Stability and Reversible Oxidation of Sub-Nanometric Cu5 Metal Clusters: Integrated Experimental Study and Theoretical Modeling.

Sub-nanometer metal clusters have special physical and chemical properties, significantly different from those of nanoparticles. However, there is a major concern about their thermal stability and susceptibility to oxidation. In situ X-ray Absorption spectroscopy and Near Ambient Pressure X-ray Photoelectron spectroscopy results reveal that supported Cu5 clusters are resistant to irreversible oxidation at least up to 773 K, even in the presence of 0.15 mbar of oxygen. These experimental findings can be formally described by a theoretical model which combines dispersion-corrected DFT and first principles thermochemistry revealing that most of the adsorbed O2 molecules are transformed into superoxo and peroxo species by an interplay of collective charge transfer within the network of Cu atoms and large amplitude "breathing" motions. A chemical phase diagram for Cu oxidation states of the Cu5 -oxygen system is presented, clearly different from the already known bulk and nano-structured chemistry of Cu.

Light-Emitting Diode (LED) Phototherapy versus Non-LED Phototherapy Devices for Hyperbilirubinemia in Neonates: A Systematic Review and Meta-analysis.

This review was conducted to evaluate the efficacy of light-emitting diode (LED) phototherapy as compared with the conventional phototherapy in neonates with unconjugated hyperbilirubinemia and their adverse effects. We searched the following databases right from their inception till April, 2021: MEDLINE, EMBASE, Cochrane Library, and LILACS. Randomized clinical trials (RCTs) comparing the LED phototherapy with other light sources, which enrolled newborns (term and preterm) with unconjugated hyperbilirubinemia were included. We included 21 articles in this review. The treatment with the LED light therapy had a lower failure rate as compared with the non-LED one (RR = 0.60, 95% CI: 0.39-0.94). The mean duration of phototherapy was significantly shorter in the group with the LED light source as compared with the one with the non-LED light source (mean difference [hours]: -8.07, 95% CI: -8.45 to -7.68), regardless of the type of non-LED units. However, the rate of bilirubin showed a comparable decline (mean difference [mg/dL/h]: 0.01, 95% CI: -0.00, 0.03) in both the light sources, irrespective of irradiance or distance. No studies reported primary outcomes related to the neurotoxicity effects of hyperbilirubinemia in neonates. The LED light devices caused a significantly higher risk of hypothermia. Neonates were at a lower risk of developing hyperthermia and skin rash with the LED light therapy. Our findings provide support for the use of LED light source phototherapy due to its better clinical efficacy, which is evidenced by its shorter duration and lower rate of treatment failure, as compared with the non-LED light sources. KEY POINTS: · The efficacy of phototherapy is dependent on specific characteristics of light sources of phototherapy devices.. · LED phototherapy demonstrated better efficacy with shorter duration and lower rate of treatment failure.. · Adverse effects of phototherapy devices such as hypothermia, hyperthermia, and skin rash should be monitored..

Differentiating Botulinum Neurotoxin-Producing Clostridia with a Simple, Multiplex PCR Assay.

Diverse members of the genus Clostridium produce botulinum neurotoxins (BoNTs), which cause a flaccid paralysis known as botulism. While multiple species of clostridia produce BoNTs, the majority of human botulism cases have been attributed to Clostridium botulinum groups I and II. Recent comparative genomic studies have demonstrated the genomic diversity within these BoNT-producing species. This report introduces a multiplex PCR assay for differentiating members of C. botulinum group I, C. sporogenes, and two major subgroups within C. botulinum group II. Coding region sequences unique to each of the four species/subgroups were identified by in silico analyses of thousands of genome assemblies, and PCR primers were designed to amplify each marker. The resulting multiplex PCR assay correctly assigned 41 tested isolates to the appropriate species or subgroup. A separate PCR assay to determine the presence of the ntnh gene (a gene associated with the botulinum neurotoxin gene cluster) was developed and validated. The ntnh gene PCR assay provides information about the presence or absence of the botulinum neurotoxin gene cluster and the type of gene cluster present (ha positive [ha+] or orfX+). The increased availability of whole-genome sequence data and comparative genomic tools enabled the design of these assays, which provide valuable information for characterizing BoNT-producing clostridia. The PCR assays are rapid, inexpensive tests that can be applied to a variety of sample types to assign isolates to species/subgroups and to detect clostridia with botulinum neurotoxin gene (bont) clusters.IMPORTANCE Diverse clostridia produce the botulinum neurotoxin, one of the most potent known neurotoxins. In this study, a multiplex PCR assay was developed to differentiate clostridia that are most commonly isolated in connection with human botulism cases: C. botulinum group I, C. sporogenes, and two major subgroups within C. botulinum group II. Since BoNT-producing and nontoxigenic isolates can be found in each species, a PCR assay to determine the presence of the ntnh gene, which is a universally present component of bont gene clusters, and to provide information about the type (ha+ or orfX+) of bont gene cluster present in a sample was also developed. The PCR assays provide simple, rapid, and inexpensive tools for screening uncharacterized isolates from clinical or environmental samples. The information provided by these assays can inform epidemiological studies, aid with identifying mixtures of isolates and unknown isolates in culture collections, and confirm the presence of bacteria of interest.

