Comparison of the correction of the femoral offset after the use of a stem with modular neck and its monoblock homologue in total primary hip arthroplasty. / Comparación de la corrección del offset femoral tras el empleo de un vástago monobloque y un vástago con cuello modular en la artroplastia total de cadera primaria.

INTRODUCTION AND OBJECTIVE: Dual modularity stems were introduced with the theoretical advantage of restoring hip anatomy more precisely through femoral offset and limb length adjustment. Interchangeable necks allow for intraoperative angulation, anteversion and length changes. Our objective is to study whether a better femoral offset correction is achieved with the H MAX-M® prosthesis (Limacorporate, San Daniele, Italy) compared to its monoblock counterpart. MATERIAL AND METHODS: A prospective cohort study was conducted by means of consecutive sampling on adult patients undergoing total hip arthroplasty with the diagnosis of coxarthrosis between January 2011 and December 2015. This cohort has two arms, one arm included patients who underwent modular neck arthroplasty and the other included patients who underwent monoblock total hip arthroplasty. Radiographic offset measurement of the operated hip and the contralateral hip was performed, and the difference between both values was calculated. The mean of the measurements obtained for each arm of the cohort were compared with each other. RESULTS: No statistically significant differences were observed in the difference in offset between the operated hip and the contralateral hip (P=.323). No statistically significant differences were observed in the correction of the femoral offset, determined as the difference between the operated hip and the contralateral hip (P=.323). Nor were differences observed in the postoperative offset values (P=.097). It should be noted that for both designs, the majority group is the one with restored offset (P=.001).

Comparación de la corrección del offset femoral tras el empleo de un vástago monobloque y un vástago con cuello modular en la artroplastia total de cadera primaria / Comparison of the correction of the femoral offset after the use of a stem with modular neck and its monoblock homologue in total primary hip arthroplasty

Introducción y objetivos: Los vástagos con doble modularidad fueron introducidos con la ventaja teórica de restaurar de forma más precisa la anatomía de la cadera a través del ajuste del offset femoral y la longitud de miembros. Los cuellos intercambiables permiten cambios intraoperatorios de angulación, anteversión y longitud. Nuestro objetivo es estudiar si se consigue una mejor corrección del offset femoral con la prótesis H MAX-M® (Limacorporate, San Daniele, Italia) frente a su homólogo monobloque. Material y métodos: Se realizó un estudio de cohortes prospectivo mediante muestreo consecutivo sobre pacientes intervenidos de artroplastia total de cadera con el diagnóstico de coxartrosis desde enero de 2011 hasta diciembre 2015. Esta cohorte posee 2 brazos, un brazo incluyó a los pacientes intervenidos mediante vástago con cuello modular y el otro a los pacientes intervenidos mediante vástago monobloque. Se realizó la medición radiográfica del offset de la cadera intervenida, la cadera contralateral y se calculó la diferencia entre ambos valores. Las medias de las mediciones obtenidas para cada brazo de la cohorte se compararon entre sí. Resultados: No se han observado diferencias estadísticamente significativas en la corrección del offset femoral entre el grupo modular y monobloque, determinado como la diferencia de offset entre la cadera operada y la cadera contralateral (p=0,323). Tampoco se observaron diferencias en los valores de offset postoperatorio (p=0,097). Cabe decir que tanto para la prótesis modular como para la prótesis monobloque el grupo mayoritario es aquel con offset restaurado (p=0,001).(AU)

Introduction and objective: Dual modularity stems were introduced with the theoretical advantage of restoring hip anatomy more precisely through femoral offset and limb length adjustment. Interchangeable necks allow for intraoperative angulation, anteversion and length changes. Our objective is to study whether a better femoral offset correction is achieved with the H MAX-M® prosthesis (Limacorporate, San Daniele, Italy) compared to its monoblock counterpart. Material and methods: A prospective cohort study was conducted by means of consecutive sampling on adult patients undergoing total hip arthroplasty with the diagnosis of coxarthrosis between January 2011 and December 2015. This cohort has two arms, one arm included patients who underwent modular neck arthroplasty and the other included patients who underwent monoblock total hip arthroplasty. Radiographic offset measurement of the operated hip and the contralateral hip was performed, and the difference between both values was calculated. The mean of the measurements obtained for each arm of the cohort were compared with each other. Results: No statistically significant differences were observed in the difference in offset between the operated hip and the contralateral hip (P=.323). No statistically significant differences were observed in the correction of the femoral offset, determined as the difference between the operated hip and the contralateral hip (P=.323). Nor were differences observed in the postoperative offset values (P=.097). It should be noted that for both designs, the majority group is the one with restored offset (P=.001).(AU)

