Tratamiento de las fracturas maxilofaciales en un hospital cubano durante la pandemia de COVID-19

Introducción: La epidemiología de las fracturas maxilofaciales varía en dependencia de los estilos de vida, el nivel cultural y el estatus socioeconómico en diferentes zonas geográficas. Objetivo: Caracterizar epidemiológica y terapéuticamente a los pacientes con fracturas maxilofaciales, atendidos en un hospital universitario cubano durante la pandemia de COVID-19. Métodos: Se realizó un estudio observacional, descriptivo y transversal a los pacientes atendidos en el Servicio de Cirugía Maxilofacial del Hospital General Universitario "Carlos Manuel de Céspedes" de Bayamo, provincia Granma, durante el 1 de enero y el 31 de diciembre de 2020. Se estudiaron variables epidemiológicas y terapéuticas. Resultados: Se incluyeron 85 pacientes con 220 fracturas. Los hombres fueron los más afectados (n = 74; 87,06 %) y la proporción hombre/mujer resultó de 6,73:1. El grupo etario de 41-60 años (n = 40; 47,06 %) sobresalió. En el 38,89 % de los casos el trauma se relacionó con violencia interpersonal. Cincuenta y cuatro pacientes (63,52 %) tuvieron fracturas del complejo cigomático. El ángulo mandibular constituyó la localización anatómica más afectada. Las fracturas mandibulares se trataron fundamentalmente mediante reducción cerrada. Conclusiones: El perfil epidemiológico de las fracturas maxilofaciales se destacó en los pacientes adultos masculinos debido, principalmente, a la violencia interpersonal. Las fracturas complejas del tercio medio facial se trataron por método abierto. La distribución temporal de los casos mostró el impacto de la COVID-19 en la epidemiología de estos traumas.

Introduction: The epidemiology of maxillofacial fractures varies according to lifestyles, cultural level and socioeconomic status in different geographical areas. Objective: To characterize epidemiologically and therapeutically the patients with maxillofacial fractures treated in a Cuban university hospital during the COVID-19 pandemic. Methods: An observational, descriptive and cross-sectional study was carried out on patients attended at the Maxillofacial Surgery Service of the General University Hospital "Carlos Manuel de Céspedes" of Bayamo, Granma province, between January 1 and December 31, 2020. Epidemiological and therapeutic variables were studied. Results: 85 patients with 220 fractures were included. Men were the most affected (n = 74; 87.06 %) and the male/female ratio was 6.73:1. The age group 41-60 years (n = 40; 47.06 %) stood out. In 38.89 % of the cases the trauma was related to interpersonal violence. Fifty-four patients (63.52 %) had fractures of the zygomatic complex. The mandibular angle was the most damaged anatomical location. Fractures were treated primarily by closed reduction. Conclusions: The epidemiological profile of maxillofacial fractures was prominent in adult male patients mainly due to interpersonal violence. Complex fractures of the midfacial third were treated by open method. The temporal distribution of the cases showed the impact of COVID-19 on the epidemiology of these traumas.

Vision Impairments in Young Adults with Down Syndrome.

People with Down syndrome have more visual problems than the general population. They experience premature ageing, and they are expected to also have an acceleration in worsening visual function. A prospective observational study which includes visual acuity, refractive error, accommodation, binocular and colour vision was performed on young adults with (n = 69) and without (n = 65) Down syndrome and on a senior group (n = 55) without Down syndrome. Results showed significant differences in visual acuity between groups (p < 0.001), and it can be improved with a new prescription in 40% of the participants with Down syndrome. Regarding the accommodative state, no significant differences were found between groups of young people. Concerning binocular vision, 64.7% of strabismus was observed in the group with Down syndrome (p < 0.001). Visual abnormalities are significant in young adults with Down syndrome and are different from those of older people without Down syndrome, some of which can be improved by providing the optimal prescription as well as regular eye examinations.

Maternal stress increases risk of allergic lung inflammation in adult mice.

BACKGROUND: Allergies are increasing worldwide. The presence of atopic diseases in the mother propagates the onset of allergic diseases in the offspring with a considerably stronger penetrance than atopic diseases of the father. Such observation challenges genetic predispositions as the sole cause of allergic diseases. Epidemiological studies suggest that caregiver stress in the perinatal period may predispose offspring to asthma. Only one group has studied the link between prenatal stress and neonatal asthma susceptibility in a murine model. OBJECTIVES: We aimed to study if the neonatal increased risk of developing allergic lung inflammation persists after puberty and if there are sex differences in susceptibility. METHODS: Pregnant BALB/c mice were subjected to a single restraint stress exposure at day 15 of gestation. Pups were separated by gender and subjected to a well-known sub-optimal asthma model after puberty. RESULTS: Adult mice born to stressed dams were more susceptible to developing allergic pulmonary inflammation since an increase in the number of eosinophils in bronchoalveolar lavage (BAL), a greater peribronchial and perivascular infiltrate, a higher proportion of mucus-producing cells, and increased IL-4 and IL-5 levels in BAL were detected compared to control mice. These effects were more profound in females than males. Moreover, only females from stressed dams showed an increase in IgE levels. CONCLUSIONS: Increased litter susceptibility to develop allergic lung inflammation induced by maternal stress persists after puberty and is more potent in females than in male mice.

