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BACKGROUND: Psychogenic Non-Epileptic Seizures (PNES) and Functional Motor Disorders (FMDs) commonly represent the main clinical manifestations of Functional Neurological Disorders (FNDs). Despite their high prevalence in pediatric neurological services, literature on this topic is still spare for this population. The present study aimed to deepen the clinical knowledge of a pediatric FNDs sample through a demographic and clinical characterization of the most recurrent clinical patterns during the pediatric age. Moreover, a comparison of neuropsychological and psychopathological profiles of PNES and FMD patients was carried out to identify specific vulnerabilities and therapeutic targets linked with these different clinical manifestations. MATERIALS AND METHODS: A total of 43 FNDs patients (age range 7-17 years old) were retrospectively included in our study, enrolled in two subgroups: 20 with FMDs and 23 with PNES diagnosis. They were inpatients and outpatients referred over a period of 5 years and a standardized neurological, neuropsychological (WISC-IV/WAIS-IV), and psychiatric (CDI-2, MASC-2, ADES, DIS-Q, PID-5) evaluation was assessed. RESULTS: In PNES patients the most common clinical phenotypes were functional tonic-clonic (52%) and atonic (32%) manifestations while in the FMDs group were gait alterations (60%), functional myoclonus (35%), and tremor (35%). A higher frequency of cognitive impairment was reported in PNES patients with higher anxiety-depressive symptom rates than FMDs patients. CONCLUSIONS: Notably, specific neurocognitive and psychopathological profiles were described in PNES and FMDs, highlighting higher cognitive and psychiatric vulnerabilities in PNES, suggesting as well different strategy for therapeutic approaches.
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Trastornos de Conversión , Trastornos Motores , Humanos , Trastornos Motores/diagnóstico , Estudios Retrospectivos , Convulsiones/complicaciones , Convulsiones/diagnóstico , Trastornos de Conversión/complicaciones , Trastornos de Conversión/diagnóstico , Ansiedad/psicología , ElectroencefalografíaRESUMEN
BACKGROUND AND AIMS: Colonoscopy aims to early detect and remove precancerous colorectal polyps, thereby preventing development of colorectal cancer (CRC). Recently, computer-aided detection (CADe) systems have been developed to assist endoscopists in polyp detection during colonoscopy. The aim of this study was to investigate feasibility and safety of a novel CADe system during real-time colonoscopy in three European tertiary referral centers. METHODS: Ninety patients undergoing colonoscopy assisted by a real-time CADe system (DISCOVERY; Pentax Medical, Tokyo, Japan) were prospectively included. The CADe system was turned on only at withdrawal, and its output was displayed on secondary monitor. To study feasibility, inspection time, polyp detection rate (PDR), adenoma detection rate (ADR), sessile serrated lesion (SSL) detection rate (SDR), and the number of false positives were recorded. To study safety, (severe) adverse events ((S)AEs) were collected. Additionally, user friendliness was rated from 1 (worst) to 10 (best) by endoscopists. RESULTS: Mean inspection time was 10.8 ± 4.3 min, while PDR was 55.6%, ADR 28.9%, and SDR 11.1%. The CADe system users estimated that < 20 false positives occurred in 81 colonoscopy procedures (90%). No (S)AEs related to the CADe system were observed during the 30-day follow-up period. User friendliness was rated as good, with a median score of 8/10. CONCLUSION: Colonoscopy with this novel CADe system in a real-time setting was feasible and safe. Although PDR and SDR were high compared to previous studies with other CADe systems, future randomized controlled trials are needed to confirm these detection rates. The high SDR is of particular interest since interval CRC has been suggested to develop frequently through the serrated neoplasia pathway. CLINICAL TRIAL REGISTRATION: The study was registered in the Dutch Trial Register (reference number: NL8788).
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Juniperus , Adenoma/diagnóstico , Pólipos del Colon/diagnóstico por imagen , Pólipos del Colon/patología , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Computadores , Estudios de Factibilidad , HumanosRESUMEN
Pseudo-aneurysms of the arteries of the lower limbs are a possible complication of leg trauma. Complications include rupture, infection, pain and distal embolization. This is a case of a 24-year-old man hospitalized after a car accident, in which we discovered a 1-cm large pseudo-aneurysm of the right superficial femoral artery. The pseudo-aneurysm in first place was treated by the interventional-radiologist for an endovascular repair by embolization with ONYX 34, but during the procedure the copolymer embolized in the arterial axe with complete obstruction of blood-flow in the lower limb. An urgent open surgical revascularization was then attempted by our team with the result of complete patency of the femoro-popliteal axis and of the tibial vessels. Embolization with ONYX is an effective and safe method, but it is susceptible to this type of complication for larger pseudo-aneurysms, where it is required an introduction of a larger quantity of polymer.
