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Introduction: The implementation of people-centred care requires strategies that respond to local conditions and contexts, with the participation of local stakeholders in collaborative approaches such as co-design. Within this framework, the authors performed a literature review to identify the most implemented practices in health and social care services for co-designing digital solutions., Methods: The literature review was conducted following five steps: (i) Definition of the Keywords and their relations; (ii) Definition of the selection criteria; (iii) Search in PubMed; (iv) Selection of papers; and (v) Analysis of the selected papers., Results: 20 papers addressed to co-design health digital solutions with stakeholders were analysed in terms of the activities implemented and participants involved., Discussion: Previous studies using co-design methods for the deployment of health digital solutions employed a wide range of activities, most of them combining activities and/or mixed target groups., Conclusion: Co-design is the key to deliver people-centred care as it allows to involve stakeholders in the development of health digital solutions. Implementing one or more of the co-design methods identified in this literature review should be considered to better address the needs and specific projects and target groups., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Layer-specific experimental data for human aortic tissue suggest that, in aged arteries and arteries with non-atherosclerotic intimal thickening, the innermost layer of the aorta increases significantly its stiffness and thickness, becoming load-bearing. However, there are very few computational studies of abdominal aortic aneurysms (AAAs) that take into account the mechanical contribution of the three layers that comprise the aneurysmal tissue. In this paper, a three-layered finite element model is proposed from the simplest uniaxial stress state to geometrically parametrized models of AAAs with different asymmetry values. Comparisons are made between a three-layered artery wall and a mono-layered intact artery, which represents the complex behavior of the aggregate adventitia-media-intima in a single layer with averaged mechanical properties. Likewise, the response of our idealized geometries is compared with similar experimental and numerical models. Finally, the mechanical contributions of adventitia, media and intima are analyzed for the three-layered aneurysms through the evaluation of the mean stress absorption percentage. Results show the relevance and necessity of considering the inclusion of tunica intima in multi-layered models of AAAs for getting accurate results in terms of peak wall stresses and displacements.

Tissue-specific DNA methylation patterns are created by transcription factors that recruit methylation and demethylation enzymes to cis-regulatory elements. To date, it is not known whether transcription factors are needed to continuously maintain methylation profiles in development and mature tissues or whether they only establish these marks during organ development. We queried the role of the pioneer factor FoxA in generating hypomethylated DNA at liver enhancers. We discovered a set of FoxA-binding sites that undergo regional, FoxA-dependent demethylation during organ development. Conditional ablation of FoxA genes in the adult liver demonstrated that continued FoxA presence was not required to maintain the hypomethylated state, even when massive cell proliferation was induced. This study provides strong evidence for the stable, epigenetic nature of tissue-specific DNA methylation patterns directed by lineage-determining transcription factors during organ development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Multiple Myeloma (MM) is a malignant hematologic disorder and the second most common blood cancer. Interleukin-6 (IL-6) has been identified as a crucial factor for the proliferation and survival of MM cells and the overexpression of IL-6 receptor is being studied as a molecular target for therapeutic and diagnostic use in myelomas and other comorbidities. Tocilizumab is a humanized monoclonal antibody that binds IL-6R., Objective: We aim to label and evaluate Fab(Tocilizumab) with 99m Technetium or Cy7 as potential MM imaging agents., Methods: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37°C, derivatized with NHS-HYNIC-Tfa and radiolabeled with 99m Tc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h., Results: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with 99mTc via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i., Conclusion: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

On September 20, 2017, Hurricane Maria made landfall in Puerto Rico as a Category 4 hurricane with sustained winds of 155 miles per hour and torrential rains that ravaged the United States territory. In the midst of the crisis, several hundred thousand Maria survivors boarded humanitarian flights and cruise ships, seeking refuge on the United States mainland. More than three years later, tens of thousands of post-Maria migrants remain on the mainland as long-term emigres. In this article, we lay the theoretical/conceptual groundwork for researchers and practitioners interested in understanding the experiences of post-Maria migrants. Specifically, we aim to assist readers in thinking deeply about: [1] why many Puerto Ricans relocated, [2] the experiences of post-Maria migrants en movimiento , and [3] how such experiences shape their lives, behavior, and well-being. In understanding the experiences of post-Maria migrants, several theories/constructs emerge as especially salient. These include "push and pull" models, cultural stress theory and its transnational variants, the concept of crisis migration, and models of cumulative risk. We provide a succinct overview of each of these theories/constructs and describe the broad perspectives that serve as a foundational or orienting paradigm for our work (i.e., the life course perspective, the strengths perspective, and an ecodevelopmental framework). Finally, we provide illustrations of how these theories/concepts apply to emerging data from the Adelante Boricua study, an ongoing research project with post-Maria migrant youth and their parents, supported by funding from the National Institute on Minority Health and Health Disparities., (© Southern Criminal Justice Association 2021.)

Introduction: Sibaté is a municipality located in the central region of Colombia, where the first asbestos-cement facility of the country has been in operation since 1942. Both a malignant pleural mesothelioma cluster and landfilled zones with the presence of an underground friable asbestos layer have been identified in Sibaté. There is still limited knowledge regarding the history of the construction of landfilled zones, and what kinds of materials were deposited. The current study aims to improve our understanding of the history and characteristics of the landfilled zones present in Sibaté., Methods: Two participatory workshops with inhabitants of Sibaté were conducted to determine when the landfilled zones were built and their location. Information collected in participatory workshops was crossed with both topographic maps and aerial photographs, giving special attention to zones within the urban area of the municipality that in the past were inundated with water from El Muña Reservoir. An opportunistic soil sampling campaign was conducted in suspected landfilled zones that had not been previously sampled, during the replacement of pipelines of the drainage system ordered by the municipality., Results: The analysis of historical topographic maps, combined with the interpretation of aerial photographs, confirmed the disposal of residues in areas that were previously inundated with water from El Muña Reservoir, creating landfilled zones in the urban area of Sibaté. On top of these landfilled zones, a football stadium and a football field with an athletic track were built. The location of landfilled zones identified using geographic analysis was similar to the location identified analyzing maps constructed by inhabitants of Sibaté in participatory workshops. The four soil samples collected during an opportunistic sampling campaign confirmed the presence in new locations of the underground friable asbestos layer discovered in previous studies., Discussion: Based on the extension of the landfilled zones, the presence of friable asbestos in these areas, and the close proximity to a school and residential dwellings, there could have been major dispersion events of asbestos fibers in the urban area of Sibaté during the disposal of residue materials and the construction of the landfilled zones. Thus, important asbestos exposures may have occurred among residents of Sibaté, which is aggravated by the fact that during those years, more than 50% of the population of Sibaté was 25 years old or younger. Although the results of the current study improved our understanding of the processes and chronology associated with the landfilled zones, the uncertainty regarding their exact location remains significant. It is important to continue investigating the adverse health effects resulting from this potential asbestos exposure source., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Malignant gliomas are the most common malignant and aggressive primary brain tumors in adults, the prognosis being-especially for glioblastomas-extremely poor. There are no effective treatments yet. However, tyrosine kinase receptor (TKR) inhibitors and boron neutron capture therapy (BNCT), together, have been proposed as future therapeutic strategies. In this sense in our ongoing project of developing new anti-glioblastoma drugs, we identified a sunitinib-carborane hybrid agent, 1 , with both in vitro selective cytotoxicity and excellent BNCT-behavior. Consequently, we studied the ability of compound 1 to inhibit TKRs, its promotion of cellular death processes, and its effects on the cell cycle. Moreover, we analyzed some relevant drug-like properties of 1 , i.e., mutagenicity and ability to cross the blood-brain barrier. These results encouraged us to perform an in vivo anti-glioblastoma proof of concept assay. It turned out to be a selective FLT3, KIT, and PDGFR-β inhibitor and increased the apoptotic glioma-cell numbers and arrested sub-G1-phase cell cycle. Its in vivo activity in immunosuppressed mice bearing U87 MG human glioblastoma evidenced excellent anti-tumor behavior.