The Transcription Factors AcuK and AcuM Influence Siderophore Biosynthesis of Aspergillus fumigatus.

The mold Aspergillus fumigatus employs two high-affinity uptake systems, reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA), for the acquisition of the essential trace element iron. SIA has previously been shown to be crucial for virulence in mammalian hosts. Here, we show that a lack of AcuK or AcuM, transcription factors required for the activation of gluconeogenesis, decreases the production of both extra- and intracellular siderophores in A. fumigatus. The lack of AcuM or AcuK did not affect the expression of genes involved in RIA and SIA, suggesting that these regulators do not directly regulate iron homeostasis genes, but indirectly affect siderophore production through their influence on metabolism. Consistent with this, acetate supplementation reversed the intracellular siderophore production defect of ΔacuM and ΔacuK. Moreover, ΔacuM and ΔacuK displayed a similar growth defect under iron limitation and iron sufficiency, which suggests they have a general role in carbon metabolism apart from gluconeogenesis. In agreement with a potential role of the glyoxylate cycle in adaptation to iron starvation, transcript levels of the malate synthase-encoding acuE were found to be upregulated by iron limitation that is partially dependent on AcuK and AcuM. Together, these data demonstrate the influence of iron availability on carbon metabolism.

Biomimetic Analogues of the Desferrioxamine E Siderophore for PET Imaging of Invasive Aspergillosis: Targeting Properties and Species Specificity.

The pathogenic fungus Aspergillus fumigatus utilizes a cyclic ferrioxamine E (FOXE) siderophore to acquire iron from the host. Biomimetic FOXE analogues were labeled with gallium-68 for molecular imaging with PET. [68Ga]Ga(III)-FOXE analogues were internalized in A. fumigatus cells via Sit1. Uptake of [68Ga]Ga(III)-FOX 2-5, the most structurally alike analogue to FOXE, was high by both A. fumigatus and bacterial Staphylococcus aureus. However, altering the ring size provoked species-specific uptake between these two microbes: ring size shortening by one methylene unit (FOX 2-4) increased uptake by A. fumigatus compared to that by S. aureus, whereas lengthening the ring (FOX 2-6 and 3-5) had the opposite effect. These results were consistent both in vitro and in vivo, including PET imaging in infection models. Overall, this study provided valuable structural insights into the specificity of siderophore uptake and, for the first time, opened up ways for selective targeting and imaging of microbial pathogens by siderophore derivatization.

Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis.

