Plasmon-enhanced multi-photon excited photoluminescence of Au, Ag, and Pt nanoclusters.

In this work, we have studied the multi-photon excited photoluminescence from metal nanoclusters (NCs) of Au, Ag and Pt embedded in Al2O3matrix by ion implantation. The thermal annealing process allows to obtain a system composed of larger plasmonic metal nanoparticles (NPs) surrounded by photoluminescent ultra-small metal NCs. By exciting at 1064 nm, visible emission, ranging from 450 to 800 nm, was detected. The second and fourth-order nature of the multiphoton process was verified in a power-dependent study measured for each sample below the damage threshold. Experiments show that Au and Ag NCs exhibit a four-fold enhanced multiphoton excited photoluminescence with respect to that observed for Pt NCs, which can be explained as a result of a plasmon-mediated near-field process that is of less intensity for Pt NPs. These findings provide new opportunities to combine plasmonic nanoparticles and photoluminescent nanoclusters inside a robust inorganic matrix to improve their optical properties. Plasmon-enhanced multiphoton excited photoluminescence from metal nanoclusters may find potential application as ultrasmall fluorophores in multiphoton sensing, and in the development of solar cells with highly efficient energy conversion modules.

Workplace aggressions on hospital workers: A current and prevalent problem with a high demand for training.

BACKGROUND: Workplace aggressions on hospital workers is a very frequent and under-reported problem. OBJECTIVE: The novel objective of our study was to analyze the number of workplace aggressions per hospital worker. Other objectives of the study were to analyze the management knowledge and interest in receiving training on aggressions by hospital workers. METHODS: An anonymous survey was handed out among all professionals in a university hospital. RESULTS: A total of 1118 anonymous surveys were collected. The responders declared that throughout their working life they had suffered some sort of verbal aggression in the hospital in 766 cases (68.5%) and physical aggression in 393 cases (35.2%). Multiple logistic regression analyses found higher risk of receiving physical and verbal aggression in the nursing category and in the Emergency, Critical Care or Psychiatry Units, and a higher risk of receiving physical aggression in women. The score on the level of personal knowledge regarding the legal, physical, and psychological management of aggressions (score 0-10 for each of the 3 aspects) was 2.91±2.68 in legal management, 2.97±2.77 in psychological management and 2.91±2.76 in physical management. The opinion about the interest of receiving training (score from 0 to 10) on the legal management of hospital aggressions was 8.90±1.72, on psychological management was 8.85±1.78 and on physical management was 8.88±1.78. CONCLUSIONS: Workplace aggression on hospital workers mainly affects women, the nursing category and the Emergency, Critical Care or Psychiatry Units. Hospital workers showed little knowledge on the topic but a great interest in receiving training.

Are GES carbapenemases underdiagnosed? An allelic discrimination assay for their accurate detection and differentiation.

GES (Guiana Extended Spectrum) carbapenemases belong to "minor class A carbapenemases" and its prevalence could be underestimated due to the lack of specific tests. The aim of this study was to develop an easy PCR method to differentiate between GES ß-lactamases with or without carbapenemase activity, based on an allelic discrimination system of SNPs that encode E104K and G170S mutations, without need of sequencing. Two pair of primers and Affinity Plus probes, labeled with different fluorophores; FAM/IBFQ and YAK/IBFQ, were designed for each one of the SNPs. This allelic discrimination assay allows to detect in real time the presence of all type of GES- ß-lactamases, being able to differentiate between carbapenemases and extended-spectrum ß-lactamase (ESBL), through a quick PCR test that avoid costly sequencing approaches and could help to decrease the current underdiagnosis of minor carbapenemases that scape of phenotypic screenings.

Tuning the aspect ratio of silver nanospheroids embedded in silica: erratum.

We present a corrigendum to our Letter [Opt. Lett.35, 703 (2010)10.1364/OL.35.000703]. In the original Letter we inadvertently included in Fig. 2(a) a TEM micrograph corresponding to a different, but very similar, sample. This corrigendum replaces Fig. 2(a) with a correct version. Since the main results are rather based in optical absorption measurements, and their modeling by using the T-matrix method, this correction does not affect the results and conclusions of the original Letter.

