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.

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.

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

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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..

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.

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.

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.

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.

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.

Trastornos tiroideos en pacientes adultos con insuficiencia renal crónica / Thyroid disorders in adult patients with chronic renal failure

RESUMEN Introducción: el hipotiroidismo puede asociarse a la insuficiencia renal crónica, solapándose sus síntomas. Objetivo: determinar la frecuencia y características clínicas de los trastornos tiroideos silentes en pacientes adultos con insuficiencia renal crónica. Metodología: estudio observacional, correlacional, prospectivo, multicéntrico. Se incluyeron varones y mujeres, mayores de edad, portadores de insuficiencia renal crónica, que asistieron al Hospital Nacional (Itauguá) y Hospital Militar (Asunción) durante 2020. Los sujetos que dieron su consentimiento fueron sometidos a la determinación del perfil tiroideo. Se incluyeron a sujetos en terapia predialítica y dialítica, se excluyeron a conocidos portadores de enfermedades tiroideas. Se midieron variables demográficas y clínicas. Los datos fueron sometidos a estadística descriptiva y analítica. El protocolo fue aprobado por el Comité de Ética de la Universidad Privada del Este. Resultados: ingresaron al estudio 103 mujeres y 115 varones, con edad media 58 y 57 años, respectivamente. Se halló sobrepeso en 52,4 % y obesidad en 16,6 %. El 66 % se encontraba en estadio 5 de insuficiencia renal y predominó la etiología diabética e hipertensiva. La anemia se encontró en 90 %. Respecto al perfil tiroideo, se encontró 20,2 % en rango normal, 12,4 % en hipotiroidismo clínico, 15,6 % en hipotiroidismo subclínico, 20,2 % con síndrome del enfermo eutiroideo y 31,6 % con síndrome T3 bajo. Se halló asociación significativa entre la depuración de creatinina y los estados tiroideos. Conclusión: en 28 % se halló algún grado de hipotiroidismo. Se recomienda el tamizaje del funcionamiento tiroideo en pacientes con insuficiencia renal crónica.

ABSTRACT Introduction: hypothyroidism can be associated with chronic kidney failure and its symptoms can overlap Objectives: to determine the frequency and clinical characteristics of silent thyroid disorders in adult patients with chronic renal failure. Methodology: we conducted an observational, correlational, prospective, multicenter study. We included adults' men and women, with chronic kidney failure, who attended the National Hospital (Itauguá) and the Military Hospital (Asunción) during 2020. The subjects who gave their consent were invited to the determination of the serum thyroid profile. Subjects in predialytic and dialytic therapy were included. Known carriers of thyroid diseases were excluded. Demographic and clinical variables were measured. We applied descriptive and analytical statistics. The protocol was approved by the Ethics Committee of the Private University of the East. Results: we included 103 women and 115 men, with a mean age of 58 and 57 years, respectively. Overweight was found in 52.4 % and obesity in 16.6 %. In 66 % of the cases the patients were in stage 5 of renal failure. Diabetic and hypertensive origin was the predominated etiology. Anemia was found in 90 %. Regarding the thyroid profile, 20.2 % were found in the normal range, 12.4 % in clinical hypothyroidism, 15.6 % in subclinical hypothyroidism, 20.2 % with euthyroid sick syndrome and 31.6 % with low T3 syndrome. A significant association was found between creatinine clearance and thyroid status. Conclusion: 28 % had some degree of hypothyroidism. Thyroid function screening is recommended in patients with chronic renal failure.

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.

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.

Intrusion errors during verbal fluency task in amyotrophic lateral sclerosis.

BACKGROUND: Numerous studies have noted the presence of a dysexecutive component of the ALS-FTD. The most widely replicated result refers to the significantly reduced verbal fluency of ALS patients when compared to healthy people. As ALS patients have motor alterations that interfere with production, qualitative studies have the advantage of being independent of the degree of motor disability and revealing patients' cognitive state. This study examined the production differences between 42 ALS patients who presented with different degrees of dementia and motor impairment and 42 healthy people. Production processes were studied by extending the administration time of a letter fluency task to 2 minutes for the phonemic verbal fluency (PVF) and semantic verbal fluency (SVF) categories. This ensured that the qualitative aspects of verbal fluency were addressed, paying special attention to the new perseverations and intrusions, as well as any clinical correlates that may exist. RESULTS: The ALS patients produced a significantly lower number of responses in PVF (p = .017) and SVF (p = .008). The rest of the indicators for frontal lobe alteration also suggested the existence of a dysfunction. The most remarkable results were the number of intrusions on the PVF task, which was much higher in the ALS group (p = .002). However, the number of perseverations did not differ significantly. CONCLUSIONS: This study highlights the value of intrusions in addressing cognitive deterioration in ALS patients. This deterioration seems to be independent of the degree of motor impairment and of behavioural alterations. Therefore, the value of the intromissions on the verbal fluency task was highlighted as an indicator of a new cognitive alteration, which can be easily evaluated, even retrospectively.

