Orthopantomography Versus Cone Beam Computed Tomography for the Assessment of the Proximity of Posterior Maxillary Apexes with the Maxillary Sinus: A Cross-sectional Study.

BACKGROUND: The lack of knowledge of the relation of the maxillary sinus with the apexes of maxillary posterior teeth can lead to important complications during common dental procedures. This can be avoided using different imaging techniques, such as orthopantomography (OPG) and cone beam computed tomography (CBCT). The present study aims to compare the performance of OPG with CBCT in measuring the vertical distance of the apexes of posterior-superior teeth to the maxillary sinus. METHODS: This study corresponded to a cross-sectional study. OPGs and CBCT scans were obtained from the same individuals, and the qualitative and quantitative vertical distance of the apexes in relation to the maxillary sinus was categorized and measured in mm. RESULTS: A total of 28 pairs of OPGs and CBCT scans from the same patients were obtained. About 381 roots were analysed, which included 89 upper first premolars, 51 upper second premolars, 115 upper first molars, and 126 upper second molars. Projection/protrusion was observed with more frequency in molars, specially 1º molars in both OPG (n= 75, 65.2%) and CBCT (n= 31, 27%); however, 106 more cases (27.9%) were classified as projected in the OPG compared to CBCT (p < 0.05). When comparing the performance of the OPG and CBTC for analysing all roots qualitatively, there was a 57.8% agreement between both techniques. This difference was statistically significant (p <0.0001). Statistically significant differences were also observed when comparing the millimetric differences. CONCLUSION: This study showed that OPG is not an accurate technique to observe the relationship between the maxillary sinus and the apexes of the upper posterior teeth. In those cases where precision is required when performing dental procedures in this area, CBCT should be used. When not available, the clinicians should be aware of the limitations of the OPG and add other complementary techniques.

Anatomical variations and abnormalities of the maxillary region and clinical implications: A systematic review and metaanalysis.

OBJECTIVE: The objective of this review is to investigate and analyze the anatomical variations present in the maxillary sinus (MS), through the examination of the prevalence of these variations, as well as the corresponding prevalence of clinically significant pathologies and complications associated with them. METHODS: The search process was carried out in the following databases; MEDLINE, SCIELO, WOS, CINHAL, SCOPUS, and GOOGLE SCHOLAR, using as search terms; "Maxillary bone," "Maxillary sinus," "Paranasal sinus," "Anatomical variations," "Sinusitis" and "Clinical anatomy." RESULTS: A total of 26 articles and 12969 samples were included, from which 12,594 subjects had their sex recorded giving a total of 5802 males and 6792 females. The variants reported by the included were Haller cells, Concha Bullosa, Number of septa, Hypoplastic sinus, Agger Nasi, Thickening of the MS mucosa, Deviation of the nasal septum, Accessory ostium, and Onodi cells. Among the mentioned, the ones that presented the greatest number of studies (between 8 and 10 studies included) were: the Haller Cells, the Concha Bullosa, and the Number of septa, where prevalence was 0.30, 0.36, 0.39 respectively. These variations can lead to sinusitis, cause some types of tumors, or affect neighboring structures that could be compromised by this variation. CONCLUSION: As a result, it is certainly complex to distinguish the presence of anatomical variations from pathological abnormalities. Therefore, knowledge of the different variations and their clinical relationships could be a useful asset for clinicians dedicated to this region.

Análisis de las Variaciones Anatómicas y Dimensionales del Canal Nasopalatino Mediante Tomografía Computarizada de Haz Cónico / Analysis of the Anatomical and Dimensional Variations of the Nasopalatine Canal by Cone Beam Computed Tomography

El conocimiento anatómico del canal nasopalatino (CNP) es fundamental para la realización de cirugías en el sector anterior del maxilar y así prever posibles complicaciones. El objetivo de este trabajo es evaluar y determinar las variaciones anatómicas y dimensionales del CNP según sexo, edad y estado dental. Este estudio transversal analizó un total de 251 imágenes de TCHC obtenidas de la base de datos del Servicio de Imagenología Oral y Maxilofacial de la Facultad de Odontología de la Universidad Andrés Bello, Viña del Mar, Chile. Para evaluar la asociación estadística entre variaciones del CNP con sexo, edad y estado dentario se realizó la prueba T de Student, chi-cuadrado y ANOVA (p0,05). Además, se detectó diferencia significativa entre el estado dentario y la dimensión de la tabla vestibular en relación con el CNP (p<0,01). Se deben considerar las variaciones de CNP para evitar posibles complicaciones durante los procedimientos quirúrgicos.