Economic impact of periprosthetic hip fractures / Impacto económico de las fracturas periprotésicas de cadera

Introduction: Hip replacement is one of the most successful operations in orthopaedic surgery. Periprosthetic hip fractures (PPHF) have very serious consequences for the patient, and they also entail a very important economic impact on healthcare systems. The aim of the study was to provide the first detailed cost analysis of PPHF in a traumatology and orthopaedics service in a third level hospital in Spain. Methods: The study included all patients admitted between 2009 and 2019 with a diagnosis of “PPHF”. We assessed hospital stay cost, total cost of the operating theatre, cost of the implants used, analyses, consultations with other specialists, rehabilitation sessions, radiological tests, microbiology, blood transfusions and other surgical operations during the same admission. Results: 78 patients were included in the study, 49 women and 29 men, with a mean age of 78.74 years (R 45–92). 69 patients received surgical treatment, 75% had open reduction and internal fixation (ORIF), and 25% had revision surgery. The total cost was €1,139,650.17. The average cost was €14,610.90. Significantly higher costs were incurred for revision compared to ORIF treatments, admissions that lasted more than 30 days, and patients who required more than one operation during admission. The most costly factors were the hospital stay (46%), the cost of the surgery itself (35%), and the implants (24%). Conclusions: Revision arthroplasty versus ORIF treatment, admissions lasting more than 30 days, and patients requiring more than one operation on admission incurred significantly higher costs. The average cost, from a hospital perspective, generated by a PPHF was €14,610.90. The most costly factors were, in descending order, the hospital stay, the cost of the surgery itself, and the implants. It is necessary to establish protocols and updated therapeutic algorithms in the perioperative management of PPHF in order to reduce both morbidity rates and associated costs.(AU)

Introducción: La artroplastia de cadera es una de las operaciones con mejores resultados en cirugía ortopédica. Las fracturas periprotésicas de cadera (FPPC) tienen consecuencias muy graves para el paciente y además suponen un impacto económico muy importante para los sistemas sanitarios. El objetivo del estudio es realizar el primer análisis detallado de los costes de las FPPC en un Servicio de Cirugía Ortopédica y Traumatología en un hospital universitario de tercer nivel en España. Métodos: El estudio incluyó a todos los pacientes ingresados entre 2009 y 2019 con el diagnóstico de «FPPC». Se evaluaron el coste de la estancia hospitalaria, el coste total del quirófano, el coste de los implantes utilizados, los análisis de sangre, las consultas con otros especialistas, las sesiones de rehabilitación, las pruebas radiológicas, la microbiología, las transfusiones de sangre y otras intervenciones quirúrgicas durante el mismo ingreso. Resultados: Se incluyó a un total de 78 pacientes, 49 mujeres y 29 hombres, con una edad media de 78,74 años (R 45-92); 69 pacientes recibieron tratamiento quirúrgico, el 75% se sometió a reducción abierta y fijación interna (RAFI) y el 25% a revisión protésica. El coste total fue de 1.139.650,17 €. El coste medio fue de 14.610,90 €. Los costes fueron significativamente más elevados en la revisión protésica que en la RAFI, en los ingresos que duraron más de 30 días y en los pacientes que requirieron más de una intervención quirúrgica durante el ingreso. Los factores que más influyeron en el coste fueron la estancia hospitalaria (46%), el coste de la intervención quirúrgica (35%) y el de los implantes (24%). Conclusiones: La cirugía de revisión protésica frente a RAFI, los ingresos de más de 30 días y los pacientes que requirieron más de una intervención quirúrgica durante el ingreso supusieron costes significativamente mayores. El coste medio, desde el punto de vista hospitalario, generado por una FPPC fue de 14.610,90 €.(AU)

[Artículo traducido] Impacto económico de las fracturas periprotésicas de cadera / Economic impact of periprosthetic hip fractures