Cabina de desinfección de personas para reducir la transmisión de COVID-19 en la comunidad / Disinfection booth for people to reduce the transmission of COVID-19 in the community

RESUMEN La pandemia de COVID-19 ha puesto a los gobiernos del mundo ante una situación sin precedentes en la cual es necesario tomar decisiones rápidas con respecto a las mejores estrategias para disminuir la transmisión. Como parte de estas estrategias, en muchos lugares del mundo se están implementando cabinas de desinfección de personas en la comunidad. El presente documento busca evaluar la efectividad y seguridad de la cabina de desinfección de personas para uso en la comunidad a través de una búsqueda exhaustiva en las principales bases de datos bibliográficas así como en las prinicipales instituciones relevantes a nivel mundial. Después de realizar la búsqueda, encontramos tres documentos técnicos en los que no se recomienda el uso de estas tecnologías debido a que no hay evidencia suficiente y por ser de potencial riesgo para las personas por afección en mucosas. Otro documento de recomendación de la OMS, si bien no menciona a la tecnología específicamente, menciona que se debería evitar el rociamiento de sustancias desinfectantes en las personas por riesgos en la salud. En conclusión, no encontramos evidencia científica que respalde el uso de esta tecnología.

ABSTRACT The COVID-19 pandemic has put the world's governments in an unprecedented situation in which it is necessary to make quick decisions regarding the best strategies to reduce transmission. As part of these strategies, disinfection booths in the community are being implemented in many parts of the world. This document seeks to evaluate the effectiveness and safety of the disinfection booth for people to use in the community through an exhaustive search in the main bibliographic databases as well as in the main relevant institutions worldwide. After conducting the search, we found three technical documents in which the use of these technologies is not recommended because there is insufficient evidence and because they are of potential risk for people due to mucosal conditions. Another WHO recommendation document, although it does not specifically mention technology, mentions that the spraying of disinfecting substances should be avoided in people due to health risks. In conclusion, we found no scientific evidence to support the use of this technology.

Intervenciones farmacológicas para el tratamiento de la Enfermedad por Coronavirus (COVID-19) / Pharmacological interventions for the treatment of Coronavirus Disease (COVID-19)

RESUMEN Varios fármacos han sido propuestos como alternativas terapéuticas para COVID-19. Se efectuó una búsqueda sistematica en MEDLINE (vía PubMed) hasta el 20 de marzo de 2020, con el fin de identificar la evidencia disponible sobre intervenciones farmacológicas para tratamiento específico de COVID-19. 947 publicaciones fueron identificadas y 15 estudios seleccionados: 3 ensayos clínicos, 5 series de casos y 7 reportes de casos. La calidad de la evidencia procedente de ensayos clínicos fue evaluada según la metodología GRADE. La evidencia existente para hidroxicloroquina, favipiravir y lopinavir/ritonavir procede de ensayos clínicos que reportan resultados favorables para los dos primeros fármacos en tanto que no se observó ningún beneficio al adicionar lopinavir/ritonavir al tratamiento estándar. Sin embargo, debido a las limitaciones metodológicas, la evidencia es de muy baja certeza para hidroxicloroquina y de baja certeza para favipiravir y lopinavir/ritonavir. Respecto al uso de arbidol interferón, o el uso combinado de estos con lopinavir/ritonavir, la evidencia es limitada ya que deriva de serie de casos o reporte de casos con resultados no determinantes. No se identificaron estudios que permitan determinar la eficacia y seguridad de intervenciones farmacológicas frente a COVID-19.

ABSTRACT Several drugs have been proposed as therapeutic alternatives for COVID-19. An electronic systematic search of MEDLINE (via PubMed) was carried out until March 20th 2020, in order to identify the available evidence on pharmacological interventions for specific treatment of COVID-19. The quality of the evidence from clinical trials was evaluated according to the GRADE methodology. 947 publications were identified and 15 studies were selected: 3 clinical trials, 5 case series and 7 case reports. The existing evidence for hydroxychloroquine, favipiravir and lopinavir/ritonavir comes from clinical trials reporting favorable results for the first two drugs, while no benefit was observed when lopinavir/ritonavir was added to standard treatment. However, due to methodological issues, the evidence for hydroxychloroquine is very low. For favipiravir and lopinavir/ritonavir the evidence is low. Regarding the use of arbidol interferon, or the combined use of these with lopinavir/ritonavir, the evidence is limited since it derives from case series or case report with non-determining results. No studies were identified that reliably demonstrate the efficacy and safety of any pharmacological intervention against COVID-19.

