Control hospitalario de la diabetes y de la hiperglucemia: una auditoría en hospitales españoles / Inpatient management of diabetes and hyperglycemia: an audit of Spanish hospitals

Objetivos Evaluación de la calidad de la asistencia a los pacientes con diabetes mellitus ingresados en España. Métodos Estudio transversal que incluyó a 1.193 (26,7%) pacientes con diabetes tipo 2 o hiperglucemia de un total de 4.468 pacientes ingresados en los servicios de medicina interna de 53 hospitales (España). Se recogieron datos demográficos, adecuación de la monitorización de la glucemia capilar, tratamiento administrado durante el ingreso y terapia recomendada al alta. Resultados La edad mediana fue de 80 años (74-87), 561 (47%) pacientes eran mujeres, con un índice de Charlson de 4 (2-6) puntos, siendo clasificados frágiles 742 (65%). La mediana de glucemia al ingreso fue de 155 (119-213) mg/dL. Al tercer día de ingreso el número de glucemias capilares en objetivo (80-180mg/dL) fue de 792/1.126 (70,3%) en el predesayuno, 601/1.083 (55,4%) en la precomida, 591/1.073 (55,0%) en la precena y 317/529 (59,9%) durante la noche. Se observó hipoglucemia en 35 (0,9%) pacientes. El tratamiento durante el ingreso fue realizado con insulina en escala móvil en 352 (40,5%) pacientes, insulina basal y análogos de insulina rápida en 434 (50%) y dieta exclusivamente en 101 (9,1%). Un total de 735 (61,6%) pacientes disponían de un valor reciente de HbA1c. En el alta se incrementó el uso de iSGLT2 (30,1 vs. 21,6%; p<0,001) y el uso de insulina basal (25,3 vs. 10,1%; p<0,001). Conclusiones Existe un excesivo uso de insulina en escala móvil, una deficiente información de los valores de HbA1c y una prescripción aún deficiente de tratamientos con beneficio cardiovascular al alta (AU)

Objectives Evaluation of the quality of care for patients with diabetes mellitus admitted to hospitals in Spain. Methods Cross-sectional study in one day that included 1193 (26.7%) patients with type 2 diabetes or hyperglycemia out of 4468 patients admitted to the internal medicine departments of 53 hospitals in Spain. We collected demographic data, adequacy of capillary glycemic monitoring, treatment administered during admission, and recommended therapy at discharge. Results The median age of the patients was 80 years (74-87), of which 561 (47%) were women, with a Charlson index of 4 points (2-6), and 742 (65%) were fragile. Median blood glucose on admission was 155mg/dL (119-213). On the third day, the number of capillary blood glucose levels in target (80-180mg/dL) was pre-breakfast 792/1126 (70.3%), pre-lunch 601/1083 (55.4%), pre-dinner 591/1073 (55.0%) and night 317/529 (59.9%). A total of 35 patients (0.9%) were suffering from hypoglycemia. Treatment during hospitalization was performed with sliding scale insulin in 352 (40.5%) patients, with basal insulin and rapid insulin analogs in 434 (50%), or with diet exclusively in 101 (9.1%). A total of 735 (61.6%) patients had a recent HbA1c value. At the time of discharge, the use of iSGLT2 increased significantly (30.1% vs. 21.6%; p<0.001), as well as the use of basal insulin (25.3% vs. 10.1%; p<0.001). Conclusions There is an excessive use of insulin on a sliding scale as well as deficient information on HbA1c values and an even deficient prescription at the discharge of treatments with cardiovascular benefit (AU)

[Patients with COPD hospitalized due to COVID-19 in Spain: a comparison between the first and second wave]. / Pacientes con EPOC hospitalizados por COVID-19 en España: comparación entre la primera y la segunda ola.

