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A phenomenon that also causes impairment in the received signal strength of the RF signal in satellite links operating at frequencies above 10 GHz, especially in those systems that operate at higher frequencies with small fade margins, is the tropospheric scintillation that occurs in the lower layer of the troposphere. In order to estimate the intensity, i.e. the variance between the scintillation amplitude fluctuations, there are several models in the literature, whose accuracy depends on the locality in which the models are implemented. In this Letter, new models are developed for the prediction of tropospheric scintillation that adjusts to localities in Spain, specifically Madrid city, based on measurements of the aforementioned phenomenon reported from Spain and the bios-inspired technique Cuckoo Search (CS). The results obtained, evaluated in terms of the root mean square error, were totally satisfactory, being the most outstanding cases the improved versions of the Ortgies-T, Statistical Temperature and Humidity 2 and Statistical Temperature and Refractivity 2 models. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To assess the effectiveness of laser surgery in fetuses with a cystic lung lesion with systemic arterial blood supply (hybrid lung lesion) at risk of perinatal death. Methods A cohort of five consecutive fetuses with a large hybrid lung lesion associated with hydrops and/or pleural effusion with severe lung compression was selected for percutaneous ultrasound-guided fetal laser ablation of the feeding artery ( FLAFA) before 32 weeks' gestation in a single tertiary national referral center in Queretaro, Mexico. The primary outcomes were survival and need for postnatal surgery. Results FLAFA was performed successfully in all cases at a median gestational age of 24.9 (range, 24.4-31.7) weeks. After fetal intervention, dimensions in both lungs increased and fluid effusions resolved in all cases. All cases were delivered liveborn at term at a median gestational age of 39.6 (range, 38.0-39.7) weeks, without respiratory morbidity or need for oxygen support, resulting in perinatal survival of 100%. During follow-up, three (60%) cases showed progressive regression of the entire lung mass and did not require postnatal surgery, whereas in two (40%) cases a progressive decrease in size of the mass was observed but a cystic portion of the lung mass persisted and postnatal lobectomy was required. Conclusion In fetuses with large hybrid lung lesions at risk of perinatal death, FLAFA is feasible and could improve survival and decrease the need for postnatal surgery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

The known distribution of the Iberian lynx Lynx pardinus within the Iberian Peninsula since the Middle Pleistocene and the lack of reliable records of Eurasian lynx Lynx lynx in this region have led to the assumption that the Iberian lynx was the sole inhabitant of Iberia. In this study, we identified ancient mitochondrial DNA (a total of 337 base pairs from the control region and cytochrome b) from eight northern Iberian lynx remains as Eurasian lynx. These results confirm the presence of Eurasian lynx in northern Iberia from the Pleistocene/ Holocene boundary until just a few centuries ago. The paleontological record and our data indicate a population replacement of the Iberian lynx by the Eurasian lynx during the Pleistocene/ Holocene transition in the Cantabrian cornice of Spain. Phylogeographic patterns of Late Pleistocene and Holocene Eurasian lynx from Iberia, France, Italy and Denmark show that this felid had a more complex phylogeographic history in the past than modern day populations suggest. [ABSTRACT FROM AUTHOR]

Assessment of fetal strain using speckle-tracking software has been reported for characterising cardiac function in several clinical scenarios. The objective of this study was to construct gestational age (GA) based reference values for left ventricle (LV) longitudinal strain in normal fetuses, between 24-37 weeks of gestation, with automated cardiac motion quantification software (aCMQ-QLab), widely used in postnatal echocardiography. EP19.10: Gestational age-adjusted reference ranges for fetal LV longitudinal strain by automated cardiac motion quantification between 24-37 weeks of gestation. [Extracted from the article]

In the context of 3D reconstruction, we present a static multi-texturing system yielding a seamless texture atlas calculated by combining the colour information from several photos from the same subject covering most of its surface. These pictures can be provided by shooting just one camera several times when reconstructing a static object, or a set of synchronized cameras, when dealing with a human or any other moving object. We suppress the colour seams due to image misalignments and irregular lighting conditions that multi-texturing approaches typically suffer from, while minimizing the blurring effect introduced by colour blending techniques. Our system is robust enough to compensate for the almost inevitable inaccuracies of 3D meshes obtained with visual hull-based techniques: errors in silhouette segmentation, inherently bad handling of concavities, etc. [ABSTRACT FROM AUTHOR]

