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OBJECTIVE: Data from trials demonstrated that abatacept (ABA) has a good safety and efficacy profile in treating rheumatoid arthritis. We have studied the retention rate of ABA in a real-life cohort of patients with rheumatoid arthritis. METHODS: This is a monocentric, retrospective study including patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism 2010 criteria who started treatment with ABA. The Kaplan-Meier method was applied to evaluate the ABA retention rate. RESULTS: This analysis was conducted on 161 patients [male/female 21/140, median age 65 years, interquartile range (IQR) 18.7, median disease duration 169 months, IQR 144.0]. 111 patients (68.9%) received ABA subcutaneously. ABA was associated with methotrexate in 61.9% of patients and was the first biological disease-modifying antirheumatic drug in 41%. We observed a median ABA survival of 66 months [95% confidence interval (CI) 57.3-74.7], with a retention rate of 88% at 6 months and 50.9% at 5 years. Drug survival was significantly higher in patients treated with ABA subcutaneously and in male patients (p=0.039 and p=0.018, respectively). Adjusted for main confounders, female gender was the main predictor of withdrawal (hazard ratio 5.1, 95% CI 1.2-21.3). CONCLUSIONS: Our study shows that better survival is associated with subcutaneous administration and male gender, confirming ABA effectiveness.
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Abatacept , Antirreumáticos , Artritis Reumatoide , Humanos , Abatacept/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Anciano , Antirreumáticos/uso terapéutico , Persona de Mediana Edad , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Resultado del Tratamiento , Estimación de Kaplan-Meier , Quimioterapia Combinada , Estudios de CohortesRESUMEN
Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10-15) and the gene ontology (GO) terms for mtDNA metabolism (p = 1.43 × 10-8) and mtDNA replication (p = 1.2 × 10-7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell-related traits, kidney function, liver function and overall (p = 0.044) and non-cancer mortality (p = 6.56 × 10-4).
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Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Megacariocitos/fisiología , Mitocondrias/genética , Activación Plaquetaria , Polimorfismo de Nucleótido Simple , Anciano , Proliferación Celular , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Nucleótidos/metabolismo , FenotipoRESUMEN
The results obtained in a measurement campaign concerning internal contamination by the gamma-emitting radionuclides of a large number of individuals are presented in this work. The aim is to assess the effectiveness of the spectrometric method in an emergency response following a nuclear power plant accident or a spread of radionuclides in the atmosphere due to an act of terrorism. An HPGe portable spectrometer, deployed in a collective protection apparatus, was used for both whole-body and thyroid measurements. An adult bottle mannequin absorption (BOMAB) and thyroid phantoms were used to evaluate the detector performance. The BOMAB phantom was provided by the Italian Institute of Ionizing Radiation Metrology (INMRI) for the ENEA intercomparison exercise. Thyroid phantoms were provided by the Belgian Nuclear Research Centre for the 'Child and Adult Thyroid Monitoring After Reactor Accident' European intercomparison exercise. The instrument performance was further evaluated by collecting spectral data from healthy volunteers, using acquisition times of 180 s and 100 s, respectively, for the whole-body and thyroid measurements. The detector showed good accuracy in quantifying radionuclide activities in the adult BOMAB and in the thyroids of persons of all ages. The proposed method allows us to detect in vivo activity leading to a committed effective dose E(50) and committed thyroid equivalent doses H T greater than 2 mSv due to all gamma-emitting fission products, if the scan is performed within five days after intake. Assuming, for instance, an acute inhalation of 137Cs and 131I, the obtained detection limit values for adults lead to a E(50) value equal to 0.08 mSv and an H T value of 0.27 mSv. The E(50) and H T values show that the proposed method can be successfully used when the dose assessment must be rapidly performed for a large number of individuals in the eventuality of the scenarios previously mentioned.