Introduction: Hip replacement is one of the most successful operations in orthopaedic surgery. Periprosthetic hip fractures (PPHF) have very serious consequences for the patient, and they also entail a very important economic impact on healthcare systems. The aim of the study was to provide the first detailed cost analysis of PPHF in a traumatology and orthopaedics service in a third level hospital in Spain. Methods: The study included all patients admitted between 2009 and 2019 with a diagnosis of “PPHF”. We assessed hospital stay cost, total cost of the operating theatre, cost of the implants used, analyses, consultations with other specialists, rehabilitation sessions, radiological tests, microbiology, blood transfusions and other surgical operations during the same admission. Results: 78 patients were included in the study, 49 women and 29 men, with a mean age of 78.74 years (R 45–92). 69 patients received surgical treatment, 75% had open reduction and internal fixation (ORIF), and 25% had revision surgery. The total cost was €1,139,650.17. The average cost was €14,610.90. Significantly higher costs were incurred for revision compared to ORIF treatments, admissions that lasted more than 30 days, and patients who required more than one operation during admission. The most costly factors were the hospital stay (46%), the cost of the surgery itself (35%), and the implants (24%). Conclusions: Revision arthroplasty versus ORIF treatment, admissions lasting more than 30 days, and patients requiring more than one operation on admission incurred significantly higher costs. The average cost, from a hospital perspective, generated by a PPHF was €14,610.90. The most costly factors were, in descending order, the hospital stay, the cost of the surgery itself, and the implants. It is necessary to establish protocols and updated therapeutic algorithms in the perioperative management of PPHF in order to reduce both morbidity rates and associated costs.(AU)

Introducción: La artroplastia de cadera es una de las operaciones con mejores resultados en cirugía ortopédica. Las fracturas periprotésicas de cadera (FPPC) tienen consecuencias muy graves para el paciente y además suponen un impacto económico muy importante para los sistemas sanitarios. El objetivo del estudio es realizar el primer análisis detallado de los costes de las FPPC en un Servicio de Cirugía Ortopédica y Traumatología en un hospital universitario de tercer nivel en España. Métodos: El estudio incluyó a todos los pacientes ingresados entre 2009 y 2019 con el diagnóstico de «FPPC». Se evaluaron el coste de la estancia hospitalaria, el coste total del quirófano, el coste de los implantes utilizados, los análisis de sangre, las consultas con otros especialistas, las sesiones de rehabilitación, las pruebas radiológicas, la microbiología, las transfusiones de sangre y otras intervenciones quirúrgicas durante el mismo ingreso. Resultados: Se incluyó a un total de 78 pacientes, 49 mujeres y 29 hombres, con una edad media de 78,74 años (R 45-92); 69 pacientes recibieron tratamiento quirúrgico, el 75% se sometió a reducción abierta y fijación interna (RAFI) y el 25% a revisión protésica. El coste total fue de 1.139.650,17 €. El coste medio fue de 14.610,90 €. Los costes fueron significativamente más elevados en la revisión protésica que en la RAFI, en los ingresos que duraron más de 30 días y en los pacientes que requirieron más de una intervención quirúrgica durante el ingreso. Los factores que más influyeron en el coste fueron la estancia hospitalaria (46%), el coste de la intervención quirúrgica (35%) y el de los implantes (24%). Conclusiones: La cirugía de revisión protésica frente a RAFI, los ingresos de más de 30 días y los pacientes que requirieron más de una intervención quirúrgica durante el ingreso supusieron costes significativamente mayores. El coste medio, desde el punto de vista hospitalario, generado por una FPPC fue de 14.610,90 €.(AU)

Economic impact of periprosthetic hip fractures. / [Artículo traducido] Impacto económico de las fracturas periprotésicas de cadera.

INTRODUCTION: Hip replacement is one of the most successful operations in orthopaedic surgery. Periprosthetic hip fractures (PPHF) have very serious consequences for the patient, and they also entail a very important economic impact on healthcare systems. The aim of the study was to provide the first detailed cost analysis of PPHF in a traumatology and orthopaedics service in a third level hospital in Spain. METHODS: The study included all patients admitted between 2009 and 2019 with a diagnosis of «PPHF¼. We assessed hospital stay cost, total cost of the operating theatre, cost of the implants used, analyses, consultations with other specialists, rehabilitation sessions, radiological tests, microbiology, blood transfusions and other surgical operations during the same admission. RESULTS: Seventy-eight patients were included in the study, 49 women and 29 men, with a mean age of 78.74 years (R 45-92). Sixty-nine patients received surgical treatment, 75% had open reduction and internal fixation (ORIF), and 25% had revision surgery. The total cost was €1 139 650.17. The average cost was €14 610.90. Significantly higher costs were incurred for revision compared to ORIF treatments, admissions that lasted more than 30 days, and patients who required more than one operation during admission. The most costly factors were the hospital stay (46%), the cost of the surgery itself (35%), and the implants (24%). CONCLUSIONS: Revision arthroplasty versus ORIF treatment, admissions lasting more than 30 days, and patients requiring more than one operation on admission incurred significantly higher costs. The average cost, from a hospital perspective, generated by a PPHF was €14 610.90. The most costly factors were, in descending order, the hospital stay, the cost of the surgery itself, and the implants. It is necessary to establish protocols and updated therapeutic algorithms in the perioperative management of PPHF in order to reduce both morbidity rates and associated costs.