Analysis of vault prediction in phakic implantable phakic collamer lenses: manufacturer's calculator vs theoretical formulae vs clinical practice.

BACKGROUND: Implantable collamer phakic (ICL) intraocular lens sizing calculations are necessary to avoid complications associated to inadequate sizing. Historically, Holladay R, Dougherty, Hernández-Matamoros, and other authors have tried to create new formulas that solve calculation problems and provide higher reliability. In addition, in recent years, the appearance of new equipment, parameters, and formulas have led to significant progress. This paper compares the sizing according to manufacturer's method and other methods. METHODS: Forty-three eyes of 24 patients with EVO ICL implanted, with at least 1 year of follow-up, were analysed. The analysed variables were white to white (WTW), anterior chamber depth (ACD), ACW (angle-to-angle), crystalline lens rise (CLR), ICL size, vault measured at 1 week and 1 year after surgery, ICL size, and vault predicted by Nakamura-2 as well as vault size predicted by Igarashi. RESULTS: Sizing calculation with Online Calculation and Ordering System according to WTW and ACD is a good indicator with 86% success rate. The calculation with Nakamura 2 suggests larger ICL sizes in 32.5% of cases and smaller in 18.6% of cases, while the resulting Vault according to Igarashi obtains better results without significant differences. CONCLUSIONS: ICL sizing according WTW and ACD, using the manufacturer's algorithm, seems to be the most predictable method compared to other algorithms using other variables. The surgeon's expertise also has a high importance in the final ICL size election.

Crosstalk between tumor and stroma modifies CLIC4 cargo in extracellular vesicles.

Mouse models of breast cancer have revealed that tumor-bearing hosts must express the oxidoreductase CLIC4 to develop lung metastases. In the absence of host CLIC4, primary tumors grow but the lung premetastatic niche is defective for metastatic seeding. Primary breast cancer cells release EVs that incorporate CLIC4 as cargo and circulate in plasma of wildtype tumor-bearing hosts. CLIC4-deficient breast cancer cells also form tumors in wildtype hosts and release EVs in plasma, but these EVs lack CLIC4, suggesting that the tumor is the source of the plasma-derived EVs that carry CLIC4 as cargo. Paradoxically, circulating EVs are also devoid of CLIC4 when CLIC4-expressing primary tumors are grown in CLIC4 knockout hosts. Thus, the incorporation of CLIC4 (and perhaps other factors) as EV cargo released from tumors involves specific signals from the surrounding stroma determined by its genetic composition. Since CLIC4 is also detected in circulating EVs from human breast cancer patients, future studies will address its association with disease.

The oxidoreductase CLIC4 is required to maintain mitochondrial function and resistance to exogenous oxidants in breast cancer cells.

The chloride intracellular channel-4 (CLIC4) is one of the six highly conserved proteins in the CLIC family that share high structural homology with GST-omega in the GST superfamily. While CLIC4 is a multifunctional protein that resides in multiple cellular compartments, the discovery of its enzymatic glutaredoxin-like activity in vitro suggested that it could function as an antioxidant. Here, we found that deleting CLIC4 from murine 6DT1 breast tumor cells using CRISPR enhanced the accumulation of reactive oxygen species (ROS) and sensitized cells to apoptosis in response to H2O2 as a ROS-inducing agent. In intact cells, H2O2 increased the expression of both CLIC4 mRNA and protein. In addition, increased superoxide production in 6DT1 cells lacking CLIC4 was associated with mitochondrial hyperactivity including increased mitochondrial membrane potential and mitochondrial organelle enlargement. In the absence of CLIC4, however, H2O2-induced apoptosis was associated with low expression and degradation of the antiapoptotic mitochondrial protein Bcl2 and the negative regulator of mitochondrial ROS, UCP2. Furthermore, transcriptomic profiling of H2O2-treated control and CLIC4-null cells revealed upregulation of genes associated with ROS-induced apoptosis and downregulation of genes that sustain mitochondrial functions. Accordingly, tumors that formed from transplantation of CLIC4-deficient 6DT1 cells were highly necrotic. These results highlight a critical role for CLIC4 in maintaining redox-homeostasis and mitochondrial functions in 6DT1 cells. Our findings also raise the possibility of targeting CLIC4 to increase cancer cell sensitivity to chemotherapeutic drugs that are based on elevating ROS in cancer cells.

Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence.