BACKGROUND: The impact of extended use of ART in developing countries has been enormous. A thorough understanding of all factors contributing to the success of antiretroviral therapy is required. The current study aims to investigate the value of cross-sectional drug resistance monitoring using DNA and RNA oligonucleotide ligation assays (OLA) in treatment cohorts in low-resource settings. The study was conducted in the first cohort of children gaining access to structured ART in Peru. METHODS: Between 2002-5, 46 eligible children started the standard regimen of AZT, 3TC and NFV Patients had a median age of 5.6 years (range: 0.7-14y), a median viral load of 1.7·105 RNA/ml (range: 2.1·10(3) - 1.2·10(6)), and a median CD4-count of 232 cells/µL (range: 1-1591). Of these, 20 patients were classified as CDC clinical category C and 31/46 as CDC immune category 3. At the time of cross-sectional analysis in 2005, adherence questionnaires were administered. DNA OLAs and RNA OLAs were performed from frozen PBMC and plasma, RNA genotyping from dried blood spots. RESULTS: During the first year of ART, 44% of children experienced virologic failure, with an additional 9% failing by the end of the second year. Virologic failure was significantly associated with the number of resistance mutations detected by DNA-OLA (p < 0.001) during cross-sectional analysis, but also with low immunologic CDC-scores at baseline (p < 0.001). Children who had been exposed to unsupervised short-term antiretrovirals before starting structured ART showed significantly higher numbers of resistance mutations by DNA-OLA (p = 0.01). Detection of M184V (3TC resistance) by RNA-OLA and DNA-OLA demonstrated a sensitivity of 0.93 and 0.86 and specificity of 0.67 and 0.7, respectively, for the identification of virologic failure. The RT mutations N88D and L90M (NFV resistance) detected by DNA-OLA correlated with virologic failure, whereas mutations at RT position 215 (AZT resistance) were not associated with virologic failure. CONCLUSIONS: Advanced immunosuppression at baseline and previous exposures to unsupervised brief cycles of ART significantly impaired treatment outcomes at a time when structured ART was finally introduced in his cohort. Brief maternal exposures to with AZT +/- NVP for the prevention of mother-to-child transmission did not affect treatment outcomes in this group of children. DNA-OLA from frozen PBMC provided a highly specific tool to detect archived drug resistance. RNA consensus genotyping from dried blood spots and RNA-OLA from plasma consistently detected drug resistance mutations, but merely in association with virologic failure.

Gene expression response of the non-target gastropod Physella acuta to Fenoxycarb, a juvenile hormone analog pesticide.

Pesticides are an environmental problem. The search for new pest control methods has focused on compounds with low or no toxic effects in non-target organisms. Analogs of the juvenile hormone (JH) interfere endocrine system of arthropods. However, the lack of effect on non-target species requires confirmation. This article analyzes the impact of Fenoxycarb, an analog of JH, on Physella acuta, an aquatic gastropod. For 1 week, animals were exposed to 0.01, 1, and 100 µg/L and the RNA was isolated to analyze the gene expression by retrotranscription and Real-Time PCR. Forty genes related to the endocrine system, the DNA repair mechanisms, the detoxification mechanisms, oxidative stress, the stress response, the nervous system, hypoxia, energy metabolism, the immune system, and apoptosis were analyzed. Three of the genes, AchE, HSP17.9, and ApA, showed responses to the presence of Fenoxycarb at 1 µg/L, with no statistically significant responses in the rest of the genes and at the remaining concentrations. From the results, it can be concluded that Fenoxycarb shows a weak response at the molecular level in P. acuta in the tested time and concentrations. However, Aplysianin-A, a gene related to immunity, was altered so the long-term effect could be relevant. Therefore, additional research is required to confirm the safety of Fenoxycarb in non-arthropod species in the long term.

Insight into ADHD diagnosis with deep learning on Actimetry: Quantitative interpretation of occlusion maps in age and gender subgroups.

Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in childhood that often persists into adulthood. Objectively diagnosing ADHD can be challenging due to the reliance on subjective questionnaires in clinical assessment. Fortunately, recent advancements in artificial intelligence (AI) have shown promise in providing objective diagnoses through the analysis of medical images or activity recordings. These AI-based techniques have demonstrated accurate ADHD diagnosis; however, the growing complexity of deep learning models has introduced a lack of interpretability. These models often function as black boxes, unable to offer meaningful insights into the data patterns that characterize ADHD. OBJECTIVE: This paper proposes a methodology to interpret the output of an AI-based diagnosis system for combined ADHD in age and gender-stratified populations. METHODS: Our system is based on the analysis of 24 hour-long activity records using Convolutional Neural Networks (CNNs) to classify spectrograms of activity windows. These windows are interpreted using occlusion maps to highlight the time-frequency patterns explaining ADHD activity. RESULTS: Significant differences in the frequency patterns between ADHD and controls both in diurnal and nocturnal activity were found for all the populations. Temporal dispersion also presented differences in the male population. CONCLUSION: The proposed interpretation techniques for CNNs highlighted gender- and age-related differences between ADHD patients and controls. Leveraging these differences could potentially lead to improved diagnostic accuracy, especially if a larger and more balanced dataset is utilized. SIGNIFICANCE: Our findings pave the way for the development of an AI-based diagnosis system for ADHD that offers interpretability, thereby providing valuable insights into the underlying etiology of the disease.