Economic impact of periprosthetic hip fractures.

INTRODUCTION: Hip replacement is one of the most successful operations in orthopaedic surgery. Periprosthetic hip fractures (PPHF) have very serious consequences for the patient, and they also entail a very important economic impact on healthcare systems. The aim of the study was to provide the first detailed cost analysis of PPHF in a traumatology and orthopaedics service in a third level hospital in Spain. METHODS: The study included all patients admitted between 2009 and 2019 with a diagnosis of "PPHF". We assessed hospital stay cost, total cost of the operating theatre, cost of the implants used, analyses, consultations with other specialists, rehabilitation sessions, radiological tests, microbiology, blood transfusions and other surgical operations during the same admission. RESULTS: 78 patients were included in the study, 49 women and 29 men, with a mean age of 78.74 years (R 45-92). 69 patients received surgical treatment, 75% had open reduction and internal fixation (ORIF), and 25% had revision surgery. The total cost was €1,139,650.17. The average cost was €14,610.90. Significantly higher costs were incurred for revision compared to ORIF treatments, admissions that lasted more than 30 days, and patients who required more than one operation during admission. The most costly factors were the hospital stay (46%), the cost of the surgery itself (35%), and the implants (24%). CONCLUSIONS: Revision arthroplasty versus ORIF treatment, admissions lasting more than 30 days, and patients requiring more than one operation on admission incurred significantly higher costs. The average cost, from a hospital perspective, generated by a PPHF was €14,610.90. The most costly factors were, in descending order, the hospital stay, the cost of the surgery itself, and the implants. It is necessary to establish protocols and updated therapeutic algorithms in the perioperative management of PPHF in order to reduce both morbidity rates and associated costs.

Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson / Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases

Introducción: La neuroinflamación está involucrada en la fisiopatología de diferentes trastornos neurológicos, en particular la enfermedad de Alzheimer (EA) y la enfermedad de Parkinson (EP). Las alteraciones en la barrera hematoencefálica pueden permitir la entrada al sistema nervioso central de linfocitos periféricos, los cuales pueden participar en la patología de las enfermedades. Objetivo: Evaluar el perfil de linfocitos periféricos en pacientes con EA y EP y su asociación con la enfermedad y su progresión. Métodos: Se incluyeron 20 pacientes con EA, 20 pacientes con EP y un grupo de individuos sanos. Diez de los pacientes con EA y 12 de los pacientes con EP fueron evaluados una segunda vez de 17 a 27 meses después del inicio del estudio. Las subpoblaciones de linfocitos y su estado de activación se determinaron mediante citometría de flujo. Todos los pacientes fueron evaluados neurológicamente utilizando escalas validadas internacionalmente. Resultados: Los pacientes con EA y EP mostraron un aumento significativo en los niveles de linfocitos activados, linfocitos susceptibles a la apoptosis, células T de memoria central y células T y B reguladoras con respecto a los sujetos sanos. A medida que las enfermedades progresaron se observó una disminución significativa de las células activadas (CD4+ CD38+ y CD8+ CD38+ en EP y EA; CD4+ CD69+ y CD8+ CD69+ en EP), de las células T susceptibles a la apoptosis y de algunas poblaciones reguladoras (CD19+ CD5+ IL10+ en EP y EA; CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ en EP). En pacientes con EA la progresión de la enfermedad se asoció con porcentajes más bajos de CD4 + CD38 + y mayores porcentajes de células CD4 efectoras al comienzo del estudio. Se observaron diferencias significativas entre ambas enfermedades. Conclusiones: Este estudio proporciona evidencia de cambios en los fenotipos de linfocitos periféricos asociados a EA y EP y a su gravedad. [...] (AU)

Introduction: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. Objective: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. Methods: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. Results: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. Conclusions: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases. (AU)

Spatiotemporal expression pattern of miR-205, miR-26a-5p, miR-17-5p, let-7b-5p, and their target genes during different stages of corpus luteum in Egyptian buffaloes.