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BACKGROUND: The familial nonmedullary thyroid cancer (FNMTC) is suspected to be a Mendelian condition in up to 3-8% of thyroid cancers. The susceptibility chromosomal loci and genes of 95% of FNMTC cases remain to be characterized. The inheritance of FNMTC appears to be autosomal dominant with incomplete penetrance and variable expressivity. The finding of the causative gene of FNMTC and the identification of patients at risk that need genetic testing were our aim. METHODS: We analyzed by whole-exome sequencing patients and non-affected relatives of five families with at least two family members affected by papillary thyroid cancer, selecting for new or extremely rare variants with predicted pathogenic value. RESULTS: A family showed, in all three affected members, a new loss-of-function variant (frameshift deletion) in BROX gene at 1q41 that was absent from all internal and external databases. In a second family with three affected relatives, we found an additional new BROX variant. The smaller families presented no variants in BROX or in the other causative genes studied. CONCLUSIONS: BROX could be a new causative gene for FNMTC. Variants in BROX may result in the haploinsufficiency of a key gene involved in the morphogenesis of MVBs, in the endosomal sorting of cargo proteins, and in EGFR. Functional studies are needed to support this result. The thorough genomic analysis by NGS in all families with three or more affected members should become a routine approach to obtain a comprehensive genetic view and find confirmative second cases.
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Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Haploinsuficiencia , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adulto , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Cáncer Papilar Tiroideo/etiología , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/etiología , Neoplasias de la Tiroides/metabolismoRESUMEN
PURPOSE: We aimed to verify if 1 year-testosterone-replacement therapy could produce a psychopathological recovery and a satisfactory quality of life in Klinefelter syndrome (KS) patients compared to matched healthy controls. Further, we analyzed personality traits and coping strategies, an issue not yet examined in androgen-treated KS patients. We also enquired whether any of the sociodemographic and psychological variables might predict a patient's general and sexual life satisfaction. METHODS: The Quality of Life Enjoyment and Satisfaction Questionnaire and the Temperament and Character Inventory-Revised were administered to both 23 KS patients and matched healthy subjects. Psychopathology was investigated by the Symptom Checklist-90-Revised (SCL-90-R) and the Mini-mental State Examination. The COPE Inventory was used to identify cognitive and behavioral strategies to manage disease-related distress. RESULTS: In testosterone-treated KS patients, when compared with controls, SCL-90-R subscales analysis evidenced high psychological distress, mainly presented as obsessive thoughts, hanger-hostility, phobias, and psychoticism. Self-directedness and self-transcendence, along with the prevalent use of emotion-focused coping strategies, outlined the personality of our KS patients. Depression and somatization proved to be predictors of general life dissatisfaction. Depression, anger-hostility, and paranoid ideation, instead, emerged as predictors of sexual life dissatisfaction. CONCLUSION: Endocrinologists should cooperate with mental health providers to foster a better outcome of the disease in KS patients.
