Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior.

BACKGROUND: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. METHODS: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. RESULTS: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. CONCLUSIONS: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.

Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells.

We previously described the role of low-density lipoprotein (LDL) in aggressiveness in papillary thyroid cancer (PTC). Moreover, the MAPK signaling pathway in the presence of BRAF V600E mutation is associated with more aggressive PTC. Although the link between MAPK cascade and LDL receptor (LDLR) expression has been previously described, it is unknown whether LDL can potentiate the adverse effects of PTC through it. We aimed to investigate whether the presence of LDL might accelerate the oncogenic processes through MAPK pathway in presence or absence of BRAF V600E in two thyroid cell lines: TPC1 and BCPAP (wild-type and BRAF V600E, respectively). LDLR, PI3K-AKT and RAS/RAF/MAPK (MEK)/ERK were analyzed via Western blot; cell proliferation was measured via MTT assay, cell migration was studied through wound-healing assay and LDL uptake was analyzed by fluorometric and confocal analysis. TPC1 demonstrated a time-specific downregulation of the LDLR, while BCPAP resulted in a receptor deregulation after LDL exposition. LDL uptake was increased in BCPAP over-time, as well as cell proliferation (20% higher) in comparison to TPC1. Both cell lines differed in migration pattern with a wound closure of 83.5 ± 9.7% after LDL coculture in TPC1, while a loss in the adhesion capacity was detected in BCPAP. The siRNA knockdown of LDLR in LDL-treated BCPAP cells resulted in a p-ERK expression downregulation and cell proliferation modulation, demonstrating a link between LDLR and MAPK pathway. The modulation of BRAF-V600E using vemurafenib-impaired LDLR expression decreased cellular proliferation. Our results suggest that LDLR regulation is cell line-specific, regulating the RAS/RAF/MAPK (MEK)/ERK pathway in the LDL-signaling cascade and where BRAF V600E can play a critical role. In conclusion, targeting LDLR and this downstream signaling cascade, could be a new therapeutic strategy for PTC with more aggressive behavior, especially in those harboring BRAF V600E.

Chitosan-Silica Hybrid Biomaterials for Bone Tissue Engineering: A Comparative Study of Xerogels and Aerogels.

Chitosan (CS) is a natural biopolymer that shows promise as a biomaterial for bone-tissue regeneration. However, because of their limited ability to induce cell differentiation and high degradation rate, among other drawbacks associated with its use, the creation of CS-based biomaterials remains a problem in bone tissue engineering research. Here we aimed to reduce these disadvantages while retaining the benefits of potential CS biomaterial by combining it with silica to provide sufficient additional structural support for bone regeneration. In this work, CS-silica xerogel and aerogel hybrids with 8 wt.% CS content, designated SCS8X and SCS8A, respectively, were prepared by sol-gel method, either by direct solvent evaporation at the atmospheric pressure or by supercritical drying in CO2, respectively. As reported in previous studies, it was confirmed that both types of mesoporous materials exhibited large surface areas (821 m2g-1-858 m2g-1) and outstanding bioactivity, as well as osteoconductive properties. In addition to silica and chitosan, the inclusion of 10 wt.% of tricalcium phosphate (TCP), designated SCS8T10X, was also considered, which stimulates a fast bioactive response of the xerogel surface. The results here obtained also demonstrate that xerogels induced earlier cell differentiation than the aerogels with identical composition. In conclusion, our study shows that the sol-gel synthesis of CS-silica xerogels and aerogels enhances not only their bioactive response, but also osteoconduction and cell differentiation properties. Therefore, these new biomaterials should provide adequate secretion of the osteoid for a fast bone regeneration.

Structure-Related Mechanical Properties and Bioactivity of Silica-Gelatin Hybrid Aerogels for Bone Regeneration.