Objective ADHD Diagnosis Using Convolutional Neural Networks Over Daily-Life Activity Records.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most common neurobehavioral disorder in children and adolescents. However, its etiology is still unknown, and this hinders the existence of reliable, fast and inexpensive standard diagnostic methods. OBJECTIVE: This paper proposes an end-to-end methodology for automatic diagnosis of the combined type of ADHD. METHODS: Diagnosis is based on the analysis of 24 hour-long activity records using Convolutional Neural Networks to classify spectrograms of activity windows. RESULTS: We achieve up to [Formula: see text] average sensitivity, [Formula: see text] specificity and AUC values over [Formula: see text]. Overall, our figures overcome those obtained by actigraphy-based methods reported in the literature as well as others based on more expensive (and not so convenient) acquisition methods. CONCLUSION: These results reinforce the idea that combining deep learning techniques together with actimetry can lead to a robust and efficient system for objective ADHD diagnosis. SIGNIFICANCE: Reliance on simple activity measurements leads to an inexpensive and non-invasive objective diagn-ostic method, which can be easily implemented with daily devices.

Exploring the Catalytic Properties of Unsupported and TiO2-Supported Cu5 Clusters: CO2 Decomposition to CO and CO2 Photoactivation.

In this work, we explore the decomposition of CO2 on unsupported and TiO2-supported Cu5 clusters via computational modeling, using both finite cluster and periodic slab structures of the rutile TiO2(110) surface. While the energy needed for C=O bond breaking is already significantly reduced upon adsorption onto the unsupported metal catalyst (it drops from 7.8 to 1.3 eV), gas desorption before bond activation is still the inevitable outcome due to the remaining barrier height even at 0 K. However, when the Cu5 cluster itself is supported on TiO2, reactant and product adsorption is strongly enhanced, the barrier for bond breaking is further reduced, and a spontaneous decomposition of the molecule is predicted. This finding is linked to our previous work on charge-transfer processes in the Cu5-TiO2 system triggered by solar photons, since a combination of both phenomena at suitable temperatures would allow for a photoinduced activation of CO2 by sunlight.

The impact and cost-effectiveness of combined HIV prevention scenarios among transgender women sex-workers in Lima, Peru: a mathematical modelling study.

BACKGROUND: HIV incidence remains high among transgender women in Lima, Peru, most of whom report sex work. On the basis of a stakeholder analysis and health system capacity assessment, we designed a mathematical model to guide HIV programmatic planning among transgender women sex workers (TWSW) in Lima. METHODS: Using a deterministic compartmental model, we modelled HIV transmission among TWSW, their stable partners, and their clients to estimate the impact and cost-effectiveness of combinations of interventions compared with the standard of care on reducing HIV incidence over a 10-year period. We simulated HIV transmission accounting for differences in sexual positioning in anal intercourse and condom use by partner type and fitted the model to HIV surveillance data using Latin hypercube sampling. The interventions we considered were 15% relative increase in condom use with clients and 10% relative increase with stable partners; increase in antiretroviral treatment (ART) coverage at CD4 count lower than 500 cells per mm3 and greater than or equal to 500 cells per mm3; and 15% pre-exposure prophylaxis (PrEP) coverage using generic and branded formulations. We considered a basic scenario accounting for current limitations in the Peruvian HIV services and an enhanced scenario assuming achievement of the UNAIDS 90-90-90 targets and general improvements in HIV services. The 50 best fits according to log-likelihood were used to give the minimum and maximum values of intervention effect for each combination. We used disability-adjusted life-years (DALYs) to measure the negative health outcomes associated with HIV infection that could be averted through the interventions investigated and calculated incremental cost-effectiveness ratios to compare their cost-effectiveness. FINDINGS: Under the basic scenario, combining the four interventions of increasing condom use with clients and stable partners, extending ART to people with CD4 count greater than or equal to 500 cells per mm3, and 15% PrEP coverage with generic drugs would avert 47% (range 27-51) of new infections in TWSW, their clients, and their stable partners over 10 years, with an incremental cost-effectiveness ratio of US$509 per DALY averted. Under the enhanced scenario, this strategy would avert 61% (44-64) of new infections among this population with an incremental cost-effectiveness ratio of $1003 per DALY averted. Under both scenarios, implementation of this strategy approaches or surpasses the 50% incidence reduction goal and would represent a cost-effective use of country resources if generic PrEP drugs are used. The total cost of implementing this strategy under the enhanced scenario would be approximately $1·2 million per year over 10 years, corresponding to 10% of the current Global Fund's yearly contribution in Peru. INTERPRETATION: Investments in HIV services among TWSW in Lima would be cost-effective, even under stringent cost-effectiveness criteria when accounting for setting-specific resource constraints. Notable improvements in HIV testing rates, innovative interventions to increase condom use, and reduced PrEP costs will be key to achieving the 50% incidence reduction goal. Modelling studies incorporating stakeholders' perspectives and health system assessments can bring added value to HIV policy making. FUNDING: National Institutes of Health.