Comparison of the correction of the femoral offset after the use of a stem with modular neck and its monoblock homologue in total primary hip arthroplasty / Comparación de la corrección del offset femoral tras el empleo de un vástago monobloque y un vástago con cuello modular en la artroplastia total de cadera primaria

Introduction and objective: Dual modularity stems were introduced with the theoretical advantage of restoring hip anatomy more precisely through femoral offset and limb length adjustment. Interchangeable necks allow for intraoperative angulation, anteversion and length changes. Our objective is to study whether a better femoral offset correction is achieved with the H MAX-M® prosthesis (Limacorporate, San Daniele, Italy) compared to its monoblock counterpart. Material and methods: A prospective cohort study was conducted by means of consecutive sampling on adult patients undergoing total hip arthroplasty with the diagnosis of coxarthrosis between January 2011 and December 2015. This cohort has two arms, one arm included patients who underwent modular neck arthroplasty and the other included patients who underwent monoblock total hip arthroplasty. Radiographic offset measurement of the operated hip and the contralateral hip was performed, and the difference between both values was calculated. The mean of the measurements obtained for each arm of the cohort were compared with each other. Results: No statistically significant differences were observed in the difference in offset between the operated hip and the contralateral hip (P=.323). No statistically significant differences were observed in the correction of the femoral offset, determined as the difference between the operated hip and the contralateral hip (P=.323). Nor were differences observed in the postoperative offset values (P=.097). It should be noted that for both designs, the majority group is the one with restored offset (P=.001).(AU)

Introducción y objetivos: Los vástagos con doble modularidad fueron introducidos con la ventaja teórica de restaurar de forma más precisa la anatomía de la cadera a través del ajuste del offset femoral y la longitud de miembros. Los cuellos intercambiables permiten cambios intraoperatorios de angulación, anteversión y longitud. Nuestro objetivo es estudiar si se consigue una mejor corrección del offset femoral con la prótesis H MAX-M® (Limacorporate, San Daniele, Italia) frente a su homólogo monobloque. Material y métodos: Se realizó un estudio de cohortes prospectivo mediante muestreo consecutivo sobre pacientes intervenidos de artroplastia total de cadera con el diagnóstico de coxartrosis desde enero de 2011 hasta diciembre 2015. Esta cohorte posee 2 brazos, un brazo incluyó a los pacientes intervenidos mediante vástago con cuello modular y el otro a los pacientes intervenidos mediante vástago monobloque. Se realizó la medición radiográfica del offset de la cadera intervenida, la cadera contralateral y se calculó la diferencia entre ambos valores. Las medias de las mediciones obtenidas para cada brazo de la cohorte se compararon entre sí. Resultados: No se han observado diferencias estadísticamente significativas en la corrección del offset femoral entre el grupo modular y monobloque, determinado como la diferencia de offset entre la cadera operada y la cadera contralateral (p=0,323). Tampoco se observaron diferencias en los valores de offset postoperatorio (p=0,097). Cabe decir que tanto para la prótesis modular como para la prótesis monobloque el grupo mayoritario es aquel con offset restaurado (p=0,001).(AU)

[The role of eslicarbazepine acetate in the treatment of focal-onset epilepsy in pediatric age: practical issues]. / Papel del acetato de eslicarbazepina en el tratamiento de la epilepsia de origen focal en la edad pediátrica: consideraciones prácticas.

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) of the carboxamide family and structurally related to carbamazepine and oxcarbazepine, although it has pharmacological differences that may have relevant implications of clinical utility. Since 2009 in Europe, ESL has been indicated for use in adults as adjuvant therapy in patients with partial-onset seizures (currently called focal-onset), with or without secondary generalization (with or without evolution to bilateral tonic-clonic, in current terminology). In 2017, the indication for adjunctive therapy of patients with partial-onset seizures with or without secondary generalization was extended to its use as monotherapy in adults and as adjuvant therapy in adolescents and children older than 6 years. A group of experts carried out this review aimed at the aspects of most interest in the clinical practice of the use of ESL in the pediatric population, including differential aspects from other AEDs. Aspects such as efficacy, dosage, clinical response depending on age, tolerability and its management, neurocognitive and behavioral profile, need for monitoring of any analytical parameter, role of plasma level monitoring, possible added value of the once-daily administration, clinical situations in which the addition of ESL would be recommended, use with other sodium channel blockers, how to switch from carbamazepine/oxcarbazepine, potential interactions with other AEDs, potential interactions with drugs other than AEDs, and some practical issues that require additional research.

