Asociación del colesterol remanente con el grado de control glucémico y la presencia de complicaciones microvasculares en personas con diabetes mellitus tipo 1 / Association of remnant cholesterol with glycemic control and presence of microvascular complications in individuals with type 1 diabetes mellitus

Introducción Este trabajo investiga la relación entre el colesterol remanente, las métricas de glucosa y las complicaciones crónicas de la diabetes tipo 1 en individuos con sistemas flash de glucosa. Material y métodos Se recopilaron variables clínicas y métricas de glucosa de personas usuarias de sensores de glucosa. Se llevaron a cabo modelos estadísticos para estudiar la asociación del colesterol remanente con las métricas de glucosa, así como con la retinopatía y la nefropatía diabética. Resultados Se incluyeron 383 personas con una edad de 48,3±16,2 años, siendo un 54,1% mujeres, con un colesterol remanente de 16±10mg/dl. Los resultados mostraron que el colesterol remanente se asocia a un menor tiempo en rango (p=0,015) y a un mayor tiempo por encima del rango (p=0,003). La nefropatía diabética fue la única complicación que se asoció con un colesterol remanente mayor a 30mg/dl, OR: 8,93: IC 95%: 2,99-26,62; p<0,001. Conclusión El colesterol remanente se asocia de forma independiente con la hiperglucemia y la nefropatía diabética en personas con diabetes tipo 1. (AU)

Introduction This study examines the relationship between remnant cholesterol, glucose metrics, and chronic complications of type 1 diabetes in users of glucose monitoring systems. Material and methods Clinical variables and glucose metrics were collected from individuals using glucose sensors. Statistical models were employed to investigate the association of remnant cholesterol with glucose metrics, diabetic retinopathy, and diabetic nephropathy. Results A total of 383 individuals, aged 48.3±16.2 years, with 54.1% women, and a remnant cholesterol level of 16±10mg/dL, were included. The results demonstrated that remnant cholesterol was associated with less time within the target range (P=.015) and more time above the target range (P=.003). Diabetic nephropathy was the only complication associated with remnant cholesterol levels exceeding 30mg/dL; OR: 8.93; 95% CI: 2.99-26.62, P<.001. Conclusion Remnant cholesterol is independently associated with hyperglycemia and diabetic nephropathy in individuals with type 1 diabetes. (AU)

Asociación del colesterol remanente con el grado de control glucémico y la presencia de complicaciones microvasculares en personas con diabetes mellitus tipo 1 / Association of remnant cholesterol with glycemic control and presence of microvascular complications in individuals with type 1 diabetes mellitus

Introducción Este trabajo investiga la relación entre el colesterol remanente, las métricas de glucosa y las complicaciones crónicas de la diabetes tipo 1 en individuos con sistemas flash de glucosa. Material y métodos Se recopilaron variables clínicas y métricas de glucosa de personas usuarias de sensores de glucosa. Se llevaron a cabo modelos estadísticos para estudiar la asociación del colesterol remanente con las métricas de glucosa, así como con la retinopatía y la nefropatía diabética. Resultados Se incluyeron 383 personas con una edad de 48,3±16,2 años, siendo un 54,1% mujeres, con un colesterol remanente de 16±10mg/dl. Los resultados mostraron que el colesterol remanente se asocia a un menor tiempo en rango (p=0,015) y a un mayor tiempo por encima del rango (p=0,003). La nefropatía diabética fue la única complicación que se asoció con un colesterol remanente mayor a 30mg/dl, OR: 8,93: IC 95%: 2,99-26,62; p<0,001. Conclusión El colesterol remanente se asocia de forma independiente con la hiperglucemia y la nefropatía diabética en personas con diabetes tipo 1. (AU)

Introduction This study examines the relationship between remnant cholesterol, glucose metrics, and chronic complications of type 1 diabetes in users of glucose monitoring systems. Material and methods Clinical variables and glucose metrics were collected from individuals using glucose sensors. Statistical models were employed to investigate the association of remnant cholesterol with glucose metrics, diabetic retinopathy, and diabetic nephropathy. Results A total of 383 individuals, aged 48.3±16.2 years, with 54.1% women, and a remnant cholesterol level of 16±10mg/dL, were included. The results demonstrated that remnant cholesterol was associated with less time within the target range (P=.015) and more time above the target range (P=.003). Diabetic nephropathy was the only complication associated with remnant cholesterol levels exceeding 30mg/dL; OR: 8.93; 95% CI: 2.99-26.62, P<.001. Conclusion Remnant cholesterol is independently associated with hyperglycemia and diabetic nephropathy in individuals with type 1 diabetes. (AU)

Association of remnant cholesterol with glycemic control and presence of microvascular complications in individuals with type 1 diabetes mellitus.