Objective: This work aimed to compare the characteristics, progress, and prognosis of patients with COPD hospitalized due to COVID-19 in Spain in the first wave with those of the second wave. Material and methods: This is an observational study of patients hospitalized in Spain with a diagnosis of COPD included in the SEMI-COVID-19 registry. The medical history, symptoms, analytical and radiological results, treatment, and progress of patients with COPD hospitalized in the first wave (from March to June 2020) versus those hospitalized in the second wave (from July to December 2020) were compared. Factors associated with poor prognosis, defined as all-cause mortality and a composite endpoint that included mortality, high-flow oxygen therapy, mechanical ventilation, and ICU admission, were analyzed. Results: Of the 21,642 patients in the SEMI-COVID-19 Registry, 6.9% were diagnosed with COPD: 1,128 (6.8%) in WAVE1 and 374 (7.7%) in WAVE2 (p = 0.04). WAVE2 patients presented less dry cough, fever and dyspnea, hypoxemia (43% vs 36%, p < 0.05), and radiological condensation (46% vs 31%, p < 0.05) than WAVE1 patients. Mortality was lower in WAVE2 (35% vs 28.6%, p = 0.01). In the total sample, mortality and the composite outcome of poor prognosis were lower among patients who received inhalation therapy. Conclusions: Patients with COPD admitted to the hospital due to COVID-19 in the second wave had less respiratory failure and less radiological involvement as well as a better prognosis. These patients should receive bronchodilator treatment if there is no contraindication for it.

Pacientes con EPOC hospitalizados por COVID-19 en España: comparación entre la primera y la segunda ola / Patients with COPD hospitalized due to COVID-19 in Spain: a comparison between the first and second wave

Objetivo Comparar las características, evolución y pronóstico de los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) hospitalizados por COVID-19 en España en la primera ola con los de la segunda ola. Material y métodos Estudio observacional de los pacientes hospitalizados en territorio español con diagnóstico de EPOC incluidos en el registro SEMI-COVID-19. Se compararon los antecedentes, la clínica, los resultados analíticos y radiológicos, el tratamiento y la evolución de los pacientes con EPOC hospitalizados en la primera ola (desde marzo hasta junio del 2020 [OLA1]) frente a los que fueron ingresados en la segunda ola (desde julio hasta diciembre del 2020 [OLA2]). Se analizaron los factores de mal pronóstico, definidos como mortalidad por todas las causas y un evento combinado que incluía mortalidad, oxigenoterapia con alto flujo, ventilación mecánica e ingreso en la unidad de cuidados intensivos (UCI). Resultado De 21.642 pacientes del registro SEMI-COVID-19, están diagnosticados de EPOC 6,9%, 1.128 (6,8%) en la OLA1 y 374 (7,7%) en la OLA2 (p = 0,04). Los pacientes de la OLA2 presentan menos tos seca, fiebre y disnea, hipoxemia (43 vs. 36%, p < 0,05) y condensación radiológica (46 vs. 31%, p < 0,05) que los de la OLA1. La mortalidad es menor en la OLA2 (35 vs. 28,6%, p = 0,01). En el global de pacientes la mortalidad y la variable combinada de mal pronóstico fue menor entre aquellos que recibieron tratamiento inhalador. Conclusiones Los pacientes con EPOC con ingreso hospitalario por COVID-19 en la segunda ola presentan menos insuficiencia respiratoria y menor afectación radiológica, con mejor pronóstico. Estos deben recibir tratamiento broncodilatador si no hay contraindicación para el mismo (AU)

Objective This work aimed to compare the characteristics, progress, and prognosis of patients with COPD hospitalized due to COVID-19 in Spain in the first wave with those of the second wave. Material and methods This is an observational study of patients hospitalized in Spain with a diagnosis of COPD included in the SEMI-COVID-19 registry. The medical history, symptoms, analytical and radiological results, treatment, and progress of patients with COPD hospitalized in the first wave (from March to June 2020) versus those hospitalized in the second wave (from July to December 2020) were compared. Factors associated with poor prognosis, defined as all-cause mortality and a composite endpoint that included mortality, high-flow oxygen therapy, mechanical ventilation, and ICU admission, were analyzed. Results Of the 21,642 patients in the SEMI-COVID-19 Registry, 6.9% were diagnosed with COPD: 1,128 (6.8%) in WAVE1 and 374 (7.7%) in WAVE2 (p = 0.04). WAVE2 patients presented less dry cough, fever and dyspnea, hypoxemia (43% vs 36%, p < 0.05), and radiological condensation (46% vs 31%, p < 0.05) than WAVE1 patients. Mortality was lower in WAVE2 (35% vs 28.6%, p = 0.01). In the total sample, mortality and the composite outcome of poor prognosis were lower among patients who received inhalation therapy. Conclusions Patients with COPD admitted to the hospital due to COVID-19 in the second wave had less respiratory failure and less radiological involvement as well as a better prognosis. These patients should receive bronchodilator treatment if there is no contraindication for it (AU)

