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Abstract Background The rate of suicide attempts by patients with bipolar disorder is high. In addition to patient and country specific factors, environmental factors may contribute to suicidal behavior. Sunlight has multiple diverse impacts on human physiology and behavior. Solar insolation is defined as the electromagnetic energy from the sun striking a surface area on earth. We previously found that a large change in solar insolation between the minimum and maximum monthly values was associated with an increased risk of suicide attempts in patients with bipolar I disorder. Methods The association between solar insolation and a history of suicide attempts in bipolar disorder was again investigated using an international database with 15% more data and more sites at diverse locations and countries. Results Data were available from 5641 patients with bipolar I disorder living at a wide range of latitudes in 41 countries in both hemispheres. A large change in solar insolation between the minimum and maximum monthly values was associated with a history of suicide attempts in patients with bipolar I disorder, a replication of our prior analysis. The estimated model also associated state sponsored religion in the onset country, female gender, a history of alcohol or substance abuse, and being part of a younger birth cohort with a history of suicide attempts. Conclusions A large change between the minimum and maximum monthly values of solar insolation was associated with a history of suicide attempts in bipolar I disorder, replicating our prior research. Physicians should be aware that daylight has wide ranging physiological and psychiatric impacts, and that living with large changes in solar insolation may be associated with an increased suicide risk.

Abstract G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in humans. The binding and dissociation of ligands tunes the inherent conformational flexibility of these important drug targets towards distinct functional states. Here we show how to trigger and resolve protein-ligand interaction dynamics within the human adenosine A2A receptor. For this, we designed seven photochemical affinity switches derived from the anti-Parkinson’s drug istradefylline. In a rational approach based on UV/Vis spectroscopy, time-resolved absorption spectroscopy, differential scanning fluorimetry and cryo-crystallography, we identified compounds suitable for time-resolved serial crystallography. Our analysis of millisecond-scale dynamics revealed how trans-to-cis isomerization shifts selected istradefylline derivatives within the binding pocket. Depending on the chemical nature of the ligand, interactions between extracellular loops 2 and 3, acting as a lid on the binding pocket, are disrupted and rearrangement of the orthosteric binding pocket is invoked upon ligand dissociation. This innovative approach provides insights into GPCR dynamics at the atomic level, offering potential for developing novel pharmaceuticals.

Abstract Objective This study aims to investigate the interrelationship of risk factors for suicidal behaviour and their influence on attempt severity in a sample of adolescents who have recently attempted suicide. For it a network analyse was performed. Method Data from a sample of adolescents from 12 to 17 years of age with documented suicide attempts were collected and analysed in the context of a larger study conducted in Spain called SURVIVE. Several factors were examined including age, sex, depression, trauma, impulsivity, and substance abuse. Graph analysis was performed to identify relationships and centrality measures among these factors. Results A total of 267 participants were enrolled: 233 females and 34 males with a mean age of 15.00 years (SD = 1.52). The results indicate that age and sex do not have a notable relationship with attempt severity in adolescents. Emotional and behavioural difficulties, measured by the Strengths and Difficulties Questionnaire (SDQ), have the greatest influence on other variables. Depression and childhood trauma show varying degrees of association with suicidal behaviour, as does motor impulsivity. Substance use does not appear to be strongly related to suicide attempt severity. The number of suicide attempts is strongly correlated with emotional and behavioural difficulties, depression, and childhood trauma. Lethality of suicide attempts and intensity of suicidal ideation do not show significant associations with the other variables. Conclusion This study identifies significant risk factors for adolescent suicide. Emotional and behavioural symptoms, depression, and childhood trauma are strongly linked to suicidal behaviour. However, age, sex, and substance abuse show minimal correlation. Assessing emotional difficulties and depressive symptoms using specific questionnaires could be crucial in evaluating suicidal behaviour in adolescents.

The application of personalized medicine in patients with first-episode psychosis (FEP) requires tools for classifying patients according to their response to treatment, considering both treatment efficacy and toxicity. However, several limitations have hindered its translation into clinical practice. Here, we describe the rationale, aims and methodology of Applied Pharmacogenetics to Predict Response to Treatment of First Psychotic Episode (the FarmaPRED-PEP project), which aims to develop and validate predictive algorithms to classify FEP patients according to their response to antipsychotics, thereby allowing the most appropriate treatment strategy to be selected. These predictors will integrate, through machine learning techniques, pharmacogenetic (measured as polygenic risk scores) and epigenetic data together with clinical, sociodemographic, environmental, and neuroanatomical data. To do this, the FarmaPRED-PEP project will use data from two already recruited cohorts: the PEPS cohort from the “Genotype-Phenotype Interaction and Environment. Application to a Predictive Model in First Psychotic Episodes” study (the PEPs study from the Spanish abbreviation) (N=335) and the PAFIP cohort from “Clinical Program on Early Phases of Psychosis” (PAFIP from the Spanish abbreviation) (N = 350). These cohorts will be used to create the predictor, which will then be validated in a new cohort, the FarmaPRED cohort (N = 300). The FarmaPRED-PEP project has been designed to overcome several of the limitations identified in pharmacogenetic studies in psychiatry: (1) the sample size; (2) the phenotype heterogeneity and its definition; (3) the complexity of the phenotype and (4) the gender perspective. The global reach of the FarmaPRED-PEP project is to facilitate the effective deployment of precision medicine in national health systems.

Objective: This study is an open clinical trial. The aim of this study was to show the changes that occur in the viscoelastic properties of the plantar fascia (twenty healthy volunteers) measured by SEL and the changes in the plantar fascia temperature measured by thermography after the application of a 448 kHz capacitive resistive monopolar radiofrequency (CRMR) in active healthy subjects immediately after treatment and at the 1-week follow-up.Methods: Furthermore, to analyze if an intervention with 448 kHz CRMR in the plantar fascia of the dominant lower limb produces a thermal response in the plantar fascia of the non-dominant lower limb. The final objective was to analyze the level of association between the viscoelastic properties of the PF and the temperature before and after the intervention with 448 kHz CRMR.Results: Our results showed that a temperature change, which was measured by thermography, occurred in the plantar fascia after a single intervention (T0-T1) and at the 1-week follow up (T1-T2).Conclusion: However, no changes were found in the viscoelastic properties of the plantar fascia after the intervention or at the 1-week follow up. This is the first study to investigate changes in both plantar fascia viscoelastic properties and in plantar fascia temperature after a radiofrequency intervention.