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Exposición a la Radiación/análisis , Monitoreo de Radiación/instrumentación , Liberación de Radiactividad Peligrosa , Glándula Tiroides/efectos de la radiación , Recuento Corporal Total/instrumentación , Radioisótopos de Cesio/análisis , Humanos , Radioisótopos de Yodo/análisis , Maniquíes , TerrorismoRESUMEN
In order to properly respond to an emergency caused by an accident in a nuclear power plant with a spread of radionuclides in the atmosphere, we propose a field procedure to perform a large-scale individual thyroid monitoring of internal contamination due to inhalation of 131I, by means of non-spectrometric equipment, in particular dose rate meters. Specific attention is paid to the individual monitoring of children, because of the very high radiosensitivity of the child's thyroid to the carcinogenic effects of ionising radiation. The device performance was evaluated by measuring mock iodine sources provided in the Child and Adult Thyroid Monitoring After Reactor Accident (CAThyMARA) intercomparison and, just for a scintillator dose rate meter, by means of 60 s acquisitions of healthy volunteers' thyroids. All the devices showed a remarkable accuracy in quantification of equivalent 131I activity in the thyroids of persons of all ages. The selected scintillator dose rate meter showed detection limit values resulting in a maximum committed equivalent dose to thyroid HT, assuming an acute 131I inhalation occurred five days before the measurement, equal to 10 mSv (related to five-year-old children). Considering the level of HT values associated with the calculated detection limit activities, the proposed procedure has a significant sensitivity to be used for fast internally thyroid monitoring in nuclear or radiological emergencies, allowing daily monitoring a large amount of individuals.
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Radioisótopos de Yodo/análisis , Monitoreo de Radiación/instrumentación , Liberación de Radiactividad Peligrosa , Glándula Tiroides/efectos de la radiación , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo de Radiación/métodosRESUMEN
Despite the formal analogy with the Higgs particle, the amplitude fluctuations of the order parameter in weakly coupled superconductors do not identify a real mode with a Lorentz-invariant dynamics. Indeed, its resonance occurs at 2Δ_{0}, which coincides with the threshold 2E_{gap} for quasiparticle excitations that spoil any relativistic dynamics. Here we investigate the fate of the Higgs mode in the unconventional case where 2E_{gap} becomes larger than 2Δ_{0}, as due to strong coupling or strong disorder. We show that also in this situation, the amplitude fluctuations never identify a real mode at 2Δ_{0}, since such a "bosonic" limit is always reached via strong mixing with the phase fluctuations, which dominate the low-energy part of the spectrum. Our results have direct implications for the interpretation of the subgap optical absorption in disordered superconductors.
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BACKGROUND: Nasal polyposis (NP) is an inflammatory disease of the upper nasal airways frequently present in CF patients. Interferon-Related Developmental Regulator 1 (IFRD1) gene was reported as a possible modifier of CF lung disease severity. Three IFRD1 SNPs were analyzed to investigate a possible effect on the development of NP in CF patients. METHODS AND PATIENTS: The DNA of 143 patients with CF (40 with and 103 without NP) was purified from peripheral blood samples. IFRD1 SNPs (rs7817, rs3807213, rs6968084) were genotyped by restriction enzyme analysis. RESULTS: The T allele of the common polymorphisms rs7817 and the rs7817-rs3807213 haplotype were associated with NP (p = 0.002 and 0.004, respectively). CONCLUSIONS: These results showed the association of the IFRD1-rs7817 polymorphism with NP in CF patients.
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Fibrosis Quística/complicaciones , Proteínas Inmediatas-Precoces/genética , Pólipos Nasales/genética , Adulto , Fibrosis Quística/genética , Femenino , Haplotipos , Humanos , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
Plaque hemorrhage, inflammation and microvessel density are key determinants of plaque vulnerability in native coronary atherosclerosis (ATS). This study investigates the role of intraplaque hemorrhage (IPH) and its relation with inflammation and microvessels in cardiac allograft vasculopathy (CAV) in posttransplanted patients. Seventy coronary plaques were obtained from 12 patients who died because of CAV. For each patient we collected both native heart and the allograft, at the time of transplantation and autopsy, respectively. Intralesion inflammation, microvessels and IPH were assessed semi-quantitatively. IPH was observed in 21/35 (60%) CAV lesions and in 8/35 (22.9%) native ATS plaques, with a strong association between fibrocellular lesions and IPH (p = 0.0142). Microvessels were detected in 26/35 (74.3%) of CAV lesions with perivascular leakage as sign of endothelial damage in 18/26 (69.2%). IPH was strongly associated with microvessels (p < 0.0001). Inflammation was present in 31/35 (88.6%) of CAV lesions. CAV IPH+ lesions were characterized by presence of both fresh and old hemorrhage in 12/21 (57.1%). IPH, associated with microvessel damage and inflammation, is an important feature of CAV. Fresh and old intralesion hemorrhage suggests ongoing remodeling processes promoting the lesion progression and vulnerability.
