A global phylogenomic analysis of the shiitake genus Lentinula.

Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes. We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia-Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase (lecsl) and γ-glutamyl transpeptidase (leggt), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula. Paralogs of both genes that are unique to Lentinula (lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes. The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation.

Loss of mGlu5 receptors in somatostatin-expressing neurons alters negative emotional states.

Subtype 5 metabotropic glutamate receptors (mGlu5) are known to play an important role in regulating cognitive, social and valence systems. However, it remains largely unknown at which circuits and neuronal types mGlu5 act to influence these behavioral domains. Altered tissue- or cell-specific expression or function of mGlu5 has been proposed to contribute to the exacerbation of neuropsychiatric disorders. Here, we examined how these receptors regulate the activity of somatostatin-expressing (SST+) neurons, as well as their influence on behavior and brain rhythmic activity. Loss of mGlu5 in SST+ neurons elicited excitatory synaptic dysfunction in a region and sex-specific manner together with a range of emotional imbalances including diminished social novelty preference, reduced anxiety-like behavior and decreased freezing during retrieval of fear memories. In addition, the absence of mGlu5 in SST+ neurons during fear processing impaired theta frequency oscillatory activity in the medial prefrontal cortex and ventral hippocampus. These findings reveal a critical role of mGlu5 in controlling SST+ neurons excitability necessary for regulating negative emotional states.

Breaking the Mucin Barrier: A New Affinity Chromatography-Mass Spectrometry Approach to Unveil Potential Cell Markers and Pathways Altered in Pseudomyxoma Peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin. RESULTS: This manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP. CONCLUSIONS: In sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies.

Crosstalk between cholesterol and PIP2 in the regulation of Kv7.2/Kv7.3 channels.

The activity of neuronal Kv7.2/Kv7.3 channels is critically dependent on PIP2 and finely modulated by cholesterol. Here, we report the crosstalk between cholesterol and PIP2 in the regulation of Kv7.2/Kv7.3 channels. Our results show that currents passing through Kv7.2/Kv7.3 channels in cholesterol-depleted cells, by acute application of methyl-ß-cyclodextrin (MßCD), were less sensitive to PIP2 dephosphorylation strategies than those of control cells, suggesting that cholesterol depletion enhances the Kv7.2/Kv7.3-PIP2 interaction. In contrast, the sensitivity of Kv7.2/Kv7.3 channels to acute membrane cholesterol depletion by MßCD was not altered in mutant channels with different apparent affinities for PIP2.

Vulnerability of Eastern Tropical Pacific chondrichthyan fish to climate change.

Climate change is an environmental emergency threatening species and ecosystems globally. Oceans have absorbed about 90% of anthropogenic heat and 20%-30% of the carbon emissions, resulting in ocean warming, acidification, deoxygenation, changes in ocean stratification and nutrient availability, and more severe extreme events. Given predictions of further changes, there is a critical need to understand how marine species will be affected. Here, we used an integrated risk assessment framework to evaluate the vulnerability of 132 chondrichthyans in the Eastern Tropical Pacific (ETP) to the impacts of climate change. Taking a precautionary view, we found that almost a quarter (23%) of the ETP chondrichthyan species evaluated were highly vulnerable to climate change, and much of the rest (76%) were moderately vulnerable. Most of the highly vulnerable species are batoids (77%), and a large proportion (90%) are coastal or pelagic species that use coastal habitats as nurseries. Six species of batoids were highly vulnerable in all three components of the assessment (exposure, sensitivity and adaptive capacity). This assessment indicates that coastal species, particularly those relying on inshore nursery areas are the most vulnerable to climate change. Ocean warming, in combination with acidification and potential deoxygenation, will likely have widespread effects on ETP chondrichthyan species, but coastal species may also contend with changes in freshwater inputs, salinity, and sea level rise. This climate-related vulnerability is compounded by other anthropogenic factors, such as overfishing and habitat degradation already occurring in the region. Mitigating the impacts of climate change on ETP chondrichthyans involves a range of approaches that include addressing habitat degradation, sustainability of exploitation, and species-specific actions may be required for species at higher risk. The assessment also highlighted the need to further understand climate change's impacts on key ETP habitats and processes and identified knowledge gaps on ETP chondrichthyan species.

