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1.
Otolaryngol Pol ; 78(2): 29-34, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38623858

RESUMEN

<b><br>Introduction:</b> Although PET/CT is effective for staging HNSCC, its impact on patient management is somewhat controversial. For this reason, we considered it necessary to carry out a study in order to verify whether PET/CT helps to improve the prognosis and treatment in patients. This study was designed to address the impact of PET-FDG imaging when used alongside CT in the staging and therapeutic management of patients with HNSCC.</br> <b><br>Material and methods:</b> Data was collected from 169 patients diagnosed with HNSCC with both CT and PET/CT (performed within a maximum of 30 days of each other). It was evaluated whether discrepancies in the diagnosis of the two imaging tests had impacted the treatment.</br> <b><br>Results:</b> The combined use of CT and PET/CT led to a change in the treatment of 67 patients, who represented 39.7% of the sample. In 27.2% of cases, it entailed a change in the type of treatment which the patient received. In 3.0% of the cases, using both diagnostic tests led to modifications of the therapeutic intention of our patients.</br> <b><br>Conclusions:</b> Using PET/CT in addition to the conventional imaging method in staging resulted in more successful staging and more appropriate therapeutic decision-making.</br>.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/terapia , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/terapia , Estadificación de Neoplasias
2.
Acta Otolaryngol ; 142(7-8): 627-633, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36131532

RESUMEN

INTRODUCTION: Squamous cell carcinoma (SCC) of the vocal cord in stages I or II can be treated with radiotherapy (RT) or transoral CO2 laser microsurgery (TLM), with good oncological results. OBJECTIVES: To study the survival of patients with SCC of the vocal cord in early stages, treated with RT or TLM, in a tertiary hospital. MATERIAL AND METHODS: Disease-free survival (DFS), specific survival (SS), and overall survival (OS) were studied in patients diagnosed with stage I and II SCC of the vocal cord, for a span of 10 years of follow-up, based on sociodemographic characteristics of the patient and the primary treatment (TLM or RT). RESULTS: Both treatments achieved good survival rates. However, long-term SS was greater in patients treated with TLM compared to those treated with RT (91.7% vs. 50%, respectively, p = .001). In addition, patients treated with TLM presented a higher OS in the short term than those treated with RT (99.0% vs. 89.1%, respectively. p = .004). CONCLUSIONS AND SIGNIFICANCE: Primary treatment with TLM obtained better results than RT in the survival of patients with SCC of the vocal cord in the early stages.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Laríngeas , Terapia por Láser , Dióxido de Carbono , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Supervivencia sin Enfermedad , Glotis/patología , Glotis/cirugía , Humanos , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Terapia por Láser/métodos , Microcirugia/métodos , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del Tratamiento
4.
Braz J Otorhinolaryngol ; 88 Suppl 4: S143-S151, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34933818

RESUMEN

OBJECTIVE: The aim of this study is to find out if a single imaging test is enough to follow-up on an oncological post-treatment patient. In such a case, we would know which was more valuable after comparing the two, by CT or PET-CT. METHODS: Between January 2012 and July 2018, we collected data from all patients with previous medical history who were treated with a head and neck squamous cell carcinoma in our hospital, through surgery or by using an organ preservation protocol which we had done. Patients were required to have a CT and a PET-CT performed in a maximum period of 30 days between techniques. We compared the post post-treatment stage given to each case by using only the physical examination (only the CT and the PET-CT), with the ones given by the Tumor Board. After treatment, we analysed the similarity through Cramer's V statistic test. RESULTS: We performed a comparative analysis, obtaining a correlation of 0.426 between the stages given by the Tumor Board and the one assigned based on physical examination, without imaging techniques. By only using the computed tomography as an imaging method the correlation was 0.565, whereas with only the use of positron emission computed technology, it was estimated at 0.858. When we compared the statistical association between stages using exclusively one of the two imaging techniques, the correlation was 0.451. CONCLUSION: Independent of the modality, we have demonstrated that in patients who have received previous treatment, there was a higher correlation in the stages with respect to the diagnostic method conducted by the Tumor Board using PET-CT as the sole image. LEVEL OF EVIDENCE: Level 1.


