Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation.

Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.

FLAIRR-Seq: A Method for Single-Molecule Resolution of Near Full-Length Antibody H Chain Repertoires.

Current Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) using short-read sequencing strategies resolve expressed Ab transcripts with limited resolution of the C region. In this article, we present the near-full-length AIRR-seq (FLAIRR-seq) method that uses targeted amplification by 5' RACE, combined with single-molecule, real-time sequencing to generate highly accurate (99.99%) human Ab H chain transcripts. FLAIRR-seq was benchmarked by comparing H chain V (IGHV), D (IGHD), and J (IGHJ) gene usage, complementarity-determining region 3 length, and somatic hypermutation to matched datasets generated with standard 5' RACE AIRR-seq using short-read sequencing and full-length isoform sequencing. Together, these data demonstrate robust FLAIRR-seq performance using RNA samples derived from PBMCs, purified B cells, and whole blood, which recapitulated results generated by commonly used methods, while additionally resolving H chain gene features not documented in IMGT at the time of submission. FLAIRR-seq data provide, for the first time, to our knowledge, simultaneous single-molecule characterization of IGHV, IGHD, IGHJ, and IGHC region genes and alleles, allele-resolved subisotype definition, and high-resolution identification of class switch recombination within a clonal lineage. In conjunction with genomic sequencing and genotyping of IGHC genes, FLAIRR-seq of the IgM and IgG repertoires from 10 individuals resulted in the identification of 32 unique IGHC alleles, 28 (87%) of which were previously uncharacterized. Together, these data demonstrate the capabilities of FLAIRR-seq to characterize IGHV, IGHD, IGHJ, and IGHC gene diversity for the most comprehensive view of bulk-expressed Ab repertoires to date.

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).

Automatic Determination of the Non-Covalent Stable Conformations of the NO2-Pyrene Cluster in Full Dimensionality (81D) Using the vdW-TSSCDS Approach.

We present the detailed topographical characterisation (stationary points and minimum energy paths connecting them) of the full dimensional (81D) intermolecular potential energy surface associated with the non-covalent interactions between the NO2 radical and the pyrene (C16H10) molecule. The whole procedure is (quasi) fully automated. We have used our recent algorithm vdW-TSSCDS as implemented on the freely-available AutoMekin software package. To this end, a series of inexpensive classical trajectories using forces from a low-level (semi-empirical) theory are used to sample the configuration space of the system in the search for candidates to first order saddle points. These guess structures are determined by means of a graph-theory based algorithm using the concept of adjacency matrix. Low-level optimizations are followed by re-optimizations at a final high-level of theory (DFT and CCSD(T)-F12 in our case.). The resulting set of stationary points and paths connecting them constitutes the so-called reaction network. In the case of NO2-pyrene, this network exhibits four major basins which can be characterized by their point-group symmetry. A central one, of global C2 symmetry, comprises the global minimum (as well as all other permutationally related conformers) together with the corresponding C2v saddle points connecting them. This central basin is connected to three others of lower C1 symmetry. The latter can be distinguished by the projection of the position of the NO2 nitrogen atom on the pyrene plane in combination with the relative orientation of the oxygen pair pointing either inwards, outwards, upwards or downwards.

Morphochromatic spectrum through gonad development stages of the razor surgeonfish, Prionurus laticlavius (Valenciennes, 1846) (Actinopterygii: Acanthuriformes).

Gonad development stages (GDS) are a critical tool that can be easily applied in fisheries to visually discriminate mature from immature organisms and assess their reproductive condition. This study proposes a morphochromatic scale to define gonad development stages for razor surgeonfish (Prionurus laticlavius) based on morphological and structural assessments of the gonad, histologically validated using multivariate dummy matrices modeled through multiple linear regression analyses. Gonads of 271 specimens were photographed prior to preservation to describe their shape, size, color, and turgor for morphochromatic analysis. Later, gonads were processed using standard histological methods. An oocyte growth scale was designed based on oocyte diameter and follicular wall thickness for each stage. In addition, five morphochromatic gonad development stages were histologically validated: immature, developing, spawning capable, regressing, and regenerating. Morphochromatic variations were observed in the last three stages in both sexes. Results show that gonad morphology and structure of P. laticlavius are similar to those of other acanthurids, albeit with some asymmetric and morphological differences, as well as gonad morphochromatic in both sexes. These findings confirm that maturation is species-specific. Also, although not a critical character, gonad colouration was found to play a major role in distinguishing between gonad development stages along with shape, size, vascularity (females), and folds (males). Therefore, gonad colouration should not be entirely overlooked because doing so may lead to errors in determining sexual maturity stages.