Early intervention in bipolar disorder: the Jano program at Hospital Universitario Marqués de Valdecilla.

UNLABELLED: In order to improve relapse and recurrence prevention in bipolar disorder, the purposes of this paper are: (i) to summarize the evidence published on treatments for this disorder, particularly on psychological interventions in its early phases; (ii) to provide a description of the Jano Intervention and Research Program on the Early Phases of Bipolar Disorder, which is being developed at Valdecilla Hospital (Santander, Spain). Firstly, we review the data from randomized controlled trials and systematic reviews regarding four psychotherapies proven to be effective in the treatment of bipolar disorder: psychoeducation, cognitive-behavioral therapy, family therapy and interpersonal and social rhythm therapy. Secondly, we display a systematic review on the effectiveness of psychological therapies during the early stage of bipolar disorder. Out of 456 studies, all were excluded due to not meeting the inclusion criteria. Finally, we outline the Jano Program, which provides psychiatric management, psychoeducation, psychotherapy and family therapy for patients in the early stage of bipolar disorder. Several standardized clinical, social and neuropsychological tests are administered to the patients at the beginning of the program, and also at 2, 4, 6 and 8 weeks, 3 and 6 months, 1, 2, 3 and 5 years later. CONCLUSIONS: It's necessary to enlarge the sample and finish our data collection in order to determine the effectiveness and efficiency of this kind of program, and specially of its psychological components. Early intervention for bipolar disorder may need to be adapted in some way from usual treatments to better reach our goals.

Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus.

Siderophores play an important role in fungal virulence, serving as trackers for in vivo imaging and as biomarkers of fungal infections. However, siderophore uptake is only partially characterized. As the major cause of aspergillosis, Aspergillus fumigatus is one of the most common airborne fungal pathogens of humans. Here, we demonstrate that this mold species mediates the uptake of iron chelated by the secreted siderophores triacetylfusarinine C (TAFC) and fusarinine C by the major facilitator-type transporters MirB and MirD, respectively. In a murine aspergillosis model, MirB but not MirD was found to be crucial for virulence, indicating that TAFC-mediated uptake plays a dominant role during infection. In the absence of MirB, TAFC becomes inhibitory by decreasing iron availability because the mutant is not able to recognize iron that is chelated by TAFC. MirB-mediated transport was found to tolerate the conjugation of fluorescein isothiocyanate to triacetylfusarinine C, which might aid in the development of siderophore-based antifungals in a Trojan horse approach, particularly as the role of MirB in pathogenicity restrains its mutational inactivation. Taken together, this study identified the first eukaryotic siderophore transporter that is crucial for virulence and elucidated its translational potential as well as its evolutionary conservation. IMPORTANCE Aspergillus fumigatus is responsible for thousands of cases of invasive fungal disease annually. For iron uptake, A. fumigatus secretes so-called siderophores, which are taken up after the binding of environmental iron. Moreover, A. fumigatus can utilize siderophore types that are produced by other fungi or bacteria. Fungal siderophores raised considerable interest due to their role in virulence and their potential for the diagnosis and treatment of fungal infections. Here, we demonstrate that the siderophore transporter MirB is crucial for the virulence of A. fumigatus, which reveals that its substrate, triacetylfusarinine C, is the most important siderophore during infection. We found that in the absence of MirB, TAFC becomes inhibitory by decreasing the availability of environmental iron and that MirB-mediated transport tolerates the derivatization of its substrate, which might aid in the development of siderophore-based antifungals. This study significantly improved the understanding of fungal iron homeostasis and the role of siderophores in interactions with the host.

Influence that job characteristics, personality and burnout have on fatigue in professional drivers.

