Monoclonal Gammopathy of Undetermined Significance Disguised as Chronic Neutrophilic Leukemia

We encountered a 60-year-old woman with a medical history of diabetes mellitus, osteoporosis, peripheral vascular disease, and hypertension who had earlier presented at an outside facility with knee pain, which led to a finding of elevated neutrophil count of 35×109/L. Because she was otherwise asymptomatic but continued showing elevated neutrophil levels, she sought a second opinion at our facility. Serum protein immunoelectrophoresis with immunofixation revealed an immunoglobulin A (IgA)-κ monoclonal gammopathy concentration of 1305 mg/dL (normal 80–350 mg/dL) but relatively normal concentrations of IgG of 840 mg/dL (620–1400 mg/dL) and IgM of 36 mg/dL (45–250 mg/dL). Using clonal analysis, we found a polyclonal expression pattern in all cell types analyzed. Comprehensive work-up for multiple myeloma and infectious etiology of neutrophilia was negative. We concluded that our patient’s neutrophilia may have been due to the underlying monoclonal gammopathy. This is the first case in the literature of a patient with monoclonal gammopathy of undetermined significance presenting with chronic neutrophilia, mimicking chronic neutrophilic leukemia (CNL). Patients with CNL have a poor prognosis; therefore, it is important to distinguish diagnostically between CNL and reactive neutrophilia

Spanish Preanalytical Quality Monitoring Program (SEQC), an overview of 12 years' experience

Preanalytical variables, such as sample collection, handling and transport, may affect patient results. Preanalytical phase quality monitoring should be established in order to minimize laboratory errors and improve patient safety. A retrospective study (2001-2013) of the results obtained through the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) External quality assessment (preanalytical phase) was performed to summarize data regarding the main factors affecting preanalytical phase quality. Our aim was to compare data from 2006 to 2013 with a previously published manuscript assessing the 2001-2005 period. A significant decrease in rejection rates was observed both for blood and urine samples. For serum samples, the most frequent rejection causes in the first period were non-received samples (37.5%), hemolysis (29.3%) and clotted samples (14.4%). Conversely, in the second period, hemolysis was the main rejection cause (36.2%), followed by non-received samples (34.5%) and clotted samples (11.1%). For urine samples, the main rejection cause overall was a non-received sample (up to 86.1% of cases in the second period, and 81.6% in the first). For blood samples with anticoagulant, the number of rejections also decreased. While plasma-citrate-ESR still showed the highest percentages of rejections (0.980% vs. 1.473%, p<0.001), the lowest corresponded to whole-blood EDTA (0.296% vs. 0.381%, p<0.001). For the majority of sample types, a decrease in preanalytical errors was confirmed. Improvements in organization, implementation of standardized procedures in the preanalytical phase, and participation in a Spanish external quality assessment scheme may have notably contributed to error reduction in this phase

Cold-induced growth arrest in gilthead sea bream Sparus aurata: metabolic reorganisation and recovery

There are currently no standard diets or practices to counteract or ameliorate the growth arrest and extremely poor feed conversion rates (FCR) in gilthead sea bream Sparus aurata caused by low water temperatures. The present study analysed the effects of reducing dietary lipid content from 18 to 14 % during a temperature fluctuation period. Temperature was gradually reduced from 22 degrees to 14 degrees C over a period of 5 d, and maintained at this low temperature for a further 45 d before gradual recovery over 7 d to 22 degrees C under controlled conditions, avoiding other stressors often present in cage culture conditions. Decreasing dietary lipid content at an elevated temperature (22 degrees C) did not significantly affect the standard growth rate or FCRs of the sea bream, indicating a possibility to reduce the dietary energy during the months before winter. Although cold-induced growth arrest and metabolic depression were unavoidable, a well-formulated, low-lipid diet adequately met the low energy demands at low temperatures. Analysis of plasma metabolites and liver enzyme activities demonstrated a reorganisation of liver metabolism, mainly in fish on a low-lipid diet. Recovery from low temperatures was delayed, with a higher dietary lipid content required for optimal liver condition, and mineral supplementation to maintain osmoregulation and bone formation. Our results provide useful information for fish producers and researchers, suggesting that dietary lipid contents should be reduced to allow fish to better cope with low temperatures, and that improved diets with higher lipid content are required for recovery from low temperatures.Spanish government - AGL2011-29873; Erasmus Turkish Programinfo:eu-repo/semantics/publishedVersio