Background/objectives: To analyze mortality, costs, residents and personnel characteristics, in six long-term care facilities (LTCF) during the outbreak of COVID-19 in Spain., Design: Epidemiological study., Setting: Six open LTCFs in Albacete (Spain)., Participants: 198 residents and 190 workers from LTCF A were included, between 2020 March 6 and April 5. Epidemiological data were also collected from six LTCFs of Albacete for the same period of time, including 1,084 residents., Measurements: Baseline demographic, clinical, functional, cognitive and nutritional variables were collected. 1-month and 3-month mortality was determined, excess mortality was calculated, and costs associated with the pandemics were analyzed., Results: The pooled mortality rate for the first month and first three months of the outbreak were 15.3% and 28.0%, and the pooled excess mortality for these periods were 564% and 315% respectively. In facility A, the percentage of probable COVID-19 infected residents were 33.6%. Probable infected patients were older, frail, and with a worse functional situation than those without COVID-19. The most common symptoms were fever, cough and dyspnea. 25 residents were transferred to the emergency department, 21 were hospitalized, and 54 were moved to the facility medical unit. Mortality was higher upon male older residents, with worse functionality, and higher comorbidity. During the first month of the outbreak, 65 (24.6%) workers leaved, mainly with COVID-19 symptoms, and 69 new workers were contracted. The mean number of days of leave was 19.2. Costs associated with the COVID-19 in facility A were estimated at € 276,281/month, mostly caused by resident hospitalizations, leaves of workers, staff replacement, and interventions of healthcare professionals., Conclusion: The COVID-19 pandemic posed residents at high mortality risk, mainly in those older, frail and with worse functional status. Personal and economic costs were high., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The current study aimed to evaluate the relationship between specific seminal plasma components - cholesterol (CHOL), triacylglycerols (TAG) and total protein (PROT) concentrations - and semen quality in cats. A further aim was to determine the relationship between specific seminal protein bands and semen quality., Methods: Thirteen toms, 2-5 years of age, were included. Semen collection was performed by electroejaculation every 4 weeks. Fifty-eight ejaculates were assessed for motility, velocity, volume, sperm concentration, total sperm count, viability, acrosome integrity, plasma membrane integrity and sperm morphology. Samples were divided into two groups: good semen quality (GSQ) and poor semen quality (PSQ). After evaluation, seminal plasma was separated from the sperm by centrifugation and stored at -20°C. CHOL, TAG and PROT concentrations were then assessed and seminal plasma protein profile was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)., Results: Seminal plasma CHOL and TAG concentrations, motility, velocity, sperm concentration, total sperm count and sperm morphology were significantly higher in GSQ cats compared with PSQ cats ( P <0.01). Moreover, seminal plasma SDS-PAGE analysis showed an identifiable extra band exclusively in the GSQ group., Conclusions and Relevance: Data obtained in this study showed that seminal plasma CHOL and TAG concentrations and specific protein bands could be used to improve semen evaluation in toms. In this sense, the 14 kDa protein band could be a valuable marker for semen quality in the cat and should be further investigated. However, more studies are necessary to determine its relationship with fertility.

The aim was to study number, volume, apoptosis of corpora lutea (CL), and serum P 4 concentrations in early, middle, and late diestrus of dogs. Thirty-six bitches were ovari-hysterectomized (OVX): Early Diestrus (Group [G]1; OVX 20 days after end of estrus [DEH]); Mid-diestrus (GII; OVX between 21 and 40 days after DEH), and Late-diestrus (GIII; OVX between 41 and 60 days after DEH). Before OVX a blood sample was collected to quantify P 4 . After OVX, the number of CL (NCL) was recorded, CL measured using both ultrasonography (US) and caliper (CAL), and the volume (mm 3 ) was calculated. Based on abundances of caspase-3, apoptotic luteal cells were detected. Bitches in early-diestrus had greater P 4 concentrations than bitches in mid- and late-diestrus (23.52 ± 3.78 and 10.86 ± 3.88 ng/mL; P < 0.05). The NCL, cumulative USCLV, and CALCLV were similar among diestrus stages (P > 0.30). Bitches with CL (≥5) had twice the serum P 4 concentrations as bitches with CL1-2 and CL3-4 (22.71 ± 3.70 and 10.97 ± 4.06 ng/mL; P < 0.05). There were correlations between P 4 concentrations with USCLV, CALCLV, and NCL (r = 0.64, r = 0.67, r = 0.44; P < 0.0001). When serum P 4 concentrations were adjusted for stages of diestrus, however, there were only correlations during early diestrus. The percentage of apoptotic cells was greater in GIII compared with GI and GII (13.75 ± 2.26 % compared with 4.5 ± 0.68 % and 4.6 ± 1.5 %, respectively; P < 0.05). As days of diestrus increased, number of apoptotic cells increased, and serum P 4 concentrations decreased., (Copyright © 2020 Elsevier B.V. All rights reserved.)

One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro-BNCT experiments were performed for two of the most promising hybrids, 19 and 22 . We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22 , bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA . The attractive profile of developed hybrids makes them interesting agents for combined therapy.

