Search

Background: This study aimed to assess the effectiveness of surgery in the management of vertical compensatory head posture in patients with congenital nystagmus (CN) inherited in an X-linked manner in a Chinese family and determine the molecular pathogenesis of this disease. Methods: We studied 18 members belonging to four generations in a family with congenital nystagmus. Parks shift of neutral zone surgeries were performed on 7 patients with vertical compensatory head posture from the family. In addition, head posture, visual acuity, and stereopsis of the 7 patients were evaluated before and 2-years after the displacement surgeries. Gene alternations of the disease were researched by sequencing a candidate gene (FRMD7). From each generation of the family, one patient (including the proband) and one normal control were sampled for Sanger sequencing. Results: Over a median follow-up period of 2 years, the anomalous head posture, visual acuity, and stereopsis significantly improved postoperatively (P T (p.D196Y) in exon 7 of FRMD7 was co-segregated with the disease in this family. Conclusions: Parks shift of neutral zone surgeries relieved the vertical compensatory head posture and improved visual acuity and stereopsis in the primary position of CN patients. In this study, it was concluded that a missense mutation in exon 7 (c.586G > 7, p.D196Y) in FRMD7 was possibly responsible for the disease in this family.

Objective: Our preliminary research indicates that acacetin modulates the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome, providing protection against Alzheimer’s Disease (AD) and cerebral ischemic reperfusion injury. The mechanisms of acacetin to inhibit the activation of the NLRP3 inflammasome remain fully elucidated. This study aims to investigate the effects and potential mechanisms of acacetin on various agonists induced NLRP3 inflammasome activation.Methods: A model for the NLRP3 inflammasome activation was established in mouse bone marrow-derived macrophages (BMDMs) using Monosodium Urate (MSU), Nigericin, Adenosine Triphosphate (ATP), and Pam3CSK4, separately. Western blot analysis (WB) was employed to detect Pro-caspase-1, Pro-Interleukin-1β (Pro-IL-1β) in cell lysates, and caspase-1, IL-1β in supernatants. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measured the release of IL-1β, IL-18, and Tumor Necrosis Factor-alpha (TNF-α) in cell supernatants to assess the impact of acacetin on NLRP3 inflammasome activation. The lactate dehydrogenase (LDH) release was also assessed. The Nuclear Factor Kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways related proteins were evaluated by WB, and NF-κB nuclear translocation was observed via laser scanning confocal microscopy (LSCM). Disuccinimidyl Suberate (DSS) cross-linking was employed to detect oligomerization of Apoptosis-associated Speck-like protein containing a Caspase Recruitment Domain (ASC), and LSCM was also used to observe Reactive Oxygen Species (ROS) production. Inductively Coupled Plasma (ICP) and N-(6-methoxyquinolyl) acetoethyl ester (MQAE) assays were utilized to determined the effects of acacetin on the efflux of potassium (K+) and chloride (Cl-) ions.Results: Acacetin inhibited NLRP3 inflammasome activation induced by various agonists, reducing the release of TNF-α, IL-1β, IL-18, and LDH. It suppressed the expression of Lipopolysaccharides (LPS)-activated Phosphorylated ERK (p-ERK), p-JNK, and p-p38, inhibited NF-κB p65 phosphorylation and nuclear translocation. Acacetin also reduced ROS production and inhibited ASC aggregation, thus suppressing NLRP3 inflammasome activation. Notably, acacetin did not affect K+ and Cl-ions efflux during the activation process.Conclusion: Acacetin shows inhibitory effects on both the priming and assembly processes of the NLRP3 inflammasome, positioning it as a promising new candidate for the treatment of NLRP3 inflammasome-related diseases.

Acacetin (5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3 (NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin (acacetin group) or an equal volume of saline (0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1 (Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway.

In this study, we analyzed the influence of coastal zone engineering on suspended sediment concentration (SSC) in the Yangtze River mouth based on HY-1C and Chinese GaoFen (GF) satellite data. The results show that: (1) SSC in the Yangtze River mouth is mainly in the range of 200–1300 mg/L, which changes due to natural factors as well as coastal zone engineering; (2) The sand blocking engineering effectively protects the channel from siltation, and SSC in the central line of the channel is 100–300 mg/L lower than that near the dikes in the north and south; (3) Qingcaosha Reservoir plays a stabilizing role in the hydrodynamic force, promoting the deposition of suspended matter, so that the water in the reservoir is clear. SSC inside the Qingcaosha Reservoir, located in the center of the estuary, is 100–500 mg/L lower than the high SSC water outside the reservoir; (4) The bridges interact with the current, facilitating the transport of local sediment, resulting in the increase in SSC downstream of these bridges, and obvious vortexes appear with the length up to nearly 2400 m; and (5) Corresponding protection and development suggestions were put forward as follows. A linear array of wind power plants can be built near and parallel to dikes and leading jetties; to increase the depth of the southeast end of the reservoir; and the location of the bridge should be selected in the place of river where siltation is easy. This study aimed to study the SSC distribution under the complex impact of coastal zone engineering with satellite and to provide possible improvement suggestions.

Background: Leber congenital amaurosis (LCA) is a visual disease which is caused by RPE65 mutations and results in retinal degeneration and severe vision loss in early infancy. According to previous researches, mutations of the RPE65 gene account for 16% of all cases of LCA. This study aimed to identify RPE65 gene mutations in Chinese patients with LCA. Methods: We recruited 52 sporadic patients from Peking University Third Hospital in 2016 and applied Sanger sequencing to identify variants among exons responsible for the disease. The genomic DNAs from blood leukocytes of these patients were isolated, and the entire coding region of the RPE65 gene was amplified by polymerase chain reaction. We then determined the sequence of RPE65 using ABI 3100 Genetic Analyzer. Results: Our study identified that only 1 out of the 52 patients with LCA carried the previously unreported homozygosis missense mutation c1174A>C (T392P) of the RPE65 gene. However, the mutation was associated with the disease phenotype and not detected in 100 normal controls. Conclusions: Though we identified a novel missense mutation in the RPE65 gene that causes LCA, our result indicates that RPE65 mutations may not play a major role in the LCA patients in China since only 1 out of the 52 patients carried mutation in the RPE65 gene.