TITLE: Papel del acetato de eslicarbazepina en el tratamiento de la epilepsia de origen focal en la edad pediátrica: consideraciones prácticas.El acetato de eslicarbazepina (ESL) es un fármaco antiepiléptico (FAE) de tercera generación de la familia de las carboxamidas y estructuralmente relacionado con la carbamazepina y la oxcarbazepina, aunque presenta diferencias farmacológicas que pueden tener implicaciones de utilidad clínica relevantes. Desde 2009, en Europa, el ESL está indicado para su utilización en adultos como terapia adyuvante en pacientes con crisis de inicio parcial (actualmente denominada de inicio focal), con o sin generalización secundaria (con o sin evolución a tonicoclónica bilateral, en terminología actual). En 2017, la indicación como tratamiento adyuvante de los pacientes con crisis de inicio parcial con o sin generalización secundaria se amplió a su utilización en monoterapia en adultos y en combinación en adolescentes y niños mayores de 6 años. Un grupo de expertos realizó esta revisión orientada a la práctica clínica del uso de ESL en población pediátrica, incluyendo aquellos puntos diferenciales respecto a otros FAE. Se han incluido aspectos como la eficacia, dosificación, respuesta clínica en función de la edad, tolerabilidad y su manejo, perfil neurocognitivo y conductual, necesidad de control de algún parámetro analítico, papel de la monitorización de los niveles plasmáticos, posible valor añadido de la administración única, situaciones clínicas en las que sería recomendable la adición de ESL, utilización con otros bloqueantes de los canales del sodio, realización del cambio desde carbamazepina/oxcarbazepina, potenciales interacciones con otros FAE, potenciales interacciones con otros fármacos distintos de los FAE, y algunas consideraciones prácticas que requieren una investigación adicional.

Atmospheric transport is a major pathway of microplastics to remote regions.

In recent years, marine, freshwater and terrestrial pollution with microplastics has been discussed extensively, whereas atmospheric microplastic transport has been largely overlooked. Here, we present global simulations of atmospheric transport of microplastic particles produced by road traffic (TWPs - tire wear particles and BWPs - brake wear particles), a major source that can be quantified relatively well. We find a high transport efficiencies of these particles to remote regions. About 34% of the emitted coarse TWPs and 30% of the emitted coarse BWPs (100 kt yr-1 and 40 kt yr-1 respectively) were deposited in the World Ocean. These amounts are of similar magnitude as the total estimated direct and riverine transport of TWPs and fibres to the ocean (64 kt yr-1). We suggest that the Arctic may be a particularly sensitive receptor region, where the light-absorbing properties of TWPs and BWPs may also cause accelerated warming and melting of the cryosphere.

Nitrite inhibition of microalgae induced by the competition between microalgae and nitrifying bacteria.

Outdoor microalgae cultivation systems treating anaerobic membrane bioreactor (AnMBR) effluents usually present ammonium oxidising bacteria (AOB) competition with microalgae for ammonium uptake, which can cause nitrite accumulation. In literature, nitrite effects over microalgae have shown controversial results. The present study evaluates the nitrite inhibition role in a microalgae-nitrifying bacteria culture. For this purpose, pilot- and lab-scale assays were carried out. During the continuous outdoor operation of the membrane photobioreactor (MPBR) plant, biomass retention time (BRT) of 2 d favoured AOB activity, which caused nitrite accumulation. This nitrite was confirmed to inhibit microalgae performance. Specifically, continuous 5-d lab-scale assays showed a reduction in the nitrogen recovery efficiency by 32, 42 and 80% when nitrite concentration in the culture accounted for 5, 10 and 20 mg N·L-1, respectively. On the contrary, short 30-min exposure to nitrite showed no significant differences in the photosynthetic activity of microalgae under nitrite concentrations of 0, 5, 10 and 20 mg N·L-1. On the other hand, when the MPBR plant was operated at 2.5-d BRT, the nitrite concentration was reduced to negligible values due to increasing activity of microalgae and nitrite oxidising bacteria (NOB). This allowed obtaining maximum MPBR performance; i.e. nitrogen recovery rate (NRR) and biomass productivity of 19.7 ± 3.3 mg N·L-1·d-1 and 139 ± 35 mg VSS·L-1·d-1, respectively; while nitrification rate (NOxR) reached the lowest value (13.5 ± 3.4 mg N·L-1·d-1). Long BRT of 4.5 d favoured NOB growth, avoiding nitrite inhibition. However, it implied a decrease in microalgae growth and the accumulation of nitrate in the MPBR effluent. Hence, it seems that optimum BRT has to be within the range 2-4.5 d in order to favour microalgae growth with respect to AOB and NOB.