Asunto(s)
Neoplasias de Cabeza y Cuello , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/terapia , Tomografía Computarizada por Rayos X , Estadificación de Neoplasias , Radiofármacos
5.
Braz. j. otorhinolaryngol. (Impr.) ; 87(1): 11-18, Jan.-Feb. 2021. tab
Artículo en Inglés | LILACS | ID: biblio-1153585

RESUMEN

Abstract Introduction: Head and neck squamous cell carcinoma is the seventh most common malignant tumor. The advances in treatment have improved the global survival rates in the past years, although the prognosis is still grave. Objective: The aim of the present study is to evaluate the correlation between positron emission computed tomography and computed tomography at the time of staging a previously untreated head and neck squamous cell carcinoma, and to determine which of the two imaging techniques gives us more information at the time of initial diagnosis. Methods: Data from all patients diagnosed in our hospital of head and neck squamous cell carcinoma by a biopsy of any location or unknown primary tumor was collected, between January 2012 and July 2017. In all cases, computed tomography and positron emission computed tomography were performed with a maximum of 30 days difference between them and patients had not received any prior treatment to staging. The stage given to each case was compared based solely on the physical examination, only on the computed tomography/positron emission computed tomography, with respect to the stage given by the tumor board, observing the concordance obtained through Cramer's V statistical test. Results: We performed a comparative analysis obtaining a correlation of 0.729 between the stage given by the tumor board and the one assigned based on the physical examination without imaging techniques. When only using computed tomography as an imaging method, the correlation was 0.848, whereas with only the use of positron emission computed tomography it was estimated at 0.957. When comparing the statistical association between staging using exclusively one of the two imaging techniques, correlation was 0.855. Conclusion: Positron emission computed tomography is useful for the diagnosis of head and neck squamous cell carcinoma, improving the patient's staging especially when detecting cervical and distant metastases. Therefore, we consider that the use of positron emission computed tomography for the staging of patients with head and neck squamous cell carcinoma is a diagnostic test to be considered.


Resumo Introdução: O carcinoma espinocelular de cabeça e pescoço é o sétimo tumor maligno mais comum. Os avanços no tratamento melhoraram as taxas de sobrevida global nos últimos anos, embora o prognóstico ainda seja grave. Objetivo: Avaliar a correlação entre a tomografia computadorizada por emissão de pósitrons e a tomografia computadorizada no estadiamento de carcinomas espinocelulares da cabeça e pescoço não tratados previamente e verificar qual das duas técnicas de imagem nos fornece mais informações no momento do diagnóstico inicial. Método: Os dados de todos os pacientes diagnosticados em nosso hospital com carcinoma espinocelular de cabeça e pescoço por biópsia de qualquer região ou adenopatias de origem desconhecida foram colhidos no período entre janeiro de 2012 e julho de 2017. Em todos os casos, uma tomografia computadorizada e uma tomografia computadorizada por emissão de pósitrons foram realizadas com um máximo de 30 dias de diferença entre elas. Nenhum paciente deveria ter recebido tratamento antes do estadiamento. O estadiamento atribuído a cada caso foi comparado com base apenas no exame físico, pela tomografia computadorizada ou apenas pela tomografia computadorizada por emissão de pósitrons, com relação ao estadiamento concedido pela margem tumoral, observou-se a concordância obtida pelo teste estatístico de V de Cramer. Resultado: Realizamos a análise comparativa obtendo uma correlação de 0,729 entre o estadio concedido pela margem tumoral e aquele atribuído com base no exame físico sem técnicas de imagem. Usando apenas a tomografia computadorizada como método de imagem, a correlação foi de 0,848, enquanto que a correlação com a tomografia computadorizada por emissão de pósitrons foi estimada em 0,957. Ao comparar a associação estatística entre o estadiamento usando exclusivamente uma das duas técnicas de imagem, foi de 0,855. Conclusão: Tomografia computadorizada por emissão de pósitrons é útil para o diagnóstico de carcinoma espinocelular de cabeça e pescoço, melhora o estadiamento, especialmente na detecção de metástases cervicais e à distância. Portanto, concluimos que seu uso para o estadiamento de pacientes com carcinoma espinocelular de cabeça e pescoço é um exame diagnóstico a ser considerado.


Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Sensibilidad y Especificidad , Radiofármacos , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Estadificación de Neoplasias
6.
Braz J Otorhinolaryngol ; 87(1): 11-18, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-31337597

RESUMEN

INTRODUCTION: Head and neck squamous cell carcinoma is the seventh most common malignant tumor. The advances in treatment have improved the global survival rates in the past years, although the prognosis is still grave. OBJECTIVE: The aim of the present study is to evaluate the correlation between positron emission computed tomography and computed tomography at the time of staging a previously untreated head and neck squamous cell carcinoma, and to determine which of the two imaging techniques gives us more information at the time of initial diagnosis. METHODS: Data from all patients diagnosed in our hospital of head and neck squamous cell carcinoma by a biopsy of any location or unknown primary tumor was collected, between January 2012 and July 2017. In all cases, computed tomography and positron emission computed tomography were performed with a maximum of 30 days difference between them and patients had not received any prior treatment to staging. The stage given to each case was compared based solely on the physical examination, only on the computed tomography/positron emission computed tomography, with respect to the stage given by the tumor board, observing the concordance obtained through Cramer's V statistical test. RESULTS: We performed a comparative analysis obtaining a correlation of 0.729 between the stage given by the tumor board and the one assigned based on the physical examination without imaging techniques. When only using computed tomography as an imaging method, the correlation was 0.848, whereas with only the use of positron emission computed tomography it was estimated at 0.957. When comparing the statistical association between staging using exclusively one of the two imaging techniques, correlation was 0.855. CONCLUSION: Positron emission computed tomography is useful for the diagnosis of head and neck squamous cell carcinoma, improving the patient's staging especially when detecting cervical and distant metastases. Therefore, we consider that the use of positron emission computed tomography for the staging of patients with head and neck squamous cell carcinoma is a diagnostic test to be considered.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/terapia , Humanos , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Sensibilidad y Especificidad , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Tomografía Computarizada por Rayos X
7.
J Neurosci ; 40(47): 8976-8993, 2020 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-33055278

RESUMEN

Mammalian Piezo2 channels are essential for transduction of innocuous mechanical forces by proprioceptors and cutaneous touch receptors. In contrast, mechanical responses of somatosensory nociceptor neurons evoking pain, remain intact or are only partially reduced in Piezo2-deficient mice. In the eye cornea, comparatively low mechanical forces are detected by polymodal and pure mechanosensory trigeminal ganglion neurons. Their activation always evokes ocular discomfort or pain and protective reflexes, thus being a unique model to study mechanotransduction mechanisms in this particular class of nociceptive neurons. Cultured male and female mouse mechano- and polymodal nociceptor corneal neurons display rapidly, intermediately and slowly adapting mechanically activated currents. Immunostaining of the somas and peripheral axons of corneal neurons responding only to mechanical force (pure mechano-nociceptor) or also exhibiting TRPV1 (transient receptor potential cation channel subfamily V member 1) immunoreactivity (polymodal nociceptor) revealed that they express Piezo2. In sensory-specific Piezo2-deficient mice, the distribution of corneal neurons displaying the three types of mechanically evoked currents is similar to the wild type; however, the proportions of rapidly adapting neurons, and of intermediately and slowly adapting neurons were significantly reduced. Recordings of mechano- and polymodal-nociceptor nerve terminals in the corneal surface of Piezo2 conditional knock-out mice revealed a reduced number of mechano-sensitive terminals and lower frequency of nerve terminal impulse discharges under mechanical stimulation. Eye blinks evoked by von Frey filaments applied on the cornea were lower in Piezo2-deficient mice compared with wild type. Together, our results provide direct evidence that Piezo2 channels support mechanically activated currents of different kinetics in corneal trigeminal neurons and contributes to transduction of mechanical forces by corneal nociceptors.SIGNIFICANCE STATEMENT The cornea is a richly innervated and highly sensitive tissue. Low-threshold mechanical forces activate corneal receptors evoking discomfort or pain. To examine the contribution of Piezo2, a low-threshold mechanically activated channel, to acute ocular pain, we characterized the mechanosensitivity of corneal sensory neurons. By using Piezo2 conditional knock-out mice, we show that Piezo2 channels, present in the cell body and terminals of corneal neurons, are directly involved in acute corneal mechano-nociception. Inhibition of Piezo2 for systemic pain treatment is hindered because of its essential role for mechano-transduction processes in multiple body organs. Still, topical modulation of Piezo2 in the cornea may be useful to selectively relief unpleasant sensations and pain associated with mechanical irritation accompanying many ocular surface disorders.