We report the synthesis of mesoporous silica-gelatin hybrid aerogels with 15, 25, and 30 wt. % gelatin contents, using 3-glycidoxypropyl trimethoxysilane (GPTMS) as a coupling agent, for tissue-engineering applications. Aerogels were obtained using a one-step sol-gel process followed by CO2 supercritical drying, resulting in crack-free monolith samples with bulk densities ranging from 0.41 g cm-3 to 0.66 g cm-3. Nitrogen adsorption measurements revealed an interconnected mesopore network and a general decrease in the textural parameters: specific surface areas (651-361 m2 g-1), pore volume (1.98-0.89 cm3 g-1), and pore sizes (10.8-8.6 nm), by increasing gelatin content. Thermogravimetric analysis (TGA), Fourier-transform infrared (FTIR) spectroscopy and uniaxial compression experiments confirmed that the structure, thermal properties and mechanical behavior of these aerogels changed significantly when the concentration of gelatin reached 25 wt.%, suggesting that this composition corresponds to the percolation threshold of the organic phase. In addition, the samples exhibited hydrophilic behavior and extremely fast swelling in phosphate-buffered saline (PBS), with swelling ratios from 2.32 to 3.32. Furthermore, in vitro bioactivity studies revealed a strong relationship between the kinetics of the nucleation and growth processes of hydroxyapatite in simulated body fluid (SBF) and the gelatin content. The live/dead assay revealed no cytotoxicity in HOB® osteoblasts in vitro and a positive influence on cell growth, focal adhesion development, and cytoskeletal arrangement for cell adhesion. Mineralization assays confirmed the positive effects of the samples on osteoblast differentiation. The biomaterials described are versatile, can be easily sterilized and are suitable for a wide range of applications in bone tissue-engineering, either alone or in combination with bioactive-reinforced phases.

Use of Mobile Technologies for Driving, Road Accidents, Health, and Psychological Variables in Colombian Drivers / Uso de Tecnologias Móviles para la Conducción, Accidentabilidad Vial, Salud y Variables Psicológicas en Conductores Colombianos

Abstract The aim of this investigation is to show the relationships between the use of Mobile Driving Applications and Devices (MDAD) with self-reported road accidents, anger, physical health, and subjective wellbeing, in three types of Colombian drivers. The sample is non-randomized (n = 1149) and 93.2% are male drivers. Results showed that (a) for professional drivers, there is an inverse correlation between the use of MDAD with lower driving frequency during weekdays and a higher educational level, (b) for occasional drivers, GPS use was directly associated with fatal road accidents and low driving frequency during weekdays, (C) for private drivers, correlations were found between MDAD broader usage, higher levels of both aggression and perceived driving difficulty as well as physical health problems mainly hypertension and diabetes. It is necessary to conduct in-depth research on MDAD uses, health, and driving styles, by controlling social desirability.

Resumen El objetivo de esta investigación es mostrar las relaciones entre el uso de Dispositivos y Aplicaciones Móviles para la Conducción (DAMC) con la accidentalidad vial auto reportada, la ira, la salud física y el bienestar subjetivo, en tres tipos de conductores colombianos. La muestra es no aleatoria (n = 1149) y el 93.2% son conductores varones. Los resultados muestran que (a) en conductores profesionales, hay una correlación inversa entre el uso de DAMC con una menor fre-cuencia de conducción entre semana y con un mayor nivel educativo, (b) en conductores ocasionales, mayor uso de GPS asociado con accidentes fatales y con menor frecuencia de conducción entre semana, (C) en conductores particulares, mayor uso de DAMC relacionado con niveles más altos de agresividad y de dificultad percibida para conducir, y con más problemas de salud -principalmente hipertensión y diabetes. Es necesario realizar investigaciones en profundidad acerca de los usos de DAMC, salud y estilos de conducción, mediante el control de la deseabilidad social.

Robocasting and Laser Micromachining of Sol-Gel Derived 3D Silica/Gelatin/ß-TCP Scaffolds for Bone Tissue Regeneration.

