Quantum mechanical-based strategies in drug discovery: Finding the pace to new challenges in drug design.

The expansion of the chemical space to tangible libraries containing billions of synthesizable molecules opens exciting opportunities for drug discovery, but also challenges the power of computer-aided drug design to prioritize the best candidates. This directly hits quantum mechanics (QM) methods, which provide chemically accurate properties, but subject to small-sized systems. Preserving accuracy while optimizing the computational cost is at the heart of many efforts to develop high-quality, efficient QM-based strategies, reflected in refined algorithms and computational approaches. The design of QM-tailored physics-based force fields and the coupling of QM with machine learning, in conjunction with the computing performance of supercomputing resources, will enhance the ability to use these methods in drug discovery. The challenge is formidable, but we will undoubtedly see impressive advances that will define a new era.

On the relevance of query definition in the performance of 3D ligand-based virtual screening.

Ligand-based virtual screening (LBVS) methods are widely used to explore the vast chemical space in the search of novel compounds resorting to a variety of properties encoded in 1D, 2D or 3D descriptors. The success of 3D-LBVS is affected by the overlay of molecular pairs, thus making selection of the template compound, search of accessible conformational space and choice of the query conformation to be potential factors that modulate the successful retrieval of actives. This study examines the impact of adopting different choices for the query conformation of the template, paying also attention to the influence exerted by the structural similarity between templates and actives. The analysis is performed using PharmScreen, a 3D LBVS tool that relies on similarity measurements of the hydrophobic/philic pattern of molecules, and Phase Shape, which is based on the alignment of atom triplets followed by refinement of the volume overlap. The study is performed for the original DUD-E+ database and a Morgan Fingerprint filtered version (denoted DUD-E+-Diverse; available in https://github.com/Pharmacelera/Query-models-to-3DLBVS ), which was prepared to minimize the 2D resemblance between template and actives. Although in most cases the query conformation exhibits a mild influence on the overall performance, a critical analysis is made to disclose factors, such as the content of structural features between template and actives and the induction of conformational strain in the template, that underlie the drastic impact of the query definition in the recovery of actives for certain targets. The findings of this research also provide valuable guidance for assisting the selection of the query definition in 3D LBVS campaigns.

Real-Time Object Detection for Autonomous Solar Farm Inspection via UAVs.

Robotic missions for solar farm inspection demand agile and precise object detection strategies. This paper introduces an innovative keypoint-based object detection framework specifically designed for real-time solar farm inspections with UAVs. Moving away from conventional bounding box or segmentation methods, our technique focuses on detecting the vertices of solar panels, which provides a richer granularity than traditional approaches. Drawing inspiration from CenterNet, our architecture is optimized for embedded platforms like the NVIDIA AGX Jetson Orin, achieving close to 60 FPS at a resolution of 1024 ×1376 pixels, thus outperforming the camera's operational frequency. Such a real-time capability is essential for efficient robotic operations in time-critical industrial asset inspection environments. The design of our model emphasizes reduced computational demand, positioning it as a practical solution for real-world deployment. Additionally, the integration of active learning strategies promises a considerable reduction in annotation efforts and strengthens the model's operational feasibility. In summary, our research emphasizes the advantages of keypoint-based object detection, offering a practical and effective approach for real-time solar farm inspections with UAVs.

Screening of organic chemicals associated to virgin low-density polyethylene microplastic pellets exposed to the Mediterranean Sea environment by combining gas chromatography and liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry.