INTRODUCTION: This study examines the relationship between remnant cholesterol, glucose metrics, and chronic complications of type 1 diabetes in users of glucose monitoring systems. MATERIAL AND METHODS: Clinical variables and glucose metrics were collected from individuals using glucose sensors. Statistical models were employed to investigate the association of remnant cholesterol with glucose metrics, diabetic retinopathy, and diabetic nephropathy. RESULTS: A total of 383 individuals, aged 48.3 ±â€¯16.2 years, with 54.1% women, and a remnant cholesterol level of 16 ±â€¯10 mg/dL, were included. The results demonstrated that remnant cholesterol was associated with less time within the target range (p = 0.015) and more time above the target range (p = 0.003). Diabetic nephropathy was the only complication associated with remnant cholesterol levels exceeding 30 mg/dL, OR 8.93, 95% CI (2.99-26.62), p < 0.001. CONCLUSION: Remnant cholesterol is independently associated with hyperglycemia and diabetic nephropathy in individuals with type 1 diabetes.

Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry.

BACKGROUND: Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. MATERIALS AND METHODS: Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. RESULTS: Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. CONCLUSIONS: This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.

Potentially harmful elements pollute soil and vegetation around the Atrevida mine (Tarragona, NE Spain).

Mining activity is one of the main sources to pollute soil, water and plants. An analysis of soil and plant samples around the Atrevida mining area in Catalonia (NE Spain) was preformed to determine potentially harmful elements (PHEs). Soil and plant samples were taken at eight locations around the mining area. The topsoil (0-15 cm) samples were analysed for physico-chemical properties by standard methods, by ICP-MS for Cd, Co, Cr, Cu, Fe, Ni, Pb and Zn, and were microwave-digested. Plant, root and shoot samples were digested separately, and heavy metals were analysed by AAS. Translocation factor (TF), biological concentration factor (BCF) and biological accumulation factor (BAF) were determined to assess the tolerance strategies developed by native species and to evaluate their potential for phytoremediation purposes. Soil pH was generally acid (5.48-6.72), with high soil organic matter (SOM) content and a sandy loamy or loamy texture. According to the agricultural soil values in southern Europe, our PHEs concentrations exceeded the toxicity thresholds. The highest root content of the most studied PHEs appeared in Thymus vulgaris L. and Festuca ovina L., while Biscutella laevigata L. accumulated more PHEs in shoots. The TF values were > 1 in B. laevigata L., but BAF obtained < 1, except Pb. B. laevigata L., and can be considered potentially useful for phytoremediation for having the capacity to restrict the accumulation of large PHEs amounts in roots and Pb translocation to shoots.

Functionality and Quality of Life with Parkinson's Disease after Use of a Dynamic Upper Limb Orthosis: A Pilot Study.

Parkinson's disease (PD) is a chronic, neurodegenerative movement disorder, whose symptoms have a negative impact on quality of life and functionality. Although its main treatment is pharmacological, non-pharmacological aids such as the dynamic elastomeric fabric orthosis (DEFO) merit an evaluation. Our objective is to assess the DEFO in upper limb (UL) functional mobility and in the quality of life of PD patients. A total of 40 patients with PD participated in a randomized controlled crossover study, and were assigned to a control group (CG) and to an experimental group (EG). Both groups used the DEFO for two months, the experimental group the first two months of the study and the control group the last two. Motor variables were measured in the ON and OFF states at the baseline assessment and at two months. Differences from the baseline assessment were observed in some motor items of the Kinesia assessment, such as rest tremor, amplitude, rhythm or alternating movements in the ON and OFF states with and without orthosis. No differences were found in the unified Parkinson's disease rating scale (UPDRS) or the PD quality-of-life questionnaire. The DEFO improves some motor aspects of the UL in PD patients but this does not translate to the amelioration of the standard of functional and quality-of-life scales.

A phenotypic screen of Marfan syndrome iPSC-derived vascular smooth muscle cells uncovers GSK3ß as a new target.

