Spatially Extended Charge Density Wave Switching by Nanoscale Local Manipulation in a VTe2 Monolayer.

Monolayer transition metal dichalcogenide VTe2 exhibits multiple charge density wave (CDW) phases, mainly (4 × 4) and (4 × 1). Here we report facile dynamic and tens-of-nanometer scale switching between these CDW phases with gentle bias pulses in scanning tunneling microscopy. Bias pulses purposely stimulate a reversible random CDW symmetry change between the isotropic (4 × 4) and anisotropic (4 × 1) CDWs, as well as CDW phase slips and rotation. The switching threshold of ∼1.0 V is independent of bias polarity, and the switching rate varies linearly with the tunneling current. Density functional theory calculations indicate that a coherent CDW phase switching incurs an energy barrier of ∼2.0-3.0 eV per (4 × 4) unit cell. While there is a challenge in understanding the observed large-area CDW random fluttering, we provide some possible explanations. The ability to manipulate electronic CDW phases sheds new light on tailoring CDW properties on demand.

Adsorption and dissociation of hydrogen molecules over S-vacancies in a Nb-doped MoS2monolayer.

Motivated by the recent interest in the hydrogen energy, we have carried out a complete study of the catalytic activity of a defective molybdenum disulfide monolayer (MoS2) by means of density functional theory (DFT) calculations. The MoS2monolayer is characterized by a nonreactive basal plane. In principle, its catalytic activity is concentrated at the edges, but an alternative way to increase such activity is obtained by creating active sites where the molecules can dissociate. These defects can be easily produced experimentally by different techniques. In our study, we have performed an atomic, energetic and electronic analysis of a hydrogen molecule adsorbed on a MoS2monolayer. In a first step, we have found that the H2molecule remains physisorbed over both doped-free and Nb-doped MoS2monolayers, showing that the Nb atom does not increase the poor reactivity of the clean MoS2layer. Interestingly, our energetic results suggest that the vacancies will prefer to be formed close to the Nb atoms in the doped monolayer, but the small energy difference would allow the formation in non-doped like sites. Theoretically, we found out the conditions for the molecular dissociation on a S vacancy. In both cases, with and without Nb, the molecule should rotate from the original perpendicular position to an almost parallel orientation jumping an energetic barrier. After that, the atoms are separated binding to the Mo atoms around the missing S atom. Ourab initiomolecular dynamics simulations show that for low pressure conditions (using one single molecule in the system) the H2prefers to desorb from the vacancy, while for larger pressures (when additional H2molecules are added to the system) the molecule is finally dissociated on the vacancy. Our long simulations confirm the great stability of the structure with the two H atoms binding to the Mo atoms close to the vacancy. Finally, the inclusion of a third (or a fourth) H atom in the vacancy leads to the formation and desorption of a H2molecule, leaving one (or two) atoms in the vacancy.

Hardware Acceleration of Digital Pulse Shape Analysis Using FPGAs.

The BC501A sensor is a liquid scintillator frequently used in nuclear physics for detecting fast neutrons. This paper describes a hardware implementation of digital pulse shape analysis (DPSA) for real-time analysis. DPSA is an algorithm that extracts the physically relevant parameters from the detected BC501A signals. The hardware solution is implemented in a MicroTCA system that provides the physical, mechanical, electrical, and cooling support for an AMC board (NAMC-ZYNQ-FMC) with a Xilinx ZYNQ Ultrascale-MP SoC. The Xilinx FPGA programmable logic implements a JESD204B interface to high-speed ADCs. The physical and datalink JESD204B layers are implemented using hardware description language (HDL), while the Xilinx high-level synthesis language (HLS) is used for the transport and application layers. The DPSA algorithm is a JESD204B application layer that includes a FIR filter and a constant fraction discriminator (CFD) function, a baseline calculation function, a peak detection function, and an energy calculation function. This architecture achieves an analysis mean time of less than 100 µs per signal with an FPGA resource utilization of about 50% of its most used resources. This paper presents a high-performance DPSA embedded system that interfaces with a 1 GS/s ADC and performs accurate calculations with relatively low latency.