Background: Congenital nystagmus (CN) is characterized by conjugated, spontaneous, and involuntary ocular oscillations. It is an inherited disease and the most common inheritance pattern is X-linked CN. In this study, our aim is to identify the disease-causing mutation in a large sixth-generation Chinese family with X-linked CN. Methods: It has been reported that mutations in four-point-one, ezrin, radixin, moesin domain-containing 7 gene (FRMD7) and G protein-coupled receptor 143 gene (GPR143) account for the majority patients of X-linked nystagmus. We collected 8 ml blood samples from members of a large sixth-generation pedigree with X-linked CN and 100 normal controls. FRMD7 and GPR143 were scanned by polymerase chain reaction (PCR)-based DNA sequencing assays, and multiplex PCR assays were applied to detect deletions. Results: We identified a previously unreported deletion covering 7 exons in GPR143 in a Chinese family. The heterozygous deletion from exon 3 to exon 9 of GPR143 was detected in all affected males in the family, while it was not detected in other unaffected relatives or 100 normal controls. Conclusions: This is the first report of molecular characterization in GPR143 gene in the CN family. Our results expand the spectrum of GPR143 mutations causing CN and further confirm the role of GPR143 in the pathogenesis of CN.

Background: Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this study, the aim is to identify the genetic cause of a five-generation Chinese autosomal dominant congenital cataract family. Methods: Whole exome sequencing (WES) was performed on three affected and one unaffected member of the family, known causative genes were scanned first. Sanger sequencing was used to validate co-segregation of the candidate variant in the family. The impact on the transcript and amino acid sequences of the variant was further analyzed. Results: We identified a novel splice donor site mutation c. 2825+1G >A in EPHA2 that was absent in public and in-house databases and showed co-segregation in the family. This variant resulted in an altered splice that led to protein truncation. Conclusions: The mutation we identified was responsible for congenital cataract in our studied family. Our findings broaden the spectrum of causative mutations in EPHA2 gene for congenital cataract and suggest that WES is an efficient strategy to scan variants in known causative genes for genetically heterogeneous diseases.

We analyzed the distribution of chlorophyll-a (Chla) in the Bohai Sea area based on data from the geosynchronous orbit optical satellite Gaofen-4 (GF-4), which was launched in 2015, carrying a panchromatic multispectral sensor (PMS). This is the first time the geosynchronous orbit optical satellite GF-4 remote-sensing data has been used in China to detect the Chla change details in the Bohai Sea. A new GF-4 retrieved model was established based on the relationship between in situ Chla value and the reflectance combination of 2 and 4 bands, with the R2 of 0.9685 and the total average relative error of 37.42%. Twenty PMS images obtained from 2017 to 2019 were applied to analyze Chla in Bohai sea. The results show that: (1) the new built Chla inversion model PMS-1 for the GF-4 PMS sensor can extract Chla distribution details in the Bohai Sea well. The high Chla content in the Bohai Sea is mainly located in coastal areas, such as the top of Laizhou Bay, Bohai Bay and Liaodong Bay, with the value being around 13 µg/L. The concentration of Chla in the Bohai Strait and northern Yellow Sea is relatively low with the value being around 5 µg/L. (2). Taking full advantage of the continuous observation of geostationary orbit satellite, GF-4 with a high-resolution sensor PMS of 50 m can effectively detect short-term change (changes within 10 min) in Chla concentration. The changes mainly appear at the southwest and northeast costal area as well as in the center of Bohai Sea with the change value of around 3 µg/L. (3) The change of Chla concentration in the Bohai sea is related to the environmental factors such as seawater temperature, salinity, illumination and nutrient salts, as well as the dynamic factors such as wind, flow field and tidal current.

BackgroundEmerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3‐mediated angiogenesis and cardiac remodeling. Methods and ResultsOur experiments were performed on SIRT3 knockout and age‐matched wild‐type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days. After angiotensin II infusion, SIRT3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild‐type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen III expression, leading to cardiac fibrosis. Silencing SIRT3 facilitated angiotensin II–induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover, SIRT3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin‐mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell–specific SIRT3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild‐type mice with similar stimuli. ConclusionsCollectively, these findings suggest that SIRT3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy.

Abstract Background Variant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain. Methods National, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected. Results The mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group. Conclusions The EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment.

Northern corn leaf blight (NCLB), caused by Setosphaeria turcica, is a major fungal disease affecting maize production in sub-Saharan Africa. Utilizing host plant resistance to mitigate yield losses associated with NCLB can serve as a cost-effective strategy. In this study, we conducted a high-resolution genome-wide association study (GWAS) in an association mapping panel and linkage mapping with three doubled haploid (DH) and three F3 populations of tropical maize. These populations were phenotyped for NCLB resistance across six hotspot environments in Kenya. Across environments and genotypes, NCLB scores ranged from 2.12 to 5.17 (on a scale of 1–9). NCLB disease severity scores exhibited significant genotypic variance and moderate-to-high heritability. From the six biparental populations, 23 quantitative trait loci (QTLs) were identified, each explaining between 2.7% and 15.8% of the observed phenotypic variance. Collectively, the detected QTLs explained 34.28%, 51.37%, 41.12%, 12.46%, 12.11%, and 14.66% of the total phenotypic variance in DH populations 1, 2, and 3 and F3 populations 4, 5, and 6, respectively. GWAS, using 337,110 high-quality single nucleotide polymorphisms (SNPs), identified 15 marker–trait associations and several putative candidate genes linked to NCLB resistance in maize. Joint linkage association mapping (JLAM) identified 37 QTLs for NCLB resistance. Using linkage mapping, JLAM, and GWAS, several QTLs were identified within the genomic region spanning 4 to 15 Mbp on chromosome 2. This genomic region represents a promising target for enhancing NCLB resistance via marker-assisted breeding. Genome-wide predictions revealed moderate correlations with mean values of 0.45, 0.44, 0.55, and 0.42 for within GWAS panel, DH pop1, DH pop2, and DH pop3, respectively. Prediction by incorporating marker-by-environment interactions did not show much improvement. Overall, our findings indicate that NCLB resistance is quantitative in nature and is controlled by few major-effect and many minor-effect QTLs. We conclude that genomic regions consistently detected across mapping approaches and populations should be prioritized for improving NCLB resistance, while genome-wide prediction results can help incorporate both major- and minor-effect genes. This study contributes to a deeper understanding of the genetic and molecular mechanisms driving maize resistance to NCLB.

