Impact Of PET/CT On Treatment In Patients With Head And Neck Squamous Cell Carcinoma.

<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>.

Enterobacter sp. DBA51 produces ACC deaminase and promotes the growth of tomato (Solanum lycopersicum L.) and tobacco (Nicotiana tabacum L.) plants under greenhouse condition.

Bacterial isolated from rhizospheric soil associated with the semi-desertic plant Coronilla juncea L. were screened for 1-aminocyclopropane-1-carboxylate deaminase (ACCD) activity, a common trait for plant-growth-promoting rhizobacteria (PGPR). Among bacterial isolates, strain DBA51 showed phosphate solubilizing index (PSI), producing indole acetic acid (IAA), and with the hemolysis-negative test. Sequencing and analysis of the 16S rDNA gene identified DBA51 as Enterobacter. DBA51 did not show antagonistic activity in vitro against bacterial (Clavibacter michiganensis, Pseudomonas syringae pv. tomato DC3000 and Pectobacterium cacticidum FHLGJ22) and fungal phytopathogens (Alternaria sp., Fusarium oxysporum fsp. lycopersici, Fusarium oxysporum fsp. cubense M5, and Rhizoctonia sp.). Root inoculations with DBA51 in tomato (Solanum lycopersicum L.) and tobacco (Nicotiana tabacum L.) plants were performed under greenhouse conditions. Plant height (20 %) and root biomass (40 %) were significantly enhanced in tomato plants inoculated with DBA51 compared to non-inoculated plants, although for tobacco plants, only root biomass (27 %) showed significant differences with DBA51. In addition, physiological parameters such as photosynthetic rate (µmol CO2 m-2 s-1), stomatal conductance (mol H2O m-2 s-1), and transpiration rate (mmol H2O m-2 s-1) were also evaluated, and no differences were detected between DBA51-inoculated and control treatment in tomato and tobacco leaves. The observed results indicate that the DBA51 strain could be used as a biofertilizer to improve yields of horticultural crops.

Correlation between PET-CT and ct in the staging after the treatment of head and neck squamous cell carcinoma

Abstract 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.

Survival study in early stages of glottis cancer, stratified by treatment.

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.

Correlation between PET-CT and ct in the staging after the treatment of head and neck squamous cell carcinoma.

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.

Correlation between PET/CT and CT in the staging prior to the treatment of head and neck squamous cell carcinoma / Correlação entre PET/TC e TC no estadiamento pré tratamento do carcinoma espinocelular de cabeça e pescoço

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.

Correlation between PET/CT and CT in the staging prior to the treatment of head and neck squamous cell carcinoma.

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.

Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study).

PURPOSE: To assess the sustained and acute effects, as well as the influence of sustained consumption on the acute effects, of orange juice (OJ) with a natural hesperidin content and hesperidin-enriched OJ (EOJ) on blood (BP) and pulse (PP) pressures in pre- and stage-1 hypertensive individuals. METHODS: In a randomized, parallel, double-blind, placebo-controlled trial, participants (n = 159) received 500 mL/day of control drink, OJ, or EOJ for 12 weeks. Two dose-response studies were performed at baseline and after 12 weeks. RESULTS: A single EOJ dose (500 mL) reduced systolic BP (SBP) and PP, with greater changes after sustained treatment where a decrease in diastolic BP (DBP) also occurred (P < 0.05). SBP and PP decreased in a dose-dependent manner relative to the hesperidin content of the beverages throughout the 12 weeks (P < 0.05). OJ and EOJ decreased homocysteine levels at 12 weeks versus the control drink (P < 0.05). After 12 weeks of EOJ consumption, four genes related to hypertension (PTX3, NLRP3, NPSR1 and NAMPT) were differentially expressed in peripheral blood mononuclear cells (P < 0.05). CONCLUSION: Hesperidin in OJ reduces SBP and PP after sustained consumption, and after a single dose, the chronic consumption of EOJ enhances its postprandial effect. Decreases in systemic and transcriptomic biomarkers were concomitant with BP and PP changes. EOJ could be a useful co-adjuvant tool for BP and PP management in pre- and stage-1 hypertensive individuals.

Radiotherapy versus laser microsurgery in the treatment of early glottic cancer.

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.

Metabolic syndrome and risk of cancer: a study protocol of case-control study using data from the Information System for the Development of Research in Primary Care (SIDIAP) in Catalonia.