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Trasplante de Corazón/efectos adversos , Hemorragia/patología , Placa Aterosclerótica/patología , Adulto , Aloinjertos , Enfermedad de la Arteria Coronaria/patología , Humanos , Inflamación/etiología , Microvasos/patología , Persona de Mediana EdadRESUMEN
AIM: This study aimed to determine the causes of postoperative emesis (PE) in neonates with infantile hypertrophic pyloric stenosis (IHPS) after laparoscopic pyloromyotomy (LP). METHODS: Retrospective review of the hospital database for infants with IHPS managed between 2000 and 2010 was performed. Relevant data were collected from the clinical records in the Medocs(®) system and used for statistical analysis. RESULTS: During the 10-year period, 95 patients with IHPS were identified and 43 (36 boys and seven girls) fulfilled the inclusion criteria. PE occurred in 21 infants (48.8%), of which nine presented with manifestations of enteric infections, with confirmed diagnosis in four. PE was significantly higher in the fast track feeding protocol (FTFP) group 12/15 compared with the conventional slow feeding protocol (CSFP) group 8/21 (p = 0.019). Gastro-oesophageal reflux (GER) confirmed by 24-h impedance monitoring was responsible for PE in three. Operative revision for suspected incomplete pyloromyotomy was performed in five infants. However, incomplete myotomy could only be confirmed in two infants during surgery. CONCLUSION: Postoperative emesis in IHPS after LP requires careful evaluation as it can be a result of enteric viral infections, aggressive feeding protocols or GER. Decisions to perform reoperations for incomplete myotomy after LP due to PE are challenging.
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Náusea y Vómito Posoperatorios , Estenosis Hipertrófica del Piloro/cirugía , Píloro/cirugía , Femenino , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Virosis/epidemiología , Virosis/etiologíaRESUMEN
This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted.
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After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Nivel de Atención , Humanos , Fibrosis Quística/terapia , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Asesoramiento Genético , Pruebas Genéticas/métodos , Recién NacidoRESUMEN
BACKGROUND: New aspects have emerged in the clinical and diagnostic scenarios of insulinoma: current guidelines have lowered the diagnostic insulin threshold to 3 µU/ml in the presence of hypoglycemia (<55 mg/dl); post-prandial hypoglycemia has been reported as the only presenting symptom; preexisting diabetes mellitus (DM) was recognized in some patients. AIM: To evaluate clinical features, diagnostic criteria and glucose metabolic profile in a monocentric series of patients affected by insulinomas including two subgroups: sporadic and multiple endocrine neoplasia type-1 syndrome (MEN-1). SUBJECTS AND METHODS: Clinical, pathological and biochemical data regarding 33 patients were analyzed. RESULTS: following the current guidelines the 72-h fasting test was initially positive in all cases but one. In this case the test, initially negative, became positive after a 2-yr follow-up. Nadir insulin level was ≥ 3 µU/ml but <6 µU/ml in 3 patients and ≥ 6 µU/ml in the remaining 30 cases. At presentation, 27 patients (82%) reported only fasting symptoms, 3 (9%) only post-prandial and 3 (9%) both. Seven cases (21%) had previously been affected by type 2 DM or impaired glucose metabolism. CONCLUSIONS: In our series the new cut-off of insulin increased the sensitivity of the 72-h fasting test from 87% to 97%. The absence of hypoglycemia during the test cannot definitively rule out the diagnosis and the test should be repeated in every highly suspicious case. Post-prandial hypoglycemia can be the only presenting symptom. DM may be associated with the occurrence of insulinoma. So that a possible diagnosis of insulinoma must not be ignored if previous impaired glucose handling is evident.