Objectives. Professional drivers drive for many hours without rest. This factor, in addition to the characteristics of the job, the vehicle, the environment and the driver, causes driver fatigue. Fatigue is one of the most common risk factors when driving because it causes drowsiness, decreases drivers' attention and may make them fall asleep at the wheel. In this article we propose a predictive model for professional drivers using the following variables: age, number of children, time spent at work, time spent inside the vehicle, personality, job characteristics (JDS), job content (JCQ) and burnout. Method. Participants were 509 professional drivers from various transport sectors recruited by non-probabilistic sampling. SPSS version 25.0 was used for statistical analysis. Results. The predictive capacity of variables that cause driver fatigue was determined. Exhaustion best predicts fatigue positively, while openness to experience best predicts it negatively. Burnout and certain personality characteristics are good predictors, whereas other variables, such as JCQ and JDS, are weak predictors. Conclusions. This study extends our knowledge of the factors that cause fatigue in professional drivers and underlines the importance of designing interventions aimed at reducing the incidence of fatigue, promoting greater driver well-being and lowering the incidence of accidents.

Variables that predict burnout in professional drivers.

Objectives. Stress maintained over time leads to a state of exhaustion known as burnout syndrome. This syndrome constitutes an occupational health problem, leading to high absenteeism. It can also mean that workers come to the workplace feeling unwell, which increases occupational collisions and injuries at work. In this study, we developed a predictive model of burnout in professional drivers using the following indicators: age, hours worked, seniority, educational level, fatigue, personality, attitudes toward driving, safety behaviors in the vehicle, and work characteristics and content. Method. A total of 523 professional drivers from different transport sectors, obtained through non-probability sampling, participated in the study. We used SPSS version 25.0 to analyze the data. Results. We determined the predictive capacity of certain variables that affect drivers and cause burnout. Exhaustion can be predicted with fatigue (48.8%), professional efficiency with emotional stability (39.8%) and cynicism with lack of motivation (28%) as the best predictors. Conclusions. The results contribute to a better knowledge of those factors that cause burnout in professional drivers. It is important to design individual interventions to reduce burnout, which would help reduce sick leave and possible collisions, in addition to providing greater well-being for drivers.

DF-8: a specific scale for assessing work fatigue in professional drivers.

The study objective is to create a scale specifically for measuring driver fatigue and to analyze the scale's psychometric properties. The participants were 518 Spanish drivers. We carried out an exploratory factor analysis (EFA) and the first subsample obtained a single-item solution (eight items). We then performed a confirmatory factor analysis (CFA) with a second subsample. The results were root mean square error of approximation (rmsea) = 0.05, comparative fit index (CFI) = 0.94 and Tucker-Lewis index (TLI) = 0.92, which corroborates the previous results and maintains the same number of elements. The resulting dimension shows good reliability. The scale scores were then related to several external correlates and other scales, and showed good convergence and criteria validity. The results indicate that the scale for assessing work fatigue specifically in professional drivers - driver fatigue (DF-8) - is a reliable and valid instrument.

Age, gender, personality, burnout, job characteristics and job content as predictors of driver fatigue.

Objectives. Several studies have shown that one of the most common causes of collision is driver fatigue since fatigue causes drowsiness while driving and this decreases the driver's ability to maneuver the vehicle and increases the probability of their nodding off and falling asleep at the wheel. This may be due to a variety of personal reasons and specific factors connected to working conditions. In the present work we therefore intend to develop a predictive model for fatigue in professional drivers using the following indicators: age, gender, personality, burnout, characteristics and job content. Method. The participants were 516 professional drivers from different transport sectors, obtained through non-probabilistic sampling. SPSS version 25.0 was used for data analysis. Results. The predictive capacity of a number of variables that affect drivers by causing fatigue is determined. Fatigue can be predicted through certain variables, with the best predictor being exhaustion (48.8%). Conclusions. This research contributes to a greater knowledge of the factors that produce fatigue in professional drivers. It highlights the importance of designing interventions to reduce the incidence of fatigue, resulting in greater well-being for the driver and a lower incidence of collisions.

Resveratrol-Based MTDLs to Stimulate Defensive and Regenerative Pathways and Block Early Events in Neurodegenerative Cascades.