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Adaptación Psicológica/fisiología , Cognición , Terapia de Reemplazo de Hormonas , Síndrome de Klinefelter , Calidad de Vida , Testosterona/uso terapéutico , Adulto , Terapia de Reemplazo de Hormonas/métodos , Terapia de Reemplazo de Hormonas/psicología , Humanos , Italia/epidemiología , Síndrome de Klinefelter/epidemiología , Síndrome de Klinefelter/psicología , Síndrome de Klinefelter/terapia , Masculino , Salud Mental , Pruebas de Estado Mental y Demencia , Determinación de la Personalidad , Distrés Psicológico , Conducta SexualRESUMEN
From April 2016, carfilzomib, in combination with lenalidomide and dexamethasone (KRD), became available for use in the daily practice in Italy for patients with relapsed or refractory multiple myeloma (RRMM). We performed a retrospective survey at 14 different institutions from Southern Italy in order to evaluate patient characteristics and treatment results from an unselected series of patients treated accordingly so far. One hundred and twenty-three consecutive patients were included, with a median of 2 previous lines of therapy (range 1-9) and a median age of 63 years (range 39-82). At the time of analysis, median number of courses administered is 11 (range 1-34), and all patients are evaluable for response. Overall response rate including complete remission, very good partial remission, and partial remission is 85%. After a median follow-up of 27 months, median overall and progression-free survival are 33 and 23 months, respectively. Sixty-three patients are alive and between them, 45 (37%) are in continuous remission. Sixty patients have died (49%), mainly from progressive disease. There were 6 treatment-related deaths (5% of the whole patient population). Overall, hematological and non-hematological toxicity were manageable, mostly on outpatient basis. Arterial hypertension has been observed in 43 cases (35%) but did not lead to treatment interruption. Our data demonstrate that in real life, KRD is highly effective and well tolerated in the majority of patients with RRMM.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Dexametasona/administración & dosificación , Lenalidomida/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos/administración & dosificación , Encuestas y Cuestionarios , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/administración & dosificación , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Italia/epidemiología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/epidemiología , Supervivencia sin Progresión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Endometrial adenocarcinoma is the most prevalent type of endometrial cancer. Diagnostic codes to identify endometrial adenocarcinoma in administrative databases, however, have not been validated. OBJECTIVE: To develop and validate an algorithm for identifying the occurrence of endometrial adenocarcinoma in a health insurance claims database. METHODS: To identify potential cases among women in the HealthCore Integrated Research Database (HIRD), published literature and medical consultation were used to develop an algorithm. The algorithm criteria were at least one inpatient diagnosis or at least two outpatient diagnoses of uterine cancer (International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) 182.xx) between 1 January 2010 and 31 August 2014. Among women fulfilling these criteria, we obtained medical records and two clinical experts reviewed and adjudicated case status to determine a diagnosis. We then estimated the positive predictive value (PPV) of the algorithm. RESULTS: The PPV estimate was 90.8% (95% CI 86.9-93.6), based on 330 potential cases of endometrial adenocarcinoma. Women who fulfilled the algorithm but who, after review of medical records, were found not to have endometrial adenocarcinoma, had diagnoses such as uterine sarcoma, rhabdomyosarcoma of the uterus, endometrial stromal sarcoma, ovarian cancer, fallopian tube cancer, endometrial hyperplasia, leiomyosarcoma, or colon cancer. CONCLUSIONS: An algorithm comprising one inpatient or two outpatient ICD-9-CM diagnosis codes for endometrial adenocarcinoma had a high PPV. The results indicate that claims databases can be used to reliably identify cases of endometrial adenocarcinoma in studies seeking a high PPV.
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Parkinson disease (PD) is a common neurodegenerative disorders characterized by motor and non-motor impairments. Since the quality of life of PD patients becomes poor while pathology develops, it is imperative to improve the identification of personalized rehabilitation and treatments approaches based on the level of the neurodegeneration process. Objective and precise assessment of the severity of the pathology is crucial to identify the most appropriate treatments. In this context, this paper proposes a wearable system able to measure the motor performance of PD subjects. Two inertial devices were used to capture the motion of the lower and upper limbs respectively, while performing six motor tasks. Forty-one kinematic features were extracted from the inertial signals to describe the performance of each subjects. Three unsupervised learning algorithms (k-Means, Self-organizing maps (SOM) and hierarchical clustering) were applied with a blind approach to group the motor performance. The results show that SOM was the best classifier since it reached accuracy equal to 0.950 to group the instances in two classes (mild vs advanced), and 0.817 considering three classes (mild vs moderate vs severe). Therefore, this system enabled objective assessment of the PD severity through motion analysis, allowing the evaluation of residual motor capabilities and fostering personalized paths for PD rehabilitation and assistance.
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Enfermedad de Parkinson/fisiopatología , Rehabilitación , Algoritmos , Femenino , Humanos , Masculino , Enfermedad de Parkinson/terapia , Calidad de Vida , Aprendizaje Automático no Supervisado , Extremidad Superior/fisiopatologíaRESUMEN
PURPOSE: The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients. METHODS: This is a case-control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred and seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student's t test. Mann-Whitney test and Chi-square test. RESULTS: FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto's thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results. CONCLUSIONS: We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype.