Marfan syndrome (MFS) is a rare connective tissue disorder caused by mutations in FBN1. Patients with MFS notably suffer from aortic aneurysm and dissection. Despite considerable effort, animal models have proven to be poorly predictive for therapeutic intervention in human aortic disease. Patient-derived induced pluripotent stem cells can be differentiated into vascular smooth muscle cells (VSMCs) and recapitulate major features of MFS. We have screened 1,022 small molecules in our in vitro model, exploiting the highly proteolytic nature of MFS VSMCs, and identified 36 effective compounds. Further analysis identified GSK3ß as a recurring target in the compound screen. GSK3ß inhibition/knockdown did not ameliorate the proliferation defect in MFS-VSMCs but improved MFS-VSMC proteolysis and apoptosis and partially rescued fibrillin-1 deposition. To conclude, we have identified GSK3ß as a novel target for MFS, forming the foundation for future work in MFS and other aortic diseases.

To evaluate whether there is a relationship between occlusion and body posture as delineated by a stabilometric platform: A systematic review.

OBJECTIVE: To evaluate whether there is a relationship between occlusion and body posture evaluated using a stabilometric platform. METHODS: Observational studies that analyzed the relationship between dental occlusion (changes in mandibular position and/or dental malocclusion) and body posture evaluated with a stabilometric platform in patients older than 13 years without orthodontic or orthopedic intervention and systemically healthy were considered eligible for inclusion. PubMed, EMBASE, Science Direct, LILACS, and Google Scholar databases were searched to obtain articles published from September 2019 up to March 2020. RESULTS: Twelve articles met the inclusion criteria, of which 66.7% showed a relationship between dental occlusion and body posture, and 33.3% found no relationship. The marked heterogeneity between studies did not allow data to be combined for meta-analyses. CONCLUSION: For the mandibular positions, the postural changes were mainly in the mediolateral direction, while in the malocclusions, they were in the anteroposterior direction.

No priming, just fighting-endophytic yeast attenuates the defense response and the stress induced by Dutch elm disease in Ulmus minor Mill.

One century after the first report of Dutch elm disease (DED), there is still no practical solution for this problem threatening European and American elms (Ulmus spp.). The long breeding cycles needed to select resistant genotypes and the lack of efficient treatments keep disease incidence at high levels. In this work, the expression of defense-related genes to the causal agent of DED, Ophiostoma novo-ulmi Brasier, was analyzed in in vitro clonal plantlets from two DED-resistant and two DED-susceptible Ulmus minor Mill. trees. In addition, the effect of the inoculation of an endophytic pink-pigmented yeast (Cystobasidium sp.) on the plant's defense system was tested both individually and in combination with O. novo-ulmi. The multifactorial nature of the resistance to DED was confirmed, as no common molecular response was found in the two resistant genotypes. However, the in vitro experimental system allowed discrimination of the susceptible from the resistant genotypes, showing higher levels of oxidative damage and phenolic compounds in the susceptible genotypes after pathogen inoculation. Inoculation of the endophyte before O. novo-ulmi attenuated the plant molecular response induced by the pathogen and moderated oxidative stress levels. Niche competition, endophyte-pathogen antagonism and molecular crosstalk between the host and the endophyte are discussed as possible mechanisms of stress reduction. In sum, our results confirm the complex and heterogeneous nature of DED resistance mechanisms and highlight the possibility of using certain endophytic yeasts as biological tools to improve tree resilience against biotic stress.

Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia.

BACKGROUND: There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. CASE PRESENTATION: Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. CONCLUSIONS: Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.

Attenuation mechanisms and key parameters to enhance treatment performance in vegetation filters: A review.

In times when environmental concerns are on the rise and the search of ways to reduce waste generation and to create a circular economy is booming, Nature Based Solutions (NBSs) play a very important role. Vegetation Filters (VFs) are a type of Land Application System (LAS) in which wastewater is used to irrigate a forestry plantation to treat the water and produce biomass. VFs show multiple benefits that render this technology a suitable solution for wastewater treatment, especially for scattered populations or isolated buildings that lack of connection to sewer systems. This review aims to provide a comprehensive state of the art of VF implementation, highlighting the do's and don'ts for a successful performance focusing on those factors that are essential to water treatment. Results show that VFs have a great treatment capacity when all involving factors are considered, and their efficiency tends to increase with time, as the VF develops and "gets older". Indeed, the presence of fine-textured soils, the selection of a proper vegetation species, the use of pre-treated wastewater and a water balance-based irrigation schedule alternating wetting and -drying cycles are all factors that help to achieve the best performance. However, it is necessary to design and follow a simple but rigorous operation and maintenance schedule to avoid system failure, which could lead to NO3-N leaching towards groundwater.