Summary: Neurons receive correlated levels of excitation and inhibition, a feature that is important for proper brain function. However, how this relationship between excitatory and inhibitory inputs is established during the dynamic period of circuit wiring remains unexplored. Using multiple techniques, including in utero electroporation, electron microscopy, and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along the dendrites of developing CA1 hippocampal neurons. This correlation was present within short dendritic stretches (

En la Argentina de los años treinta, distintas voces aportaron a un debate sobre el rol del periodismo y ofrecieron representaciones contrastantes acerca de la naturaleza de esta actividad y sus relaciones deseables con el Estado y los actores políticos y sociales. En este artículo, abordo el papel protagónico que asumió el socialismo argentino en estos debates, a partir del análisis de sus discursos e iniciativas en el terreno legislativo y gremial. Argumento que, al poner en el centro de su discurso la defensa de la libertad de prensa, el socialismo argentino potenció el elemento democrático-liberal de su tradición política y modificó en forma radical su tradicional hipótesis respecto al rol del periodismo en las sociedades democráticas.

Desde diferentes perspectivas y poniendo bajo examen distintos objetos de estudio, los textos reunidos en este dossier se interrogan por los vínculos entre la política y las ideas en la Argentina entre 1880 y 1943. Para examinar la problemática, los artículos adoptan cuatro vías de análisis diferentes: los discursos intelectuales, el parlamento nacional, la prensa periódica y los conflictos laborales. Esta diversidad de estrategias, que conlleva el abordaje de problemas poco o nada atendidos por la historiografía, pero también la revisión crítica de interpretaciones canónicas, permite iluminar aspectos significativos de la dinámica política e institucional y sus vínculos con el debate de ideas y las transformaciones sociales de la Argentina liberal.

The conservation and management of marine ecosystems hinge on a comprehensive understanding of the status and trends of top predators. This review delves into the ecological significance of marine top predators, examining their roles in maintaining ecosystem stability and functioning through an integrated analysis of current scientific literature. We first assess the efficacy of various monitoring methods, ranging from traditional field observations to cutting-edge technologies like satellite tracking and environmental DNA (eDNA) analysis and evaluating their strengths and limitations in terms of accuracy, spatial coverage, and cost-effectiveness, providing resource managers with essential insights for informed decision-making. Then, by synthesizing data from diverse marine ecosystems, this study offers a comprehensive overview of the trends affecting top predator populations worldwide. We explore the multifaceted impacts of human activities, climate change, and habitat degradation on the abundance and distribution of these key species. In doing so, we shed light on the broader implications of declining top predator populations, such as trophic cascades and altered community structures. Following a thorough assessment of successful strategies for reversing the decline of top predators, a compilation of recommendations is presented, encompassing effective governance interventions. A crucial aspect of effective ecosystem-based management is the implementation of robust monitoring strategies. Mitigation measures are imperative to reverse the adverse impacts on marine top predators. We present a comprehensive array of mitigation options based on successful case studies. These include the establishment of marine protected areas, the enforcement of fisheries regulations, and the promotion of sustainable fishing practices. We deepen the synergies between these strategies and their potential to mitigate human-induced stressors on top predator populations to safeguard their pivotal role in maintaining marine ecosystem structure and function. By examining marine top predators’ ecological significance, analyzing population trends, discussing monitoring techniques, and outlining effective mitigation strategies, we provide a comprehensive resource for researchers, policymakers, and stakeholders engaged in fostering ecosystem-based management approaches. We conclude that integrating these insights into current management frameworks will be essential to safeguard both top predators and the broader marine environment for future generations.

3D-printed high-surface carbon monoliths have been fabricated and tested as catalyst supports of CO2 methanation active phases (NiO-CeO2, 12 wt% Ni). The carbon carriers show a developed microporosity and good adherence to the catalytic phases of NiO-CeO2, showing great stability and cyclability. Two monolith designs were used: a conventional parallel-channeled structure (honeycomb) and a complex 3D network of non-linear channels built upon interconnected circular sections (circles), where flow turbulences along the reactant gas path are spurred. The effect of the active phases particle size on the catalyst distribution and the overall performance has been assessed by comparing NiO-CeO2 nanoparticles of 7 nm average (Np), with a reference counterpart of uncontrolled structure (Ref). The improved radial gases diffusion in the circles monolith design is confirmed, and nanoparticles show enhanced CO2 methanation activity than the uncontrolled-size active phase at low temperatures (< 300 ºC). On the contrary, the Ref catalysts achieve higher CH4 production at higher temperatures, where the reaction kinetics is controlled by mass transfer limitations (T > 300 ºC). SEM and Hg porosimetry evidence that nanoparticles are deposited at deeper penetration through the narrow micropores of the carbon matrix of the monolithic supports, which tend to accumulate on the channels surface remaining more accessible to the reactant molecules. Altogether, this study examines the impact of the channel tortuosity and the active phase sizing on the CO2 methanation activity, serving as ground knowledge for the further rational and scalable fabrication of carbon monolith for catalytic applications.

We study the Schr\"odinger equation $\left(\mathrm{Q}_{\varepsilon}\right)$: $- \varepsilon^{2(p-1)} \Delta_p v + V(x)\, |v|^{p-2} v - |v|^{q-1}v = 0$, $x \in \mathbb{R}^N$, with $v(x) \rightarrow 0$ as $|x| \rightarrow+\infty$, for the infinite case, as given by Byeon and Wang for a situation of critical frequency, $\displaystyle \{x\in \mathbb{R}^N \, / \: V(x) = \inf V = 0\} \neq \emptyset$. In the semiclassical limit, $\varepsilon \rightarrow 0$, the corresponding limit problem is $\left(\mathrm{P}\right)$: $\Delta_p w+|w|^{q-1} w=0$, $x \in \Omega$, with $w(x)=0, x \in \partial \Omega$, where $\Omega \subseteq \mathbb{R}^N$ is a smooth bounded strictly star-shaped region related to the potential $V$. We prove that for $\left(\mathrm{Q}_{\varepsilon}\right)$ there exists a non-trivial solution with any prescribed $\mathrm{L}^{q+1}$-mass.Applying a Ljusternik-Schnirelman scheme, shows that $\left(\mathrm{Q}_{\varepsilon}\right)$ and $\left(\mathrm{P}\right)$ have infinitely many pairs of solutions. Fixed a topological level $k \in \mathbb{N}$, we show that a solution of $\left(\mathrm{Q}_{\varepsilon}\right)$, $v_{k, \varepsilon}$, sub converges, in $\mathrm{W}^{1,p}(\mathbb{R}^N)$ and up to scaling, to a corresponding solution of $\left(\mathrm{P}\right)$. We also prove that the energy of each solution, $v_{k,\eps}$ converges to the corresponding energy of the limit problem $\left(\mathrm{P}\right)$ so that the critical values of the functionals associated, respectively, to $\left(\mathrm{Q}_{\varepsilon}\right)$ and $\left(\mathrm{P}\right)$ are topologically equivalent.