Patients with COPD hospitalized due to COVID-19 in Spain: a comparison between the first and second wave.

OBJECTIVE: This work aimed to compare the characteristics, progress, and prognosis of patients with COPD hospitalized due to COVID-19 in Spain in the first wave with those of the second wave. MATERIAL AND METHODS: This is an observational study of patients hospitalized in Spain with a diagnosis of COPD included in the SEMI-COVID-19 registry. The medical history, symptoms, analytical and radiological results, treatment, and progress of patients with COPD hospitalized in the first wave (from March to June 2020) versus those hospitalized in the second wave (from July to December 2020) were compared. Factors associated with poor prognosis, defined as all-cause mortality and a composite endpoint that included mortality, high-flow oxygen therapy, mechanical ventilation, and ICU admission, were analyzed. RESULTS: Of the 21,642 patients in the SEMI-COVID-19 Registry, 6.9% were diagnosed with COPD: 1128 (6.8%) in WAVE1 and 374 (7.7%) in WAVE2 (p = 0.04). WAVE2 patients presented less dry cough, fever and dyspnea, hypoxemia (43% vs 36%, p < 0.05), and radiological condensation (46% vs 31%, p < 0.05) than WAVE1 patients. Mortality was lower in WAVE2 (35% vs 28.6%, p = 0.01). In the total sample, mortality and the composite outcome of poor prognosis were lower among patients who received inhalation therapy. CONCLUSIONS: Patients with COPD admitted to the hospital due to COVID-19 in the second wave had less respiratory failure and less radiological involvement as well as a better prognosis. These patients should receive bronchodilator treatment if there is no contraindication for it.

Effects of mesoporous SiO2-CaO nanospheres on the murine peritoneal macrophages/Candidaalbicans interface.

The use of nanoparticles for intracellular drug delivery could reduce the toxicity and side effects of the drug but, the uptake of these nanocarriers could induce adverse effects on cells and tissues after their incorporation. Macrophages play a central role in host defense and are responsible for in vivo nanoparticle trafficking. Assessment of their defense capacity against pathogenic micro-organisms after nanoparticle uptake, is necessary to prevent infections associated with nanoparticle therapies. In this study, the effects of hollow mesoporous SiO2-CaO nanospheres labeled with fluorescein isothiocyanate (FITC-NanoMBGs) on the function of peritoneal macrophages was assessed by measuring their ability to phagocytize Candidaalbicans expressing a red fluorescent protein. Two macrophage/fungus ratios (MOI1 and MOI5) were used and two experimental strategies were carried out: a) pretreatment of macrophages with FITC-NanoMBGs and subsequent fungal infection; b) competition assays after simultaneous addition of fungus and nanospheres. Macrophage pro-inflammatory phenotype markers (CD80 expression and interleukin 6 secretion) were also evaluated. Significant decreases of CD80+ macrophage percentage and interleukin 6 secretion were observed after 30 min, indicating that the simultaneous incorporation of NanoMBG and fungus favors the macrophage non-inflammatory phenotype. The present study evidences that the uptake of these nanospheres in all the studied conditions does not alter the macrophage function. Moreover, intracellular FITC-NanoMBGs induce a transitory increase of the fungal phagocytosis by macrophages at MOI 1 and after a short time of interaction. In the competition assays, as the intracellular fungus quantity increased, the intracellular FITC-NanoMBG content decreased in a MOI- and time-dependent manner. These results have confirmed that macrophages clearly distinguish between inert material and the live yeast in a dynamic intracellular incorporation. Furthermore, macrophage phagocytosis is a critical determinant to know their functional state and a valuable parameter to study the nanomaterial / macrophages / Candida albicans interface.