El cambio climático es una emergencia medioambiental que amenaza a especies y ecosistemas en todo el mundo. Los océanos han absorbido alrededor del 90% del calor antropogénico y entre el 20% y el 30% de las emisiones de carbono, lo que ha provocado su calentamiento, acidificación, desoxigenación, cambios en la estratificación de los océanos y en la disponibilidad de nutrientes, así como fenómenos extremos más pronunciados. Dadas las predicciones de cambios, hay una importante necesidad de entender cómo las especies marinas se verán afectadas. En este estudio utilizamos una Evaluación Integrada de Riesgos para evaluar la vulnerabilidad de 132 condrictios del Pacífico Tropical Oriental (PTO) a los impactos del cambio climático. Adoptando un enfoque preventivo, estimamos que la vulnerabilidad general al cambio climático es Alta para casi una cuarta parte (23%) de las especies de condrictios del PTO evaluadas y Moderada para gran parte del resto (76%). La mayoría de las especies altamente vulnerables son batoideos (77%), y una gran proporción de éstas (90%) son especies costeras o especies pelágicas que utilizan los hábitats costeros como áreas de crianza. Seis especies de batoideos tuvieron una vulnerabilidad Alta en los tres componentes de la evaluación. Esta evaluación indica que las especies costeras, en particular las que dependen de áreas de crianza costeras, son las más vulnerables al cambio climático. Es probable que el calentamiento de los océanos, junto con la acidificación y la posible desoxigenación, tenga efectos generalizados sobre las especies de condrictios del PTO, pero las especies costeras se verán también afectadas por los cambios en los aportes de agua dulce, la salinidad y el aumento del nivel del mar. Esta vulnerabilidad relacionada con el clima se ve agravada por otros factores antropogénicos que ya se están produciendo en la región, como la sobrepesca y la degradación del hábitat. La mitigación de los impactos del cambio climático sobre los condrictios del PTO implica medidas que incluyan abordar la degradación del hábitat y la sostenibilidad de la explotación pesquera, y acciones para las especies de mayor riesgo son necesarias. Esta evaluación también destaca la necesidad de comprender mejor los impactos del cambio climático en los hábitats y procesos clave del PTO y las lagunas de conocimiento identificadas en relación con las especies de condrictios del PTO.

Etiological diagnosis of recurrent acute pancreatitis.

Acute pancreatitis is the leading cause of inpatient care among gastrointestinal conditions. Despite early intervention, one-third of patients experience recurrent acute pancreatitis (RAP). A comprehensive diagnostic approach is warranted to identify and treat underlying factors in order to prevent recurrence. RAP is most frequent among men aged 30-40, smokers, and in those with excessive alcohol consumption. To identify the etiology is paramount to stratify patients according to their individual risk of RAP and for predicting an eventual evolution to chronic pancreatitis. Although the initial management of acute pancreatitis is widely homogeneous according to established guidelines, there are no defined protocols to investigate RAP. In the present editorial article we propose a structured algorithm with precise recommendations to investigate the etiology RAP as part of routine clinical practice. Although there are relevant knowledge gaps in this disease, we believe that our guidance would contribute for a more homogenous diagnostic approach of RAP in clinical practice.

Expanding the Physiological Role of Aryl-Alcohol Flavooxidases as Quinone Reductases.