IntroductionFormula feeding is the only viable nutrition alternative for infants 0–6mos who cannot breastfeed. Among the drawbacks of formula feeding, however, is potential dilution or concentration errors in the formula during preparation that may lead to infant health issues. The present study aimed to investigate the accuracy of caregiver measurements as they prepared infant formula under multiple conditions, compared with manufacturer specifications.MethodsA diverse sample of caregivers (N = 84) participated in this cross-over experimental study. Participants hand-scooped infant formula powder and poured water to prepare 4oz. and 7oz. feedings, using both a standardized set of infant formula products and participants’ own products. Linear mixed effects models were used to estimate fixed effects of target amount (4oz. versus 7oz) and products (participant versus researcher) on mean absolute percent error (MAPE) of measurement.ResultsAcross all conditions MAPE was significantly greater for measuring powder than for water (9.0% vs. 4.4%; p

Abstract background A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the ‘chemsex’ context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. Clinical finding After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3 mg/dl — elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3 weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. Conclusions The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

Serial and time-resolved macromolecular crystallography are on the rise. However, beam time at X-ray free-electron lasers is limited and most third-generation synchrotron-based macromolecular crystallography beamlines do not offer the necessary infrastructure yet. Here, a new setup is demonstrated, based on the JUNGFRAU detector and Jungfraujoch data-acquisition system, that enables collection of kilohertz serial crystallography data at fourth-generation synchrotrons. More importantly, it is shown that this setup is capable of collecting multiple-time-point time-resolved protein dynamics at kilohertz rates, allowing the probing of microsecond to second dynamics at synchrotrons in a fraction of the time needed previously. A high-quality complete X-ray dataset was obtained within 1 min from lysozyme microcrystals, and the dynamics of the light-driven sodium-pump membrane protein KR2 with a time resolution of 1 ms could be demonstrated. To make the setup more accessible for researchers, downstream data handling and analysis will be automated to allow on-the-fly spot finding and indexing, as well as data processing.

In X-ray macromolecular crystallography (MX), single-wavelength anomalous dispersion (SAD) and multi-wavelength anomalous dispersion (MAD) techniques are commonly used for obtaining experimental phases. For an MX synchrotron beamline to support SAD and MAD techniques it is a prerequisite to have a reliable, fast and well automated energy scan routine. This work reports on a continuous energy scan procedure newly implemented at the BioMAX MX beamline at MAX IV Laboratory. The continuous energy scan is fully automated, capable of measuring accurate fluorescence counts over the absorption edge of interest while minimizing the sample exposure to X-rays, and is about a factor of five faster compared with a conventional step scan previously operational at BioMAX. The implementation of the continuous energy scan facilitates the prompt access to the anomalous scattering data, required for the SAD and MAD experiments.

El avance tecnológico y el cambiante panorama mundial han planteado retos y oportunidades únicos a los sistemas educativos de todo el mundo. Por ejemplo, se ha introducido en muchos currículos la enseñanza de la programación y el pensamiento computacional como recoge la reciente ley educativa, LOMLOE, en España. Esta incorporación implica la preparación del profesorado en el orden metodológico, didáctico y tecnológico para afrontar este desafío. Por ello, se ha diseñado y validado una escala para medir las actitudes de los docentes de Educación Primaria hacia la programación, considerándola como un recurso para desarrollar el pensamiento computacional. La metodología empleada ha sido el método Delphi, con la participación de doce expertos con un alto nivel de competencia experta. Tras un riguroso proceso de dos rondas, se llegó a un consenso y se estableció la estructura final de la escala. La escala se compone de 33 ítems distribuidos en cinco dimensiones: autoeficacia, percepción de utilidad social, relevancia de la enseñanza para los estudiantes, interés y percepción en función del sexo. Según el panel de expertos, la escala de medición es válida para conocer el nivel de autoeficacia, interés y percepción de utilidad y relevancia de los docentes hacia la programación.

Abstract Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. Conclusion UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Cell therapy has proven to be a promising treatment for a range of neurological disorders, including Parkinson Disease, drug-resistant epilepsy, and stroke, by restoring function after brain damage. Nevertheless, evaluating the true effectiveness of these therapeutic interventions requires a deep understanding of the functional integration of grafted cells into existing neural networks. This review explores a powerful arsenal of molecular techniques revolutionizing our ability to unveil functional integration of grafted cells within the host brain. From precise manipulation of neuronal activity to pinpoint the functional contribution of transplanted cells by using opto- and chemo-genetics, to real-time monitoring of neuronal dynamics shedding light on functional connectivity within the reconstructed circuits by using genetically encoded (calcium) indicators in vivo. Finally, structural reconstruction and mapping communication pathways between grafted and host neurons can be achieved by monosynaptic tracing with viral vectors. The cutting-edge toolbox presented here holds immense promise for elucidating the impact of cell therapy on neural circuitry and guiding the development of more effective treatments for neurological disorders.

BackgroundThere are environmental factors that may contribute to the onset of myopia. This study aims to evaluate the children’s lifestyle changes before and after the COVID-19 lockdown and how they can influence their vision.MethodsThe same questionnaire was administered to children aged between 5 and 7 in Spain every year in September before (2017–2019) and after the COVID-19 lockdown (2020–2021). All the children also passed a vision exam consisting of the measurement of visual acuity (VA) and determination of objective and subjective refraction. Children were classified as myopes, pre-myopes, or hyperopes. The cut-off points to define the refractive error were established according to the value of the spherical equivalent (SE): hyperopia (SE > +0,75D), myopia (SE ≤ −0,5D), or pre-myopia (−0.5D 0.05). Regarding the spherical equivalent, in the pre-COVID period, the mean value was 0.75 ± 2.09D and after the COVID lockdown, it was 0.47 ± 1.88D (p

Abstract Background Individuals with serious mental illness often do not receive guideline-concordant metabolic screening and human immunodeficiency virus (HIV) testing, contributing to increased morbidity and premature mortality. This study evaluates the effectiveness of CRANIUM (Cardiometabolic Risk Assessment and treatment through a Novel Integration model for Underserved populations with Mental illness), an intervention to increase metabolic screening and HIV testing among patients with serious mental illness in a community mental health clinic compared to usual care. Methods The study used a quasi-experimental design, prospectively comparing a preventive care screening intervention at one community mental health clinic (n = 536 patients) to usual care at the remaining clinics within an urban behavioural health system (n = 4,847 patients). Psychiatrists at the intervention site received training in preventive health screening and had access to a primary care consultant, screening and treatment algorithms, patient registries, and a peer support specialist. Outcomes were the change in screening rates of A1c, lipid, and HIV testing post-intervention at the intervention site compared to usual care sites. Results Rates of lipid screening and HIV testing increased significantly at the intervention site compared to usual care, with and without multivariable adjustment [Lipid: aOR 1.90, 95% CI 1.32–2.75, P = .001; HIV: aOR 23.42, 95% CI 5.94–92.41, P