Asunto(s)
Enfermedades de la Córnea/genética , Enfermedades de la Córnea/fisiopatología , Canales Iónicos/genética , Dolor/genética , Dolor/fisiopatología , Animales , Parpadeo , Células Cultivadas , Córnea/inervación , Mecanotransducción Celular , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas , Nociceptores , Técnicas de Placa-Clamp , Estimulación Física , Terminales Presinápticos , Ganglio del Trigémino/fisiopatología
8.
Acta Otolaryngol ; 140(11): 954-958, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32677497

RESUMEN

BACKGROUND: Glottic squamous cell carcinoma (SCC) in stages I or II can be treated by transoral CO2 laser microsurgery (TLM) or exclusive radiotherapy (RT). OBJECTIVES: To compare the oncological results of patients treated with TLM, to those treated with RT, in a tertiary hospital. MATERIAL AND METHODS: Data from patients diagnosed with glottic SCC in stages I and II between 2004 and 2018 were analyzed. Response to treatment was studied in terms of recurrence, local control and laryngeal preservation. RESULTS: Of 164 patients, 63.41% received treatment with TLM and 36.58% with RT. 26.21% presented a recurrence or progression of the tumor. Both treatments obtained good local control rates (84.15% in the case of TLM and 89.6% in the case of RT) and no significant association was found between tumor recurrence and type of treatment, nor with the involvement of the anterior commissure. However, treatment with RT obtained worse laryngeal preservation rate compared to TLM (81.6% and 100% respectively) (p < .001LR). Conclusions and significance: Both treatments obtained good oncological results. There were no significant differences regarding local control. However, TLM obtained a better laryngeal preservation rate. The involvement of the anterior commissure was not a poor prognosis factor for tumor recurrence.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Glotis/cirugía , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirugía , Terapia por Láser , Microcirugia , Femenino , Humanos , Masculino , Microcirugia/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del Tratamiento
9.
Neuron ; 106(5): 712-714, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32497507

RESUMEN

In this issue of Neuron, Paricio-Montesinos et al. (2020) unveil the essential cellular elements for warm temperature detection in mice. Surprisingly, the silencing of spontaneously firing, unmyelinated, polymodal sensory afferents harboring cold-activated TRPM8 channels is the key neural mechanism.