Aryl-alcohol oxidases (AAOs) are members of the glucose-methanol-choline oxidase/dehydrogenase (GMC) superfamily. These extracellular flavoproteins have been described as auxiliary enzymes in the degradation of lignin by several white-rot basidiomycetes. In this context, they oxidize fungal secondary metabolites and lignin-derived compounds using O2 as an electron acceptor, and supply H2O2 to ligninolytic peroxidases. Their substrate specificity, including mechanistic aspects of the oxidation reaction, has been characterized in Pleurotus eryngii AAO, taken as a model enzyme of this GMC superfamily. AAOs show broad reducing-substrate specificity in agreement with their role in lignin degradation, being able to oxidize both nonphenolic and phenolic aryl alcohols (and hydrated aldehydes). In the present work, the AAOs from Pleurotus ostreatus and Bjerkandera adusta were heterologously expressed in Escherichia coli, and their physicochemical properties and oxidizing abilities were compared with those of the well-known recombinant AAO from P. eryngii. In addition, electron acceptors different from O2, such as p-benzoquinone and the artificial redox dye 2,6-Dichlorophenolindophenol, were also studied. Differences in reducing-substrate specificity were found between the AAO enzymes from B. adusta and the two Pleurotus species. Moreover, the three AAOs oxidized aryl alcohols concomitantly with the reduction of p-benzoquinone, with similar or even higher efficiencies than when using their preferred oxidizing-substrate, O2. IMPORTANCE In this work, quinone reductase activity is analyzed in three AAO flavooxidases, whose preferred oxidizing-substrate is O2. The results presented, including reactions in the presence of both oxidizing substrates-benzoquinone and molecular oxygen-suggest that such aryl-alcohol dehydrogenase activity, although less important than its oxidase activity in terms of maximal turnover, may have a physiological role during fungal decay of lignocellulose by the reduction of quinones (and phenoxy radicals) from lignin degradation, preventing repolymerization. Moreover, the resulting hydroquinones would participate in redox-cycling reactions for the production of hydroxyl free radical involved in the oxidative attack of the plant cell-wall. Hydroquinones can also act as mediators for laccases and peroxidases in lignin degradation in the form of semiquinone radicals, as well as activators of lytic polysaccharide monooxygenases in the attack of crystalline cellulose. Moreover, reduction of these, and other phenoxy radicals produced by laccases and peroxidases, promotes lignin degradation by limiting repolymerization reactions. These findings expand the role of AAO in lignin biodegradation.

Estimation of parasitaemia in imported falciparum malaria using the results of a combined rapid diagnostic test. No big help from haematological parameters.

BACKGROUND: Microscopy continues to be the mainstay for the evaluation of parasitaemia in malaria but requires laboratory support and microbiological experience. Other fast and simple methods are necessary. METHODS: A retrospective observational study of imported malaria treated from July-2007 to December-2020 was carried out to evaluate the association between the degree of parasitaemia and both rapid diagnostic tests (RDT) reactivity patterns and haematological parameters. Plasmodium falciparum monoinfections diagnosed by peripheral blood smear and/or polymerase chain reaction (PCR),which also had a positive RDT result in the same blood sample, were included in the study. RESULTS: A total of 273 patients were included. Most of them were male (n = 256; 93.8%) and visiting friends and relatives (VFR) travellers (n = 252; 92.3%). Patients with plasmodial lactate dehydrogenase (pLDH) or aldolase and histidine-rich protein 2 (HRP-2) co-reactivity (Pan/Pf pattern) had a parasitaemia range between 0 and 37% while those with just HRP-2 reactivity (P. falciparum pattern) had ranges between 0 and 1%. Not a single case of P. falciparum pattern was found for parasitaemia ranges greater than 1%, showing a negative predictive value of 100% for high parasitaemia. All the correlations between haematological parameters and parasitaemia resulted to be weak, with a maximum rho coefficient of -0.35 for lymphocytes and platelets, and of 0.40 for neutrophils-to-lymphocytes count ratio. Multivariate predictive models were constructed reflecting a poor predictive capacity. CONCLUSIONS: The reactivity pattern of RDT allows a rapid semi-quantitative assessment of P. falciparum parasitaemia in travellers with imported malaria, discriminating patients with lower parasite loads. Haematological parameters were not able to estimate parasitaemia with sufficient precision.

An educational intervention to reduce the incidence of postoperative residual curarisation: a cluster randomised crossover trial in patients undergoing general anaesthesia.