SUMMARY: Anatomical knowledge of the nasopalatine canal (PNC) is essential for performing surgeries in the anterior sector of the maxilla and thus anticipating possible complications. The objective of this work is to evaluate and determine the anatomical and dimensional variations of the CNP according to sex, age and dental status. This cross-sectional study analyzed a total of 251 CBCT images obtained from the database of the Oral and Maxillofacial Imaging Service of the Faculty of Dentistry of the Andrés Bello University, Viña del Mar, Chile. To evaluate the statistical association between CNP variations with sex, age and dental status, the Student's T test, chi-square and ANOVA (p0.05). In addition, a significant difference was detected between the dental state and the dimension of the vestibular table in relation to the CNP (p<0.01). CNP variations should be considered to avoid potential complications during surgical procedures.

On-Line Evaluation and Monitoring of Security Features of an RO-Based PUF/TRNG for IoT Devices.

The proliferation of devices for the Internet of Things (IoT) and their implication in many activities of our lives have led to a considerable increase in concern about the security of these devices, posing a double challenge for designers and developers of products. On the one hand, the design of new security primitives, suitable for resource-limited devices, can facilitate the inclusion of mechanisms and protocols to ensure the integrity and privacy of the data exchanged over the Internet. On the other hand, the development of techniques and tools to evaluate the quality of the proposed solutions as a step prior to their deployment, as well as to monitor their behavior once in operation against possible changes in operating conditions arising naturally or as a consequence of a stress situation forced by an attacker. To address these challenges, this paper first describes the design of a security primitive that plays an important role as a component of a hardware-based root of trust, as it can act as a source of entropy for True Random Number Generation (TRNG) or as a Physical Unclonable Function (PUF) to facilitate the generation of identifiers linked to the device on which it is implemented. The work also illustrates different software components that allow carrying out a self-assessment strategy to characterize and validate the performance of this primitive in its dual functionality, as well as to monitor possible changes in security levels that may occur during operation as a result of device aging and variations in power supply or operating temperature. The designed PUF/TRNG is provided as a configurable IP module, which takes advantage of the internal architecture of the Xilinx Series-7 and Zynq-7000 programmable devices and incorporates an AXI4-based standard interface to facilitate its interaction with soft- and hard-core processing systems. Several test systems that contain different instances of the IP have been implemented and subjected to an exhaustive set of on-line tests to obtain the metrics that determine its quality in terms of uniqueness, reliability, and entropy characteristics. The results obtained prove that the proposed module is a suitable candidate for various security applications. As an example, an implementation that uses less than 5% of the resources of a low-cost programmable device is capable of obfuscating and recovering 512-bit cryptographic keys with virtually zero error rate.

Relación entre el seno maxilar y ápices de dientes postero- superiores con tomografía computarizada de haz cónico / Relationship between the maxillary sinus and apices of posterior-superior teeth using cone beam computed tomography