The TGF-ß-regulated Chloride Intracellular Channel 4 (CLIC4) is an essential participant in the formation of breast cancer stroma. Here, we used data available from the TCGA and METABRIC datasets to show that CLIC4 expression was higher in breast cancers from younger women and those with early-stage metastatic disease. Elevated CLIC4 predicted poor outcome in breast cancer patients and was linked to the TGF-ß pathway. However, these associations did not reveal the underlying biological contribution of CLIC4 to breast cancer progression. Constitutive ablation of host Clic4 in two murine metastatic breast cancer models nearly eliminated lung metastases without reducing primary tumor weight, while tumor cells ablated of Clic4 retained metastatic capability in wildtype hosts. Thus, CLIC4 was required for host metastatic competence. Pre- and post-metastatic proteomic analysis identified circulating pro-metastatic soluble factors that differed in tumor-bearing CLIC4-deficient and wildtype hosts. Vascular abnormalities and necrosis increased in primary tumors from CLIC4-deficient hosts. Transcriptional profiles of both primary tumors and pre-metastatic lungs of tumor-bearing CLIC4-deficient hosts were consistent with a microenvironment where inflammatory pathways were elevated. Altogether, CLIC4 expression in human breast cancers may serve as a prognostic biomarker; therapeutic targeting of CLIC4 could reduce primary tumor viability and host metastatic competence.

Características clínicas, epidemiológicas y terapéuticas de pacientes con carcinoma epidermoide de cavidad bucal / Clinical, epidemiological and therapeutic characteristics of patients with oral cavity squamous cell carcinoma

RESUMEN Introducción: La región de la cabeza y el cuello es una de las áreas más complejas del cuerpo y el carcinoma epidermoide es la neoplasia maligna más frecuente en esta localización. Objetivo: Caracterizar, desde el punto de vista clínico, epidemiológico y terapéutico, los pacientes con carcinoma epidermoide de cavidad bucal. Métodos: Estudio observacional, descriptivo y transversal en pacientes tratados en un servicio de cirugía maxilofacial entre el 1 de enero de 2018 y el 31 de diciembre de 2020. Se analizaron variables clínicas, epidemiológicas y terapéuticas. La información se obtuvo mediante la entrevista y el examen clínico. Como medidas de resumen se utilizaron frecuencias absolutas y porcentajes. Resultados: Se estudiaron 29 pacientes, con predominio del sexo masculino (69,0 %). La edad media fue de 60,3 años (rango entre 41 y 80 años). La lengua fue la región anatómica más afectada (34,5 %) y la úlcera hundida o infiltrante la variante clínica de mayor presentación (27,6 %). El 48,3 % de las neoplasias fueron diferenciadas histológicamente. El 65,5 % de los diagnósticos se realizó en estadios avanzados de la enfermedad (etapas III y IV). Los tratamientos más utilizados fueron la cirugía (31,0 %) y la combinación de quimioterapia más radioterapia (27,6 %). Conclusión: Predominan los pacientes masculinos, las lesiones linguales, de aspecto ulcerado y diferenciadas histológicamente. La modalidad terapéutica más utilizada fue la cirugía.

ABSTRACT Introduction: Head and neck region is one of the more complex areas of the body and the squamous cell carcinoma is the most frequent malignant neoplasm in this location. Objective: To characterize, from a clinic, epidemiologic and therapeutic point of view, patients with squamous cell carcinoma of the oral cavity. Methods: Observational, descriptive and cross-sectional study with patients treated in maxillofacial surgery service between January 1, 2018 and December 31, 2020. Clinic, epidemiologic and therapeutic variables were analyzed. The information was obtained through interview and clinical examination. Absolute frequencies and percentages were used as summary measures. Results: Twenty-nine (29) patients, with a predominance of males (69.0 %), were studied. Mean age was 12 years (range between 41 and 80 years). The tongue was the most affected anatomical region (34.5 %) and the sunken or infiltrating ulcer was the most common clinical variant (27.6 %); 48.3 % of the neoplasms were differentiated histologically. 65.5 % of the diagnoses were made in advanced stages of the disease (stages III and IV). The most used treatments were surgery (31.0 %) and the combination of chemotherapy plus radiotherapy (27.6 %). Conclusion: Male patients, lingual lesions, ulcerated appearance and histologically differentiated predominated. The most used therapeutic modality was surgery.

Contribution of Kazal-Like Domains of the Serine Protease Inhibitor-1 from Toxoplasma gondii in Asthma Therapeutic Vaccination Effectiveness.

BACKGROUND: We have previously showed rTgPI-1 tolerogenic adjuvant properties in asthma treatment, turning it a promising candidate for allergen-specific immunotherapy. This therapy is an alternative treatment to control asthma that still presents several concerns related to its formulation. rTgPI-1 contains independent inhibitory domains able to inhibit trypsin and neutrophil elastase, both involved in asthma pathology. OBJECTIVES: In view of the need to design rational therapies, herein we investigated the contribution of the different inhibitory domains in rTgPI-1 therapeutic effectiveness. METHODS: BALB/c mice were rendered allergic by intraperitoneal OVA-alum sensitization and airway challenged. Once the asthmatic phenotype was achieved, mice were intranasally treated with OVA combined with the full-length recombinant protein rTgPI-1 or its truncated versions, Nt (containing trypsin-inhibitory domains) or Ct (containing neutrophil elastase-inhibitory domains). Afterward, mice were aerosol re-challenged. RESULTS: Asthmatic mice treated with the neutrophil elastase- or the trypsin-inhibitory domains separately failed to improve allergic lung inflammation. Only when all inhibitory domains were simultaneously administered, an improvement was achieved. Still, a better outcome was obtained when mice were treated with the full-length rTgPI-1. CONCLUSIONS: Adjuvant ability depends on the presence of all its inhibitory domains in a single entity, so it should be included in potential asthma treatment formulations as a full-length protein.