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Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Ayuno/efectos adversos , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hipoglucemia/complicaciones , Hipoglucemia/diagnóstico , Insulina/sangre , Insulinoma/sangre , Insulinoma/complicaciones , Insulinoma/patología , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/sangre , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Periodo Posprandial , Estudios RetrospectivosRESUMEN
In this paper, we investigate the XY model in the presence of an additional potential term that independently tunes the vortex fugacity favouring their nucleation. By increasing the strength of this term and thereby the vortex chemical potentialµ, we observe significant changes in the phase diagram with the emergence of a normal vortex-antivortex lattice as well as a superconducting vortex-antivortex crystal (lattice supersolid) phase. We examine the transition lines between these two phases and the conventional non-crystalline one as a function of both the temperature and the chemical potential. Our findings suggest the possibility of a peculiar tricritical point where second-order, first-order, and infinite-order transition lines meet. We discuss the differences between the present phase diagram and previous results for two-dimensional Coulomb gas models. Our study provides important insights into the behaviour of the modified XY model and opens up new possibilities for investigating the underlying physics of unconventional phase transitions.
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We calculate the Hall transport in a multiband system with a dominant interband interaction between carriers having electron and hole character. We show that this situation gives rise to an unconventional scenario, beyond the Boltzmann theory, where the quasiparticle currents dressed by vertex corrections acquire the character of the majority carriers. This leads to a larger (positive or negative) Hall coefficient than what may be expected on the basis of the carrier balance, with a marked temperature dependence. Our results explain the puzzling measurements in pnictides and provide a more general framework for transport properties in multiband materials.
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We consider the attractive Hubbard model with on-site disorder as a prototype of a disordered superconductor. We solve the Bogoliubov-de Gennes equations on two-dimensional finite clusters at zero temperature and evaluate the electromagnetic response to a vector potential. We find that the standard decoupling between transverse and longitudinal response does not apply in the presence of disorder. Moreover, the superfluid density is strongly reduced by the relaxation of the phase of the order parameter already at mean-field level when disorder is large. We also find that the anharmonicity of the phase fluctuations is strongly enhanced by disorder. Beyond mean field, this provides an enhancement of quantum fluctuations inducing a zero-temperature transition to a nonsuperconducting phase of disordered preformed pairs. Finally, the connection of our findings with the glassy physics for extreme dirty superconductors is discussed.
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AIM: This study reviewed the demographic, epidemiological and clinical factors of boys seen at a single centre who underwent surgical exploration for testicular torsion. METHODS: Retrospective single-centre review of boys with testicular torsion between 1996 and 2011 was made. RESULTS: Testicular torsion (right n = 43, left n = 60, bilateral n = 1) was identified in 104 boys between 0 and 18 years. Ten newborns presented with 11 intrauterine torsions. Nine torsions presented in undescended inguinal testes (one intrauterine). In 94 boys with descended testes, presentation included pain (76%), scrotal swelling (65%) and abdominal symptoms (22%). Ultrasonography was performed in 85 patients with false-negative results in 4 (4.7%). Orchiectomy was performed during initial exploration in 41, with significantly higher rates of orchiectomies in patients with late (>6 h) versus patients with early referrals (<6 h) (56% vs. 9.1%). Histological evaluation was carried out in 68 testes, with 43 resected testes demonstrating haemorrhagic necrosis. In 25 biopsied testes, histology revealed acute parenchymal bleeding (n = 14), onset of parenchymal infarction (n = 8), orchitis (n = 1) and normal tissue (n = 2). Eighty-two patients were followed up with pathological findings in four patients: testicular atrophies requiring orchiectomy (n = 2), testicular autolysis (n = 1) and small testicular vein thrombosis (n = 1). CONCLUSION: Chances of testicular salvage after torsion are higher if patients present early. The majority of patients presenting late (>6 h) require orchiectomy owing to testicular necrosis.