El conocimiento de la relación entre el seno maxilar y los ápices de los dientes posterosuperiores es fundamental para evitar complicaciones frente a distintos tratamientos. Estudio descriptivo de corte transversal, con muestra por conveniencia de 383 imágenes de raíces de dientes posterosuperiores obtenidas por medio de tomografía computarizada de haz cónico (TCHC) de un centro radiológico en Viña del Mar, Chile. Cada raíz fue clasificada según su relación vertical con el seno en 4 categorías (0: ápice no se encuentra en contacto con contorno inferior del seno; 1: ápice en contacto con seno; 2: ápice lateralmente al seno; 3: ápice se protruye en seno). Además se midió su distancia en mm. Los datos fueron analizados con estadística descriptivas. El diente más lejano al seno maxilar fue el primer premolar superior (4.2 mm), seguido por el segundo premolar superior (1 mm). En el primer molar superior la raíz más lejana fue la mesio-vestibular (MV) 1mm, seguida por la raíz disto-vestibular (DV) 0.6mm y la raíz palatina (P) -1mm. En el segundo molar superior la raíz más lejana fue P 0.4mm, luego la DV 0.3mm, y MV -0,11mm. En cuanto a las categorías, se observó que la mayoría de las raíces se encuentran alejadas del seno siendo la raíz P del primer molar superior y la raíz MV del segundo molar superior las que se encuentran mayormente protruidas (42 % y 26 % respectivamente). El primer premolar es el diente posterosuperior que se encuentra más alejado del seno maxilar y a medida que se avanza hacia posterior hay tendencia a disminuir la distancia entre los ápices y el seno maxilar.

SUMMARY: Knowledge of the relationship between the maxillary sinus and the apices of the upper posterior teeth is crucial to avoid complications when considering different treatments. A descriptive cross-sectional study was carried out, with a convenience sample of 383 images of upper posterior teeth roots, obtained by means of cone beam computed tomography (CBCT) from a radiological center in Viña del Mar, Chile. Each root was classified according to its vertical relationship with the sinus into 4 categories (0: apex is not in contact with the lower contour of the sinus; 1: apex is in contact with the sinus; 2: apex laterally to the sinus; 3: apex protrudes in sinus). In addition, its distance was measured in mm. The data were analyzed with descriptive statistics. The tooth farthest from the maxillary sinus was the maxillary first premolar (4.2 mm), followed by the maxillary second premolar (1 mm). In the upper first molar, the most distant root was the mesiobuccal (MV) 1mm, followed by the distobuccal root (DV) 0.6mm and the palatal root (P) -1mm. In the upper second molar, the furthest root was P 0.4mm, then DV 0.3mm, and MV -0.11mm. In reference to the categories, it was observed that most of the roots are far from the sinus, with the P root of the first upper molar and the MV root of the second upper molar being the most protruding (42 % and 26 % respectively). The first premolar is the posterior maxillary tooth that is furthest from the maxillary sinus and as one advances posteriorly there is a tendency to decrease the distance between the apices and the maxillary sinus.

Treatment With Adalimumab 80 mg Every Other Week in Inflammatory Bowel Disease: Results of Treatment Intensification in Clinical Practice.

Background: Loss of response to anti-tumor necrosis factor drugs in patients with inflammatory bowel disease (IBD) is frequent and, in case of low drug levels, treatment intensification is recommended. In addition, in cases in which clinical response without attainment of remission (clinical, endoscopic, or radiological), intensification could be justified since higher drug levels are associated with better outcomes. For adalimumab (ADA), the standard intensification regimen is 40 mg every week (ew). Availability of ADA 80 mg prefilled pens has enabled every other week (eow) intensification. We assessed the clinical efficacy of intensification with ADA 80 mg eow. Methods: This retrospective study was conducted at a tertiary hospital in Spain. Patients with IBD receiving maintenance ADA 80 mg eow with clinical, biomarker, and drug-level assessments were included. Demographics and clinical, biological, and endoscopic evaluation of the disease before and after ADA intensification, and pharmacokinetic assessments, were collected. Results: Eighty-seven patients (72 Crohn's disease, 15 ulcerative colitis; average age 50 years) were included. Reasons for ADA intensification were: low ADA levels-<5 µg mL-1-(17%), low ADA levels-<5 µg mL-1-without clinical response (63%), clinical response without clinical remission (15%) and active disease on objective evaluation (including colonoscopy, magnetic resonance imaging, capsule endoscopy, and/or intestinal ultrasound; 5%). Following treatment intensification to ADA 80 mg eow, 75 patients (86%) were in clinical remission and 69 (79.3%) were in biologic remission (clinical remission and normalization of biomarkers). After a median follow-up of 19 months (interquartile range 13-25), 63 patients (72%) remained on treatment and in clinical remission. There were no serious infections, hospitalizations, or deaths. Drug costs did not increase with the 80 mg eow regimen versus a standard intensification regimen. Conclusions: ADA intensification to 80 mg eow was safe, effective, and did not increase drug costs versus standard intensification to 40 mg ew in our experience.