Inhabitants of Sibaté (Colombia) report that between approximately 1975 and 1985 asbestos-containing materials (ACM) were dumped at different locations in the urban area of the municipality. Starting in around 1986, the dumping of materials resulted in landfilled zones, on top of which different facilities were then constructed. In a previous study, an underground friable asbestos layer was discovered in these landfilled zones. However, potential exposure to asbestos on the surface of landfilled zones in Sibaté has not been determined. In the current study, the U.S. EPA Activity-Based Sampling (ABS) methodology was adapted and applied in three scenarios located on potential landfilled areas in Sibaté, to estimate the current risk of exposure to asbestos through inhalation, and the resulting excess lifetime cancer risk (ELCR). For this purpose, generic ABS in a football stadium, and specific ABS in both a public playground and a school courtyard were conducted. Personal, area and blank samples were collected and analyzed using phase contrast microscopy (PCM) and transmission electron microscopy (TEM) following NIOSH 7400 and ISO 13794 methods, respectively. Exposure point concentrations were determined and compared against the action level for asbestos in air (ALAA), and were also used to calculate the ELCR of each scenario. A total of 25 airborne asbestos samples were collected, and 22 of these (12 personal samples, 7 area samples and 3 blank samples) were analyzed using PCM. Eighteen of these samples (12 personal, 3 area samples and 3 blank samples) were analyzed using TEM. The total asbestos structures concentration of personal samples ranged from non-detected to 0.326 S/cc (i.e., total asbestos structures counts ranged from 0 to 12). All samples had PCM-Equivalent asbestos structures concentrations below analytical sensitivity. Of the 22 samples analyzed, 18 were overloaded with particles. Although chrysotile and actinolite were identified in some personal samples, suggesting a potential risk of asbestos exposure, the ELCR was at U.S. EPA acceptable risk levels. Since the ABS methodology was applied in a limited number of scenarios and a small number of samples were collected, these results should be interpreted with caution and additional sampling campaigns are required to fully understand the risk of asbestos exposure in Sibaté. Methodological and analytical challenges encountered in the current study are discussed in detail, which could inform future ABS studies, not only in Sibaté, but also in other areas with asbestos-contaminated soils., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Understanding stress-strain relationships in arteries is important for fundamental investigations in mechanobiology. Here we demonstrate the essential role of chemoelasticity in determining the mechanical properties of arterial tissues. Stepwise stress-relaxation uniaxial tensile tests were carried out on samples of porcine thoracic aortas immersed in a hyperosmotic solution. The tissue deformations were tracked using optical coherence tomography (OCT) during the tensile tests and digital volume correlation (DVC) was used to obtain measurements of depth-resolved strains across the whole thickness of the tested aortas. The hyperosmotic solution exacerbated chemoelastic effects, and we were able to measure different manifestations of these chemoelastic effects: swelling of the media inducing a modification of its optical properties, and existence of a transverse tensile strain. For the first time ever to our best knowledge, 3D strains induced by chemoelastic effects in soft tissues were quantified thanks to the OCT-DVC method. Without doubt, chemoelasticity plays an essential role in arterial mechanobiology in vivo and future work should focus on characterizing chemoelastic effects in arterial walls under physiological and disease conditions. STATEMENT OF SIGNIFICANCE: Chemoelasticity, coupling osmotic phenomena and mechanical stresses, is essential in soft tissue mechanobiology. For the first time ever, we measure and analyze 3D strain fields induced by these chemoelastic effects thanks to the unique combination of OCT imaging and digital volume correlation., (Copyright © 2019. Published by Elsevier Ltd.)

Despite the existing research, the etiology of rheumatoid arthritis (RA), an autoimmune disease remains poorly understood with early and accurate diagnosis difficult to achieve. MicroRNAs (miRNAs) play an important role in biological processes as modulators of transcription and translation. Previous studies have demonstrated a downregulation of several genes in early RA stages and in addition, miRNAs may serve as early biomarkers of subclinical changes in early RA. When comparing the four groups (ANOVA P < 0.01, fold change > 4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways. Moreover, ROC analysis showed values of AUC 0.76 and P < 0.05 for miR 361-5p, identifying this miRNA as a potential biomarker of disease. We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The spontaneous breathing trial (SBT) assesses the risk of weaning failure by evaluating some physiological responses to the massive venous return increase imposed by discontinuing positive pressure ventilation. This trial can be very demanding for some critically ill patients, inducing excessive physical and cardiovascular stress, including muscle fatigue, heart ischemia and eventually cardiac dysfunction. Extubation failure with emergency reintubation is a serious adverse consequence of a failed weaning process. Some data suggest that as many as 50% of patients that fail weaning do so because of cardiac dysfunction. Unfortunately, monitoring cardiovascular function at the time of the SBT is complex. The aim of our study was to explore if central venous pressure (CVP) changes were related to weaning failure after starting an SBT. We hypothesized that an early rise on CVP could signal a cardiac failure when handling a massive increase on venous return following a discontinuation of positive pressure ventilation. This CVP rise could identify a subset of patients at high risk for extubation failure., Methods: Two-hundred and four mechanically ventilated patients in whom an SBT was decided were subjected to a monitoring protocol that included blinded assessment of CVP at baseline, and at 2 minutes after starting the trial (CVP-test). Weaning failure was defined as reintubation within 48-hours following extubation. Comparisons between two parametric or non-parametric variables were performed with student T test or Mann Whitney U test, respectively. A logistic multivariate regression was performed to determine the predictive value on extubation failure of usual clinical variables and CVP at 2-min after starting the SBT., Results: One-hundred and sixty-five patients were extubated after the SBT, 11 of whom were reintubated within 48h. Absolute CVP values at 2-minutes, and the change from baseline (dCVP) were significantly higher in patients with extubation failure as compared to those successfully weaned. dCVP was an early predictor for reintubation (OR: 1.70 [1.31,2.19], p<0.001)., Conclusions: An early rise in CVP after starting an SBT was associated with an increased risk of extubation failure. This might represent a warning signal not captured by usual SBT monitoring and could have relevant clinical implications., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos exposure sources in the town., Methods: A health and socioeconomic survey was implemented door-to-door to identify potential asbestos-related diseases. Several self-reported mesothelioma cases were identified, and for confirmation purposes, copies of the medical record with the histopathology report were obtained. A panel of six physicians analyzed the medical records. Information of validated cases was used to estimate the male and female age-adjusted incidence rate for Sibaté. Based on reports of the existence of potential asbestos-contaminated landfills, topographic maps, a digital elevation model, and current satellite images were crossed using a geographic information system to identify potential landfilled areas, and soils samples were collected in some of these areas., Results: A total of 355 surveys were completed, and 29 self-reported mesothelioma cases were identified. Twenty-five of these cases have been persons who had lived at some moment of their lives in Sibaté. It was possible to obtain copies of the medical diagnosis for 17 cases. Of these, the panel of physicians classified 15 cases as certain pleural mesothelioma, one as probable, and one as not mesothelioma. Based on this information, the estimated age-adjusted incidence rate of mesothelioma in Sibaté was 3.1 × 10 5 persons-year for males and 1.6 × 10 5 persons-year for females. These rates are high in comparison to those reported in other cities, regions, and countries of the world. Using geographic information systems, landfilled zones in the urban area of Sibaté were identified, on top of which a school and different sports facilities were built. The analysis of four soil samples collected in landfilled zones, confirmed the existence of an underground layer of friable and non-friable asbestos., Conclusion: The collected evidence suggests the presence of a malignant pleural mesothelioma cluster in Sibaté., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: The purpose of this document is to establish practical recommendations on neurogenic bladder (NB) management based on scientific evidence and medical and nursing perspective in Spinal Cord Injury (SCI) Units as a first multidisciplinary consensual approach in Spain. METHODS: This paper reports results from the first modified Delphi consensus building exercise on this procedure. A committee of recognised opinion-leaders in rehabilitation and urology with special interest in NB was constituted. A working group formed by rehabilitation doctors, urologists and nursing staff of SCI and Neurorehabilitation Units of a number of Spanish hospitals and specialised centres associated with the panel of NB experts have prepared this document. RESULTS: This review provided an overview of the main aspects described by the different clinical guidelines already available and highlighted the need to focus on recommendations in special priority situations in which there was no consensus. In view of the considerable impact this condition has on quality of life, patients should be offered help to better understand the disorder and they should be taught how to use the treatment techniques to obtain satisfactory results and promote their autonomy. CONCLUSIONS: This article presents a version of guidelines for patients with NB. The guidelines define the clinical profile of patients to provide the best evidence- based care and also an overview of the current drug and surgical treatments of NB.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by chronic and symmetrical inflammation of synovial tissue with subsequent joint destruction. SUMO1 is an important regulator of apoptosis through non-canonical mechanism in synovial fibroblasts, and POU2AF1 is a known B-cell transcriptional co-activator. The specific objective of this study was to measure the expression of SUMO1 and POU2AF1 on first-degree relatives of patients with RA and also in the preclinical and clinical stages of RA and describe their possible role in RA physiopathology. Blood samples were collected from ACPA+, ACPA-, early and established RA subjects recruited. ACPAs and CarP autoantibodies were determined by ELISA Eurodiagnostica CCplus kit according to previously described protocols. RNA was isolated from blood samples; the purity as integrity was determined. Gene expression analysis was made by RT-qPCR using specific primers for SUMO1 and POU2AF1 mRNAs; relative expression was determined according to the 2 -ΔΔct method procedure. Significant differences in the expression of both, SUMO1 and POU2AF1 were identified when comparing arthritis versus healthy or ACPA+ individuals, suggesting that the down regulation of such genes starts after the onset of symptoms in RA patients. Also, a significant correlation was identified for POU2AF1 and disease progression whit a downward trend for those with established RA. The implications of such gene down regulation are discussed in the context of RA physiopathology., (© 2019 John Wiley & Sons Ltd.)