Background and Purpose: Despite the importance of mitochondrial Ca(2+) to metabolic regulation and cell physiology, little is known about the mechanisms that regulate Ca(2+) entry into the mitochondria. Accordingly, we established a system to determine the role of the mitochondrial Ca(2+) uniporter in an isolated heart model, at baseline and during increased workload following β-adrenoceptor stimulation.Experimental Approach: Cardiac contractility, oxygen consumption and intracellular Ca(2+) transients were measured in ex vivo perfused murine hearts. Ru360 and spermine were used to modify mitochondrial Ca(2+) uniporter activity. Changes in mitochondrial Ca(2+) content and energetic phosphate metabolite levels were determined.Key Results: The addition of Ru360 , a selective inhibitor of the mitochondrial Ca(2+) uniporter, induced progressively and sustained negative inotropic effects that were dose-dependent with an EC50 of 7 μM. Treatment with spermine, a uniporter agonist, showed a positive inotropic effect that was blocked by Ru360 . Inotropic stimulation with isoprenaline elevated oxygen consumption (2.7-fold), Ca(2+) -dependent activation of pyruvate dehydrogenase (5-fold) and mitochondrial Ca(2+) content (2.5-fold). However, in Ru360 -treated hearts, this parameter was attenuated. In addition, β-adrenoceptor stimulation in the presence of Ru360 did not affect intracellular Ca(2+) handling, PKA or Ca(2+) /calmodulin-dependent PK signalling.Conclusions and Implications: Inhibition of the mitochondrial Ca(2+) uniporter decreases β-adrenoceptor response, uncoupling between workload and production of energetic metabolites. Our results support the hypothesis that the coupling of workload and energy supply is partly dependent on mitochondrial Ca(2+) uniporter activity. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxias ( SCA) are a heterogeneous group of neurodegenerative disorders. CAG (cytosine-adenine-guanine) trinucleotide repeat expansions in the causative genes have been identified as the cause of different SCA. In this study, we simultaneously genotyped SCA1, SCA2, SCA3, SCA6, and SCA7 applying a fluorescent multiplex polymerase chain reaction assay. We analyzed 10 families with SCA (64 patients) from five different communities of Veracruz, a Mexican southeastern state, and identified 55 patients for SCA7 and 9 for SCA2, but none for SCA1, SCA3, or SCA6. To our knowledge, this sample represents one of the largest series of SCA7 cases reported worldwide. Genotyping of 300 healthy individuals from Mexican population and compiled data from different ethnicities showed discordant results concerning the hypothesis that SCA disease alleles arise by expansion of large normal alleles. [ABSTRACT FROM AUTHOR]

We introduce a novel methodology for mapping academic institutions based on their journal publication profiles. We believe that journals in which researchers from academic institutions publish their works can be considered as useful identifiers for representing the relationships between these institutions and establishing comparisons. However, when academic journals are used for research output representation, distinctions must be introduced between them, based on their value as institution descriptors. This leads us to the use of journal weights attached to the institution identifiers. Since a journal in which researchers from a large proportion of institutions published their papers may be a bad indicator of similarity between two academic institutions, it seems reasonable to weight it in accordance with how frequently researchers from different institutions published their papers in this journal. Cluster analysis can then be applied to group the academic institutions, and dendrograms can be provided to illustrate groups of institutions following agglomerative hierarchical clustering. In order to test this methodology, we use a sample of Spanish universities as a case study. We first map the study sample according to an institution's overall research output, then we use it for two scientific fields ( Information and Communication Technologies, as well as Medicine and Pharmacology) as a means to demonstrate how our methodology can be applied, not only for analyzing institutions as a whole, but also in different disciplinary contexts. [ABSTRACT FROM AUTHOR]

Two hundred and five isolates of Pasteurella multocida from pigs were phenotypically and genetically characterised by determining their biovar, capsular type, virulence-associated genes and pulsed-field gel electrophoresis (PFGE) profiles. All isolates were identified as P multocida subspecies multocida and most were assigned to biovar 3 (58 per cent) and biovar 2 (39.5 per cent). Biovar 1 represented 2.4 per cent of the isolates. According to the capsular type, the great majority of the isolates (79.0 per cent) belonged to capsular type A, 18.5 per cent belonged to capsular type D and 2.4 per cent were of capsular type F. All isolates harboured ompH, psl, oma87, ptfA, nanB, nanH, tonB, hgbA, sodA and sodC genes, while none of them possessed the transferrin-binding protein gene tbpA. The prevalence of toxA, pfhaA and hgbB genes was variable (7.8, 40.5 and 60.5 per cent of the isolates, respectively). After PFGE typing, isolates of biovar 2 and 3 were grouped in two different clusters (A and B) at a level of 45 per cent similarity. In addition, isolates of biovar 2 and 3 exhibited statistically significant differences (P<0.05) in the virulence-associated hgbB and pfhA genes (biovar 3 was hgbB+ pfhA-, while biovar 2 was hgbB- pfhA+). [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the degree of elasticity (DE) and the mechanical properties of wheat kernels including bread wheat, soft wheat, and durum wheat. The wheat kernels were tested for uniaxial compression and stress relaxation tests which showed force-deformation curves exhibiting two points of inflection (PI). The study concludes that PI regions presented high DE but was reduced in the endosperm region.

Purification and characterisation of pepper ( Capsicum annuum L) chloroplasts and chromoplasts isolated from commercial green, red and yellow mature fruits were undertaken. Induction of the synthesis of several antioxidants in organelles isolated from mature fruits was found. The ultrastructure of organelles and the presence and activity of SOD isozymes and enzymes involved in the ASC-GSH cycle, together with the non-enzymatic antioxidant content and some oxidative parameters, were analysed. It was found that lipids, rather than proteins, seem to be a target for oxidation in the chromoplasts. The ascorbate and glutathione contents were elicited during differentiation of chloroplasts into chromoplasts in both red and yellow fruits. The activity of SOD and of components of the ASC-GSH cycle was up-regulated, suggesting that these enzymes may play a role in the protection of plastids and could act as modulators of signal molecules such as O2˙− and H2O2 during fruit maturation. The presence of an Mn-SOD in chromoplasts isolated from yellow pepper fruits was also investigated in terms of structural and antioxidant differences between the two cultivars. [ABSTRACT FROM AUTHOR]

Intrauterine growth restricted (IUGR) fetuses have an increased risk for adverse outcomes, that may result from adaptive cardiovascular changes in conditions of placental insufficiency, which lead to cardiac deformation. Methods Longitudinal prospective cohort study in which left ventricular global longitudinal strain (LV-GLS) and its components were measured and compared between IUGR and appropriate for gestational age (AGA) fetuses. [Extracted from the article]

