Dual-Slope Path Loss Model for Integrating Vehicular Sensing Applications in Urban and Suburban Environments.

The development of intelligent transportation systems (ITS), vehicular ad hoc networks (VANETs), and autonomous driving (AD) has progressed rapidly in recent years, driven by artificial intelligence (AI), the internet of things (IoT), and their integration with dedicated short-range communications (DSRC) systems and fifth-generation (5G) networks. This has led to improved mobility conditions in different road propagation environments: urban, suburban, rural, and highway. The use of these communication technologies has enabled drivers and pedestrians to be more aware of the need to improve their behavior and decision making in adverse traffic conditions by sharing information from cameras, radars, and sensors widely deployed in vehicles and road infrastructure. However, wireless data transmission in VANETs is affected by the specific conditions of the propagation environment, weather, terrain, traffic density, and frequency bands used. In this paper, we characterize the path loss based on the extensive measurement campaign carrier out in vehicular environments at 700 MHz and 5.9 GHz under realistic road traffic conditions. From a linear dual-slope path loss propagation model, the results of the path loss exponents and the standard deviations of the shadowing are reported. This study focused on three different environments, i.e., urban with high traffic density (U-HD), urban with moderate/low traffic density (U-LD), and suburban (SU). The results presented here can be easily incorporated into VANET simulators to develop, evaluate, and validate new protocols and system architecture configurations under more realistic propagation conditions.

Orthogonal Space-Time Block Coding for Double Scattering V2V Links with LOS and Ground Reflections.

This work presents the performance analysis of space-time block codes (STBCs) for vehicle-to-vehicle (V2V) fast-fading channels in scenarios with modified line-of-sight (LOS). The objective is to investigate how the V2V MIMO (multiple-input multiple-output) system performance is influenced by two important impairments: deterministic ground reflections and an increased Doppler frequency (time-variant channels). STBCs of various coding rates (using an approximation model) are evaluated by assuming antenna elements distributed over the surface of two contiguous vehicles. A multi-ray model is used to study the multiple constructive/destructive interference patterns of the transmitted/received signals by all pairs of Tx-Rx antenna links considering ground reflections. A double scattering model is used to include the effects of stochastic channel components that depend on the Doppler frequency. The results show that STBCs are capable of counteracting fades produced by destructive self-interference components across a range of inter-vehicle distances and for a range of Doppler frequency values. Notably, the effectiveness of STBCs in deep fades is shown to outperform schemes with exclusive receive diversity, despite the interference created by the loss of orthogonality in time-varying channels with a moderate increase of Doppler frequency (mainly due to higher vehicle speeds, higher frequency or shorter time slots). Higher-order STBCs with rate losses are also evaluated using an approximation model, showing interesting gains even for low coding rate performance, particularly when accompanied by a multiple antenna receiver. Overall, these results can shed light on how to exploit transmit diversity in time-varying vehicular channels with modified LOS.

Maximal Ratio Combining Detection in OFDM Systems with Virtual Carriers Over V2V Channels.

This paper examines the performance of orthogonal frequency division multiplexing (OFDM) systems for vehicle-to-vehicle (V2V) communication channels. More specifically, a doubly selective channel under high intercarrier interference (ICI) is considered. Current solutions involve complex detection and/or reduced spectral efficiency receivers. This paper proposes the use of virtual carriers (VC) in an OFDM system with a low-complexity maximal ratio combining (MRC) detector to improve the bit error rate (BER) performance. The results show that VC provides diversity in received data, resulting in a ≥5 dB gain compared to previous OFDM systems with conventional linear/nonlinear detectors used as a reference. The detector presented in this paper has linear complexity, making it a suitable solution for real-time V2V communication systems.

[Health related to quality life of patients with hereditary angioedema in Argentina. A multicenter study]. / Calidad de vida relacionada con la salud en pacientes con angioedema hereditario de Argentina. Estudio multicéntrico.