Treatment alternatives for dry mouth: A scoping review.

Background: Saliva is a biological fluid essential for the maintenance of a proper oral health. Its absence predisposes to differences pathologies, including dental caries, fungal infections among many others, significantly affecting the oral health related quality of life (OHRQoL). There is a large variety of treatment alternatives available for dry mouth, which increases constantly. Objective: To identify new treatment alternatives for dry mouth. Material and Methods: We conducted a systematic search in PubMed/MEDLINE, Web of Science, Scopus and Ebsco. Articles published between January 2015 and January 2020 were retrieved and reviewed by two independent evaluators. Results: Nineteen studies met the inclusion criteria and were included for analysis. Local therapies were the most evaluated agents, followed by systemic and non-conventional treatments. Most local therapies showed certain utility for the management of dry mouth and the improvement of OHRQoL. These formulations were mainly based on natural agents, including malic acid, thyme honey, ginger, among others. Conclusions: Local agents are first line treatment alternatives for dry mouth sensation, with a reported efficiency that varies between studies, and with a low number of reported adverse side-effects. Nevertheless, care must be taken when interpreting these results, as is difficult to compare studies within each other due large heterogeneity in study design and outcomes being measured. Key words:Xerostomia, dry mouth, hyposalivation, saliva, mouth dryness.

Multi-Unit Serial Polynomial Multiplier to Accelerate NTRU-Based Cryptographic Schemes in IoT Embedded Systems.

Concern for the security of embedded systems that implement IoT devices has become a crucial issue, as these devices today support an increasing number of applications and services that store and exchange information whose integrity, privacy, and authenticity must be adequately guaranteed. Modern lattice-based cryptographic schemes have proven to be a good alternative, both to face the security threats that arise as a consequence of the development of quantum computing and to allow efficient implementations of cryptographic primitives in resource-limited embedded systems, such as those used in consumer and industrial applications of the IoT. This article describes the hardware implementation of parameterized multi-unit serial polynomial multipliers to speed up time-consuming operations in NTRU-based cryptographic schemes. The flexibility in selecting the design parameters and the interconnection protocol with a general-purpose processor allow them to be applied both to the standardized variants of NTRU and to the new proposals that are being considered in the post-quantum contest currently held by the National Institute of Standards and Technology, as well as to obtain an adequate cost/performance/security-level trade-off for a target application. The designs are provided as AXI4 bus-compliant intellectual property modules that can be easily incorporated into embedded systems developed with the Vivado design tools. The work provides an extensive set of implementation and characterization results in devices of the Xilinx Zynq-7000 and Zynq UltraScale+ families for the different sets of parameters defined in the NTRUEncrypt standard. It also includes details of their plug and play inclusion as hardware accelerators in the C implementation of this public-key encryption scheme codified in the LibNTRU library, showing that acceleration factors of up to 3.1 are achieved when compared to pure software implementations running on the processing systems included in the programmable devices.

Repeated Pulses of Methyl-Prednisolone in Adults Hospitalized With COVID-19 Pneumonia and Acute Respiratory Distress Syndrome: A Preliminary Before-After Study (CortiCOVID Study).