Recent evidence suggests the existence of lipid microdomains in mitochondria, apparently coexisting as structural elements with some of the mitochondrial permeability transition pore-forming proteins and members of the Bcl-2 family. The aim of this study was to investigate the relevance of the main components of membrane microdomains (e.g. cholesterol and sphingolipids) in activation of the mitochondrial permeability transition pore (mPTP) by recombinant BAX (rBAX). For this purpose, we used chemically modified renal cortex mitochondria and renal cortex mitochondria from hypothyroid rats that show a modified mitochondrial lipid composition in vivo. Oligomeric rBAX induced an enhanced permeability conformation in the mPTP of control mitochondria. rBAX failed to induce mPTP opening when the cholesterol and ganglioside content of mitochondria were modified with the chelator methyl-beta-cyclodextrin. Accordingly, hypothyroid mitochondria, with endogenously lower cholesterol and ganglioside content, showed resistance to mPTP opening induced by rBAX. These observations suggest that enriched cholesterol and ganglioside domains in the mitochondrial membranes may determine BAX interaction with the mPTP. An intriguing observation was that chemical extraction of cholesterol and ganglioside in control mitochondria did not have an effect on rBAX insertion. Conversely, in hypothyroid mitochondria, rBAX insertion was diminished dramatically compared with control mitochondria. The membrane and protein changes associated with thyroid status and their possible role in rBAX docking into the membranes are discussed. [ABSTRACT FROM AUTHOR]

Successful clearance of hepatitis C virus (HCV) infection has been associated with strong cellular immune responses against viral antigens. However, although the magnitude of these responses is clearly important for viral eradication, more studies are needed to unravel the fine specificity of the protective anti-HCV immunity in infected patients. This was the aim of the present study. Overlapping peptides spanning the sequence of HCV E2 and NS4a proteins were used to stimulate T cells from patients with chronic hepatitis C divided into three groups: naïve patients, patients who exhibited sustained response to interferon (IFN)- α therapy and patients who failed to respond to the treatment. Interleukin-2 production by stimulated cells was measured in each case. Patients with sustained response to therapy had stronger responses to E2 peptides than nonresponders, whereas naïve patients demonstrated intermediate reactivity. In the case of NS4a, responses against peptides where similar in all groups of patients. Analysis of the peptides recognized by T cells showed that responses were broad and heterogeneous, and some immunodominant epitopes, preferentially recognized by patients exhibiting sustained response to treatment, were found. These results confirm the role of cellular immune responses in viral clearance, and stress the importance of immunodominant regions within HCV antigens. These viral sequences may represent valuable immunogens for preparation of therapeutic or prophylactic vaccines. [ABSTRACT FROM AUTHOR]

Patients on chronic hemodialysis often portray high serum [K+]. Although dietary excesses are evident in many cases, in others, the cause of hyperkalemia cannot be identified. In such cases, hyperkalemia could result from decreased potassium removal during dialysis. This situation could occur if alkalinization of body fluids during dialysis would drive potassium into the cell, thus decreasing the potassium gradient across the dialysis membrane. In 35 chronic hemodialysis patients, we compared two dialysis sessions performed 7 days apart. Bicarbonate or acetate as dialysate buffers were randomly assigned for the first dialysis. The buffer was switched for the second dialysis. Serum [K+], [HCO3–], and pH were measured in samples drawn before dialysis; 60, 120, 180, and 240 min into dialysis; and 60 and 90 min after dialysis. The potassium removed was measured in the dialysate. During the first 2 hr, serum [K+] decreased equally with both types of dialysates but declined more during the last 2 hr with bicarbonate dialysis. After dialysis, the serum [K+] rebounded higher with bicarbonate bringing the serum [K+] up to par with acetate. The lower serum [K+] through the second half of bicarbonate dialysis did not impair potassium removal (295.9 ± 9.6 mmol with bicarbonate and 299.0 ± 14.4 mmol with acetate). The measured serum K+ concentrations correlated with serum [HCO3–] and blood pH during bicarbonate dialysis but not during acetate dialysis. Alkalinization induced by bicarbonate administration may cause redistribution of K during bicarbonate dialysis but this does not impair its removal. The more marked lowering of potassium during bicarbonate dialysis occurs late in dialysis, when exchange is negligible because of a low gradient. [ABSTRACT FROM AUTHOR]

This paper presents a dynamic virtual environment tool for training operators and to prove different control schemes in telerobotic systems, and describes virtual reality environments used in teleoperated robotic systems. In the presented tool, the kinematic and dynamic model of the remote environment which is manipulating the operator is considered. The paper also describes how time delays in the communication channel can be easily added to the simulator, in order to analyze their effects in the teleoperated system. Finally, some experimental results achieved with this virtual teleoperated system are shown. With the presented dynamic simulator, different control schemes designed to overcome the time delay problem could be tested. © 2005 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim: To perform a meta-analysis of studies comparing twice daily, one-week triple therapy with a proton pump inhibitor, clarithromycin (C) and amoxycillin (A) (PCA) vs. those using proton pump inhibitor, clarithromycin and a nitroimidazole (N) (PCN) for H. pylori eradication. Review methods: Selection criteria: Comparative randomized trials of PCA vs. PCN were included. Data sources: PubMed database and abstracts from congresses until September 1999. Statistics: Meta-analysis was performed combining the Odds Ratios (OR) of the individual studies in a global OR (Peto method) both on an intention-to-treat (ITT) and on a per protocol (PP) basis. Results: Twenty-two studies fulfilled the inclusion criteria. Eighteen studies reported ITT and 20 PP analysis. Mean H. pylori eradication rates were 81% (95% CI: 79–83%) ITT, and 84% (82–86%) PP with PCA, and 81% (78–83%) ITT and 84% (82–86%) PP with PCN; the odds ratio for the effect of PCA vs. PCN was 1 (0.83–1.22) on an ITT, and 0.98 (0.8–1.2) on a PP basis. Subanalysis showed that mean H. pylori eradication efficacy with PC(250 b.d.)A was 81% (78–85%) ITT, vs. 86% (83–89%) with PC(250 b.d.)N. The odds ratio for this comparison was 0.68 (0.48–0.98). Finally, when comparing PC(500 b.d.)A against PC(250 b.d.)N ITT cure rates were 77% (74–80%), and 75% (72–78%) with an odds ratio of 1.18 (0.93–1.5). Conclusion: Overall, one-week combination regimens of PCA and PCN present similar H. pylori eradication efficacy. Nevertheless, the PCN regimen obtains significantly better results when using low doses of C (250 mg b.d.). [ABSTRACT FROM AUTHOR]

