Performance of amplicon and capture based next-generation sequencing approaches for the epidemiological surveillance of Omicron SARS-CoV-2 and other variants of concern.

To control the SARS-CoV-2 pandemic, healthcare systems have focused on ramping up their capacity for epidemiological surveillance through viral whole genome sequencing. In this paper, we tested the performance of two protocols of SARS-CoV-2 nucleic acid enrichment, an amplicon enrichment using different versions of the ARTIC primer panel and a hybrid-capture method using KAPA RNA Hypercap. We focused on the challenge of the Omicron variant sequencing, the advantages of automated library preparation and the influence of the bioinformatic analysis in the final consensus sequence. All 94 samples were sequenced using Illumina iSeq 100 and analysed with two bioinformatic pipelines: a custom-made pipeline and an Illumina-owned pipeline. We were unsuccessful in sequencing six samples using the capture enrichment due to low reads. On the other hand, amplicon dropout and mispriming caused the loss of mutation G21987A and the erroneous addition of mutation T15521A respectively using amplicon enrichment. Overall, we found high sequence agreement regardless of method of enrichment, bioinformatic pipeline or the use of automation for library preparation in eight different SARS-CoV-2 variants. Automation and the use of a simple app for bioinformatic analysis can simplify the genotyping process, making it available for more diagnostic facilities and increasing global vigilance.

Decay of HIV RNA in Seminal Plasma and Rectal Fluid in Treatment-Naive Adults Starting Antiretroviral Therapy With Dolutegravir Plus Lamivudine or Bictegravir/Emtricitabine/Tenofovir Alafenamide.

BACKGROUND: Decay of HIV in seminal plasma (SP) and rectal fluid (RF) has not yet been described for the antiretroviral combination of dolutegravir (DTG) + lamivudine (3TC). METHODS: In this randomized multicenter pilot trial, males who were antiretroviral naive were randomized (2:1) to DTG + 3TC or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). HIV-1 RNA was measured in blood plasma (BP), SP, and RF at baseline; days 3, 7, 14, and 28; and weeks 12 and 24. RESULTS: Of 25 individuals enrolled, 24 completed the study (DTG + 3TC, n = 16; BIC/FTC/TAF, n = 8). No significant differences were observed between groups for median decline in HIV-1 RNA from baseline at each time point or median time to achieve HIV-1 RNA <20 copies/mL in BP and SP and <20 copies/swab in RF. HIV-1 RNA decay patterns were compared in individuals receiving DTG + 3TC. Despite significantly higher percentages for changes from baseline in BP, median (IQR) times to HIV-1 RNA suppression were shorter in SP (7 days; 0-8.75) and RF (10.5 days; 3-17.5) than in BP (28 days; 14-84; P < .001). CONCLUSIONS: Comparable HIV-1 RNA decay in BP, SP, and RF was observed between DTG + 3TC and BIC/FTC/TAF. As shown with triple-drug integrase inhibitor-based regimens, rapid HIV-1 RNA suppression in SP and RF is achieved with DTG + 3TC, despite decay patterns differing from those of BP. CLINICAL TRIALS REGISTRATION: EudraCT 2019-004109-28.

Galaxies in voids assemble their stars slowly.

Galaxies in the Universe are distributed in a web-like structure characterized by different large-scale environments: dense clusters, elongated filaments, sheetlike walls and under-dense regions, called voids1-5. The low density in voids is expected to affect the properties of their galaxies. Indeed, previous studies6-14 have shown that galaxies in voids are, on average, bluer and less massive, and have later morphologies and higher current star formation rates than galaxies in denser large-scale environments. However, it has never been observationally proved that the star formation histories (SFHs) in voids are substantially different from those in filaments, walls and clusters. Here we show that void galaxies have had, on average, slower SFHs than galaxies in denser large-scale environments. We also find two main SFH types present in all the environments: 'short-timescale' galaxies are not affected by their large-scale environment at early times but only later in their lives; 'long-timescale' galaxies have been continuously affected by their environment and stellar mass. Both types have evolved more slowly in voids than in filaments, walls and clusters.