In this work, organic chemicals associated with microplastics (MPs) exposed to a coastal anthropogenized environment for up to eight weeks have been screened for, in order to discern the (de)sorption dynamics of chemicals in the marine ecosystem. Low-density polyethylene (LDPE) pellets were studied since they represent primary MPs used by the plastic industry and a relevant input of MPs into the oceans. To maximize the coverage of chemicals that could be detected, both liquid and gas chromatography coupled to quadrupole-time-of-flight (GC-QTOF and LC-QTOF, respectively) were used. In the case of LC-QTOF, an electrospray ionization source was employed, and the compounds were investigated by combining suspect and non-target screening workflows. The GC-QTOF was equipped with an electron ionization source and compounds were screened in raw and derivatized (silylated) extracts by deconvolution and contrast to high- and low-resolution libraries. A total of 50 compounds of multifarious classes were tentatively identified. Among them, melamine and 2-ethylhexyl salicylate (EHS) were detected in the original MPs but were rapidly desorbed. Melamine was completely released into the marine environment, while EHS was partly released but a portion remained bound to the MPs. On the other hand, many other chemicals of both anthropogenic (e.g. phenanthrene or benzophenone) and natural origin (e.g. betaine and several fatty acids) accumulated onto MPs over time. Quantification of 12 unequivocally identified chemicals resulted into a total concentration of 810 µg/kg after MPs exposure for 8 weeks.

Perspectives of primary care physicians in Spain on malaria: a cross-sectional survey and retrospective review of cases.

BACKGROUND: In Spain, the risk of imported malaria has increased in recent years due to the rise in international travel and migration. Little is known about the knowledge, information sources, clinical practice, and specific needs of primary care physicians (PCPs) concerning malaria despite the pivotal role played by these professionals in managing the health of tourists. The objective of this study was to assess the knowledge, attitudes, and practices of PCPs in Spain regarding malaria. METHODS: This research analyses data from (1) a cross-sectional nationwide survey assessing the knowledge and attitudes of PCPs regarding malaria, and (2) a retrospective review of 373 malaria cases appearing in primary care medical records (PCMRs) in the Madrid area over the past 15 years to determine how cases were documented, managed, or characterized in the primary care setting. RESULTS: The survey findings reveal a modest level of self-perceived familiarity with malaria (221/360, 57.6%), even though 32.8% of the practitioners reported having delivered care for confirmed or suspected cases of the disease, these practitioners had greater knowledge of malaria (80.4%) compared to physicians who reported not having delivered care for malaria (19.6%, p < 0.001). Ten percent of the survey participants did not know the name of the mosquito that transmits malaria, and only 40.7% would promptly request malaria testing for a traveller with symptoms after a trip to an endemic area. Responses provided by younger PCPs varied to a greater extent than those of their more experienced colleagues regarding prevention practices and patient management. A review of PCMRs showed that only 65% of all patients were recorded as such. Among those registered, only 40.3% had a documented malaria episode, and of those, only 16.6% received proper follow-up. Only 23.7% of the patients with a PCMR had a record that specifically indicated travel to an endemic country or travel classified as visiting friends and relatives (VFR). CONCLUSIONS: The findings of this study underscore the critical role of PCPs in the field of travel medicine, particularly given the increase in imported malaria cases. These results highlight the need for targeted training in travel medicine and the need to ensure optimal patient education in care settings.

Intravenous Ascorbic Acid for the Prevention of Postreperfusion Syndrome in Orthotopic Liver Transplantation: Protocol for a Randomized Controlled Trial.