Summary: Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Abstract Background The widespread use of nano-biomaterials (NBMs) has increased the chance of human exposure. Although ingestion is one of the major routes of exposure to NBMs, it is not thoroughly studied to date. NBMs are expected to be dramatically modified following the transit into the oral-gastric-intestinal (OGI) tract. How these transformations affect their interaction with intestinal cells is still poorly understood. NBMs of different chemical nature—lipid-surfactant nanoparticles (LSNPs), carbon nanoparticles (CNPs), surface modified Fe3O4 nanoparticles (FNPs) and hydroxyapatite nanoparticles (HNPs)—were treated in a simulated human digestive system (SHDS) and then characterised. The biological effects of SHDS-treated and untreated NBMs were evaluated on primary (HCoEpiC) and immortalised (Caco-2, HCT116) epithelial intestinal cells and on an intestinal barrier model. Results The application of the in vitro SDHS modified the biocompatibility of NBMs on gastrointestinal cells. The differences between SHDS-treated and untreated NBMs could be attributed to the irreversible modification of the NBMs in the SHDS. Aggregation was detected for all NBMs regardless of their chemical nature, while pH- or enzyme-mediated partial degradation was detected for hydroxyapatite or polymer-coated iron oxide nanoparticles and lipid nanoparticles, respectively. The formation of a bio-corona, which contains proteases, was also demonstrated on all the analysed NBMs. In viability assays, undifferentiated primary cells were more sensitive than immortalised cells to digested NBMs, but neither pristine nor treated NBMs affected the intestinal barrier viability and permeability. SHDS-treated NBMs up-regulated the tight junction genes (claudin 3 and 5, occludin, zonula occludens 1) in intestinal barrier, with different patterns between each NBM, and increase the expression of both pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-22, IL-10). Notably, none of these NBMs showed any significant genotoxic effect. Conclusions Overall, the results add a piece of evidence on the importance of applying validated in vitro SHDS models for the assessment of NBM intestinal toxicity/biocompatibility. We propose the association of chemical and microscopic characterization, SHDS and in vitro tests on both immortalised and primary cells as a robust screening pipeline useful to monitor the changes in the physico-chemical properties of ingested NBMs and their effects on intestinal cells.

Acute myocardial ischemia induces hyperkalemia (accumulation of extracellular potassium), a major perpetrator of lethal reentrant ventricular arrhythmias. Despite considerable experimental efforts to explain this pathology in the last decades, the intimate mechanisms behind hyperkalemia remain partially unknown. In order to investigate these mechanisms, we developed a novel computational model of acute myocardial ischemia which couples a) an electrophysiologically detailed human cardiomyocyte model that incorporates modifications to account for ischemia-induced changes in transmembrane currents, with b) a model of cardiac tissue and extracellular K+ transport. The resulting model is able to reproduce and explain the triphasic time course of extracellular K+ concentration within the ischemic zone, with values of [K+]o close to 14 mmol/L in the central ischemic zone after 30 min. In addition, the formation of a [K+]o border zone of approximately 1.2 cm 15 min after the onset of ischemia is predicted by the model. Our results indicate that the primary rising phase of [K+]o is mainly due to the imbalance between K+ efflux, that increases slightly, and K+ influx, that follows a reduction of the NaK pump activity by more than 50%. The onset of the plateau phase is caused by the appearance of electrical alternans (a novel mechanism identified by the model), which cause an abrupt reduction in the K+ efflux. After the plateau, the secondary rising phase of [K+]o is caused by a subsequent imbalance between the K+ influx, which continues to decrease slowly, and the K+ efflux, which remains almost constant. Further, the study shows that the modulation of these mechanisms by the electrotonic coupling is the main responsible for the formation of the ischemic border zone in tissue, with K+ transport playing only a minor role. Finally, the results of the model indicate that the injury current established between the healthy and the altered tissue is not sufficient to depolarize non-ischemic cells within the healthy tissue.

Abstract Objectives To characterise the motion of pulmonary tumours during stereotactic body radiation therapy (SBRT) and to evaluate different margins when creating the planning target volume (PTV) on a single 4D CT scan (4DCT). Methods We conducted a retrospective single-site analysis on 30 patients undergoing lung SBRT. Two 4DCTs (4DCT1 and 4DCT2) were performed on all patients. First, motion was recorded for each 4DCT in anterior–posterior (AP), superior-inferior (SI) and rightleft (RL) directions. Then, we used 3 different margins (3,4 and 5 mm) to create the PTV, from the internal target volume (ITV) of 4DCT1 only (PTV D1 + 3, PTV D1 + 4, PTV D1 + 5). We compared, using the Dice coefficient, the volumes of these 3 PTVs, to the PTV actually used for the treatment (PTVttt). Finally, new treatment plans were calculated using only these 3 PTVs. We studied the ratio of the D2%, D50% and D98% between each new plan and the plan actually used for the treatment (D2% PTVttt, D50% PTVttt, D50% ITVttt D98% PTVttt). Results 30 lesions were studied. The greatest motion was observed in the SI axis (8.8 ± 6.6 [0.4–25.8] mm). The Dice index was higher when comparing PTVttt to PTV D1 + 4 mm (0.89 ± 0.04 [0.82–0.98]). Large differences were observed when comparing plans relative to PTVttt and PTV D1 + 3 for D98% PTVttt (0.85 ± 0.24 [0.19–1.00]). and also for D98% ITVttt (0.93 ± 0.12 [0.4–1.0]).D98% PTVttt (0.85 ± 0.24 [0.19–1.00], p value = 0.003) was statistically different when comparing plans relative to PTVttt and PTV D1 + 3. No stastistically differences were observed when comparing plans relative to PTVttt and PTV D1 + 4. A difference greater than 10% relative to D98% PTVttt was found for only in one UL lesion, located under the carina. Conclusion A single 4DCT appears feasible for upper lobe lesions located above the carina, using a 4-mm margin to generate the PTV. Advance in knowledge Propostion of a personalized SBRT treatment (number of 4DCT, margins) according to tumor location (above or under the carina).