Introduction: The use of systemic corticosteroids in severely ill patients with coronavirus disease 2019 (COVID-19) is controversial. We aimed to evaluate the efficacy and safety of corticosteroid pulses in patients with COVID-19 pneumonia. Methods: A quasi-experimental study, before and after, was performed in a tertiary referral hospital, including admitted patients showing COVID-19-associated pneumonia. The standard treatment protocol included targeted COVID-19 antiviral therapy from 23rd March 2020, and additionally pulses of methylprednisolone from 30th March 2020. The primary outcome was a composite endpoint combining oro-tracheal intubation (OTI) and death within 7 days. Results: A total of 24 patients were included. Standard of care (SOC) (before intervention) was prescribed in 14 patients, while 10 received SOC plus pulses of methylprednisolone (after intervention). The median age of patients was 64.5 years and 83.3% of the patients were men. The primary composite endpoint occurred in 13 patients (92.9%) who received SOC vs. 2 patients (20%) that received pulses of methylprednisolone (odds ratio, 0.02; 95% confidence interval, 0.001 to 0.25; p = 0.019). Length of hospitalization in survivors was shorter in the corticosteroids group (median, 14.5 [8.5-21.8] days vs. 29 [23-31] days, p = 0.003). There were no differences in the development of infections between both groups. There were 3 deaths, none of them in the corticosteroids group. Conclusions: In patients with severe pneumonia due to COVID-19, the administration of methylprednisolone pulses was associated with a lower rate of OTI and/or death and a shorter hospitalization episode.

Introducción: El uso de corticosteroides sistémicos en pacientes gravemente enfermos por enfermedad coronavírica de 2019 (covid-19) es controvertido. Nuestro objetivo fue evaluar la eficacia y la seguridad de los pulsos de corticoesteroides en los pacientes con neumonía por covid-19. Métodos: Se realizó un ensayo cuasiexperimental, tipo antes y después, en un hospital terciario de referencia que incluyó a pacientes ingresados por neumonía asociada a covid-19. El protocolo de tratamiento estándar incluía un tratamiento antiviral dirigido contra el virus de la covid-19 desde el 23 de marzo de 2020 y añadió pulsos de metilprednisolona desde el 30 de marzo de 2020. El resultado primario fue un criterio combinado compuesto por la intubación orotraqueal y el fallecimiento durante los siguientes siete días. Resultados: Se incluyó un total de 24 pacientes. El protocolo de tratamiento (antes de la intervención) se prescribió en 14 pacientes, mientras que 10 recibieron el protocolo de tratamiento además de los pulsos de metilprednisolona (después de la intervención). La edad media de los pacientes fue de 64,5 años y el 83,3% de los pacientes eran hombres. El resultado combinado primario tuvo lugar en 13 pacientes (92,9%) que recibieron el protocolo de tratamiento frente a 2 pacientes (20%) que recibieron los pulsos de metilprednisolona (odds ratio = 0,02; intervalo de confianza del 95% = 0,001-0,25; p = 0,019). La duración de la hospitalización en los supervivientes fue más corta en el grupo que recibió corticoesteroides (media = 14,5 [8,5-21,8] días frente a 29 [23-31] días, p = 0,003). No hubo diferencias en el desarrollo de infecciones entre ambos grupos. Hubo tres fallecimientos, ninguno de ellos en el grupo que recibió corticoesteroides. Conclusiones: En los pacientes con neumonía grave por covid-19, la administración de pulsos de metilprednisolona se asoció a unas tasas menores de intubación orotraqueal y/o muerte y a episodios de hospitalización más cortos.

Análisis de las características de los pacientes con necesidades paliativas en un servicio de medicina interna / Analysis of the characteristics of patients with palliative needs in an internal medicine service