BACKGROUND: Liver transplantation is the last therapeutic option for patients with end-stage liver disease. Postreperfusion syndrome (PRS), defined as a fall in mean arterial pressure of more than 30% within the first 5 minutes after reperfusion of at least 1 minute, can occur in liver transplantation as a deep hemodynamic instability with associated hyperfibrinolysis immediately after reperfusion of the new graft. Its incidence has remained unchanged since it was first described in 1987. PRS is related to ischemia-reperfusion (I/R) injury, whose pathophysiology involves the release of several mediators from both the donor and the recipient. The antioxidant effect of ascorbic acid has been studied in resuscitating patients with septic shock and burns. Even today, there are publications with conflicting results, and there is a need for further studies to confirm or rule out the usefulness of this drug in this group of patients. The addition of ascorbic acid to preservation solutions used in solid organ transplantation is under investigation to harness its antioxidant effect and mitigate I/R injury. Since PRS could be considered a manifestation of I/R injury, we believe that the possible beneficial effect of ascorbic acid on the occurrence of PRS should be investigated. OBJECTIVE: The aim of this randomized controlled trial is to assess the benefits of ascorbic acid over saline in the development of PRS in adult liver transplantation. METHODS: We plan to conduct a single-center randomized controlled trial at the Hospital Universitario Ramón y Cajal in Spain. A total of 70 participants aged 18 years or older undergoing liver transplantation will be randomized to receive either ascorbic acid or saline. The primary outcome will be the difference between groups in the incidence of PRS. The randomized controlled trial will be conducted under conditions of respect for fundamental human rights and ethical principles governing biomedical research involving human participants and in accordance with the international recommendations contained in the Declaration of Helsinki and its subsequent revisions. RESULTS: The enrollment process began in 2020. A total of 35 patients have been recruited so far. Data cleaning and analysis are expected to occur in the first months of 2024. Results are expected around the middle of 2024. CONCLUSIONS: We believe that this study could be particularly relevant because it will be the first to analyze the clinical effect of ascorbic acid in liver transplantation. Moreover, we believe that this study fills an important gap in the knowledge of the potential benefits of ascorbic acid in the field of liver transplantation, particularly in relation to PRS. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database 2020-000123-39; https://tinyurl.com/2cfzddw8; ClinicalTrials.gov NCT05754242; https://tinyurl.com/346vw7sm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50091.

The genomic history of the indigenous people of the Canary Islands.

The indigenous population of the Canary Islands, which colonized the archipelago around the 3rd century CE, provides both a window into the past of North Africa and a unique model to explore the effects of insularity. We generate genome-wide data from 40 individuals from the seven islands, dated between the 3rd-16rd centuries CE. Along with components already present in Moroccan Neolithic populations, the Canarian natives show signatures related to Bronze Age expansions in Eurasia and trans-Saharan migrations. The lack of gene flow between islands and constant or decreasing effective population sizes suggest that populations were isolated. While some island populations maintained relatively high genetic diversity, with the only detected bottleneck coinciding with the colonization time, other islands with fewer natural resources show the effects of insularity and isolation. Finally, consistent genetic differentiation between eastern and western islands points to a more complex colonization process than previously thought.

Screening and Biological Evaluation of Soluble Epoxide Hydrolase Inhibitors: Assessing the Role of Hydrophobicity in the Pharmacophore-Guided Search of Novel Hits.

The human soluble epoxide hydrolase (sEH) is a bifunctional enzyme that modulates the levels of regulatory epoxy lipids. The hydrolase activity is carried out by a catalytic triad located at the center of a wide L-shaped binding site, which contains two hydrophobic subpockets at both sides. On the basis of these structural features, it can be assumed that desolvation is a major factor in determining the maximal achievable affinity that can be attained for this pocket. Accordingly, hydrophobic descriptors may be better suited to the search of novel hits targeting this enzyme. This study examines the suitability of quantum mechanically derived hydrophobic descriptors in the discovery of novel sEH inhibitors. To this end, three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophores were generated by combining electrostatic and steric or alternatively hydrophobic and hydrogen-bond parameters in conjunction with a tailored list of 76 known sEH inhibitors. The pharmacophore models were then validated by using two external sets chosen (i) to rank the potency of four distinct series of compounds and (ii) to discriminate actives from decoys, using in both cases datasets taken from the literature. Finally, a prospective study was performed including a virtual screening of two chemical libraries to identify new potential hits, which were subsequently experimentally tested for their inhibitory activity on human, rat, and mouse sEH. The use of hydrophobic-based descriptors led to the identification of six compounds as inhibitors of the human enzyme with IC50 < 20 nM, including two with IC50 values of 0.4 and 0.7 nM. The results support the use of hydrophobic descriptors as a valuable tool in the search of novel scaffolds that encode a proper hydrophilic/hydrophobic distribution complementary to the target's binding site.