Clinical characteristics of patients hospitalized with COVID-19 in Spain: Results from the SEMI-COVID-19 Registry. / Características clínicas de los pacientes hospitalizados con COVID-19 en España: resultados del Registro SEMI-COVID-19.

BACKGROUND: Spain has been one of the countries most affected by the COVID-19 pandemic. OBJECTIVE: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. METHODS: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. RESULTS: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥80 years: 46.0%). CONCLUSIONS: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

[Clinical characteristics of patients hospitalized with COVID-19 in Spain: Results from the SEMI-COVID-19 Registry]. / Características clínicas de los pacientes hospitalizados con COVID-19 en España: resultados del Registro SEMI-COVID-19.

BACKGROUND: Spain has been one of the countries most affected by the COVID-19 pandemic. OBJECTIVE: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. METHODS: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. RESULTS: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥ 80 years: 46.0%). CONCLUSIONS: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

Prevalence of abdominal aortic aneurysm in patients with high cardiovascular risk. / Prevalencia de aneurisma de aorta abdominal en pacientes con alto riesgo cardiovascular.

BACKGROUND: To determine the prevalence of abdominal aortic aneurysm (AAA) (arterial diameter ≥30mm), in patients with high or very high cardiovascular risk (CVR) and to evaluate their clinical features. PATIENTS AND METHODS: Observational, cross-sectional and multicentric study conducted in Spanish Internal Medicine Services. We enrolled men with age >55years and women >65years who had a high or very high CVR. RESULTS: The study included 659 patients. The prevalence of AAA was 8% (53 patients). 76.9% were male with a mean age of 71±8.7years. The multivariate analysis showed an association between AAA and age (OR: 1.06; 95%CI: 1.02-1.1; P<.01), male sex (OR: 5.6; 95%CI: 1.6-18.8; P=.01), active smoking (OR: 3.22; 95%CI: 1.16-8.93; P=.024) and peripheral arterial disease (OR: 3.51; 95%CI: 1.73-7.09; P<.01). Diabetes mellitus was an independent protective factor (OR: 0.41; 95%CI: 0.22-0.78; P=.06). Those with subaneurysmal dilatation of the abdominal aorta (diameter 25-29.9mm) presented similar features as patients with AAA. CONCLUSIONS: The prevalence of AAA in patients with high CVR is high. Ultrasound screening can be performed by general practitioners. Men >65years with elevated CVR could benefit, particularly in the presence of active smoking or peripheral arterial disease.

Positioning document on incorporating point-of-care ultrasound in Internal Medicine departments. / Documento de posicionamiento sobre la incorporación de la ecografía clínica en los servicios de Medicina Interna.

This positioning document describes the most important aspects of clinical ultrasonography in the internal medicine setting, from its fundamental indications to the recommended training period. There is no question as to the considerable usefulness of this tool in the standard clinical practice of internists in numerous clinical scenarios and settings (emergencies, hospital ward, general and specific consultations and home care). Ultrasonography has a relevant impact on the practitioner's ability to resolve issues, increasing diagnostic reliability and safety and providing important information on the prognosis and progression. In recent years, ultrasonography has been incorporated as a tool in undergraduate teaching, with excellent results. The use of ultrasonography needs to be widespread. To accomplish this, we must encourage structured training and the acquisition of equipment. This document was developed by the Clinical Ultrasonography Workgroup and endorsed by the Spanish Society of Internal Medicine.

Differential effects of graphene oxide nanosheets on Candida albicans phagocytosis by murine peritoneal macrophages.