Asunto(s)
Canales Catiónicos TRPM , Animales , Frío , Calor , Ratones , Neuronas , Temperatura
10.
J Bacteriol ; 201(16)2019 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-31209076

RESUMEN

Previous work from our group indicated an association between the gastrointestinal microbiota of infants with cystic fibrosis (CF) and airway disease in this population. Here we report that stool microbiota of infants with CF demonstrates an altered but largely unchanging within-individual bacterial diversity (alpha diversity) over the first year of life, in contrast to the infants without CF (control cohort), which showed the expected increase in alpha diversity over the first year. The beta diversity, or between-sample diversity, of these two cohorts was significantly different over the first year of life and was statistically significantly associated with airway exacerbations, confirming our earlier findings. Compared with control infants, infants with CF had reduced levels of Bacteroides, a bacterial genus associated with immune modulation, as early as 6 weeks of life, and this significant reduction of Bacteroides spp. in the cohort with CF persisted over the entire first year of life. Only two other genera were significantly different across the first year of life: Roseburia was significantly reduced and Veillonella was significantly increased. Other genera showed differences between the two cohorts but only at selected time points. In vitro studies demonstrated that exposure of the apical face of polarized intestinal cell lines to Bacteroides species supernatants significantly reduced production of interleukin 8 (IL-8), suggesting a mechanism whereby changes in the intestinal microbiota could impact inflammation in CF. This work further establishes an association between gastrointestinal microbiota, inflammation, and airway disease in infants with CF and presents a potential opportunity for therapeutic interventions beginning in early life.IMPORTANCE There is growing evidence for a link between gastrointestinal bacterial communities and airway disease progression in CF. We demonstrate that infants with CF ≤1 year of age show a distinct stool microbiota versus that of control infants of a comparable age. We detected associations between the gut microbiome and airway exacerbation events in the cohort of infants with CF, and in vitro studies provided one possible mechanism for this observation. These data clarify that current therapeutics do not establish in infants with CF a gastrointestinal microbiota like that in healthy infants, and we suggest that interventions that direct the gastrointestinal microbiota closer to a healthy state may provide systemic benefits to these patients during a critical window of immune programming that might have implications for lifelong health.


Asunto(s)
Bacterias/aislamiento & purificación , Fibrosis Quística/microbiología , Heces/microbiología , Microbioma Gastrointestinal , Bacterias/clasificación , Bacterias/genética , Bacterias/crecimiento & desarrollo , Bacteroides/genética , Bacteroides/crecimiento & desarrollo , Bacteroides/aislamiento & purificación , Estudios de Cohortes , Fibrosis Quística/inmunología , Femenino , Humanos , Lactante , Masculino , Sistema Respiratorio/inmunología
11.
J Perinat Med ; 47(6): 625-630, 2019 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-31141492

RESUMEN

Background Obesity in pregnancy is increasing worldwide, reaching epidemic proportions in many countries and frequently creating challenges for obstetricians. We conducted this study to assess the effects of maternal obesity on maternal and perinatal outcomes. Methods A historical cohort study was performed on 16,609 women who delivered singleton babies in a 5-year period (2013-2017). Data were retrieved from the Cruces Perinatal Database (CPD) and only women whose prepregnancy body mass index (BMI) was known were included. Women were categorized according to the World Health Organization (WHO) classification: normal weight (BMI 20-24.9 kg/m2) and obesity (BMI ≥ 30 kg/m2). Obstetric, perinatal and neonatal outcomes were compared, and adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were calculated using the normal-weight group as the reference. Results Compared to women of normal weight (n = 9778), obese women (n = 2207) had a higher risk of preeclampsia (aOR 2.199, 95% CI: 1.46-3.29), rectovaginal group B streptococcus colonization (aOR 1.299, 95% CI: 1.14-1.47), induction of labor (aOR 1.593, 95% CI: 1.44-1.75), cesarean section (aOR 2.755, 95% CI: 2.46-3.08), cesarean section in women with a history of cesarean delivery (aOR 1.409, 95% CI: 1.03-1.92), fetal weight ≥4000 g (aOR 2.090, 95% CI: 1.803-2.422) and admission to the neonatal intensive care unit (NICU) (aOR 1.341, 95% CI: 1.12-1.59). No association was found with preterm birth (aOR 0.936, 95% CI: 0.77-1.13), stillbirth (aOR 0.921, 95% CI: 0.41-2.02) or neonatal mortality (aOR 2.205, 95% CI: 0.86-5.62). Conclusion Maternal obesity is associated with a higher risk of adverse pregnancy and perinatal outcomes. Pregnancy in this population of women should be considered and managed as high risk.