Identifying wildlife road crossing mitigation sites using a multi-data approach - A case study from southwestern Costa Rica.

Roads are one of the most widespread structures that drive habitat loss and fragmentation. But they also restrict animal movement and drive landscape-level impacts on biodiversity. The South Pacific of Costa Rica is known for its high levels of biodiversity, but little has been done to reduce road impacts upon wildlife communities. To understand these impacts and advise on possible mitigation action, we used three key data approaches: 1. Camera traps, to survey wildlife activity along two major road sections that dissect the region's protected areas and biological corridors. Seventy-eight camera traps were deployed in secondary forest patches at different distances (between 200 m and 1 km) from the roads for six months and covariates were collected to explain the patterns found. 2. Citizen science data extracted from iNaturalist to identify roadkill "hotspots" along the roads. And 3. Circuitscape analysis, to assess how landscape structure could influence animal movement. Camera traps recorded 30 terrestrial species. Ocelots and agoutis displayed a negative effect of distance from protected area, while the Apex predators displayed a positive effect toward higher forest cover and vegetation density. Circuitscape analysis showed high connectivity throughout most of the area. Only a few locations showed higher flow (bottle neck locations), which coincided with roadkill "hotspots" identified through citizen science direct observations (70 observations of 21 species). Amalgamating data from the different analyses allow us to identify four key wildlife crossing locations (one of less priority) along the Inter-American Highway. We strongly recommend the placement of under/overpasses in these locations, with the aim to ensure wildlife safe movement and connectivity of wildlife populations in the region. Culvert modifications in the area could also be considered to incorporate wildlife underpasses at a reduced cost.

Production of poly (3-hydroxybutyrate) and extracellular polymeric substances from glycerol by the acidophile Acidiphilium cryptum.

Acidiphilium cryptum is an acidophilic, heterotrophic, and metallotolerant bacteria able to use dissolved oxygen or Fe(III) as an electron sink. The ability of this extremophile to accumulate poly(3-hydroxybutyrate) (PHB) and secrete extracellular polymeric substances (EPS) has also been reported. Hence, the aim of this work is to characterize the production of PHB and EPS by the wild strain DSM2389 using glycerol in shaken flasks and bioreactor. Results showed that maximum PHB accumulation (37-42% w/w) was obtained using glycerol concentrations of 9 and 15 g L-1, where maximum dry cell weight titers reached 3.6 and 3.9 g L-1, respectively. The culture in the bioreactor showed that PHB accumulation takes place under oxygen limitation, while the redox potential of the culture medium could be used for online monitoring of the PHB production. Recovered EPS was analyzed by Fourier-transform infrared spectroscopy and subjected to gas chromatography-mass spectrometry after cleavage and derivatization steps. These analyses showed the presence of sugars which were identified as mannose, rhamnose and glucose, in a proportion near to 3.2:2.3:1, respectively. Since glycerol had not been used in previous works, these findings suggest the potential of A. cryptum to produce biopolymers from this compound at a large scale with a low risk of microbial contamination due to the low pH of the fermentation process.

Identification of the Photoreactive Species of Protonated N-Nitrosopiperidine in Acid Medium: A CASPT2 and DFT Study.

In this work, we have studied the initial reaction step after photoexcitation of protonated N-nitrosopiperidine both in the gas and condensed phases. To achieve this end, we have applied the CASPT2 and MP2 wave function methods and the density functional theory approach. It is found that the site of protonation of N-nitrosopiperidine in acid medium depends on the solvent: protonation occurs at the oxygen atom in protic solvents, while in aprotic solvents, the proton is bonded at the N-atom of the amine moiety. Furthermore, protonation at such an N-atom is the unique protonated species that absorbs in the visible range and directly dissociates into aminium radical cation and nitric oxide.

CASPT2 study of the electronic structure and photochemistry of protonated N-nitrosodimethylamine (NDMA-H+) at 453 nm.