Perirenal Fat Surface Area and Oncologic Outcome in Elective Colon Cancer Surgery.

BACKGROUND: Central obesity is associated with surgical difficulties, but few studies explore the relationship with long-term results after colon cancer surgery. OBJECTIVE: The purpose of this study was to investigate the association between perirenal fat surface area, a proxy for total visceral fat, and oncologic outcome after intestinal resection for colon cancer. DESIGN: We investigated the association between perirenal fat surface area (exposure) on recurrence and death (outcome) in patients undergoing surgery with curative intent for colon cancer. SETTINGS: The study was conducted at Stockholm South General Hospital, serving a population of 600,000. PATIENTS: Patients (N = 733) without metastases at diagnosis who had a preoperative CT and had undergone elective colon resection between 2006 and 2016 were included. MAIN OUTCOME MEASURES: We compared overall survival, recurrence-free survival, and cause-specific survival by perirenal fat surface area. RESULTS: Patients with high perirenal fat surface area (fourth quartile) had more often left-sided tumors (45% vs 32% in the first quartile) and experienced more postoperative complications (29% vs 13%), but there were no differences in pathologic T and N stage, radicality of surgery, or adjuvant chemotherapy treatment. Overall survival decreased by increasing cancer stage but was not different between perirenal fat surface area categories. The HR for recurrence-free survival per centimeter squared increase in perirenal fat surface area was 1.00 (95% CI, 0.99-1.01) adjusted for age, sex, ASA category, tumor location, and postoperative complication Clavien-Dindo ≥2. The cumulative incidence of recurrence with death as a competing risk was not statistically different between perirenal fat surface area categories (p = 0.06). Subgroup analyses showed a nonsignificant tendency for men with low perirenal fat surface area to have a lower risk of recurrence and women a higher risk. LIMITATIONS: In all register-based studies there can be randomly distributed errors. The results can only be generalized to colon resections. Our cohort ranged over a large year span. CONCLUSIONS: We found no association between perirenal fat surface area and overall survival, recurrence-free survival, or cause-specific cumulative incidence of recurrence in patients undergoing colon resection for cancer. See Video Abstract at http://links.lww.com/DCR/B326. LA SUPERFICIE DE GRASA PERIRRENAL Y EL RESULTADO ONCOLGICO EN CIRUGA ELECTIVA DE CNCER DE COLON: ANTECEDENTES:La obesidad central está asociada con dificultades quirúrgicas, pero pocos estudios exploran la relación de los resultados a largo plazo después de cirugía de cáncer de colon.OBJETIVO:Investigar la asociación entre la superficie de la grasa perirrenal, como un indicador de la grasa visceral total y el resultado oncológico después de una resección intestinal por cáncer de colon.DISEÑO:Se estudió la asociación entre el área de la superficie de la grasa perirrenal (expuesta) con la recurrencia y la muerte (resultado) de pacientes sometidos a cirugía con intención curativa por cáncer de colon.AJUSTES:Atención brindada por el Hospital General del Sur de Estocolmo a una población de 600,000 habitantes.PACIENTES:Aquellos pacientes sin metástasis (n = 733) en el momento del diagnóstico que tuvieron una tomografía computada preoperatoria y que se sometieron a una resección electiva de colon entre 2006-2016.PRINCIPALES MEDIDAS DE RESULTADO:Comparamos la sobrevida general, la sobrevida libre de recurrencia y la sobrevida específica de la causa, por área de superficie de grasa perirrenal.RESULTADOS:Los pacientes con una mayor área de superficie de grasa perirrenal (cuarto cuartil) tuvieron más frecuentemente tumores del lado izquierdo (45% frente a 32% en el primer cuartil) y sufrieron más complicaciones postoperatorias (29% frente a 13%), pero no hubieron diferencias en el Estadío patológico T y N, ni en lo radical de la cirugía o del tratamiento de quimioterapia adyuvante. La supervivencia general disminuyó al aumentar el estadio del cáncer, pero no fue diferente entre las categorías de área de superficie grasa perirrenal. La razón de riesgo para la sobrevida libre de recurrencia por aumento de cm2 en el área de la superficie grasa perirrenal fue de 1.00 (intervalo de confianza del 95%: 0.99-1.01) ajustada por edad, sexo, categoría de la Sociedad Americana de Anestesiólogos, ubicación del tumor y complicación postoperatoria según Clavien-Dindo ≥ 2) La incidencia acumulada de recurrencia con muerte como un riesgo competitivo no fue estadísticamente diferente entre las categorías de área de superficie grasa perirrenal (p = 0.06). Los análisis de subgrupos mostraron una tendencia no significativa para que los hombres con un área de superficie menor en grasa perirrenal tengan un menor riesgo de recurrencia y las mujeres un mayor riesgo.LIMITACIONES:En todos los estudios basados en registros puede haber errores distribuidos aleatoriamente. Los resultados solo pueden generalizarse a resecciones de colon. Nuestra cohorte osciló durante un gran lapso de años.CONCLUSIONES:No se encontró asociación entre el área de superficie de la grasa perirrenal y la sobrevida general, ni con la sobrevida libre de recurrencia o la incidencia acumulada de recurrencia específica de la causa en pacientes sometidos a resección de colon por cáncer. Consulte Video Resumen en http://links.lww.com/DCR/B326. (Traducción-Dr Xavier Delgadillo).