Abstract Gamma-aminobutyric acid (GABA)-releasing interneurons modulate neuronal network activity in the brain by inhibiting other neurons. The alteration or absence of these cells disrupts the balance between excitatory and inhibitory processes, leading to neurological disorders such as epilepsy. In this regard, cell-based therapy may be an alternative therapeutic approach. We generated light-sensitive human embryonic stem cell (hESC)-derived GABAergic interneurons (hdIN) and tested their functionality. After 35 days in vitro (DIV), hdINs showed electrophysiological properties and spontaneous synaptic currents comparable to mature neurons. In co-culture with human cortical neurons and after transplantation (AT) into human brain tissue resected from patients with drug-resistant epilepsy, light-activated channelrhodopsin-2 (ChR2) expressing hdINs induced postsynaptic currents in human neurons, strongly suggesting functional efferent synapse formation. These results provide a proof-of-concept that hESC-derived neurons can integrate and modulate the activity of a human host neuronal network. Therefore, this study supports the possibility of precise temporal control of network excitability by transplantation of light-sensitive interneurons.

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients’ increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients.

Ecuadorian small producers use crossbred animals with a low level of genetic improvement, which are fed with alternative feeds to decrease production costs. The objective of this study was to evaluate the effects of geographical location and three diets according to the amount of cassava and taro incorporated into the feed (T1 conventional feed; T2 and T3 with 32% and 42% of cassava and taro, respectively) in pigs reared under the backyard system. The results did not show many differences between the treatments for morphological traits; however, between geographical locations, significant differences were evidenced. The fat content from the first rib was higher in the T1 group. The intramuscular fat percentage was higher in the T1 group, contrary to the protein levels, which were higher in the T3 group in Esmeraldas and the T2 group in Ro Chico. In the gastrointestinal tract (GIT) and its attached organs, differences were found in the empty stomach weight, full and empty small intestine weight, liver weight, and total GIT weight, with the T2 and T3 groups having the largest and heaviest. Cassava and taro did not affect the morphometric behavior and quality of the carcass but increased the amount of protein in the meat and the weight of the GIT. Geographical location was also observed to have a significant effect.

The emerging field of Advanced Air Mobility (AAM) holds great promise for revolutionizing transportation by enabling the efficient, safe, and sustainable movement of people and goods in urban and regional environments. AAM encompasses a wide range of electric vertical take-off and landing (eVTOL) aircraft and infrastructure that support their operations. In this work, we first present a new airspace structure by considering different layers for standard-performing vehicles (SPVs) and high-performing vehicles (HPVs), new AAM services for accommodating such a structure, and a holistic contingency management concept for a safe and efficient traffic environment. We then identify the requirements and development process of a testing and simulation infrastructure for AAM demonstrations, which specifically aim to explore the decentralized architecture of the proposed concept and its use cases. To demonstrate the full capability of AAM, we develop an infrastructure that includes advanced U-space services, real and simulated platforms that are suitable for future AAM use cases such as air cargo delivery and air taxi operations, and a co-simulation environment that allows all of the AAM elements to interact with each other in harmony. The considered infrastructure is envisioned to be used in AAM integration-related efforts, especially those focusing on U-space service deployment over a complex traffic environment and those analyzing the interaction between the operator, the U-space service provider (USSP), and the air traffic controller (ATC).

Advanced Air Mobility (AAM) is a concept that is expected to transform the current air transportation system and provide more flexibility, agility, and accessibility by extending the operations to urban environments. This study focuses on flight test, integration, and analysis considerations for the feasibility of the future AAM concept and showcases the outputs of the Air Mobility Urban-Large Experimental Demonstration (AMU-LED) project demonstrations at Cranfield University. The purpose of the Cranfield demonstrations is to explore the integrated decentralized architecture of the AAM concept with layered airspace structure through various use cases within a co-simulation environment consisting of real and simulated standard-performing vehicle (SPV) and high-performing vehicle (HPV) flights, manned, and general aviation flights. Throughout the real and simulated flights, advanced U-space services are demonstrated and contingency management activities, including emergency operations and landing, are tested within the developed co-simulation environment. Moreover, flight tests are verified and validated through key performance indicator analysis, along with a social acceptance study. Future recommendations on relevant industrial and regulative activities are provided.

Abstract Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p

Summary: Background: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. Findings: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28–3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13–2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63– 4.80) or troponin (OR 1.89; 95% 1.03–3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61–2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96–5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17–2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. Interpretation: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. Funding: NIH.

Purpose. This study was aimed at verifying both the intraobserver and interobserver reliability of measuring plantar fascia stiffness for a given image in healthy active adults. Methodology. This study is reported following the Guidelines of Reporting Reliability and Agreement Studies. A total of 20 plantar fascia from healthy volunteers were analyzed. The thickness of the plantar fascia was measured vertically from the anterior edge of the inferior calcaneal border to the inferior border of the plantar fascia and the ultrasound elastography measurement was taken at the calcaneal insertion of the plantar fascia with the region of interest one centimeter away from the insertion. Results. The ultrasound strain elastography measurements: the right intraobserver 1 showed an ICC value of 0.9 and the left intraobserver 1 showed an ICC value of 0.78, while the right intraobserver 2 showed an ICC value of 0.91 and the left intraobserver 2 showed an ICC value of 0.83. Interobserver measurements showed excellent reliability with a right ICC value of 0.8 and a left ICC value of 0.9 for the plantar fascia thickness measurements. Discussion. The results of this study showed a strong correlation between left and right plantar fascia thickness. The intraobserver reliability was excellent for both plantar fascia ultrasound strain elastography and thickness measurements, with interobserver measurements showing excellent reliability.

Abstract To describe fundus autofluorescence (FAF) patterns in premature infants and to determine whether FAF increases gradually with increasing post-gestational age. This was a cross-sectional, observational and descriptive case series. FAF images were obtained from patients screened for Retinopathy of Prematurity. The presence of the following hypo-autofluorescence areas/structures was graded and ranked: macular pigment (foveal centre), optic nerve head, peripapillary vessels/vascular arcade (PP/VA), and equatorial vessels (EqV). Ranks were attributed to the number of structures visualized from the posterior pole towards the periphery. The rank of FAF could then be analysed by Spearman’s correlation against age. Additionally, patients were divided by age into group 1 ( 40 WCGA). Differences between groups were tested with the Mann–Whitney U test. Thirteen patients were analysed. The mean WCGA at examination was 47.85 weeks. Spearman’s correlation showed a strong positive correlation (r = 0.714) (P = 0.006) of FAF and WCGA. The Mann–Whitney U test revealed that the PP/VA and EqV were significantly more visible at > 40 WCGA than at