OBJETIVOS: Analizar la prevalencia de pacientes con necesidad de cuidados paliativos (NCP) en pacientes fallecidos en un servicio de medicina interna (MI), así como las diferencias en la asistencia médica recibida en las últimas 48 h de vida en función de la identificación de situación de "asistencia paliativa" en la historia clínica. MATERIAL Y MÉTODOS: Para el primer objetivo se realizó un estudio observacional, transversal y retrospectivo, incluyendo a todos los pacientes que fallecieron en MI del Hospital Vega Baja entre enero y junio 2017. Se consideró que los pacientes tenían NCP si presentaban un NECPAL CCOMS-ICO(c) positivo y una puntuación en índice PALIAR > 7,5 al ingreso. Entre los pacientes con NCP se realizó un estudio de casos-controles en función de su identificación o no en la historia clínica mediante el código diagnóstico "asistencia paliativa". Se analizaron diferencias relacionadas con la asistencia clínica en las últimas 48 h entre ambos grupos. RESULTADOS: Hubo 120 fallecimientos durante el periodo de estudio, lo que supuso un 12 % de los ingresos en MI. De estos, 98 (82 %) presentaban NCP al ingreso. Predominó la trayectoria de "fragilidad" al final de la vida (43,8 %). Los pacientes del grupo de "asistencia paliativa" fueron expuestos en menor proporción a administración de fluidoterapia intensiva (un 36 % frente a un 93,6 %; p < 0,01), antibioticoterapia intravenosa (un 32 % frente a un 93,6 %; p < 0,01), utilización de ventilación mecánica no invasiva (un 2 % frente a un 17 %, p < 0,01), extracciones analíticas (un 24 % frente a un 100 %, p < 0,01). En este grupo de pacientes se administró en una mayor proporción sedación paliativa en las últimas 48 horas (un 90 % frente a un 29,7 %; p < 0,01). CONCLUSIONES: Una elevada proporción de los pacientes que fallecen en los servicios de MI cumplen criterios de NCP desde el ingreso. La no identificación en la historia clínica se ha asociado a mayor número de maniobras diagnóstico-terapéuticas invasivas y menos utilización de sedación paliativa

OBJECTIVES: To analyse the prevalence of patients in need of palliative care (NPC) among people deceased in an Internal Medicine (IM) service, as well as the diferences in medical care received within the last 48 hours depending on wether the need of palliative care is identified in the medical history or not. MATERIAL AND METHODS: An observational, cross-sectional and retrospective study was conducted for the first objective, including all deceased patients in the hospital Vega Baja IM service between January and June 2017. A NECPAL CCOMS-ICO affirmative response and a score in PALIAR Index greater than 7.5 were considered as need of palliative care. A case-control study was subsequently conducted among the patients in NPC, based on the identification or not of a need of palliative care diagnosis in the medical history. The differences in clinical care over the last 48 hours were analysed between both groups. RESULTS: There were 120 deceases during the study period, which represented 12 % of IM service admissions; 98 of these (82 %) presented with NPC on the day of admission. The end-of-life trajectory "frailty" was predominant (43.8 %). The group of patients identified as in NPC were exposed to a lesser extent to intensive fluid therapy (36 % vs 93 %; p < 0.01), endovenous antibiotic therapy (32 % vs 93.6 %; p < 0.01), use of noninvasive mechanical ventilation (2 % vs 17 %, p < 0.01), and blood tests (24 % vs 100 %, p < 0.01). Moreover, this group was offered palliative sedation in a greater proportion (90% vs 29.7 %; p < 0.01). CONCLUSIONS: A high proportion of deceased patients in IM services meet NPC criteria since admission. Failure to identifiy this in the medical history is associated with a greater number of invasive diagnostic and terapeutic maneuvers, and less use of palliative sedation

Una puntuación de riesgo genético predice recurrencias en pacientes jóvenes con infarto agudo de miocardio / A genetic risk score predicts recurrent events after myocardial infarction in young adults