By replacing a phenolic ring of (E)-resveratrol with an 1,3,4-oxadiazol-2(3H)-one heterocycle, new resveratrol-based multitarget-directed ligands (MTDLs) were obtained. They were evaluated in several assays related to oxidative stress and inflammation (monoamine oxidases, nuclear erythroid 2-related factor, quinone reductase-2, and oxygen radical trapping) and then in experiments of increasing complexity (neurogenic properties and neuroprotection vs okadaic acid). 5-[(E)-2-(4-Methoxyphenyl)ethenyl]-3-(prop-2-yn-1-yl)-1,3,4-oxadiazol-2(3H)-one (4e) showed a well-balanced MTDL profile: cellular activation of the NRF2-ARE pathway (CD = 9.83 µM), selective inhibition of both hMAO-B and QR2 (IC50s = 8.05 and 0.57 µM), and the best ability to promote hippocampal neurogenesis. It showed a good drug-like profile (positive in vitro central nervous system permeability, good physiological solubility, no glutathione conjugation, and lack of PAINS or Lipinski alerts) and exerted neuroprotective and antioxidant actions in both acute and chronic Alzheimer models using hippocampal tissues. Thus, 4e is an interesting MTDL that could stimulate defensive and regenerative pathways and block early events in neurodegenerative cascades.

Analysis of the impact of three phthalates on the freshwater gastropod Physella acuta at the transcriptional level.

Plastic pollution is one of the leading environmental problems. Phthalates are widely used plastic additives released into the environment. Although the effects of phthalates on vertebrates have been extensively studied, there is a knowledge gap regarding their effects on invertebrates. This work analyzes the impact of three phthalates, diethyl phthalate (DEP), benzyl butyl phthalate (BBP), and bis-(2-ethylhexyl) phthalate (DEHP), on the gastropod Physella acuta at the molecular level to establish the putative pathways involved in its response to them. By real-time PCR, we obtained the expression profile of 30 genes in animals exposed for 1 week to 0.1, 10, and 1000 µg/L of each phthalate. The genes cover DNA repair, detoxification, apoptosis, oxidative and stress responses, immunity, energy reserves, and lipid transport. The results show that while DEP and DEHP did not alter the mRNA levels, BBP modulated almost all the analyzed genes. It can be concluded that the impact of BBP is extensive at the molecular level. However, it cannot be dismissed that the increase in transcriptional activity is a general response due to this compound's well-known role as an endocrine disruptor. Additional research is needed to elucidate the differences observed in the impact of these compounds on the gastropod P. acuta.

Computational Characterization of the Intermixing of Iron Triade (Fe, Co, and Ni) Surfaces and Sub-nanometric Clusters with Atomic Gold.

Dispersion-corrected density functional theory (DFT-D3) is applied to model iron triade (Fe, Co, and Ni) surfaces upon exchange of surface atoms with atomic gold. One first goal is to analyze the contact problem at the triade surface-Au interface and to correlate our findings with recent observations on iron triade nanoparticles (with diameters of around 5 nm) passivated by a few layers of gold. For this purpose, we analyze: (1) the energies of substitution; (2) the restructuring of the iron triade surfaces upon the atomic exchange; (3) the density of the orbitals bearing the largest projection on d(Au) atomic orbitals and, particularly, their overlap with orbitals from neighboring atoms of the triade surfaces; (4) the modification of the electronic density of states; and (5) the redistribution of the electronic density upon intermixing of Au and triade atoms. Inspite of the similarities between Ni, Co, and Fe in the condensed phase, significant differences are found in the features characterizing the exchange process. In particular, we find a better integration of the Au atom on the substitutional site of the Ni(001) surface than on those of the Fe(001) and Co(001) surfaces. This is in agreement with the fact that the electronic density of states is almost indistinguishable before and after Ni-Au intermixing. This outcome is correlated with the experimental observation on the allowing transition of Ni-Au core-shell nanoparticles before reaching the melting temperature. Our second objective is to explore the Au-triade atom intermixing process in sub-nanometric clusters, finding that it is energetically more favored than at solid surfaces yet endothermic at 0 K. This feature is explained as the result of the structural fluxionality characterizing clusters at the sub-nanometer scale. Entropy contributions make mixed Au-Ni clusters more stable than the unmixed counterpart already at 650 K while unmixed Co clusters remain energetically more favored up to 1295 K and iron clusters are predicted to be stable against intermixing over the experimentally relevant range of temperatures (up to 1100 °C). Remarkably, the net charge donated from the three triade atoms to atomic gold upon intermixing is similar in triade sub-nanometeric clusters and at extended triade surfaces. Gold clusters are prone to host Fe, Co, and Ni atoms at the center of their structures and the exchange process is predicted to be exothermic at 0 K even for a small cluster made of 13 atoms. More generally, our work highlights the importance of the polarity of the chemical bond between unlike metal atoms in alloys.