Asunto(s)
Cesárea/estadística & datos numéricos , Diabetes Gestacional/epidemiología , Obesidad Materna , Preeclampsia/epidemiología , Complicaciones del Embarazo , Nacimiento Prematuro/epidemiología , Adulto , Índice de Masa Corporal , Femenino , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Edad Materna , Obesidad Materna/diagnóstico , Obesidad Materna/epidemiología , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Embarazo de Alto Riesgo , España/epidemiología , Mortinato/epidemiología
12.
Nat Microbiol ; 4(1): 155-163, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30455469

RESUMEN

The essential nutrient choline is metabolized by gut bacteria to the disease-associated metabolite trimethylamine (TMA). However, most of the choline obtained via the diet and present in the human body is incorporated into larger metabolites, including the lipid phosphatidylcholine (PC). Here, we report that many choline-utilizing gut microorganisms can hydrolyse PC using a phospholipase D (PLD) enzyme and further convert the released choline to TMA. Genetic and in vitro characterization of the PLD from Escherichia coli MS 200-1 showed this enzyme is essential for bacterial hydrolysis of PC and prefers this substrate. PLDs are also found in gut bacterial isolates that are unable to convert choline to TMA, suggesting that additional members of the gut microbiota may influence access to this substrate. Unexpectedly, this PLD is only distantly related to characterized PLDs from pathogenic bacteria, suggesting a distinct evolutionary history. Together, these results reveal a previously underappreciated role for gut microorganisms in phospholipid metabolism and a potential target for inhibiting TMA production.


Asunto(s)
Colina/metabolismo , Escherichia coli/metabolismo , Metilaminas/metabolismo , Fosfatidilcolinas/metabolismo , Fosfolipasa D/metabolismo , Microbioma Gastrointestinal , Humanos
13.
Evol Appl ; 11(5): 593-613, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29875805

RESUMEN

Urbanization is a growing concern challenging the evolutionary potential of wild populations by reducing genetic diversity and imposing new selection regimes affecting many key fitness traits. However, genomic footprints of urbanization have received little attention so far. Using RAD sequencing, we investigated the genomewide effects of urbanization on neutral and adaptive genomic diversity in 140 adult great tits Parus major collected in locations with contrasted urbanization levels (from a natural forest to highly urbanized areas of a city; Montpellier, France). Heterozygosity was slightly lower in the more urbanized sites compared to the more rural ones. Low but significant effect of urbanization on genetic differentiation was found, at the site level but not at the nest level, indicative of the geographic scale of urbanization impact and of the potential for local adaptation despite gene flow. Gene-environment association tests identified numerous SNPs with small association scores to urbanization, distributed across the genome, from which a subset of 97 SNPs explained up to 81% of the variance in urbanization, overall suggesting a polygenic response to selection in the urban environment. These findings open stimulating perspectives for broader applications of high-resolution genomic tools on other cities and larger sample sizes to investigate the consistency of the effects of urbanization on the spatial distribution of genetic diversity and the polygenic nature of gene-urbanization association.

14.
Gut Microbes ; 9(5): 437-451, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29405826

RESUMEN

The discovery of enzymes responsible for previously unappreciated microbial metabolic pathways furthers our understanding of host-microbe and microbe-microbe interactions. We recently identified and characterized a new gut microbial glycyl radical enzyme (GRE) responsible for anaerobic metabolism of trans-4-hydroxy-l-proline (Hyp). Hyp dehydratase (HypD) catalyzes the removal of water from Hyp to generate Δ1-pyrroline-5-carboxylate (P5C). This enzyme is encoded in the genomes of a diverse set of gut anaerobes and is prevalent and abundant in healthy human stool metagenomes. Here, we discuss the roles HypD may play in different microbial metabolic pathways as well as the potential implications of this activity for colonization resistance and pathogenesis within the human gut. Finally, we present evidence of anaerobic Hyp metabolism in sediments through enrichment culturing of Hyp-degrading bacteria, highlighting the wide distribution of this pathway in anoxic environments beyond the human gut.