This article presents an analysis of the concept of plagiarism in order to show the wide spectrum of manifestations that can be considered as such when committing a transgression of intellectual property, carried out with the intention of deceiving the authors' true contribution and the originality and novelty of the information. The article describes the concurrent circumstances in intentional plagiarism, and the damage that this misconduct causes in the credibility of the scientific system, in which authorship credit is the foundation of the academic career, of the prestige of the author in the scientific community, and the basis for research funding. Some circumstances are favouring this fraud: the pressure exerted on researchers by the criteria used for promotion and reward that prioritise the quantity of works on their quality, the existence of a market for the purchase and sale of scientific articles, and the proliferation of predatory journals that operate without or minimal ethical standards. Finally, the paper highlights the convenience of the adoption of criteria that prioritise the intrinsic quality of the work versus its quantity, including the active involvement of the institutions in the development of active policies for the prevention, detection, and punishment of the cases of potential fraud, and emphasize that, in the end, the prevention of fraud relies on the individual adoption of an ethical and responsible behaviour., (Copyright © 2018 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

The physiopathology of rheumatoid arthritis (RA) is mediated by proinflammatory cytokines, some of which are regulated by the JAK/STAT pathway. Tofacitinib is a JAK inhibitor, but its role in the regulation of microRNAs (miRNAs) is unknown. There is also no information regarding the role of miRNAs in the clinical relapse/remission of RA. The present project aims to identify a signature profile of miRNA expression in a subgroup of RA patients who had to discontinue tofacitinib treatment (because of the ending of a 5-year open-label clinical trial) and to describe the expression of miRNAs during RA remission or flare-up. The relative expression of 61 miRNAs was determined in serum samples with the Firefly™ BioWorks assay. Statistical analysis was performed by means of Student's t-test and heatmap analysis was performed with Firefly™ Analysis Workbench software and in the software GraphPad® Prism v5.0. Target prediction and Gene Ontology analysis were carried out using bioinformatic tools. We found a distinctive signature of miRNA expression associated with relapse, featuring upregulated expression of hsa‑miR‑432‑5p (p < 0.05). We also found upregulation of hsa‑miR‑194‑5p (p < 0.05) in samples of patients with RA flare-up. Gene Ontology analysis of the target genes for hsa‑miR‑432‑5p was performed to identify relevant pathways associated with relapse; the implications of these pathways in the physiopathology of RA are discussed. Tofacitinib treatment does not have a direct effect on the expression of measured miRNAs. The changes in hsa‑miR‑432‑5p and hsa‑miR‑194‑5p are associated with the regulation of proinflammatory pathways and RA flare-up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The aim of the study was to determine the time after treatment with a 4.7 mg deslorelin implant until Tomcat spermatogenesis activity was restored, and seminal parameters reached pre-implant values. Tomcats (n = 6) were randomly assigned to one of two treatments. Three cats (n = 3) received a deslorelin implant (4.7 mG; Suprelorin ® , Virbac, France) in the interscapular subcutaneous region whereas three (n = 3) received no implant and served as control group. Semen samples were collected by electroejaculation every 4 wk from 3 mo before treatment (pretreatment samples) until reestablishment of pre-treatment sperm quality, 32 mo post-implant insertion (PI). Each semen sample was assessed for motility, velocity, concentration, total sperm count, viability, acrosome integrity, plasma membrane integrity and sperm morphology. After semen collection, testicular volume and presence/absence of penile spines were recorded. Additionally, blood samples were taken to measure testosterone concentration. An increase in sperm concentration and total sperm count was present 1 mo PI despite of an abrupt decrease in serum testosterone concentrations after 2-4 weeks. This initial stimulatory effect was followed by a decrease in seminal parameters, reduction of testicular volume and disappearance of penile spines 2 mo PI. A single Suprelorin ® 4.7 mg implant suppressed sperm production for 22-25 months. No clinically side effect was observed during the study period. All toms returned to their initial seminal quality 23-28 months after treatment. Therefore, we conclude that Suprelorin ® 4.7 mg is a safe option for reversible reproduction control during long periods in tomcats., (Copyright © 2018. Published by Elsevier B.V.)

Pretargeted imaging, based on the highly reactive process between [1,2,4,5]tetrazines with trans-cyclooctene (TCO), appears as an attractive strategy to overcome disadvantages associated with traditional radioimmunoconjugates. To be successful, the radiolabeled component should react in vivo with the conjugated antibody and the non reactive excess clear fast from the organism. Herein, we explore the in vivo effects of hydrophilic linker incorporation into [1,2,4,5]tetrazine systems bearing a 6-hydrazinonicotinyl (HYNIC) moiety for technetium-99m coordination. Incorporation of a polypeptide chain containing hydrophilic aminoacids, resulted in a derivative with renal clearance. Pretargeted bevacizumab imaging was used as proof of concept.