In this work, we have studied the photodissociation of the protonated derivatives of N-nitrosodimethylamine [(CH3)2N-NO] with the CASPT2 method. It is found that only one of the four possible protonated species of the dialkylnitrosamine compound absorbs in the visible region at 453 nm, that is, N-nitrosoammonium ion [(CH3)2NH-NO]+. This species is also the only one whose first singlet excited state is dissociative to directly yield the aminium radical cation [(CH3)2NHN·]+ and nitric oxide. In addition, we have studied the intramolecular proton migration reaction {[(CH3)2N-NOH]+ → [(CH3)2NH-NO]+} both in the ground and excited state (ESIPT/GSIPT); our results indicate that this process is not accessible neither in the ground nor in the first excited state. Furthermore, as a first approximation, MP2/HF calculations on the nitrosamine-acid complex indicate that in acidic solutions of aprotic solvents, only [(CH3)2NH-NO]+ is formed.

Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute calculous cholecystitis in patients over 90 years of age.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard of care for acute calculous cholecystitis; however, in patients at high risk for surgery, particularly in the elderly, insertion of a percutaneous catheter drainage (PCD) at gallbladder is recommended. Current evidence suggests that PCD may have less favorable outcomes than LC, but also that LC-associated complications increase in direct relation to patient age. There is no recommendation supported by robust evidence to decide between one or the other procedure in super elderly patients. METHODS: A retrospective observational cohort study was designed to analyze the surgical outcomes of super elderly patients with cholecystitis who underwent LC versus PCD for treatment. The surgical outcomes of a subgroup of high-risk patients were also analyzed. RESULTS: A total of 96 patients who met the inclusion criteria between 2014 and 2021 were included. The median age of patients were 92 years (IQR: 4.00) with a female predominance (58.33%). The overall morbidity rate in the series was 36.45% and mortality rate was 7.29%. There was no statistically significant difference when compared to the associated morbidity and mortality among patients who underwent LC versus those who underwent PCD, neither in the analysis of the complete series or in the subgroup of high-risk patients. CONCLUSIONS: The morbidity and mortality associated with the two most frequently recommended therapeutic options for operating super elderly patients with acute cholecystitis are high. We found no evidence of superiority in outcomes for either of the two procedures in this age group.

Antiproliferative Potential of Olneya tesota PF2 Lectin in Human Acute Monocytic Leukemia Cells.

Acute monocytic leukemia is a type of myeloid leukemia that develops in monocytes. The current clinical therapies for leukemia are unsatisfactory due to their side effects and nonspecificity toward target cells. Some lectins display antitumor activity and may specifically recognize cancer cells by binding to carbohydrate structures on their surface. Therefore, this study evaluated the response of the human monocytic leukemia cell lines THP-1 to the Olneya tesota PF2 lectin. The induction of apoptosis and reactive oxygen species production in PF2-treated cells was evaluated by flow cytometry, and the lectin-THP-1 cell interaction and mitochondrial membrane potential were evaluated by confocal fluorescence microscopy. PF2 genotoxicity was evaluated by DNA fragmentation analysis via gel electrophoresis. The results showed that PF2 binds to THP-1 cells, triggers apoptosis and DNA degradation, changes the mitochondrial membrane potential, and increases reactive oxygen species levels in PF2-treated THP-1 cells. These results suggest the potential use of PF2 for developing alternative anticancer treatments with enhanced specificity.

The effects of phylogeny, habitat and host characteristics on the thermal sensitivity of helminth development.

Helminth parasites are part of almost every ecosystem, with more than 300 000 species worldwide. Helminth infection dynamics are expected to be altered by climate change, but predicting future changes is difficult owing to lacking thermal sensitivity data for greater than 99.9% of helminth species. Here, we compiled the largest dataset to date on helminth temperature sensitivities and used the Metabolic Theory of Ecology to estimate activation energies (AEs) for parasite developmental rates. The median AE for 129 thermal performance curves was 0.67, similar to non-parasitic animals. Although exceptions existed, related species tended to have similar thermal sensitivities, suggesting some helminth taxa are inherently more affected by rising temperatures than others. Developmental rates were more temperature-sensitive for species from colder habitats than those from warmer habitats, and more temperature sensitive for species in terrestrial than aquatic habitats. AEs did not depend on whether helminth life stages were free-living or within hosts, whether the species infected plants or animals, or whether the species had an endotherm host in its life cycle. The phylogenetic conservatism of AE may facilitate predicting how temperature change affects the development of helminth species for which empirical data are lacking or difficult to obtain.

Human disturbance and shifts in vertebrate community composition in a biodiversity hotspot.

