Dynamic mechanical behavior of starch-based scaffolds in dry and physiologically simulated conditions: effect of porosity and pore size

The three-dimensional scaffolds of a blend of starch and poly(L-lactic) acid, SPLA70, were produced using compression molding of polymer/salt mixture followed by leaching of salt. One series of scaffolds were prepared with varying polymer-to-salt ratio while keeping the salt size constant, and the other series of scaffolds were prepared with varying salt sizes while keeping the polymer-to-salt ratio constant. The X-ray microcomputed tomography and scanning electron microscopy assay were used to analyze the porous morphologies, porosity and distribution of porosity of the porous scaffolds. Salt-free and integrated SPLA70 scaffolds with porosities ranging from 74% to 82% and pore sizes of 125–250 to 500–1000 lm can be fabricated using the present fabrication technique. The water uptake of the SPLA70 scaffolds increases with increasing porosities and also with increasing pore size. In dry state, the storage modulus decreases with increasing porosity and also with increasing pore size. The normalized modulus values are related to normalized density of the scaffolds by a power-law function with an exponent between 2 and 3. For the immersed scaffolds under physiological conditions, the storage modulus was less dependent on porosity and pore size. However, the loss factor increased significantly compared with dry state measurements. The present study clearly shows that the mechanical performance of porous polymeric constructs in dry and in immersed state is completely different, and for comparison with biomechanical performance of tissues, the tests should ideally be performed in immersed state

Architectural model for interoperability between healthcare service providers in Colombia

En la actualidad Gobiernos, IPS y desarrolladores de software enfrentan la necesidad de mejorar la eficiencia de los sistemas de información en salud mediante una adecuada gestión de la información y la implementación de TICS. Una de las áreas de interés, es el desarrollo de perfiles de interoperabilidad que permita intercambiar información y mejorar la colaboración entre los diferentes actores del sistema de salud. El objetivo del presente artículo es definir y validar un modelo arquitectónico de interoperabilidad entre sistemas de información de IPS en Colombia. El modelo, sustentando en normatividad Colombiana, sugiere el uso de SOA como referencia para definir la arquitectura software y el estándar HL7 para el intercambio de mensajes y documentos clínicos. Posteriormente se evalúa el modelo mediante un grupo de profesionales con experiencia en desarrollo de sistemas de información y una prueba piloto basada en dos escenarios de interoperabilidad en tres IPS de Popayán. El modelo busca aportar una metodología de modelamiento y desarrollo de software en IPS y empresas desarrolladoras, mejorando así el nivel de entendimiento y control sobre las transacciones de información presentes en la prestación de servicios.Nowadays governments, health services organizations and software developers face the need to improve the efficiency of information systems in health through information management and ICT implementation. One of the areas of interest is the development of interoperability profiles that allow exchange information and improve collaboration between different actors in the health system. The aim of this paper is to define and validate an architectural model of interoperability between information systems on IPS in Colombia. The model, grounded in Colombian legislation, suggests the use of SOA as a reference to define the software architecture and HL7 standard for the exchange of messages and clinical documents. Subsequently the model is evaluated by a group of professionals with experience in information systems development and piloted based on two interoperability scenarios in three IPS of Popayán. The model aims to provide a methodology for software modeling and development among health services organizations, improving the level of understanding and control over information transactions present in the delivery of services

Severe cardiac and abdominal manifestations without lung involvement in a child With COVID-19

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic, affecting humans of all ages. Clinical features of the pediatric population have been published, but there is not yet enough information to make a definitive description. Fever is typical, as it is respiratory symptom. Rarely are the infection and complications severe, and, when they are, it is almost always in a patient with another underlying disease. However, some otherwise healthy children with COVID-19 do suffer critical organ injury, such as acute myocarditis, heart failure and gastrointestinal inflammation. The mechanism of these organ damages remains unclear. An otherwise normally healthy 13-year-old male was admitted to the pediatric intensive care unit with acute abdomen pain, possible myocarditis and a suspected diagnosis of COVID-19. Noteworthy basal findings were ventricular extrasystoles in the electrocardiogram (EKG) and moderate left ventricular systolic dysfunction. Chest X-ray was normal. Blood tests revealed altered levels of inflammation factors (C-reactive protein (CRP), D-dimer, fibrinogen, interleukin 6 (IL-6)), lymphopenia and elevated cardiac enzymes. The first test for polymerase chain reaction (PCR) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was negative. The patient’s condition worsened, and he entered cardiogenic shock (hypotension, tachycardia and oliguria). He was vomiting continuously, which made pain control difficult; imaging of his abdomen was undertaken. There was no response to fluid resuscitation, and so milrinone and epinephrine were administered. Empiric treatment began with azithromycin, foscarnet, carnitine and immunoglobulins. Hydroxychloroquine was given before the results of repeated SARSCoV-2 and serology tests were available. Tocilizumab was administered once COVID-19 had been confirmed and massive inflammation had been observed. Progressively the clinical situation and the levels of the parameters studied improved. The patient was discharged 8 days after admission. Most children with SARS-CoV-2 infection are asymptomatic or present only mild symptoms. However, physicians should be aware of atypical and severe manifestations that may occur in the hyperinflammatory phase of the illness