BACKGROUND: No doubt that the corpus luteum (CL) plays a vital role in the regulation of female cyclicity in mammals. The scenarios among microRNAs (miRNAs) and their target genes and steroid hormones {estradiol (E2) and progesterone (P4)} are required for better understanding the molecular regulation of CL during its formation, maturation, and regression. We aimed to (I) study the changes in the relative abundance of miR-205, miR-26a-5p, miR-17-5p, and let-7b-5p and their target genes: LHCGR, CASP3, PCNA, AMH, and PLA2G3, during different stages of corpus luteum in Egyptian buffaloes, and (II) and to address different scenarios between steroid concentrations in the serum and the expression pattern of selected miRNAs and their targets. METHODS: The paired ovaries and blood samples were collected from apparently healthy 50 buffalo cows at a private abattoir. The ovaries bearing CL were macroscopically divided according to their morphological structure and color into hemorrhagic (CLH), developing (CLD), mature (CLM), regressed (CLR), and albicans (CLA). Small pieces from different stages of CL (CLH, CLD, CLM, CLR, and CLA) were cut and immediately kept at - 80 °C for total RNA isolation and qRT-PCR. The serum was separated for steroid level estimation. RESULTS: The LHCGR was expressed during different stages of CL, and the peak of expression was at the mid-luteal stage. The CASP3 revealed a stage-specific response at different stages of CL. The PCNA has an essential role in cellular proliferation in buffaloes CL. Both expression patterns of PLA2G3 and AMH were found over the various developmental and regression stages. It was noticed that miR-205 is conserved to target LHCGR and CASP3 transcripts. Moreover, CASP3 and AMH were targeted via miR-26a-5p. Additionally, the CASP3 and PLA2G3 were targeted via let-7b-5p. The P4 level reached its peak during CLM. There were positive and negative strong correlations between miRNAs (miR-26a-5p and miR-205), target genes (LHCGR and CASP3) during different stages of CL, and steroid hormones in the serum. CONCLUSIONS: Taken together, the orchestrated pattern among miRNAs, target genes, and steroid hormones is essential for maintaining the proper development and function of CL in buffalo cows.

Extracellular vesicles in low volume uterine lavage and serum: novel and promising biomarker for endometritis in Arabian mares.

BACKGROUND: Extracellular vesicles (EVs) are a promising biomarker and play a vital role in cell-cell communication. This study aimed (I) to identify and characterize EVs from low volume uterine lavage (LVL) and serum in mares with endometritis, compared to healthy controls and (II) to measure serum levels of interleukin 6 (IL-6), and prostaglandins (PGF2α and PGE2). Mares were divided into 30 sub-fertile (endometritis) and 20 fertile (controls). Serum and LVL was collected for EV isolation, and determination of serum levels of inflammatory mediators. Characterization and visualization of EVs were done by electron microscopy, dynamic light scattering and flow cytometry. RESULTS: Serial ultracentrifugation of LVL and use of a commercial kit for serum were strategies for EVs isolation. Mares with endometritis released higher amounts of larger size EVs. The EVs from mares with endometritis differentially expressed CD9 and CD63, compared to controls. Mares suffering from endometritis evoked higher levels of inflammatory mediators. CONCLUSIONS: Thus, EVs could be used for a better understanding the regulatory mechanisms associated with developing endometritis in mares.

First detection of SARS-CoV-2 variant B.1.1.529 (Omicron) in Ecuador.

The National Institute of Research and Public Health reported the first local record of the Omicron variant detected in Ecuador. A fully vaccinated subject returned from South Africa with a negative RT-PCR. We present the cumulative frequency of the variants in Ecuador and a phylogenetic analysis of this new Omicron.

The EMA review of trastuzumab emtansine (T-DM1) for the adjuvant treatment of adult patients with HER2-positive early breast cancer.