Purpose: To study the rhenium-188 labeling of polyamidoamine (PAMAM) generation 4 (G4) dendrimer and its evaluation on biodistribution and chromosomal aberrations in melanoma cells induced by ionizing radiation as potential treatment agent., Materials and Methods: Dendrimers were first conjugated with Suc-HYNIC (succinimidyl 6-hydrazinopyridine-3-carboxylic acid hydrochloride). Dendrimer-HYNIC was then incubated with 188 ReO 4 - . Biodistribution was performed administrating 188 Re-dendrimer to normal (NM) or melanoma-bearing mice (MBM). Chromosome aberration test was conducted in order to measure treatment capacity of 188 Re-dendrimer in melanoma cells., Results: Radiolabeling yield of dendrimer was approx. 70%. Biodistribution studies in NM showed blood clearance with hepatic and renal depuration. MBM showed a similar pattern of biodistribution with tumor uptake of 6% of injected dose. Aberrant metaphases quantified in control cells were 7%, increasing to 29.5% in cells treated with 15μCi (0.555 MBq) of 188 Re-dendrimer for 24 h., Conclusions: 188 Re-dendrimer can produce double-stranded breaks in DNA induced by ionizing radiation in melanoma cells in vitro.

Background: Hip fractures are a public health problem worldwide, and several factors are involved with post-operative mortality. The aim of this study was to identify the pre-operative factors associated with increased mortality in elderly patients with hip fractures in a developing country during the first post-operative year., Methods: An ambidirectional cohort study was conducted with patients ≥ 65 years of age who underwent hip surgery due to a hip fracture caused by a fall from a standing position. Socio-demographic data, time to surgery, and comorbidities measured by the Charlson Comorbidity Index (CCI) were recorded. One-year mortality from all causes was the primary outcome, and 30-day and 6-month mortality were the secondary outcomes. Log-rank test was used to evaluate survival, and Cox's proportional hazard regression was used to detect the factors associated with increased mortality., Results: 478 patients who underwent hip surgery were included in this study. The mean age was 80.2 ± 9.9, and 297 (62%) were females. There were 150 (31.4%) deaths at the end of the first follow-up year, and the mean of surgical delay was 8.8 days ± 6.4. Patients who underwent surgery during the first 4 days (Log-rank test < 0.001) after hip fracture occurred and patients with a CCI ≤ 2 (Log-rank test < 0.001) showed better survival (90%), comparing to mortality (52%) of patients with a CCI ≥ 3 and surgical delay > 4 days. The age ≥ 80 years (Hazard ratio 2.55 (HR), 95% confidence interval (CI) 1.70 to 3.84, p < 0.001), CCI ≥ 3 (HR 1.61, 95% CI 1.14-2.26, p 0.006), surgical delay > 4 days (HR 2.41, 95% CI 1.38-4.21, p 0.006), and haemoglobin < 10 g/dl (HR 1.51, 95% CI 1.06-2.15, p 0.02) were associated with increased 1-year mortality. In addition, 30-day mortality was associated with age ≥ 80 years (HR 4.15, 95% CI 1.98-8.70, p < 0.001), CCI ≥ 3 (HR 1.80, 95% CI 1.08-2.99, p 0.023), pre-surgical time >48 h (HR 3.0, 95% CI 1.58-5.92, p 0.001), and surgical delay > 4 days (HR 3.0, 95% CI 1.33-6.81, p 0.008); and 6-month mortality was associated with surgical delay > 4 days (HR 2.72, 95% CI 1.42-5.23, p 0.003), and haemoglobin < 10 g/dl (HR 1.56, 95% CI 1.04-2.33, p < 0.028)., Conclusions: Surgical delay greater than 4 days and Charlson Comorbidity Index ≥ 3 were found as factors associated with increased mortality, along with anaemia < 10 g/dl and age ≥ 80 years. A similar mortality rate was found in this study compared to the rates reported by the literature, despite a surgical delay of 8.8 days., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

New 1,7-closo-carboranylanilinoquinazoline hybrids have been identified as EGFR inhibitors, one of them with higher affinity than the parent compound erlotinib. The comparative docking analysis with compounds bearing bioisoster-substructures, demonstrated the relevance of the 3D aromatic-boron-rich moiety for interacting into the EGFR ATP binding region. The capability to accumulate in glioma cells, the ability to cross the blood-brain barrier and the stability on simulated biological conditions, render these molecules as lead compounds for further structural modifications to obtain dual action drugs to treat glioblastoma., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The aim is to develop a new tool to evaluate postpartum sexual function and dyspareunia which will facilitate better evaluation of perineal pain in woman after vaginal delivery., Design: The development and validation of the Carol Postpartum Sexual Function and Dyspareunia Assessment Scale., Setting: The Obstetrics and Gynecology Service of a University Hospital in central Spain., Participants: 102 women after being attended for vaginal birth, and 5 midwife assessors., Findings: 81women reinitiated sexual activity (with vaginal intercourse) during the first three months postpartum. The Carol Postpartum Sexual Function and Dyspareunia Assessment Scale (Carol Scale) was internally reliable with a Cronbach-α value of 0.79 (95%CI0.72-0.85). Cronbach-α coefficients for Carol Scale domains were: preparation for the sexual activity 0.69 (95%CI0.55-0.79), pain or discomfort on caressing the vulval area 0.86 (95%CI0.79-0.91), pain or discomfort related to vaginal intercourse 0.93 (95%CI0.90-0.95) and pain or discomfort after vaginal intercourse 0.86 (95%CI0.78-0.91)., Conclusions: The Carol Postpartum Sexual Function and Dyspareunia Assessment Scale is valid and reliable for measuring sexual function and postpartum dyspareunia in women after being attended for vaginal birth., Implications for Practice: The Carol Scale could be used both clinically and in research to improve the quality of care for the mother after childbirth. The scale could help to identify problems in the reinitiation of postpartum sexual activity and, therefore, could contribute to widening the clinical information about these women and help in decision making., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To analyze prognostic variables that impact on the trial without catheter after tamsulosin in patients with acute urine retention., Methods: Retrospective analysis of a prospective database of a cohort of successive patients with acute urinary retention due to benign prostatic hyperplasia attended at the urology emergency room during one year time period. We analyzed the clinical and radiological characteristics and the international prostatic symptom score questionnaire of a total 65 male patients., Results: The trial without catheter after tamsulosin showed positive results in 25 patients (38%) and failed in the remaining 40 (62%). In multivariate analysis, none of the analyzed variables resulted in an independent predictive factor for spontaneous micturition after the trial without catheter. However, the severe IPSS (p=0.085) presented an important statistical tendency for predicting failure of spontaneous micturition, as well as we found that the 84% of diabetic patients presented failure to the trial with catheter., Conclusions: The only variable that impact negatively on the trial without catheter was the severe IPSS with an approximation to statistical significance. The presence of diabetes as a related factor is a hypothesis that should be investigated with a higher number of cases.