BACKGROUND: Metabolic syndrome (MS) is defined by the clustering of specific metabolic disorders in one subject. MS is highly prevalent globally and currently considered a growing public health concern. MS comprises obesity, hypertension, dyslipidaemia and insulin resistance. Mechanisms linking MS with cancer are poorly understood, and it is as yet unknown if MS confers a greater risk than the risk entailed by each of its separate components. The main objective of this study is to compare the association between MS and 14 site-specific cancer against the association between one or two individual components of MS and cancer. The secondary objective is to evaluate the time elapsed since the diagnosis of MS and the subsequent onset of cancer within the 2006-2017 period by sex. METHODS AND ANALYSIS: A case-control study will be conducted for the main objective and a cohort of patients with MS will be followed for the evaluation of the second objective. Incident cases of fourteen types of cancer in patients ≥40 years of age diagnosed prospectively will be selected from electronic primary care records in the Information System for Research in Primary Care (SIDIAP database; www.sidiap.org). The SIDIAP database includes anonymous data from 6 million people (80% of the Catalan population) registered in 286 primary healthcare centres. Each matched control (four controls for each case) will have the same inclusion date, the same sex and age (±1 year) than the paired case. Logistic regression and a descriptive analysis and Kaplan-Meier analysis will be performed, in accordance with the objectives. ETHICS AND DISSEMINATION: The protocol of the study was approved by the IDIAP Jordi Gol Clinical Research Ethics Committee (protocol P17/212). The study's findings will be published in a peer-reviewed journal and disseminated at national and international conferences and oral presentations to researchers, clinicians and policy makers.

[IgG4 related disease with exclusive sinonasal involvement: A case report and literature review]. / Enfermedad relacionada con IgG4 con afectación exclusiva nasosinusal: presentación de un caso clínico y revisión de la literatura.

IgG4 related disease (igG4-RD) is a pathological process which integrates a large number of diseases of unknown pathogenesis, considered as being exclusive to many different organs. Diagnosis is established through histological, radiological and serological criteria. Treatment is based on long term corticosteroids; rituximab being used only in refractory cases. It is unusual for this entity to be found exclusively in the head and neck, without systemic involvement; there are only a few reported cases to date. We present a case of a nasosinusal IgG4-RD orbital tumor with paranasal sinus involvement. The accurate diagnosis made early onset corticosteroid treatment possible and the patient is currently asymptomatic.

Use of Alexis retractor in thyroid and parathyroid surgery. / Uso de retractor Alexis en cirugía de tiroides y paratiroides.

In thyroid and parathyroid surgical procedures, good visibility of the thyroid gland is essential. This is traditionally achieved by means of traction sutures of the dermo-plastysmal flaps to the drapes of the operative field, producing tension and even damage to the skin. The Alexis® retractor ring improves exposure and facilitates stable access to the thyroid, protecting the skin from injury during the intervention.

Versión española del COPE-48: evaluación del afrontamiento en pacientes psiquiátricos ambulatorios / The epanish version of the COPE-48: assessing coping strategies in psychiatric outpatients

Introducción: La utilización el COPE en contextos clínicos permite conocer las estrategias que utilizan las personas para afrontar situaciones estresantes y por ende incidir sobre ellas mediante tratamiento psicológico. Objetivo: presentar a la comunidad científica de habla hispana la versión española del COPE-48 junto con las propiedades psicométricas obtenidas en una muestra de personas adultas con psicopatología. Métodos: la muestra estuvo formada por 301 participantes (62.5% mujeres). Resultados: la consistencia interna media de las escalas es de 0.81. Nuestros resultados muestran un patrón diferencial en la utilización de las estrategias según el género. Conclusiones: la administración del COPE-48 en contextos clínicos es de gran utilidad práctica, puesto que permite conocer de modo rápido, fácil y preciso las estrategias más frecuentemente utilizadas por los pacientes para afrontar situaciones altamente demandantes. Dicho conocimiento permite intervenir mediante tratamiento psicológico para instaurar, potenciar o minimizar las estrategias necesarias para afrontar una determinada situación comprometida.

Introduction: In clinical settings, the COPE questionnaire allows to assess the strategies people use to cope with stressful situations and therefore, if needed, to modify them through psychological treatment. Objective: The aim of this study is to offer to the Spanish-speaking scientific community the Spanish version of the COPE-48 along with the psychometric properties obtained in a sample of adults with psychopathology. Material and Methods: The sample consisted of 301 participants (62.5% women). Results: The average internal consistency of the scales was 0.81. Our results showed a gender pattern in the use of the coping strategies. Conclusions: In clinical settings, the administration of the COPE-48 allows a quick, easy and accurate assessment of the most frequently used strategies to cope with highly demanding situations. This knowledge makes possible to intervene with psychological treatment and whenever appropriate to establish, enhance or minimize the strategies needed to face difficult situations.

Construcción emergente del concepto: cuidado profesional de enfermería / Emerging concept construction: professional nursing care / Construção emergente do conceito: cuidado profissionais de enfermagem

El objetivo del presente trabajo fue la construcción del concepto cuidado profesional de enfermería. Las aportaciones se encaminan a la dimensión profesional del campo de la ciencia de la enfermería. Es un estudio cualitativo con enfoque Hermenéutico, en 20 enfermeras, mediante entrevistas semiestructuradas a profundidad. El análisis fue de contenido. El cuidado profesional lo conceptualizan como el cuidado de la vida de las personas que solicitan sus servicios. Con ello, el hacer de la enfermera viene a ser un acto profesional y no un acto de buenas intensiones, con la obligación de asumir conductas de cuidado, que conlleva principios y normas establecidas por la disciplina. Las enfermeras entienden que se requiere de conocimientos constantes. La conceptualización del cuidado profesional que se apoya en la práctica, ofrece un acercamiento a la construcción de la Ciencia de la Enfermería.

The aim of this study was to help construct a professional nursing care concept. The contributions are aimed at the professional dimension of the science of nursing. This is a qualitative study with a hermeneutic approach involving 20 nurses in semi-structured interviews submitted to content analysis. Professional care is conceptualized as caring for the lives of people who seek their services. Thus, the job of the nurse becomes a professional act and not an act of good intentions with the obligation of assuming care conduct, involving principles and standards established by the discipline. Nurses understand that knowledge requires continuous updating. The conceptualization of professional care based on practice offers an approach to the construction of the Science of Nursing.

O objetivo deste trabalho foi a construção do conceito de cuidado profissional de enfermagem. As contribuições seencaminham a dimensão profissional do campo da ciência da enfermagem. É um estudo qualitativo com abordagem hermenêutica. Participaram 20 enfermeiras. Os dados foram coletados por meio de entrevistas semiestruturadas a profundidade e foi realizada análise de conteúdo. As enfermeiras conceitualizam o cuidado profissional como o cuidado da vida das pessoas que procuram seus serviços. Com isto, o fazer da enfermeira se torna um ato profissional e não um ato de boas intenções, com a obrigação de assumir condutas de cuidado que envolvem princípios e regras estabelecidas pela disciplina. As enfermeiras entendem que são necessários conhecimentos permanentes. A conceptualização do cuidado profissional -que se apoia na prática, oferece uma aproximação para a construção da Ciência da Enfermagem.

Propuesta de validación de indicadores y estándares para el manejo del dolor en el paciente / Proposal for validation of indicators and standards for pain management in the patient / Proposta de validação estandares e indicadores para o manuseio do dor em paciente

El dolor es una experiencia sensorial y emocional desagradable relacionada con daño a los tejidos. El objetivo fue validar los estándares e indicadores para el manejo del dolor. Es un estudio transversal y descriptivo. Se utilizó el modelo de estándares de A. Donavedis. El universo fueron 150 enfermeras y la muestra 109. El proceso de validación se realizó en tres etapas: En laprimera se utilizó la técnica delphi en 24 enfermeras expertas con dos rondas. En la segunda una prueba piloto en el 10% de la muestra, en donde se validó la consistencia con el alfa de Cronbach con índices de validación de exactitud mayores a 0,711. En la tercera, se midió la precisión utilizando el Modelo de Capacidad de Procesos (Icp). En conclusión el instrumento se validó contres estándares: 7 de estructura, 13 de proceso y 4 de resultado todos con un Icp máximo mayores a uno.

Metabolic syndrome as a cardiovascular disease risk factor: patients evaluated in primary care.

To estimate the prevalence of metabolic syndrome (MS) in a population receiving attention in primary care centers (PCC) we selected a random cohort of ostensibly normal subjects from the registers of 5 basic-health area (BHA) PCC. Diagnosis of MS was with the WHO, NCEP and IDF criteria. Variables recorded were: socio-demographic data, CVD risk factors including lipids, obesity, diabetes, blood pressure and smoking habit and a glucose tolerance test outcome. Of the 720 individuals selected (age 60.3 +/- 11.5 years), 431 were female, 352 hypertensive, 142 diabetic, 233 pre-diabetic, 285 obese, 209 dyslipemic and 106 smokers. CVD risk according to the Framingham and REGICOR calculation was 13.8 +/- 10% and 8.8 +/- 9.8%, respectively. Using the WHO, NCEP and IDF criteria, MS was diagnosed in 166, 210 and 252 subjects, respectively and the relative risk of CVD complications in MS subjects was 2.56. Logistic regression analysis indicated that the MS components (WHO set), the MS components (IDF set) and the female gender had an increased odds ratio for CVD of 3.48 (95CI%: 2.26-5.37), 2.28 (95%CI: 1.84-4.90) and 2.26 (95%CI: 1.48-3.47), respectively. We conclude that MS and concomitant CVD risk is high in ostensibly normal population attending primary care clinics, and this would necessarily impinge on resource allocation in primary care.