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Síndrome de Klinefelter/fisiopatología , Glándula Tiroides/fisiología , Centros Médicos Académicos , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/fisiopatología , Humanos , Hipogonadismo/sangre , Hipogonadismo/fisiopatología , Italia , Síndrome de Klinefelter/sangre , Masculino , Persona de Mediana Edad , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/fisiopatología , Pruebas de Función de la Tiroides , Hormonas Tiroideas/sangre , Tirotropina/sangre , Adulto JovenRESUMEN
Rapid fluctuations of the oxygen content of both natural and anthropogenic origin are relatively common in freshwater environments. Fish adaptation to these conditions implies tolerance of both low levels of oxygen availability and reoxygenation. Hypoxia tolerance in fish has been widely studied, but the involvement of mitochondria in the response of fish to rapid hypoxia/reoxygenation stress is less known. Zebrafish, a floodplain species, is likely facing significant changes in dissolved oxygen in its natural environment and displays a moderate ability to tolerate hypoxia. In the present study, we report the effects of an acute hypoxia/reoxygenation stress (H/R) protocol on mitochondrial functionality (respiration, complex activities, rate of H2O2 release) and redox state (level of HPs and protein oxidation) of muscle tissue. In parallel, the animal metabolic performance (routine metabolism, nitrogen excretion and swimming performance) was measured. Additionally, the recovery from H/R was tested 20 h after treatment. A significant stimulation by H/R of muscle mitochondrial respiration and H2O2 release was observed, which was only in part counteracted by stimulation of the antioxidant system, resulting in an increased level of lipid peroxides and protein carbonyls. In parallel, H/R increased the animal oxygen consumption and urea excretion rate and reduced routine activity. A significant strong reduction of endurance at 80% Ucrit was also observed. Most of the altered parameter did not recover 20 h after reoxygenation. These data indicate a significant alteration of zebrafish muscle mitochondrial state after acute H/R, associated with changes in tissue redox state and locomotor performance.
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Embrión no Mamífero/fisiología , Mitocondrias Musculares/fisiología , Oxígeno/fisiología , Natación/fisiología , Pez Cebra/fisiología , Animales , Respiración de la Célula , Oxidación-Reducción , Pez Cebra/embriologíaRESUMEN
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by disabling motor and non-motor symptoms. Idiopathic hyposmia (IH), a reduced olfactory sensitivity, is a preclinical marker for the pathology and affects >95% of PD patients. In this paper, SensHand V1 and SensFoot V2, two inertial wearable sensors for upper and lower limbs, were developed to acquire motion data in ten tasks of the MDS-UPDRS III. Fifteen healthy subjects of control, 15 IH people, and 15 PD patients were enrolled. Seventy-one parameters per side were computed by spatiotemporal and frequency data analysis, and the most significant were selected to distinguish among the different classes. Performances of supervised learning algorithms (i.e., Support Vector Machine (SVM), and Random Forest (RF)) were compared on two-group and three-group classification and considering upper and lower limbs separately or together as a full system. Excellent results were obtained for healthy vs. patients classification (accuracy 1.00 for RF, and 0.97 for SVM), and good results were achieved by including IH subjects (0.92 F-measure with RF) within a three-group classification. Overall, the best performances were obtained using the full system with an RF classifier. The system is, thus, suitable to support an objective PD diagnosis. Furthermore, combining motion analysis with a validated olfactory screening test, people at risk for PD can be appropriately analyzed, and subtle changes in motor performance that characterize the prodromal phase and the early PD onset can be identified.
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Trastornos del Olfato/etiología , Enfermedad de Parkinson/diagnóstico , Máquina de Vectores de Soporte , Dispositivos Electrónicos Vestibles , Algoritmos , HumanosRESUMEN
We report on the preliminary results obtained out of a wearable module designed to be encompassed within a ring-shaped system aimed at providing healthcare services. The module is composed of two sensors for the measuring of Galvanic Skin Response (GSR) and Heart Rate Variability (HRV). A first device validation was carried out by involving four subjects who were asked to perform tasks providing different stress-related statuses. A comparison of physiological parameters measured by the module with those measured by a commercial HRV-GSR sensor chosen as gold standard was made. Two out of the three HRV parameters and all of the GSR parameters measured with the module resulted consistent (mostly differing less than 10%) with the same parameters measured by the gold standard. The work reported in this paper set a milestone for the realization of a system exploiting sensor fusion to provide active ageing, stress detection, activity recognition and e-health services has been achieved.