Improving membrane photobioreactor performance by reducing light path: operating conditions and key performance indicators.

Microalgae cultivation has been receiving increasing interest in wastewater remediation due to their ability to assimilate nutrients present in wastewater streams. In this respect, cultivating microalgae in membrane photobioreactors (MPBRs) allows decoupling the solid retention time (SRT) from the hydraulic retention time (HRT), which enables to increase the nutrient load to the photobioreactors (PBRs) while avoiding the wash out of the microalgae biomass. The reduction of the PBR light path from 25 to 10 cm increased the nitrogen and phosphorus recovery rates, microalgae biomass productivity and photosynthetic efficiency by 150, 103, 194 and 67%, respectively.The areal biomass productivity (aBP) also increased when the light path was reduced, reflecting the better use of light in the 10-cm MPBR plant. The capital and operating operational expenditures (CAPEX and OPEX) of the 10-cm MPBR plant were also reduced by 27 and 49%, respectively. Discharge limits were met when the 10-cm MPBR plant was operated at SRTs of 3-4.5 d and HRTs of 1.25-1.5 d. At these SRT/HRT ranges, the process could be operated without a high fouling propensity with gross permeate flux (J20) of 15 LMH and specific gas demand (SGDp) between 16 and 20 Nm3air·m-3permeate, which highlights the potential of membrane filtration in MPBRs. When the continuous operation of the MPBR plant was evaluated, an optical density of 680 nm (OD680) and soluble chemical oxygen demand (sCOD) were found to be good indicators of microalgae cell and algal organic matter (AOM) concentrations, while dissolved oxygen appeared to be directly related to MPBR performance. Nitrite and nitrate (NOx) concentration and the soluble chemical oxygen demand:volatile suspended solids ratio (sCOD:VSS) were used as indicators of nitrifying bacteria activity and the stress on the culture, respectively. These parameters were inversely related to nitrogen recovery rates and biomass productivity and could thus help to prevent possible culture deterioration.

Effect of ambient temperature variations on an indigenous microalgae-nitrifying bacteria culture dominated by Chlorella.

Two outdoor photobioreactors were operated to evaluate the effect of variable ambient temperature on an indigenous microalgae-nitrifying bacteria culture dominated by Chlorella. Four experiments were carried out in different seasons, maintaining the temperature-controlled PBR at around 25 °C (by either heating or cooling), while the temperature in the non-temperature-controlled PBR was allowed to vary with the ambient conditions. Temperatures in the range of 15-30 °C had no significant effect on the microalgae cultivation performance. However, when the temperature rose to 30-35 °C microalgae viability was significantly reduced. Sudden temperature rises triggered AOB growth in the indigenous microalgae culture, which worsened microalgae performance, especially when AOB activity made the system ammonium-limited. Microalgae activity could be recovered after a short temperature peak over 30 °C once the temperature dropped, but stopped when the temperature was maintained around 28-30 °C for several days.

Supporting the improvement of air quality management practices: The "FAIRMODE pilot" activity.

This paper presents the first outcomes of the "FAIRMODE pilot" activity, aiming at improving the way in which air quality models are used in the frame of the European "Air Quality Directive". Member States may use modelling, combined with measurements, to "assess" current levels of air quality and estimate future air quality under different scenarios. In case of current and potential exceedances of the Directive limit values, it is also requested that they "plan" and implement emission reductions measures to avoid future exceedances. In both "assessment" and "planning", air quality models can and should be used; but to do so, the used modelling chain has to be fit-for-purpose and properly checked and verified. FAIRMODE has developed in the recent years a suite of methodologies and tools to check if emission inventories, model performance, source apportionment techniques and planning activities are fit-for-purpose. Within the "FAIRMODE pilot", these tools are used and tested by regional/local authorities, with the two-fold objective of improving management practices at regional/local scale, and providing valuable feedback to the FAIRMODE community. Results and lessons learnt from this activity are presented in this paper, as a showcase that can potentially benefit other authorities in charge of air quality assessment and planning.