BACKGROUND: The incidence of postoperative residual curarisation remains unacceptably high. We assessed whether an educational intervention on perioperative neuromuscular block management can reduce it. METHODS: In this multicentre, cluster randomised crossover trial, centres were allocated to receive an educational intervention either in a first or a second period. The educational intervention consisted of a lecture about neuromuscular management key points, including quantitative neuromuscular monitoring and use of reversal agents. The lecture was streamed to allow repetition. Additionally, memory cards were distributed in each operating theatre. The primary outcome was postoperative residual curarisation in the PACU. Secondary outcomes were frequency of quantitative neuromuscular monitoring, use of reversal agents, and incidence of postoperative pulmonary complications during hospital stay. Measurements were performed before randomisation and after the first and the second period. The effect of the educational intervention was estimated using multivariable mixed effects logistic regression models. RESULTS: We included 2314 subjects in 34 Spanish centres. Postoperative residual curarisation incidence was not affected by the educational intervention (odds ratio [OR] 0.90 [95% confidence interval {CI}: 0.51-1.58]; P=0.717 and 1.30 [0.73-2.30]; P=0.371] for first and second time-period interaction). The educational intervention increased the quantitative neuromuscular monitor usage (OR 2.04 [95% CI: 1.31-3.19]; P=0.002), the use of reversal agents was unchanged (OR 0.79 [95% CI: 0.50-1.26]; P=0.322), and the incidence of postoperative pulmonary complications decreased (OR 0.19 [95% CI: 0.10-0.35]; P<0.001). CONCLUSIONS: An educational intervention on perioperative neuromuscular block management did not reduce the incidence of postoperative residual curarisation nor increase reversal, despite increased quantitative neuromuscular monitoring. Sugammadex reversal was associated with reduced postoperative residual curarisation. The educational intervention was associated with a decrease in postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03128151.

HESML: a real-time semantic measures library for the biomedical domain with a reproducible survey.

BACKGROUND: Ontology-based semantic similarity measures based on SNOMED-CT, MeSH, and Gene Ontology are being extensively used in many applications in biomedical text mining and genomics respectively, which has encouraged the development of semantic measures libraries based on the aforementioned ontologies. However, current state-of-the-art semantic measures libraries have some performance and scalability drawbacks derived from their ontology representations based on relational databases, or naive in-memory graph representations. Likewise, a recent reproducible survey on word similarity shows that one hybrid IC-based measure which integrates a shortest-path computation sets the state of the art in the family of ontology-based semantic measures. However, the lack of an efficient shortest-path algorithm for their real-time computation prevents both their practical use in any application and the use of any other path-based semantic similarity measure. RESULTS: To bridge the two aforementioned gaps, this work introduces for the first time an updated version of the HESML Java software library especially designed for the biomedical domain, which implements the most efficient and scalable ontology representation reported in the literature, together with a new method for the approximation of the Dijkstra's algorithm for taxonomies, called Ancestors-based Shortest-Path Length (AncSPL), which allows the real-time computation of any path-based semantic similarity measure. CONCLUSIONS: We introduce a set of reproducible benchmarks showing that HESML outperforms by several orders of magnitude the current state-of-the-art libraries in the three aforementioned biomedical ontologies, as well as the real-time performance and approximation quality of the new AncSPL shortest-path algorithm. Likewise, we show that AncSPL linearly scales regarding the dimension of the common ancestor subgraph regardless of the ontology size. Path-based measures based on the new AncSPL algorithm are up to six orders of magnitude faster than their exact implementation in large ontologies like SNOMED-CT and GO. Finally, we provide a detailed reproducibility protocol and dataset as supplementary material to allow the exact replication of all our experiments and results.

Genomic Analysis Enlightens Agaricales Lifestyle Evolution and Increasing Peroxidase Diversity.