Understanding how human modification of the landscape shapes vertebrate community composition is vital to understanding the current status and future trajectory of wildlife. Using a participatory approach, we deployed the largest camera-trap network in Mesoamerica to date to investigate how anthropogenic disturbance shapes the occupancy and co-occurrence of terrestrial vertebrate species in a tropical biodiversity hotspot: the Osa Peninsula, Costa Rica. We estimated species richness in different categories of land protection with rarefaction analysis and estimated the expected occupancy with a joint species distribution model that included covariates for anthropogenic disturbance, land protection, habitat quality, and habitat availability. Areas with the most stringent land-use protections (e.g., Corcovado National Park, 24 species [95% CI 23-25]) harbored significantly more species than unprotected areas (20 species [19.7-20.3]), mainly due to a reduced presence of large-bodied species of conservation concern in unprotected areas (e.g., jaguar Panthera onca and white-lipped peccary Tayassu pecari). Small-bodied generalist species, such as opossums (Didelphidae) and armadillos (Dasypus novemcinctus), in contrast, were more common at disturbed sites, resulting in a significant difference in vertebrate community composition between sites with low and high disturbance. Co-occurrence of species was also mainly associated with response to disturbance. Similar responses to disturbance create two groups of species, those whose site-level occupancy usually increased as anthropogenic disturbance increased and those whose estimated occupancy decreased. The absence of large-bodied species entails an important loss of ecological function in disturbed areas and can hinder forest development and maintenance. Efforts to protect and restore forested landscapes are likely having a positive effect on the abundance of some threatened species. These efforts, however, must be sustained and expanded to increase connectivity and ensure the long-term viability of the wildlife community.

Perturbaciones Humanas y Cambios en la Composición de la Comunidad de Vertebrados en un Punto Caliente de Biodiversidad Resumen El entendimiento de cómo las modificaciones humanas del paisaje conforman la composición de las comunidades de vertebrados es vital para entender el estado actual y la trayectoria futura de la fauna. Mediante una estrategia participativa, desplegamos la mayor red de cámaras trampa en Mesoamérica hasta la fecha para investigar cómo la perturbación antropogénica determina la ocupación y coocurrencia de las especies terrestres de vertebrados en un punto caliente de biodiversidad tropical: la Península de Osa, Costa Rica. Estimamos la riqueza de especies en diferentes categorías de protección de suelo con un análisis de rarefacción y estimamos la ocupación esperada con un modelo de distribución conjunta de especies que incluyó covariables para la perturbación antropogénica, la protección del suelo, la calidad del hábitat y la disponibilidad del hábitat. Las áreas con la protección más estricta de uso de suelo (p. ej.: Parque Nacional Corcovado, 24 especies [95% CI 23-25]) albergaron significativamente a más especies que las áreas desprotegidas (20 especies [19.7-20.3]), principalmente debido a la presencia reducida de especies de talla grande de interés para la conservación en las áreas desprotegidas (p. ej.: el jaguar Panthera onca, el pecarí de labios blancos, Tayassu pecari). Al contrario, las especies generalistas de talla pequeña, como las zarigüeyas (Didelphidae) y el armadillo (Dasypus novemcinctus) fueron más comunes en los sitios perturbados, lo que resulta en una diferencia significativa en la composición de las comunidades de vertebrados entre los sitios con una perturbación baja y alta. La coocurrencia de especies también estuvo asociada principalmente con la respuesta a la perturbación. Las respuestas similares a la perturbación crean dos grupos de especies: aquellas cuya ocupación a nivel de sitio generalmente incrementó conforme incrementó la perturbación antropogénica y aquellas cuya ocupación estimada disminuyó. La ausencia de especies de talla grande conlleva una pérdida importante de la función ecológica en las áreas perturbadas y puede dificultar el desarrollo y mantenimiento del bosque. Los esfuerzos para proteger y restaurar los paisajes forestales probablemente estén teniendo un efecto positivo sobre la abundancia de algunas especies amenazadas. Estos esfuerzos, sin embargo, deben ser sostenidos y expandidos para incrementar la conectividad y asegurar la viabilidad a largo plazo de la comunidad faunística.

Nitrene formation is the first step of the thermal and photochemical decomposition reactions of organic azides.