Retinal Protection from LED-Backlit Screen Lights by Short Wavelength Absorption Filters.

(1) Background: Ocular exposure to intense light or long-time exposure to low-intensity short-wavelength lights may cause eye injury. Excessive levels of blue light induce photochemical damage to the retinal pigment and degeneration of photoreceptors of the outer segments. Currently, people spend a lot of time watching LED screens that emit high proportions of blue light. This study aims to assess the effects of light emitted by LED tablet screens on pigmented rat retinas with and without optical filters. (2) Methods: Commercially available tablets were used for exposure experiments on three groups of rats. One was exposed to tablet screens, the other was exposed to the tablet screens with a selective filter and the other was a control group. Structure, gene expression (including life/death, extracellular matrix degradation, growth factors, and oxidative stress related genes), and immunohistochemistry in the retina were compared among groups. (3) Results: There was a reduction of the thickness of the external nuclear layer and changes in the genes involved in cell survival and death, extracellular matrix turnover, growth factors, inflammation, and oxidative stress, leading decrease in cell density and retinal damage in the first group. Modulation of gene changes was observed when the LED light of screens was modified with an optical filter. (4) Conclusions: The use of short-wavelength selective filters on the screens contribute to reduce LED light-induced damage in the rat retina.

Carcinoma epidermoide intraoral y factores de riesgo asociados: un estudio de casos y controles / Oral squamous cell carcinoma and associated risk factors: A case-control study

Introducción: El carcinoma epidermoide es la neoplasia maligna más frecuente de la cabeza y el cuello, por lo que un conocimiento adecuado sobre sus factores de riesgo podría disminuir su morbimortalidad. Objetivo: Identificar la asociación causal entre algunos factores de riesgo y la aparición del carcinoma epidermoide de la cavidad bucal. Métodos: Estudio observacional, analítico, de casos y controles en pacientes tratados en el servicio de cirugía maxilofacial del Hospital General Provincial Carlos Manuel de Céspedes entre el 1 de enero de 2018 y el 31 de diciembre de 2020. Para el análisis estadístico de los factores de riesgo se midió la fuerza de la asociación con el odds ratio y sus intervalos de confianza (IC 95 por ciento) y luego se realizó un análisis multivariado. Resultados: Se trabajó con 87 pacientes (29 casos y 58 controles). El 68,96 % (n = 20) de los casos fueron pacientes masculinos y su promedio de edad fue de 63,03 años. Las personas con antecedentes de consumo de alcohol tuvieron un riesgo 16 veces mayor de padecer la enfermedad (OR: 16,03). La higiene bucal deficiente (OR: 5,23; IC 95 por ciento: 1,18-23,29; p = 0,030) y la exposición a irritantes traumáticos (OR: 4,41; IC 95 por ciento: 1,01-19,23; p = 0,048) fueron también factores de riesgo. Conclusión: Existe una fuerte asociación entre la presencia de la enfermedad y el antecedente de consumo de alcohol, la exposición a irritantes traumáticos y la higiene bucal deficiente(AU)

Introduction: Squamous cell carcinoma is the most frequent neoplasm of the head and neck. An adequate knowledge about its risk factors could reduce its morbidity and mortality. Objective: To identify the causal association between some risk factors and the apparition of the oral squamous cell carcinoma. Methods: Observational, analytic and case-control study conducted with patients treated at Carlos Manuel de Céspedes Provincial General Hospital's maxillofacial surgery service between January 1, 2018 and December 31, 2020. For the statistical analysis of the risk factors, the strength of the association with the Odds Ratio and its confidence intervals (95 percent CI) was measured and later a multivariate analysis was performed. Results: The sample was comprised of 87 patients (29 cases and 58 controls). The 68.96 percent of the cases (n=20) were male patients and their average age was 63.03 years. People with history of alcohol consumption showed a 16 times greater risk (OR=16.03). Poor oral hygiene (OR: 5.23; CI 95 percent: 1.18-23.29; p=0.030) and traumatic irritants (OR: 4.41; CI 95 percent: 1.01-19.23; p=0.048) were risk factors too. Conclusion: A strong association between the disease and the antecedent of alcohol consumption, the exposition to traumatic irritating and the poor oral hygiene was identified(AU)

Measurement of the Intraocular Pressure Elevation During Laser-Assisted In Situ Keratomileusis Flap Creation Using a Femtosecond Laser Platform.