The Distinctive Evolution of orfX Clostridium parabotulinum Strains and Their Botulinum Neurotoxin Type A and F Gene Clusters Is Influenced by Environmental Factors and Gene Interactions via Mobile Genetic Elements.

Of the seven currently known botulinum neurotoxin-producing species of Clostridium, C. parabotulinum, or C. botulinum Group I, is the species associated with the majority of human botulism cases worldwide. Phylogenetic analysis of these bacteria reveals a diverse species with multiple genomic clades. The neurotoxins they produce are also diverse, with over 20 subtypes currently represented. The existence of different bont genes within very similar genomes and of the same bont genes/gene clusters within different bacterial variants/species indicates that they have evolved independently. The neurotoxin genes are associated with one of two toxin gene cluster types containing either hemagglutinin (ha) genes or orfX genes. These genes may be located within the chromosome or extrachromosomal elements such as large plasmids. Although BoNT-producing C parabotulinum bacteria are distributed globally, they are more ubiquitous in certain specific geographic regions. Notably, northern hemisphere strains primarily contain ha gene clusters while southern hemisphere strains have a preponderance of orfX gene clusters. OrfX C. parabotulinum strains constitute a subset of this species that contain highly conserved bont gene clusters having a diverse range of bont genes. While much has been written about strains with ha gene clusters, less attention has been devoted to those with orfX gene clusters. The recent sequencing of 28 orfX C. parabotulinum strains and the availability of an additional 91 strains for analysis provides an opportunity to compare genomic relationships and identify unique toxin gene cluster characteristics and locations within this species subset in depth. The mechanisms behind the independent processes of bacteria evolution and generation of toxin diversity are explored through the examination of bacterial relationships relating to source locations and evidence of horizontal transfer of genetic material among different bacterial variants, particularly concerning bont gene clusters. Analysis of the content and locations of the bont gene clusters offers insights into common mechanisms of genetic transfer, chromosomal integration, and development of diversity among these genes.

Diseases Costs and Impact of the Caring Role on Informal Carers of Children with Neuromuscular Disease.

This study aims to evaluate the costs of informal care for children with neuromuscular disease and evaluate how physical and psychological health is associated with socio-demographic variables. A cross sectional design was used with a convenience sample of 110 carers that participated in this study. Participants were recruited from Spanish hospitals and rare diseases organizations. Economic costs and sociodemographic aspects were assessed using the economic costs questionnaire and the sociodemographic questionnaire. Physical and psychological health was evaluated using the CarerQol-7D, PHQ-15, Barthel Index, Zarit Overload Scale and Satisfaction with Life Scale. Carers of children with neuromuscular disease spent a large percentage of their annual income in physical therapy, psychological care and speech therapy. Informal costs differed according to the degree of dependency of the child. These were higher in those caregivers whose child under their care presented low functional independence. The loss of work productivity was related to marital status, use of professional services and the child's dependency. Finally, carers who were female, single or separated and without a job showed worse physical and psychological health. The results highlighted that carers have to face a number of high costs because of the non-existence of social protection and due to the child's diagnosis.

Effects of Teleassistance on the Quality of Life of People With Rare Neuromuscular Diseases According to Their Degree of Disability.

Rare neuromuscular diseases (RNMDs) are a group of pathologies characterized by a progressive loss of muscular strength, atrophy, fatigue, and other muscle-related symptoms, which affect quality of life (QoL) levels. The low prevalence, high geographical dispersion and disability of these individuals involve difficulties in accessing health and social care services. Teleassistance is presented as a useful tool to perform psychosocial interventions in these situations. The main aim of this research is to assess the effects of a teleassistance psychosocial program on the QoL levels of people with RNMDs who have different levels of disability. A sample of 73 participants was divided into an experimental group (n = 40), which participated in the intervention, and a control wait list group (n = 33). QoL was evaluated through the SIP and the SF-36, and disability through the WHO-DAS II. The participants with a moderate to severe level of disability were those who most benefited from the intervention. The results also revealed that the psychosocial teleassistance program was suitable to improve physical and psychosocial aspects of people suffering from a rare neuromuscular disease with a moderate level of disability, but just psychosocial aspects in those with a severe level of disability.