Macrophages, as effector cells involved in the innate and adaptive immunity, play a key role in the response to nanomaterials as graphene oxide (GO) and in their cellular uptake. The interactions at the interface of GO nanosheets, macrophages and microbial pathogens need to be assessed to determine the possible impairment of the immune system induced by biomedical treatments with this nanomaterial. Here, we have evaluated by flow cytometry and confocal microscopy the ability of murine peritoneal macrophages to phagocytose the fungal pathogen Candida albicans, alive or heat-killed, after treatment with poly(ethylene glycol-amine)-derivatized GO nanosheets (PEG-GO). After GO treatment, differences in fungal phagocytosis were observed between macrophages that had taken up GO nanosheets (GO+ population) and those that had not (GO- population). GO treatment increased the ingested alive yeasts in GO- macrophages, whereas phagocytosis diminished in the GO+ population. Ingestion of heat-killed yeasts was slightly higher in both GO- and GO+ populations when comparing with control macrophages. For the first time, we show that GO uptake by macrophages modulates its phagocytic capability, affecting differentially the subsequent ingestion of either alive or heat-killed yeasts. Enhanced ingestion of heat-killed yeast by GO-treated macrophages suggests a beneficial role of this nanomaterial for the clearance of dead microorganisms during infection.

ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis.

Class IA phosphoinositide 3-kinases (PI3Ks) are essential to function of normal and tumor cells, and to modulate immune responses. T lymphocytes express high levels of p110α and p110δ class IA PI3K. Whereas the functioning of PI3K p110δ in immune and autoimmune reactions is well established, the role of p110α is less well understood. Here, a novel dual p110α/δ inhibitor (ETP-46321) and highly specific p110α (A66) or p110δ (IC87114) inhibitors have been compared concerning T cell activation in vitro, as well as the effect on responses to protein antigen and collagen-induced arthritis in vivo. In vitro activation of naive CD4(+) T lymphocytes by anti-CD3 and anti-CD28 was inhibited more effectively by the p110δ inhibitor than by the p110α inhibitor as measured by cytokine secretion (IL-2, IL-10, and IFN-γ), T-bet expression and NFAT activation. In activated CD4(+) T cells re-stimulated through CD3 and ICOS, IC87114 inhibited Akt and Erk activation, and the secretion of IL-2, IL-4, IL-17A, and IFN-γ better than A66. The p110α/δ inhibitor ETP-46321, or p110α plus p110δ inhibitors also inhibited IL-21 secretion by differentiated CD4(+) T follicular (Tfh) or IL-17-producing (Th17) helper cells. In vivo, therapeutic administration of ETP-46321 significantly inhibited responses to protein antigen as well as collagen-induced arthritis, as measured by antigen-specific antibody responses, secretion of IL-10, IL-17A or IFN-γ, or clinical symptoms. Hence, p110α as well as p110δ Class IA PI3Ks are important to immune regulation; inhibition of both subunits may be an effective therapeutic approach in inflammatory autoimmune diseases like rheumatoid arthritis.

Effects of nanocrystalline hydroxyapatites on macrophage polarization.

Silicon substituted and nanocrystalline hydroxyapatites have attracted the attention of many researchers due to their up-regulation in osteoblast cell metabolism and enhanced bioreactivity, respectively. On the other hand, the biomaterial success or failure depends ultimately on the immune response triggered after its implantation. Macrophages are the main components of the innate immune system with an important role in healing and tissue remodelling due to their remarkable functional plasticity, existing in a whole spectrum of functional populations with varying phenotypic features. The effects of nanocrystalline hydroxyapatite (nano-HA) and nanocrystalline silicon substituted hydroxyapatite (nano-SiHA) on the macrophage populations defined as pro-inflammatory (M1) and reparative (M2) phenotypes have been evaluated in the present study using RAW 264.7 cells and mouse peritoneal macrophages as in vitro models. M1 and M2 macrophage phenotypes were characterized by flow cytometry and confocal microscopy by the expression of CD80 and CD163, known as M1 and M2 markers, respectively. The polarization of primary macrophages towards the M1 or M2 phenotype was induced with the pro-inflammatory stimulus LPS or the anti-inflammatory stimulus IL-10, respectively, evaluating the biomaterial effects under these conditions. Our results show that both nano-HA and nano-SiHA favour the macrophage polarization towards an M2 reparative phenotype, decreasing M1 population and ensuring an appropriate response in the implantation site of these biomaterials designed for bone repair and bone tissue engineering.

