51%) considered working abroad and 81% believed the professional standing in Spain was worse than in other countries. After finishing their residency, only 22 were offered a job at their training hospital. Just 16% of participants had a permanent employment contract and 87% were concerned (score of ≥ 5 on a scale of 1-10) about their job stability. In addition, one quarter of the participants in our study showed an interest in increasing their research activity. CONCLUSIONS: The choice of subspecialty in medical oncology may depend on job opportunities after residency rather than personal interest. The abundance of temporary contracts may have influenced the job stability concerns observed. Future mentoring strategies should engage in building a long-term career path for young medical oncologists.


Asunto(s)
Oncología Médica , Oncólogos , Humanos , Femenino , Masculino , España , Encuestas y Cuestionarios , Empleo
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