Abstract Background Feline leishmaniosis is a vector-borne parasitic disease caused by Leishmania spp. Leishmania infection in dogs is prevalent in the Mediterranean basin, but in other animals, such as cats, it could also play a role in the epidemiology of the disease. Information on the geographical distribution and epidemiological features of L. infantum infection in cats is scarce, particularly in urban stray cats living in regions where canine leishmaniosis is endemic. As diagnosis can be challenging, combining different serological and molecular methods is a useful approach. Our aim was to investigate the prevalence of infection of L. infantum in apparently healthy stray cats in an endemic region of Spain (Zaragoza city) using serological and molecular methods, and to compare the results of the different techniques. Methods The prevalence of Leishmania infection was studied in stray cats captured in urban and peri-urban areas of Zaragoza. Blood was collected from each animal for serology and molecular analysis. Three serological methods, namely the immunofluorescent antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA) and western blot (WB), were used to detect L. infantum antibodies and a real-time PCR (qPCR) assay was used to detect L. infantum DNA. The results were analyzed by Fisher’s exact test and Cohen’s kappa statistic (κ) to assess the level of agreement between the diagnostic techniques. Results Serological analysis of blood samples from 180 stray cats revealed 2.2% (4/179) Leishmania infection positivity by IFAT, 2.8% (5/179) by ELISA and 14.5% (26/179) by WB. Leishmania DNA was detected by qPCR in 5.6% (10/179) of the cats. Sixteen cats (8.9%) tested positive by only one serological technique and four tested positive by all three serological methods used. The overall rate of infected cats (calculated as the number of cats seropositive and/or qPCR positive) was 15.6%, and only two cats tested positive by all the diagnostic methods. A significant association was found between male cats and a positive qPCR result. Comparison of the techniques revealed a fair agreement in seropositivity between blood qPCR and IFAT (κ = 0.26), blood qPCR and ELISA (κ = 0.24), WB and ELISA (κ = 0.37) and WB and IFAT (κ = 0.40). The highest agreement between seropositive results was between IFAT and ELISA (κ = 0.89), and the lowest was between blood qPCR and WB (κ = 0.19). The prevalence of the feline leukemia virus antigen was 4.49% (8/178 cats) and that of the feline immunodeficiency virus (FIV) antibody was 6.74% (12/178), while co-infection with both retroviruses was observed in one female cat (1/178). Leishmania ELISA and IFAT seropositivity were statistically associated with FIV status by the chi-square test. Conclusions The results obtained in this study, using serological tests and qPCR, indicate the existence of L. infantum asymptomatic infection in apparently healthy stray cats in the city of Zaragoza, an endemic area in Spain.

Objective To study changes in supraspinatus tendon elasticity after a 448 kHz capacitive resistive monopolar radiofrequency (CRMR) intervention in professional badminton players. Design Double-blinded randomized clinical trial. Setting All participants were recruited in a private care practice. Participants were randomized to receive either a CRMR treatment (n = 19) or placebo (n = 19). Subjects Professional badminton players (n = 38). Intervention A total of nine intervention (three per week) with CRMR at 448 kHz were carried out in the experimental group. The same intervention without an active CRMR current was carried out in the control group. Main measures Mean values of three different regions of the supraspinatus tendon were reported at baseline (T1), immediately after the intervention (T2) and one week after the end of the whole intervention program (T3) using quantitative ultrasound strain elastography (SEL). Results There were statistically significant differences in the supraspinatus tendon elasticity immediately after the intervention (p=

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme.

Background: The development of an integral and global treatment to improve the quality of life in those with fibromyalgia syndrome (FMS) is challenging. The aim of this study is to investigate the impact of whole-body photobiomodulation (PBM) on pain perception, functionality, quality of soft tissue, central sensitisation and psychological factors in patients suffering with FMS. Methods: This study is a randomised, placebo-controlled clinical trial. A total of 44 participants will be recruited in a private care practice and randomised to receive either a whole-body PBM therapy programme or placebo in the same care centre. The parameters of the PBM programme are as follows: wavelengths of red and near-infrared LEDs 50:50 ratio with 660–850 nanometers; fluence of 25.2 J/cm 2 ; treatment time of 1200 s and a total power emitted of 967 W. Treatment sessions will be 3 times weekly for a period of 4 weeks, totalling 12 treatment sessions. Primary outcome will be pain (Numeric Pain Rating Scale; Widespread Pain Index; Symptom Severity Score). Secondary outcomes will be functionality (Fibromyalgia Impact Questionnaire; the Leisure Time Physical Activity Instrument), quality of soft tissue (elastography), central sensitisation (pain pressure threshold and the Autonomic Symptom Profile) and psychological factors (Pain Catastrophising scale, Tampa Scale, Self-Efficacy questionnaire). Assessments will be at baseline (T1), after session 6 (T2), after treatment (T3) and 2 weeks (T4), 3 (T5) and 6 (T6) month follow-up. Discussion: PBM therapy has been shown to reduce pain and inflammation and to increase the rate of tissue repair for a wide range of conditions, but its potential use as a whole-body treatment in FM is yet to be explored. This trial will investigate whether whole-body PBM therapy is effective at reducing pain intensity, improving functionality, quality of soft tissue, central sensitisation symptoms and psychological measurements. Furthermore, 3- and 6-month follow-up will investigate long-term efficacy of this treatment. Trial registration: NCT04248972. Registered on January 29, 2020, https://clinicaltrials.gov/ct2/show/NCT04248972?term=navarro-ledesma+santiago&draw=2&rank=2 .

IntroductionAlthough salvage and adjuvant radiotherapy (RT) are effective in prostate cancer (PC) patients, 30%–40% of men will have disease progression. The objective was to describe the pattern of recurrence in PC patients with biochemical failure (BF) following postoperative RT.MethodsWe retrospectively analyzed 935 PC patients treated from 2009 to 2019 with adjuvant or salvage RT at the Institut de Cancérologie de l’Ouest. Of these, 205 (22%) developed BF of whom 166 underwent imaging. Patients with identified radiologic failure prior any specific treatment were included to determine the site of relapse categorized as local (L)-only, locoregional (LR), or metastatic (M) recurrence. Main disease characteristics and RT fields were examined in relation to sites of recurrence.ResultsOne hundred forty-one patients were identified with 244 sites of failure on imaging. Of these, 108 patients had received RT to the PB alone and 33 RT to the PB and pelvic lymph nodes (PB+PLN). Androgen-deprivation therapy was used concomitantly in 50 patients (35%). The median PSA at imaging was 1.6 ng/ml (range, 0–86.7). In all, 74 patients (52%) had M disease (44% in the PB group and 79% in the PB+PLN group), 61 (43%) had LR failure (52% in the PB alone group and 15% in the PB+PLN group), and six (4%) had L-only failure, at a median of 26.7 months (range, 5–110.3) from RT. Metastases were in extra-pelvic LN (37 (15%)), bones (66 (27%)), and visceral organs (eight (3%)). Fifty-three (48%) of the pelvic LN failures in the PB group would have been encompassed by standard PLN RT volume.ConclusionWe found that most patients evaluated for BF after postoperative RT recurred outside the RT field. Isolated pelvic nodal failure was rare in those receiving RT to the PB+PLN but accounted for half of failures in those receiving PB alone RT. Imaging directed salvage treatment could be helpful to personalize radiation therapy plan.