In this work, the decomposition of a prototypical azide, isopropyl azide, both in the ground and excited states, has been investigated through the use of multiconfigurational CASSCF and MS-CASPT2 electronic structure approaches. Particular emphasis has been placed on the thermal reaction starting at the S0 ground state surface. It has been found that the azide thermally decomposes via a stepwise mechanism, whose rate-determining step is the formation of isopropyl nitrene, which is, in turn, the first step of the global mechanism. After that, the nitrene isomerizes to the corresponding imine derivative. Two routes are possible for such a decomposition: (i) a spin-allowed path involving a transition state; and (ii) a spin-forbidden one via a S0/T0 intersystem crossing. Both intermediates have been determined and characterised. Their associated relative energies have been found to be quite similar, 45.75 and 45.52 kcal mol-1, respectively. To complete this study, the kinetics of the singlet and triplet channels are modeled with the MESMER (Master Equation Solver for Multi-Energy Well Reactions) code by applying the RRKM and Landau-Zener (with WKB tunnelling correction) theories, respectively. It is found that the canonical rate-coefficients of the singlet path are 2-orders of magnitude higher than the rate-coefficients of the forbidden reaction. In addition, the concerted mechanism has been investigated that would lead to the formation of the imine derivative and nitrogen extrusion in the first step of the decomposition. After a careful analysis of CASSCF calculations with different active spaces and their comparison with single electronic configuration methods (MP2 and B3LYP), the concerted mechanism is discarded.

Photochemistry of 1-Phenyl-1-diazopropane and Its Diazirine Isomer: A CASSCF and MS-CASPT2 Study.

In this work, we studied the wavelength (520 or 350 nm) dependence of the photochemical decomposition of 1-phenyl-1-diazopropane (PDP) and 1-phenyl-1-propyl diazirine (PED) by means of high-level ab initio quantum chemical calculations (CASSCF and MS-CASPT2) to obtain qualitative and quantitative results. It is found that the photochemistry of PDP is governed by nonradiative deactivation processes that can involve one or two S1/S0 conical intersections (CI1 and CI2) depending on the wavelength of the radiation; CI2 is only accessible at the shortest wavelength. It is demonstrated that the main intermediate of the photochemistry of the titled compounds is 1-ethyl-1-phenyl carbene (EPC). Upon irradiation of PDP with the 520 nm light, the carbene is always generated in its ground state as closed-shell singlet carbene. In contrast, the 350 nm radiation can directly decompose PDP into S1 carbene (open shell) and N2 when the conical intersection CI2 is avoided. Once the carbene is formed in the S1 state, it can experience excited state intramolecular proton transfer along a seam of crossing (ESIPT-SC) of the S1 and S0 states to yield the alkene derivative; that is, the proton transfer reaction takes places on a degenerate potential energy surface where the two electronic states have equal energy. In addition, it is found that EPC absorbs at 350 nm (double excitations); therefore, there is another possible route that can induce as well a slightly different photochemistry in changing the wavelength of the radiation because the shortest wavelength (when it is intense enough) decreases the amount of available EPC or generates a highly vibrationally excited state of the carbene; that is, after 350 nm excitation, the carbene intermediate can deactivate via radiation emission or can decay through a cascade of conical intersections to its first excited state (S1), where ESIPT-SC is operative again.

Use of plasma late on cardiopulmonary bypass in patients undergoing left ventricular assist device implantation.

Coagulopathy is common during left ventricular assist device (LVAD) implantation, treatment of which can be challenging given the often-limited ability for the right ventricle to accommodate volume transfusion after device initiation with 20% to 40% of patients developing right ventricular failure (RVF). Transfusion of plasma late on cardiopulmonary bypass (CPB) combined with ultrafiltration may replace clotting factors while reducing volume administration. We compared outcomes in patients undergoing LVAD implantation receiving plasma on CPB and ultrafiltration with traditional transfusion practices. Co-primary outcomes needed for blood product transfusion in the first 6 and 24 hours after CPB. Secondary outcomes included metrics of morbidity and mortality. 396 patients were analyzed (59 plasma on CPB). Patients receiving plasma on CPB had a greater volume of blood products transfused (3764 vs. 2741 mL first 6 hours; 6059 vs. 4305 mL first 24 hours) in unadjusted analysis. In adjusted analysis, plasma transfusion on CPB with ultrafiltration had no significant effect on the primary outcomes of blood products given in the first 6 hours (estimated effect size 982 [-428, 2392] mL, P = .17) and 24 hours (estimated effect size 1076 [-904, 3057] mL, P = .29). Patients receiving plasma on CPB were more likely on either vasopressors or inotropes at 24 hours after ICU admission (P = .01), however, indices of coagulopathy and RVF were similar between groups. While prospective studies would be necessary to definitively evaluate the clinical utility of this strategy, no signal for benefit was observed suggesting plasma should not be used for this purpose.