Kinesiotaping in discopathies and degenerative spinal diseases: systematic review / Kinesiotaping em discopatias e doenças degenerativas da coluna vertebral: revisão sistemática / Kinesiotaping en discopatías y enfermedades degenerativas de la columna vertebral: revisión sistemática

ABSTRACT Neuromuscular taping or kinesiotaping is a technique widely used in spinal disorders. However, the scientific evidence of its use in discopathies and degenerative spine pathology is unknown. This study aimed to analyze the published clinical trials on neuromuscular taping in subjects with discopathies and degenerative spinal injuries. For this purpose, a literature search was performed following PRISMA guidelines in the following databases: PubMed, Web of Science (WOS), Scopus, Medline, and Cinahl. In analyzing bias and methodological quality, we used: the PEDro scale, Van Tulder criteria, and risk of bias analysis of the Cochrane Collaboration. A total of 5 articles were included that obtained a mean score of 6.2 on the PEDro scale. There is moderate evidence that, in the short term, neuromuscular taping reduces analgesic consumption and improves the range of motion and muscle strength in the posterior musculature. In addition, there is limited evidence that it can improve quality, while the scientific evidence on the effect of neuromuscular taping on pain is contradictory. The application of neuromuscular taping on discopathies and degenerative processes of the spine should be cautiously undertaken until more conclusive results are obtained, and the long-term effects are assessed. Level of evidence I; Systematic review.

Resumo: A bandagem neuromuscular ou kinesiotaping é uma técnica de bandagem amplamente utilizada em distúrbios da coluna vertebral. Entretanto, a evidência científica para seu uso em discopatias e na patologia degenerativa da coluna são desconhecidas. Objetivo: O objetivo deste trabalho foi analisar ensaios clínicos publicados sobre bandagem neuromuscular em sujeitos com discopatias e lesões degenerativas da coluna vertebral. Para este fim, foi realizada uma pesquisa bibliográfica seguindo as diretrizes do PRISMA nas seguintes bases de dados: PubMed, Web of Science (WOS), Scopus, Medline e Cinahl. Na análise de viés e qualidade metodológica, foram utilizados: escala PEDro, critérios de Van Tulder e análise de risco de viés da Colaboração Cochrane. Um total de 5 artigos foi incluído com uma pontuação média de 6,2 na escala PEDro. Há evidências moderadas de que, a curto prazo, a bandagem neuromuscular reduz o consumo de analgésicos, melhora a amplitude de movimento e a força muscular na musculatura posterior. Além disso, há evidências limitadas de que pode melhorar a qualidade, enquanto as evidências científicas sobre o efeito da bandagem neuromuscular na dor são contraditórias. A aplicação da bandagem neuromuscular em discopatias e processos degenerativos da coluna vertebral deve ser feita com cautela até que resultados mais conclusivos sejam obtidos e os efeitos a longo prazo sejam avaliados. Nível de evidência I; Revisão sistemática.

Resumen: El vendaje neuromuscular o kinesiotaping es una técnica de vendaje que se utiliza ampliamente en trastornos raquídeos. Sin embargo, se desconoce la evidencia científica de uso en discopatías y patología degenerativa de la columna. El objetivo de este trabajo consistió en analizar los ensayos clínicos publicados sobre el vendaje neuromuscular en sujetos con discopatías y lesiones degenerativas del raquis. Para ello, se realizó una búsqueda bibliográfica siguiendo las directrices PRISMA en las siguientes bases de datos: PubMed, Web of Science (WOS), Scopus, Medline y Cinahl. En el análisis de sesgo y calidad metodológica se utilizaron: escala PEDro, criterios de Van Tulder y análisis del riesgo de sesgo de la Colaboración Cochrane. Se incluyeron un total de 5 artículos que obtuvieron una puntuación media de 6,2 en la escala PEDro. Existe evidencia moderada de que, a corto plazo, el vendaje neuromuscular reduce el consumo de analgésicos, mejora el rango de movimiento y fuerza muscular en la musculatura posterior. Además, existe evidencia limitada de que puede mejorar la calidad, mientras que la evidencia científica sobre el efecto del vendaje neuromuscular en el dolor es contradictoria. La aplicación de vendaje neuromuscular es discopatías y procesos degenerativos del raquis debe realizarse con cautela a la espera de que se obtengan resultados más concluyentes y se valoren los efectos a largo plazo. Nivel de evidencia I; Revisión sistemática.