Introduction: Childhood obesity is a principal concern worldwide. Guatemalan households have the highest prevalence of double burden of malnutrition in the world. These households are self-identified as indigenous and live with lower incomes in rural communities. However, there are limited data on risk factors for childhood obesity and limited information regarding the school environments, especially in rural communities. The objectives of this study were to determine the prevalence of overweight and obesity in a sample of rural schoolchildren, evaluate whether there is significant variability across schools, and characterize the food environment around public elementary schools in rural communities. Methods: A cross-sectional study was conducted in four rural public schools within three villages of El Progreso, a Department (state) of Guatemala, located about 60 km east of Guatemala City. Anthropometric measures and sociodemographic information for 398 schoolchildren and their mothers were collected in 2018. Environmental audits of food outlets and food advertisements were completed for a 250- and 500-meter radius around schools. Food outlets and food advertisements were categorized as healthy and less healthy, or acceptable or not acceptable, respectively, using international protocols. One-way ANOVA was used to compare schools and continuous demographic variables. Fisher’s LSD post hoc test was used to examine differences between schools. Chi-Squared tests were conducted to evaluate differences between categorical demographic variables, overweight and obesity, and variables regarding food environments. A logistic regression was used to examine factors associated with overweight and obesity and variability across schools, adjusted for household income, child sex and age, and maternal education and age. Results: The overall percentage of overweight and obesity among schoolchildren across all four schools was 32.4%. There was a higher percentage of less healthful food outlets compared to healthful food outlets and overall food outlets within

This study evaluated the influence of rearing system (cultured vs. wild rearing systems), and fish sex on carcass and flesh traits of A. rivulatus, raised in Ecuador. Three hundred mature specimens from A. rivulatus were captured, 150 from each origin. Slaughter yield and dress-out resulted similar for both rearing system, and average fillet yield for cultured fish was significantly higher than for wild fish, while cooking loss was significantly lower. Dress-out was significantly higher in females. Significant differences were found in wet percentage, ash, fat and protein content in both rearing systems, but only wet percentage was significantly affected by sex. Palmitic, oleic and arachidonic acids had the maximum percentage of saturated (SFA) and mono/poly unsaturated (MUFA/ PUFA) fatty acids, respectively. In cultured and wild fish, differentiations were also found in PUFA/SFA, docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA), atherogenicity (IA), and thrombogenicity (IT) indices, along with P, K, Mg, Cu and Fe. Sex and rearing system significantly influenced most of the analyzed characteristics of carcass and flesh of A. rivulatus. Fillet high yield and its proximate composition categorize A. rivulatus as a suitable food. These results provide valuable nutritional information about native species for consumers in Ecuador. Highlights: • The rearing system (cultured vs. wild rearing systems), and fish sex affect the carcass and flesh traits of A. rivulatus. • Fillet high yield and its proximate composition categorize A. rivulatus as a suitable food. • The proximate composition of fillet from cultured A. rivulatus is more adequate than those of wild A. rivulatus. • The cultured A. rivulatus contains higher n-3 and n-6 PUFA percentages and adequate n-3/n-6 ratio.

Pork production in Ecuador is of significant economic and nutritional importance. Many of these operations are family- or backyard-based and utilize alternative feed ingredients to reduce production costs. The current study aimed to determine the chemical composition of cooked cassava and taro, and to evaluate their inclusion in the feed of backyard pigs during the growth and fattening phases. A total of 42 castrated pigs from two geographic locations in Ecuador were studied over a period of 100 days, during which their weight and measurements were recorded at three-week intervals. At the end of the experiment, ileum samples were collected from the slaughtered pigs in order to calculate the apparent digestibility of the feed. The crude protein levels of cassava and taro were found to be 3.2% and 2.1%, respectively. The combination of cooked cassava and taro was found to be a suitable replacement for corn, with the best results observed in the group receiving a diet incorporating 21% each of cassava and taro. Analysis of the ileal content also revealed that this group exhibited the highest nitrogen assimilation from the diet.

The abolition of the milk quota system in April 2015 has implied a transition towards a new “system” in which non-policy and non-EU elements have become important drivers of the EU dairy market. In terms of its contribution, after reviewing some of the existing literature, this article presents a theoretical framework to understand “irregular” supply behaviour, while it empirically identifies an “inverse” supply curve for the EU dairy sector. In doing so, milk prices have been decomposed by following the procedure proposed by James P. Houck. This exercise confirms the non-reversibility, and therefore an asymmetric response, in the behaviour of milk supply for most EU Member States. Moreover, this article also presents the results of a “stress” test of the dairy sector in order to analyse the responses of dairy production in a context of the asymmetrical behaviour of dairy farmers and assess the competitiveness of the dairy sector at Member State level. The outcomes emphasise the high competitiveness of the Irish dairy sector and suggest a deterioration of the competitiveness in the case of the United Kingdom and France. From the policy-making perspective, the identification of this type of farmer’s reactions is key for an appropriate design of policy interventions and crisis management strategies.

Purpose Most modeling studies on radiofrequency cardiac ablation (RFCA) are based on limited-domain models, which means the computational domain is restricted to a few centimeters of myocardium and blood around the active electrode. When mimicking constant power RFCA procedures (e.g., atrial fibrillation ablation) it is important to know how much power is absorbed around the active electrode and how much in the rest of the tissues before reaching the dispersive electrode. Methods 3D thorax full models were built by progressively incorporating different organs and tissues with simplified geometries (cardiac chamber, cardiac wall, subcutaneous tissue and skin, spine, lungs and aorta). Other 2D limited-domain models were also built based on fragments of myocardium and blood. The electrical problem was solved for each model to estimate the spatial power distribution around the active electrode. Results From 79 to 82% of the power was absorbed in a 4 cm-radius sphere around the active electrode in the full thorax model at active electrode insertion depths of between 0.5 and 2.5 mm, while the impedance values ranged from 104 to 118 Ω, which were consistent with those found (from 83 to 103 Ω) in a 4 cm radius cylindrical limited domain model. Conclusion The applied power in limited-domain RFCA models is approximately 80% of that applied in full thorax models, which is equivalent to the power programed in a clinical setting.