The design and synthesis of sol-gel silica-based hybrid materials and composites offer significant benefits to obtain innovative biomaterials with controlled porosity at the nanostructure level for applications in bone tissue engineering. In this work, the combination of robocasting with sol-gel ink of suitable viscosity prepared by mixing tetraethoxysilane (TEOS), gelatin and ß-tricalcium phosphate (ß-TCP) allowed for the manufacture of 3D scaffolds consisting of a 3D square mesh of interpenetrating rods, with macropore size of 354.0 ± 17.0 µm, without the use of chemical additives at room temperature. The silica/gelatin/ß-TCP system underwent irreversible gelation, and the resulting gels were also used to fabricate different 3D structures by means of an alternative scaffolding method, involving high-resolution laser micromachining by laser ablation. By this way, 3D scaffolds made of 2 mm thick rectangular prisms presenting a parallel macropore system drilled through the whole thickness and consisting of laser micromachined holes of 350.8 ± 16.6-micrometer diameter, whose centers were spaced 1312.0 ± 23.0 µm, were created. Both sol-gel based 3D scaffold configurations combined compressive strength in the range of 2-3 MPa and the biocompatibility of the hybrid material. In addition, the observed Si, Ca and P biodegradation provided a suitable microenvironment with significant focal adhesion development, maturation and also enhanced in vitro cell growth. In conclusion, this work successfully confirmed the feasibility of both strategies for the fabrication of new sol-gel-based hybrid scaffolds with osteoconductive properties.

Fibrinolysis versus thoracoscopy: Comparison of results in empyema management in the child.

OBJECTIVE: The objective of this study is to compare the outcome of treatment with drainage and urokinase (UK) versus thoracoscopy (TS) in pleural empyema secondary to complicated pneumonia. METHODS: This was a retrospective study of patients with complicated parapneumonic effusions between 2008 and 2019 treated with UK or TS. Epidemiological and evolutionary data compared days of fever, antibiotic, pre- and postprocedure stay, time to radiological resolution, and complications. The results were expressed as medians and the comparisons were made by the Mann-Whitney U-test. RESULTS: Of 143 patients with NC, 46 were empyemas (26 men), 25 were treated with TS, and 10 were treated with UK. The remaining 11 received combined treatment, being excluded from the study. There were no significant differences between TS versus UK in age (median 4 vs. 3 years), days of fever before the procedure (4 vs. 2) and after (2 vs. 2), days of antibiotic treatment before the procedure (4 vs. 4), overall hospital stay (15 vs. 13 days), and months until radiological normalization (2 vs. 2). The complications related to the therapy were scarce in both groups and had no impact on evolution. Patients with TS had a longer preprocedural stay (4 vs. 1; P < 0.001) and required fewer days of subsequent antibiotic after procedure (8 vs. 11; P = 0.03), and a shorter overall antibiotic treatment time (11 vs. 16; P = 0.03). They also had a shorter post-TS stay (9 vs. 12 days), although this difference did not become significant (P = 0.09). CONCLUSIONS: In our experience, the results obtained with both procedures are quite similar, although patients undergoing TS had a better evolution (fewer days of antibiotic and a tendency to less hospitalization), despite having been performed a priori in more evolved patients.

"Anomalías en la posición renal". Kidney position abnormalities.

Kidney development is a complex process that begins during the fifth to ninth weeks of life. Different types of renal congenital anomalies exist; however, they are rare and usually asymptomatic. Renal ectopia is a rare malformation that affects 0.01-0.05% of patients. Of all the locations, the most frequent is the pelvic (55%). We present a case of a 21-year-old man with bilateral renal ectopia.

“Anomalías en la posición renal”. Kidney position abnormalities

Kidney development is a complex process that begins during the fifth to ninth weeks of life. Different types of renal congenitalanomalies exist; however, they are rare and usually asymptomatic. Renal ectopia is a rare malformation that affects 0.01-0.05%of patients. Of all the locations, the most frequent is the pelvic (55%). We present a case of a 21-year-old man with bilateral renalectopia. (AU)

11-Deoxycorticosterone Producing Adrenal Hyperplasia as a Very Unusual Cause of Endocrine Hypertension: Case Report and Systematic Review of the Literature.

Background and Objectives: 11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of. Design and Methods: We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021. Results: We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions. Conclusions: 11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable. Systematic Review Registration: Open Science Framework, 10.17605/OSF.IO/NR7UV.

Traumatic events, psychological symptoms, and aggression in male and female prisoners.