Son presentados 100 niños con diagnóstico clínico de Impétigo de los cuales 70 fueron estudiados bacteriológicamente. La signo sintomatología es la habitualmente descripta en este tipo de afección y el principal germen involucrado fue el Estreptococo que predominó más a menor edad del paciente. fue más afectado el sexo masculino y no se detectaron durante el estudio complicaciones atribuibles a esta patología, ya sea por extensión o a la debida a fenómenos con participación inmunológica.

Abstract Natural origin products are an appealing substitute for nonbiodegradable materials in the production of new materials to improve the packaging properties and to extend the shelf life quality of foods. The objective of this study was to formulate, elaborate, select, partially characterize, and evaluate the biological properties of an edible film based on pectin, candelilla wax, and glycerol, added with pomegranate peel polyphenols (PPP). An exploratory design 2k Box Hunter and Hunter was made, followed by a Box‐Behnken design 3k to evaluate the properties of water vapor permeability (WVP) of the film, resulting in the film with 0.75% w/v of pectin, 0.2% w/v of candelilla wax, 0.05% v/v of glycerol and 0.02% w/v of PPP with one of the lowest values of WVP (1.78E−10 g/m.s.Pa). After characterization, this treatment showed good structural and optical properties and low humidity values compared to a control film. PPP showed the inhibitory capacity for DPPH (61.2%) and ABTS (48.5%) radicals and reducing activity with the reduction of ferric ion (FRAP) reaching a value of 1676.5 mg TE/g PPP.

Summary: Dysregulated neuronal excitability is a hallmark of amyotrophic lateral sclerosis (ALS). We sought to investigate how functional changes to the axon initial segment (AIS), the site of action potential generation, could impact neuronal excitability in ALS human induced pluripotent stem cell (hiPSC) motor neurons. We find that early TDP-43 and C9orf72 hiPSC motor neurons show an increase in the length of the AIS and impaired activity-dependent AIS plasticity that is linked to abnormal homeostatic regulation of neuronal activity and intrinsic hyperexcitability. In turn, these hyperactive neurons drive increased spontaneous myofiber contractions of in vitro hiPSC motor units. In contrast, late hiPSC and postmortem ALS motor neurons show AIS shortening, and hiPSC motor neurons progress to hypoexcitability. At a molecular level, aberrant expression of the AIS master scaffolding protein ankyrin-G and AIS-specific voltage-gated sodium channels mirror these dynamic changes in AIS function and excitability. Our results point toward the AIS as an important site of dysfunction in ALS motor neurons.

An assessment framework of marine ecosystem services (ES) indicators to quantify the socio-ecological effectiveness of nature-based solutions (NBS) and nature-inclusive harvesting (NIH) under climate-driven changes was developed. It creates a common understanding about the health status of ecosystems, their services (ES), and the impact of implementing NBS&NIH to inform policymakers and the public. The two NBS considered were restoration and conservation which need to be performed considering the sustainable harvesting of marine resources (NIH). The interaction between the biodiversity indicators with the socioeconomic, response and pressure indicators was established using the ES cascade. However, it was also linked to other environmental (e.g., DAPSI(W)R(M)) and economic frameworks such as the Standard National Account (SNA) and the System of Environment Economic Accounting (SEEA). A set of 155 multidisciplinary indicators were identified through a literature review and their effectiveness in measuring ES under changing climate. Biodiversity & environmental as well as Pressure indicators are the most numerous in the list representing 34 % and 23 % of the total respectively, while only 12 % of the used Indicators below to the economic dimension. Socioeconomic indicators considering CC are rarely contemplated, except for a short list redefining output and demand approach indicators to aggregate a carbon footprint valuation. For cultural services economic indicators dominate, whereas sparse for provisioning and regulating. The 70 % of the selected indicators were also empirically verified with 27 European storylines. Storylines have high coverage of biodiversity, environmental indicators, and CC indicators (91 %), lower coverage of economic (71 %) and poorer related to social (31 %) indicators. Harvest, pressure and/or habitats are clearly the groups of indicators majority used when evaluating the ES on marine and coastal ecosystems both in terms of the number of used indicators but also, the frequency of use. Despite the increase of ES research, this study identifies 14 substantial gaps or weaknesses limiting the guidance for NBS&NIH implementation derived from the employment of an unbalanced (between dimensions and key groups) number of quantitative indicators.

Aim of study: To analyse the territorial potential of Cantabria to produce grass-fed milk. Area of study: Cantabria (N Spain) is a territory associated with livestock, in particular cattle and grasslands. Over the last few decades, the livestock sector has been immersed in a process of structural adjustment, leading to a reduction in the number of farms, an increase in their size and the intensification of production. Moreover, the market is being increasingly supplied with milk labelled “grass fed”, due to growing consumer interest in healthier and more environmentally friendly products. Material and methods: To do this, 99 livestock farms were classified according to the percentage of fresh grass (FG) in the spring diet of the lactating cows (non-grass-fed:

Abstract Objective There is growing evidence for an association between anxiety and an increased risk of dementia, but it is not clear whether anxiety is a risk factor or a prodromic symptom. In this study, we investigated if clinically significant anxiety increases the risk of developing Alzheimer's disease (AD) up to 10 years later. Methods We used data from the longitudinal Zaragoza Dementia and Depression (ZARADEMP) Project. Excluding subjects with dementia at baseline left us with 3044 individuals aged >65 years. The Geriatric Mental State‐Automated Geriatric Examination for Computer Assisted Taxonomy (GMS‐AGECAT) package was used to identify cases and subcases of anxiety. AD was diagnosed by a panel of research psychiatrists according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV) criteria. Multivariate survival analysis with a competing risk regression model was performed. Results We observed a significant association between clinically significant anxiety at baseline and AD risk within a 10‐year follow‐up (SHR 2.82 [95% CI 1.21–6.58]), after controlling for confounders including depression. In contrast, isolated symptoms of anxiety were not significantly associated with an increased incidence of AD. Conclusion Our results support the hypothesis that clinically significant anxiety is an independent risk factor for AD and not just a prodromic symptom. Future studies should clarify if treating anxiety reduces the incidence of AD.