La acuicultura favorece la soberanía alimentaria en Ecuador, mantiene sus medios de vida y potencia el incremento de los ingresos de la unidad familiar. La especie de agua dulce Cichlasoma festae representa una importante especie de gran uso local. En este estudio nuestro objetivo fue modelizar el crecimiento de alevines de Cichlasoma festae producidos en sistemas intensivos con tecnología Biofloc. El estudio duró 90 días y se llevó a cabo en la Finca experimental “La María”, en la Universidad Técnica Estatal de Quevedo (UTEQ). Se situaron 15 jaulas dentro de un estanque circular de hormigón armado con Biofloc y se introdujeron 300 alevines de C. festae con un peso de 4,9 g. Quincenalmente, se midieron en 75 alevines de C. festae los parámetros biométricos individuales de longitud total, peso y altura. Diariamente se midieron los parámetros fisicoquímicos del agua de Biofloc (pH, temperatura, oxígeno, nitrógeno amoniacal total y sólidos en suspensión). El crecimiento se determinó utilizando modelos de regresión y en una segunda etapa se ajustó el peso al modelo seleccionado de mejor ajuste que fue: Log-Y Raíz Cuadrada-X que explica el 98,3% de la variabilidad en Peso. Con este estudio podemos concluir que la tecnología Biofloc podría ser una alternativa para la producción intensiva de especies nativas. En investigaciones futuras será necesario avanzar en el conocimiento de las condiciones del Biofloc propias para cada especie, biomasa de cultivo, estrategias de aireación para cada una de las etapas de crecimiento y así potenciar y optimizar los cultivos.

ABSTRACT: Background: Little is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals. Methods: PubMed and Web of Science were searched until November 2020 in this PRISMA compliant meta-analysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were two-tailed with α=0.05. Findings: 75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges’ g=0.753, 95%CI=0.495-1.012) and 24 (Hedges’ g=0.836, 95%CI=0.463-1.209), but not ≥36 months (Hedges’ g=0.315. 95%CI=-0.176–0.806). Negative symptoms improved at 12 (Hedges’ g=0.496, 95%CI=0.315–0.678), but not 24 (Hedges’ g=0.499, 95%CI=-0.137–1.134) or ≥36 months (Hedges’ g=0.033, 95%CI=-0.439–0.505). Depressive symptoms improved at 12 (Hedges’ g=0.611, 95%CI=0.441–0.782) and 24 (Hedges’ g=0.583, 95%CI=0.364–0.803), but not ≥36 months (Hedges’ g=0.512 95%CI=-0.337–1.361). Functioning improved at 12 (Hedges’ g=0.711, 95%CI=0.488–0.934), 24 (Hedges’ g=0.930, 95%CI=0.553–1.306) and ≥36 months (Hedges’ g=0.392, 95%CI=0.117–0.667). Remission from CHR-P status occurred in 33.4% (95%CI=22.6–44.1%) at 12 months, 41.4% (95%CI=32.3–50.5%) at 24 months and 42.4% (95%CI=23.4–61.3%) at ≥36 months. Heterogeneity across the included studies was significant and ranged from I2=53.6% to I2=96.9%. The quality of the included studies (mean±SD) was 4.6±1.1 (range=2-8). Interpretation: CHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. Prolonged duration of care may be needed for this patient population to optimize outcomes. Funding: None.

Diffractive multifocal intraocular lenses (IOLs) modulate chromatic aberration and reduce it at certain distances due to interactions between the refractive and diffractive chromatic components. However, the extent to which computer modeling and on bench measurements of IOL chromatic aberration translate to chromatic aberration in patients implanted with these multifocal IOLs (MIOLs) is not yet fully understood. In this study, we compare the chromatic difference of focus and longitudinal chromatic aberrations in pseudophakic patients implanted with different IOL designs (monofocal and trifocal IOLs) and materials (hydrophobic and hydrophilic), and compared them with predictions from computer eye models and on bench measurements with the same IOLs. Patient data consisted of results from 63 pseudophakic eyes reported in four different studies and obtained psychophysically in the visual testing channel of a custom-developed polychromatic adaptive optics system. Computational predictions were obtained using ray tracing on computer eye models, and modulation transfer function (MTF) on bench measurements on physical eye models. We found that LCA (in vivo/simulated) for far vision was 1.37 ± 0.08 D/1.19 D for monofocal hydrophobic, 1.21 ± 0.08 D/0.88 D for monofocal hydrophilic, 0.99 ± 0.06 D/1.19 D for MIOL hydrophobic, and 0.82 ± 0.05 D/0.88 D for MIOL hydrophilic. For intermediate and near vision, LCA (in vivo/simulated) was 0.67 ± 0.10 D/0.75 D and 0.23 ± 0.08 D/0.19 D for MIOL hydrophobic and 0.27 ± 0.15 D/0.38 D and 0.15 ± 0.15 D/−0.13 D for MIOL hydrophilic, respectively. In conclusion, computational ray tracing and on bench measurements allowed for evaluating in vivo chromatic aberration with different materials and designs for multifocal diffractive intraocular lenses.

Aim: To determine the safety and efficacy of self-administered outpatient parenteral antibiotic treatment (S-OPAT) within a hospitalization-at-home (HaH) program to manage a urinary tract infection (UTI) in patients referred directly from a hospital ED.Materials and Methods: This was a retrospective study of UTI episodes in patients treated initially in the ED, who were subsequently enrolled in a HaH program to receive S-OPAT. Epidemiological, clinical, and microbiological data were recorded. Safety was evaluated by means of mortality and the occurrence of unexpected hospital returns (reason, intra-hospital death) during the domiciliary period. The efficacy was evaluated considering the healing rate and analysis of mortality and repeat hospital admissions because of the UTI recurrence during the first month after discharge.Results: A total of 268 episodes of UTI were analyzed; the mean age of patients was 59.3 years, and 53% were female. The Charlson index was 1.97. The most common types of UTI were acute pyelonephritis and urosepsis. In 61.4% of urine cultures, microbiological documentation was obtained. E. coli was the most commonly isolated microorganism. A total of 27 strains of multidrug resistant microorganisms (MRD) were recorded. The most commonly used antimicrobial drug was ceftriaxone. There was one reported death. Clinical complications that resulted in returning to hospital occurred in 3.4% of cases. The healing rate was 96.5%. During the month after discharge, 4.4% of patients required repeat admission because of the UTI recurrence.Conclusion: S-OPAT within a HaH program in patients with UTI who are referred directly from ED is safe and effective.