Gender Diversity Among Youth Attending an Intensive Interdisciplinary Pain Treatment Program.

Transgender and gender diverse (TGD) youth with chronic pain may be at unique risk for psychological distress and associated functional impairment, yet research on the intersection of chronic pain and gender identity is lacking. In a retrospective chart review of 491 participants admitted to a pediatric intensive interdisciplinary pain treatment (IIPT) program in the midwestern United States over an approximately 4-year period, 6.11% were TGD. TGD participants who completed the IIPT program reported significant and large improvements in anxiety, depression, pain catastrophizing, and functional ability. At baseline, TGD participants presented as more emotionally distressed and functionally impaired compared to age-matched, cisgender peers. When accounting for baseline scores, TGD participants who completed the IIPT program reported similar scores to cisgender peers at discharge, yet TGD youth were significantly less likely than cisgender peers to complete the IIPT program. Future directions and implications for clinical practice are discussed.

The Regulation of Mitochondrial Replacement Techniques Around the World.

Mitochondrial replacement techniques (MRTs, also referred to as mitochondrial replacement therapies) have given hope to many women who wish to have genetically related children but have mitochondrial DNA mutations in their eggs. MRTs have also spurred deep ethical disagreements and led to different regulatory approaches worldwide. In this review, we discuss the current regulation of MRTs across several countries. After discussing the basics of the science, we describe the current law and policy directions in seven countries: the United Kingdom, the United States, Canada, Australia, Germany, Israel, and Singapore. We also discuss the emerging phenomenon of medical tourism (also called medical travel) for MRTs to places like Greece, Spain, Mexico, and Ukraine. We then pull out some key findings regarding similarities and differences in regulatory approaches around the world.

Optical coherence tomography versus other biomarkers: Associations with physical and cognitive disability in multiple sclerosis.

BACKGROUND: Optical coherence tomography (OCT) is a biomarker of neuroaxonal loss in multiple sclerosis (MS). OBJECTIVE: The objective was to assess the relative role of OCT, next to magnetic resonance imaging (MRI) and serum markers of disability in MS. METHODS: A total of 100 patients and 52 controls underwent OCT to determine peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layers (GCIPL). Serum neurofilament light chain (sNfL), total lesion volume (TLV), and brain parenchymal fraction (BPF) were also assessed. The associations of OCT with disability were examined in linear regression models with correction for age, vision, and education. RESULTS: In patients, pRNFL was associated with the Symbol Digit Modalities Test (SDMT; p = 0.030). In the multivariate analysis including sNfL and MRI measures, pRNFL (ß = 0.19, p = 0.044) and TLV (ß = -0.24, p = 0.023) were the only markers associated with the SDMT. pRNFL (p < 0.001) and GCIPL (p < 0.001) showed associations with the Expanded Disability Status Scale (EDSS). In the multivariate analysis, GCIPL showed the strongest association with the EDSS (ß = -0.32, p < 0.001) followed by sNfL (ß = 0.18, p = 0.024). CONCLUSION: The associations of OCT measures with cognitive and physical disability were independent of serum and brain MRI markers of neuroaxonal loss. OCT can be an important tool for stratification in MS, while longitudinal studies using combinations of biomarkers are warranted.

Gene editing of putative cAMP and Ca2+ -regulated proteins using an efficient cloning-free CRISPR/Cas9 system in Trypanosoma cruzi.