Purpose: The purpose of this study was to measure the intraocular pressure (IOP) elevation during laser assisted in situ keratomileusis (LASIK) flap creation using the WaveLight FS200 femtosecond (FS) laser platform. Methods: We conducted an ex vivo experimental study in an animal model. The WaveLight FS200 FS laser platform was used to perform the corneal LASIK flap in freshly enucleated porcine eyes. We measured the changes in IOP from the application of the suction ring (suctioning phase) through the creation of the lamellar corneal flap (cutting phase). The IOP was recorded using a manometric technique with direct cannulation to the anterior chamber. Results: Nine freshly enucleated porcine eyes were included in the study. The mean baseline IOP before the procedure was 20.33 ± 5.9 mm Hg. The mean IOP increase over baseline IOP was 32.33 ± 11.3 mm Hg at the suctioning phase, and 38.22 ± 11.3 mm Hg at the cutting phase. The total surgical time needed to complete the procedure was 29.5 ± 4.4 seconds. Conclusions: The WaveLight FS200 FS laser platform produces a low to moderate increase in IOP during LASIK flap creation. Translational Relevance: The WaveLight FS200 is a safe FS laser platform because it induces a low to moderate IOP increase during LASIK flap creation.

Impacto de la invasión perineural en pacientes con cáncer de lengua tratados en el Instituto Nacional de Oncología y Radiobiología / Impact of perineural invasion in patients with tongue cancer treated at the National Institute of Oncology and Radiobiology / Impacto da invasão perineural em pacientes com câncer de língua tratados no National Institute of Oncology and Radiobiology

RESUMEN El conocimiento de los factores pronósticos del carcinoma escamoso de cabeza y cuello es de gran importancia, pues ayudan a predecir el futuro evolutivo de la enfermedad y a comprender hechos de su fisiopatología también, permiten comparar tratamientos, agrupar a los pacientes con pronóstico semejante, diseñar ensayos clínicos incluso, seleccionar el tratamiento ideal para cada paciente. Se realizó un estudio observacional, descriptivo, longitudinal y retrospectivo con el objetivo de evaluar el impacto de la invasión perineural en pacientes con cáncer de lengua tratados en el Instituto de Oncología y Radiobiología (INOR) con un universo de 62 pacientes. Se tuvieron en cuenta variables como: edad, sexo, color de la piel, grado histológico, etapa clínica, tipo de lesión, técnica quirúrgica utilizada y factores pronósticos mayores. Se establecieron 2 grupos uno sin presencia de invasión perineural y otro con invasión perineural. El mayor número de casos se presentó en el grupo de 55-64 años en ambos grupos, con mayor incidencia del sexo masculino y color de la piel blanca. El carcinoma epidermoide bien diferenciado prevaleció en ambos grupos con 54,3 % y 50,0. La técnica quirúrgica más utilizadas en el grupo de pacientes con presencia de invasión perineural fue las glosectomías parciales más disección selectiva de cuello, los bordes de sección quirúrgicos positivos fue el factor pronóstico mayor más frecuente en los pacientes con invasión perineural con 56,3 % y significación estadística p=0,021. Las recaídas, local, regional y a distancia, estuvieron presentes en todos los pacientes que presentaron la invasión perineural estadísticamente significativo p=0,010.

ABSTRACT Knowledge of the prognostic factors of squamous cell carcinoma of the head and neck is of great importance, as they help to predict the future evolution of the disease and to understand facts about its pathophysiology, they also allow comparing treatments, grouping patients with a similar prognosis, designing trials clinicians even select the ideal treatment for each patient. An observational, descriptive, longitudinal and retrospective study was carried out with the objective of evaluating the impact of perineural invasion in patients with tongue cancer treated at the Institute of Oncology and Radiobiology (INOR) with a universe of 62 patients. Variables such as: age, sex, skin color, histological grade, clinical stage, type of lesion, surgical technique used and major prognostic factors were taken into account. Two groups were established, one without the presence of perineural invasion and the other with perineural invasion. The highest number of cases occurred in the 55-64 age group in both groups, with a higher incidence of males and white skin color. Well-differentiated squamous cell carcinoma prevailed in both groups with 54.3% and 50.0. The surgical technique most used in the group of patients with the presence of perineural invasion was partial glosectomies plus selective neck dissection, positive surgical section margins were the most frequent major prognostic factor in patients with perineural invasion with 56.3% and statistical significance p = 0.021. Relapses, local, regional and distant, were present in all patients who presented statistically significant perineural invasion p = 0.010.