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate of trastuzumab [a monoclonal antibody against human epidermal growth factor receptor 2 (HER2)] and DM1 (an inhibitor of tubulin polymerisation). It was initially approved in the European Union for the treatment of adult patients with HER2-positive unresectable locally advanced or metastatic breast cancer (BC) who had previously received trastuzumab and taxanes. On 18 December 2019, a variation of the marketing authorisation was approved extending this use to the adjuvant therapy of adult patients with HER2-positive early BC who have residual invasive disease in the breast and/or lymph nodes after neoadjuvant taxane-based and HER2-targeted therapy. A phase III randomised, multicentre, open-label trial compared T-DM1 with trastuzumab as adjuvant therapy in patients with HER2-positive early BC who had received preoperative chemotherapy and HER2-targeted therapy followed by surgery, with a finding of invasive residual disease in the breast and/or axillary lymph nodes. The study met its primary endpoint by showing an increased 3-year invasive disease-free survival rate in the T-DM1 arm (88.3%) compared with the trastuzumab arm (77.0%), with an unstratified hazard ratio of 0.50 (95% confidence interval: 0.39-0.64). There was a higher incidence of hepatotoxicity (37.3% versus 10.6%), thrombocytopenia (28.5% versus 2.4%), peripheral neuropathy (32.3% versus 16.9%), haemorrhage (29.2% versus 9.6%) and pulmonary toxicity (2.8% versus 0.8%) in the T-DM1 arm compared with the control arm. The aim of this manuscript was to summarise the scientific review of the application leading to regulatory approval of this additional indication in the European Union.

New insights into molecular aspects of sperm-oviductal binding in Egyptian buffaloes using an in vitro model: Effects of oviductal segments and media.

We aimed (I) to simulate an in vivo milieu, through establishing an in vitro paradigm to study sperm-oviductal interactions using different segments of oviduct, as well as different incubation media, and (II) to investigate spatial changes of oviductal gene expression. Two experiments were designed; one was to investigate the yield of oviduct aggregates from different oviduct segments; in the second experiment, we observed effects of different incubation media on sperm-oviductal binding. Oviduct cell pellets before (control) and after sperm binding were collected for RNA isolation and gene expression. Isthmus resulted in a higher aggregate yield and possessed the highest affinity towards spermatozoa. The different segments of oviduct showed clear changes in gene expression after sperm binding. TALP medium promoted formation of a higher number of oviduct aggregates towards spermatozoa. Different media resulted in profound alterations in isthmus gene expression. Collectively, isthmus segment in TALP media showed the highest binding affinity to spermatozoa. At the molecular level, our in vitro model was successful for simulation in vivo milieu. Thus, our findings could be used as a simple tool to gain more insights into the molecular regulation of sperm movement, selection and affinity for oviductal binding in buffaloes.

Impact of nano-selenium on nuclear maturation and genes expression profile of buffalo oocytes matured in vitro.

Supplementation of maturation media with antioxidant (bulk form) improves oocyte maturation. However, the influence of adding antioxidant (nano-particles) on oocyte maturation is not well known. We aimed to evaluate the effect of selenium nano-particles (SeNP) and bulk selenium (Se) on buffalo oocytes maturation, in terms nuclear maturation and molecular level. Oocytes were distributed into four groups; 1st group was control, 2nd group was supplied with Se (10 ng/ml), 3rd and 4th groups were supplied with 1 µg/ml SeNP (67 nm), and SeNP (40 nm), respectively. Matured oocytes were fixed and stained to determine nuclear maturation. Oocytes and COC after IVM were stored at - 80 °C, for RNA isolation and qRT-PCR for selected genes. The Se and seNP (40 nm) had a positive effect on oocytes nuclear maturation rates. Apoptosis-related cysteine peptidase (CASP3) was reduced in all supplemented groups. Anti-Mullerian hormone (AMH) was up-regulated in oocytes supplemented with SeNP (40 nm). In COC, AMH increased in group supplemented with SeNP (67 nm). In oocytes, phospholipase A2 group III (PLA2G3) decreased in all supplemented groups. While in COC, PLA2G3increased in group supplied with Se. In COC, luteinizing hormone/choriogonadotropin receptor (LHCGR) increased in groups supplied with Se or SeNP (40 nm).Glutathione peroxidase 4 (GPX4) increased in all supplemented groups, in oocytes and COC. In oocytes, superoxide dismutase (SOD) was up-regulated in supplemented groups {Se and SeNP (67 nm)}.The DNA methyltransferase (DNMT) in oocytes was reduced in supplemented groups. In oocytes, the POU class 5 homeobox 1 (OCT4) increased in all supplemented groups. In COC, the OCT4 was over-expressed in group supplemented with SeNP (40 nm). Selenium supplementation in bulk or nano-particle improved in vitro buffalo oocytes maturation, viaup-regulation of antioxidant defense and development competence genes. SeNP (smaller size, 40 nm) induced higher expression of antioxidant gene.