The Dipilto Batholith is one of the largest plutonic complexes (~1,200 km2) of the Chortís block. It is located at northwestern Nicaragua in Central America. We present paleomagnetic, rock magnetic, and petrographic results from 34 sites (269 samples) of this batholith and some associated dikes. Four U‐Pb (zircon) isotopic ages were obtained from samples collected through the intrusive body in order to gain insight into the timing of silicic magmatism in the southern Chortís block and its possible tectonic and paleogeographic connections with the southwestern North America Plate during the Early Cretaceous. The paleomagnetic analyses of 16 selected sites indicate a large counterclockwise rotation (~101°), with a related paleolatitude of 28.7°N, and isotopic ages ranging from 119.08 ± 0.37 to 112.69 ± 0.44 Ma. Our results imply an updated tectonic model resulted from an inherited peri‐Gondwanan position and open the discussion of at least three possible tectonic scenarios for the Chortís block during the Early Cretaceous: (1) Chortís block with an angle of ~45° with respect to the southwestern margin of North America. This would imply the removal of an in‐between continental or oceanic crust segment by subduction or subduction erosion; (2) Chortís block immediately juxtaposed to the southwestern margin of North America, being part of extension‐compression events of the Guerrero Terrane‐Arperos basin; or (3) Chortís block juxtaposed to North America, but with intraplate deformation resulting in overestimated counterclockwise rotation for a tectonic decoupled block, called herein the "Dipilto block." Plain Language Summary: The plate tectonic evolution of the Caribbean region and North America have been a topic of discussion for more than 40 years. This and several previous studies on the rocks of Central America suggest that this region belonged to the south‐southwest of the tectonic plate of North America (currently southern Mexico) since at least 80 million years. To demonstrate this, we use the paleomagnetism of 34 sites of the Dipilto Batholith at northwestern Nicaragua, belonging to the continental crust domain named Chortís block, and U‐Pb dates to determine the spatial and temporal relationship of Central America. Our results show that at least since the Early Cretaceous (110 million years) the Chortís block was adjacent to the southwestern region of North America. In other words, this implies that the Chortís block belonged to the southwestern part of Mexico, probably next to the geological Guerrero terrane. The new paleogeographic information redefines the tectonic evolution and the causes and consequences of the geological record of this region of Mexico and Central America since the Early Cretaceous. Key Points: Paleomagnetism and geochronology of the Early Cretaceous Dipilto Batholith (southern Chortís block)Large counterclockwise rotation (~101°) and a paleolatitude of 28.7°N, with respect to the North American Plate in Early Cretaceous timeThree scenarios of the Chortís block; (1) large gap between North America; (2) part of the Guerrero Terrane; and (3) intraplate deformation [ABSTRACT FROM AUTHOR]