Objective: Establish the relationship between the types of traumatic experiences, number of traumas, age at the time of traumatic events with psychopathological symptoms and aggression in an Ecuadorian prison. Method: A cross-sectional study with 101 offenders from Ambato's Detention Center in Ecuador. Results: Of the prisoners in this sample, 27 have PTSD. Incarcerated individuals who have suffered intentional trauma, multiple traumas, and trauma before the age of 18 show higher levels of psychopathological symptoms and aggression. Conclusions: This study highlights the importance of mental health care in prisons. Research outcomes are relevant for future investigation in Latin American prisons for the design and implementation of trauma-related interventions. Trauma-focused interventions can prevent violence and mitigate its consequences. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Actitudes protectoras relacionadas con la seguridad vial en conductores de Villavicencio (Colombia) / Protective Attitudes Related to Road Safety Among Drivers in Villavicencio (Colombia)

Resumen La inseguridad vial es un tema de interés para la sociedad, por sus implicaciones y consecuencias en cuanto al costo social, económico y en la salud pública. El objetivo del presente estudio fue conocer el nivel de actitudes protectoras hacia la seguridad vial en conductores de la ciudad colombiana de Villavicencio. Para esto se empleó un instrumento de 18 ítems sobre conductas de riesgo, conductas de prevención y emociones en la conducción. La muestra conformada por 1018 conductores fue de disponibilidad. Los resultados muestran una fiabilidad interna alta del instrumento y una estructura factorial de cuatro dimensiones. Además, los hombres, los conductores de taxis y de camionetas, las personas con menor nivel educativo o con estado civil de unión libre, mostraron los niveles más altos de conductas de riesgo y de velocidad excesiva. El nivel de ira al manejar fue mayor en las personas separadas. Si bien condiciones como la edad, el sexo, el estado civil, el nivel de escolaridad y factores como el tipo de vehículo, las fallas técnicas del vehículo, el ambiente y el diseño de las vías públicas influyen, de algún modo, en el comportamiento de los conductores, es, en últimas, el elemento subjetivo en la conducción la variable clave en la explicación de la accidentalidad vial. No obstante, los comportamientos desfavorables hacia la seguridad vial pueden modificarse mediante un programa formativo que se fundamente en un modelo de cambio de actitudes.

Abstract Road insecurity is a topic of interest for society, due to its implications and consequences in terms of social, economic, and public health costs. This paper aimed to determine the level of protective attitudes towards road safety in drivers from Villavicencio, Colombia. For this purpose, an 18-item instrument was used, measuring risk behaviors, preventive behaviors, and emotions while driving. The sample was non-randomized, with 1018 car, bus, motorcycle, taxi, van, or truck drivers. Results showed high internal reliability of the instrument and a factorial structure with four dimensions. Also, male, taxi, and van/truck drivers, people with low educational levels, or with a marital status of free union showed the highest levels of risk behaviors and excessive speed. The anger level while driving was higher for divorced people. Although conditions such as age, sex, marital status, level of education, and factors such as vehicle type, vehicle technical issues, and environment and road design have some influence on drivers' behaviors, it is ultimately the subjective element in driving the key variable explaining road accidents. However, unfavorable road safety behaviors can be modified through a training program based on an attitude change model.

Evidence of autochthonous transmission of urinary schistosomiasis in Almeria (southeast Spain): An outbreak analysis.

BACKGROUND: Schistosomiasis is endemic in 78 countries belonging to tropical and subtropical areas. However, autochthonous transmission of urogenital schistosomiasis was reported in Corsica (France) in 2013. We present evidence of autochthonous transmission of urogenital schistosomiasis in Almería (Spain) in 2003. METHODS: Description of the outbreak in farmers and subsequent epidemiological studies aimed at searching for Bulinus snails and their genotypic characteristics. RESULTS: The outbreak affected 4 farmers out of a group of 5 people who repeatedly bathed that summer in an irrigation pool in the area. Two of them presented macroscopic hematuria with bilharziomas, showing the presence of Schistosoma eggs in bladder biopsies. Two others were asymptomatic but the serology for schistosomiasis was positive. In 2015, the presence of the vector Bulinus truncatus was demonstrated in Almería in water collections of appropriate characteristics. DNA sequencing proving that local B. truncatus species were base-to-base identical to B. truncatus from Senegal. CONCLUSIONS: We present a new outbreak of autochthonous transmission of urogenital schistosomiasis in Europe. Although no new cases of autochthonous transmission have been reported, some other cases may have occurred at that time or later on and be unnoticed as many cases of schistosomiasis are asymptomatic or present mild and unspecific symptoms.