As actors of global carbon cycle, Agaricomycetes (Basidiomycota) have developed complex enzymatic machineries that allow them to decompose all plant polymers, including lignin. Among them, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles. Comparative analysis of 52 Agaricomycetes genomes (14 of them sequenced de novo) reveals that Agaricales possess a large diversity of hydrolytic and oxidative enzymes for lignocellulose decay. Based on the gene families with the predicted highest evolutionary rates-namely cellulose-binding CBM1, glycoside hydrolase GH43, lytic polysaccharide monooxygenase AA9, class-II peroxidases, glucose-methanol-choline oxidase/dehydrogenases, laccases, and unspecific peroxygenases-we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. The changes in the enzymatic toolkit of ancestral Agaricales are correlated with the evolution of their ability to grow not only on wood but also on leaf litter and decayed wood, with grass-litter decomposers as the most recent eco-physiological group. In this context, the above families were analyzed in detail in connection with lifestyle diversity. Peroxidases appear as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes, consistent with their essential role in lignin degradation and high evolutionary rates. This includes not only expansions/losses in peroxidase genes common to other basidiomycetes but also the widespread presence in Agaricales (and Russulales) of new peroxidases types not found in wood-rotting Polyporales, and other Agaricomycetes orders. Therefore, we analyzed the peroxidase evolution in Agaricomycetes by ancestral-sequence reconstruction revealing several major evolutionary pathways and mapped the appearance of the different enzyme types in a time-calibrated species tree.

SPION nanoparticles for delivery of dopaminergic isoquinoline and benzazepine derivatives.

Superparamagnetic iron nanoparticles (SPIONs) have become one of the most useful colloidal systems in nanomedicine. We report here the preparation of new hybrid core@shell systems based on SPION nanoparticles coated with a SiO2 shell (SPION@SiO2) and functionalized with carboxyl groups (SPION@SiO2-COOH). A series of new N-alkylamino- and N-alkylamido-terminated 1-phenyl- tetrahydroisoquinolines (THIQs) and 3-tetrahydrobenzazepines (THBs) derivatives presenting -SMe and -Cl groups, respectively, with potential dopaminergic activity, are synthesized and incorporated to the hybrid system. We include the synthetic details for THIQs and THBs derivatives preparation and investigate the influence of the terminal-functional group as well as the number of carbon atoms linked to THIQ and THB molecules during the coupling to the SPION@SiO2-COOH. Nuclear magnetic resonance (NMR) and electron ionization mass spectrometry (EI-MS) are used to characterize the synthesized THIQs and THBs. High-angle annular dark-field transmission electron microscopy (HAADF-TEM), energy dispersive X-ray transmission electron microscopy (EDX-TEM), and proton high-resolution magic angle spinning NMR spectroscopy1H HRMAS-NMR) are used to confirm the presence of THB and THIQ molecules onto the surface of the nanoparticles. The hybrid SPION@SiO2-THIQ and THB systems show significant activity toward the D2 receptor, reaching Ki values of about 20 nM, thus having potential application in the treatment of central nervous system (CNS) diseases.

Malignancy of intraductal papillary neoplasm of the bile duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is an uncommon disease which was first included in the World Health Organization classification of neoplasms in 2010. A 64-year-old female was admitted to the hospital because of a hepatic lesion incidentally diagnosed during acute cholangitis. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a well delimited 70 mm mass, with a predominant cystic component and hyperenhancement of papillary internal branching, consistent with a hydatid cyst. However, malignancy could not be excluded. The patient rapidly developed an acute abdomen syndrome, thus precluding a liver biopsy. A new urgent CT was performed to rule out a complication of the cystic lesion. A left hepatectomy was performed and the anatomopathological study confirmed the diagnosis of IPNB with a focus of cholangiocarcinoma therein. During follow up, the patient developed peritoneal carcinomatosis, received palliative chemotherapy and finally died.

Mesalazine induced interstitial pneumonitis in the COVID era.

Mesalazine is the most widely used aminosalicylate for induction and maintenance of remission in patients with mild-to-moderate ulcerative colitis (UC). Drug-induced hypersensitivity pneumonitis is considered very rare (<1/10.000 patients). Due to its rarity and the scarce cases reported, mesalazine-induced lung injury needs to be highly suspected in a patient with onset of respiratory symptoms and UC under treatment with salicylates. It should make the clinician formulate a differential diagnosis that includes not only infections (tuberculosis, bacterial...) or the inflammatory bowel disease itself, but also the current coronavirus disease 2019 (COVID-19) since their clinical and radiological manifestations may be very similar.

Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme. / Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices.

AIM: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. PATIENTS AND METHODS: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). CONCLUSION: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.

Anthropometric assessment of schoolchildren from the La Mancha-Centro health area. Comparison with the Spanish Cross-Sectional Growth Study 2010.

OBJECTIVES: To determine weight, height and body mass index (BMI) of schoolchildren from the La Mancha-Centro health area and compare them with those determined by the Spanish Cross-sectional Growth Study 2010 (SCGS-2010). METHODS: Cross-sectional study of 954 schoolchildren aged 6-12 years. Mean, standard deviation, and percentile distributions of weight, height, and BMI by gender and age were obtained. Differences in each 6-month age group were analyzed. RESULTS: There was a progressive increase in BMI with age, which was significant in girls from nine years of age on and in boys from 8.5 years on. From age 10, average BMI was 2.3 kg/m2 higher than at younger ages (p < 0.001). The biggest difference between genders occurred at age 12: 2 ± 0.98 kg/m2 higher in boys (p = 0.042). Overall, no significant differences were found in weight, height and BMI vs. SCGS-2010, although mean weight of male children from La Mancha-Centro aged between 8.5 and 11.5 years was 3.9 kg higher than that of the rest of Spanish male children. CONCLUSIONS: Anthropometric parameters of schoolchildren from La Mancha-Centro do not significantly differ from national standards; however, preadolescent males from La Mancha-Centro weigh almost 4 kg more.

OBJETIVOS: Determinar peso, talla e índice de masa corporal (IMC) de escolares del área de salud La Mancha-Centro y compararlos con los definidos en el Estudio Transversal Español de Crecimiento 2010 (ETEC-2010). MÉTODOS: Estudio transversal de 954 escolares entre 6 y 12 años. Se obtuvieron media, desviación estándar y distribuciones percentilares de peso, talla e IMC por sexo y edad. Se analizaron las diferencias en cada grupo semestral de edad. RESULTADOS: Existió incremento progresivo del IMC con la edad, significativo en las niñas a partir de los nueve años y en los niños desde los 8.5 años. Desde los 10 años, el IMC promedio resultó 2.3 kg/m2 superior al de edades menores (p < 0.001); la mayor diferencia entre los sexos ocurrió a los 12 años: 2 ± 0.98 kg/m2 más en los varones (p = 0.042). Globalmente no se hallaron diferencias significativas de peso, talla e IMC con el ETEC-2010, aunque el peso medio de los niños manchegos de 8.5 a 11.5 años fue 3.9 kg mayor que el del resto de los niños españoles. CONCLUSIONES: Los parámetros antropométricos de los escolares manchegos no difieren de los estándares nacionales; sin embargo, los varones preadolescentes manchegos pesan casi 4 kg más.

Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain.

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.

Drought affects carbon partitioning into volatile organic compound biosynthesis in Scots pine needles.

The effect of drought on the interplay of processes controlling carbon partitioning into plant primary and secondary metabolisms, such as respiratory CO2 release and volatile organic compound (VOC) biosynthesis, is not fully understood. To elucidate the effect of drought on the fate of cellular C sources into VOCs vs CO2 , we conducted tracer experiments with 13 CO2 and position-specific 13 C-labelled pyruvate, a key metabolite between primary and secondary metabolisms, in Scots pine seedlings. We determined the stable carbon isotope composition of leaf exchanged CO2 and VOC. Drought reduced the emission of the sesquiterpenes α-farnesene and ß-farnesene but did not affect 13 C-incorporation from 13 C-pyruvate. The labelling patterns suggest that farnesene biosynthesis partially depends on isopentenyl diphosphate crosstalk between chloroplasts and cytosol, and that drought inhibits this process. Contrary to sesquiterpenes, drought did not affect emission of isoprene, monoterpenes and some oxygenated compounds. During the day, pyruvate was used in the TCA cycle to a minor degree but was mainly consumed in pathways of secondary metabolism. Drought partly inhibited such pathways, while allocation into the TCA cycle increased. Drought caused a re-direction of pyruvate consuming pathways, which contributed to maintenance of isoprene and monoterpene production despite strongly inhibited photosynthesis. This underlines the importance of these volatiles for stress tolerance.