Abstract Background The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use by older adults with bipolar disorder as part of a larger survey project about information seeking. Methods A paper-based survey about information seeking by patients with bipolar disorder was developed and translated into 12 languages. The survey was anonymous and completed between March 2014 and January 2016 by 1222 patients in 17 countries. All patients were diagnosed by a psychiatrist. General estimating equations were used to account for correlated data. Results Overall, 47% of older adults (age 60 years or older) used the Internet versus 87% of younger adults (less than 60 years). More education and having symptoms that interfered with regular activities increased the odds of using the Internet, while being age 60 years or older decreased the odds. Data from 187 older adults and 1021 younger adults were included in the analysis excluding missing values. Conclusions Older adults with bipolar disorder use the Internet much less frequently than younger adults. Many older adults do not use the Internet, and technology tools are suitable for some but not all older adults. As more health services are only available online, and more digital tools are developed, there is concern about growing health disparities based on age. Mental health experts should participate in determining the appropriate role for digital tools for older adults with bipolar disorder.

We conducted a rapid, mixed-methods assessment to understand how COVID-19 affected Latinx sexual minority men (LSMM) and transgender women (LTGW). Using a computer-assisted telephone interviewing software, one interviewer called 52 participants (randomly sampled from a larger HIV prevention pilot study aiming to increase HIV knowledge and testing frequency; n = 36 LSMM and n = 16 LTGW) between 04/27/20-05/18/20. We quantified core domains using the Epidemic-Pandemic Impacts Inventory scale and provided important context through open-ended qualitative questions assessing: 1) COVID-19 infection history and experiences with quarantine; 2) Health and healthcare access; 3) Employment and economic impact of COVID-19. Participants reported increases in physical conflict or verbal arguments with a partner (13.5%) or other adult(s) (19.2%) due to stressors associated with the safer-at-home order. Participants also reported increased alcohol consumption (23.1%), problems with sleep (67.3%) and mental health (78.4%). Further, disruptions in access to Pre-Exposure Prophylaxis or PrEP-a daily pill to prevent HIV-occurred (33.3% of 18 participants who reported being on PrEP). Many said they received less medical attention than usual (34.6%), and LTGW reported delays in critical gender-affirming hormones/procedures. Half of the participants lost their jobs (50.0%); many undocumented participants relayed additional financial concerns because they did not qualify for financial assistance. Though no COVID-19 infections were noted, COVID-19 dramatically impacted other aspects of health and overall wellbeing of LSMM and LTGW. Public health responses should address the stressors faced by LSMM and LTGW during the COVID-19 pandemic and the impact on wellbeing.

Abstract In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in significant adverse effects. Transplanting dopaminergic neurons derived from stem cells could restore dopamine levels without additional motor complications. However, the transplanted cells disperse in vivo and it is not possible to stimulate them on demand to modulate dopamine release to prevent dyskinesia. In order to address these issues, this paper presents a multifunctional leaky optoelectrical fiber for potential neuromodulation and as a cell substrate for application in combined optogenetic stem cell therapy. Pyrolytic carbon coated optical fibers are laser ablated to pattern micro‐optical windows to permit light leakage over a large area. The pyrolytic carbon acts as an excellent electrode for the electrochemical detection of dopamine. Human neural stem cells are genetically modified to express the light sensitive opsin channelrhodopsin‐2 and are differentiated into dopaminergic neurons on the leaky optoelectrical fiber. Finally, light leaking from the micro‐optical windows is used to stimulate the dopaminergic neurons resulting in the release of dopamine that is detected in real‐time using chronoamperometry.

To characterize the traditional systems of small pig producers in Jipijapa (Manabí, Ecuador) and to classify farms into representative categories, we interviewed fifty-five farmers from seven communities considering four dimensions: social, organizational, production methods, and local food resources. Multiple correspondence analyses and hierarchical clusters were carried out using the Ward method. The analysis differentiated communities based on social, productive, and local resource variables, showing three factors that accounted for 85.3% of the total variance: the socioeconomic dimension, related to the welfare of families, explained 34.4% of the variation, the care provided to animals explained 30.9%, and the management practices for the supply of food explained 20%. We identified five clusters that shared common characteristics: Group 1 included farmers from Albajacal, wage workers, and Creole pig breeders, Group 2 included farmers raising pigs under lockdown conditions, Group 3 typified traditional farms from the La Cuesta community, Group 4 included landowners, and Group 5 included professionalized farmers in Colón Alfaro. We also studied the supplied alternative food formulations made up of crop surpluses. The role of small pig farmers is a social activity linked to the location, the crops of each area, and the specific practices for the care of animals.

The Guayas, located in Ecuador, is the largest basin in the Pacific Ocean and has an inventory of 123 native freshwater species. Most of these are endemic species that are threatened or at-risk due to anthropogenic activity and the modification, fragmentation, and destruction of habitats. The aim of this study was to determine the morphometric variation in three wild populations of Brycon dentex in the Guayas basin rivers and their connections to fishing management and environmental conditions. A total of 200 mature fish were captured, and 26 morphometric parameters were measured. The fishing policies (Hypothesis 1) and environmental conditions (Hypothesis 2) were considered fixed factors and were validated by t-tests. The morphological variation among the three populations (Hypothesis 3) was validated through a discriminant analysis. Fishing policies and resource management were found to generate morphological differences associated with body development. In addition, the environmental conditions were found to influence the size and structure of Brycon dentex populations. The analyzed populations were discriminated by the generated morphometric models, which differentiated Cluster 1 (Quevedo and Mocache rivers) with high fishing pressure from Cluster 2 (Pintado river) with medium–low fishing pressure. Morphometric differentiation by discriminant analysis is a direct and economic methodology that can be applied as an indicator of diversity maintenance.

The goal of FOCUS, which stands for Frailty Management Optimization through EIPAHA Commitments and Utilization of Stakeholders’ Input , is to reduce the burden of frailty in Europe. The partners are working on advancing knowledge of frailty detection, assessment, and management, including biological, clinical, cognitive and psychosocial markers, in order to change the paradigm of frailty care from acute intervention to prevention. FOCUS partners are working on ways to integrate the best available evidence from frailty-related screening tools, epidemiological and interventional studies into the care of frail people and their quality of life. Frail citizens in Italy, Poland and the UK and their caregivers are being called to express their views and their experiences with treatments and interventions aimed at improving quality of life. The FOCUS Consortium is developing pathways to leverage the knowledge available and to put it in the service of frail citizens. In order to reach out to the broadest audience possible, the FOCUS Platform for Knowledge Exchange and the platform for Scaling Up are being developed with the collaboration of stakeholders. The FOCUS project is a development of the work being done by the European Innovation Partnership on Active and Healthy Ageing (EIPAHA), which aims to increase the average healthy lifespan in Europe by 2020 while fostering sustainability of health/social care systems and innovation in Europe. The knowledge and tools developed by the FOCUS project, with input from stakeholders, will be deployed to all EIPAHA participants dealing with frail older citizens to support activities and optimize performance.