Effect of Washing Treatment on the Textural Properties and Bioactivity of Silica/Chitosan/TCP Xerogels for Bone Regeneration.

Silica/biopolymer hydrogel-based materials constitute very attractive platforms for various emerging biomedical applications, particularly for bone repair. The incorporation of calcium phosphates in the hybrid network allows for designing implants with interesting biological properties. Here, we introduce a synthesis procedure for obtaining silica-chitosan (CS)-tricalcium phosphate (TCP) xerogels, with CS nominal content varying from 4 to 40 wt.% and 10 to 20 wt.% TCP. Samples were obtained using the sol-gel process assisted with ultrasound probe, and the influence of ethanol or water as washing solvents on surface area, micro- and mesopore volume, and average pore size were examined in order to optimize their textural properties. Three washing solutions with different soaking conditions were tested: 1 or 7 days in absolute ethanol and 30 days in distilled water, resulting in E1, E7, and W30 washing series, respectively. Soaked samples were eventually dried by evaporative drying at air ambient pressure, and the formation of interpenetrated hybrid structures was suggested by Fourier transformed infrared (FTIR) spectroscopy. In addition the impact that both washing solvent and TCP content have on the biodegradation, in vitro bioactivity and osteoconduction of xerogels were explored. It was found that calcium and phosphate-containing ethanol-washed xerogels presented in vitro release of calcium (2-12 mg/L) and silicon ions (~60-75 mg/L) after one week of soaking in phosphate-buffered saline (PBS), as revealed by inductive coupled plasma (ICP) spectroscopy analysis. However, only the release of silicon was detected for water-washed samples. Besides, all the samples exhibited in vitro bioactivity in simulated body fluid (SBF), as well as enhanced in vitro cell growth and also significant focal adhesion development and maturation.

Identification of blood glucose patterns in patients with type 1 diabetes using continuous glucose monitoring and clustering technique.

OBJECTIVE: To show that statistical techniques allow for obtaining a reduced number of four-hour glucose profiles that can identify any glucose behavior in patients with type 1 diabetes mellitus. PATIENTS AND METHODS: A retrospective study of 10 patients with type 1 diabetes mellitus was conducted using data collected by continuous glucose monitoring. A data mining technique based on decision trees called CHAID (Chi-square Automatic Interaction Detection) was used to classify glucose profiles into groups using two decision criteria. These were 1, the seven days of the week and 2, different time slots, the day being divided into six sections of four hours each. Clustering was performed according to the glucose levels recorded using the statistically significant differences found. RESULTS: Significant differences (P-value <.05) and dependencies were seen between the glucose profiles classified depending on the independent variables 'day of the week' and 'time slot'. The relationships found were different for each patient, showing the need for individualized studies. CONCLUSIONS: The results obtained will facilitate mathematical modeling of glucose, and can be used to develop an individualized classifier for each patient that categorizes glucose profiles based on the day of the week and time slot variables. Using this classifier, it will be possible to predict the glucose levels of the patient knowing on which day of the week and in which time slot he/she is, leading to more precise models. Healthcare professionals will also be able to improve patient habits and therapies.

What to do when the parathyroid gland is not found during a transcervical exploration?

The most frequent cause of suboptimal results in a parathyroid adenoma resection is an ectopic location, mainly in the anterior mediastinum. These cases may not always be resected through a traditional cervical access. We present 2 cases of primary hyperparathyroidism who underwent an unsuccessful bilateral cervical exploration due to parathyroid tissue located inside the thymic gland. A video-assisted thoracoscopic surgery thymectomy with intraoperative determination of blood parathormone levels was performed. A 50% reduction of intraoperatory parathyroid hormone blood from the highest basal level at 5 and 10 min after resection was obtained. Final pathological results showed an intra-thymic parathyroid adenoma in the first patient and an intra-thymic focus of parathyroid hyperplasia in the second patient. In conclusion, video-assisted thoracoscopic surgery thymectomy could be the optimal approach to resect ectopic parathyroid adenomas located in the anterior mediastinum.