The 70 kilodalton heat shock proteins (Hsp70) are highly conserved molecular chaperones which have a crucial role in the stress response of the cell. In mammals, the Hsp70 proteins are encoded by a cluster of three genes: HSPA1A, HSPA1B and HSPA1L. In bovines, this cluster is located on chromosome 23 downstream of the major histocompatibility complex (BoLA). We detected inconsistencies in the location of markers on the Hsp70 genes reported in the literature that pointed to a potential deletion in the bovine reference genome UMD 3.1.1. An in silico analysis of the bovine genomic region of the Hsp70 cluster, using available information from public databases, confirmed the existence of a deletion of 11.1-kb spanning the HSPA1B gene and the intergenic region between HSPA1B and HSPA1A. Although we originally considered this an assembly error, it is most likely a particular condition of L1 Dominette 01449, the cow sequenced in the Bovine Genome Project. Moreover, we suggest a new classification of bovine Hsp70 sequences reported in NCBI and a reassignment of the location of SNPs from dbSNP that map to the deletion on BTA23. We also compared the location of selected transcription factor binding sites on the promoters of HSPA1A and HSPA1B. The results generated in the present work could be helpful to refine the reference genome of an important livestock species and also to understand the role and the regulation of the bovine Hsp70 genes., (© 2017 Stichting International Foundation for Animal Genetics.)

Exposure assessments are key tools to conduct epidemiological studies. Since 2010, 28 riveters from 18 brake repair shops with different characteristics and workloads were sampled for asbestos exposure in Bogotá, Colombia. Short-term personal samples collected during manipulation activities of brake products, and personal samples collected during non-manipulation activities were used to calculate 103 8-h TWA PCM-equivalent personal asbestos concentrations. The aims of this study are to identify exposure determinant variables associated with the 8-h TWA personal asbestos concentrations among brake mechanics, and propose different models to estimate potential asbestos exposure of brake mechanics in an 8-h work-shift. Longitudinal-based multivariate linear regression models were used to determine the association between personal asbestos concentrations in a work-shift with different variables related to work tasks and workload of the mechanics, and some characteristics of the shops. Monte Carlo simulations were used to estimate the 8-h TWA PCM-Eq personal asbestos concentration in work-shifts that had manipulations of brake products or cleaning activities of the manipulation area, using the results of the sampling campaigns. The simulations proposed could be applied for both current and retrospective studies to determine personal asbestos exposures of brake mechanics, without the need of sampling campaigns or historical data of air asbestos concentrations.

Objective: To identify Spanish funded paediatric research published in general paediatric journals included in the Web of Science (WoS) from 2010 to 2014) and those published in the Anales de Pediatría. To examine the relationship between funding and the prestige of the journals. To describe the journal conditions to meet the open access criteria., Material and Method: Spanish funded paediatric articles (FA) were identified by using the WoS Funding Agency field, and by reviewing the original documents for the Anales de Pediatria (AP). For the FA published in AP the number and kind of funding agencies were identified. The possible differences in citations between FA and non-funded was assessed for articles published in this journal using the Kruskal-Wallis non-parametric test. For general journals, the patterns of distribution of FA and non-FA were investigated according to the quartile of the journal. The journal's self-archiving conditions were described using Sherpa/romeo database., Results: Funding was received for 27.5%, being 16.6% for those published in AP. In these, 105 funding agencies were identified, with 80% being national. The FA published in AP did not receive significantly more citations. In general journals, the presence of FA is greater in Q1 and Q2 journals. More than half (56%) of articles were published in subscription journals. All journals that publish FA allow self-archiving in repositories, but with embargos of at least 12 months., Conclusions: The role of AP in the dissemination of FA is still limited. Embargos in self-archiving permits compliance of Spanish open access mandate, but may hinder compliance in Europe., (Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Multiple myeloma is the second most common hematological malignancy. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6., Objective: To radiolabel Tocilizumab with 99mTechnetium as a potential imaging agents for MM., Methods: IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S). Tocilizumab was derivatized with NHS-HYNIC-Tfa and radiolabeling with 99mTc. Radiochemical stability was determined. In-vitro binding and immunoreactive fraction assays were performed. Biodistribution and SPECT/CT imaging were evaluated in healthy BALB/c and MM-bearing BALB/c nude mice., Results: LCM studies allowed us to demonstrate that U266, NCI-H929 and MM1S cells present high expression of IL-6R in cell membrane. Radiolabeling was carried out in a fast, reproducible, easy and stable way having high radiochemical purity and did not interfere with epitope recognition. The immunoreactive fraction of 99mTc- HYNIC-Tocilizumab was 86.35%. Biodistribution showed a high uptake in liver, spleen, gastrointestinal tract and kidneys. SPECT/CT imaging of MM-bearing BALB/c nude mice showed liver uptake and a high tumor selective uptake at 24 hours., Conclusions: Our results support the potential role of 99mTc-HYNIC-Tocilizumb as a novel MM radiotracer for targeting IL-6 expression in-vivo. We describe the development of a formulation kit to radiolabeling monoclonal antibodies in a clinical setting. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for MM disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Introduction: Rituximab was the first monoclonal antibody approved for the treatment of B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen. This antibody has also the potential to be used as a specific fluorescent and radiolabel agent for targeting NHL., Objective: To radiolabel rituximab with technetium-99m (99mTc) or Cy7 and evaluate both probes as potential imaging agents for NHL., Methods: Rituximab was derivatized with the trifluoroacetyl hydrazino protected form of succinimidyl ester of HYNIC and radiolabeled with 99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and single-photon emission computed tomography/computed tomography (SPECT/CT) were performed. Raji cells were transfected with luciferase for bioluminescent NHL imaging up to 21 days. Rituximab was labeled with Cy7 for in vivo noninvasive fluorescence imaging up to 96 h., Results: Radiolabeling was carried out in a fast, reproducible, easy, and stable way with high radiochemical purity and did not interfere with epitope recognition. Biodistribution and SPECT/CT studies showed high liver and discrete tumor uptake. Bioluminescence and fluorescence studies helped us evaluate rituximab-Cy7 in Raji subcutaneous engraftment in BALB/c nude mice., Conclusions: Our results support the potential use of rituximab labeled either with 99mTc or Cy7 as a molecular imaging tool for staging, restaging, and guiding surgical excision of tumors, which merits further evaluation., (© 2017 S. Karger AG, Basel.)