Proof of concept of the potential of a machine learning algorithm to extract new information from conventional SARS-CoV-2 rRT-PCR results.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been and remains one of the major challenges modern society has faced thus far. Over the past few months, large amounts of information have been collected that are only now beginning to be assimilated. In the present work, the existence of residual information in the massive numbers of rRT-PCRs that tested positive out of the almost half a million tests that were performed during the pandemic is investigated. This residual information is believed to be highly related to a pattern in the number of cycles that are necessary to detect positive samples as such. Thus, a database of more than 20,000 positive samples was collected, and two supervised classification algorithms (a support vector machine and a neural network) were trained to temporally locate each sample based solely and exclusively on the number of cycles determined in the rRT-PCR of each individual. Overall, this study suggests that there is valuable residual information in the rRT-PCR positive samples that can be used to identify patterns in the development of the SARS-CoV-2 pandemic. The successful application of supervised classification algorithms to detect these patterns demonstrates the potential of machine learning techniques to aid in understanding the spread of the virus and its variants.

Uncovering temperature-dependent exciton-polariton relaxation mechanisms in hybrid organic-inorganic perovskites.

Hybrid perovskites have emerged as a promising material candidate for exciton-polariton (polariton) optoelectronics. Thermodynamically, low-threshold Bose-Einstein condensation requires efficient scattering to the polariton energy dispersion minimum, and many applications demand precise control of polariton interactions. Thus far, the primary mechanisms by which polaritons relax in perovskites remains unclear. In this work, we perform temperature-dependent measurements of polaritons in low-dimensional perovskite wedged microcavities achieving a Rabi splitting of [Formula: see text] = 260 ± 5 meV. We change the Hopfield coefficients by moving the optical excitation along the cavity wedge and thus tune the strength of the primary polariton relaxation mechanisms in this material. We observe the polariton bottleneck regime and show that it can be overcome by harnessing the interplay between the different excitonic species whose corresponding dynamics are modified by strong coupling. This work provides an understanding of polariton relaxation in perovskites benefiting from efficient, material-specific relaxation pathways and intracavity pumping schemes from thermally brightened excitonic species.

Armonización Curricular Farmacéutica en Iberoamérica. Documento de trabajo de la Conferencia Iberoamericana de Facultades de Farmacia (COIFFA) / Pharmaceutical Curriculum Harmonization in Ibero-America. Working document of the Ibero-American Conference of Faculties of Pharmacy (COIFFA)

La Conferencia Iberoamericana de Facultades de Farmacia (COIFFA) viene desarrollando desde su fundación como Conferencia Hispanoamericana (COHIFFA) en 1992, en la Universidad de los Andes (Mérida, Venezuela) una amplia labor en el ámbito de la formación y educación farmacéutica. Esta labor se ha traducido en declaraciones sucesivas desde la efectuada en Santiago (Chile) hasta la más reciente de Xochimilco (México). El grado de avance que han experimentado las ciencias y la práctica farmacéutica en las últimas décadas ha sido espectacular. Así se refleja en documentos de organismos y foros nacionales e internacionales. A esto se une las facilidades que en el ámbito de la movilidad internacional procuran tanto las Universidades a través de sus convenios bilaterales, como los organismos nacionales e internacionales de América Latina y de la Unión Europea, a través de los proyectos y convocatorias pertinentes. Todo ello hace aconsejable la elaboración por parte de COIFFA de un documento marco de consenso, en donde se recoja la problemática que el trascendental tema de la armonización de los estudios de farmacia conlleva. Los esfuerzos que ha venido realizando COIFFA se han traducido en la elaboración durante el Simposio Biregional Unión Europea-América Latina celebrado en junio de 2018 Xochimilco (México), de un documento de trabajo. Tres mesas de discusión coordinadas han tenido por objeto: I) el análisis y definición de perfil de egreso y de los mínimos curriculares; II) el análisis de los términos utilizados en la denominación de programas académicos títulos universitarios y distintas actividades; y III) el análisis y propuestas de mecanismos de colaboración y cofinanciación interinstitucionales Universidad-Gobierno-Empresa. (AU)

The Ibero-American Conference of Faculties of Pharmacy (COIFFA) has been developing a wide-ranging task in the field of pharmaceutical training and education since its foundation as Hispanic-American Conference (COHIFFA) in 1992, at the Universidad de los Andes (Mérida, Venezuela). This work has been materialized into successive statements from the one made in Santiago (Chile) to the most recent one in Xochimilco (Mexico). The degree of progress that the sciences and pharmaceutical practice have experienced in recent decades has been spectacular. This is reflected in documents from national and international organizations and forums. To this is added the facilities that, in the field of international mobility, universities get through their bilateral agreements, as well as with national and international organizations in Latin America and the European Union, through the relevant projects and calls. All this makes advisable the elaboration on the part of COIFFA of a framework document of consensus, where the problematic that the transcendental subject of the harmonization of the pharmacy studies entails be covered. The efforts that COIFFA has been carrying out have resulted in the elaboration of a working document at the Biregional European Union-Latin America Symposium held in June 2018 in Xochimilco (Mexico). Three coordinated working groups were there devoted to: I) the analysis and definition of the graduate profile, as well as the common minimum topics to be included in the “pensum”; II) the analysis of the terms to be used in the denomination of academic programs, university degrees and various related activities; III) the analysis and proposals for cooperation mechanisms and properly ways of University-Government-Company co-financing. (AU)

Case report: BA.1 subvariant showing a BA.2-like pattern using a variant-specific PCR assay due to a single point mutation downstream the spike 69/70 deletion.

BACKGROUND: SARS-CoV-2 variant tracking is key to the genomic surveillance of the COVID-19 pandemic. While next-generation sequencing (NGS) is commonly used for variant determination, it is expensive and time-consuming. Variant-specific PCR (vsPCR) is a faster, cheaper method that detects specific mutations that are considered variant-defining. These tests usually rely on specific amplification when a mutation is present or a specific melting temperature peak after amplification. CASE PRESENTATION: A discrepant result between vsPCR and NGS was found in seventeen SARS-CoV-2 samples from Galicia, Spain. A cluster of BA.1 Omicron SARS-CoV-2 variant showed a BA.2-like melting temperature pattern due to a point mutation (C21772T) downstream the deletion of the spike amino acids 69/70. As the 69/70 deletion is widely used for differentiation between BA.1 and BA.2 by vsPCR, C21772T can cause BA.1 samples to be misinterpreted as BA.2. Over a thousand BA.1 sequences in the EpiCoV database contain this mutation. CONCLUSIONS: To our knowledge, this is the first case of a point mutation causing a vsPCR algorithm to misclassify BA.1 samples as BA.2. This is an example of how mutations in the probe target area of vsPCR tests based on melting curve analysis can lead to variant misclassification. NGS confirmation of vsPCR results is relevant for the accuracy of the epidemiological surveillance. In order to overcome the possible impact of novel mutations, diagnostic tools must be constantly updated.

Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC.

Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients.

Surface-Assisted Synthesis of N-Containing π-Conjugated Polymers.

On-surface synthesis has recently emerged as a powerful strategy to design conjugated polymers previously precluded in conventional solution chemistry. Here, an N-containing pentacene-based precursor (tetraazapentacene) is ex-professo synthesized endowed with terminal dibromomethylene (:CBr2 ) groups to steer homocoupling via dehalogenation on metallic supports. Combined scanning probe microscopy investigations complemented by theoretical calculations reveal how the substrate selection drives different reaction mechanisms. On Ag(111) the dissociation of bromine atoms at room temperature triggers the homocoupling of tetraazapentacene units together with the binding of silver adatoms to the nitrogen atoms of the monomers giving rise to a N-containing conjugated coordination polymer (P1). Subsequently, P1 undergoes ladderization at 200 °C, affording a pyrrolopyrrole-bridged conjugated polymer (P2). On Au(111) the formation of the intermediate polymer P1 is not observed and, instead, after annealing at 100 °C, the conjugated ladder polymer P2 is obtained, revealing the crucial role of metal adatoms on Ag(111) as compared to Au(111). Finally, on Ag(100) the loss of :CBr2 groups affords the formation of tetraazapentacene monomers, which coexist with polymer P1. Our results contribute to introduce protocols for the synthesis of N-containing conjugated polymers, illustrating the selective role of the metallic support in the underlying reaction mechanisms.

Amikacin pharmacokinetics in elderly patients with severe infections.

OBJECTIVE: The aim of this study was to characterize the population pharmacokinetics of amikacin in elderly patients by means of nonlinear mixed effects modelling and to propose initial dosing schemes to optimize therapy based on PK/PD targets. METHOD: A total of 137 elderly patients from 65 to 94 years receiving intravenous amikacin and routine therapeutic drug monitoring at Hospital Universitario Severo Ochoa were included. Concentration-time data and clinical information were retrospectively collected; initial doses of amikacin ranged from 5.7 to 22.5 mg/kg/day and each patient provided between 1 and 10 samples. RESULTS: Amikacin pharmacokinetics were best described by a two-compartment open model; creatinine clearance (CrCL) was related to drug clearance (2.75 L/h/80 mL/min) and it was augmented 28% when non-steroidal anti-inflammatory drugs were concomitantly administered. Body mass index (BMI) influenced the central volume of distribution (17.4 L/25 kg/m2). Relative absolute prediction error was reduced from 33.2% (base model) to 17.9% (final model) when predictive performance was evaluated with a different group of elderly patients. A nomogram for initial amikacin dosage was developed and evaluated based on stochastic simulations considering final model to achieve PK/PD targets (Cmax/MIC>10 and AUC/MIC>75) and to avoid toxic threshold (Cmin<2.5 mg/L). CONCLUSION: Initial dosing approach for amikacin was designed for elderly patients based on nonlinear mixed effects modeling to maximize the probability to attain efficacy and safety targets considering individual BMI and CrCL.

Revealing Weak Dimensional Confinement Effects in Excitonic Silver/Bismuth Double Perovskites.

Lead-free perovskites are attracting increasing interest as nontoxic materials for advanced optoelectronic applications. Here, we report on a family of silver/bismuth bromide double perovskites with lower dimensionality obtained by incorporating phenethylammonium (PEA) as an organic spacer, leading to the realization of two-dimensional double perovskites in the form of (PEA)4AgBiBr8 (n = 1) and the first reported (PEA)2CsAgBiBr7 (n = 2). In contrast to the situation prevailing in lead halide perovskites, we find a rather weak influence of electronic and dielectric confinement on the photophysics of the lead-free double perovskites, with both the 3D Cs2AgBiBr6 and the 2D n = 1 and n = 2 materials being dominated by strong excitonic effects. The large measured Stokes shift is explained by the inherent soft character of the double-perovskite lattices, rather than by the often-invoked band to band indirect recombination. We discuss the implications of these results for the use of double perovskites in light-emitting applications.

Consecuencias en salud (mortalidad e institucionalización) de la fractura de cadera en la población anciana. Estudio de cohortes poblacional en Segovia / Health consequences (mortality and institutionalization) of hip fracture among the elderly people: Population cohort study in Segovia

Objetivo: Conocer las consecuencias sociosanitarias de la fractura de cadera (FC). Diseño: Estudio de cohortes históricas de una población mayor de 75 años de un área sanitaria durante un periodo de 5 años. Emplazamiento: Área de Salud de Segovia. Participantes: Todos los pacientes mayores de 75 años con diagnóstico de FC, excluyendo desplazados o transeúntes. Intervenciones: Se analizaron los cambios sociosanitarios que se producen tras la FC con respecto a su situación basal y las variables que más influyen en la mortalidad e institucionalización. Medidas principales: Se registraron 1.159FC, con una incidencia anual constante de 10,7‰. La prevalencia fue mayor en mujeres: 7,4 vs. 3,7%. Resultados: El perfil basal fue una mujer de 87 años pluripatológica, no-institucionalizada, que conserva su independencia para la vida diaria y que sufre una FC por una caída accidental en su domicilio. Al final del periodo de estudio un 51% fueron institucionalizados permanentemente influyendo negativamente el tener un peor deterioro mental, una peor dependencia y los reingresos posteriores, además fallecieron un 45,5%, un 25,5% durante el primer año; las condiciones más desfavorables fueron: ser previamente dependiente, tener un deterioro mental severo y sexo masculino, y dentro de las comorbilidades la más influyente fue el tener una anemia previa. Conclusiones: Nuestros datos confirman el deterioro de la autonomía-capacidad funcional tras una FC, en consonancia con lo publicado, y han permitido identificar qué ancianos son los que tienen mayor riesgo de complicaciones a corto y medio plazo (institucionalización y muerte).(AU)

Objective: In order to know the social and health consequences of hip fractures (HF). Design: A retrospective cohort study of an entire health area was carried out in patients aged 75 or more, over a period of 5 years. Site: Segovia Health Area. Participants: All patients older than 75 years with a diagnosis of HF, excluding displaced and passerby. Interventions: The socio-sanitary changes that occur after the HF in respect to their baseline situation (family situation, comorbidities, dependence and mental situation) and the variables which most influence mortality and institutionalization after the HF were analyzed. Main measurements: One thousand one hundred fifty-nine HF were recorded, with a constant annual incidence of 10.7‰. The prevalence was higher in women: 7.4% versus 3.7%. Results: The baseline profile is a pluripatological, non-institutionalized, 87-year-old woman, who retains her independent in her daily life and suffers from a HF due to an accidental fall in her home. At the end of the study period 51% were permanently institutionalized, negatively influencing having worse mental deterioration, worse dependence and subsequent readmissions and in addition, 45.5% died, 25.5% during the first year. The most unfavorable conditions were being previously dependent, having severe mental deterioration, male and within the comorbidities the most influential was previously having an anemia. Conclusions: Our data confirms the deterioration of the autonomy-functional capacity after a HF, in line with what has been published, and has allowed to identify which elderly people are at the greatest risk of complications in the short and medium term (institutionalization and death).(AU)

[Health consequences (mortality and institutionalization) of hip fracture among the elderly people: Population cohort study in Segovia]. / Consecuencias en salud (mortalidad e institucionalización) de la fractura de cadera en la población anciana. Estudio de cohortes poblacional en Segovia.

OBJECTIVE: In order to know the social and health consequences of hip fractures (HF). DESIGN: A retrospective cohort study of an entire health area was carried out in patients aged 75 or more, over a period of 5 years. SITE: Segovia Health Area. PARTICIPANTS: All patients older than 75 years with a diagnosis of HF, excluding displaced and passerby. INTERVENTIONS: The socio-sanitary changes that occur after the HF in respect to their baseline situation (family situation, comorbidities, dependence and mental situation) and the variables which most influence mortality and institutionalization after the HF were analyzed. MAIN MEASUREMENTS: One thousand one hundred fifty-nine HF were recorded, with a constant annual incidence of 10.7‰. The prevalence was higher in women: 7.4% versus 3.7%. RESULTS: The baseline profile is a pluripatological, non-institutionalized, 87-year-old woman, who retains her independent in her daily life and suffers from a HF due to an accidental fall in her home. At the end of the study period 51% were permanently institutionalized, negatively influencing having worse mental deterioration, worse dependence and subsequent readmissions and in addition, 45.5% died, 25.5% during the first year. The most unfavorable conditions were being previously dependent, having severe mental deterioration, male and within the comorbidities the most influential was previously having an anemia. CONCLUSIONS: Our data confirms the deterioration of the autonomy-functional capacity after a HF, in line with what has been published, and has allowed to identify which elderly people are at the greatest risk of complications in the short and medium term (institutionalization and death).

Hole-Transporting Materials for Perovskite Solar Cells Employing an Anthradithiophene Core.

A decade after the report of the first efficient perovskite-based solar cell, development of novel hole-transporting materials (HTMs) is still one of the main topics in this research field. Two of the main advance vectors of this topic lie in obtaining materials with enhanced hole-extracting capability and in easing their synthetic cost. The use of anthra[1,9-bc:5,10-b'c']dithiophene (ADT) as a flat π-conjugated frame for bearing arylamine electroactive moieties allows obtaining two novel highly efficient HTMs from very cheap precursors. The solar cells fabricated making use of the mixed composition (FAPbI3)0.85(MAPbBr3)0.15 perovskite and the novel ADT-based HTMs show power conversion efficiencies up to 17.6% under 1 sun illumination compared to the 18.1% observed when using the benchmark compound 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD). Detailed density functional theory calculations allow rationalization of the observed opto-electrochemical properties and predict a flat molecular structure with a low reorganization energy that supports the high conductivity measured for the best-performing HTM.

Prevalencia y caracterización del dolor irruptivo oncológico en pacientes hospitalizados en Vigo. Estudio Dolopaho / Prevalence and characterization of breakthough cancer pain in hospitalized patients in Vigo. The Dolopaho study

Introducción: El dolor sigue siendo en la actualidad un problema no resuelto en los pacientes con cáncer. A pesar de los avances en el tratamiento del dolor en los últimos años, persisten lagunas que dificultan un tratamiento global, como es el caso del dolor irruptivo oncológico (DIO). Objetivos: Evaluar la prevalencia de DIO de una muestra de pacientes ingresados en un servicio de oncología médica, analizar si el dolor era el principal motivo de ingreso en estos pacientes, así como determinar si existe un infradiagnóstico y, por tanto, un infratratamiento en los mismos previamente al ingreso. Métodos: Estudio observacional prospectivo. Se reclutaron los pacientes de forma consecutiva, independientemente del motivo de ingreso. Las variables analizadas en relación con el dolor irruptivo fueron las siguientes: presencia de dolor irruptivo según el algoritmo de Davies; semejanza de los episodios de dolor irruptivo entre sí y respecto al dolor basal; número de crisis de dolor a lo largo del día y a lo largo de la semana; escala visual analógica del dolor irruptivo; tiempo desde el inicio del dolor hasta su máxima intensidad medida en los siguientes rangos: < 5 min, 5-30 min, > 30 min; la duración de los episodios: < 5 min, 5-30 min, > 30 min; desencadenantes del dolor irruptivo (incidental, espontáneo); percepción individual de la alteración en la calidad de vida y efectividad de los fármacos utilizados. Resultados: Se incluyeron un total de 115 pacientes. En la muestra analizada el 33,9 % de los pacientes presentaron dolor irruptivo, de ellos el 95 % recibían tratamiento con opioides mayores, pero en solo el 56 % de los casos se asociaron a opioides de liberación ultrarrápida. Conclusión: El manejo de los pacientes con DIO continúa siendo un reto a día de hoy. Cerca de la mitad de los pacientes con dolor irruptivo no habían recibido tratamiento adecuado en nuestro estudio y, por tanto, probablemente no estaban bien caracterizados. (AU)

Background: Pain is often inadequately treated in patients with cancer. Although in recent years there have been major advances in the treatment of pain, there are still gaps for a global treatment, such as breakthrouth cancer pain (BCP). Objectives: The main objective was to evaluate the prevalence of BCP in a sample of patients admitted to a oncology medical department, in order to see whether pain is the main reason for admission in these patients, as well as to determine whether they were correctly treated and diagnosed before admission. Methods: An observational, prospective study. Patients were enrolled consecutively, regardless of reason for admission. The variables analyzed in relation to breakthrough pain were the following: presence of breakthrough pain according to the Davies scale; similarities of breakthrough pain events to each other and to baseline pain; number of irruptive pain events throughout the day and throughout the week; visual analogue scale of breakthrough pain; time between the onset of breakthrough pain and maximum intensity as measured in the following ranges: < 5 minutes, 5-30 minutes, > 30 minutes; duration of the breakthrough pain event (< 5 minutes, 5-30 minutes, > 30 minutes); triggers of breakthrough pain (incidental, spontaneous); perceived quality of life impairment and effectiveness of the drugs used. Results: A total of 115 patients consecutively admitted were analyzed regardless of reason for admission. In the analyzed sample, 33.9 % of patients had breakthrouth pain, and 95 % of the patients with breakthrough pain received treatment with strong opioids, though only in 56.4 % of cases associated with ultra-rapid-release opioids.Conclusions: The management of BCP is still a challenge. About half of patients with breakthrough cancer pain had not received adecuated treatment in our study, and were therefore poorly diagnosed. (AU)

Dynamics of the Decay of Human Immunodeficiency Virus (HIV) RNA and Distribution of Bictegravir in the Genital Tract and Rectum in Antiretroviral-naive Adults Living With HIV-1 Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (Spanish HIV/AIDS Research Network, PreEC/RIS 58).

BACKGROUND: The pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)-1 RNA in genital fluids and the rectum have not yet been addressed. METHODS: We conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: The study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41-3.79), 4.19 (2.98-4.70), and 2.56 (1.61-3.56) log10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1-923) ng/mL, 74.1 (6.0-478.5) ng/g, and 61.6 (14.4-1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively. CONCLUSIONS: BIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL). CLINICAL TRIALS REGISTRATION: EudraCT 2018-002310-12.

Pooling for SARS-CoV-2 control in care institutions.

BACKGROUND: Workers and residents in Care Homes are considered at special risk for the acquisition of SARS-CoV-2 infection, due to the infectivity and high mortality rate in the case of residents, compared to other containment areas. The role of presymptomatic people in transmission has been shown to be important and the early detection of these people is critical for the control of new outbreaks. Pooling strategies have proven to preserve SARS-CoV-2 testing resources. The aims of the present study, based in our local experience, were (a) to describe SARS-CoV-2 prevalence in institutionalized people in Galicia (Spain) during the Coronavirus pandemic and (b) to evaluate the expected performance of a pooling strategy using RT-PCR for the next rounds of screening of institutionalized people. METHODS: A total of 25,386 Nasopharyngeal swab samples from the total of the residents and workers at Care Homes in Galicia (March to May 2020) were individually tested using RT-PCR. Prevalence and quantification cycle (Cq) value distribution of positives was calculated. Besides, 26 pools of 20 samples and 14 pools of 5 samples were tested using RT-PCR as well (1 positive/pool). Pooling proof of concept was performed in two populations with 1.7 and 2% prevalence. RESULTS: Distribution of SARS-CoV-2 infection at Care Homes was uneven (0-60%). As the virus circulation global rate was low in our area (3.32%), the number of people at risk of acquiring the infection continues to be very high. In this work, we have successfully demonstrated that pooling of different groups of samples at low prevalence clusters, can be done with a small average delay on Cq values (5 and 2.85 cycles for pools of 20 and 5 samples, respectively). CONCLUSIONS: A new screening system with guaranteed protection is required for small clusters, previously covered with individual testing. Our proposal for Care Homes, once prevalence zero is achieved, would include successive rounds of testing using a pooling solution for transmission control preserving testing resources. Scale-up of this method may be of utility to confront larger clusters to avoid the viral circulation and keeping them operative.

Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study.

OBJECTIVE: To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. METHODS: We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/µL, not starting c-ART; and group B, CD4<500 cells/µL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. RESULTS: The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30-43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. CONCLUSIONS: In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.

Spatial Charge Separation as the Origin of Anomalous Stark Effect in Fluorous 2D Hybrid Perovskites.

2D hybrid perovskites (2DP) are versatile materials, whose electronic and optical properties can be tuned through the nature of the organic cations (even when those are seemingly electronically inert). Here, it is demonstrated that fluorination of the organic ligands yields glassy 2DP materials featuring long-lived correlated electron-hole pairs. Such states have a marked charge-transfer character, as revealed by the persistent Stark effect in the form of a second derivative in electroabsorption. Modeling shows that electrostatic effects associated with fluorination, combined with the steric hindrance due to the bulky side groups, drive the formation of spatially dislocated charge pairs with reduced recombination rates. This work enriches and broadens the current knowledge of the photophysics of 2DP, which will hopefully guide synthesis efforts toward novel materials with improved functionalities.

Azatruxene-Based, Dumbbell-Shaped, Donor-π-Bridge-Donor Hole-Transporting Materials for Perovskite Solar Cells.

Three novel donor-π-bridge-donor (D-π-D) hole-transporting materials (HTMs) featuring triazatruxene electron-donating units bridged by different 3,4-ethylenedioxythiophene (EDOT) π-conjugated linkers have been synthesized, characterized, and implemented in mesoporous perovskite solar cells (PSCs). The optoelectronic properties of the new dumbbell-shaped derivatives (DTTXs) are highly influenced by the chemical structure of the EDOT-based linker. Red-shifted absorption and emission and a stronger donor ability were observed in passing from DTTX-1 to DTTX-2 due to the extended π-conjugation. DTTX-3 featured an intramolecular charge transfer between the external triazatruxene units and the azomethine-EDOT central scaffold, resulting in a more pronounced redshift. The three new derivatives have been tested in combination with the state-of-the-art triple-cation perovskite [(FAPbI3 )0.87 (MAPbBr3 )0.13 ]0.92 [CsPbI3 ]0.08 in standard mesoporous PSCs. Remarkable power conversion efficiencies of 17.48 % and 18.30 % were measured for DTTX-1 and DTTX-2, respectively, close to that measured for the benchmarking HTM spiro-OMeTAD (18.92 %), under 100 mA cm-2 AM 1.5G solar illumination. PSCs with DTTX-3 reached a PCE value of 12.68 %, which is attributed to the poorer film formation in comparison to DTTX-1 and DTTX-2. These PCE values are in perfect agreement with the conductivity and hole mobility values determined for the new compounds and spiro-OMeTAD. Steady-state photoluminescence further confirmed the potential of DTTX-1 and DTTX-2 for hole-transport applications as an alternative to spiro-OMeTAD.