Asunto(s)
Bacterias/enzimología , Proteínas Bacterianas/metabolismo , Microbioma Gastrointestinal , Hidroliasas/metabolismo , Hidroxiprolina/metabolismo , Anaerobiosis , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Proteínas Bacterianas/genética , Tracto Gastrointestinal/microbiología , Humanos , Hidroliasas/genética , Hidroxiprolina/química , Redes y Vías Metabólicas , Metagenoma , Microbiota , Filogenia
15.
Cell Host Microbe ; 22(3): 279-290.e7, 2017 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-28844887

RESUMEN

Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.


Asunto(s)
Bacterias/metabolismo , Colina/metabolismo , Epigénesis Genética , Intestinos/microbiología , Enfermedades Metabólicas/genética , Enfermedades Metabólicas/metabolismo , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Metilación de ADN , Femenino , Microbioma Gastrointestinal , Humanos , Mucosa Intestinal/metabolismo , Masculino , Enfermedades Metabólicas/microbiología , Ratones Endogámicos C57BL
17.
Cell Metab ; 23(4): 573-5, 2016 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-27076072

RESUMEN

Thrombosis plays an important role in cardiovascular disease (CVD). Platelet activation is an essential step in the genesis and propagation of atherothrombotic complications. In a recent publication, Zhu and colleagues report that gut microbe-derived TMAO enhances platelet responsiveness and thrombosis, providing a novel mechanistic connection between microbes and CVD (Zhu et al., 2016).


Asunto(s)
Dieta , Trombosis , Enfermedades Cardiovasculares , Humanos , Interacciones Microbianas
18.
Cancer Immunol Immunother ; 65(1): 47-59, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26611618

RESUMEN

Reduced expression of HLA class I is an important immune escape mechanism from cytotoxic T cells described in various types of malignancy. It often correlates with poor prognosis and resistance to therapy. However, current knowledge about the frequency, underlying molecular mechanisms, and prognostic value of HLA class I and II alterations in prostate cancer (PC) is limited. Immunohistochemical analysis demonstrated that 88 % of the 42 studied cryopreserved prostate tumors have at least one type of HLA alteration as compared to adjacent normal prostate epithelium or benign hyperplasia. Total loss of HLA-I expression found in 50 % of tumors showed an association with increased incidence of tumor relapse, perineural invasion, and high D'Amico risk. The remaining HLA-I-positive tumors demonstrated locus and allelic losses detected in 26 and 12 % of samples, respectively. Loss of heterozygosity at chromosome 6 was detected in 32 % of the studied tumors. Molecular analysis revealed a reduced expression of B2M, TAP2, tapasin and NLRC5 mRNA in microdissected HLA-I-negative tumors. Analysis of twelve previously unreported cell lines derived from neoplastic and normal epithelium of cancerous prostate revealed different types of HLA-I aberration, ranging from locus and/or allelic downregulation to a total absence of HLA-I expression. The high incidence of HLA-I loss observed in PC, caused by both regulatory and structural defects, is associated with more aggressive disease development and may pose a real threat to patient health by increasing cancer progression and resistance to T-cell-based immunotherapy.