Single-nucleotide polymorphism associations with efficacy and toxicity in metastatic castration-resistant prostate cancer treated with cabazitaxel.

Background: The aim of this study was to evaluate the impact of certain single-nucleotide polymorphisms (SNPs) in cabazitaxel activity and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: 56 SNPs in five genes (CYP3A4, CYP3A5, ABCB1, TUBB1 and CYP2C8) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed. Results:TUBB1-rs151352 (hazard ratio: 0.52) and CYP2C8-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and CYP2C8-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. ABCB1-rs17327624 correlated with severe toxicity ≥grade 3 (odds ratio: 8.56) and CYP2C8-rs11572093 with asthenia (odds ratio: 8.12). Conclusion: Genetic variants in mCRPC patients could explain different outcomes with cabazitaxel. Nonetheless, the small sample size and the high number of SNPs analyzed mean that the results are only hypothesis-generating and require further validation.

Assisted versus referred pharmacy smoking interventions for patients with thoracic malignancies or pulmonary nodules.

BACKGROUND: Tobacco use is the foremost preventable cause of death, disease, and disability in the United States. Continued tobacco use in malignant disease contributes to treatment failure and disease progression. Pharmacists are pivotal to tobacco cessation counseling, management, and follow up. METHODS: This retrospective, observational, single-center, cohort study of ambulatory cancer patients was designed to assess the impact of assisted versus "Ask, Advise, Refer" (AAR) pharmacy-driven smoking cessation interventions on patient-reported quit rates at 30- and 90-days. Those included were currently smoking or recently quit adults with a thoracic malignancy or nodule. Those in the assisted intervention were offered nicotine replacement therapy (NRT) for free according to a personalized quit plan. After July 1, 2020, patients were enrolled in the AAR intervention, whereby participants were referred to obtain NRT through insurance or external resources. Both clinical interventions were provided as standard of care. RESULTS: 129 participants were included (assisted n = 83; AAR n = 46) with baseline characteristics evenly matched. After excluding those unable to be reached at 30-days, 30 (44.8%) in the assisted intervention quit smoking versus 11 (27.5%) in the AAR intervention, p = 0.08. Lung cancer patients were more likely to report quitting at 30-days in the assisted intervention, 16 (64.0%) versus 5 (29.4%) in the AAR intervention, p = 0.03. After excluding those unable to be reached at 90-days, 30 (45.5%) in the assisted intervention quit versus 11 (35.5%) in the AAR intervention, p = 0.35. CONCLUSIONS: Pharmacy-led smoking cessation initiatives that include providing NRT are especially impactful on smoking cessation in lung cancer patients.

Mimicking human ingestion of microplastics: Oral bioaccessibility tests of bisphenol A and phthalate esters under fed and fasted states.

Notwithstanding the fact that microplastic fragments were encountered in the human stool, little effort has been geared towards elucidating the impact of chemical additives upon the human health. In this work, standardized bioaccessibility tests under both fasting and fed conditions are herein applied to the investigation of human oral bioaccessibility of plastic additives and monomers (i.e. eight phthalate esters (PAEs) and bisphenol A (BPA)) in low-density polyethylene (LDPE) and polyvinyl chloride (PVC) microplastics. The generation of phthalate monoesters is evaluated in the time course of the bioaccessibility tests. Maximum gastric and gastrointestinal bioaccessibility fractions are obtained for dimethyl phthalate, diethyl phthalate and BPA, within the range of 55-83%, 40-68% and 37-67%, respectively, increasing to 56-92% and 41-70% for dimethyl phthalate and diethyl phthalate, respectively, whenever their hydrolysis products are considered. Bioaccessibility fractions of polar PAEs are dependent upon the physicochemical characteristics of the microplastics, with greater bioaccessibility for the rubbery polymer (LDPE). With the method herein proposed, oral bioaccessible pools of moderately to non-polar PAEs can be also accurately assessed for risk-assessment explorations, with values ranging from 1.8% to 32.2%, with again significantly larger desorption percentages for LDPE. Our results suggested that the highest gastric/gastrointestinal bioaccessibility of the eight PAEs and BPA is reached under fed-state gastrointestinal extraction conditions because of the larger amounts of surface-active biomolecules. Even including the bioaccessibility factor within human risk assessment/exposure studies to microplastics, concentrations of dimethyl phthalate, di-n-butyl phthalate and BPA exceeding 0.3% (w/w) may pose severe risks after oral uptake in contrast to the more hydrophobic congeners for which concentrations above 3% (w/w), except for diethylhexyl phthalate, would be tolerated.