The use of a suitable propagation model for coverage prediction is key during the planning and dimensioning process of a digital terrestrial television (DTT) system. This study optimises one of the most detailed models for this purpose, i.e. Recommendation ITU-R.P.1812-4, with the aim of improving its accuracy in propagation path loss prediction for DTT systems in outdoor environments of Caracas city, Venezuela. For model adjustment, it is used the bioinspired technique particle swarm optimisation (PSO) and received signal level measurements performed in DTT systems in Caracas city under fixed reception conditions. The results, quantitatively analysed by RMS error and grey relation grade and mean absolute percentage error, shows a significant increase of the accuracy of optimised model in comparison with the original version and even with others propagation models. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of laser surgery in fetuses with a cystic lung lesion with systemic arterial blood supply (hybrid lung lesion) at risk of perinatal death.Methods: A cohort of five consecutive fetuses with a large hybrid lung lesion associated with hydrops and/or pleural effusion with severe lung compression was selected for percutaneous ultrasound-guided fetal laser ablation of the feeding artery (FLAFA) before 32 weeks' gestation in a single tertiary national referral center in Queretaro, Mexico. The primary outcomes were survival and need for postnatal surgery.Results: FLAFA was performed successfully in all cases at a median gestational age of 24.9 (range, 24.4-31.7) weeks. After fetal intervention, dimensions in both lungs increased and fluid effusions resolved in all cases. All cases were delivered liveborn at term at a median gestational age of 39.6 (range, 38.0-39.7) weeks, without respiratory morbidity or need for oxygen support, resulting in perinatal survival of 100%. During follow-up, three (60%) cases showed progressive regression of the entire lung mass and did not require postnatal surgery, whereas in two (40%) cases a progressive decrease in size of the mass was observed but a cystic portion of the lung mass persisted and postnatal lobectomy was required.Conclusion: In fetuses with large hybrid lung lesions at risk of perinatal death, FLAFA is feasible and could improve survival and decrease the need for postnatal surgery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Low-count monoclonal B-cell lymphocytosis (MBL lo ) has been associated with an underlying immunodeficiency and has recently emerged as a new risk factor for severe COVID-19. Here, we investigated the kinetics of immune cell and antibody responses in blood during COVID-19 of MBL lo versus non-MBL patients. For this study, we analyzed the kinetics of immune cells in blood of 336 COVID-19 patients (74 MBL lo and 262 non-MBL), who had not been vaccinated against SARS-CoV-2, over a period of 43 weeks since the onset of infection, using high-sensitivity flow cytometry. Plasma levels of anti-SARS-CoV-2 antibodies were measured in parallel by ELISA. Overall, early after the onset of symptoms, MBL lo COVID-19 patients showed increased neutrophil, monocyte, and particularly, plasma cell (PC) counts, whereas eosinophil, dendritic cell, basophil, and lymphocyte counts were markedly decreased in blood of a variable percentage of samples, and with a tendency toward normal levels from week +5 of infection onward. Compared with non-MBL patients, MBL lo COVID-19 patients presented higher neutrophil counts, together with decreased pre-GC B-cell, dendritic cell, and innate-like T-cell counts. Higher PC levels, together with a delayed PC peak and greater plasma levels of anti-SARS-CoV-2-specific antibodies (at week +2 to week +4) were also observed in MBL lo patients. In summary, MBL lo COVID-19 patients share immune profiles previously described for patients with severe SARS-CoV-2 infection, associated with a delayed but more pronounced PC and antibody humoral response once compared with non-MBL patients., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Clinical and biological variables like genetic aberrations at diagnosis and the levels of measurable residual disease (MRD) are the most powerful biomarkers to predict the outcome of paediatric leukaemia. Recently, a model integrating the genetic abnormalities, transcriptional identity, and leukaemia stemness measured as leukaemic stem cell score (pLSC6) has been proposed to identify high-risk paediatric acute myeloid leukaemia (AML) patients. However, the role of epigenetics in defining prognosis still needs to be established. We evaluated the role of 89 miRNAs regulating stemness and their contribution to predicting outcomes in 110 paediatric patients with acute leukaemia. We identified a 24-miRNA signature capable of distinguishing paediatric AML patients with excellent or poor outcomes. We validated these results in an independent cohort using public repository-based data. The 24-miRNA signature was significantly associated with the leukaemic stemness scores and the underlying genetics of patients. Notably, the combination of classical prognostic factors (MRD and genetics), the pLSC6 score and the 24-miRNA signature had a higher capacity to predict the overall and event-free survival than each variable individually. Our 24-miRNA signature provides epigenetic data to integrate into genetics, MRD and stemness-related leukaemic scores to refine risk stratification in paediatric AML patients., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

The molecular complexity displayed in acute myeloid leukemia (AML) hinders patient stratification and treatment decisions. Previous studies support the utility of using specific gene panels for this purpose. Focusing on two salient features of AML, the production of reactive oxygen species (ROS) by NADPH oxidases (NOX) and metabolism, we aimed to identify a gene panel that could improve patient stratification. A pairwise comparison of AML versus healthy gene expression revealed the downregulation of four members of the NOX2 complex including CYBB (coding for NOX2) in AML patients. We analyzed the expression of 941 genes related to metabolism and found 28 genes with expression correlated to CYBB. This panel of 29 genes (29G) effectively divides AML samples according to their prognostic group. The robustness of 29G was confirmed by 6 AML cohort datasets with a total of 1821 patients (overall accuracies of 85%, 78%, 80%, 75%, 59% and 83%). An expression index (EI) was developed according to the expression of the selected discriminatory genes. Overall Survival (OS) was higher for low 29G expression index patients than for the high 29G expression index group, which was confirmed in three different datasets with a total of 1069 patients. Moreover, 29G can dissect intermediate-prognosis patients in four clusters with different OS, which could improve the current AML stratification scheme. In summary, we have found a gene signature (29G) that can be used for AML classification and for OS prediction. Our results confirm NOX and metabolism as suitable therapeutic targets in AML., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Introduction: Family studies provide a suitable approach to analyzing candidate endophenotypes of schizophrenia, including cognitive features., Objective: To characterize different neurocognitive functions in a group of patients with first episode of psychosis (FEP), their first-degree relatives (parents and siblings), and healthy controls (HC), in order to identify potential endophenotypes for schizophrenia spectrum disorders (SSD)., Methods: Participants were assessed in the context of a national project in Spain called PAFIP-FAMILIAS. They completed the same neuropsychological battery, which included tests of verbal memory, visual memory, processing speed, working memory, executive functions, motor dexterity, attention, and theory of mind. Group comparisons were performed using one-way ANOVA, followed by tests of multiple comparisons when appropriate., Results: One hundred thirty-three FEP patients were included, as well as 244 of their first-degree relatives (146 parents and 98 siblings) and 202 HC. In general, relatives showed an intermediate performance between the HC and the FEP patients in all neurocognitive domains. However, the domains of executive functions and attention stood out, as relatives (especially parents) showed similar performance to FEP patients. This was replicated when selecting patients subsequently diagnosed with schizophrenia and their relatives., Conclusion: These findings suggest that executive and attention dysfunctions might have a family aggregation and could be relevant cognitive endophenotypes for psychotic disorders. The study shows the potential of exploring intra-family neuropsychological performance supporting neurobiological and genetic research in SSD., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To explore if the entire duration of active psychosis (DAP) is related to neurocognitive performance at baseline and at 3-year follow-up in patients with first episode psychosis (FEP)., Methods: DAP was estimated for 481 FEP patients. A neuropsychological battery was administered to measure neurocognitive specific domains, and a global indicator of neurocognitive impairment (global deficits score, GDS) was calculated. According to the DAP quartiles, four subgroups were formed, and these were compared. In addition, a logistic regression analysis was carried out to predict neurocognitive impairment at 3-year follow-up., Results: FEP patients with the longest DAP (more than 18.36 months) presented a more severe global neurocognitive impairment evidenced in their GDS, both at baseline (F = 5.53; p˂ .01) and at 3-year follow-up (F = 4.16; p˂ .01). Moreover, a subgroup of participants with DAP between 7.40 and 18.36 months showed a specific attentional decline over the 3-year follow-up (F = 3.089; p˂ .05).The logistic regression model showed that sex (Wald = 7.29, p < .010), premorbid adjustment (Wald = 7.24, p < .010), attention (Wald = 12.10, p < .001), verbal memory (Wald = 16.29, p < .001) and visual memory (Wald = 9.41, p < .010) were significant predictors of neurocognitive impairment 3 years after the FEP. The variables composing the DAP were not significant predictors in this model., Conclusions: DAP seems to be related to global neurocognitive impairment in FEP patients. These findings contribute in several ways to our understanding of the effects of active psychosis on the brain, and provide the basis for future research., (© 2020 John Wiley & Sons Australia, Ltd.)