Physiological responses of date palm (Phoenix dactylifera) seedlings to seawater and flooding.

In their natural environment along coast lines, date palms are exposed to seawater inundation and, hence, combined stress by salinity and flooding. To elucidate the consequences of this combined stress on foliar gas exchange and metabolite abundances in leaves and roots, date palm seedlings were exposed to flooding with seawater and its major constituents under controlled conditions. Seawater flooding significantly reduced CO2 assimilation, transpiration and stomatal conductance, but did not affect isoprene emission. A similar effect was observed upon NaCl exposure. By contrast, flooding with distilled water or MgSO4 did not affect CO2 /H2 O gas exchange or stomatal conductance significantly, indicating that neither flooding itself, nor seawater sulfate, contributed greatly to stomatal closure. Seawater exposure increased Na and Cl contents in leaves and roots, but did not affect sulfate contents significantly. Metabolite analyses revealed reduced abundances of foliar compatible solutes, such as sugars and sugar alcohols, whereas nitrogen compounds accumulated in roots. Reduced transpiration upon seawater exposure may contribute to controlling the movement of toxic ions to leaves and, therefore, can be seen as a mechanism to cope with salinity. The present results indicate that date palm seedlings are tolerant towards seawater exposure to some extent, and highly tolerant to flooding.

Optimizing operational parameters for the enzymatic production of furandicarboxylic acid building block.

BACKGROUND: 2,5-Furandicarboxylic acid (FDCA) is a precursor for green plastics due to its structural similarity to terephthalic acid, a common precursor of oil-derived polymers, and its potential production from sugars obtained from plant biomass. Hydroxymethylfurfural oxidase (HMFO) has been reported as a promising biocatalyst for FDCA production since it can convert bio-based 5-hydroxymethylfurfural (HMF) into FDCA building block. This three-step oxidation reaction occurs through the diformylfuran and 2,5-formylfurancarboxylic acid (FFCA) intermediates. Several efforts have been made for the development of HMFO variants that increase FDCA yields by improving their activities over the reaction intermediates. However, there is still limited insight into how operational conditions can influence these enzymatic reactions. The setup of optimal reaction conditions would enable to understand potential problems hampering the effective industrial production of this bioplastic precursor using HMFO as biocatalyst. RESULTS: In this work, several parameters affecting the performance of Methylovorus sp HMFO oxidizing HMF have been analyzed for the wild-type enzyme, and its V367R and W466F single variants, V367R/W466F double variant, and I73V/H74Y/G356H/V367R/T414K/A419Y/A435E/W466F (8BxHMFO) octuple variant. Our results show how the oxidation of HMF by HMFO enzymes is highly influenced by pH, with different optimal pH values for the different improved variants. Moreover, the enzymes are not stable at high hydrogen peroxide concentrations and their activity is inhibited by the FFCA intermediate in a pH-dependent way. These limitations can be efficiently overcome with the addition of catalase to the reaction medium, which removes the hydrogen peroxide formed during the oxidations, and the controlled dosage of the substrate to limit the amount of FFCA accumulated in the reaction. The different behavior of wild-type HMFO and its variants against pH, hydrogen peroxide and FFCA highlights the importance of considering each variant as an individual enzyme with its own operational conditions for an eventual industrial FDCA production. CONCLUSIONS: This work provides information of those parameters that condition a high production of FDCA by HMFO. Unraveling these factors allowed to increase the FDCA yields by using the most stable enzymes at their optimal pH for HMF oxidation, removing the peroxide with catalase, and avoiding FFCA accumulation by controlling substrate and/or enzyme concentration. These above findings will be useful when planning a future scale-up of these conversions and will provide new viewpoints for the design of HMFO variants that render a more effective performance during HMF conversion into FDCA.