OBJECTIVE: To describe health relaed quality of life in a cohort of stable adult outpatients with hereditary an-gioedema (HAE) with validated tools. METHODS: An observational, cross-sectional, and descriptive study was performed, carried out in patients with hereditary angioedema, coming from the City of Buenos Aires and its provinces: Corrientes, Chubut, Entre Ríos and Santa Fe. The HAE-QoL and SF-12v2 health questionnaires were applied to assess the related quality of life. with health. RESULTS: 100 patients were included; median age: 41.5 years (range: 18-77); 65% were female, and 79% had type 1 HAE. Asymptomatic, mild, moderate and severe cases accounted for 6, 29, 38, and 27% of participants, respectively. Seventeen percent of patients were receiving long-term prophylaxis. Icatibant was the most fre-quent treatment for acute episodes. All health domains SF-12v2 scores were lower than expected in general population, excepting "vitality" and "physical functioning". Total and all specific domains HAE-QoL scores were reduced. Differences between women and men and in every age-defined group were demonstrated for sev-eral specific domains. CONCLUSIONS: Health relaed to quality life was notably reduced in Argentinean patients with HAE, when imple-menting the HAE.QoL, and SF-12v2 questionnaries. The need for multidisciplinary strategies approaching this complex disease is highlighted.

OBJECTIVO: Describir la calidad de vida relacionada con la saluden pacientes adultos, ambulatorios y estables con angioedema hereditario, mediante cuestionarios validados. MÉTODOS: Estudio descriptivo, transversal y observacional, llevado a cabo en pacientes con angioedema here-ditario, procedentes de la Ciudad de Buenos Aires y sus provincias: Corrientes, Chubut, Entre Ríos y Santa Fe. Se aplicaron los cuestionarios HAE-QoL y SF-12v2 para evaluar la calidad de vida relacionada con la salud. RESULTADOS: Se incluyeron 100 pacientes, con mediana de edad de 41.5 años (rango: 18-77), principalmente de género femenino (65%). La forma más frecuente de angioedema hereditario fue el tipo 1 (79%). Los casos asintomáticos, leves, moderados y severos representaron el 6, 29, 38 y 27%, respectivamente. El 17% recibía profilaxis a largo plazo. Icatibant fue el tratamiento más prescrito para los episodios agudos de angioedema. Todos los puntajes de los dominios de salud del SF-12v2 fueron menores de lo esperado, excepto "vitalidad" y "funcionamiento físico". Se observó disminución en los puntajes totales y en todos los dominios del HAE-QoL. Se reconocieron diferencias entre las mujeres y los hombres, y para grupo etario en los puntajes de los dominios específicos. CONCLUSIONES: La calidad de vida relacionada con la salud disminuyó considerablemente en pacientes argentinos con angioedema hereditario al aplicar los cuestionarios HAE-QoL y SF-12v2. Es importante desarrollar estra-tegias multidisciplinarias para abordar esta enfermedad compleja.

Leptospirosis con enfermedad de Weil que debuta como abdomen agudo. Reporte de caso / Leptospirosis with Weil Syndrome debuting with acute abdomen, Case Report

La leptospirosis es una enfermedad de distribución mundial que se ubica dentro de las zoonosis, siendo un punto de partida importante el ambiente donde se desarrolla el paciente, pasa de ser una infección leve, hasta su presentación más complicada que es el síndrome de Weil (presentación diseminada), que al no detectarse a tiempo se relaciona con altas tasas de mortalidad. Su diagnóstico de probabilidad se establece por medio del criterio clínico (signos y síntomas de sospecha), más el nexo epidemiológico, el cual podrá corroborarse con los resultados de los estudios complementarios (marcadores inmunológicos), siendo indispensable para el tratamiento un soporte oportuno y la selección adecuada del esquema antibiótico. A continuación, se expone un caso de una mujer de 25 años con antecedente personal de infección por SARS-CoV-2 (RT-PCR positivo) cuatro meses antes de su ingreso, que presento leptospirosis que debutó con dolor abdominal simulando un abdomen agudo que motivó realización de laparoscopia exploratoria. La serología para leptospira fue positiva y el paciente recibió tratamiento antibiótico específico con evolución favorable.

Leptospirosis is a disease of worldwide that is considered within zoonoses. It is important to know the environment where the patient performs its activities. The clinical presentation goes from a mild infection to its more complicated presentation, the Weil´s Syndrome (disseminated affectation), which is related to high mortality rates if not detected in time. Its probability diagnosis is established based on clinical criteria (signs and symptoms of suspicion), plus the epidemiological link, which can be corroborated with the results of complementary studies (immunological markers). This is essential for the adequate treatment and selection of the antibiotic scheme. The following is a case of a 25-years-old woman with a personal history of SARS-Co V-2 infection (RT-PCR positive) four months before admission, who presented Leptospirosis that debuted with abdominal pain simulating an acute abdomen that required exploratory laparoscopy. Serology for Leptospira was positive and the patient received specific antibiotic treatment with favorable evolution

Security in V2I Communications: A Systematic Literature Review.

Recently, the number of vehicles equipped with wireless connections has increased considerably. The impact of that growth in areas such as telecommunications, infotainment, and automatic driving is enormous. More and more drivers want to be part of a vehicular network, despite the implications or risks that, for instance, the openness of wireless communications, its dynamic topology, and its considerable size may bring. Undoubtedly, this trend is because of the benefits the vehicular network can offer. Generally, a vehicular network has two modes of communication (V2I and V2V). The advantage of V2I over V2V is roadside units' high computational and transmission power, which assures the functioning of early warning and driving guidance services. This paper aims to discover the principal vulnerabilities and challenges in V2I communications, the tools and methods to mitigate those vulnerabilities, the evaluation metrics to measure the effectiveness of those tools and methods, and based on those metrics, the methods or tools that provide the best results. Researchers have identified the non-resistance to attacks, the regular updating and exposure of keys, and the high dependence on certification authorities as main vulnerabilities. Thus, the authors found schemes resistant to attacks, authentication schemes, privacy protection models, and intrusion detection and prevention systems. Of the solutions for providing security analyzed in this review, the authors determined that most of them use metrics such as computational cost and communication overhead to measure their performance. Additionally, they determined that the solutions that use emerging technologies such as fog/edge/cloud computing present better results than the rest. Finally, they established that the principal challenge in V2I communication is to protect and dispose of a safe and reliable communication channel to avoid adversaries taking control of the medium.

Evaluating Link Lifetime Prediction to Support Computational Offloading Decision in VANETs.

In urban mobility, Vehicular Ad Hoc Networks (VANETs) provide a variety of intelligent applications. By enhancing automobile traffic management, these technologies enable advancements in safety and help decrease the frequency of accidents. The transportation system can now follow the development and growth of cities without sacrificing the quality and organisation of its services thanks to safety apps that include collision alerts, real-time traffic information, and safe driving applications, among others. Applications can occasionally demand a lot of computing power, making their processing impractical for cars with limited onboard processing capacity. Offloading of computation is encouraged by such a restriction. However, because vehicle mobility operations are dynamic, communication times (also known as link lifetimes) between nodes are frequently short. VANET applications and processes are impacted by such communication delays (e.g., the offloading decision when using the Computational Offloading technique). Making an accurate prediction of the link lifespan between vehicles is therefore challenging. The effectiveness of the communication time estimation is currently constrained by the link lifespan prediction methods used in the computational offloading process. This work investigates five machine learning (ML) algorithms to predict the link lifetime between nodes in VANETs in different scenarios. We propose the procedures required to carry out the link lifetime prediction method using existing ML techniques. The tactic creates datasets with the features the models need to learn and be trained. The SVR and XGBoost algorithms that were selected as part of the assessment process were trained. To make the prediction using the trained models, we modified the lifespan prediction function from an offloading approach. To determine the viability of applying link lifespan predictions from the models trained in the road and urban scenarios, we conducted a performance study. The findings indicate that compared to the conventional prediction strategy described in the literature, the suggested link lifetime prediction via regression approaches decreases prediction error rates. An offloading method from the literature is extended by the selected SVR. The task loss and recovery rates might be significantly reduced using the SVR. XGBoost outperformed its ML competitors in task recovery or drop rate by 70% to 80% in an assessed hypothesis compared to an offloading choice technique in the literature. With greater offloading rates from an application on the VANET, this effort is intended to give better efficiency in estimating this data using machine learning in various vehicular settings.

Trastornos mentales y calidad de vida relacionada con la salud en profesionales de Unidades de Cuidados Intensivos / Mental disorders and health-related quality of life in Intensive Care Units professionals

Resumen Los profesionales de la salud de las Unidades de Cuidados Intensivos (UCI) enfrentan situaciones de sufrimiento humano, competitividad y demanda, que podrían perjudicar su calidad de vida y su salud mental. El objetivo del estudio fue describir los trastornos mentales comunes y la calidad de vida relacionada con la salud en profesionales de la salud de la UCI en Salvador, Brasil. Este estudio transversal con 195 profesionales utilizó un cuestionario sociodemográfico y laboral, el Self-Reporting Questionnaire (SRQ-20) de trastornos mentales comunes y el 36-Item Short Form Health Survey (SF-36v2) de calidad de vida relacionada con la salud. El 29.7 % de los profesionales presentaron trastornos mentales comunes, especialmente entre profesionales de enfermería (RP = 2.28; IC 1.19-4.39; p = .007). La calidad de vida relacionada con la salud para todos los profesionales estuvo disminuida, principalmente en función social (44.25 ± 10.15) y rol emocional (45.86 ± 10.58). El SRQ-20 correlacionó fuertemente con los dominios dolor corporal (r = -.502), salud general (r = -.526), vitalidad (r = -.656), función social (r = -.608), salud mental (r = -.631) y el componente de salud mental (r = -.638) del SF-36v2 (p < .01). Los profesionales con trastornos mentales comunes mostraron una calidad de vida relacionada con la salud más deteriorada, esencialmente en dominios del componente de salud mental, y refirieron también dolor corporal. Es necesario discutir e implementar estrategias de evaluación, prevención y promoción de la salud mental entre los profesionales de las UCI para que sean consideradas dentro de las políticas de salud laboral.

Kinect v2-Assisted Semi-Automated Method to Assess Upper Limb Motor Performance in Children.

The interruption of rehabilitation activities caused by the COVID-19 lockdown has significant health negative consequences for the population with physical disabilities. Thus, measuring the range of motion (ROM) using remotely taken photographs, which are then sent to specialists for formal assessment, has been recommended. Currently, low-cost Kinect motion capture sensors with a natural user interface are the most feasible implementations for upper limb motion analysis. An active range of motion (AROM) measuring system based on a Kinect v2 sensor for upper limb motion analysis using Fugl-Meyer Assessment (FMA) scoring is described in this paper. Two test groups of children, each having eighteen participants, were analyzed in the experimental stage, where upper limbs' AROM and motor performance were assessed using FMA. Participants in the control group (mean age of 7.83 ± 2.54 years) had no cognitive impairment or upper limb musculoskeletal problems. The study test group comprised children aged 8.28 ± 2.32 years with spastic hemiparesis. A total of 30 samples of elbow flexion and 30 samples of shoulder abduction of both limbs for each participant were analyzed using the Kinect v2 sensor at 30 Hz. In both upper limbs, no significant differences (p < 0.05) in the measured angles and FMA assessments were observed between those obtained using the described Kinect v2-based system and those obtained directly using a universal goniometer. The measurement error achieved by the proposed system was less than ±1° compared to the specialist's measurements. According to the obtained results, the developed measuring system is a good alternative and an effective tool for FMA assessment of AROM and motor performance of upper limbs, while avoiding direct contact in both healthy children and children with spastic hemiparesis.

Visualizing Street Pavement Anomalies through Fog Computing V2I Networks and Machine Learning.

Analyzing data related to the conditions of city streets and avenues could help to make better decisions about public spending on mobility. Generally, streets and avenues are fixed as soon as they have a citizen report or when a major incident occurs. However, it is uncommon for cities to have real-time reactive systems that detect the different problems they have to fix on the pavement. This work proposes a solution to detect anomalies in streets through state analysis using sensors within the vehicles that travel daily and connecting them to a fog-computing architecture on a V2I network. The system detects and classifies the main road problems or abnormal conditions in streets and avenues using Machine Learning Algorithms (MLA), comparing roughness against a flat reference. An instrumented vehicle obtained the reference through accelerometry sensors and then sent the data through a mid-range communication system. With these data, the system compared an Artificial Neural Network (supervised MLA) and a K-Nearest Neighbor (Supervised MLA) to select the best option to handle the acquired data. This system makes it desirable to visualize the streets' quality and map the areas with the most significant anomalies.

Prediction of molecular interactions and physicochemical properties relevant for vasopressin V2 receptor antagonism.

We have developed two ligand- and receptor-based computational approaches to study the physicochemical properties relevant to the biological activity of vasopressin V2 receptor (V2R) antagonist and eventually to predict the expected binding mode to V2R. The obtained quantitative structure activity relationship (QSAR) model showed a correlation of the antagonist activity with the hydration energy (EH2O), the polarizability (P), and the calculated partial charge on atom N7 (q6) of the common substructure. The first two descriptors showed a positive contribution to antagonist activity, while the third one had a negative contribution. V2R was modeled and further relaxed on a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocoline (POPC) membrane by molecular dynamics simulations. The receptor antagonist complexes were guessed by molecular docking, and the stability of the most relevant structures was also evaluated by molecular dynamics simulations. As a result, amino acid residues Q96, W99, F105, K116, F178, A194, F307, and M311 were identified with the probably most relevant antagonist-receptor interactions on the studied complexes. The proposed QSAR model could explain the molecular properties relevant to the antagonist activity. The contributions to the antagonist-receptor interaction appeared also in agreement with the binding mode of the complexes obtained by molecular docking and molecular dynamics. These models will be used in further studies to look for new V2R potential antagonist molecules.

Validation of Angle Estimation Based on Body Tracking Data from RGB-D and RGB Cameras for Biomechanical Assessment.

Motion analysis is an area with several applications for health, sports, and entertainment. The high cost of state-of-the-art equipment in the health field makes it unfeasible to apply this technique in the clinics' routines. In this vein, RGB-D and RGB equipment, which have joint tracking tools, are tested with portable and low-cost solutions to enable computational motion analysis. The recent release of Google MediaPipe, a joint inference tracking technique that uses conventional RGB cameras, can be considered a milestone due to its ability to estimate depth coordinates in planar images. In light of this, this work aims to evaluate the measurement of angular variation from RGB-D and RGB sensor data against the Qualisys Tracking Manager gold standard. A total of 60 recordings were performed for each upper and lower limb movement in two different position configurations concerning the sensors. Google's MediaPipe usage obtained close results compared to Kinect V2 sensor in the inherent aspects of absolute error, RMS, and correlation to the gold standard, presenting lower dispersion values and error metrics, which is more positive. In the comparison with equipment commonly used in physical evaluations, MediaPipe had an error within the error range of short- and long-arm goniometers.

Direct inhibition of CaV2.3 by Gem is dynamin dependent and does not require a direct alfa/beta interaction.

The Rad, Rem, Rem2, and Gem/Kir (RGK) sub-family of small GTP-binding proteins are crucial in regulating high voltage-activated (HVA) calcium channels. RGK proteins inhibit calcium current by either promoting endocytosis or reducing channel activity. They all can associate directly with Ca2+ channel ß subunit (CaVß), and the binding between CaVα1/CaVß appears essential for the endocytic promotion of CaV1.X, CaV2.1, and CaV2.2 channels. In this study, we investigated the inhibition of CaV2.3 channels by RGK proteins in the absence of CaVß. To this end, Xenopus laevis oocytes expressing CaV2.3 channels devoid of auxiliary subunit were injected with purified Gem and Rem and found that only Gem had an effect. Ca currents and charge movements were reduced by injection of Gem, pointing to a reduction in the number of channels in the plasma membrane. Since this reduction was ablated by co-expression of the dominant-negative mutant of dynamin K44A, enhanced endocytosis appears to mediate this reduction in the number of channels. Thus, Gem inhibition of CaV2.3 channels would be the only example of a CaVß independent promotion of dynamin-dependent endocytosis.

Carrier Diversity Incorporation to Low-Complexity Near-ML Detection for Multicarrier Systems over V2V Radio Channel.

Inter-carrier interference (ICI) in vehicle to vehicle (V2V) orthogonal frequency division multiplexing (OFDM) systems is a common problem that makes the process of detecting data a demanding task. Mitigation of the ICI in V2V systems has been addressed with linear and non-linear iterative receivers in the past; however, the former requires a high number of iterations to achieve good performance, while the latter does not exploit the channel's frequency diversity. In this paper, a transmission and reception scheme for low complexity data detection in doubly selective highly time varying channels is proposed. The technique couples the discrete Fourier transform spreading with non-linear detection in order to collect the available channel frequency diversity and successfully achieving performance close to the optimal maximum likelihood (ML) detector. When compared with the iterative LMMSE detection, the proposed system achieves a higher performance in terms of bit error rate (BER), reducing the computational cost by a third-part when using 48 subcarriers, while in an OFDM system with 512 subcarriers, the computational cost is reduced by two orders of magnitude.

Prevalencia y factores asociados a la intención de vacunarse contra la COVID-19 en el Perú / Prevalence and factors associated with the intention to be vaccinated against COVID-19 in Peru

RESUMEN Objetivos: Estimar la prevalencia y los factores asociados a la intención de vacunación (IDV) contra la COVID-19 en el Perú. Materiales y métodos: Estudio transversal analítico utilizando una encuesta realizada por la Universidad de Maryland, EUA, en Facebook. La variable dependiente fue la IDV. Se calcularon razones de prevalencia (RP) crudas y ajustadas, con sus intervalos de confianza al 95% (IC95%), mediante modelos lineales generalizados de la familia Poisson para evaluar la asociación de variables sociodemográficas, el cumplimiento de estrategias comunitarias de mitigación, los síntomas de la COVID-19, la salud mental y la aceptación de la vacunación ante la recomendación (AVR) por diversos actores y autoridades sanitarias. Resultados: Se analizaron los datos de 17 162 adultos. La prevalencia general de la IDV fue del 74,9%. Se asociaron a una menor prevalencia de la IDV ser de sexo femenino (RP=0,95; IC95%:0,94-0,97), vivir en un pueblo (RP=0,95; IC95%:0,91-0,99) o en una aldea u otra área rural (RP=0,90; IC95%:0,86-0,93) y la AVR de políticos (RP=0,89; IC95%: 0,87-0,92). Contrariamente, tener síntomas de COVID-19 (RP=1,06; IC95%:1,03-1,09), inseguridad económica (RP=1,04; IC95%: 1,01-1,06), miedo a enfermar o que un familiar enferme de COVID-19 (RP=1,49; IC95%: 1,36-1,64) y la AVR de familiares y amigos (RP=1,10; IC95%: 1,08-1,12), trabajadores de la salud (RP=1,29; IC95%: 1,26-1,32), la Organización Mundial de la Salud (RP=1,34; IC95%: 1,29-1,40) y funcionarios del gobierno (RP=1,18; IC95%: 1,15-1,22) se asociaron con mayor prevalencia de IDV. Conclusiones: Tres cuartas partes de los encuestados manifiestan IDV. Existen factores potencialmente modificables que podrían mejorar la aceptación de la vacuna.

ABSTRACT Objectives: To estimate the prevalence and factors associated with the intention to be vaccinated (ITV) against COVID-19 in Peru. Materials and methods: Analytical cross-sectional study using the survey conducted by the University of Maryland, USA, on Facebook. The dependent variable is the ITV. Crude and adjusted prevalence ratios (PR) were calculated, with their 95% confidence intervals (95% CI) using generalized linear models of the Poisson family, in order to evaluate the association of sociodemographic variables, compliance with community mitigation strategies, symptoms of COVID-19, mental health and acceptance of vaccination before the recommendation (AVR) by various actors and health authorities, with the ITV. Results: Data from 17,162 adults were analyzed. The overall prevalence of the ITV was 74.9%. A lower prevalence of the ITV was associated with the female sex (PR=0.95; 95% CI: 0.94-0.97), living in a town (PR=0.95; 95% CI: 0.91-0.99) or village or other rural area (PR=0.90; 95% CI: 0.86-0.93) and the AVR of politicians (PR=0.89; 95% CI: 0.87-0.92). Conversely, having COVID-19 symptoms (PR=1.06; 95% CI: 1.03-1.09), economic insecurity (PR=1.04; 95% CI: 1.01-1.06), fears of becoming seriously ill or that a family member becomes seriously ill from COVID-19 (PR=1.49; 95% CI: 1.36-1.64) and the AVR of family and friends (PR=1.10; 95% CI: 1.08-1.12), healthcare workers (PR=1.29; 95% CI: 1.26-1.32), World Health Organization (PR=1.34; 95% CI: 1.29-1.40) and government officials (PR=1.18; 95% CI: 1.15-1.22) was associated with a higher prevalence of the ITV. Conclusions: Three-quarters of the respondents had the ITV. There are potentially modifiable factors that could improve vaccine acceptance.

Development and Evaluation of a Set of Spike and Receptor Binding Domain-Based Enzyme-Linked Immunosorbent Assays for SARS-CoV-2 Serological Testing.

The implementation and validation of anti-SARS-CoV-2 IgG serological assays are reported in this paper. S1 and RBD proteins were used to coat ELISA plates, and several secondary antibodies served as reporters. The assays were initially validated with 50 RT-PCR positive COVID-19 sera, which showed high IgG titers of mainly IgG1 isotype, followed by IgG3. Low or no IgG2 and IgG4 titers were detected. Then, the RBD/IgG assay was further validated with 887 serum samples from RT-PCR positive COVID-19 individuals collected at different times, including 7, 14, 21, and 40 days after the onset of symptoms. Most of the sera were IgG positive at day 40, with seroconversion happening after 14-21 days. A third party conducted an additional performance test of the RBD/IgG assay with 406 sera, including 149 RT-PCR positive COVID-19 samples, 229 RT-PCR negative COVID-19 individuals, and 28 sera from individuals with other viral infections not related to SARS-CoV-2. The sensitivity of the assay was 99.33%, with a specificity of 97.82%. All the sera collected from individuals with infectious diseases other than COVID-19 were negative. Given the robustness of this RBD/IgG assay, it received approval from the sanitary authority in Mexico (COFEPRIS) for production and commercialization under the name UDISTEST-V2G®.

The role of feedback projections in feature tuning and neuronal excitability in the early primate visual system.

A general assumption in visual neuroscience is that basic receptive field properties such as orientation and direction selectivity are constructed within intrinsic neuronal circuits and feedforward projections. In addition, it is assumed that general neuronal excitability and responsiveness in early visual areas is to a great extent independent of feedback input originating in areas higher in the stream. Here, we review the contribution of feedback projections from MT, V4 and pulvinar to the receptive field properties of V2 neurons in the anesthetized and paralyzed monkey. Importantly, our results contradict both of these assumptions. We separately inactivated each of these three brain regions using GABA pressure injections, while simultaneously recording V2 single unit activity before and hours after inactivation. Recordings and GABA injections were carried out in topographically corresponding regions of the visual field. We outline the changes in V2 activity, responsiveness and receptive field properties for early, mid and late post-injection phases. Immediately after injection, V2 activity is globally suppressed. Subsequently, there is an increase in stimulus-driven relative to spontaneous neuronal activity, which improves the signal-to-noise coding for the oriented moving bars. Notably, V2 tuning properties change substantially relative to its pre-injection selectivity profile. The resulting increase or decrease in selectivity could not be readily predicted based on the selectivity profile of the inactivated site. Finally, V2 activity rebounds before returning to it pre-injection profile Our results show that feedback projections profoundly impact neuronal circuits in early visual areas, and may have been heretofore largely underestimated in their physiological role.

Expanding the Phenotypic and Genotypic Spectrum of Bietti Crystalline Dystrophy.

The rare form of retinal dystrophy, Bietti crystalline dystrophy, is associated with variations in CYP4V2, a member of the cytochrome P450 family. This study reports patients affected by typical and atypical Bietti crystalline dystrophy, expanding the spectrum of this disease. This is an observational case series of patients with a clinical and molecular diagnosis of Bietti crystalline dystrophy that underwent multimodal imaging. Four unrelated patients are described with two known variants, c.802-8_810del17insGC and c.518T > G (p.Leu173Trp), and one novel missense variant, c.1169G > T (p.Arg390Leu). The patient with the novel homozygous variant had the most severe phenotype resulting in macular hole formation and retinal detachment in both eyes. To the best of our knowledge, there is no association of these features with Bietti crystalline dystrophy. Patient 1 was the youngest patient and had the mildest phenotype with crystals in the retina without chorioretinal atrophy and visual complaints. Patients 2 and 3 presented with fewer crystals and chorioretinal atrophy. These three patients presented a classic phenotype. The fourth patient presented with an atypical and severe phenotype. This study reveals a new genotype and new phenotype associated with this disorder.

Recognition through GRP78 is enhanced in the UK, South African, and Brazilian variants of SARS-CoV-2; An in silico perspective.

New SARS-CoV-2 variants emerged in the United Kingdom and South Africa in December 2020 in concomitant with the Brazillian variant in February 2021 (B.1.1.248 lineage) and currently sparking worldwide during the last few months. The new strain 501.V2 in South Africa bears three mutations in the spike receptor-binding domain (RBD); K417 N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage has 12 mutations. In the current study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wild-type and mutated isoforms. Additionally, the cell-surface Glucose Regulated Protein 78 (CS-GRP78) associated with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-S RBD) is modeled at the presence of these mutant variants of the viral spike. The results showed that E484K and N501Y are critical in viral spike recognition through either ACE2 or CS-GRP78. The mutated variants (the UK, South African, and Brazilian) of the spike RBD tightly bind to GRP78 more than in the case of the wild-type RBD. These results point to the potent role of GRP78 with ACE2 in the attachment of the new variants, which could be a key for the design of inhibitors to block SARS-CoV-2 attachment and entry to the host cell.

The Drosophila ortholog of the schizophrenia-associated CACNA1A and CACNA1B voltage-gated calcium channels regulate memory, sleep and circadian rhythms.

Schizophrenia exhibits up to 80% heritability. A number of genome wide association studies (GWAS) have repeatedly shown common variants in voltage-gated calcium (Cav) channel genes CACNA1C, CACNA1I and CACNA1G have a major contribution to the risk of the disease. More recently, studies using whole exome sequencing have also found that CACNA1B (Cav2.2 N-type) deletions and rare disruptive variants in CACNA1A (Cav2.1 P/Q-type) are associated with schizophrenia. The negative symptoms of schizophrenia include behavioural defects such as impaired memory, sleep and circadian rhythms. It is not known how variants in schizophrenia-associated genes contribute to cognitive and behavioural symptoms, thus hampering the development of treatment for schizophrenia symptoms. In order to address this knowledge gap, we studied behavioural phenotypes in a number of loss of function mutants for the Drosophila ortholog of the Cav2 gene family called cacophony (cac). cac mutants showed several behavioural features including decreased night-time sleep and hyperactivity similar to those reported in human patients. The change in timing of sleep-wake cycles suggested disrupted circadian rhythms, with the loss of night-time sleep being caused by loss of cac just in the circadian clock neurons. These animals also showed a reduction in rhythmic circadian behaviour a phenotype that also could be mapped to the central clock. Furthermore, reduction of cac just in the clock resulted in a lengthening of the 24 h period. In order to understand how loss of Cav2 function may lead to cognitive deficits and underlying cellular pathophysiology we targeted loss of function of cac to the memory centre of the fly, called the mushroom bodies (MB). This manipulation was sufficient to cause reduction in both short- and intermediate-term associative memory. Memory impairment was accompanied by a decrease in Ca2+ transients in response to a depolarizing stimulus, imaged in the MB presynaptic terminals. This work shows loss of cac Cav2 channel function alone causes a number of cognitive and behavioural deficits and underlying reduced neuronal Ca2+ transients, establishing Drosophila as a high-throughput in vivo genetic model to study the Cav channel pathophysiology related to schizophrenia.