Prótesis total de cadera primaria con par de fricción cerámica sobre cerámica de cuarta generación: resultados clínicos y de supervivencia con un seguimiento mínimo de 5 añosl / Primary total hip arthroplasty with fourth-generation ceramic bearings: clinical and survival results with a minimum follow-up of 5 years

Objetivo: Evaluar los resultados clínicos y la supervivencia de las prótesis de cadera primarias con par cerámica-cerámica (C-C) de cuarta generación implantadas en nuestro centro con un seguimiento mínimo de 5 años. Material y método: Se estudiaron 205 artroplastias primarias de cadera realizadas entre 2008 y 2012. Los resultados clínicos, prequirúrgicos y a los 5años de seguimiento fueron evaluados mediante el Harris Hip Score (HHS), el Short Form-36 (SF-36), el Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) y la escala analógica visual (EVA). Radiológicamente se estudiaron la posición de los componentes protésicos, la osteólisis periprotésica, el aflojamiento de los componentes protésicos y las roturas de los componentes cerámicos. Se registraron los eventos adversos relacionados con el par según su diámetro, con especial atención a las luxaciones protésicas y a la presencia de ruidos. La supervivencia con punto final como revisión protésica por cualquier causa fue estimada mediante el método de Kaplan-Meier. Resultados: Se obtuvieron mejorías significativas del HHS (88,7% de resultados buenos o excelentes), SF-36, WOMAC y EVA, p<0,001. Se presentaron 19 eventos adversos relacionados con la prótesis (4 fracturas periprotésicas, 4 luxaciones, 2 infecciones superficiales, 1 movilización del cotilo, 2 ruidos, 4 aflojamientos asépticos y 2 roturas del cuello protésico); el 47,3% necesitaron revisión. La supervivencia acumulada de las prótesis fue del 97,5% (IC95%: 96,4-98,5). No encontramos diferencias en la supervivencia, en eventos adversos protésicos, en la incidencia de ruidos o luxaciones y en los resultados clínicos entre los diferentes diámetros empleados. Conclusiones: Las prótesis primarias de cadera con par de fricción cerámica-cerámica de cuarta generación han mostrado una buena supervivencia a medio plazo y buenos resultados clínicos

Objective: To evaluate the clinical results and survival of primary hip prosthesis with ceramic delta bearings (C-C) with a minimum follow-up of 5years. Material and method: A total of 205 primary hip arthroplasties performed between 2008 and 2012 were studied. The clinical results, pre-surgical and at 5years of follow-up were evaluated using the Harris Hip Score (HHS), the Short Form-36 (SF-36), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the visual analogue scale (VAS). The position of the prosthetic components, periprosthetic osteolysis, loosening of the prosthetic components and ruptures of the ceramic components were studied radiologically. The adverse events related to bearings were recorded according to their diameter, paying special attention to prosthetic dislocations and the presence of noise. Survival with an endpoint of prosthetic revision for any cause was estimated using the Kaplan-Meier method. Results: Significant improvements were obtained in the HHS (88.7% of good/excellent results), SF36, WOMAC and EVA, P<.001. There were 19 adverse events related to the prosthesis (4 periprosthetic fractures, 4 dislocations, 2 superficial infections, 1 mobilization of the cup, 2 noises, 4 aseptic loosenings and 2 breaks of the prosthetic neck); 47.3% needed revision. The cumulative survival of the prostheses was 97.5% (95%CI: 96.4-98.5). No differences were found in survival, prosthetic adverse events, noise incidence or dislocations and clinical results among the different diameters used. Conclusions: Primary hip prostheses with fourth-generation ceramic bearings showed good survival in the medium term, and good clinical results

Primary total hip arthroplasty with fourth-generation ceramic bearings: Clinical and survival results with a minimum follow-up of 5 years. / Prótesis total de cadera primaria con par de fricción cerámica sobre cerámica de cuarta generación: resultados clínicos y de supervivencia con un seguimiento mínimo de 5 años.

