Feed restriction during the early life of ewe lambs (F0) triggers the transfer of epigenetic marks to the next generation, thus impairing the reproductive performance of F1. However, the effects of ...this factor on milk production and composition, including its abundance in regulatory miRNA (many of which are contained in exosomes, small vesicles of endocytic origin that play a role in the modulation of immune response of the offspring) has not been tested so far. Therefore, in this study, the replacement ewe lambs (F0) obtained in a previous project (a group of ewes fed milk replacer ad libitum –ADL– vs. a group of ewes restricted –RES– to 62.5 % the intake level of milk replacer during the suckling period) were raised under similar post-weaning conditions and mated to obtain the progeny (F1). The F1 female lambs were also mated to obtain F2. Milk production was recorded during the peak lactation period of F1, and milk samples were obtained for each gland (udder half) separately to measure chemical composition, somatic cell counts (SCC), and bacteria counts. Moreover, exosomes were also isolated from the milk of each gland separately to obtain the miRNAome following a Next Generation Sequencing approach. No significant differences were found in either milk production of F1, chemical composition of milk (fat, protein, lactase), or bacteriology (colony forming units, CFU). However, SCC was reduced significantly in milk samples of F1-RES dairy sheep, whereas the abundance of five miRNAs was also modified. Thus, oar-miR-150, oar-miR-221, oar-miR-23a, oar-miR-27a, oar-miR-376c were all down modulated in F1-RES when compared to F1-ADL. Most of these miRNAs have been found to play a role in biological functions such as development, apoptosis, muscle differentiation, reproduction, or milk production. However, the exosomes extracted from the milk of these sheep (F1-RES) did not affect the production of IL-9 and IL-2 cytokines after in vitro culture with CaCo-2 cells. This study reveals that nutritional programming events such as feed restriction may drive the abundance of not only SCC but also some milk's bioactive components such as miRNAs, although it is not clear if these changes may modulate the immune response at the intestinal level of the offspring.
•Feed restriction of ewes (F0) causes nutritional programming of the offspring (F1).•The somatic cell counts of the F1 milk is reduced by this event.•The miRNAome of the F1 milk exosomes is also affected by this circumstance.•The expression of cytokines by Caco-2 cells is not altered by these changes.
Objective:
A bibliometric study was undertaken of peer-reviewed publications on atypical antipsychotic drugs (AADs) from the United Kingdom and the findings are presented herein.
Methods:
We selected ...the documents from the Scopus database. We applied several production and dispersion bibliometric indicators, including Price’s law on the growth of the scientific literature, and Bradford’s law. We also calculated a so-called ‘participation index’ across different countries. The bibliometric data were thereafter correlated with social and health data from the UK, including total per capita expenditure on health and gross domestic expenditure.
Results:
A total of 4156 original manuscripts were published within the timeframe 1967–2015. Our results are in accord with Price’s law, with scientific output demonstrating exponential growth (r = 0.9227, as against an r = 0.8766 after adjustment). The drugs most widely evaluated were clozapine (465 documents), olanzapine (263) and risperidone (248). Stratification into Bradford zones produced a nucleus represented by the Journal of Psychopharmacology (168 articles) and British Journal of Psychiatry (159 articles). A total of 1250 different journals were evaluated.
Conclusions:
Publications on AADs in the UK have shown exponential growth across the studied period, which is in line with the progressively burgeoning novel AAD releases. No evidence of a saturation point was observed.
The objectives were to determine the impact of frailty and disability on 30-day mortality and whether the addition of these variables to HFRSS EFFECT risk score (FBI-EFFECT model) improves the ...short-term mortality predictive capacity of both HFRSS EFFECT and BI-EFFECT models in older patients with acute decompensated heart failure (ADHF) atended in the emergency department. We performed a retrospective analysis of OAK Registry including all consecutive patients ≥65 years old with ADHF attended in 3 Spanish emergency departments over 4 months. FBI-EFFECT model was developed by adjusting probabilities of HFRSS EFFECT risk categories according to the 6 groups (G1: non frail, no or mildly dependent; G2: frail, no or mildly dependent; G3: non frail, moderately dependent; G4: frail, moderately dependent; G5: severely dependent; G6: very severely dependent).We included 596 patients (mean age: 83 SD7; 61.2% females). The 30-day mortality was 11.6% with statistically significant differences in the 6 groups (p < 0.001). After adjusting for HFRSS EFFECT risk categories, we observed a progressive increase in hazard ratios from groups G2 to G6 compared with G1 (reference). FBI-EFFECT had a better prognostic accuracy than did HFRSS EFFECT (log-rank p < 0.001; Net Reclassification Improvement NRI = 0.355; p < 0.001; Integrated Discrimination Improvement IDI = 0.052; p ;< 0.001) and BI-EFFECT (log-rank p = 0.067; NRI = 0.210; p = 0.033; IDI = 0.017; p = 0.026). In conclusion, severe disability and frailty in patients with moderate disability are associated with 30-day mortality in ADHF, providing additional value to HFRSS EFFECT model in predicting short-term prognosis and establishing a care plan.