Effects of Caffeine Consumption on Attention Deficit Hyperactivity Disorder (ADHD) Treatment: A Systematic Review of Animal Studies.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. ADHD impairments arise from irregularities primarily in dopamine (DA) and norepinephrine (NE) circuits within the prefrontal cortex. Due to ADHD medication's controversial side effects and high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caffeine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evidence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal studies is lacking. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to 1 September 2021. Caffeine treatment increases attention and improves learning, memory, and olfactory discrimination without altering blood pressure and body weight. These results are supported at the neuronal/molecular level. Nonetheless, the role of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that the cognitive effects of caffeine found in animal models could be translated to human ADHD, particularly during adolescence.

Tuning HAuCl4/Sodium Citrate Stoichiometry to Fabricate Chitosan-Au Nanocomposites.

Nanocomposite engineering of biosensors, biomaterials, and flexible electronics demand a highly tunable synthesis of precursor materials to achieve enhanced or desired properties. However, this process remains limited due to the need for proper synthesis-property strategies. Herein, we report on the ability to synthesize chitosan-gold nanocomposite thin films (CS/AuNP) with tunable properties by chemically reducing HAuCl4 in chitosan solutions and different HAuCl4/sodium citrate molar relationships. The structure, electrical, and relaxation properties of nanocomposites have been investigated as a function of HAuCl4/sodium citrate molar relation. It was shown that gold particle size, conductivity, Vogel temperature (glass transition), and water content strongly depend upon HAuCl4/sodium citrate relationships. Two relaxation processes have been observed in nanocomposites; the α-relaxation process, related to a glass transition in wet CS/AuNP films, and the σ-relaxation related to the local diffusion process of ions in a disordered system. The ability to fine-tune both α- and σ-relaxations may be exploited in the proper design of functional materials for biosensors, biomaterials, and flexible electronics applications.

Cariprazina como alternativa farmacológica en el tratamiento de la psicosis en la enfermedad de Parkinson / Cariprazine as a pharmacological alternative in the treatment of psychosis in Parkinson's disease

Introducción: La enfermedad de Parkinson (EP) se presenta de forma frecuente como complicación con la presencia de síntomas psicóticos.ObjetivoDescribir el proceso terapéutico de los síntomas psicóticos asociado a la EP evaluando posibles alternativas farmacológicas.Caso clínicoMujer de 41 años con diagnóstico precoz de EP (con diagnóstico de EP a edad temprana), mala respuesta al tratamiento dopaminérgico, con la presencia de síntomas psicóticos y la necesidad de implantación de neuroestimulación profunda. Ingresa por una nueva presentación de síntomas psicóticos estando en tratamiento con dosis bajas de levodopa.ResultadoSe produce una mala respuesta a la clozapina y se ensaya el tratamiento con cariprazina con mejoría sintomática, buena tolerabilidad y nulos efectos secundarios.ConclusionesCariprazina puede ser una alternativa ante el fracaso del tratamiento con clozapina. (AU)

Introduction: Parkinson's disease (PD) frequently presents as a complication with the presence of psychotic symptoms.ObjectiveTo describe the therapeutic process of PD-related psychotic symptoms, evaluating possible pharmacological alternatives.Clinical caseA 41-year-old woman with early diagnosis of PD (diagnosed at an early age), poor response to dopaminergic treatment, with the presence of psychotic symptoms and the need for a deep brain stimulator. The patient was admitted due to new onset of psychotic symptoms while on low-dose levodopa.ResultAfter poor response to treatment with clozapine, cariprazine was tried with improvement of symptoms, good tolerability, and no side effects.ConclusionsCariprazine may be an alternative in the event of clozapine treatment failure. (AU)

Development and application of an in-house library and workflow for gas chromatography-electron ionization-accurate-mass/high-resolution mass spectrometry screening of environmental samples.