Abstract Background As a result of the technological progress, the use of sensors for crop survey has substantially increased, generating valuable information for modelling agricultural data. Plant spectroscopy jointly with statistical modeling can potentially help to assess certain chemical components of interest present in plants, which may be laborious and expensive to obtain by direct measurements. In this research, the phosphorus content in wheat grain is modeled using reflectance information measured by a hyperspectral sensor at different wavelengths. A Bayesian procedure for selecting variables was used to identify the set of the most important spectral bands. Additionally, three different models were evaluated: the first model assumes that the observations are independent, the other two models assume that the observations are spatially correlated: one of the proposed models, assumes spatial dependence using a Conditionally Autoregressive Model (CAR), and the other through an exponential correlogram. The goodness of fit of the models was evaluated by means of the Deviance Information Criterion, and the predictive power is evaluated using cross validation. Results We have found that CAR was the model that best fits and predicts the data. Additionally, the selection variable procedure in the CAR model reveals which wavelengths in the range of 500–690 nm are the most important. Comparing the vegetative indices with the CAR model, it was observed that the average correlation of the CAR model exceeded that of the vegetative indices by 23.26%, − 1.2% and 22.78% for the year 2010, 2011 and 2012 respectively; therefore, the use of the proposed methodology outperformed the vegetative indices in prediction. Conclusions The proposal to predict the phosphorus content in wheat grain using Bayesian approach, reflect with the results as a good alternative.

Abstract Fostering a culture of continuous improvement through regular monitoring of genetic trends in breeding pipelines is essential to improve efficiency and increase accountability. This is the first global study to estimate genetic trends across the International Maize and Wheat Improvement Center (CIMMYT) tropical maize breeding pipelines in eastern and southern Africa (ESA), South Asia, and Latin America over the past decade. Data from a total of 4152 advanced breeding trials and 34,813 entries, conducted at 1331 locations in 28 countries globally, were used for this study. Genetic trends for grain yield reached up to 138 kg ha−1 yr−1 in ESA, 118 kg ha−1 yr−1 South Asia and 143 kg ha−1 yr−1 in Latin America. Genetic trend was, in part, related to the extent of deployment of new breeding tools in each pipeline, strength of an extensive phenotyping network, and funding stability. Over the past decade, CIMMYT’s breeding pipelines have significantly evolved, incorporating new tools/technologies to increase selection accuracy and intensity, while reducing cycle time. The first pipeline, Eastern Africa Product Profile 1a (EA-PP1a), to implement marker-assisted forward-breeding for resistance to key diseases, coupled with rapid-cycle genomic selection for drought, recorded a genetic trend of 2.46% per year highlighting the potential for deploying new tools/technologies to increase genetic gain.

Abstract The degree of exposure of fishing communities to environmental changes can be partially determined by the vulnerability of the target species and the landings composition. Hence, identifying the species that ecologically most contribute to the vulnerability of the landings are key steps to evaluate the risk posed by climate change. We analyse the temporal variability in intrinsic sensitivity and the ecological vulnerability of the Portuguese fisheries landings, considering the species proportions derived both from the weights and revenues. To account for the diversification of species of each fleet, we explored the species dependence of the fishery in combination with the vulnerability of them. The analyses were carried out separately for three fleet typologies and three regions. Opposite to what has been observed at a global scale, the ecological sensitivity of the fisheries landings between 1989 and 2015 did not display a decline across areas or fishing fleets. Considering each fleet independently, for trawling, where average vulnerability was lower than in the other fleets, the sensitivity of the landings increased since the 2000s. On the other hand, the high vulnerability found in multi-gear fleets was compensated by diversification of the species caught, while purse-seine fleets targeted low vulnerability species but presented a high fishery dependence on few species. The results highlight the importance of combining information on ecological vulnerability and diversification of fishing resources at a regional scale while providing a measure of the ecological exposure to climate change.

Schizophrenia is highly heritable and characterized by widespread brain abnormalities. Here, the authors identify schizophrenia polygenic risk associated multimodal frontotemporal network that can serve as a transdiagnostic brain signature specific to schizophrenia.

Summary: Excitatory synapses are typically described as single synaptic boutons (SSBs), where one presynaptic bouton contacts a single postsynaptic spine. Using serial section block-face scanning electron microscopy, we found that this textbook definition of the synapse does not fully apply to the CA1 region of the hippocampus. Roughly half of all excitatory synapses in the stratum oriens involved multi-synaptic boutons (MSBs), where a single presynaptic bouton containing multiple active zones contacted many postsynaptic spines (from 2 to 7) on the basal dendrites of different cells. The fraction of MSBs increased during development (from postnatal day 22 [P22] to P100) and decreased with distance from the soma. Curiously, synaptic properties such as active zone (AZ) or postsynaptic density (PSD) size exhibited less within-MSB variation when compared with neighboring SSBs, features that were confirmed by super-resolution light microscopy. Computer simulations suggest that these properties favor synchronous activity in CA1 networks.

The upgrade of the A Toroidal LHC ApparatuS (ATLAS) hadronic Tile Calorimeter (TileCal) Low-Voltage Power Supply (LVPS) forms a part of the Phase-II Upgrade preparations undertaken by the ATLAS experiment for the data taking during the High-Luminosity Large Hadron Collider era. This paper serves to provide a detailed overview of the development of a Burn-in test station for an upgraded LVPS component known as a Brick. The production, quality assurance testing, and all associated apparatus are being jointly undertaken by the University of the Witwatersrand (Wits) and the University of Texas at Arlington (UTA). These Bricks are radiation-hard transformer-coupled buck converters that function to step-down bulk 200 VDC power to the 10 VDC required by the on-detector electronics. To ensure the high reliability of the Bricks, once installed within the TileCal, a Burn-in test station has been designed and built. The Burn-in station functions to implement a Burn-in procedure on eight Bricks simultaneously. This procedure subjects the Bricks to sub-optimal operating conditions, which function to accelerate their ageing, as well as to stimulate failure mechanisms. This results in elements of the Brick that would fail prematurely within the TileCal failing within the Burn-in station or experience performance degradation that can be detected by follow-up testing effectively screening out the non-performative sub-population. The Burn-in station is of fully custom design in both its hardware and software. The development of the test station will be explored in detail; the preliminary Burn-in procedure to be employed will be provided; the preliminary and final commissioning of the test station will be presented. The paper will culminate in the presentation and discussion of the Burn-in of a V8.4.2 Brick and the future outlook of the project.