Evaluation of the influence of main groundwater ions on arsenic removal by limestones through column experiments.

The influence of common groundwater major ions on arsenic (As) retention by native limestones was studied through column experiments. Columns were packed with rock particles (0.5-1.41 mm) and fed with solutions containing As, and chloride (Cl), sulfate, bicarbonate or fluoride (F) in concentrations similar to those measured in one of the most As-rich wells of Mexico. Besides, other solutions were also treated containing multiples or submultiples of those anion concentrations. Physico-chemical parameters, As, and each anion concentrations were determined weekly along 4 months. After the end of the experiments rocks collected from the top of the columns were analyzed by XRF, XRD, and SEM-WDS. Concentrations of As decreased from 1.2 mg/L to values below the Mexican drinking water standard (0.025 mg/L), since the first week in the solutions containing F or Cl keeping low values afterwards, indicating that they do not interfere with As removal. However, although As strongly decreased in the solutions containing sulfate since the first week, it started to increase from the 12th week in the highest concentrated solution. Bicarbonate was the anion affecting most As retention, since, after its decrease below 0.025 mg/L in the 2nd week for both solutions (30 mg/L and 300 mg/L), it started to increase since the 7th week in the most concentrated one, but maintained a low concentration in the least concentrated solution. Saturation index calculations and XRD analyses did not evidence the formation of As minerals. However, SEM elemental maps and XRF analyses showed the presence of As on the rocks after the treatments. Results indicate that As may be retained by sorption. Sulfate and bicarbonate compete with As for sorption sites. Results showed that native limestones are an option for treating As polluted water. Experiments also indicated that bicarbonate and sulfate may interfere with As removal depending on their concentrations.

Inflammatory response induced by Helicobacter pylori infection in lung.

Helicobacter pylori is a microorganism that in the last years has been associated with extragastric disorders such as respiratory diseases, however, its impact on lung is partially understood. The aim of this work was to study infection impact of H. pylori on the inflammatory markers expression at the pulmonary level using an animal model. Infection was performed by BALB/c wild type (WT) mice orotracheal instillation with 20 µl of 1 × 108H. pylori reference strain suspension once per day throughout 3 days. Inflammatory response was evaluated at 3, 7, 14, 21 and 30 days post infection. Lung was aseptically removed and pulmonary edema index values showed a significant change at 30 days of infection. Hematoxylin-Eosin (H-E) stain allowed to visualizing H. pylori presence in lung samples at 3 days of infection near the phagocytic cells or in the alveoli lumen. Bronchoalveolar lavage (BAL) was used for inflammatory response evaluation. Lactate dehydrogenase values showed a gradual increase in infected animals along infection time. Protein concentrations in mg/ml from BAL increased significantly at 7 days in infected animals. Macrophages viability obtained from BAL, decreased at the first moment of infection, maintaining constant values along contamination time. Results obtained demonstrate an inflammatory response in lung after orotracheal H. pylori infection and suggest that the pathogenic mechanism is strongly evidenced by tissue damage, endothelial dysfunction inflammatory mediators and markers expression at the pulmonary level.

Weighting the impact of virulence on the outcome of Pseudomonas aeruginosa bloodstream infections.