Background
Content-based image retrieval (CBIR) is an application of machine learning used to retrieve images by similarity on the basis of features. Our objective was to develop a CBIR system that ...could identify images containing the same polyp (‘polyp fingerprint’).
Methods
A machine learning technique called Bag of Words was used to describe each endoscopic image containing a polyp in a unique way. The system was tested with 243 white light images belonging to 99 different polyps (for each polyp there were at least two images representing it in two different temporal moments). Images were acquired in routine colonoscopies at Hospital Clínic using high-definition Olympus endoscopes. The method provided for each image the closest match within the dataset.
Results
The system matched another image of the same polyp in 221/243 cases (91%). No differences were observed in the number of correct matches according to Paris classification (protruded: 90.7% vs. non-protruded: 91.3%) and size (
<
10 mm: 91.6% vs. > 10 mm: 90%).
Conclusions
A CBIR system can match accurately two images containing the same polyp, which could be a helpful aid for polyp image recognition.
Coaches at the professional level are often concerned about negative side effects from testing and intensive resistance training periods, and they are not willing to base their training prescriptions ...on data obtained from semiprofessional or amateur football players. Consequently, the purpose of this study was to analyze the reliability and effectiveness of two adductor injury active prevention programs using the adductor/abductor ratio and deficit between legs, on the basis of adduction-abduction power output during the exercises proposed, in professional football players. Forty-eight professional football players undertook complementary strength training for the adductor and abductor muscles in their dominant and non-dominant legs, once or twice a week throughout the playing season. The volume of the session was determined by the adductor/abductor ratio and the deficit between legs in the last session training measured. The number and severity of muscle injuries per 1000 h of exposure were recorded. Both prevention programs showed a very low rate of adductor injury (0.27 and 0.07 injuries/1000 h) with mild-to-moderate severity, maintaining a balance in percentage asymmetry between dominant and non-dominant legs for adductor (10.37%) and in the adductor/abductor ratio (0.92) in top professional football players throughout the season. The strength conditioning program proposed can help to prevent adductor muscle injuries in top professional football players.
Resumo Este artigo aborda a questão da representação desproporcional de estudantes que pertencem a minorias (em particular migrantes/estrangeiros) na educação especial do Estado espanhol. Apesar de ...ser um fenômeno amplamente estudado em diversas latitudes, na Espanha foram escassas as pesquisas neste sentido. Por meio de uma análise estatística crítica, aproximamo-nos de um fenômeno que revela diferenças significativas dependendo dos territórios em que ocorre, e as diferenças são tão significativas que nos levam a questionar se os procedimentos de diagnóstico são os que estão "patologizando" as diferenças culturais. O fenômeno é considerado relevante para sua compreensão como mais uma concretização das estratégias de construção da diferença que operam no sistema educacional. Em suma, nosso objetivo é contribuir para a compreensão multidimensional e interdisciplinar da desigualdade educacional ligada à presença da população imigrante/estrangeira, adotando a educação especial como contexto central.
Abstract This article addresses the issue of the disproportionate representation of students belonging to minorities (specifically migrants/foreigners) in special education in Spain. Despite being a phenomenon widely studied in the world over, in Spain there has been little research in this regard. Through a critical statistical analysis, we approach a phenomenon that reveals significant differences according to the territories in which it occurs, and the differences are so important that they lead us to wonder if it is the diagnostic procedures that are "pathologizing" the cultural differences. The phenomenon is considered relevant for its understanding as one more concretion of the strategies for the construction of difference that operate in the educational system. In short, our objective is to contribute to the multidimensional and interdisciplinary understanding of educational inequality linked to the presence of the immigrant/foreign population, taking special education as the central context.
Background
HIV infection of the CNS is the principle cause of HIV-associated dementia in adults and encephalopathy in children. Gene therapy techniques such as small interfering RNA (siRNA) possess ...great potential in drug development, but first they must overcome the key obstacle of reaching the interior of the affected cells. A successful delivery vector for anti-HIV drugs that is capable of crossing the blood-brain barrier (BBB) could provide a way of addressing this issue. Non-viral vectors such as dendrimers offer a means for effectively delivering and transfecting siRNA to the target cells.
Objective
To evaluate the application of gene therapy for reducing HIV replication in human astrocytes.
Methods
We used the 2G-NN16 amino-terminated carbosilane dendrimer as a method for delivering siRNA to HIV-infected human astrocytes. We tested the cytotoxicity in human astrocytoma cells caused by 2G-NN16 and dendriplexes formed with siRNA (siRNA/2G-NN16) by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium-bromide (MTT) and lactate dehydrogenase assays. The ability to transfect human astrocytes with siRNA/2G-NN16 dendriplexes was tested by flow cytometry and immunofluorescence microscopy. To assess the potential capability of siRNA/2G-NN16 dendriplexes for crossing the BBB, we used an
in vitro
transcytosis assay with bovine brain microvascular endothelial cells. HIV-1 inhibition assays using 2G-NN16 and siRNA/2G-NN16 dendriplexes were determined by quantification of the viral load from culture supernatants of the astrocytes.