OBJECTIVE: To evaluate the clinical results and survival of primary hip prosthesis with ceramic delta bearings (C-C) with a minimum follow-up of 5years. MATERIAL AND METHOD: A total of 205 primary hip arthroplasties performed between 2008 and 2012 were studied. The clinical results, pre-surgical and at 5years of follow-up were evaluated using the Harris Hip Score (HHS), the Short Form-36 (SF-36), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the visual analogue scale (VAS). The position of the prosthetic components, periprosthetic osteolysis, loosening of the prosthetic components and ruptures of the ceramic components were studied radiologically. The adverse events related to bearings were recorded according to their diameter, paying special attention to prosthetic dislocations and the presence of noise. Survival with an endpoint of prosthetic revision for any cause was estimated using the Kaplan-Meier method. RESULTS: Significant improvements were obtained in the HHS (88.7% of good/excellent results), SF36, WOMAC and EVA, P<.001. There were 19 adverse events related to the prosthesis (4 periprosthetic fractures, 4 dislocations, 2 superficial infections, 1 mobilization of the cup, 2 noises, 4 aseptic loosenings and 2 breaks of the prosthetic neck); 47.3% needed revision. The cumulative survival of the prostheses was 97.5% (95%CI: 96.4-98.5). No differences were found in survival, prosthetic adverse events, noise incidence or dislocations and clinical results among the different diameters used. CONCLUSIONS: Primary hip prostheses with fourth-generation ceramic bearings showed good survival in the medium term, and good clinical results.

Resource recovery from sulphate-rich sewage through an innovative anaerobic-based water resource recovery facility (WRRF).

This research work proposes an innovative water resource recovery facility (WRRF) for the recovery of energy, nutrients and reclaimed water from sewage, which represents a promising approach towards enhanced circular economy scenarios. To this aim, anaerobic technology, microalgae cultivation, and membrane technology were combined in a dedicated platform. The proposed platform produces a high-quality solid- and coliform-free effluent that can be directly discharged to receiving water bodies identified as sensitive areas. Specifically, the content of organic matter, nitrogen and phosphorus in the effluent was 45 mg COD·L-1, 14.9 mg N·L-1 and 0.5 mg P·L-1, respectively. Harvested solar energy and carbon dioxide biofixation in the form of microalgae biomass allowed remarkable methane yields (399 STP L CH4·kg-1 CODinf) to be achieved, equivalent to theoretical electricity productions of around 0.52 kWh per m3 of wastewater entering the WRRF. Furthermore, 26.6% of total nitrogen influent load was recovered as ammonium sulphate, while nitrogen and phosphorus were recovered in the biosolids produced (650 ± 77 mg N·L-1 and 121.0 ± 7.2 mg P·L-1).

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. METHODS: We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. RESULTS: Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. CONCLUSIONS: HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of 'immune cold' TNBCs.

Associations between genomic stratification of breast cancer and centrally reviewed tumour pathology in the METABRIC cohort.

The integration of genomic and transcriptomic profiles of 2000 breast tumours from the METABRIC [Molecular Taxonomy of Breast Cancer International Consortium] cohort revealed ten subtypes, termed integrative clusters (IntClust/s), characterised by distinct genomic drivers. Central histopathology (N = 1643) review was undertaken to explore the relationship between these ten molecular subtypes and traditional clinicopathological features. IntClust subtypes were significantly associated with histological type, tumour grade, receptor status, and lymphocytic infiltration (p < 0.0001). Lymph node status and Nottingham Prognostic Index [NPI] categories were also significantly associated with IntClust subtype. IntClust 3 was enriched for tubular and lobular carcinomas, the latter largely accounting for the association with CDH1 mutations in this cluster. Mucinous carcinomas were not present in IntClusts 5 or 10, but did not show an association with any of the remaining IntClusts. In contrast, medullary-like cancers were associated with IntClust 10 (15/26). Hormone receptor-positive tumours were scattered across all IntClusts. IntClust 5 was dominated by HER2 positivity (127/151), including both hormone receptor-positive (60/72) and hormone receptor-negative tumours (67/77). Triple-negative tumours comprised the majority of IntClust 10 (132/159) and around a quarter of IntClust 4 (52/217). Whilst the ten IntClust subtypes of breast cancer show characteristic patterns of association with traditional clinicopathological variables, no IntClust can be adequately identified by these variables alone. Hence, the addition of genomic stratification has the potential to enhance the biological relevance of the current clinical evaluation and facilitate genome-guided therapeutic strategies.