Understanding the relationship between environmental temperature and the biological traits of organisms is fundamental to inferring the potential impacts of climate change. In the case of marine poikilotherm species, seawater temperature is one of the main driving forces of biological processes, with consequences at higher levels of organization such as population and ecosystem. In this study, we analysed differences in maximum carapace width (CWmax), size at maturation, relative size at maturation, and duration of the reproductive season for the green crab (Carcinus maenas) along a temperature gradient. An extensive review of bibliographic data was performed on studies published between 1962 and 2020, gathering C. maenas data from 55 different populations, spread over 20 degrees of latitude and 14.2 °C of sea surface temperature (SST). In addition, green crab data were collected at five different lagoons and estuaries along the continental Portuguese coast. The relationship between average SST and CWmax, age of maturation, reduction of size at maturation, and duration of egg bearing was analysed to understand the role of SST in driving variation in these C. maenas characteristics across a latitudinal gradient. There was a significant relationship between SST and CWmax for males and SST and CW of females at maturation, respectively. The results extrapolate for each local projected temperature increase caused by climate change and suggest an effect on the morphometric and reproductive traits of C. maenas across regions. These changes comprise an overall reduction in C. maenas body size, an enlargement of the reproductive season, a shortening in the duration of larval developmental time, and a decrease in the relative size of crabs at maturation. Secondary consequences on the fecundity and connectivity of populations are discussed.

Abstract Increased intra-abdominal pressure (IAP) is common among post-surgical patients and may cause organ dysfunction. However, its impact after kidney transplantation on early postoperative complications and graft recovery remains unclear. We designed a prospective, observational cohort study to describe the prevalence and determinants of IAP, as well as its effect on delayed graft function, postoperative complications, and graft recovery. IAP was measured in 205 kidney transplant recipients every 8 h during the first 72 h after surgery using the urinary bladder technique. Intra-abdominal hypertension was defined as IAP ≥ 12 mmHg. Patients were followed for 6 months or until graft failure/death. Mean IAP was 12 ± 3.3 mmHg within the first 24 h. 78% of subjects presented with intra-abdominal hypertension during the first 72 h. Increased IAP was associated with higher renal resistive index [r = 0.213; P = 0.003] and lower urine output [r = − 0.237; P

The approach to Spanish esotericism in the early-modern period continues to be notably marginal among specialists. At the crossroads of cultural history and political history, we investigate both the characteristics of esoteric practices and representations in 16th century Spain and the representational struggles between the hostile discourses of Christian orthodoxy and the apologetics of esotericists. We approach the “Silva de varia lección” (1540) by Pedro Mexía (who was to be appointed in 1548 Imperial Chronicler of Carlos V) to focus both on the peculiarities of his specific representation of magic-astrological rings and on the characteristics of his apologetic speech regarding the criticism of Christian orthodoxy.

Abstract Climate change is already impacting fisheries with species moving across fishing areas, crossing institutional borders, and thus creating conflicts over fisheries management. In this scenario, scholars agree that adaptation to climate change requires that fisheries increase their social, institutional, and ecological resilience. The resilience or capacity of a fishery to be maintained without shifting to a different state (e.g., collapse) is at stake under climate change impacts and overexploitation. Despite this urgent need, applying the resilience concept in a spatially explicit and quantitative manner to inform policy remains unexplored. We take a resilience approach and operationalize the concept in industrial fisheries for two species that have been observed to significantly shift distribution in European waters: hake (Merluccius merluccius) and cod (Gadus morhua), in the context of the European Union institutional settings. With a set of resilience factors from the literature and by means of contemporary and historic data, we select indicators that are combined into an index that measures resilience on the ecologic, socioeconomic, and institutional dimensions of the fishery. We find that the resilience index varies among species and countries, with lower resilience levels in the socioeconomic dimension of the fisheries. We also see that resilience largely depends on the overexploitation status of the fishery. The results highlight the need to address social and institutional settings to enhance fisheries adaptation to climate change and allow to inform on climate resilient adaptation pathways for the fisheries.

We carry out a multivariate exploratory analysis of the reports of criminal activity in Ecuador during the COVID-19 pandemic in the year 2020. This is presented as a comparative study between citizen insecurity before, during and after national lockdown. Since the number of cases and the population's compliance with distancing measures varied throughout the country, reports of criminal activity were studied by province. To analyze the data we used the R package GGEBiplotGUI. As a result, we noticed some significant differences between the criminal activity before, during and after the emergency state was declared in the country. The numbers of all cases dropped dramatically and the trends in types of criminal activities changed differently in each province.

Este artículo analiza las prácticas de gestión informativa llevadas a cabo por el socialismo argentino y examina su papel en la construcción del internacionalismo socialista entre 1890 y 1930. En base a un examen de la cobertura internacional realizada por el periódico La Vanguardia, y a documentos de distintos archivos, se argumenta que la información constituyó un problema práctico de relevancia significativa en los años dorados del internacionalismo socialista en la medida en que estableció los términos y alcances de la cooperación y la solidaridad transnacionales desde un espacio periférico como era el Atlántico sudamericano.

Assessing the effects of fishing activity and environmental variability on fishing species might help to understand their fluctuations and to manage them accordingly. However, despite the increasing number of studies linking fisheries and environmental data, few had a multi-species approach considering flatfish species and different age groups. Therefore, this study aims to determine the effects of environmental and fishing related variables on commercial flatfish species across different regions of the Portuguese coast. For that, sea surface temperature, North Atlantic Oscillation, upwelling index, wind components, river discharges and fishing effort were related to landings per unit effort (LPUE) of five commercial flatfish species (Pleuronectes platessa, Dicologlossa cuneata, Microchirus spp., Solea lascaris, and Solea solea) fished by the artisanal fleet along different regions of Portuguese coast (Northwestern coast, Southwestern coast, and Southern coast), using a multi-model statistical approach from 1989 to 2009. The fishing effort had the same effect along the life cycle and was negatively related with LPUE trends for most of the species. Regarding to environmental variability, during early phases (larval to juvenile – age-group-0) the factors that affected the recruitment, in addition to being related to the physiological needs (e.g., sea surface temperature) of individuals that will trigger growth and survival, were related to larval transport and dispersion from offshore spawning areas to coastal nursery habitats beyond (e.g., wind components and upwelling). For juvenile and young-adult phases (age-groups I and II), the effects of environmental variability appeared to be linked to physiological needs important for growth and maturation (e.g., temperature). Concluding, different effects were observed depending on the region, species, and life-cycle phase. Therefore, these environmental-fishing relationships should be used when managing local fishing resources.