RESUMO O conhecimento dos fatores prognósticos do carcinoma espinocelular de cabeça e pescoço é de grande importância, pois ajudam a prever a evolução futura da doença e a compreender fatos sobre sua fisiopatologia, permitem também comparar tratamentos, agrupar pacientes com prognósticos semelhantes, delinear ensaios os médicos até selecionam o tratamento ideal para cada paciente. Foi realizado um estudo observacional, descritivo, longitudinal e retrospectivo com o objetivo de avaliar o impacto da invasão perineural em pacientes com câncer de língua atendidos no Instituto de Oncologia e Radiobiologia (INOR) com um universo de 62 pacientes. Foram consideradas variáveis ​​como: idade, sexo, cor da pele, grau histológico, estádio clínico, tipo de lesão, técnica cirúrgica utilizada e principais fatores prognósticos. Dois grupos foram estabelecidos, um sem presença de invasão perineural e outro com invasão perineural. O maior número de casos ocorreu na faixa etária de 55 a 64 anos em ambos os grupos, com maior incidência no sexo masculino e na cor da pele branca. O carcinoma espinocelular bem diferenciado prevaleceu em ambos os grupos com 54,3% e 50,0. A técnica cirúrgica mais utilizada no grupo de pacientes com presença de invasão perineural foi glosectomias parciais mais esvaziamento cervical seletivo, margens de secção cirúrgica positivas foram o principal fator prognóstico mais frequente em pacientes com invasão perineural com 56,3% e significância estatística p = 0,021. As recidivas, locais, regionais e à distância, estiveram presentes em todos os pacientes que apresentaram invasão perineural estatisticamente significativa p = 0,010.

Synergistic effect of GRA7 and profilin proteins in vaccination against chronic Toxoplasma gondii infection.

Toxoplasmosis is a zoonotic disease with worldwide prevalence in humans and warm-blooded animal populations. In livestock Toxoplasma gondii is the causal agent of significant economic losses since it can cause abortions in goats and sheep. It is estimated that one third of the world population is infected. Although there are effective therapies for acute infection, these are sometimes poorly tolerated, teratogenic, and have a long administration time. Considering the deficiencies that exist related to the prevention and treatment of toxoplasmosis, the development of a safe and effective vaccine would be extremely valuable in fighting against this infection. In the present work, we characterize for the first time the adjuvant and immunogenic potential of a recombinant profilin protein (rTgPF), in a vaccine formulation alone or in combination with the well-known GRA7 antigen candidate in a murine toxoplasmosis model. Since TgPF acts as a ligand for TLR11 and 12 inducing innate immune responses that promote type 1 adaptive responses, we first study the capacity of the mix rGRA7 + rTgPF to initiate an immune response by evaluating dendritic cell activation. Both rTgPF and rGRA7 induces activation of mouse BMDCs more efficiently than the single proteins, evidenced by increased expression of CD80 and CD86 co-stimulatory proteins and secretion of IL-6, IL-10 and IL-12 cytokines after in vitro stimulation. The sum of the effects of rGRA7 and rTgPF on BMDCs maturation led us to assay them in a vaccination protocol. BALB/c mice vaccinated with this mix elicited a Th1-biased immunity via the induction of lymphocyte proliferation, activation of CD4+T cells and increased IFN-γ production that resulted in enhanced protection against chronic Toxoplama gondii infection. Profilin per se induce only cellular immunity but augments the effect of rGRA7 immune responses when used together, thus allowing us to postulate rTgPF as a potential adjuvant in a protein vaccine.

Impacto de la invasión perineural en pacientes con cáncer de lengua tratados en el Instituto Nacional de Oncología y Radiobiología / Impact of perineural invasion in patients with tongue cancer treated at the National Institute of Oncology and Radiobiology

El conocimiento de los factores pronósticos del carcinoma escamoso de cabeza y cuello es de gran importancia, pues ayudan a predecir el futuro evolutivo de la enfermedad y a comprender hechos de su fisiopatología también, permiten comparar tratamientos, agrupar a los pacientes con pronóstico semejante, diseñar ensayos clínicos incluso, seleccionar el tratamiento ideal para cada paciente. Se realizó un estudio observacional, descriptivo, longitudinal y retrospectivo con el objetivo de evaluar el impacto de la invasión perineural en pacientes con cáncer de lengua tratados en el Instituto de Oncología y Radiobiología (INOR) con un universo de 62 pacientes. Se tuvieron en cuenta variables como: edad, sexo, color de la piel, grado histológico, etapa clínica, tipo de lesión, técnica quirúrgica utilizada y factores pronósticos mayores. Se establecieron 2 grupos uno sin presencia de invasión perineural y otro con invasión perineural. El mayor número de casos se presentó en el grupo de 55-64 años en ambos grupos, con mayor incidencia del sexo masculino y color de la piel blanca. El carcinoma epidermoide bien diferenciado prevaleció en ambos grupos con 54,3 por ciento y 50,0. La técnica quirúrgica más utilizadas en el grupo de pacientes con presencia de invasión perineural fue las glosectomías parciales más disección selectiva de cuello, los bordes de sección quirúrgicos positivos fue el factor pronóstico mayor más frecuente en los pacientes con invasión perineural con 56,3 por ciento y significación estadística p = 0,021. Las recaídas, local, regional y a distancia, estuvieron presentes en todos los pacientes que presentaron la invasión perineural estadísticamente significativo p = 0,010(AU)