INTRODUCCIÓN Y OBJETIVOS: Evaluar si una puntuación de riesgo genético (GRS) mejora la predicción de eventos recurrentes en pacientes jóvenes con infarto agudo de miocardio (IAM) e identifica una forma de aterosclerosis más agresiva. MÉTODOS: Se diseñó un estudio prospectivo con pacientes <55 años, no diabéticos, ingresados por IAM. Se realizó un test genético, una tomografía computarizada cardiaca y determinación de varios biomarcadores. Se analizó la asociación de un GRS compuesto por 11 variantes genéticas con la aparición de un objetivo primario combinado (muerte cardiovascular, evento recurrente u hospitalización cardiovascular). RESULTADOS: Se siguió a 81 pacientes durante una mediana de 4,1 años, y se documentaron 24 eventos. La prevalencia de variantes de riesgo fue superior en 9 de los 11 alelos frente a población general. El GRS se asoció con recurrencias, particularmente cuando los niveles basales de colesterol-LDL estaban elevados. En el modelo multivariado, teniendo como referencia el tercil de bajo riesgo genético, el HR para el grupo de riesgo intermedio fue de 10,2 (IC95% 1,1-100,3; p = 0,04) y de alto riesgo 20,7 (2,4-181,0; p = 0,006) si el colesterol-LDL era≥2,8 mmol/l (≥ 110mg/dl). La incorporación del GRS al modelo multivariado mejoró el estadístico C (ΔC-statistic=0,086), el cNRI (30%) y el IDI (0,05). El TC cardiaco detectó ateromatosis calcificada frecuentemente, pero tuvo un valor pronóstico limitado. No se detectó una asociación entre metaloproteinasas, GRS y recurrencias. CONCLUSIONES: En una población de pacientes jóvenes no diabéticos con IAM, una puntuación de riesgo genético puede predecir recurrencias y mejorar los modelos clínicos de estratificación pronóstica, especialmente en aquellos pacientes con colesterol-LDL basal elevado

INTRODUCTION AND OBJECTIVES: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis. METHODS: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization). RESULTS: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8 mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences. CONCLUSIONS: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels

A genetic risk score predicts recurrent events after myocardial infarction in young adults.

INTRODUCTION AND OBJECTIVES: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis. METHODS: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization). RESULTS: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences. CONCLUSIONS: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels.

Risk factors for pleural effusion recurrence in patients with malignancy.

BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model. RESULTS: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.

VLSI Design of Trusted Virtual Sensors.

This work presents a Very Large Scale Integration (VLSI) design of trusted virtual sensors providing a minimum unitary cost and very good figures of size, speed and power consumption. The sensed variable is estimated by a virtual sensor based on a configurable and programmable PieceWise-Affine hyper-Rectangular (PWAR) model. An algorithm is presented to find the best values of the programmable parameters given a set of (empirical or simulated) input-output data. The VLSI design of the trusted virtual sensor uses the fast authenticated encryption algorithm, AEGIS, to ensure the integrity of the provided virtual measurement and to encrypt it, and a Physical Unclonable Function (PUF) based on a Static Random Access Memory (SRAM) to ensure the integrity of the sensor itself. Implementation results of a prototype designed in a 90-nm Complementary Metal Oxide Semiconductor (CMOS) technology show that the active silicon area of the trusted virtual sensor is 0.86 mm 2 and its power consumption when trusted sensing at 50 MHz is 7.12 mW. The maximum operation frequency is 85 MHz, which allows response times lower than 0.25 µ s. As application example, the designed prototype was programmed to estimate the yaw rate in a vehicle, obtaining root mean square errors lower than 1.1%. Experimental results of the employed PUF show the robustness of the trusted sensing against aging and variations of the operation conditions, namely, temperature and power supply voltage (final value as well as ramp-up time).

Pleural Touch Preparations and Direct Visualization of the Pleura during Medical Thoracoscopy for the Diagnosis of Malignancy.