OBJECTIVES: We assessed the association between the lethality of Pseudomonas aeruginosa in a Caenorhabditis elegans model and outcomes of P. aeruginosa bloodstream infections. METHODS: A total of 593 P. aeruginosa bloodstream isolates recovered from a prospective Spanish multicentre study were analysed. Clinical variables, susceptibility profiles and Type III Secretion System (TTSS) genotypes (exoU/exoS genes) were available from previous studies. A C. elegans virulence score (CEVS) was used, classifying the isolates into high (CEVS 4-5), intermediate (CEVS 3) and low (CEVS 1-2) virulence. The main outcome analysed was 30-day mortality. RESULTS: Up to 75% (446/593) of the isolates showed a high-virulence phenotype, and 17% (101/593) a low-virulence one. No association between virulence phenotype and the main outcome variable (30-day mortality) was found (29/101 (28.7%) versus 127/446 (28.5%), p 1). However, an inverse association between C. elegans virulence and multidrug-resistant and extensively drug-resistant profiles was documented (OR 0.655 (95% CI 0.571-0.751) and OR 0.523 (95% CI 0.436-0.627), p <0.001, respectively), whereas the exoU genotype was significantly more frequent among isolates showing high virulence (10/101 (9.9%) versus 112/446 (25.1%), p <0.001). Moreover, although significance was not reached, strains showing a high-virulence phenotype tended to be associated with community-acquired infections (1/101 (1%) versus 25/446 (5.6%), p 0.065), whereas low-virulence phenotypes tended to be associated with a higher illness severity (such as higher median Pitt score: 2 (1-4) versus 1 (0-3), p 0.036, or initial multiorgan dysfunction: 17/101 (16.8%) versus 41/446 (9.2%), p 0.024), with some underlying conditions (such as chronic renal failure 24/101 (23.8%) versus 59/446 (13.2%), p 0.013), and with the respiratory source of infections (17/101 (16.8%) versus 45/446 (10.1%), p 0.058). CONCLUSIONS: Our results indicate that the P. aeruginosa virulence phenotype in a C. elegans model correlates with virulence genotype (TTSS) and resistance profile, but it is a poor prognostic marker of mortality in bloodstream infections.

Acidosis con hiperlactacidemia por metformina: frecuencia de su diagnóstico en la práctica clínica habitual y relación con la insuficiencia renal / Metformin-associated hyperlactacidaemia acidosis: Diagnosis rate in standard clinical practice and its relationship with renal failure

Antecedentes y objetivos: Estudio observacional sobre la diferencia entre el número de casos diagnosticados en situación clínica habitual de acidosis con hiperlactacidemia sospechosa de ser causada por metformina y su incidencia según la ficha técnica. Adicionalmente se exploró la relación con la función renal de la acidosis hiperlactacidémica por metformina. Pacientes: Se identificaron los casos de acidosis entre los años 2013 y 2014 mediante el análisis del CMBD y las peticiones al laboratorio. Se seleccionó a los pacientes que presentaban lactato venoso > 2,7 mmol/L en el momento de ser atendidos y para los que constaba el uso ambulatorio de metformina. La relación causal con la metformina fue evaluada independientemente por varios investigadores. Los casos incidentes se calcularon con base en el número de pacientes a los que se les había dispensado un medicamento que contuviera metformina durante el mismo periodo en el área estudiada. Resultados: Se identificaron 476 casos de acidosis, de los que en 20 se consideró que la metformina era sospechosa de causar el cuadro de acidosis con hiperlactacidemia, lo que supone una incidencia de 6,57/10.000 pacientes. El 85% de los casos presentaban insuficiencia renal aguda. Conclusiones: La incidencia aparente de acidosis con hiperlactacidemia en pacientes tratados con metformina es mayor que la establecida en la ficha técnica (inferior a 1/10.000). El desarrollo de acidosis con hiperlactacidemia por metformina está relacionado con el deterioro agudo de la función renal

Background and objectives: Observational study on the difference between the number of cases of acidosis with hyperlactacidaemia suspected of being caused by metformin diagnosed in standard clinical practice and the incidence of this condition according to the datasheet. The study also explored the relationship between renal function and metformin-associated hyperlactacidaemia acidosis. Patients: We identified cases of acidosis between 2013 and 2014 by analysing the minimum basic data set and laboratory requests. We selected patients who presented venous lactate levels >2.7 mmol/L at the time they were treated and for whom the use of outpatient metformin was confirmed. The causal relationship with metformin was independently evaluated by several researchers. The incident cases were calculated based on the number of patients who had been dispensed a drug containing metformin during the same period in the study area. Results: We identified 476 cases of acidosis. Metformin was suspected of causing the condition of acidosis with hyperlactacidaemia in 20 of these cases, which represents an incidence rate of 6.57/10,000 patients. Eighty-five percent of the cases presented acute renal failure. Conclusions: The apparent incidence of acidosis with hyperlactacidaemia in patients treated with metformin is greater than that established in the datasheet (<1/10,000). The onset of metformin-associated hyperlactacidaemia acidosis is related to acute renal impairment