Spanish validation and factor structure of the Prenatal Distress Questionnaire Revised (NuPDQ).

BACKGROUND: Due to an absence of maternal stress being measured in routine prenatal care by clinicians, prenatal stress has become a serious problem which is associated with poorer obstetric outcomes, as well as worse maternal and infant health. For that reason, the aim of this study was the translation, validation and adaptation of Prenatal Distress Questionnaire Revised (NuPDQ) in a Spanish sample. METHODS: Three-hundred and seventy-one pregnant women were assessed using the NuPDQ, the Prenatal Distress Questionnaire, Perceived Stress Scale and the Connor-Davidson Resilience Scale. The NuPDQ was translated into Spanish by the backtranslation method and administered to participants. RESULTS: A confirmatory factor analysis revealed the established unidimensional structure to be a poor fit to data with the Spanish version. An exploratory factor analysis suggested a five-factor structure with 14 items. The instrument had good reliability, convergent and discriminant validity psychometric properties. CONCLUSIONS: The five-factor 14-item NuPDQ is useful to assess pregnancy-specific stress in Spanish pregnant women. It may be appropriate to use this instrument in order to identify pregnant women with high pregnancy-specific stress to try to prevent negative consequences derived from those high levels.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Predicting Future Renal Function Decline in Patients with Autosomal Dominant Polycystic Kidney Disease Using Mayo Clinic Classification.

INTRODUCTION: Mayo clinic classification (MCC) has been proposed in patients with autosomal dominant polycystic kidney disease (ADPKD) to identify who may experience a rapid decline of renal function. Our aim was to validate this predictive model in a population from southern Spain. METHODS: ADPKD patients with measurements of height-adjusted total kidney volume (HtTKV) and baseline estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were selected. Last eGFR was estimated with Mayo Clinic (MC) equation and bias and accuracy were studied. We also analyzed predictive capacity of MCC classes using survival analysis and Cox regression models. RESULTS: We included 134 patients with a mean follow-up of 82 months. While baseline eGFR was not different between classes, last eGFR decreased significantly with them. eGFR variation rate was different according to the MCC class with a more rapid decline in 1C, 1D, and 1E classes. Final eGFR predicted was not significantly different from the real one, with an absolute bias of 0.6 ± 17.0 mL/min/1.73 m2. P10 accuracy was low ranging from 37.5 to 59.5% in classes 1C, 1D, and 1E. Using MC equation, the rate of eGFR decline was underestimated in 1C, 1D, and 1E classes. Cox regression analysis showed that MCC class is a predictor of renal survival after adjusting with baseline eGFR, age, sex, and HtTKV, with 1D and 1E classes having the worst prognosis. CONCLUSION: MCC classification is able to identify patients who will undergo a more rapid decline of renal function in a Spanish population. Prediction of future eGFR with MC equation is acceptable as a group, although it shows a loss of accuracy considering individual values. The rate of eGFR decline calculated using MC equation can underestimate the real rate presented by patients of 1C, 1D, and 1E classes.

Tensorpac: An open-source Python toolbox for tensor-based phase-amplitude coupling measurement in electrophysiological brain signals.

Despite being the focus of a thriving field of research, the biological mechanisms that underlie information integration in the brain are not yet fully understood. A theory that has gained a lot of traction in recent years suggests that multi-scale integration is regulated by a hierarchy of mutually interacting neural oscillations. In particular, there is accumulating evidence that phase-amplitude coupling (PAC), a specific form of cross-frequency interaction, plays a key role in numerous cognitive processes. Current research in the field is not only hampered by the absence of a gold standard for PAC analysis, but also by the computational costs of running exhaustive computations on large and high-dimensional electrophysiological brain signals. In addition, various signal properties and analyses parameters can lead to spurious PAC. Here, we present Tensorpac, an open-source Python toolbox dedicated to PAC analysis of neurophysiological data. The advantages of Tensorpac include (1) higher computational efficiency thanks to software design that combines tensor computations and parallel computing, (2) the implementation of all most widely used PAC methods in one package, (3) the statistical analysis of PAC measures, and (4) extended PAC visualization capabilities. Tensorpac is distributed under a BSD-3-Clause license and can be launched on any operating system (Linux, OSX and Windows). It can be installed directly via pip or downloaded from Github (https://github.com/EtienneCmb/tensorpac). By making Tensorpac available, we aim to enhance the reproducibility and quality of PAC research, and provide open tools that will accelerate future method development in neuroscience.