Trypanosoma cruzi, the agent of Chagas disease, must adapt to a diversity of environmental conditions that it faces during its life cycle. The adaptation to these changes is mediated by signaling pathways that coordinate the cellular responses to the new environmental settings. Cyclic AMP (cAMP) and Calcium (Ca2+ ) signaling pathways regulate critical cellular processes in this parasite, such as differentiation, osmoregulation, host cell invasion and cell bioenergetics. Although the use of CRISPR/Cas9 technology prompted reverse genetics approaches for functional analysis in T. cruzi, it is still necessary to expand the toolbox for genome editing in this parasite, as for example to perform multigene analysis. Here we used an efficient T7RNAP/Cas9 strategy to tag and delete three genes predicted to be involved in cAMP and Ca2+ signaling pathways: a putative Ca2+ /calmodulin-dependent protein kinase (CAMK), Flagellar Member 6 (FLAM6) and Cyclic nucleotide-binding domain/C2 domain-containing protein (CC2CP). We endogenously tagged these three genes and determined the subcellular localization of the tagged proteins. Furthermore, the strategy used to knockout these genes allows us to presume that TcCC2CP is an essential gene in T. cruzi epimastigotes. Our results will open new venues for future research on the role of these proteins in T. cruzi.

Binaural Beat Effects on Attention: A Study Based on the Oddball Paradigm.

The impact of binaural beats (BBs) on human cognition and behavior remains and various methods have been used to measure their effect, including neurophysiological, psychometric, and human performance evaluations. The few approaches where the level of neural synchronicity and connectivity were measured by neuroimaging techniques have only been undertaken in spontaneous mode. The present research proposes an approach based on the oddball paradigm to study BB effect by estimating the level of attention induced by BBs. Evoked activity of 25 young adults between 19 and 24 years old with no hearing impairments nor clinical neurological history were analyzed. The experiment was conducted in two different sessions of 24.5 min. The first part consisted of 20-min BB stimulation in either theta (BBθ) or beta (BBß). After the BB stimulation, an oddball paradigm was applied in each BB condition to assess the attentional effect induced by BBs. Attention enhancement is expected for BBß with respect to BBθ. Target event related potentials (ERPs) were mainly analyzed in the time and time-frequency domains. The frequency analysis was based on continuous wavelet transform (CWT), event-related spectral perturbation (ERSP), and inter-trial phase coherence (ITPC). The study revealed that the P300 component was not significantly different between conditions (BBθ vs. BBß). However, the target grand average ERP in BBθ condition was mainly composed of 8 Hz-frequency components, appearing before 400 ms post-stimulus, and mainly on the centro-parietal regions. In contrast, the target grand average ERP in BBß condition was mainly composed of frequency components below 6 Hz, mainly appearing at 400 ms post-stimulus on the parieto-occipital regions. Furthermore, ERPs in the BBθ condition were more phase locked than the BBß condition.

Genealogical obscurement: mitochondrial replacement techniques and genealogical research.

Mitochondrial replacement techniques (MRTs) are a new group of biotechnologies that aim to aid women whose eggs have disease-causing deleteriously mutated mitochondria to have genetically related healthy children. These techniques have also been used to aid women with poor oocyte quality and poor embryonic development, to have genetically related children. Remarkably, MRTs create humans with DNA from three sources: nuclear DNA from the intending mother and father, and mitochondrial DNA from the egg donor. In a recent publication Françoise Baylis argued that MRTs are detrimental for genealogical research via mitochondrial DNA because they would obscure the lines of individual descent. In this paper, I argue that MRTs do not obscure genealogical research, but rather that MRT-conceived children can have two mitochondrial lineages. I argue for this position by showing that MRTs are reproductive in nature and, thus, they create genealogy.

Respect for human rights as a component of organisational well-being: factor structure analysis in three countries of Latin America.

People with psychosocial disabilities are often discriminated against and experience violations of their human rights. With the QualityRights program, World Health Organisation highlights that one of element founding the quality of services is the respect for users' rights, in the belief that there is no quality of care without respect for human rights and vice versa. To date, studies explored the issue mainly in Europe. In this sense, the purpose of the study is to verify if the perception of respect for patients' rights is a component of organisational well-being for mental health workers in three countries of Latin America (Argentina, Colombia, Peru). A random sample representative of professionals working in three mental healthcare networks in Argentina, Colombia, and Peru was enrolled (n = 310). Each health worker completed a questionnaire on sociodemographic data and the Well-Being at work and respect for human rights (WWRR). The WWRR consists of seven items on satisfaction at work, beliefs about users' satisfaction in received care, the satisfaction of work's organisation, respect of users' and staff's human rights, adequacy of resources, and perceived needs of resources in the mental health service. The principal components analysis of the instrument was carried out with Varimax rotation and Kaiser normalisation (including all components with Eigen value > 1). The total explained variance was 67.2%. Item 6 saturated in one single factor, and the first five items saturated in factor 1 with factor loadings ranging from 0.52 to 0.86. Parallel test suggested a one-factor structure as acceptable. The results show in three countries of Latin America that the more workers perceive that the human rights of users are respected, the more satisfied they are of own work. This article confirms previous observations in Italy, North Macedonia, Tunisia and Palestine.