Prediction of osteoporotic hip fracture in postmenopausal women through patient-specific FE analyses and machine learning.

A great challenge in osteoporosis clinical assessment is identifying patients at higher risk of hip fracture. Bone Mineral Density (BMD) measured by Dual-Energy X-Ray Absorptiometry (DXA) is the current gold-standard, but its classification accuracy is limited to 65%. DXA-based Finite Element (FE) models have been developed to predict the mechanical failure of the bone. Yet, their contribution has been modest. In this study, supervised machine learning (ML) is applied in conjunction with clinical and computationally driven mechanical attributes. Through this multi-technique approach, we aimed to obtain a predictive model that outperforms BMD and other clinical data alone, as well as to identify the best-learned ML classifier within a group of suitable algorithms. A total number of 137 postmenopausal women (81.4 ± 6.95 years) were included in the study and separated into a fracture group (n = 89) and a control group (n = 48). A semi-automatic and patient-specific DXA-based FE model was used to generate mechanical attributes, describing the geometry, the impact force, bone structure and mechanical response of the bone after a sideways-fall. After preprocessing the whole dataset, 19 attributes were selected as predictors. Support Vector Machine (SVM) with radial basis function (RBF), Logistic Regression, Shallow Neural Networks and Random Forest were tested through a comprehensive validation procedure to compare their predictive performance. Clinical attributes were used alone in another experimental setup for the sake of comparison. SVM was confirmed to generate the best-learned algorithm for both experimental setups, including 19 attributes and only clinical attributes. The first, generated the best-learned model and outperformed BMD by 14pp. The results suggests that this approach could be easily integrated for effective prediction of hip fracture without interrupting the actual clinical workflow.

Management of male anterior urethral strictures in adults. Results from a national survey among urologists in Spain. / Manejo de la estenosis de uretra anterior del varón. Resultados de una encuesta nacional entre urólogos que ejercen en España.

INTRODUCTION AND OBJECTIVE: Assessment of urethral stricture (US) management seems important to evaluate the quality of attention and plan educational interventions. We aim to investigate the practice patterns on diagnostic and therapeutic approaches to adult male anterior US among urologists in Spain. MATERIALS AND METHODS: 23-question on-line survey conducted among all members of AEU (Spanish Urological Association). Demography data and practices on evaluation and treatment of US were included. 1737 invitation letters sent by email, with 21.7% response rate. Data were prospectively collected during 2016. Descriptive analysis and univariate comparisons conducted using X2 test. Statistical significance considered when P≤.05. RESULTS: Responders were mainly from Tertiary and Teaching University Hospitals. 63.2% treated≥10 patients/year with US. Retrograde urethrogram (RUG) was the commonest diagnostic tool followed by uroflowmetry (UF), and internal urethrotomy under direct vision (DVIU) the most frequent treatment. 84.4% limited DVIU for US≤1.5cm. 62.3% performed≤5 urethroplasties/year. Anastomotic urethroplasties were performed by 75.7% and graft repairs by 68.9%. Dorsal grafting was preferred rather than ventral. Non-transecting techniques were used by 23.9%. UF was the most common follow-up tool. 88.4% felt that referral units were required. Tertiary hospitals used Patient Reported Outcome Measure (PROM) questionnaires more frequently than secondary centres. High-volume urologists were more likely to use non-transecting techniques and to choose urethroplasty as first choice procedure. CONCLUSIONS: Male anterior US in Spain are treated by many urologists, mainly using endoscopic procedures. RUG is preferred for diagnosis, and UF for follow-up. A high percentage of urologists perform urethroplasties, mainly anastomotic repairs, but in low volume.