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Torsión del Cordón Espermático , Adolescente , Factores de Edad , Austria/epidemiología , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Necrosis , Orquiectomía , Pronóstico , Estudios Retrospectivos , Torsión del Cordón Espermático/diagnóstico , Torsión del Cordón Espermático/epidemiología , Torsión del Cordón Espermático/cirugía , Testículo/patología , Ultrasonografía DopplerRESUMEN
This paper is the first in a series providing updated guidance on the definition, evaluation and management of people with a Cystic Fibrosis Transmembrane conductance Regulator (CFTR)-Related Disorder (CFTR-RD). The need for this update relates to more precise characterisation of CFTR gene variants and improved assessment of CFTR protein dysfunction. The exercise is co-ordinated by the European CF Society Standards of Care Committee and Diagnostic Network Working Group and involves stakeholder engagement. This first paper was produced by a core group using an extensive literature review and papers graded for their quality. Subsequent wider stakeholder agreement was achieved. The definition of a CFTR-RD remains "a clinical condition with evidence of CFTR protein dysfunction that does not fulfil the diagnostic criteria for CF". Clearer guidance on CFTR dysfunction and relevant CFTR variants will be provided. Thresholds for clinical presentations are presented and the paradigm that pathobiological processes may be evident in more than one organ is agreed. In this paper we reflect on the early patient journey, highlighting that CF specialists as well as other relevant specialists should be involved in the care of people with a CFTR-RD.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Humanos , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Fibrosis Quística/diagnóstico , Fibrosis Quística/genética , Fibrosis Quística/terapia , Nivel de Atención , Mutación , Transporte IónicoRESUMEN
We demonstrate passive mode-locking of a Raman fiber laser using a nanotube-based saturable absorber coupled to a net normal dispersion cavity. This generates highly chirped 500 ps pulses. These are then compressed down to 2 ps, with 1.4 kW peak power, making it a simple wavelength-versatile source for various applications.
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The effects of the concomitant infection by COVID-19 and Burkholderia cepacia (Bc) in CF are not known. We describe the case of a 34 years woman with CF, colonized by Bc and found SARS-CoV2 positive. In the first hospital week she suffered acute respiratory failure and chest imaging showed interstitial involvement and multiple thickenings. She was treated with antibiotics, dexamethasone, remdesivir and heparin, with gradual improvement and discharge at day 20th. The reciprocal role of SARS-CoV-2 and Bc, their potential interactions and the contribution of the individual therapies to the favourable outcome are unclear. It is debatable whether it was SARS-CoV2 that triggered a Bc pulmonary exacerbation or if the chronic Bc infection facilitated the development of a COVID-19 more aggressive than usually seen in CF. If the latter hypothesis were confirmed by similar cases, Bc colonization should be regarded as a risk factor for severe COVID-19 expression in CF.
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Infecciones por Burkholderia/complicaciones , Infecciones por Burkholderia/diagnóstico , Burkholderia cenocepacia , COVID-19/complicaciones , COVID-19/diagnóstico , Fibrosis Quística/complicaciones , Adulto , Infecciones por Burkholderia/terapia , COVID-19/terapia , Fibrosis Quística/terapia , Femenino , HumanosRESUMEN
Genetic discoveries on Schizophrenia remain challenging. Traditional approaches have provided clues, but no genes. Novel theories that must account for extensive heterogeneity, including high discordance of monozygotic (MZD) twins, are needed. To this end, the extensive repeats of the human genome may provide the predisposition for DNA replication errors operational at every cell cycle during meiosis and mitosis. These errors will shower the genome with replication errors including copy number variations. Depending on the timing and the genes involved, this will contribute to the mutational load and disease. The evidence for such a mechanism in schizophrenia is emerging.
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Dosificación de Gen/genética , Esquizofrenia/genética , Enfermedades en Gemelos/genética , Predisposición Genética a la Enfermedad , Humanos , Gemelos MonocigóticosRESUMEN
The first case reported in the literature of a rare disease called necrotizing scialometaplasia (NS), dates back to 1973 when Abrams et al. described the main histological features of this disease. In this article we describe the rare clinical case of a young woman came to our observation for a double ulcer in the middle portion of the hard palate, aching, that histological examination showed compatible with a diagnosis of NS and preceded his appearance a haemorrhagic conjunctival suffusion left. We have provided a complete description of all the investigations in which the patient underwent and its treatment. We have also outlined the major etiological hypotheses of SN, histological features that point to a correct diagnosis, clinical features and prognostic and finally we reflected on the rare and interesting overlap in clinical manifestations palatal and conjunctival those trying to find a possible explanation.