Objective: To describe the role of Anales de Pediatría in highlighting Spanish paediatric research, and to identify the journals with which it competes internationally., Material and Method: Spanish paediatric articles, including those from Anales de Pediatría were identified using the Paediatrics category of the Science Citation Index (2010-2014), and their volume and document type was analysed. For original articles and review articles, the year, the citation and journal of publication was studied. The journals were classified as general and specialised. The productivity of general journals was analysed according to their language, JCR quartile, and article access., Results: A total of 2,701 Spanish paediatric papers were identified, accounting for 2.8% of the paediatrics world output. More than two-thirds (68%) of papers were articles that received an average number of 4.97 citations per article. The 965 papers published in Anales de Pediatría accounted for 38.7% of the Spanish paediatric output, and for 1% of the paediatric world publications. A mean of 1.03 citations per article were received for 439 (45.4%) articles and reviews. Of the 106 journals identified, 82 were classified as specialised (1,196 articles) and 24 as general (741 articles). Anales de Pediatría published 60% of the articles in general journals. The rest of articles (309) were published in general journals published in English (82.8%), with a best position in the JCR ranking (83.4%) and mainly by subscription (73.8%)., Conclusions: Anales de Pediatría plays an important role in providing international visibility to a large volume of Spanish scientific production in paediatrics. The results presented are a still only a snapshot of this role that could be used in the near future for assessing its evolution and the changes that could be made in order to improve its quality, positioning and competitiveness., (Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Asbestos and non-asbestos containing brake products are currently used in low- and middle-income countries like Colombia. Because brake products are distributed detached from their supports, they require manipulation before installation, which release fibers and expose workers. Previous studies of our research group have documented exposures in excess of the widely accepted 0.1 f/cm(3) exposure guideline. The aim of this study is to identify factors associated with non-compliance of the 8-h time weighted average (TWA) 0.1 f/cm(3) asbestos occupational limit among brake mechanics (i.e. riveters). Eighteen brake repair shops (BRS) located in Bogotá (Colombia) were sampled during 3 to 6 consecutive days for the entire work-shift. Personal and short-term personal samples were collected following NIOSH methods 7400 and 7402. Longitudinal based logistic regression models were used to determine the association between the odds of exceeding the 8-h TWA 0.1 f/cm(3) asbestos occupational limit and variables such as type of tasks performed by workers, workload (number of products manipulated daily), years of experience as riveters, and shop characteristics. These models can be used to estimate the odds of being currently or historically overexposed when sampling data do not exist. Since the information required to run the models can vary for both retrospective and current asbestos occupational exposure studies, three models were constructed with different information requirements. The first model evaluated the association between the odds of non-compliance with variables related to the workload, the second model evaluated the association between the odds of non-compliance with variables related to the manipulation tasks, and the third model evaluated the association between the odds of non-compliance with variables related with both the type of tasks performed by workers and the workload. Variables associated with the odds of non-compliance included conducting at least one manipulation activity with beveling and grinding of asbestos and non-asbestos containing brake products during the work shift, the location of the worker in the shop during non-manipulation activities, cleaning activities of the manipulation area, the years of experience working as riveters, and the number of asbestos and non-asbestos containing brake products manipulated daily. These models could be useful for current and retrospective occupational studies, in determining the odds of non-compliance of the asbestos occupational limit among brake mechanics., (© The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

The segment of the facial nerve (FN) between its emergence from the skull through the stylomastoid foramen and its bifurcation at the parotid area is referred to as the FN trunk (FNT). Injury to the facial nerve trunk is among the most undesirable outcomes following different otologic, plastic, maxillofacial, and neurosurgical procedures. These procedures frequently involve manipulation and isolation of this segment, and meticulous dissection should be practiced to avoid iatrogenic damage to the nerve. Identification and exposure of the FN trunk, however, may be difficult because it is surrounded by dense connective tissue. This dissection becomes even more difficult and risky when the normal anatomy is distorted.During a routine left conservative superficial parotidectomy of a Pleomorphic Adenoma in the superficial lobe of the left parotid gland, duplication of the FNT was encountered. The FNT after its exit through the stylomastoid foramen, split into 2 main divisions, which rejoined before its penetration into the parotid gland. To the best of our knowledge, this variation has not been previously reported.

Objective To determine whether a tilting system located in the seat of a chair allows for performing voluntary macro-repositioning movements of the pelvis in order to reduce the perception of pain after a prolonged period in the sitting posture. Methods Eight women participated in the experiment. They were asked to sit on the chair with the tilting system and the chair without the tilting system for sixty minutes on two different days but carried out at the same time of day. Discomfort was assessed with the visual analogic scale. Results people used the tilting system to do postural changes of macro-repositioning. However, these movements were less than the movements done with the body, not using the system. Moreover, discomfort perception was the same for each chair. This might be due to the fact that total of macro-repositioning movements did not change. Conclusion Future research should evaluate the effect of tilting systems that provide macro-repositioning in a controlled form, not like in this study. Also, it is necessary to study if these types of automatic systems contribute to the reduction of the discomfort due to a prolonged period in the sitting posture.

Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a (99m)Tc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity. Radiolabeling studies demonstrated that the HYNIC tetrazine was labeled with (99m)Tc at an efficiency of >95% and was radiochemically stable. (99m)Tc-HYNIC tetrazine reacted with the TCO-CC49 mAb in vitro demonstrating its selective reactivity. In vivo biodistribution studies revealed non-specific liver and GI uptake due to the hydrophobic property of the compound, however pretargeted SPECT imaging studies demonstrated tumor visualization confirming the success of the cycloaddition reaction in vivo. These results demonstrated the potential of (99m)Tc-HYNIC-tetrazine for tumor imaging with pretargeted mAbs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

Objectives: Asbestos has been used in a broad variety of industrial products, including clutch discs of the transmission system of vehicles. Studies conducted in high-income countries that have analyzed personal asbestos exposures of transmission mechanics have concluded that these workers are exposed to asbestos concentrations in compliance with the US Occupational Safety and Health Administration (US OSHA) occupational standards. Clutch facings are the friction component of clutch discs. If clutch facings are sold separated from the support, they require manipulation before installation in the vehicle. The manipulation of asbestos containing clutch facings is performed by a group of mechanics known as riveters, and includes drilling, countersinking, riveting, sanding, and occasionally grinding, tasks that can potentially release asbestos fibers, exposing the mechanics. These manipulation activities are not reported in studies conducted in high-income countries. This study analyzes personal asbestos exposures of transmission mechanics that manipulate clutch facings., Methods: Air sampling campaigns in two transmission repair shops (TRS) were conducted in November 2012 and July 2013 in Bogotá, Colombia. Four workers employed in these TRS were sampled (i.e. three riveters and one supervisor). Personal samples (n = 39), short-term personal samples (n = 49), area samples (n = 52), blank samples (n = 8), and background samples (n = 2) were collected in both TRS during 3-5 consecutive days, following US National Institute for Occupational Safety and Health (US NIOSH) methods 7400 and 7402. Asbestos samples were analyzed by an American Industrial Hygiene Association accredited laboratory., Results: On at least one of the days sampled, all riveters were exposed to asbestos concentrations that exceeded the US OSHA permissible exposure limit or the Colombian permissible limit value. Additionally, from the forty-seven 30-min short-term personal samples collected, two (4.3%) exceeded the US OSHA excursion limit of 1 f cm(-3)., Conclusions: In this study, we identified that the working conditions and use of asbestos containing transmission products expose transmission mechanics to asbestos concentrations that exceed both the Colombian and OSHA standards. The potential consequences for the health of these workers are of great concern., (© The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Asbestos brake linings and blocks are currently used in heavy vehicle brake repair shops (BRSs) in Bogotá, Colombia. Some brake products are sold detached from their supports and without holes, requiring manipulation before installation. The aim of this study was to assess asbestos exposures and conduct a preliminary evaluation of respiratory health in workers of heavy vehicles in BRSs. To estimate asbestos exposures, personal and area samples were collected in two heavy vehicle BRSs. Each shop was sampled during six consecutive days for the entire work shift. Personal samples were collected on 10 workers including riveters, brake mechanics, and administrative staff. Among workers sampled, riveters had the highest phase contrast microscopy equivalent (PCME) asbestos concentrations, with 8-h time-weighted average (TWA) personal exposures ranging between 0.003 and 0.157 f/cm(3). Respiratory health evaluations were performed on the 10 workers sampled. Three workers (30%) had circumscribed pleural thickening (pleural plaques), with calcifications in two of them. This finding is strongly suggestive of asbestos exposure. The results of this study provide preliminary evidence that workers in heavy vehicle BRSs could be at excessive risk of developing asbestos-related diseases.