Formation of titanium monoxide (001) single-crystalline thin film induced by ion bombardment of titanium dioxide (110).

A plethora of technological applications justify why titanium dioxide is probably the most studied oxide, and an optimal exploitation of its properties quite frequently requires a controlled modification of the surface. Low-energy ion bombardment is one of the most extended techniques for this purpose and has been recently used in titanium oxides, among other applications, to favour resistive switching mechanisms or to form transparent conductive layers. Surfaces modified in this way are frequently described as reduced and defective, with a high density of oxygen vacancies. Here we show, at variance with this view, that high ion doses on rutile titanium dioxide (110) induce its transformation into a nanometric and single-crystalline titanium monoxide (001) thin film with rocksalt structure. The discovery of this ability may pave the way to new technical applications of ion bombardment not previously reported, which can be used to fabricate heterostructures and interfaces.

The burden of non-motor symptoms in Parkinson's disease using a self-completed non-motor questionnaire: a simple grading system.

BACKGROUND: Non-motor symptoms (NMS) of Parkinson's disease (PD) affect virtually every patient, yet they are under-recognized and under-treated. The NMS Questionnaire (NMSQuest) is a validated 30-item self-assessment instrument useful for NMS screening in clinic. OBJECTIVE: Development of a straight forward grading classification of the burden of non-motor symptoms in PD based on the number of NMS as assessed by the NMS Questionnaire. METHODS: In an observational, cross-sectional, international study of 383 consecutive patients distribution of the declared NMS as per NMSQuest was analyzed according to previously published levels based on the Non-Motor Symptoms Scale and also the median and interquartile range (IR, percentiles 25 and 75) of the total NMSQuest scores. After post hoc checking, these values were proposed as cut-off points for estimating NMS burden based only on the accumulation of symptoms. RESULTS: Burden and number of NMS correlate closely (r ≥ 0.80). On the basis of this finding, five levels (0 = No NMS to 4 = Very severe) of NMSQuest grading were proposed after identification of their cut-offs by ordinal logistic regression and median and interquartile range distribution. These values coincided almost completely with those obtained by median and interquartile range in an independent sample. Concordance between this classification and HY staging was weak (weighted kappa = 0.30), but was substantial (weighted kappa = 0.68) with the Non-Motor Symptoms Scale grading. CONCLUSION: Completion of NMSQuest and subsequent grading of the burden could allow the health care professional to approach the severity of NMS burden using the self completed NMSQuest in a primary care setting.

In vitro evaluation of graphene oxide nanosheets on immune function.

HYPOTHESIS: Graphene oxide (GO) has attracted the scientific community attention due to its novel properties and wide range of potential applications including hyperthermia cancer therapy. However, little is known about the GO effects on the immune function which involves both innate and adaptive defence mechanisms through the activation of different cell populations and secretion of several cytokines. The effect of different GO nanosheets designed for hyperthermia cancer therapy on macrophage and lymphocyte function should be determined before using GO for this application. EXPERIMENTS: The effects of GO nanosheets with 1 (1-GOs) and 6 arms (6-GOs) of polyethylene glycol on RAW-264.7 macrophages and primary splenocytes (as approximation to the in vivo situation) were evaluated through the proinflammatory cytokine secretion and the modulation of cell proliferation in the presence of specific stimuli for either T-lymphocytes (concanavalin A, anti-CD3 antibody) or B-lymphocytes/macrophages (lipopolysaccharide). FINDINGS: 6-GOs significantly increased the secretion of TNF-α by RAW-264.7 macrophages without alteration of IL-6 and IL-1ß levels. The treatment of primary splenocytes with 1-GOs and 6-GOs in the presence of concanavalin A, anti-CD3 antibody and lipopolysaccharide, produced significant dose-dependent decreases of cell proliferation and IL-6 levels, revealing weak inflammatory properties of GOs which are favourable for hyperthermia cancer therapy.