First report of Irpex rosettiformis causing white root rot in avocado trees in Michoacán, México.

In México, avocado production is an important economic source. In the last season it generated $ 3. 27 billion USD of foreign currency in the country. Irpex spp. are wood decay fungi. In the period 2019-2022, in the state of Michoacán (19°13' N; 101°55' W), México, basidiomes of Irpex sp. were observed on the base of trunks and crowns of 5-years-old and older avocado (Persea americana) trees. The trees exhibited disease symptoms that included white root rot, leaf yellowing, small leaves, branch diebacks, generalized defoliation, apical flaccidity, abundant but small sun burnt fruits due to the lack of foliage, and after 2-4 years of first disease appearance, the infected trees died. In the place where fungus was established, abundant white and cottony mycelium was formed, which caused trees decay. The incidence of the disease in the sampled orchards was estimated to be 30% per ha with 350 - 400 trees, which was determined through a simple sampling design focused on trees with signs and symptoms of the disease due to the phytopathogen. Samples of infected tissue (roots and stems) and fungal basidiomes were collected from 90 trees (5-6 per orchard). The symptomatic avocado trees studied were randomly selected from 17 orchards. For the fungal macroscopic characterization, the synoptic keys described by Gilbertson and Ryvarden (1986) and by Largent (1973) were used. The samples showed typical structures corresponding to Irpex sp., including rosettes, annual basidiomes, a system of monomitic hyphae, and subglobose basidiospores. In vitro fungal isolation from basidiomes and infected tree tissues was done according to the protocol of Agrios (2004). The fungal strains were maintained on PDA at 28 °C. At 16 days of incubation the colonies were opaque, whitish with fluffy and corky mycelium. Microscopic analysis of the fungus showed typical yellowish spores, with an ellipsoid shape of 3-4 x 4-5.5 µm (50 accounted structures per isolate [N=19]) and basidia of 20-25 x 4.5-5.5 µm (n=20 basidiomes). For molecular characterization, two molecular markers were used, the internal transcribed spacer rDNA-ITS1 5.8 rDNA-ITS2 (ITS; White et al. 1990) and the large ribosomal subunit (LSU; Vilgalys and Hester 1990). The PCR reaction was performed as described by Martínez-González et al. (2017). The consensus sequences were compared with those deposited in the NCBI-GenBank, using the BLASTN 2.2.19 tool (Zhang et al. 2000), the samples showed 99% match with the species, Irpex rosettiformis. GenBank accession numbers of the submitted isolates are summarized in supplementary Table 4. To test Koch's postulates, 3-months old avocado plants grown in greenhouse conditions were inoculated (n = 10 per each isolate [N= 19]) on the roots with 3 g of I. rosettiformis mycelium. The experiment was done twice with 20 non-inoculated plants as control. After 67 days, basidiomes (50 x 70 x 1.5 mm in average) were observed where the disease incidence was >77%, with subsequent tree decline. The pathogen was re-isolated in vitro in PDA and its identity was confirmed by morphological characteristics of mycelium. This work shows that I. rosettiformis is not only a wood decay fungus, but also a phytopathogen, the causative agent of white root rot disease in P. americana var. drymifolia, cultivar 'Hass', which establishes a precedent for monitoring and preventing its proliferation to other regions in the American continent and the world where nursery avocado seedlings are exported.