Encapsulated pine bark polyphenolic extract during gastrointestinal digestion: bioaccessibility, bioactivity and oxidative stress prevention

Polyphenolic extracts from pine bark have reported different biological actions and promising beneficial effects on human health. However, its susceptibility to environmental stresses (temperature, storage, etc.) and physiological human conditions prequires the development of efficient protection mechanisms to allow effective delivering of functionality. The aim of this work was to encapsulate pine bark extract rich phenolic compounds by spray-drying using maltodextrin, and understand the influence of encapsulation on the antioxidant and antimicrobial activity and bioaccessibility of phenolic compounds during gastrointestinal digestion. The optimized process conditions allowed good encapsulation efficiency of antioxidant phenolic compounds. The microencapsulation was effective in protecting those compounds during gastrointestinal conditions, controlling their delivery and enhancing its health benefits, decreasing the production of reactive oxygen species implicated in the process of oxidative stress associated with some pathologies. Finally, this encapsulation system was able to protect these extracts against acidic matrices, making the system suitable for the nutritional enrichment of fermented foods or fruit-based beverages, providing them antimicrobial protection, because the encapsulated extract was effective against Listeria innocua. Overall, the designed system allowed protecting and appropriately delivering the active compounds, and may find potential application as a natural preservative and/or antioxidant in food formulations or as bioactive ingredient with controlled delivery in pharmaceuticals or nutraceuticals.This research was funded by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020-Programa Operacional Regional do Norte. The study was also supported by program INTERREG V-B Sudoe (REDVALUE, SOE1/P1/E0123) and by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (MSCARISE; FODIAC; 778388). P.F.-S. is supported by a doctoral advanced training fellowship (call NORTE69-2015-15), funded under the scope of Norte2020 (NORTE-08-5369-FSE-000036). R.I. thanks the University of Lleida for the UdL-Impuls post-doctoral contract.info:eu-repo/semantics/publishedVersio

The Influence of IS1301 in the Capsule Biosynthesis Locus on Meningococcal Carriage and Disease

Previously we have shown that insertion of IS1301 in the sia/ctr intergenic region (IGR) of serogroup C Neisseria meningitidis (MenC) isolates from Spain confers increased resistance against complement-mediated killing. Here we investigate the significance of IS1301 in the same location in N. meningitidis isolates from the UK. PCR and sequencing was used to screen a collection of more than 1500 meningococcal carriage and disease isolates from the UK for the presence of IS1301 in the IGR. IS1301 was not identified in the IGR among vaccine failure strains but was frequently found in serogroup B isolates (MenB) from clonal complex 269 (cc269). Almost all IS1301 insertions in cc269 were associated with novel polymorphisms, and did not change capsule expression or resistance to human complement. After excluding sequence types (STs) distant from the central genotype within cc269, there was no significant difference for the presence of IS1301 in the IGR of carriage isolates compared to disease isolates. Isolates with insertion of IS1301 in the IGR are not responsible for MenC disease in UK vaccine failures. Novel polymorphisms associated with IS1301 in the IGR of UK MenB isolates do not lead to the resistance phenotype seen for IS1301 in the IGR of MenC isolates

Essential role of HDAC6 in the regulation of PD-L1 in melanoma

Indexación: Web of Science; Scopus.Histone deacetylases (HDACs), originally described as histone modifiers, have more recently been deMonstrated to target a variety of other proteins unrelated to the chromatin environment. In this context, our present work demonstrates that the pharmacological or genetic abrogation of HDAC6 in primary melanoma samples and cell lines, down-regulates the expression of PD-L1, an important co-stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD-1 in T-cells. Our data suggests that this novel mechanism of PD-L1 regulation is mainly mediated by the influence of HDAC6 over the recruitment and activation of STAT3. Additionally, we observed that selective HDAC6 inhibitors impairs tumor growth and reduce the in vim expression of several inhibitory checkpoint molecules and other regulatory pathways involved in immunosurveillance. Most importantly, these results provide a key pre-clinical rationale and justification to further study isotype selective HDAC6 inhibitors as potential immuno-modulatory agents in cancer. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.http://onlinelibrary.wiley.com/doi/10.1016/j.molonc.2015.12.012/abstract;jsessionid=DB86CF943DA7FD358A75C2CEEAD4D7C4.f03t0