Resumen: Introducción y objetivos: La pandemia por COVID-19 causada por infección del virus SARS-CoV-2 ha saturado al sistema sanitario español, afectándose la atención de las enfermedades cardiovasculares. Queremos cuantificar el impacto de la pandemia en el número de las intervenciones quirúrgicas cardíacas analizando los grupos relacionados con el diagnóstico (GRD) más prevalentes de nuestra especialidad. Métodos: A instancias de la Sociedad Española de Cirugía Cardiovascular y Endovascular, se solicitó a todos los centros nacionales que quisieron participar, los datos de los códigos de GRD números 162 (cirugía sobre válvulas cardíacas con infarto o diagnóstico complejo), 163 (cirugía sobre válvulas cardíacas sin infarto o diagnóstico complejo), 165 (bypass coronario con infarto o diagnóstico complejo), 166 (bypass coronario sin infarto o diagnóstico complejo) y 167 (otros procedimientos cardiotorácicos o vasculares torácicos) entre el 1 de marzo de 2020 y el 30 de septiembre de 2020 (siete meses), y como período control las mismas fechas de 2019. Resultados: Se recibieron los datos de 24 hospitales, 22 públicos y dos privados. Existió un descenso global en el número de intervenciones del 30% (rango -19 a -42%, p < 0,001) de 4.648 en 2019 a 3.262 en 2020 (-1.386 de diferencia), siendo +7% para el GRD 162 (p = 0,500), -37% para el 163 (p = 0,001), -9% para el 165 (p = 0,304), -32% para el 166 (p = 0,001), y -16% para el 167 (p = 0,062). Conclusiones: Existió un descenso global de cirugías estadísticamente significativo en 2020 del 30% respecto del 2019 entre el 1 de marzo y el 30 de septiembre. Abstract: Introduction and objectives: The COVID-19 pandemic caused by the SARS-CoV-2 virus infection has saturated the Spanish health system, affecting the care of cardiovascular diseases. In this phase 2 of the SECCE-COVID-19 study we want to quantify the impact of the pandemic on the number of cardiac surgeries by analyzing the most prevalent diagnostic-related groups (DRGs) in our specialty. Methods: At the request of the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE), all the centers in the national territory that wanted to participate were asked for the data of the DRG codes number 162 (surgery on heart valves with infarction or complex diagnosis), 163 (surgery on heart valves without infarction or complex diagnosis), 165 (coronary bypass with infarction or complex diagnosis), 166 (coronary bypass without infarction or complex diagnosis) and 167 (other cardiothoracic or thoracic vascular procedures) between March 1, 2020 and September 30, 2020 (7 months), and as a control period the same dates of the year 2019. Results: Data were received from 24 Hospital Centers, 22 public and 2 private. There was a global decrease in the number of interventions of 30% (Range -19 a -42%, p < 0.001) from 4648 in 2019 to 3262 in 2020 (-1386 difference), being +7% for the GRD 162 (p = 0.500), -37% for 163 (p = 0.001), -9% for 165 (p = 0,304), -32% for 166 (p = 0.001) and -16% for 167(p = 0.062). Conclusions: There was a statistical significant global decrease in surgeries in 2020 of 30% compared to 2019 between March 1 and September 30.

Abstract Alterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. All participants received resting state functional MRI to characterise functional brain networks and proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate concentrations in the frontal cortex. Study A investigated the relationship between frontal cortex glutamate concentrations and network connectivity in individuals with schizophrenia and healthy controls. Study B also used 1H-MRS, and scanned individuals with schizophrenia and healthy controls before and after a challenge with the glutamatergic modulator riluzole, to investigate the relationship between changes in glutamate concentrations and changes in network connectivity. In both studies the network based statistic was used to probe associations between glutamate and connectivity, and glutamate associated networks were then characterised in terms of their overlap with canonical functional networks. Study A involved 76 individuals with schizophrenia and 82 controls, and identified a functional network negatively associated with glutamate concentrations that was concentrated within the salience network (p 0.85). Study B involved 19 individuals with schizophrenia and 17 controls and found that increases in glutamate concentrations induced by riluzole were linked to increases in connectivity localised to the salience network (p 0.4). Frontal cortex glutamate concentrations are associated with inter-areal functional connectivity of a network that localises to the salience network. Changes in network connectivity in response to glutamate modulation show an opposite effect compared to the relationship observed at baseline, which may complicate pharmacological attempts to simultaneously correct glutamatergic and connectivity aberrations.

Abstract Background Acute intermittent porphyria (AIP) is a genetic disease characterized by acute neurovisceral attacks. Long-term clinical conditions, chronic symptoms and impaired health related quality of life (HRQoL) have been reported during non-attack periods but mainly in patients with recurrent attacks. Our aim was to investigate these aspects in sporadic AIP (SA-AIP) and latent AIP (L-AIP) patients. Fifty-five participants, 27 SA-AIP (

Abstract This is the first attempt to apply an expert-based ecological vulnerability assessment of the effects of climate change on the main marine resources of Portugal. The vulnerability, exposure, sensitivity, adaptive capacity, and expected directional effects of 74 species of fish and invertebrates of commercial interest is estimated based on criteria related to their life-history and level of conservation or exploitation. This analysis is performed separately for three regions of Portugal and two scenarios of climate change (RCP 4.5 and RCP 8.5). To do that, the fourth assessment report IPCC framework for vulnerability assessments was coupled to the outputs of a physical-biogeochemical model allowing to weight the exposure of the species by the expected variability of the environmental variables in the future. The highest vulnerabilities were found for some migratory and elasmobranch species, although overall vulnerability scores were low probably due to the high adaptive capacity of species from temperate ecosystems. Among regions, the highest average vulnerability was estimated for the species in the Central region while higher vulnerabilities were identified under climate change scenario RCP 8.5 in the three regions, due to higher expected climatic variability. This work establishes the basis for the assessment of the vulnerability of the human activities relying on marine resources in the context of climate change.

Abstract Background COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p

Objetivos: El objetivo de este trabajo es determinar la proporción de ansiedad en estudiantes españoles de medicina durante la pandemia de COVID-19. Metodología: 31 estudiantes del grado de medicina de una universidad española contestaron un cuestionario on-line en abril del 2020. La escala GAD-7 se utilizó para evaluar sintomatología ansiosa autorreportada, y se utilizaron los puntos de corte para clasificarlos en ansiedad probable. Resultados: El 64,5% de la muestra presentó ansiedad, siendo más prevalente entre mujeres y los más jóvenes. Conclusiones: La prevalencia de ansiedad en la muestra analizada sugiere la necesidad de evaluar sintomatología ansiosa entre los estudiantes de medicina durante la pandemia de COVID-19 y establecer programas de apoyo psicológico adecuados. Estudios epidemiológicos futuros con muestras amplias y representativas se hacen necesarios para hacer un seguimiento de la salud mental de este colectivo.