Knowledge of the prognostic factors of squamous cell carcinoma of the head and neck is of great importance, as they help to predict the future evolution of the disease and to understand facts about its pathophysiology, they also allow comparing treatments, grouping patients with a similar prognosis, designing trials clinicians even select the ideal treatment for each patient. An observational, descriptive, longitudinal and retrospective study was carried out with the objective of evaluating the impact of perineural invasion in patients with tongue cancer treated at the Institute of Oncology and Radiobiology (INOR) with a universe of 62 patients. Variables such as: age, sex, skin color, histological grade, clinical stage, type of lesion, surgical technique used and major prognostic factors were taken into account. Two groups were established, one without the presence of perineural invasion and the other with perineural invasion. The highest number of cases occurred in the 55-64 age group in both groups, with a higher incidence of males and white skin color. Well-differentiated squamous cell carcinoma prevailed in both groups with 54.3 percent and 50.0. The surgical technique most used in the group of patients with the presence of perineural invasion was partial glosectomies plus selective neck dissection, positive surgical section margins were the most frequent major prognostic factor in patients with perineural invasion with 56.3 percent and statistical significance p = 0.021. Relapses, local, regional and distant, were present in all patients who presented statistically significant perineural invasion p = 0.010(EU)

Evolution of visual acuity, flap thickness, and optical density after laser in situ keratomileusis performed with a femtosecond laser.

PURPOSE: To describe the postoperative evolution of visual acuity, flap morphology, and stromal optical density femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). SETTING: Clínica Rementería, Madrid, Spain. DESIGN: Prospective case series. METHODS: The study comprised 44 consecutive eyes that had FS-LASIK performed with the WaveLight FS200 and the Allegretto excimer laser to correct myopia. Visual outcomes, flap thickness, and stromal optical density were assessed 1 day, 1 week, 1 month, and 3 months postoperatively. RESULTS: A statistically significant improvement in the mean uncorrected distance visual acuity at 1 day (0.94 ± 0.2) and 1 week (0.93 ± 0.2) to 1 month (1.04 ± 0.2) and 3 months (1.11 ± 0.1) postoperatively (P < .05). At 3 months postoperatively, the femtosecond laser had good outcomes in efficacy (0.98 ± 0.1), safety (0.98 ± 0.1), and predictability (100% of eyes were within ± 0.5 D of emmetropia). The femtosecond-created flaps were slightly thicker than intended, the mean SD intraflap was 7.1 µm, the range between the thickest and thinnest points in each flap was 25.4 µm, and the mean flap thickness homogeneity was 7.6 µm at 3 months postoperatively. A progressive decrease in the optical density of the flap stroma and the residual stromal bed was detected during follow-up. CONCLUSIONS: The femtosecond laser study appears to be a safe, effective, and predictable platform to obtain LASIK flaps. The flaps were planar and homogeneous but slightly thicker than intended. The optical density of the flap stroma was slightly higher at early follow-up and decreased over time.

Fenotipo de la haptoglobina y presencia de enfermedad vascular subclínica: estudio poblacional / Phenotype of haptoglobin and presence of subclinical vascular disease: Population study

Introducción y objetivos: La haptoglobina es una proteína implicada en la protección frente al daño oxidativo producido por el hierro de la hemoglobina. Esta proteína es polimórfica, con 3 isomorfas prevalentes en la población. Los portadores de la isoforma Hp2-2 tienen una menor capacidad antioxidante, y en la población con diabetes, un mayor riesgo de enfermedad vascular subclínica y de complicaciones cardiovasculares. Nuestro objetivo fue evaluar si dicha isomorfa se asocia con un mayor riesgo de arteriosclerosis carotídea en sujetos con y sin diabetes, libres de enfermedad cardiovascular. Pacientes y métodos: Estudio realizado en una población de entre 45 y 74años de edad seleccionada aleatoriamente del área noroeste de Madrid. Los participantes fueron caracterizados en cuanto a su estatus glucémico mediante una sobrecarga oral de glucosa y la determinación de la concentración de Hb1Ac. A todos ellos se les determinó el fenotipo de la haptoglobina mediante un ensayo inmunoenzimático y la presencia de arteriosclerosis carotídea mediante ecografía. Resultados: De los 1.256 participantes incluidos en el presente análisis (edad media 61,6 ± 6 años, 41,8% varones), la distribución de las isoformas de la haptoglobina fue la siguiente: Hp1-1: 13,3%, Hp1-2: 48,5% y Hp2-2: 38,2%. En comparación con los sujetos Hp1-1 y Hp1-2, aquellos con el fenotipo Hp2-2 tuvieron una mayor prevalencia de dislipemia (53,3% vs 43%, p < 0,0001) e hipertensión arterial (39,2% vs 32,2%, p = 0,012), y recibieron con más frecuencia tratamiento con estatinas (31,5% vs 21,6%, p < 0,0001) y con antihipertensivos (38,4% vs 30,8%, p = 0,006). Los portadores de la isoforma Hp2-2 tuvieron una mayor prevalencia de placas carotídeas (OR: 1,35; IC 95%: 1,07-1,69; p = 0,011), sin diferencias en dicha prevalencia en función del estatus glucémico. No existieron diferencias en el grosor íntima-media entre los diferentes fenotipos. La relación del fenotipo Hp2-2 con la presencia de placas en carótida fue independiente de la edad, del sexo, de la presencia de factores de riesgo (dislipemia, hipertensión y diabetes), de la concentración de colesterol LDL, proteína C reactiva y ácido úrico, de la presión arterial y del tratamiento con estatinas y antihipertensivos (OR: 1,31; IC 95%: 1,01-1,70; p = 0,044). Conclusión: Los sujetos con el fenotipo Hp2-2 de la haptoglobina tienen una mayor prevalencia de arteriosclerosis carotídea, que es independiente de la presencia de otros factores de riesgo cardiovascular y de su estatus glucémico