Impaired response of blood neutrophils to cell-death stimulus differentiates AQP4-IgG-seropositive NMOSD from MOGAD.

BACKGROUND: In neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neutrophils are found in CNS lesions. We previously demonstrated that NMOSD neutrophils show functional deficiencies. Thus, we hypothesized that neutrophil accumulation in the CNS may be facilitated by impairments affecting mechanisms of neutrophil death. OBJECTIVE: To evaluate cell death in blood neutrophils from aquaporin-4 (AQP4)-IgG-seropositive NMOSD and MOGAD patients as well as matched healthy controls (HC) using in vitro assays. METHODS: Twenty-eight AQP4 + NMOSD and 19 MOGAD patients in stable disease phase as well as 45 age- and sex-matched HC were prospectively recruited. To induce cell death, isolated neutrophils were cultured with/without phorbol 12-myristate 13-acetate (PMA). Spontaneous and PMA-induced NETosis and apoptosis were analyzed using 7-AAD and annexin-V by flow cytometry. Caspase-3 was assessed by western blot. Myeloperoxidase-DNA complexes (MPO-DNA), MPO and elastase were evaluated by ELISA, and cell-free DNA (cfDNA) by a fluorescence-based assay. Reactive oxygen species (ROS) were evaluated by a dihydrorhodamine 123-based cytometric assay. Serum GM-CSF, IL-6, IL-8, IL-15, TNF-ɑ and IL-10 were evaluated by multiplex assays, and neurofilament light chain (NfL) by single-molecule array assay. RESULTS: In response to PMA, neutrophils from AQP4 + NMOSD but not from MOGAD patients showed an increased survival, and subsequent reduced cell death (29.6% annexin V+ 7-AAD+) when compared to HC (44.7%, p = 0.0006). However, AQP4 + NMOSD also showed a mild increase in annexin V+ 7-AAD- early apoptotic neutrophils (24.5%) compared to HC (20.8%, p = 0.048). PMA-induced reduction of caspase-3 activation was more pronounced in HC (p = 0.020) than in AQP4 + NMOSD neutrophils (p = 0.052). No differences were observed in neutrophil-derived MPO-DNA or serum levels of MPO, elastase, IL-6, IL-8 and TNF-ɑ. IL-15 levels were increased in both groups of patients. In AQP4 + NMOSD, an increase in cfDNA, GM-CSF and IL-10 was found in serum. A positive correlation among cfDNA and NfL was found in AQP4 + NMOSD. CONCLUSIONS: AQP4 + NMOSD neutrophils showed an increased survival capacity in response to PMA when compared to matched HC neutrophils. Although the data indicate that the apoptotic but not the NETotic response is altered in these neutrophils, additional evaluations are required to validate this observation.

Enhancing Diversity in the Ophthalmology Workforce.

Health care teams are most effective at addressing complex problems and improving health outcomes for underserved populations when team members bring diverse life experiences and perspectives to the effort. With rates of visual impairment expected to increase in the United States by 2050, especially among minority populations, diversification of the ophthalmology workforce will be critical in reducing disparities in access to and quality of vision health care. Currently, ophthalmology is less diverse with respect to race, ethnicity, and gender than graduating medical classes and other medical specialties, as well as the general US population. In addition, data on diversity in sexual orientation and gender identity, socioeconomic status, and disability are lacking in ophthalmology. The Minority Ophthalmology Mentoring and Rabb-Venable Excellence in Ophthalmology Programs are examples of initiatives to increase racial and ethnic diversity in the workforce and can serve as models for increasing other aspects of inclusiveness. Other strategies for improving vision health care for all Americans include continuing to support existing diversity programs and creating new ones; addressing unconscious and implicit bias in medical school, residency, and faculty selections; conducting holistic reviews of medical school and residency applications; diversifying selection committees and leadership; and encouraging faculty development of underrepresented groups.

Early inflammatory changes and CC chemokine ligand-8 upregulation in the heart contribute to uremic cardiomyopathy.