Single-use technologies, in particular disposable bioreactor bags, have become integral within the biopharmaceutical community. However, safety concerns arose upon the identification of toxic leachable compounds derived from the plastic materials. Although the leachable bis(2,4-di-tert-butylphenyl)-phosphate (bDtBPP) has been previously shown to inhibit CHO cell growth, it is critical to determine if other compounds like this are still present in subsequent generations of films for industrial application. This study compares the performance of CHO cells, CHO-K1, and CHO-DP12, cultured in media conditioned in an older single-use bioreactor (SUB) film (F-1) and a newer generation film (F-2) from the same vendor. CHO cells cultured in media conditioned for 7 days in the F-1 film demonstrated significantly reduced growth and antibody productivity profiles when compared to controls and media conditioned for the same time period in the newer F-2 film. Proteomic profiling of CHO cells cultured in the F-1 conditioned media identified differentially expressed proteins involved in oxidative stress response as well as compromised ATP synthesis. These potentially metabolically compromised cells exhibited reduced oxidative phosphorylation activity as well as lower glycolytic metabolism, characteristic of slower growing cells. Nonvolatile and metal leachables analysis of film extracts by LC-MS revealed a reduction in the abundance of the analyzed leachates from F-2 films when compared to F-1 films including bDtBPP, potentially explaining improved CHO cell growth in F-2 conditioned media. Furthermore, in vitro endocrine disruptor testing of the known leachable revealed this molecule to possess the potential to act as an androgen antagonist. This study demonstrates an improvement in the materials composition used in modern generations of SUBs for safe application in the bioprocess., (© 2019 American Institute of Chemical Engineers.)

Background and Objectives: Substance use disorders (SUDs) have high comorbidities with psychiatric disorders. Childhood and adolescence are particularly vulnerable developmental periods for the onset of SUDs. The objective of this study was to explore the differences, if any, between Mexican adolescents and young adults with respect to the prevalences of groups of psychiatric disorders, the types of substances used and the social factors involved., Methods: This cross-sectional study included 781 patients evaluated at the Youth Integration Center in Mexico City. The diagnostic criteria for SUDs and psychiatric disorders were defined according to the DSM-IV and ICD-10. Associations between SUDs and psychiatric disorders were evaluated via multivariate analysis using logistic regression models., Results: The adolescents were more frequently substance abusers, whereas the adults had legal problems more often than the adolescents. We showed that adolescents using inhalants or cocaine were 1.62 more likely to have attention deficit hyperactivity disorder (ADHD). Moreover, adults using inhalants were 3.33 times more likely to meet the criteria for a psychotic disorder., Discussion and Conclusions: We found that adolescents diagnosed with ADHD were more likely to have problems with use or abuse of or dependence on inhalants, and an elevated prevalence of parental SUDs was found in both the adolescent and adult groups., Scientific Significance: Our findings indicate that earlier diagnosis and intervention are necessary in adolescents with ADHD and/or parental SUDs to prevent more advanced psychiatric diseases and adverse social consequences during adulthood. (Am J Addict 2018;XX:1-7)., (© 2018 American Academy of Addiction Psychiatry.)

Integrin α6β4 is a major component of hemidesmosomes that mediate the stable anchorage of epithelial cells to the underlying basement membrane. Integrin α6β4 has also been implicated in cell proliferation and migration and in carcinoma progression. The third and fourth fibronectin type III domains (FnIII-3,4) of integrin β4 mediate binding to the hemidesmosomal proteins BPAG1e and BPAG2, and participate in signalling. Here, it is demonstrated that X-ray crystallography, small-angle X-ray scattering and double electron-electron resonance (DEER) complement each other to solve the structure of the FnIII-3,4 region. The crystal structures of the individual FnIII-3 and FnIII-4 domains were solved and the relative arrangement of the FnIII domains was elucidated by combining DEER with site-directed spin labelling. Multiple structures of the interdomain linker were modelled by Monte Carlo methods complying with DEER constraints, and the final structures were selected against experimental scattering data. FnIII-3,4 has a compact and cambered flat structure with an evolutionary conserved surface that is likely to correspond to a protein-interaction site. Finally, this hybrid method is of general application for the study of other macromolecules and complexes.