RATIONALE: During diagnostic thoracoscopy, talc pleurodesis after biopsy is appropriate if the probability of malignancy is sufficiently high. Findings on direct visual assessment of the pleura during thoracoscopy, rapid onsite evaluation (ROSE) of touch preparations (touch preps) of thoracoscopic biopsy specimens, and preoperative imaging may help predict the likelihood of malignancy; however, data on the performance of these methods are limited. OBJECTIVES: To assess the performance of ROSE of touch preps, direct visual assessment of the pleura during thoracoscopy, and preoperative imaging in diagnosing malignancy. METHODS: Patients who underwent ROSE of touch preps during thoracoscopy for suspected malignancy were retrospectively reviewed. Malignancy was diagnosed on the basis of final pathologic examination of pleural biopsy specimens. ROSE results were categorized as malignant, benign, or atypical cells. Visual assessment results were categorized as tumor studding present or absent. Positron emission tomography (PET) and computed tomography (CT) findings were categorized as abnormal or normal pleura. Likelihood ratios were calculated for each category of test result. RESULTS: The study included 44 patients, 26 (59%) with a final pathologic diagnosis of malignancy. Likelihood ratios were as follows: for ROSE of touch preps: malignant, 1.97 (95% confidence interval [CI], 0.90-4.34); atypical cells, 0.69 (95% CI, 0.21-2.27); benign, 0.11 (95% CI, 0.01-0.93); for direct visual assessment: tumor studding present, 3.63 (95% CI, 1.32-9.99); tumor studding absent, 0.24 (95% CI, 0.09-0.64); for PET: abnormal pleura, 9.39 (95% CI, 1.42-62); normal pleura, 0.24 (95% CI, 0.11-0.52); and for CT: abnormal pleura, 13.15 (95% CI, 1.93-89.63); normal pleura, 0.28 (95% CI, 0.15-0.54). CONCLUSIONS: A finding of no malignant cells on ROSE of touch preps during thoracoscopy lowers the likelihood of malignancy significantly, whereas finding of tumor studding on direct visual assessment during thoracoscopy only moderately increases the likelihood of malignancy. A positive finding on PET and/or CT increases the likelihood of malignancy significantly in a moderate-risk patient group and can be used as an adjunct to predict malignancy before pleurodesis.

HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p.

Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFß, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1ß, TNF-α, MCP-1 and VCAM-1, through NFkB activity. In addition, HIF-1α inhibition induced proximal tubule cells proliferation but it did not induce compensatory apoptosis, both in vivo. In vitro, HIF-1α knockdown in HK2 cells subjected to hypoxia/reoxygenation (H/R) promote cell entry into S phase, correlating with in vivo data. HIF-1α interference leads to downregulation of miR-127-3p and induction of its target gene Bcl6 in vivo. Moreover, modulation of miR-127-3p in HK2 cells subjected to H/R results in EMT regulation: miR127-3p inhibition promote loss of e-cadherin and induction of α-SMA and collagen I. In conclusion, HIF-1α induction during reperfusion is a protector mechanism implicated in a normal renal tissue repair after I/R.

MRI fused with prone FDG PET/CT improves the primary tumour staging of patients with breast cancer.

OBJECTIVE: Our aim was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in primary tumour staging of patients with breast cancer. METHODS: This retrospective study evaluated 45 women with 49 pathologically proven breast carcinomas. MRI and prone PET-CT scans with time-of-flight and point-spread-function reconstruction were performed with the same dedicated breast coil. The studies were assessed by a radiologist and a nuclear medicine physician, and evaluation of fused images was made by consensus. The final diagnosis was based on pathology (90 lesions) or follow-up ≥ 24 months (17 lesions). RESULTS: The study assessed 72 malignant and 35 benign lesions with a median size of 1.8 cm (range 0.3-8.4 cm): 31 focal, nine multifocal and nine multicentric cases. In lesion-by-lesion analysis, sensitivity, specificity, positive and negative predictive values were 97%, 80%, 91% and 93% for MRI, 96%, 71%, 87%, and 89% for prone PET, and 97%. 94%, 97% and 94% for MRI fused with PET. Areas under the curve (AUC) were 0.953, 0.850, and 0.983, respectively (p < 0.01). CONCLUSIONS: MRI fused with FDG-PET is more accurate than FDG-PET in primary tumour staging of breast cancer patients and increases the specificity of MRI. KEY POINTS: • FDG PET-CT may improve the specificity of MRI in breast cancer staging. • MRI fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose PET-CT has better overall diagnostic performance than MRI. • The clinical role of fused PET-MRI has not yet been established.

Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells.

Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

Factors related to increased resting energy expenditure in men with liver cirrhosis.

OBJECTIVE: Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. PATIENTS AND METHODS: We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. RESULTS: REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, ß-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P<0.05), nonprotein respiratory quotient (P<0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P<0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA-IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. CONCLUSION: Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice.