Resonant Fragmentation of the Water Cation by Electron Impact: a Wave-Packet Study.

We have investigated the dissociation of a resonant state that can be formed in low energy electron scattering from H2 O+ . We have chosen the second triplet resonance above the B ˜ 2 A ' ${{{\tilde{\rm {B}}}}\;^2 {\rm{A{^\prime}}}}$ ( B ˜ 2 B 2 ) ${{\rm{(\tilde{B}}}\;^2 {\rm{B}}_2 )}$ state of H2 O+ whose autoionization mainly produces H2 O+ ( X ˜ 2 A ' ' ${{{\tilde{\rm {X}}}}\;^2 {\rm{A{^\prime}{^\prime}}}}$ ). We have considered both dissociation of the resonant state itself, dissociative recombination (DR), or the dissociation of the H2 O+ cation after autodetachment, dissociative excitation (DE). The time-evolution of a wave packet on the potential energy surfaces of the resonance and cationic states shows, for the initial conditions studied, that the probability for DR is about 38 % while the probability for DE is negligible.

Etiopathogenic role of ERK5 signaling in sarcoma: prognostic and therapeutic implications.

Sarcomas constitute a heterogeneous group of rare and difficult-to-treat tumors that can affect people of all ages, representing one of the most common forms of cancer in childhood and adolescence. Little is known about the molecular entities involved in sarcomagenesis. Therefore, the identification of processes that lead to the development of the disease may uncover novel therapeutic opportunities. Here, we show that the MEK5/ERK5 signaling pathway plays a critical role in the pathogenesis of sarcomas. By developing a mouse model engineered to express a constitutively active form of MEK5, we demonstrate that the exclusive activation of the MEK5/ERK5 pathway can promote sarcomagenesis. Histopathological analyses identified these tumors as undifferentiated pleomorphic sarcomas. Bioinformatic studies revealed that sarcomas are the tumors in which ERK5 is most frequently amplified and overexpressed. Moreover, analysis of the impact of ERK5 protein expression on overall survival in patients diagnosed with different sarcoma types in our local hospital showed a 5-fold decrease in median survival in patients with elevated ERK5 expression compared with those with low expression. Pharmacological and genetic studies revealed that targeting the MEK5/ERK5 pathway drastically affects the proliferation of human sarcoma cells and tumor growth. Interestingly, sarcoma cells with knockout of ERK5 or MEK5 were unable to form tumors when engrafted into mice. Taken together, our results reveal a role of the MEK5/ERK5 pathway in sarcomagenesis and open a new scenario to be considered in the treatment of patients with sarcoma in which the ERK5 pathway is pathophysiologically involved.

Evaluation of Patient Experience With A Model of Coordinated Telematic Pharmaceutical Care Between Hospital and Rural Pharmacies in Spain: A Proof of Concept.

Purpose: To determine the usefulness of a coordinated pharmaceutical care model between the specialized hospital setting and the rural community care setting, based on the incorporation of telepharmacy based on Capacity-Motivation-Opportunity (CMO) methodology to improve patient experience with hospital medication prescriptions. Patients and Methods: Prospective cohort study in outpatients receiving telepharmacy based on CMO-based pharmaceutical care in rural areas in Spain between January and November 2021, conducted by the pharmacy department of four hospitals and 29 rural communities' pharmacy. Each patient was followed for 48 weeks on both face-to-face and telematic visits, scheduled and unscheduled at the patients' request. Patient experience (IEXPAC questionnaire), and satisfaction (EVASAF) were determined. Secondary variables included pharmaceutical care interventions, care coordination and clinical variables (compliance with pharmacotherapeutic objectives according to the clinical conditions of each patient), additionally measurement of individual holistic results (EQ5D-5L score) was evaluated. Results: A new telepharmacy tool (called Telemaco) was developed for a multidisciplinary healthcare team (available at: https://inteligeniapps.com/telemaco/) that includes seven different functionalities. We evaluated the first 20 patients (50% women) were included. Their median age was 66.0 years (IQR=14). A total of 215 visits were made (adding 150 video calls). A total of 64 visits were unscheduled (29.7%). The patient´s experience showed improvement (7.4 vs 9.5, p<0.005). The results of the EVASAF questionnaire were also higher (44 vs 48, p<0.001). Overall, 573 pharmaceutical interventions were performed. A difference was observed in patients who achieved the intended pharmacotherapeutic objectives: 48.5 vs 88.2 (p< 0.001). The mean EQ-5D-5L score was 74.7 ± 3.3 at baseline and 80.6 ± 3.6 points at the end (p>0.05). Conclusion: Telepharmacy based on the CMO-PC model, using the "Telemaco" tool, has improved the patient experience, satisfaction, and offered other advantages over the traditional model, including more pharmaceutical interventions adapted to the needs of each patient.

P38 MAPK and Radiotherapy: Foes or Friends?

Over the last 30 years, the study of the cellular response to ionizing radiation (IR) has increased exponentially. Among the various signaling pathways affected by IR, p38 MAPK has been shown to be activated both in vitro and in vivo, with involvement in key processes triggered by IR-mediated genotoxic insult, such as the cell cycle, apoptosis or senescence. However, we do not yet have a definitive clue about the role of p38 MAPK in terms of radioresistance/sensitivity and its potential use to improve current radiotherapy. In this review, we summarize the current knowledge on this family of MAPKs in response to IR as well as in different aspects related to radiotherapy, such as their role in the control of REDOX, fibrosis, and in the radiosensitizing effect of several compounds.

Assessing patient experience with a Telepharmacy model coordinated in the hospital and rural pharmacy setting: The TELEMACO project.

OBJECTIVE: To determine variation in patient experience with a model of Telepharmacy coordinated in the specialist hospital and rural pharmacy setting. METHOD: A pre-post experimental analytical study. A set of common essential  pharmacy tasks based on the capacity-motivation-opportunity method will be  performed in each participating site. A a Telepharmacy software will be  designed to include the following functionalities: history of patient  pharmaceutical profiling and prioritization; scheduled appointment book;  unscheduled visit record; generic participant communication wall; patient- professional instantaneous messaging chat; video calls; monitoring of  treatment adherence; and evaluation of patient-reported outcomes. Inclusion  criteria: age older than 18 years; being on regular hospital pharmacy follow-up for the last 6 months; using a stable drug therapy (without treatment changes  in the last 6 months); using a chronic hospital outpatient prescription (any  prescription valid for at least 6 months); living in any of the municipalities  served by the participating pharmacies or using the services of a participating  pharmacy located near the usual place of residence; granting informed consent prior to inclusion in the study. A 48-week follow-up will be performed of each  patient. The primary endpoint will be variation in patient experience, as  assessed using the "Instrumento de Evaluación de la eXperiencia del PAciente  Crónico" scale at baseline and at the end of the follow-up period. CONCLUSIONS: The incorporation, development and implementation of a  coordinated Telepharmacy care model will help us determine whether this  model is useful in improving patient follow-up and communication with pharmacy professionals at different levels of healthcare.

OBJETIVO: Determinar la variación en la experiencia del paciente con un modelo de atención farmacéutica coordinada entre farmacia hospitalaria y  farmacia rural especializado y el rural de atención comunitaria, basado en la  incorporación de la Telefarmacia.Método: Estudio analítico experimental de intervención antes-después. Para desarrollar el proyecto se realizarán una serie de procedimientos comunes e indispensables, basados en la metodología capacidad-motivación- oportunidad, en cada uno de los centros. Se diseñará una aplicacion  informática de Telefarmacia que contemplará, entre otras, las siguientes  funcionalidades: historial de caracterización y priorización farmacoterapéutica  de los pacientes; agenda de visitas programadas y registro de visitas no  programadas; muro de comunicación genérica entre participantes; chat de  mensajería instantánea entre pacientes y profesionales; videollamadas;  onitorización de la adherencia a la medicación y valoración de cuestionarios de  resultados reportados por pacientes. Se incluirán: pacientes mayores de 18  años; en seguimiento habitual en consultas externas de farmacia hospitalaria  durante más de 6 meses previo al inicio del estudio; que se encuentren en  situación estable desde el punto de vista farmacoterapéutico (sin cambios de  tratamientos en los últimos 6 meses); que tengan prescrito, al menos, un  tratamiento crónico de dispensación en oficina de farmacia (prescripción con  una vigencia de más de 6 meses de cualquier fármaco); que residan  habitualmente en las localidades de las oficinas de farmacia participantes en el  estudio o que acudan a las mismas por cercanía a su lugar de residencia  habitual; y que otorguen su consentimiento informado de participación. Cada  paciente tendrá un seguimiento de 48 semanas. La variable principal será la  diferencia en la experiencia del paciente, valorada mediante la escala  Instrumento de Evaluación de la eXperiencia del PAciente Crónico", desde el  inicio hasta el final de seguimiento. CONCLUSIONES: La puesta en marcha, desarrollo e implementación de la metodología de atención farmacéutica coordinada, basada en la  Telefarmacia, permitirá identificar, a partir de su medición, si esta metodología consigue llevar a cabo un seguimiento más oportuno de los  pacientes incluidos, y si proporciona una mejor experiencia de los mismos en  su relación con los profesionales farmacéuticos que les atienden en los  diferentes niveles de atención sanitaria.

Evaluación de la experiencia del paciente conun modelo de atención farmacéutica telemática coordinada entre farmacia hospitalaria y farmaciarural. Proyecto TELÉMACO / Assessing patient experience with a Telepharmacy model coordinated in the hospital and rural pharmacy setting: The TELEMACO project

Objetivo: Determinar la variación en la experiencia del paciente con unmodelo de atención farmacéutica coordinada entre farmacia hospitalariay farmacia rural especializado y el rural de atención comunitaria, basadoen la incorporación de la Telefarmacia.Método: Estudio analítico experimental de intervención antes-después. Paradesarrollar el proyecto se realizarán una serie de procedimientos comunes eindispensables, basados en la metodología capacidad-motivación-oportunidad, en cada uno de los centros.Se diseñará una aplicacion informática de Telefarmacia que contemplará,entre otras, las siguientes funcionalidades: historial de caracterización y priorización farmacoterapéutica de los pacientes; agenda de visitas programadasy registro de visitas no programadas; muro de comunicación genérica entreparticipantes; chat de mensajería instantánea entre pacientes y profesionales;videollamadas; monitorización de la adherencia a la medicación y valoración de cuestionarios de resultados reportados por pacientes.Se incluirán: pacientes mayores de 18 años; en seguimiento habitual en consultas externas de farmacia hospitalaria durante más de 6 meses previo al inicio del estudio; que se encuentren en situación estable desde el punto de vistafarmacoterapéutico (sin cambios de tratamientos en los últimos 6 meses). (AU)

Objective: To determine variation in patient experience with a model ofTelepharmacy coordinated in the specialist hospital and rural pharmacysetting.Method: A pre-post experimental analytical study. A set of commonessential pharmacy tasks based on the capacity-motivation-opportunitymethod will be performed in each participating site.A a Telepharmacy software will be designed to include the followingfunctionalities: history of patient pharmaceutical profiling and prioritization; scheduled appointment book; unscheduled visit record; generic participant communication wall; patient-professional instantaneous messagingchat; video calls; monitoring of treatment adherence; and evaluation ofpatient-reported outcomes.Inclusion criteria: age older than 18 years; being on regular hospital pharmacy follow-up for the last 6 months; using a stable drug therapy (withouttreatment changes in the last 6 months); using a chronic hospital outpatientprescription (any prescription valid for at least 6 months); living in any ofthe municipalities served by the participating pharmacies or using theservices of a participating pharmacy located near the usual place ofresidence; granting informed consent prior to inclusion in the study. A48-week follow-up will be performed of each patient. The primary endpoint will be variation in patient experience, as assessedusing the “Instrumento de Evaluación de la eXperiencia del PAciente Crónico” scale at baseline and at the end of the follow-up period.Conclusions: The incorporation, development and implementation ofa coordinated Telepharmacy care model will help us determine whetherthis model is useful in improving patient follow-up and communication withpharmacy professionals at different levels of healthcare. (AU)

Wearable system for outdoor air quality monitoring in a WSN with cloud computing: Design, validation and deployment.

Breathing poor-quality air is a global threat at the same level as unhealthy diets or tobacco smoking, so the availability of affordable instrument for the measurement of air pollutant levels is highly relevant for human and environmental protection. We developed an air quality monitoring platform that comprises a wearable device embedding low-cost metal oxide semiconductor (MOS) gas sensors, a PM sensor, and a smartphone for collecting the data using Bluetooth Low Energy (BLE) communication. Our own developed app displays information about the air surrounding the user and sends the gathered geolocalized data to a cloud, where the users can map the air quality levels measured in the network. The resulting device is small-sized, light-weighted, compact, and belt-worn, with a user-friendly interface and a low cost. The data collected by the sensor array are validated in two experimental setups, first in laboratory-controlled conditions and then against referential pollutant concentrations measured by standard instruments in an outdoor environment. The performance of our air quality platform was tested in a field testing campaign in Barcelona with six moving devices acting as wireless sensor nodes. Devices were trained by means of machine learning algorithms to differentiate between air quality index (AQI) referential concentration values (97% success in the laboratory, 82.3% success in the field). Humidity correction was applied to all data.

ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.

Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5-KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.

Benchmarking the driver acceleration impact on vehicle energy consumption and CO2 emissions.

The study proposes a methodology for quantifying the impact of real-world heterogeneous driving behavior on vehicle energy consumption, linking instantaneous acceleration heterogeneity and CO2 emissions. Data recorded from 20 different drivers under real driving are benchmarked against the Worldwide Harmonized Light Vehicle Test Cycle (WLTC), first by correlating the speed cycle with individual driver behavior and then by quantifying the CO2 emissions and consumption. The vehicle-Independent Driving Style metric (IDS) is used to quantify acceleration dynamicity, introducing driving style stochasticity by means of probability distribution functions. Results show that the WLTC cycle assumes a relatively smooth acceleration style compared to the observed ones. The method successfully associates acceleration dynamicity to CO2 emissions. We observe a 5% difference in the CO2 emissions between the most favourable and the least favourable case. The intra-driver variance reached 3%, while the inter-driver variance is below 2%. The approach can be used for quantifying the driving style induced emissions divergence.

Portable Electronic Nose Based on Digital and Analog Chemical Sensors for 2,4,6-Trichloroanisole Discrimination.

2,4,6-trichloroanisole (TCA) is mainly responsible for cork taint in wine, which causes significant economic losses; therefore, the wine and cork industries demand an immediate, economic, noninvasive and on-the-spot solution. In this work, we present a novel prototype of an electronic nose (e-nose) using an array of digital and analog metal-oxide gas sensors with a total of 31 signals, capable of detecting TCA, and classifying cork samples with low TCA concentrations (≤15.1 ng/L). The results show that the device responds to low concentrations of TCA in laboratory conditions. It also differentiates among the inner and outer layers of cork bark (81.5% success) and distinguishes among six different samples of granulated cork (83.3% success). Finally, the device can predict the concentration of a new sample within a ±10% error margin.

Classification for Staging and Managing Patients with Biopolymer-induced Human Adjuvant Disease.

Biopolymer-induced human adjuvant disease (BHAD) is a chronic clinical condition that requires surgical intervention, regardless of the presence of symptoms, to minimize the risk of functional, aesthetic, and systemic sequelae and the development of conditions simulating autoimmune disease. We propose a classification for BHAD on the basis of course of the disease, which will make it possible to assess the damage and difficulty in patients, leading to a more appropriate therapeutic approach. METHODS: A protocol study was implemented. A casuistry of patients with a diagnosis of autoimmune/inflammatory syndrome induced by adjuvants was taken into account according to the Shoenfeld criteria. Qualitative variables were analyzed through frequencies and percentages, and quantitative variables were analyzed with measures of central tendency and dispersion. The diagnostic validity of the signs and symptoms was analyzed using some paraclinical tests. RESULTS: A total of 190 patients diagnosed with autoimmune/inflammatory syndrome induced by adjuvants with biopolymers in the buttocks and who underwent a surgical procedure by the open, masked technique between January 2017 and December 2020 were selected. Considering each sign and symptom, the location of the biopolymers in different planes, and pathophysiology of the clinical course of the disease, a classification was proposed that takes into account diagnostic imaging findings, local clinical signs, systemic symptoms, systemic clinical signs, and autoimmune markers. CONCLUSION: Some signs associated with biomarkers with sensitivity and specificity values can influence the pretest decision to request paraclinicals, improving the diagnostic probability and cost effectiveness in these patients.

A Novel Bike-Mounted Sensing Device with Cloud Connectivity for Dynamic Air-Quality Monitoring by Urban Cyclists.

We present a device based on low-cost electrochemical and optical sensors, designed to be attached to bicycle handlebars, with the aim of monitoring the air quality in urban environments. The system has three electrochemical sensors for measuring NO2 and O3 and an optical particle-matter (PM) sensor for PM2.5 and PM10 concentrations. The electronic instrumentation was home-developed for this application. To ensure a constant air flow, the input fan of the particle sensor is used as an air supply pump to the rest of the sensors. Eight identical devices were built; two were collocated in parallel with a reference urban-air-quality-monitoring station and calibrated using a neural network (R2 > 0.83). Several bicycle routes were carried out throughout the city of Badajoz (Spain) to allow the device to be tested in real field conditions. An air-quality index was calculated to facilitate the user's understanding. The results show that this index provides data on the spatiotemporal variability of pollutants between the central and peripheral areas, including changes between weekdays and weekends and between different times of the day, thus providing valuable information for citizens through a dedicated cloud-based data platform.

Low-Cost Air Quality Measurement System Based on Electrochemical and PM Sensors with Cloud Connection.

This paper presents a portable device for outdoor air quality measurement that provides concentration values for the main pollutants: NO2, NO, CO, O3, PM2.5 and PM10, and other values such as temperature, humidity, location, and date. The device is based on the use of commercial electrochemical gas and optical particle matter sensors with a careful design of the electronics for reducing the electrical noise and increasing the accuracy of the measurements. The result is a low-cost system with IoT technology that connects to the Internet through a GSM module and sends all real-time data to a cloud platform with storage and computational potential. Two identical devices were fabricated and installed on a mobile reference measurement unit and deployed in Badajoz, Spain. The results of a two-month field campaign are presented and published. Data obtained from these measurements were calibrated using linear regression and neural network techniques. Good performance has been achieved for both gaseous pollutants (with a Pearson correlation coefficient of up to 0.97) and PM sensors.

Haemophilus urethritis in males: A series of 30 cases.

INTRODUCTION AND OBJECTIVES: Pathogens such as Haemophilus spp. have been associated with non-gonococcal urethritis, but their role is unproven. To describe the clinical characteristics and therapeutic outcomes in male patients diagnosed with Haemophilus spp. urethritis. METHODS: We carried out a retrospective study of all patients who presented to our hospital (in either the emergency department or the outpatient clinic) between July 2016 and April 2018 in whom Haemophilus spp. was isolated in the urethral samples. We enrolled 30 men with Haemophilus spp.-positive urethritis, including coinfections with Neisseria gonorrhoeae and Chlamydia trachomatis. Clinical, laboratory, demographic, and behavioral data were obtained by reviewing medical histories. RESULTS: The mean age of the patients was 36.6 years (range 21-87). Seventeen patients (63%) reported being exclusively heterosexual. Three patients (10%) were HIV infected, all of them with an undetectable viral load. The most common clinical presentation was mucopurulent urethral discharge, in 13 patients (43%). The antibiotic treatment achieved a complete clinical resolution in 73%. CONCLUSIONS: Haemophilus urethritis affected men regardless of their sexual orientation or HIV status. Unprotected oral sex may play a role in its transmission. The limitations of the study preclude verification of the pathogenic role of Haemophilus spp. in acute urethritis, but clinical response after antibiotic treatment suggests that Haemophilus spp. can play such a role.

A classical and semiclassical study of collisions between Xq+ ions and water molecules.

Collisions of He2+, Li3+ and C3+ ions with water molecules are studied at energies ranging between 20 keV u-1 and 500 keV u-1. Three methods are employed: the classical trajectory Monte Carlo (CTMC), the expansion of the scattering wave function in terms of asymptotic frozen molecular orbitals (AFMO) and a lattice method to numerically solve the time-dependent Schrödinger equation (GridTDSE). Total cross sections for single ionization, single electron capture, transfer ionization and electron production are calculated and compared with previous close-coupling calculations and experiments. The fragmentation branching ratios are discussed.

Early Phase of Type 1 Diabetes Decreases the Responsiveness of C-Fiber Nociceptors in the Temporomandibular Joint of Rats.

Diabetes is a chronic degenerative disease that represent a major threat to public health worldwide. Once the disease is established, one of the major concerns about the diabetes complications is the development of neuropathy. This study established an experimental model that evaluates the effect of type 1 diabetes on nociceptive challenges in the temporomandibular joint (TMJ). Streptozotocin-induced type 1 (STZ 75 mg/Kg) diabetes inhibited the responsiveness of C-fibers nociceptors located in the TMJ of Wistar rats since seventh day after the disease induction. Diabetes-induced hyporesponsiveness of C-fibers nociceptors was associated with significantly reduction of protein level of neuropeptides Substance P and Calcitonin Gene Related Peptide. Diabetic animals pre-treated with Protein Kinase C (PKC)-α and -ß inhibitor (GO6976) or PKC-ß inhibitor (LY333531) significantly increased capsaicin-induced nociception in the TMJ higher protein levels of Na+/K+-ATPase pump in the trigeminal ganglia. On the other hand, although diabetes inhibits formalin-induced nociception higher protein levels of pro-inflammatory cytokine IL1-ß and chemokine CINC-1/CXCL-1 were observed. Overall, the results of the present work suggest that diabetes causes a hyporesponsiveness of C-fiber and a potentialization of the inflammatory response which may result in the degenerative process of periarticular tissues without pain perception.

Electrosynthesis of N-Methylisatin.

Isatin in a solution of dry N,N-dimethylformamide/NaClO4 is electroreduced in the presence of CH3I. N-methylisatin (NMI) is obtained in quantitative molar yield and high current efficiency by controlled potential electrolysis (CPE). NMI and N-methylisatoic anhydride are the reaction products when CPE is performed in the absence of CH3I, but adding it once the CPE was completed. The water effect on the identity and yield of the reaction product(s) is investigated. Reaction pathways are proposed.

Rh(III)-Catalyzed [5 + 2] Oxidative Annulation of Cyclic Arylguanidines and Alkynes to 1,3-Benzodiazepines. A Striking Mechanistic Proposal from DFT.

A novel and mild Rh(III)-catalyzed [5 + 2] oxidative annulation between cyclic arylguanidines and alkynes efficiently affords 1,3-benzodiazepines (pentacyclic guanidines). The use of O2 as the sole oxidant in place of commonly used metal oxidants such as AgOAc clearly improves the efficiency of the oxidative annulation process. The mechanism of the cycloaddition most likely involves the formation of an eight-membered rhodacycle. DFT calculations support a striking mechanistic proposal for the [5 + 2] oxidative annulation.

Nonadiabatic fragmentation of H2O+ and isotopomers. Wave packet propagation using ab initio wavefunctions.

The fragmentation of the water cation from its B[combining tilde] 2B2 electronic state, allowing the participation of the X[combining tilde] 2B1, Ã 2A1 and C[combining tilde] 2B1 states in the process, is simulated using the extended capabilities of the collocation GridTDSE code to account for the nonadiabatic propagation of wave packets in several potential energy surfaces connected by nonadiabatic couplings. Molecular data are calculated ab initio. Two initial wave packets are considered to reproduce two different experiments. The isotopic effect in the fragmentation of D2O+ and HDO+ is also studied and the results show very good agreement with the experimental cleavage preference in the fragmentation of HDO+.