Adiponectin and resistin modulate the progression of Alzheimer´s disease in a metabolic syndrome model

Metabolic syndrome (MetS), a cluster of metabolic conditions that include obesity, hyperlipidemia, and insulin resistance, increases the risk of several aging-related brain diseases, including Alzheimer’s disease (AD). However, the underlying mechanism explaining the link between MetS and brain function is poorly understood. Among the possible mediators are several adipose-derived secreted molecules called adipokines, including adiponectin (ApN) and resistin, which have been shown to regulate brain function by modulating several metabolic processes. To investigate the impact of adipokines on MetS, we employed a diet-induced model to induce the various complications associated with MetS. For this purpose, we administered a high-fat diet (HFD) to both WT and APP/PSN1 mice at a pre-symptomatic disease stage. Our data showed that MetS causes a fast decline in cognitive performance and stimulates Aβ42 production in the brain. Interestingly, ApN treatment restored glucose metabolism and improved cognitive functions by 50% while decreasing the Aβ42/40 ratio by approximately 65%. In contrast, resistin exacerbated Aβ pathology, increased oxidative stress, and strongly reduced glucose metabolism. Together, our data demonstrate that ApN and resistin alterations could further contribute to AD pathology

Imported Plasmodium falciparum malaria in HIV-infected patients: a report of two cases

As HIV becomes a chronic infection, an increasing number of HIV-infected patients are travelling to malaria-endemic areas. Association of malaria with HIV/AIDS can be clinically severe. Severe falciparum malaria is a medical emergency that is associated with a high mortality, even when treated in an Intensive Care Unit. This article describes two cases of HIV-positive patients, who returned from malaria-endemic areas and presented a parasitaemia > 5% of erythrocytes and clinical signs of severe falciparum malaria, both with > 350 CD4 cell count/μl, absence of chemoprophylaxis and successful response. Factors like drug interactions and the possible implication of anti-malarial therapy bioavailability are all especially interesting in HIV-malaria co-infections

Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration

Aims The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections. Methods and results Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot-spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799-0.93] marginally met the prespecified success criterion (lower 95% CI >= 0.8), while the ICC for the hot-spot method (0.83; 95% CI = 0.74-0.90) did not. Visually, interobserver concordance in location of selected hot-spots varies between cases. The median times for scoring were 9 and 6 min for global and hot-spot methods, respectively. Conclusions The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further

Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration

Pathological analysis of the nuclear proliferation biomarker Ki67 has multiple potential roles in breast and other cancers. However, clinical utility of the immunohistochemical (IHC) assay for Ki67 immunohistochemistry has been hampered by unacceptable between-laboratory analytical variability. The International Ki67 Working Group has conducted a series of studies aiming to decrease this variability and improve the evaluation of Ki67. This study tries to assess whether acceptable performance can be achieved on prestained core-cut biopsies using a standardized scoring method. Sections from 30 primary ER+ breast cancer core biopsies were centrally stained for Ki67 and circulated among 22 laboratories in 11 countries. Each laboratory scored Ki67 using three methods: (1) global (4 fields of 100 cells each); (2) weighted global (same as global but weighted by estimated percentages of total area); and (3) hot-spot (single field of 500 cells). The intraclass correlation coefficient (ICC), a measure of interlaboratory agreement, for the unweighted global method (0.87; 95% credible interval (CI): 0.81–0.93) met the prespecified success criterion for scoring reproducibility, whereas that for the weighted global (0.87; 95% CI: 0.7999–0.93) and hot-spot methods (0.84; 95% CI: 0.77–0.92) marginally failed to do so. The unweighted global assessment of Ki67 IHC analysis on core biopsies met the prespecified criterion of success for scoring reproducibility. A few cases still showed large scoring discrepancies. Establishment of external quality assessment schemes is likely to improve the agreement between laboratories further. Additional evaluations are needed to assess staining variability and clinical validity in appropriate cohorts of samples

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Improved imputation quality of low-frequency and rare variants in European samples using the 'Genome of the Netherlands'

Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with 'true' genotypes typed on ImmunoChip in three European populations (Dutch, British, and Italian). GoNL showed significant improvement in the imputation quality for rare variants (MAF 0.05-0.5%) compared with 1000G. In Dutch samples, the mean observed Pearson correlation, r 2, increased from 0.61 to 0.71. W

The CMB power spectrum out to l=1400 measured by the VSA

We have observed the cosmic microwave background (CMB) in three regions of sky using the Very Small Array (VSA) in an extended configuration with antennas of beamwidth 2 degrees at 34 GHz. Combined with data from previous VSA observations using a more compact array with larger beamwidth, we measure the power spectrum of the primordial CMB anisotropies between angular multipoles l = 160 - 1400. Such measurements at high l are vital for breaking degeneracies in parameter estimation from the CMB power spectrum and other cosmological data. The power spectrum clearly resolves the first three acoustic peaks, shows the expected fall off in power at high l and starts to constrain the position and height of a fourth peak.Comment: 6 pages with 5 figures, MNRAS in press (minor corrections