This work presents an optimized gas chromatography-electron ionization-high-resolution mass spectrometry (GC-EI-HRMS) screening method. Different method parameters affecting data processing with the Agilent Unknowns Analysis SureMass deconvolution software were optimized in order to achieve the best compromise between false positives and false negatives. To this end, an accurate-mass library of 26 model compounds was created. Then, five replicates of mussel extracts were spiked with a mixture of these 26 compounds at two concentration levels (10 and 100 ng/g dry weight in mussel, 50 and 500 ng/mL in extract) and injected in the GC-EI-HRMS system. The results of these experiments showed that accurate mass tolerance and pure weight factor (combination of reverse-forward library search) are the most critical factors. The validation of the developed method afforded screening detection limits in the 2.5-5 ng range for passive sampler extracts and 1-2 ng/g for mussel sample extracts, and limits of quantification in the 0.6-3.2 ng and 0.1-1.8 ng/g range, for the same type of samples, respectively, for 17 model analytes. Once the method was optimized, an accurate-mass HRMS library, containing retention indexes, with ca. 355 spectra of derivatized and non-derivatized compounds was generated. This library (freely available at https://doi.org/10.5281/zenodo.5647960 ), together with a modified Agilent Pesticides Library of over 800 compounds, was applied to the screening of passive samplers, both of polydimethylsiloxane and polar chemical integrative samplers (POCIS), and mussel samples collected in Galicia (NW Spain), where a total of 75 chemicals could be identified.

Zenithal isotropic object counting by localization using adversarial training.

Counting objects in images is a very time-consuming task for humans that yields to errors caused by repetitiveness and boredom. In this paper, we present a novel object counting method that, unlike most of the recent works that focus on the regression of a density map, performs the counting procedure by localizing each single object. This key difference allows us to provide not only an accurate count but the position of every counted object, information that can be critical in some areas such as precision agriculture. The method is designed in two steps: first, a CNN is in charge of mapping arbitrary objects to blob-like structures. Then, using a Laplacian of Gaussian (LoG) filter, we are able to gather the position of all detected objects. We also propose a semi-adversarial training procedure that, combined with the former design, improves the result by a large margin. After evaluating the method on two public benchmarks of isometric objects, we stay on par with the state of the art while being able to provide extra position information.

Cuidados y atención hospitalaria en un niño con osteogénesis imperfecta

RESUMEN Introducción: La osteogénesis imperfecta es un trastorno hereditario del tejido conectivo que condiciona fragilidad ósea y susceptibilidad a fracturas. Es una enfermedad sistémica con posibilidad de afectación esquelética y extraesquelética. Su cuidado es, por tanto, multidisciplinar y el papel de los profesionales de la pediatría es primordial. Objetivo: Aportar información sobre las características y el cuidado de la osteogénesis imperfecta, a través de la descripción de un caso clínico. Pesentación del caso: Niño de 2 años y 3 meses de edad, de origen argelino y de padres consanguíneos. Fue diagnosticado en su país de origen de una forma recesiva de osteogénesis imperfecta en los primeros meses de vida por fracturas a repetición. Conclusiones: La manipulación cuidadosa, el control del dolor y el apoyo emocional, entre otros, son fundamentales. Los profesionales de pediatría, como agentes activos en estos casos, deben conocer las peculiaridades del cuidado de pacientes con osteogénesis imperfecta para evitar y detectar complicaciones asociadas. En las familias el conocimiento conlleva además, una toma de conciencia sanitaria acerca de esta enfermedad.