SEOM clinical guideline for the management of immune-related adverse events in patients treated with immune checkpoint inhibitors (2019).

The use of immune checkpoint inhibitors has emerged as an effective treatment option for patients with several tumor types. By increasing the activity of the immune system, they can induce inflammatory side effects, which are often termed immune-related adverse events. These are pathophysiologically unique toxicities, compared with those from other anticancer therapies. In addition, the spectrum of the target organs is very broad. Immune-inflammatory adverse events can be life threatening. Prompt diagnosis and pharmacological intervention are instrumental to avoid progression to severe manifestations. Consequently, clinicians require new skills to successfully diagnose and manage these events. These SEOM guidelines have been developed with the consensus of ten medical oncologists. Relevant studies published in peer-review journals were used for the guideline elaboration. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation.

Ubiquitin-proteasomal regulation of chromatin remodeler INO80 in the nucleus accumbens mediates persistent cocaine craving.

Neuroadaptations in the nucleus accumbens (NAc) underlie cue-induced cocaine craving that intensifies ("incubates") during abstinence and is believed to contribute to persistent relapse vulnerability. Changes in gene expression often govern perpetual behavioral abnormalities, but epigenetic plasticity during prolonged abstinence from drug exposure is poorly understood. We examined how E3 ubiquitin ligase TRIM3 dysregulates chromatin remodeler INO80 to mediate cocaine craving during prolonged abstinence. We found that INO80 expression increased in the NAc on abstinence day 30 (AD30) but not on AD1 following cocaine self-administration. Furthermore, TRIM3, which mediates degradation of INO80, was reduced on AD30, along with TRIM3-INO80 interaction. Viral-mediated gene transfer of INO80 or TRIM3 governed cocaine craving during prolonged abstinence. Lastly, chromatin immunoprecipitation followed by massively parallel DNA sequencing identified INO80-mediated transcriptional regulation of predicted pathways associated with cocaine plasticity. Together, these results demonstrate a novel ubiquitin-proteasomal-epigenetic mechanism by which TRIM3-INO80 mediates cocaine craving during prolonged abstinence.

Potentially toxic elements in commonly consumed fish species from the western Mediterranean Sea (Almería Bay): Bioaccumulation in liver and muscle tissues in relation to biometric parameters.

Marine pollution is one of today's most relevant problems. Public awareness has been raised about the harmful potential of heavy metals (HMs) accumulating in edible fish and possibly ending up in human diet through the food chain. This study aimed to characterize and evaluate As, Cd, Cr, Cu, Ni and Pb contents in four edible fish species from the western Mediterranean Sea. Liver and muscle toxic elements were determined by GF-AAS in Mullus surmuletus, Merluccius merluccius, Auxis rochei and Scomber japonicus from Almería Bay (Spain). Muscular composition, biometrics and trophic levels were also determined. The mean PTE concentration levels (mg kg-1, DW) in fish muscle tissue were: As (2.90-53.74), Cd (0.01-0.18), Cr (0.53-2.01), Cu (0.78-6.93), Ni (0.06-0.24), Pb (0.0-0.32). These concentrations did not exceed the maximum limits set by European legislation (Commission Regulation (EC) No. 1881/2006) for the intake of these marine species. Accumulation of toxic elements tends to be seen in the liver (As (7.31-26.77), Cd (0.11-8.59), Cr (0.21-2.94), Cu (2.64-16.90), Ni (0.16-1.03), Pb (0.0-0.99)). As was the element at highest risk in this Mediterranean region, especially due to red mullet values in muscle. The high As contents with living habits as benthic species that feed near the coast. HMs, especially muscle Cd contents, were associated with higher contents of lipids and organic matter, and bigger specimen size (length and weight), while As was linked to higher fish protein content. However, these relationships between potentially toxic elements (PTE) and biometric indices and body composition parameters depend on species. Finally, the THQ indices indicated that eating fish from Almería Bay poses no human health risk despite pollution from the Almería coastline.