Objective: To analyze the association between grip span of a manual flower cutting tool and maximum peak force exerted by each finger in the operating hand during apprehension., Methods: An experiment was conducted in which 11 women performed the stem cut of a flower. These women did not suffer from carpal tunnel syndrome. Grip span was calculated when they exerted the maximum peak force with each finger., Results: The main finding of the study reveals that fingers exert the maximum peak force when the grip span values are the same for everyone. However, due to the shape of the tool commonly used in the Colombian flower industry (first order level), each finger reaches its maximum peak force at different times, bypassing the full capacity of each finger's grip force., Conclusion: These findings could be used to improve the mechanical advantage of manual cutting tools to reduce risk factors for carpal tunnel syndrome due to overexertion., (Copyright belongs to the Societat Catalana de Salut Laboral.)

We described herein a simple and efficient microwave assisted synthesis of HYNIC analogues. Two different activated esters of HYNIC, the hydrazine protected with a trifluoroacetyl group (5) and the free hydrazine (6) were conjugated to the monoclonal antibody Nimotuzumab. Technetium-99m radiolabeling of Nimotuzumab was achieved with high efficiency using 5 and 6 derivates. The NHS-HYNIC-Tfa derivate allowed better labeling yields during longer times of preservation of the conjugated antibody.

Objective: To describe a case of urachal adenocarcinoma treated with robotic assisted laparoscopic partial cystectomy and en-bloc exeresis of urachus and umbilicus and bibliographic review., Methods: A 63 year-old man with hematuria and hypogastric pain. He was diagnosed of urachal adenocarcinoma by transurethral resection and axial tomography. We performed a robotic assisted laparoscopic partial cystectomy using a da Vinci® S HD (Intuitive Surgical System) device. We describe the surgical technique and examine total length of time for surgery and for console, pathology report, margin status, postoperative outcome and oncological status 7 months after surgery., Results: 4 ports were used for robotic arms and one additional for the assistant. Cystoscopy was performed during surgery to mark tumor margins. Bladder was closed using a running suture with Poliglactin 0. Total length time for surgery was 2hs 28 minutes, console time was 1h54'. Two days later patient was discharged and no complication was reported. After two weeks Foley cathether was removed and bladder volume was 300ml. Pathology report informed undifferentiated urachal adenocarcinoma with perivesical tissue infiltration with margins free from tumor, corresponding to Sheldon IIIB and Ontario III classification. Seven months later patient was fee from recurrence., Conclusion: Robotic assisted laparoscopy partial cystectomy with en-bloc exeresis of urachal and umbilicus is feasible.

Vascular endothelial growth factor (VEGF) is one of the classic factors involved in tumor-induced angiognesis in several solid tumors. Bevacizumab, a monoclonal antibody against VEGF, can be used as an imaging tool in preclinical studies. The aim of this study was to radiolabel Bevacizumab with (99m)Tc and to evaluate in vivo its imaging properties in an adenocarcinoma animal model. For this purpose, Bevacizumab was derivatized with Suc-HYNIC as a bifunctional coupling agent. A mixture of Tricine/SnCl(2).2H(2)O was added to Bevacizumab-HYNIC and radiolabeled with (99m)TcO(4)(-). The radiochemical stability of the radiolabeled antibody was assessed. Biodistribution and scintigraphy imaging were performed in normal CD1 female mice and in spontaneous adenocarcinoma tumor bearing CD1 mice (n = 5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc-HYNIC-Bevacizumab was 1.37 ± 0.51% and 5.33 ± 2.13% at 4 and 24 h postinjection, respectively. Scintigraphy image studies showed tumor selective uptake of (99m)Tc-HYNIC-Bevacizumab in the tumor-bearing mice. We conclude that (99m)Tc-HYNIC-Bevacizumb has the potential to be used as a tracer for tumor imaging in preclinical studies.

Introduction: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies., Objective: To radiolabel bevacizumab with [(99m)Tc(CO)3(OH2)3](+) and evaluate it in vivo and in vitro for melanoma imaging properties., Methods: Bevacizumab was radiolabeled with [(99m)Tc(CO)3(OH2)3](+) ion in saline. The radiochemical stability of the labeled antibody was assessed. The biodistribution and scintigraphy imaging of the radiolabeled antibody were evaluated in normal C57BL/6J mice and in C57BL/6J mice bearing murine B16F1 melanoma tumors. Immunoreactivity of bevacizumab to murine tumors was determined from direct immunofluorescence and immunoblotting assays., Results: We demonstrate that (99m)Tc(CO)3-bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc(CO)3-bevacizumab was 2.64 and 2.51 %ID/g at 4 and 24 h postinjection. Scintigraphy image studies showed tumor selective uptake of (99m)Tc(CO)3-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples., Conclusions: (99m)Tc(CO)3-bevacizumab could be used as an approach for tumor nuclear imaging in preclinical studies. This should be useful to provide insights into the angiogenic stimulus before and after chemotherapy, which might help improve current antitumor therapy., (Copyright © 2013 S. Karger AG, Basel.)

Aplasia of major salivary glands is a rare disorder with only a handful of cases reported in the literature. The cause of congenital absence of the salivary glands has not been determined, but it may be associated with ectodermal defects of the first and second branchial arches. Patients may be asymptomatic or may experience dysphagia, xerostomia, several periodontal disease, or multiple caries. There are few reports of patients with congenital gland aplasia with cleft lip and palate. We document the case of a 41-year-old patient with repaired unilateral cleft lip palate, bilateral submandibular gland aplasia, and compensatory hypertrophy of the sublingual glands. To the best of our knowledge, there are no previous reports that can be found in the literature with a combination of such findings.