Asunto(s)
Antígenos de Histocompatibilidad Clase I/inmunología , Inmunoterapia/métodos , Neoplasias de la Próstata/inmunología , Microglobulina beta-2/inmunología , Humanos , Masculino , Recurrencia Local de Neoplasia
19.
Infect Agent Cancer ; 10: 41, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26576200

RESUMEN

BACKGROUND: Although the inclusion of the HPV vaccine has been registered in Spain since 2007, vaccination rates are lower than expected. The patients wish to be vaccinated is heavily influenced by information they have received from many source. The Knowledge of primary health care professionals affects the information provided to patients and is fundamental in the decision making. The aim of this study is to assess the opinions of primary health care professionals on the vaccine against HPV and their knowledge about HPV infection and its links to with gynecological and oropharyngeal cancer. METHODS: Cross-sectional study. A 19-item survey was drawn up. It included questions on basic aspects of HPV infection and marketed vaccines, personal opinion about the inclusion in the immunization schedules and their level of prescription and recommendation to patients in their clinical practice. From October 2013 to December 2013, 607 surveys were distributed among 20 primary health centers affiliated to the University Hospital 12 de Octubre. The results were analyzed using SPSS statistical package. RESULTS: One hundred sixty four successfully completed surveys were obtained for analysis. 89 % of the professionals knew about the relationship between HPV infection and cervical cancer, 57.3 % did not know any of the serotypes against which vaccines are targeted; 40.4 % believed that there is insufficient data to support the commercialization of the vaccines. Of these, 65.7 % argue that there is no data of its long-term effectiveness, 13.4 % that there is no data as to its side effects, 13.4 % believed that the cost effectiveness is not worthwhile. CONCLUSIONS: There is a strong controversy among health professionals regarding the marketing and inclusion of HPV vaccine in immunization schedules. However, the knowledge of the primary care health professionals on key aspects of infection and vaccine protection are insufficient. The training of professionals in vaccination, cervical pathology and HPV infection should be improved to provide objective information on the use as this vaccine for patients.

20.
J Bacteriol ; 197(17): 2859-66, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26124240

RESUMEN

UNLABELLED: Rhodobacter sphaeroides is a free-living alphaproteobacterium that contains two clusters of functional flagellar genes in its genome: one acquired by horizontal gene transfer (fla1) and one that is endogenous (fla2). We have shown that the Fla2 system is normally quiescent and under certain conditions produces polar flagella, while the Fla1 system is always active and produces a single flagellum at a nonpolar position. In this work we purified and characterized the structure and analyzed the composition of the Fla2 flagellum. The number of polar filaments per cell is 4.6 on average. By comparison with the Fla1 flagellum, the prominent features of the ultra structure of the Fla2 HBB are the absence of an H ring, thick and long hooks, and a smoother zone at the hook-filament junction. The Fla2 helical filaments have a pitch of 2.64 µm and a diameter of 1.4 µm, which are smaller than those of the Fla1 filaments. Fla2 filaments undergo polymorphic transitions in vitro and showed two polymorphs: curly (right-handed) and coiled. However, in vivo in free-swimming cells, we observed only a bundle of filaments, which should probably be left-handed. Together, our results indicate that Fla2 cell produces multiple right-handed polar flagella, which are not conventional but exceptional. IMPORTANCE: R. sphaeroides possesses two functional sets of flagellar genes. The fla1 genes are normally expressed in the laboratory and were acquired by horizontal transfer. The fla2 genes are endogenous and are expressed in a Fla1(-) mutant grown phototrophically and in the absence of organic acids. The Fla1 system produces a single lateral or subpolar flagellum, and the Fla2 system produces multiple polar flagella. The two kinds of flagella are never expressed simultaneously, and both are used for swimming in liquid media. The two sets of genes are certainly ready for responding to specific environmental conditions. The characterization of the Fla2 system will help us to understand its role in the physiology of this microorganism.


Asunto(s)
Proteínas Bacterianas/metabolismo , Flagelos/ultraestructura , Flagelina/genética , Regulación Bacteriana de la Expresión Génica/fisiología , Rhodobacter sphaeroides/ultraestructura , Proteínas Bacterianas/genética , Flagelina/metabolismo , Polimorfismo Genético , Rhodobacter sphaeroides/genética , Rhodobacter sphaeroides/metabolismo
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