Ecografía clínica abdominal y educación médica / Abdominal ultrasound and medical education

Introducción. La ecografía es una técnica muy versátil, que permite en tiempo real visualizar múltiples órganos internos y es de inestimable ayuda para la exploración física de los pacientes. Objetivo. Evaluar si la ecografía puede incorporarse en la enseñanza de la medicina y si los alumnos pueden realizar una exploración ecográfica abdominal básica sin un largo periodo de formación. Metodología. Doce estudiantes de medicina recibieron formación en ecografía abdominal básica durante un programa formativo de 15h de duración, que incluía un curso teórico-práctico de 5h y prácticas supervisadas en 20 pacientes seleccionados. Posteriormente realizamos una prueba de evaluación objetiva en la que valoramos la capacidad de los alumnos para obtener los planos ecográficos y detectar diversas enfermedades en 5 pacientes distintos. Resultados. Los estudiantes fueron capaces de identificar correctamente los planos abdominales en más del 90% de las ocasiones. Solo en el corte subcostal derecho para localizar la vesícula este porcentaje fue inferior (80%). La precisión o eficiencia global de la ecografía para el diagnóstico de los hallazgos patológicos relevantes de los enfermos fue superior al 90% (colelitiasis 91,1%; aneurisma de aorta abdominal 100%; esplenomegalia 98,3%; ascitis 100%; vena cava inferior dilatada 100%, y retención aguda de orina 100%). Conclusión. La ecografía puede ser una herramienta formativa en la enseñanza de la medicina y puede ayudar a los alumnos a mejorar la exploración física (AU)

Introduction. Ultrasound is a very versatile diagnostic modality that permits real-time visualization of multiple internal organs. It is of invaluable help for the physical examination of the patients. Aim. To assess if ultrasound can be incorporated into medical education and if the students can perform a basic abdominal ultrasound examination without the necessity of a long period of training. Methodology. Twelve medical students were trained in basic abdominal ultrasound during a 15-hour training program including a 5-hour theoretical and practical course and supervised practice in 20 selected patients. Subsequently, we conducted an evaluation test that assessed the ability of students to obtain the ultrasound views and to detect various pathologies in five different patients. Results. The students were able to correctly identify the abdominal views more than 90% of the times. This percentage was only lower (80%) in the right subcostal view to locate the gallbladder. The accuracy or global efficiency of the ultrasound for the diagnosis of relevant pathological findings of the patients was greater than 90% (91.1% gallstones, abdominal aortic aneurysm 100%; splenomegaly 98.3%, ascites 100%; dilated inferior vena cava 100%; acute urinary retention 100%). Conclusion. The ultrasound may be a feasible learning tool in medical education. Ultrasound can help students to the improve the physical examination (AU)

Suppression of CD4+ T lymphocyte activation in vitro and experimental encephalomyelitis in vivo by the phosphatidyl inositol 3-kinase inhibitor PIK-75.

Class IA phosphatidyl inositol-3 kinases (PI3-K) are important targets in cancer therapy and are essential to immune responses, particularly through costimulation by CD28 and ICOS. Thus, small PI3-K inhibitors are likely candidates to immune intervention. PIK-75 is an efficient inhibitor of the PI3-K p110alpha catalytic subunits that suppresses tumor growth, and its effects on immune and autoimmune responses should be studied. Here, we describe the effect of PIK-75 on different immune parameters in vitro and in vivo. PIK-75 at concentrations commonly used in vitro (≥0.1 μM) inhibited T and B cell activation by Concanavalin A and LPS, respectively, and survival of non-stimulated spleen cells. In naive CD4+ T lymphocytes, PIK-75 induced apoptosis of resting or activated cells that was prevented by caspase inhibitors. At low nanomolar concentrations (≤10 nM), PIK-75 inhibited naive CD4+ T cell proliferation, and IL-2 and IFN-gamma production induced by anti-CD3 plus anti-CD28. In activated CD4+ T blasts costimulated by ICOS, PIK-75 (less than 10 nM) inhibited IFN-gamma, IL-17A, or IL-21 secretion. Furthermore, PIK-75 (20 mg/kg p.o.) suppressed clinical symptoms in ongoing experimental autoimmune encephalomyelitis (EAE) and inhibited MOG-specific responses in vitro. Thus, PIK-75 is an efficient suppressor of EAE, modulating lymphocyte function and survival.