Introduction and objectives: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. Patients and methods: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. Results: Of the 1,256 participants included in the present analysis (mean age 61.6 ± 6 years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P < .0001) and arterial hypertension (39.2% vs. 32.2%, P = .012), and they more frequently received treatment with statins (31.5% vs 21.6%, P < .0001), and with antihypertensive agents (38.4% vs 30.8%, P = .006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P = .011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95% CI 1.01-1.70, P = .044). Conclusion: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status

Phenotype of haptoglobin and presence of subclinical vascular disease: Population study. / Fenotipo de la haptoglobina y presencia de enfermedad vascular subclínica: estudio poblacional.

INTRODUCTION AND OBJECTIVES: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. PATIENTS AND METHODS: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. RESULTS: Of the 1,256 participants included in the present analysis (mean age 61.6±6years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P<.0001) and arterial hypertension (39.2% vs. 32.2%, P=.012), and they more frequently received treatment with statins (31.5% vs 21.6%, P<.0001), and with antihypertensive agents (38.4% vs 30.8%, P=.006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P=.011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95%CI 1.01-1.70, P=.044). CONCLUSION: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status.

Chronic infection with the protozoan Toxoplasma gondii prevents the development of experimental atopic dermatitis in mice.

BACKGROUND: Supporting the hypothesis thatT. gondii infection protects against allergy in humans we previously demonstrated that this infection can modulate not only the susceptibility to develop respiratory allergies in mice but also suppresses allergic responses at systemic level. This latter finding suggests that T. gondii infection could prevent the onset of other allergic diseases, such as atopic dermatitis. At present, few studies have investigated the modulation of atopic dermatitis by parasite infections. OBJECTIVE: Here, we sought to investigate whether chronic infection with T. gondii is capable of modulating the development of atopic dermatitis. METHODS: Chronically infected mice were sensitized by repeated epicutaneous ovalbumin administration. Skin histopathology, humoral response, cytokine production and innate type-II lymphoid cells (ILC2) were assessed. RESULTS: A marked reduction in epidermal thickness and dermal inflammatory infiltrate along with a reduction in mast cell count was observed in infected mice compared to non-infected mice. These results correlated with a diminished TH2 and TH1 allergen specific response. Reduced type-II IL-4 and IL-5 cytokines were already detected during the first 24 h of allergen sensitization in splenocytes and draining lymph nodes from infected mice. Moreover, this reduced type-II profile in chronically infected animals correlated with diminished ILC2 number in draining lymph nodes. CONCLUSION: Chronic infection withT. gondii prevents the development of atopic dermatitis. The diminished susceptibility seems to result from changes in type-II innate immune response that may lead to the induction of a deficient TH2 response and consequently to a lower susceptibility to develop atopic dermatitis.

The transcription factor CBFB suppresses breast cancer through orchestrating translation and transcription.

Translation and transcription are frequently dysregulated in cancer. These two processes are generally regulated by distinct sets of factors. The CBFB gene, which encodes a transcription factor, has recently emerged as a highly mutated driver in a variety of human cancers including breast cancer. Here we report a noncanonical role of CBFB in translation regulation. RNA immunoprecipitation followed by deep sequencing (RIP-seq) reveals that cytoplasmic CBFB binds to hundreds of transcripts and regulates their translation. CBFB binds to mRNAs via hnRNPK and enhances translation through eIF4B, a general translation initiation factor. Interestingly, the RUNX1 mRNA, which encodes the transcriptional partner of CBFB, is bound and translationally regulated by CBFB. Furthermore, nuclear CBFB/RUNX1 complex transcriptionally represses the oncogenic NOTCH signaling pathway in breast cancer. Thus, our data reveal an unexpected function of CBFB in translation regulation and propose that breast cancer cells evade translation and transcription surveillance simultaneously through downregulating CBFB.