Results
A gradual time-controlled degradation of the 2G-NN16 dendrimer and liberation of its siRNA cargo between 12 and 24 hours was observed via gel electrophoresis. There was no cytotoxicity in HIV-infected or non-infected human astrocytoma cells when treated with up to 24 μg/mL of 2G-NN16 dendrimer or siRNA/2G-NN16 dendriplexes, and siRNA/2G-NN16 dendriplexes were seen to successfully transfect human astrocytes even after crossing an
in vitro
BBB model. More interestingly, transfected siRNA was observed to exert a biologic effect, as dendriplexes were shown to down-regulate the housekeeping gene
GAPDH
and to reduce replication of HIV-1 strains X4-HIV NL4-3 and R5-HIV BaL in human astrocytes.
Conclusions
The 2G-NN16 dendrimer successfully delivers and transfects siRNA to HIV-infected human astrocytes and achieves gene silencing without causing cytotoxicity.Both authors have contributed equally to this paper.
The production, biochemical characterization, and carbohydrate specificity of LacA β-galactosidase (locus lp_3469) belonging to the glycoside hydrolase family 42 from the probiotic organism ...Lactobacillus plantarum WCFS1 are addressed. The β-d-galactosidase activity was maximal in the pH range of 4.0–7.0 and at 30–37 °C. High hydrolysis capacity toward the β(1 → 4) linkages between galactose and glucose (lactose) or fructose (lactulose) was found. High efficiency toward galactosyl derivative formation was observed when lactose and glycerol, xylitol, or erythritol were used. Galactosyl derivatives of xylitol were characterized for the first time as 3- O -β-d-galactopyranosyl-xylitol and 1-O-β-d-galactopyranosyl-xylitol, displaying high preference of LacA β-galactosidase for the transfer of galactosyl residues from lactose to the C1 or C3 hydroxyl group of xylitol. These results indicate the feasibility of using LacA β-galactosidase for the synthesis of different galactosyl-polyols, which could be promising candidates for beneficial and appealing functional and technological applications such as novel prebiotics or hypocaloric sweeteners.
Aberrant extra-vascular expression of VE-cadherin (VEC) has been observed in metastasis associated with vasculogenic mimicry (VM); however, the ultimate reason why non-endothelial VEC favors the ...acquisition of this phenotype is not established. In this study, we show that human malignant melanoma cells have a constitutively high expression of phoshoVEC (pVEC) at Y658; pVEC is a target of focal adhesion kinase (FAK) and forms a complex with p120-catenin and the transcriptional repressor kaiso in the nucleus. FAK inhibition enabled kaiso to suppress the expression of its target genes and enhanced kaiso recruitment to KBS-containing promoters. Finally we have found that ablation of kaiso-repressed genes WNT11 and CCDN1 abolished VM. Thus, identification of pVEC as a component of the kaiso transcriptional complex establishes a molecular paradigm that links FAK-dependent phosphorylation of VEC as a major mechanism by which ectopical VEC expression exerts its function in VM.
Resetting Response to Differentiate SVT
Background
The usefulness of ventricular entrainment to differentiate AV nodal reentrant tachycardia (AVNRT) from orthodromic reciprocating tachycardia (ORT) ...by substracting the corrected postpacing interval (cPPI) from the tachycardia cycle length (TCL) or the ventriculoatrial interval during stimulation (SA) from that during tachycardia (VA) have been widely validated. However, some tachycardias are interrupted by pacing trains but may not be so by ventricular extrastimuli resulting in resetting.
Objectives
To validate prospectively the diagnostic yield of cPPI‐TCL and SA‐VA measurements after resetting and to determine the proportion of AVNRT and ORT that can be entrained and/or reset from the right ventricular apex (RVA).
Methods
223 consecutive patients with inducible AVNRT or ORT underwent pacing trains and single extrastimulus (also double extrastimuli if singles did not reset tachycardia) at the RVA. We calculated cPPI‐TCL and SA‐VA during entrainment and resetting.
Results
Entrainment could not be achieved in 15.2% of tachycardias because of consistent tachycardia interruption by pacing; resetting was observed in 99.5%. Values of cPPI‐TCL and SA‐VA > 110 milliseconds after resetting identified AVNRT as accurately as after entrainment. Values for cPPI‐TCL/ SA‐VA were: sensitivity: 98/100%; specificity: 96/98%; positive predictive value: 98/99%; negative predictive value: 98/100%.
Conclusions
Determinations of cPPI‐TCL and SA‐VA after resetting with single or double RVA extrastimuli are useful maneuvers to differentiate AVNRT from ORT and can be used for nearly every inducible AVNRT or ORT, even if they are interrupted by ventricular trains.
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