Uremic cardiomyopathy is a common complication in chronic kidney disease (CKD) patients, accounting for a high mortality rate. Several mechanisms have been proposed to link CKD and cardiac alterations; however, the early cardiac modifications that occur in CKD that may trigger cardiac remodeling and dysfunction remain largely unexplored. Here, in a mouse model of CKD induced by 5/6 nephrectomy, we first analyzed the early transcriptional and inflammatory changes that occur in the heart. Five days after 5/6 nephrectomy, RNA-sequencing showed the upregulation of 54 genes in the cardiac tissue of CKD mice and the enrichment of biological processes related to immune system processes. Increased cardiac infiltration of T-CD4+ lymphocytes, myeloid cells, and macrophages during early CKD was observed. Next, since CC chemokine ligand-8 (CCL8) was one of the most upregulated genes in the heart of mice with early CKD, we investigated the effect of acute and transient CCL8 inhibition on uremic cardiomyopathy severity. An increase in CCL8 protein levels was confirmed in the heart of early CKD mice. CCL8 inhibition attenuated the early infiltration of T-CD4+ lymphocytes and macrophages to the cardiac tissue, leading to a protection against chronic cardiac fibrotic remodeling, inflammation and cardiac dysfunction induced by CKD. Altogether, our data show the occurrence of transcriptional and inflammatory changes in the heart during the early phases of CKD and identify CCL8 as a key contributor to the early cardiac inflammatory state that triggers further cardiac remodeling and dysfunction in uremic cardiomyopathy.

High Performance Computing PP-Distance Algorithms to Generate X-ray Spectra from 3D Models.

X-ray crystallography is a powerful method that has significantly contributed to our understanding of the biological function of proteins and other molecules. This method relies on the production of crystals that, however, are usually a bottleneck in the process. For some molecules, no crystallization has been achieved or insufficient crystals were obtained. Some other systems do not crystallize at all, such as nanoparticles which, because of their dimensions, cannot be treated by the usual crystallographic methods. To solve this, whole pair distribution function has been proposed to bridge the gap between Bragg and Debye scattering theories. To execute a fitting, the spectra of several different constructs, composed of millions of particles each, should be computed using a particle-pair or particle-particle (pp) distance algorithm. Using this computation as a test bench for current field-programmable gate array (FPGA) technology, we evaluate how the parallel computation capability of FPGAs can be exploited to reduce the computation time. We present two different solutions to the problem using two state-of-the-art FPGA technologies. In the first one, the main C program uses OmpSs (a high-level programming model developed at the Barcelona Supercomputing Center, that enables task offload to different high-performance computing devices) for task invocation, and kernels are built with OpenCL using reduced data sizes to save transmission time. The second approach uses task and data parallelism to operate on data locally and update data globally in a decoupled task. Benchmarks have been evaluated over an Intel D5005 Programmable Acceleration Card, computing a model of 2 million particles in 81.57 s - 24.5 billion atom pairs per second (bapps)- and over a ZU102 in 115.31 s. In our last test, over an up-to-date Alveo U200 board, the computation lasted for 34.68 s (57.67 bapps). In this study, we analyze the results in relation to the classic terms of speed-up and efficiency and give hints for future improvements focused on reducing the global job time.

Ethical heuristics for pandemic allocation of ventilators across hospitals.

In response to the COVID-19 pandemic philosophers and governments have proposed scarce resource allocation guidelines. Their purpose is to advise healthcare professionals on how to ethically allocate scarce medical resources. One challenging feature of the pandemic has been the large numbers of patients needing mechanical ventilatory support. Guidelines have paradigmatically focused on the question of what doctors should do if they have fewer ventilators than patients who need respiratory support: which patient should get the ventilator? There is, however, an important higher level allocation problem. Namely, how are we to ethically distribute newly obtained ventilators across hospitals: which hospital should get the ventilator(s)? In this paper, we identify a set of principles for allocating newly obtained ventilators across hospitals. We focus particularly on low and middle income countries, who frequently have limited pre-existing intensive care capacity, and have needed to source additional ventilators. We first provide some background. Second, we argue that the main population healthcare aim during the COVID-19 pandemic should be to save the most lives. Next, we assess a series of potential heuristics or principles that could be used to guide allocation: allocation to the most densely populated cities, random allocation, allocation based on the ratio of patients to ICU personnel, prioritisation in terms of intrahospital mortality, prioritisation of younger populations, and prioritisation in terms of population mortality. We conclude by providing a plausible ranking of the principles, while noting a number of epistemological challenges, in terms of how they best further the aim of increasing the probability of saving the most lives.

Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin.

Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin (endo coumarin-resveratrol-inspired hybrid) and trans-6-styrylcoumarin (exo coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with trans-6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than trans-resveratrol.

Exercise in Older Adults to Prevent Depressive Symptoms at the Time of Covid-19: Results of a Randomized Controlled Trial with Follow-Up.

Background: This study aimed to verify, through a randomized controlled trial, whether a medium-intensity mixing/aerobic/anaerobic exercise (accessible to older adults even with mild chronic diseases) can effectively counteract depressive episodes. A characteristic of the trial was that the follow-up coincided (unscheduled) with the lockdown due to Covid-19. Methods: Participants (N=120) were randomized into an intervention group, performing physical exercise, and a control group. Participants, aged 65 years and older, belonged to both genders, living at home, and cleared a medical examination, were evaluated with a screening tool to detect depressive episodes, the PHQ9, at pre-treatment, end of the trial (12-week), and follow-up (48-week). Results: A decrease in the frequency of depressive episodes after the trial (T1) was found in both groups; however, a statistically significant difference was observed only in the control group (p=0.0039). From T1 to follow-up (conducted during the lockdown), the frequency of depressive episodes increased in the control group, reaching a frequency equal to the time of study entry (p=0.788). In the experimental group, the frequency of depressive episodes did not change at the end of the trial but reached a statistically significant difference compared to the start of the study (p = 0.004) and was higher than the control group (p=0.028). Conclusion: Moderate-intensity physical exercise can be conducted safely, benefitting older adults even suffering from mild chronic disorders. Physical exercise seems to guarantee a long-term preventive effect towards depressive symptoms, especially in serious stressful situations such as the lockdown due to the Covid-19 pandemic.

Nonlinear Analysis of Rotational Springs to Model Semi-Rigid Frames.

This paper explains the mathematical foundations of a method for modelling semi-rigid unions. The unions are modelled using rotational rather than linear springs. A nonlinear second-order analysis is required, which includes both the effects of the flexibility of the connections as well as the geometrical nonlinearity of the elements. The first task in the implementation of a 2D Beam element with semi-rigid unions in a nonlinear finite element method (FEM) is to define the vector of internal forces and the tangent stiffness matrix. After defining the formula for this vector and matrix in the context of a semi-rigid steel frame, an iterative adjustment of the springs is proposed. This setting allows a moment-rotation relationship for some given load parameters, dimensions, and unions. Modelling semi-rigid connections is performed using Frye and Morris' polynomial model. The polynomial model has been used for type-4 semi-rigid joints (end plates without column stiffeners), which are typically semi-rigid with moderate structural complexity and intermediate stiffness characteristics. For each step in a non-linear analysis required to adjust the matrix of tangent stiffness, an additional adjustment of the springs with their own iterative process subsumed in the overall process is required. Loops are used in the proposed computational technique. Other types of connections, dimensions, and other parameters can be used with this method. Several examples are shown in a correlated analysis to demonstrate the efficacy of the design process for semi-rigid joints, and this is the work's application content. It is demonstrated that using the mathematical method presented in this paper, semi-rigid connections may be implemented in the designs while the stiffness of the connection is verified.

Fatal Case of Crimean-Congo Hemorrhagic Fever Caused by Reassortant Virus, Spain, 2018.

In August 2018, a fatal autochthonous case of Crimean-Congo hemorrhagic fever was confirmed in western Spain. The complete sequence of the viral genome revealed circulation of a new virus because the genotype differs from that of the virus responsible for another case in 2016. Practitioners should be alert to possible new cases.