Identification of blood glucose patterns in patients with type1 diabetes using continuous glucose monitoring and clustering techniques. / Identificación de patrones de glucemia en pacientes con diabetes tipo1 mediante monitorización continua de glucosa y técnicas de clusterización.

OBJECTIVE: To show that statistical techniques allow for obtaining a reduced number of four-hour glucose profiles that can identify any glucose behavior in patients with type1 diabetes mellitus. MATERIAL AND METHODS: A retrospective study of 10 patients with type1 diabetes mellitus was conducted using data collected by continuous glucose monitoring. A data mining technique based on decision trees called CHAID (Chi-square Automatic Interaction Detection) was used to classify glucose profiles into groups using two decision criteria. These were: 1, the seven days of the week, and 2, different time slots, the day being divided into six sections of four hours each. Clustering was performed according to the glucose levels recorded using the statistically significant differences found. RESULTS: Significant differences (P<.05) and dependencies were seen between the glucose profiles classified depending on the independent variables 'day of the week' and 'time slot'. The relationships found were different for each patient, showing the need for individualized studies. CONCLUSIONS: The results obtained will facilitate mathematical modeling of glucose, and can be used to develop an individualized classifier for each patient that categorizes glucose profiles based on the day of the week and time slot variables. Using this classifier, it will be possible to predict the glucose levels of the patient knowing on which day of the week and in which time slot he/she is, leading to more precise models. Healthcare professionals will also be able to improve patient habits and therapies.

LDL, HDL and endocrine-related cancer: From pathogenic mechanisms to therapies.

Cholesterol is essential for a variety of functions in endocrine-related cells, including hormone and steroid production. We have reviewed the progress to date in research on the role of the main cholesterol-containing lipoproteins; low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and their impact on intracellular cholesterol homeostasis and carcinogenic pathways in endocrine-related cancers. Neither LDL-cholesterol (LDL-C) nor HDL-cholesterol (HDL-C) was consistently associated with endocrine-related cancer risk. However, preclinical studies showed that LDL receptor plays a critical role in endocrine-related tumor cells, mainly by enhancing circulating LDL-C uptake and modulating tumorigenic signaling pathways. Although scavenger receptor type BI-mediated uptake of HDL could enhance cell proliferation in breast, prostate, and ovarian cancer, these effects may be counteracted by the antioxidant and anti-inflammatory properties of HDL. Moreover, 27-hydroxycholesterol a metabolite of cholesterol promotes tumorigenic processes in breast and epithelial thyroid cancer. Furthermore, statins have been reported to reduce the incidence of breast, prostate, pancreatic, and ovarian cancer in large clinical trials, in part because of their ability to lower cholesterol synthesis. Overall, cholesterol homeostasis deregulation in endocrine-related cancers offers new therapeutic opportunities, but more mechanistic studies are needed to translate the preclinical findings into clinical therapies.

MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer.

Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We correlated the expression of miRNAs with the SLN status and the outcome of axillary lymph node dissection (ALND) in 60 patients with early breast cancer. We profiled the expression of miRNAs in paired breast tumor samples and SLNs using the NextSeq500 Illumina platform and key findings were validated by qPCR. MultiMiR Bioconductor and Reactome pathways analysis were performed to identify target genes and signaling pathways affected by altered expressed miRNAs. Our results show that nine miRNAs were differentially expressed in tumor tissues (q ≤ 0.05). In tumor samples, a 13.5-fold up-regulation of miR-7641-2 (q < 0.001) and a 2.9-fold down-regulation of miR-1291 (q < 0.001) were associated with tumors with positive SLNs. However, only down-regulation of miR-1291 (q = 0.048) remained significant in paired SLNs samples. Interestingly, a 10.5 up-regulation of miR-1291 in SLNs samples was associated with additional axillary lymph node involvement (q < 0.001). The enrichment analyses showed that canonical and non-canonical WNT pathways and negative regulation of various receptor tyrosine kinases signaling pathways were targets of miR-1291 and supports the role of miR-1291 as a tumor suppressor gene (TSG). Further studies are warranted to investigate the use of miR-1291 as a surrogate biomarker of SLN node metastasis in patients with early-stage breast cancer.