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Técnicas Biosensibles , Dispositivos Electrónicos Vestibles , Respuesta Galvánica de la Piel , Frecuencia CardíacaRESUMEN
Clinical manifestations of Zika, dengue, and chikungunya virus infections are very similar, making it difficult to reach a diagnosis based only on clinical grounds. In addition, there is an intense cross-reactivity between antibodies directed to Zika virus and other flaviviruses, and an accurate Zika diagnosis is best achieved by real-time RT-PCR. However, some real-time RT-PCR show better performance than others. To reach the best possible Zika diagnosis, the analytic sensitivity of some probe-based real-time RT-PCR amplifying Zika virus RNA was evaluated in spiked and clinical samples. We evaluated primers and probes to detect Zika virus, which had been published before, and tested sensitivity using serum spiked and patient samples by real-time RT-PCR. When tested against spiked samples, the previously described primers showed different sensitivity, with very similar results when samples from patients (serum and urine) were analyzed. Real-time RT-PCR designed to amplify Zika virus NS1 showed the best analytical sensitivity for all samples.
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Fiebre Chikungunya/diagnóstico , Dengue/diagnóstico , ARN Viral/genética , Infección por el Virus Zika/diagnóstico , Virus Zika/genética , Protocolos Clínicos , Coinfección , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: Preclinical diagnosis of Parkinson's disease (PD) is nowadays a topic of interest as the neuropathological process could begin years before the appearance of motor symptoms. Several symptoms, among them hyposmia, could precede motor features in PD. In the preclinical phase of PD, a subclinical reduction in motor skills is highly likely. In this pilot study, we investigate a step-by-step method to achieve preclinical PD diagnosis. MATERIAL AND METHODS: We used the IOIT (Italian Olfactory Identification Test) to screen a population of healthy subjects. We identified 20 subjects with idiopathic hyposmia. Hyposmic subjects underwent an evaluation of motor skills, at baseline and after 1 year, using motion analysis sensors previously created by us. RESULTS: One subject showed significant worsening in motor measurements. In this subject, we further conducted a dopaminergic challenge test monitored with the same sensors and, finally, he underwent [123 I]-FP/CIT (DaTscan) SPECT brain imaging. The results show that he is probably affected by preclinical PD. CONCLUSIONS: Our pilot study suggests that the combined use of an olfactory test and motor sensors for motion analysis could be useful for a screening of healthy subjects to identify those at a high risk of developing PD.
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Diagnóstico Precoz , Destreza Motora , Trastornos del Olfato/etiología , Enfermedad de Parkinson/diagnóstico , Dispositivos Electrónicos Vestibles , Anciano , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Proyectos PilotoRESUMEN
BACKGROUND: Thyroidectomy is one of the most common intervention in general surgery and, after the turn of the century, its rate has sharply increased, along with a worldwide increased incidence of differentiated thyroid cancers. Therefore, injuries of the recurrent laryngeal nerve have become one of the most frequent cause of surgical malpractice claims, mostly following surgery for benign pathology. MAIN BODY: Even if the incidence of definitive paralysis is generally lower than 3%, during the last 20 years in Italy, the number of claims for damages has sharply raised. As a consequence, a lot of defensive medicine has been caused by this issue, and a witch-hunt has been accordingly triggered, so determining mostly a painful and lasting frustration for the surgeons, who sometimes are compelled to pay a lot of money for increasing insurance premiums and lawyers fees. Recurrent laryngeal nerve injury should be considered as a potentially catastrophic predictable but not preventable event, rather than the result of a surgical mistake. CONCLUSION: Purposes of the Authors are analyzing incidence, conditions of risk, and mechanisms of recurrent laryngeal nerve injuries, underlining notes of surgical technique and defining medical practice recommendations useful to reduce the risk of malpractice lawsuits and judgments against surgeons.
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Mala Praxis/economía , Complicaciones Posoperatorias/economía , Traumatismos del Nervio Laríngeo Recurrente/economía , Tiroidectomía/efectos adversos , Femenino , Humanos , Incidencia , Italia/epidemiología , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Traumatismos del Nervio Laríngeo Recurrente/epidemiología , Traumatismos del Nervio Laríngeo Recurrente/etiología , Traumatismos del Nervio Laríngeo Recurrente/prevención & control , Neoplasias de la Tiroides/cirugía , Tiroidectomía/economía , Tiroidectomía/métodos , Resultado del TratamientoRESUMEN
Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants are bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression are positively correlated in prostate tumours. TET2 is expressed in normal prostate tissue and reduced in a subset of tumours from the Cancer Genome Atlas (TCGA). Small interfering RNA-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3/PSA) expression. Published data reveal TET2 binding sites and hydroxymethylcytosine proximal to KLK3. A gene co-expression network identified using TCGA prostate tumour RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. The co-expression signature is conserved across 31 TCGA cancers suggesting a putative role for TET2 as an energy sensor (of 2-OG) that modifies aspects of androgen-AR signalling. Decreased TET2 mRNA expression in TCGA PCa tumours is strongly associated with reduced patient survival, indicating reduced expression in tumours may be an informative biomarker of disease progression and perhaps metastatic disease.
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Proteínas de Unión al ADN/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Receptores Androgénicos/metabolismo , Proliferación Celular/fisiología , Proteínas de Unión al ADN/genética , Dioxigenasas , Células HEK293 , Humanos , Intrones , Calicreínas/genética , Calicreínas/metabolismo , Ácidos Cetoglutáricos/metabolismo , Masculino , Polimorfismo de Nucleótido Simple , Antígeno Prostático Específico/genética , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas/genética , Receptores Androgénicos/genética , Succinatos/metabolismoRESUMEN
BACKGROUND: The real efficacy of selenium supplementation in Hashimoto's thyroiditis (HT) is still an unresolved issue. OBJECTIVES: We studied the short-term effect of L-selenomethionine on the thyroid function in euthyroid patients with HT. Our primary outcome measures were TSH, thyroid hormones, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) levels and thyroid echogenicity after 6 months of L-selenomethionine treatment. The secondary outcome measure was serum CXCL10 levels. METHODS: In a placebo-controlled randomized prospective study, we have enrolled untreated euthyroid patients with HT. Seventy-six patients were randomly assigned to receive L-selenomethionine 166 µg/die (SE n = 38) or placebo (controls n = 38) for 6 months. TSH, free T4 (FT4), free T3 (FT3), TPOAb and CXCL10 serum levels were assayed at time 0, after 3 and 6 months. An ultrasound examination of the left and right thyroid lobe in transverse and longitudinal sections was performed. A rectangular region, the region of interest, was selected for analysis. RESULTS: TSH, FT4, FT3, TPOAb, thyroid echogenicity and CXCL10 were not statistically different between SE and control groups at time 0, after 3 and 6 months. In the SE group, FT4 levels were significantly decreased (P < 0.03) after 3 months, while FT3 increased (P < 0.04) after 3 and 6 months versus baseline values. In the control group, the FT3 decreased after 3 and 6 months (P < 0.02) compared to baseline. CONCLUSION: The short-term L-selenomethionine supplementation has a limited impact on the natural course in euthyroid HT. Our results tip the balance toward the ineffectiveness of short-term L-selenomethionine supplementation in HT.
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Biomarcadores/sangre , Enfermedad de Hashimoto/tratamiento farmacológico , Selenio/administración & dosificación , Adolescente , Adulto , Suplementos Dietéticos , Femenino , Humanos , Inmunoensayo , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Selenio/sangre , Hormonas Tiroideas/sangre , Adulto JovenRESUMEN
Posidonia oceanica is an endemic seagrass in the Mediterranean Sea, where it provides important ecosystem services and sustains a rich and diverse ecosystem. P. oceanica meadows extend from the surface to 40 meters depth. With the aim of boosting research in this iconic species, we generated a comprehensive RNA-Seq data set for P. oceanica by sequencing specimens collected at two depths and two times during the day. With this approach we attempted to capture the transcriptional diversity associated with change in light and other depth-related environmental factors. Using this extensive data set we generated gene predictions and identified an extensive catalogue of potential Simple Sequence Repeats (SSR) markers. The data generated here will open new avenues for the analysis of population genetic features and functional variation in P. oceanica. In total, 79,235 contigs were obtained by the assembly of 70,453,120 paired end reads. 43,711 contigs were successfully annotated. A total of 17,436 SSR were identified within 13,912 contigs.