Proba-3: ESA’s Small Satellites Precise Formation Flying Mission to Study the Sun’s Inner Corona as Never Before

This paper showcases ESA’s Proba-3 mission as a demonstration of how small satellites, in combination with formation flying technology, can achieve relevant scientific goals and perform scientific measurements not possible otherwise, all within a tight cost and programmatic context. The study of the Sun inner corona down to 1.1 solar radius can only be performed by creating in space artificial eclipses with a large distance between a Coronograph instrument and an occulting disk, much bigger than the size of any spacecraft that can fit within a launcher. Proba-3 will achieve these enhanced scientific observations by controlling two small satellites (~1.5 m cubes in the 200-300kg range) as a 150 m long ‘large virtually rigid structure’ by maintaining millimetre and arc second relative precision. In effect the paired satellites will fly as a giant virtual satellite creating an ‘externally occulted’ coronagraph, in which a satellite imager is shielded from glaring sunlight by an occulting disk on the other satellite, forming an artificial eclipse. Precise station keeping for Coronagraphy will be kept for 6 consecutive hours within each 20 hour orbit for a minimum total of 1000 hours of scientific observations over the 2 years of mission lifetime. This will be achieved autonomously, without relying on the ground for active control of the formation. In addition, Proba-3 will practically demonstrate formation flying technologies enabling other future science missions: station-keeping at different relative distances (from 25 m up to 250 m); approaching and separating in precise formation without losing millimetre precision; the capability to repoint the formation as a virtual rigid body away from the Sun and the combination of station keeping, resizing and re-targeting manoeuvres. Proba-3 is at full speed in the assembly, integration and verification phase, with the aim of launching Proba-3 in two years’ time. The paper describes the overall Proba-3 mission concept and detailed design, the different challenges that were overcome in spacecraft design, formation flying metrology and control, and the need to implement novel verification and operation approaches to achieve the world’s first precise formation flying mission

A pragmatic health centre-based evaluation comparing the effectiveness of a PCV13 schedule change from 3+0 to 2+1 in a high pneumococcal carriage and disease burden setting in Malawi: a study protocol

INTRODUCTION: Streptococcus pneumoniae (the pneumococcus) is commonly carried as a commensal bacterium in the nasopharynx but can cause life-threatening disease. Transmission occurs by human respiratory droplets and interruption of this process provides herd immunity. A 2017 WHO Consultation on Optimisation of pneumococcal conjugate vaccines (PCV) Impact highlighted a substantial research gap in investigating why the impact of PCV vaccines in low-income countries has been lower than expected. Malawi introduced the 13-valent PCV (PCV13) into the national Expanded Programme of Immunisations in 2011, using a 3+0 (3 primary +0 booster doses) schedule. With evidence of greater impact of a 2+1 (2 primary +1 booster dose) schedule in other settings, including South Africa, Malawi's National Immunisations Technical Advisory Group is seeking evidence of adequate superiority of a 2+1 schedule to inform vaccine policy. METHODS: A pragmatic health centre-based evaluation comparing impact of a PCV13 schedule change from 3+0 to 2+1 in Blantyre district, Malawi. Twenty government health centres will be randomly selected, with ten implementing a 2+1 and 10 to continue with the 3+0 schedule. Health centres implementing 3+0 will serve as the direct comparator in evaluating 2+1 providing superior direct and indirect protection against pneumococcal carriage. Pneumococcal carriage surveys will evaluate carriage prevalence among children 15-24 months, randomised at household level, and schoolgoers 5-10 years of age, randomly selected from school registers. Carriage surveys will be conducted 18 and 33 months following 2+1 implementation. ANALYSIS: The primary endpoint is powered to detect an effect size of 50% reduction in vaccine serotype (VT) carriage among vaccinated children 15-24 months old, expecting a 14% and 7% VT carriage prevalence in the 3+0 and 2+1 arms, respectively. ETHICS AND DISSEMINATION: The study has been approved by the Malawi College of Medicine Research Ethics Committee (COMREC; Ref: P05.19.2680), the University College London Research Ethics Committee (Ref: 8603.002) and the University of Liverpool Research Ethics Committee (Ref: 5439). The results from this study will be actively disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04078997