Broad-spectrum amino-acid racemases (Bsrs) enable bacteria to generate noncanonical D-amino acids, the roles of which in microbial physiology, including the modulation of cell-wall structure and the dissolution of biofilms, are just beginning to be appreciated. Here, extensive crystallographic, mutational, biochemical and bioinformatic studies were used to define the molecular features of the racemase BsrV that enable this enzyme to accommodate more diverse substrates than the related PLP-dependent alanine racemases. Conserved residues were identified that distinguish BsrV and a newly defined family of broad-spectrum racemases from alanine racemases, and these residues were found to be key mediators of the multispecificity of BrsV. Finally, the structural analysis of an additional Bsr that was identified in the bioinformatic analysis confirmed that the distinguishing features of BrsV are conserved among Bsr family members.

Oxidant stress, among other effectors, is implicated in the sequel of myocardial reperfusion injury. It is generally accepted that maintaining the balance between oxidant and antioxidant signalling within the cell provides protection against reperfusion damage. The cardioprotective strategy of postconditioning (PC) reduces reperfusion injury through complex mechanisms; however, the contribution of the antioxidant system has not been fully investigated. In this study, isolated rat hearts were subjected to PC after 30 min global ischaemia, and then to 5 min (IR5) or 60 min of reperfusion (IR60). Postconditioning significantly increased the left ventricular developed pressure and the double product (heart rate × left ventricular developed pressure) for both early (PC5) and prolonged reperfusion (PC60, PC before 60 min of reperfusion). Necrotic tissue diminished to 10.8% in PC60 hearts, compared with 49% of infarct size measured in IR60 hearts (P < 0.05 versus IR60). Also, protein carbonylation and malondialdehyde levels decreased and were correlated with a significant augmentation in CuZn superoxide dismutase activity (P < 0.05, PC60 versus IR60) and increased glutathione redox state (GSH:GSSG ratio; P < 0.05, PC60 versus IR60). Diethylthiocarbamate, a non-selective superoxide dismutase inhibitor, significantly diminished the protection afforded by PC when administered throughout the protocol. However, administration of this inhibitor only during reperfusion had no effect on PC-induced cardioprotection. These results indicate that non-enzymatic antioxidants account for the protective effect of PC, modifying the oxidant stress caused by ischaemic reperfusion in rats. The contribution of CuZn superoxide dismutase activity in the observed cardioprotective effect is less clear, and could be relevant if acting in concert with other PC-activated mechanisms.

Phosphoglycerate kinase (PGK) is a widespread two-domain enzyme that plays a critical role in the glycolytic pathway. Several glycolytic enzymes from streptococci have been identified as surface-exposed proteins that are involved in streptococcal virulence by their ability to bind host proteins. This binding allows pneumococcal cells to disseminate through the epithelial and endothelial layers. Crystallization of PGK from Streptococcus pneumoniae yielded orthorhombic crystals (space group I222, unit-cell parameters a = 62.73, b = 75.38, c = 83.63 Å). However, the unit cell of these crystals was not compatible with the presence of full-length PGK. Various analytical methods showed that only the N-terminal domain of PGK was present in the I222 crystals. The ternary complex of PGK with adenylyl imidodiphosphate (AMP-PNP) and 3-phospho-D-glycerate (3PGA) produced monoclinic crystals (space group P2(1), unit-cell parameters a = 40.35, b = 78.23, c = 59.03 Å, β = 96.34°). Molecular replacement showed that this new crystal form contained full-length PGK, thereby indicating the relevance of including substrates in order to avoid proteolysis during the crystallization process., (© 2011 International Union of Crystallography. All rights reserved.)

The integrin alpha6beta4 is a receptor for laminins and provides stable adhesion of epithelial cells to the basement membranes. In addition, alpha6beta4 is important for keratinocyte migration during wound healing and favours the invasion of carcinomas into surrounding tissue. The cytoplasmic domain of the beta4 subunit is responsible for most of the intracellular interactions of the integrin; it contains four fibronectin type III domains and a Calx-beta motif. The crystal structure of the Calx-beta domain of beta4 was determined to 1.48 A resolution. The structure does not contain cations and biophysical data support the supposition that the Calx-beta domain of beta4 does not bind calcium. Comparison of the Calx-beta domain of beta4 with the calcium-binding domains of Na(+)/Ca(2+)-exchanger 1 reveals that in beta4 Arg1003 occupies a position equivalent to that of the calcium ions in the Na(+)/Ca(2+)-exchanger. By combining mutagenesis and thermally induced unfolding, it is shown that Arg1003 contributes to the stability of the Calx-beta domain. The structure of the Calx-beta domain is discussed in the context of the function and intracellular interactions of the integrin beta4 subunit and a putative functional site is proposed.

We present the case of a 63-year-old man who underwent surgical closure of a paravalvular mitral leak. Immediately after surgery, transesophageal echocardiography revealed the appearance of a mediastinal hematoma encroaching on the left atrium and separating the esophageal probe from the posterior left atrial wall. The cause was an inadvertent puncture of the carotid artery, presumably during central venous line insertion prior to surgery.