Chronic Silymarin, Quercetin and Naringenin Treatments Increase Monoamines Synthesis and Hippocampal Sirt1 Levels Improving Cognition in Aged Rats.

Polyphenols have beneficial neurological effects delaying cognitive and motor decline in aging due to their antioxidant, antiinflammatory and neuroprotective properties. These effects could be related to SIRT1 activation (implicated in synaptic plasticity, memory and inflammation) and monoaminergic synthesis modulation. In this work, we studied in old male rats, the in vivo effects of long-term administration of different polyphenols (silymarin, quercetin and naringenin; 20 mg/kg/day i.p, 4 weeks) (Sprague-Dawley, 18 months) on cognition and motor coordination. We also analyzed in different brain regions: tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities, which mediate central monoaminergic neurotransmitters synthesis; and immunoreactivities of SIRT1 and NF-κB (total and acetylated forms). Results indicated that chronic polyphenolic treatments showed restorative effects on cognition and motor coordination consistently with the biochemical and molecular results. Polyphenols reversed the age-induced deficits in monoaminergic neurotransmitters (serotonin, noradrenaline, and dopamine), increasing TPH and TH activity. In addition, polyphenolic treatments increased SIRT1 levels and decreased NF-κB levels in hippocampus. These results confirm polyphenolic treatments as a valuable potential therapeutic strategy for attenuating inflamm-aging and brain function decline.

Wannier-Mott Excitons in Nanoscale Molecular Ices.

The absorption of light to create Wannier-Mott excitons is a fundamental feature dictating the optical and photovoltaic properties of low band gap, high permittivity semiconductors. Such excitons, with an electron-hole separation an order of magnitude greater than lattice dimensions, are largely limited to these semiconductors but here we find evidence of Wannier-Mott exciton formation in solid carbon monoxide (CO) with a band gap of >8 eV and a low electrical permittivity. This is established through the observation that a change of a few degrees K in deposition temperature can shift the electronic absorption spectra of solid CO by several hundred wave numbers, coupled with the recent discovery that deposition of CO leads to the spontaneous formation of electric fields within the film. These so-called spontelectric fields, here approaching 4×10^{7} V m^{-1}, are strongly temperature dependent. We find that a simple electrostatic model reproduces the observed temperature dependent spectral shifts based on the Stark effect on a hole and electron residing several nm apart, identifying the presence of Wannier-Mott excitons. The spontelectric effect in CO simultaneously explains the long-standing enigma of the sensitivity of vacuum ultraviolet spectra to the deposition temperature.

Tumores neuroendocrinos de origen pulmonar: reporte de un caso / Neuroendocrine tumors of lung’s origin, a case report

Introduction or case story: Young female patient (24 years-old), without known morbid precedents. She comes for a ten-days period of symptoms characterized by fever of up to 38.5 °C and a dyspnoea grade III. Physical exam showed decreased vesicular murmur on the right pulmonary base with dullness and positive vocal vibrations. Exams: Thorax X-ray: Atelectasis condensation on the right pulmonary base. CT chest scan without contrast: Nodule located in an intermediate bronchus which generates atelectasis in the basal bronchi. Fibro-bronchoscopy (FOB): A tumour-like injury blocking 100% of the right intermediate bronchus’ duct. Biopsy: Pulmonary tissue with haemorrhagic areas, granular tissue with small cellular clusters of lobular disposal and glandular shape with eccentric central nuclei cells, with homogenous chromatin and without atypical mitosis. Immunohistochemistry: Intensely positive cells to synaptophysin and CD56. Diagnosis: Neuroendocrine Typical Carcinoid Tumor. Comments: The patient evolves without progression of dyspnoea, she is waiting for a surgical resolution of tumour at National Institute of Thorax.

Introducción o historia del caso: Mujer joven de 24 años de edad, sin antecedentes mórbidos, acudió por cuadro de 10 días de evolución, de fiebre de hasta 38,5 °C y disnea grado III. Al examen físico destacó a nivel pulmonar: murmullo pulmonar disminuido en base pulmonar derecha, matidez de la misma zona y vibraciones vocales positivas. Exámenes: Radiografía de Tórax: Condensación atelectásica en base pulmonar derecha. TAC de Tórax sin contraste: Imagen nodular a nivel de bronquio intermedio, que genera atelectasia en bronquios basales. Fibrobroncoscopía (FBC): Lesión tumoral que ocluye el 100% del lumen para bronquio intermedio derecho. Biopsia: Tejido pulmonar con áreas de hemorragia, tejido granulatorio y tumor con acúmulos celulares de disposición lobular y glanduliforme, con núcleos centrales excéntricos, cromatina homogénea, sin atipias. Inmunohistoquímica: Células intensamente positivas para sinaptofisina, y CD-56. Diagnóstico: Tumor Neuroendocrino Carcinoide típico Comentarios: Paciente evoluciona sin progresión de su disnea, esperando resolución quirúrgica del tumor en Instituto Nacional del Tórax.