Abdominal ultrasound and medical education.

INTRODUCTION: Ultrasound is a very versatile diagnostic modality that permits real-time visualization of multiple internal organs. It is of invaluable help for the physical examination of the patients. AIM: To assess if ultrasound can be incorporated into medical education and if the students can perform a basic abdominal ultrasound examination without the necessity of a long period of training. METHODOLOGY: Twelve medical students were trained in basic abdominal ultrasound during a 15-h training program including a 5-h theoretical and practical course and supervised practice in 20 selected patients. Subsequently, we conducted an evaluation test that assessed the ability of students to obtain the ultrasound views and to detect various pathologies in five different patients. RESULTS: The students were able to correctly identify the abdominal views more than 90% of the times. This percentage was only lower (80%) in the right subcostal view to locate the gallbladder. The accuracy or global efficiency of the ultrasound for the diagnosis of relevant pathological findings of the patients was greater than 90% (91.1% gallstones, abdominal aortic aneurysm 100%; splenomegaly 98.3%, ascites 100%; dilated inferior vena cava 100%; acute urinary retention 100%). CONCLUSION: The ultrasound may be a feasible learning tool in medical education. Ultrasound can help students to improve the physical examination.

Porphyromonas gingivalis mediates the shedding and proteolysis of complement regulatory protein CD46 expressed by oral epithelial cells.

INTRODUCTION: Human cells express membrane-bound complement regulatory proteins to prevent complement-mediated autologous tissue damage. In this study, we hypothesized that Porphyromonas gingivalis, the major etiological agent of chronic periodontitis, causes the shedding or proteolysis of the complement regulatory protein CD46 expressed by oral epithelial cells. METHODS: Oral epithelial cells were treated with a culture of P. gingivalis before measurement of membrane-bound and shed CD46 by enzyme-linked immunosorbent assay (ELISA). The effect of soluble recombinant CD46 on secretion of interleukin-8 (IL-8) by epithelial cells was evaluated by ELISA. The susceptibility of soluble recombinant CD46 to proteolytic degradation by cells and purified Lys-gingipain of P. gingivalis was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/western immunoblotting analysis. RESULTS: Oral epithelial cells treated with a culture of P. gingivalis showed a lower reactivity with antibodies directed to CD46. ELISA revealed that such a treatment resulted in increased amounts of CD46 in the conditioned media suggesting that P. gingivalis caused the shedding of membrane-anchored CD46. Stimulation of epithelial cells with soluble recombinant CD46 induced IL-8 secretion in a dose-dependent manner. Whole cells and purified Lys-gingipain of P. gingivalis degraded recombinant CD46 in a dose-dependent manner. CONCLUSION: This study showed the ability of P. gingivalis to induce the shedding/ proteolysis of CD46 from the surface of oral epithelial cells. This may render host cells susceptible to the complement system and contribute to tissue damage and the inflammatory process in periodontitis.

Plastic properties of gold surfaces nanopatterned by ion beam sputtering.

We review the mechanical properties of defective roughened surfaces with the major emphasis on nanoindentation work. We also report novel results in which force versus penetration curves and AFM images of the nanoindented surface are compared for a flat surface of Au(001) and an Ar(+) bombarded one, both with a high and a low flux of ions. We have found that bombarded surfaces yield at a lower stress than untreated flat ones. Surfaces bombarded at high flux show a large roughness and their yield point, marking the onset of surface plasticity, decreases with respect to that of the flat surface or of the surface bombarded with a low flux. The present results are compared with earlier work on nanoindented vicinal surfaces in which the sole surface modifications with respect to the flat surface were the presence of a high density of steps. It is concluded that a softening effect due to the bombardment-induced nanostructure of the surface dominates over the hardening one due to defect creation and interaction in the surface neighbourhood.