META-R (multi-environment trial analysis in R) is a suite of R scripts linked by a graphical user interface (GUI) designed in Java language. The objective of META-R is to accurately analyze multi-environment plant breeding trials (METs) by fitting mixed and fixed linear models from experimental designs such as the randomized complete block design (RCBD) and the alpha-lattice/lattice designs. META-R simultaneously estimates the best linear and unbiased estimators (BLUEs) and the best linear and unbiased predictors (BLUPs). Additionally, it computes the variance-covariance parameters, as well as some statistical and genetic parameters such as the least significant difference (LSD) at 5% significance, the coefficient of variation in percentage (CV), the genetic variance, and the broad-sense heritability. These parameters are very important in the selection of top performing genotypes in plant breeding. META-R also computes the phenotypic and genetic correlations among environments and between traits, as well as their statistical significance. The genetic correlations between environments or traits can be visualized in a biplot graph or a tree diagram (dendrogram). Genetic correlations are very important for identifying environments with similar behavior or making indirect selection and identifying the most highly associated traits. META-R performs multi-environment analyses by using the residual maximum likelihood (REML) method; these analyses can be done by environment, across environments by grouping factors (stress conditions, nitrogen content, etc.) and across environments; the analyses across environments can be done with a pre-defined degree of heritability.

Genebanks hold comprehensive collections of wild species, wild relatives, and landraces that are useful for genetic improvement. Here, the authors report the genotype of nearly 80,000 wheat accessions using DArTseq technology to show the less explored genetic diversity.

“Sparse testing” refers to reduced multi-environment breeding trials in which not all genotypes of interest are grown in each environment. Using genomic-enabled prediction and a model embracing genotype × environment interaction (GE), the non-observed genotype-in-environment combinations can be predicted. Consequently, the overall costs can be reduced and the testing capacities can be increased. The accuracy of predicting the unobserved data depends on different factors including (1) how many genotypes overlap between environments, (2) in how many environments each genotype is grown, and (3) which prediction method is used. In this research, we studied the predictive ability obtained when using a fixed number of plots and different sparse testing designs. The considered designs included the extreme cases of (1) no overlap of genotypes between environments, and (2) complete overlap of the genotypes between environments. In the latter case, the prediction set fully consists of genotypes that have not been tested at all. Moreover, we gradually go from one extreme to the other considering (3) intermediates between the two previous cases with varying numbers of different or non-overlapping (NO)/overlapping (O) genotypes. The empirical study is built upon two different maize hybrid data sets consisting of different genotypes crossed to two different testers (T1 and T2) and each data set was analyzed separately. For each set, phenotypic records on yield from three different environments are available. Three different prediction models were implemented, two main effects models (M1 and M2), and a model (M3) including GE. The results showed that the genome-based model including GE (M3) captured more phenotypic variation than the models that did not include this component. Also, M3 provided higher prediction accuracy than models M1 and M2 for the different allocation scenarios. Reducing the size of the calibration sets decreased the prediction accuracy under all allocation designs with M3 being the less affected model; however, using the genome-enabled models (i.e., M2 and M3) the predictive ability is recovered when more genotypes are tested across environments. Our results indicate that a substantial part of the testing resources can be saved when using genome-based models including GE for optimizing sparse testing designs.

Personal assistance for people with intellectual disabilities can contribute to the application of the new paradigms of self-determination and social inclusion and to an improvement in the quality of life. Through a literature review and analysis with professional experts, experts from experience and potential users, a brief model of personal assistance was developed to be executed by community agents with professional supervision. The model considers activities in the usual spaces of people and their families, with support for the use of community formal and informal resources and the reinforcement of social support networks that continue operating once the intervention ends. With duration of 9 months, the model is developed through a 3-stage process: 1) engagement and formulation of an individualized plan, 2) implementation of the plan, and 3) participants’ learning reinforcement and transfer to support networks. The feasibility of the model in Latin American countries and the need for studies to evaluate its implementation are discussed.

Abstract Background Patisiran, an RNA interference therapeutic, has demonstrated robust reduction of wild-type and mutant transthyretin protein and was able to improve polyneuropathy and quality of life following 18 months of treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. In this 24-month Phase II open-label extension study, we evaluated the effects of patisiran treatment (0.3 mg/kg intravenously every 3 weeks) on safety, serum transthyretin levels, and clinical parameters. Efficacy assessments included modified Neuropathy Impairment Score +7 (mNIS+7) and multiple disease-relevant measures. Cardiac assessments were performed in a pre-specified cardiac subgroup. Results Twenty-seven patients entered this study, including 12 (44%) with ambulation difficulties due to their neuropathy and 11 (41%) who met criteria for the cardiac subgroup. During treatment, the majority of adverse events were mild/moderate in severity; there were no drug-related adverse events leading to treatment discontinuation. The most common drug-related adverse events were flushing and infusion-related reactions (22% each). Patisiran resulted in rapid, robust (~ 82%), and sustained reduction of mean transthyretin levels over 24 months. A mean 6.95-point decrease (improvement) in mNIS+7 from baseline was observed at 24 months. Patisiran’s impact on mNIS+7 was irrespective of concomitant tafamidis or diflunisal use, sex, or age. Clinical assessments of motor function, autonomic symptoms, disease stage, and quality of life remained stable over 24 months. No significant changes were observed for echocardiographic measures or cardiac biomarkers in the cardiac subgroup. Exploratory analyses demonstrated improvements in nerve-fiber density with corresponding reductions in amyloid burden observed in skin biopsies over 24 months. Conclusions Long-term treatment with patisiran had an acceptable safety profile and was associated with halting/improvement of polyneuropathy progression in patients with hATTR amyloidosis. Trial registration The study was registered at ClinicalTrials.gov (identifier: NCT01961921 ) on October 14, 2013.

Information transfer at synapses occurs when vesicles fuse with the plasma membrane to release neurotransmitters, which then bind to receptors at the postsynaptic membrane. The process of neurotransmitter release varies dramatically between different synapses, but little is known about how this heterogeneity emerges. The development of super-resolution microscopy has revealed that synaptic proteins are precisely organised within and between the two parts of the synapse and that this precise spatiotemporal organisation fine-tunes neurotransmission. However, it remains unclear if variability in release probability could be attributed to the nanoscale organisation of one or several proteins of the release machinery. To begin to address this question, we have developed a pipeline for correlative functional and super-resolution microscopy, taking advantage of recent technological advancements enabling multicolour imaging. Here we demonstrate the combination of live imaging of SypHy-RGECO, a unique dual reporter that simultaneously measures presynaptic calcium influx and neurotransmitter release, with post hoc immunolabelling and multicolour single molecule localisation microscopy, to investigate the structure-function relationship at individual presynaptic boutons.