Improving effect of chronic resveratrol treatment on central monoamine synthesis and cognition in aged rats.

Resveratrol is a polyphenol exhibiting antioxidant and neuroprotective effects in neurodegenerative diseases. However, neuroprotective properties during normal aging have not been clearly demonstrated. We analyzed the in vivo effects of chronic administration of resveratrol (20 mg/kg/day for 4 weeks) in old male rats (Wistar, 20 months), on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities which mediate central monoaminergic neurotransmitters synthesis, and besides, on hippocampal-dependent working memory test (radial maze). Our results show an age-related decline in neurochemical parameters that were reversed by resveratrol administration. The resveratrol treatment enhances serotonin (5-HT) levels in pineal gland, in hippocampus, and in striatum, and those of noradrenaline (NA) in hippocampus and also dopamine (DA) in striatum. These changes were largely due to an increased activity of TPH-1 (463 % in pineal gland), TPH-2 (70-51 % in hippocampus and striatum), and TH (150-36 % in hippocampus and striatum). Additionally, the observed hippocampal effects correlate with a resveratrol-induced restorative effect on working memory (radial maze). In conclusion, this study suggests resveratrol treatment as a restoring therapy for the impaired cognitive functions occurring along normal aging process, by preventing 5-HT, DA, and NA neurotransmission decline.

Intake of melatonin increases tryptophan hydroxylase type 1 activity in aged rats: Preliminary study.

Pineal melatonin is important not only for synchronization of biological rhythms, but also in the ageing process as a potential drug to relieve oxidative damage. During ageing, the nocturnal melatonin production decreases resulting in an increased incidence of disorders. Present in vivo experiments were performed to study the effects of exogenous melatonin chronically administered to old rats on the pineal biosynthesis of melatonin and the precursor serotonin (5-HT) mediated by tryptophan hydroxylase type 1 (TPH-1). Accumulation of 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition was used as a measure of the TPH-1 activity. 5-HT and its metabolite 5-HIAA were also quantified by HPLC-ED. As expected, ageing resulted in worsening of different neurochemical parameters. However, chronic intake of melatonin (1mg/kg/day, diluted in drinking water, 4 weeks) increased TPH-1 activity and significantly improved the age-induced deficits in nocturnal melatonin content in the pineal gland. Results suggest that melatonin intake (or melatonin rich foods) may contribute to recover the pineal function preventing the nocturnal descent of 5-HT and melatonin biosynthesis that normally occur in pineal gland as a consequence of ageing.

Evaluation of the use of bioethanol fuelled buses based on ambient air pollution screening and on-road measurements.

Mitigation measures to reduce greenhouse gas emissions may have adverse effects on urban air quality and human exposure to harmful pollutants. The use of bioethanol fuelled vehicles is increasing worldwide and may create new undesired pollution effects. Different measurement campaigns were performed in a pilot study to contribute to the understanding of the consequences associated with the use of bioethanol blended fuel (E95) on a series of pollutants. Ambient screening measurements of NO2, O3, acetic acid, formaldehyde and acetaldehyde were performed at different urban locations, exposed and not exposed to the circulation of bioethanol buses. In addition, volatile organic compounds were measured at the exhaust pipe of a bioethanol fuelled bus, both under idling conditions (carbonyls; DNPH cartridge) and under on-road driving conditions applying online monitoring (PTR-TOF). Higher ambient acetaldehyde values were measured at locations exposed to bioethanol fuelled buses than at locations not exposed, and very high acetaldehyde and acetic acid values were measured from the exhaust pipe during driving conditions (acetaldehyde>150 ppm; acetic acid ≈ 20-30 ppm) and modelled at close distance to the bioethanol bus. Human exposure to high concentration of acetaldehyde is expected, and it may involve a significantly increased chance in developing cancer. The high concentration of acetic acid will involve odour annoyance and significant material degradation or corrosion.