The differential diagnosis of masses encroaching on the left atrium may be challenging. We describe a case in which contrast echocardiography using a carbonated drink provided a rapid and simple way to clarify the diagnosis of an incidental mass causing extrinsic compression of the left atrium. Given its simplicity and availability, we believe that it should be considered as a first line tool for clarifying the diagnosis in cases of echocardiographic evidence of left atrial encroachment of unknown origin.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity and behavioral impairment in rodents. Previous studies suggest that oxidative stress, via free radical production, is involved in MPTP-induced neurotoxicity. The MPTP-treated mouse has been the most widely used model for assessing neuroprotective agents for Parkinson's disease. It has been reported previously that EGb761 prevents dopaminergic neurotoxicity of MPTP. This compound is multifunctional via different mechanisms. Here, we report the neuroprotective effect of EGb761 against oxidative stress induced by MPTP in C57BL/6J mice. EGb761 is a patented and well-defined mixture of active compounds extracted from Ginkgo biloba leaves, with neuroprotective effects, exerted probably via its antioxidant or free radical scavenger action. MPTP administration resulted in a significant decrease in striatal dopamine levels and tyrosine hydroxylase immunostaining in the striatum and substantia nigra pars compacta. Mice receiving EGb761 had significantly attenuated MPTP-induced loss of striatal dopamine levels and tyrosine hydroxylase immunostaining in the striatum and substantia nigra pars compacta. The neuroprotective effect of EGb761 against MPTP neurotoxicity is associated with blockade of lipid peroxidation and reduction of superoxide radical production (indicated by a down-regulation of Mn-superoxide dismutase activity), both of which are indices of oxidative stress. Behavioral analyses showed that EGb761 improved MPTP-induced impairment of locomotion in a manner that correlated with enhancement of striatal dopamine levels. These findings suggest that, in mice, EGb761 attenuates MPTP-induced neurodegeneration of the nigrostriatal pathway and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.

The molecular and supramolecular structures of 2-(1,3-dioxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-2-yl)phenyl acetate, C16-H15NO4, (I), and its para isomer, 4-(1,3-dioxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-2-yl)phenyl acetate, (II), are reported. The torsion angle between the succinimide and benzene rings depends on the position of the acetoxy substitution [89.7 (1) and 61.9 (1) degrees for (I) and (II), respectively]. The twist of the acetoxy group relative to the mean plane of the benzene ring is almost independent of the acetoxy position [66.0 (1) and 70.0 (1) degrees ]. Packing interactions for both compounds include soft C-H...X (X = O and Ph) interactions, forming chains of centrosymmetric dimers and interlinked chains for (I) and (II), respectively. In addition, three perpendicular dipole C=O...C=O interactions contribute to the supramolecular structure of (II).

In exo-2-(3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.0(2,6)]dec-8-en-4-yl)phenyl acetate, C(16)H(13)NO(5), the plane of the acetoxy group lies almost perpendicular to that of the phenyl ring [dihedral angle = 89.8 (1) degrees ], in contrast with the smaller deviations found in the para isomer exo-4-(3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.0(2,6)]dec-8-en-4-yl)phenyl acetate, C(16)H(13)NO(5), these being 63.6 (1) and 37.0 (1) degrees for the two crystallographically independent molecules. Irrespective of the position of the acetoxy group, both compounds pack through soft C-H.X (X is O or phenyl) interactions, forming interlinked centrosymmetric tetramers in the bc plane.

Background: Although triple therapies with a proton pump inhibitor, clarithromycin and either amoxycillin or metronidazole are the most widely accepted treatment for Helicobacter pylori infection, there is no consensus on how long treatment should be maintained for., Aim: To evaluate whether increasing the length of triple therapies beyond 7 days improves treatment efficacy., Methods: An extensive search of the literature was performed. Reports of randomized trials comparing different lengths of therapy were selected. Short (7-day) vs. long (10/14-day) therapies were compared, and three-way comparison of 7-day vs. 10-day, 10-day vs. 14-day and 7-day vs. 14-day therapies was performed. Meta-analysis was conducted using conventional shareware (Review Manager 4.0). The Peto Odds Ratio using a fixed model analysis was calculated for each comparison., Results: Thirteen studies were identified. Pooled 10- to 14-day therapies achieved better results than 7-day schedules. In head-to-head comparisons, only 14-day therapies were significantly better than 7-day treatments. Improvement in cure rates ranged from 7 to 9%. Comparisons of 7-day vs. 10-day and 10-day vs. 14-day also showed a non-significant trend towards better cure rates with longer therapies., Conclusions: Fourteen-day, proton pump inhibitor-based triple therapy achieves better results than 7-day schedules. Additional data are necessary to evaluate 10-day therapies.

Background: The best regimen for the treatment of Helicobacter pylori infection has yet to be defined. Four-day quadruple therapy with tetracycline, metronidazole, bismuth, and a proton pump inhibitor has been shown to obtain a very high cure rate. However, the fact that it must be taken four times daily may interfere with compliance. The objective of the study was to test the efficacy and tolerability of a new 4-day therapy with 4 drugs taken every 12 hours to cure H. pylori infection. Patients and Methods. Fifty-six consecutive patients with peptic ulcer disease and H. pylori infection were treated with an oral 4-day course with omeprazole (20 mg/12 hours), clarithromycin (500 mg/12 hours), amoxicillin (1 g/12 hours) and tinidazole (500 mg/12 hours). Efficacy of the treatment was determined at least 2 months after therapy either by biopsy (in the case of gastric ulcer) or by 13C-urea breath test. A second breath test was performed at least 6 months after therapy., Results: Two patients were lost to follow-up. Forty-nine of the remaining 54 patients were cured at the first control [intention-to-treat cure rate: 87.5% (CI 95% 75-94%); per protocol cure rate: 90.7% (CI 95% 81-98%)]. Forty-three of these 49 cured patients returned for a second 13C urea breath-test at 6-12 months. Two of them were not cured, giving a long-term cure rate of 85.5% per protocol and 73.2% by intention-to-treat. Compliance was good, although 25 patients had mild side effects., Conclusion: This particular four-day therapy is well tolerated, easy to follow, and achieves an acceptably high cure rate.