ABSTRACT Introduction: Osteogenesis imperfecta is an hereditary disorder of the connective tissue that conditions to bone fragility and sensitivity to fractures. It is a systemic disease with a possibility of skeletic and extraskeletic affectations. Therefore, its care is multidisciplinary and the role of Pediatrics professionals is paramount. Objective: Contribute with information on the characteristics and the care of osteogenesis imperfecta through the description of a clinical case. Case presentation: Boy of 2 years and 3 months old, from Algeria and with parents by blood. He was diagnosed in his country with a recesive osteogenesis imperfecta in the first months of life due to repeated fractures. Conclusions: Careful handling, pain control and emotional support, among others, are important. Pediatric professionals as active agents in these cases should know the peculiarities of the care of patients with osteogenesis imperfecta to avoid and detect asssociated complications. In the families, knowledge on this also entails sanitary awareness on the disease.

On the Use of Ridge Gap Waveguide Technology for the Design of Transverse Stub Resonant Antenna Arrays.

This paper presents some considerations on the design of a novel antenna consisting of the combination of a transverse stubs (TS) array excited by Ridge Gap Waveguides (RGWs), as well as a discussion of the experimental results obtained from a prototype that was manufactured and measured. A combination of Continuous Transverse Stubs (CTSs) is used as the starting point. Subsequently, the CTSs are modified to include some metallic blockers that split each CTS into a combination (array) of shorter TSs. This is performed in order to excite each individual TS column using a different RGW; thus, ensuring a close to uniform field distribution in the transverse plane of the TS arrays. Hence, the directivity of the antenna is increased. As a series-feed configuration is considered, the antenna keeps a resonant behaviour, having a narrow-band response. A Corporate Feeding Network (CFN) using the aforementioned RGW technology placed in the same layer as the rest of the antenna is included in the design. The radiating area of the antenna is, finally, 5.88λ0×7.12λ0 with a simulated peak gain of 26.2 dBi and a Side Lobe Level (SLL) below -13 dB. A prototype is manufactured and tested. The simulated and measured radiation patterns maintain similar shapes to those of the simulations, with very similar angular widths in both main planes, although the frequency corresponding to the highest directivity changes to 31.8 GHz. A matching bandwidth of 517 MHz and a gain of 24.5 is, finally, achieved at that frequency.

Oral conditions of the pre-Hispanic mummies of Gran Canaria (Canary Islands, Spain).

OBJECTIVE: To analyse the oral conditions of pre-Hispanic mummies from Gran Canaria (5th-11th centuries AD), comparing the results with published data from the non-mummified population. MATERIALS: 440 teeth and 764 alveoli of 30 adult mummies. METHODS: Macroscopic examination of pathological and non-pathological features of the oral cavity, using standardized criteria. RESULTS: The mummies reveal frequent dental caries (11.8%), especially affecting molars (27.6%), a high prevalence of calculus (66.3%) and periodontal disease (34.9%). The average wear is characterized by extensive dentine exposure. Periapical lesions (10.6%) and antemortem tooth loss (AMTL) (15.9%) are common. A high percentage of individuals exhibit linear enamel hypoplasia (LEH) (84%). Except for periodontitis, the data indicate the absence of significant statistical differences between the mummies and the skeletonized sample. CONCLUSIONS: The profile of the dental pathologies of the mummies indicates a carbohydrate-rich diet that contained abrasive grit from the stone querns used to grind cereals. Comparison of the oral conditions of mummified and skeletonized remains shows no differences in access to food resources, reinforcing the recent rejection of the traditional interpretation of the mummies as the pre-eminent status group of Canarian society. SIGNIFICANCE: This is the first study to delve into the oral conditions of pre-Hispanic mummified remains from Gran Canaria. The results have implications for the framing of research questions based on the social status of these mummies. LIMITATION: The preserved sample of mummified remains of ancient Canarians is small. SUGGESTION FOR FURTHER RESEARCH: Comparative analysis from a diachronic perspective would improve understanding of the historical development of ancient Canarians.