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Age-related changes in inhibitory neurotransmission in sensory cortex may underlie deficits in sensory function. Perineuronal nets (PNNs) are extracellular matrix components that ensheath some inhibitory neurons, particularly parvalbumin positive (PV+) interneurons. PNNs may protect PV+ cells from oxidative stress and help establish their rapid spiking properties. Although PNN expression has been well characterized during development, possible changes in aging sensory cortex have not been investigated. Here we tested the hypothesis that PNN+, PV+ and PV/PNN co-localized cell densities decline with age in the primary auditory cortex (A1). This hypothesis was tested using immunohistochemistry in two strains of mice (C57BL/6 and CBA/CaJ) with different susceptibility to age-related hearing loss and at three different age ranges (1-3, 6-8 and 14-24 months old). We report that PNN+ and PV/PNN co-localized cell densities decline significantly with age in A1 in both mouse strains. In the PNN+ cells that remain in the old group, the intensity of PNN staining is reduced in the C57 strain, but not the CBA strain. PV+ cell density also declines only in the C57, but not the CBA, mouse suggesting a potential exacerbation of age-effects by hearing loss in the PV/PNN system. Taken together, these data suggest that PNN deterioration may be a key component of altered inhibition in the aging sensory cortex, that may lead to altered synaptic function, susceptibility to oxidative stress and processing deficits.

En este número no se incluyeron resúmenes ni palabras clave.

La novela es uno de los vehículos artísticos que mejor han representado el pensar del ser humano a través del tiempo; de aquí el interés imperecedero en su desarrollo desde su génesis. Esto conllevará no sólo una evolución ideológica que dictará parámetros tanto con respecto al “contenido” como a las estrategias narrativas que siguen transmutándose. El mecanismo del cruce de historias revela cómo cambia de intención el mensaje de Montalvo al concluir el Amadís de Gaula con Las Sergas de Esplandián. El cambio ocurre al ver la narración como una gran orquestación sintética y simbólica del acontecer, en la que la casualidad de la aventura caballeresca es reemplazada por la causalidad del creyente.

En este número no se incluyeron resúmenes ni palabras clave.

Abstract We present an exploration of the unpolarized isovector proton generalized parton distributions (GPDs) H u−d (x, ξ, t) and E u−d (x, ξ, t) in the pseudo-distribution formalism using distillation. Taking advantage of the large kinematic coverage made possible by this approach, we present results on the moments of GPDs up to the order x 3 — including their skewness dependence — at a pion mass m π = 358 MeV and a lattice spacing a = 0.094 fm.

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Abstract Understanding the trophic and demographic dynamics of apex predators is of paramount importance for ecosystem conservation. Apex predators are usually free from predation, and thus, the main driver of population dynamics is the availability of trophic resources, which affects breeding performance. Albeit food habits have been described in many apex species, the effects of changes in the trophic niche on long‐term demographic dynamics are poorly known. We describe the long‐term (N = 25 years) changes in trophic niche breadth of a recovering golden eagle population in a Mediterranean landscape (northern Spain) and search for potential correlates with their productivity (i.e., number of fledged eaglets per controlled pair) as a proxy for their breeding performance (N = 290 pair‐years). We identified a total of 3475 prey items from 77 species; rabbits, hares, and red‐legged partridges were the most frequent prey consumed (overall 51%), followed by roe deer (10%), red‐billed chough, red foxes, and woodpigeons, all of them with >5%. Prey diversity in eagles' diet decreased during the study period. Consumption of rabbits and roe deer increased, while that of hares and partridges decreased; no significant trends were observed in the consumption of foxes, choughs, and woodpigeons. Prey diversity and red‐legged partridge consumption were negatively correlated with productivity at the territory level, while rabbits, corvids, and pigeons showed a strong positive relationship with productivity. The size of the territory showed the strongest positive relationship with productivity, while roughness was negatively correlated. Rabbits and ungulates showed negative and positive correlations with roughness, respectively, while predator consumption exhibited a negative relationship with the size of the territory. Our findings give insights into the potential trophic mechanisms driving the dynamics of recovering apex predator populations; a reduction in the trophic niche breadth toward specific groups of prey, which could be due to a higher availability and individual specificity toward these prey species, might enhance productivity at the territory level and, ultimately, influence population dynamics facilitating the recovery process. The remarkable increase in the consumption of wild ungulates, predators, and other apex consumers suggests that the current population recovery and reduced trophic niche breadth may facilitate this eagle population to exhibit its apex role and contribute to ecosystem functionality.

Abstract Conservation is prioritized based on accepted taxa. As a consequence, a conservation incentive exists to emphasize inter‐population differences to define taxa, potentially leading to taxonomic inflation. But stressing the uniqueness of threatened populations has the side effect of hindering conservation actions that promote inter‐population gene flow, such as genetic rescue. These actions may be of critical importance for severely inbred populations involved in extinction vortices, for which an inflated taxonomy can become a conservation trap. Here, we exemplify this scenario with the western capercaillie (Tetrao urogallus, Phasianidae) population in the Cantabrian Mountains, described and legally listed as a subspecies not supported by recent molecular data. The Cantabrian capercaillie population is Critically Endangered after a long‐lasting decline and a recent demographic collapse. It shows clear signs of inbreeding depression, including striking clutch size decreases as well as reduced hatchability and chick survival. This critical situation could be alleviated through a genetic rescue, but this possibility is hindered by inertias rooted in the putative uniqueness of the Cantabrian capercaillie. It had been previously argued that poor taxonomy could hamper conservation, through the oblivion of populations deserving, but not having, a taxonomic status. We show that taxonomic inflation can also become an obstacle for effective conservation.

ABSTRACT Cervical spondylotic myelopathy (CSM) is a common disease with an increased anticipated burden to health systems worldwide. Methods to predict outcomes in these patients are needed so physicians can provide more effective care. Fractional anisotropy (FA) analysis is a promising technique used to quantify how preserved the diffusion is in neural pathways. A systematic review and meta-analysis were performed using the PRISMA guidelines. Full articles available online were searched for correlation coefficients between FA values and mJOA scores. Average FA values, preoperative mJOA, and postoperative mJOA scores were gathered to perform a correlation analysis. A total of 5 articles presented correlations between FA and mJOA change and were included in the correlation meta-analysis. Correlation coefficients varied from -0.42 and 0.55. The number of patients in each study varied from 15 to 95. The Random effects model resulted in a non-significant correlation coefficient of 0.1315 (95% CI: -0.2575 to 0.4839; p= 0.5124). Spearman's correlation analysis was significant for preoperative vs postoperative mJOA (r = 0.79, p = 0.02), while preoperative FA did not correlate significantly with preoperative or postoperative mJOA. At this point, the data available in the literature is insufficient to determine a real correlation between FA and mJOA scores. More studies are necessary for a better understanding of this matter. Level of Evidence III; Study Review.

Abstract Background The arrival of new disease-modifying treatments for Alzheimer’s disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. Methods Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A − / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors. Results Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / − , AD + / − , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89. Conclusions Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer’s pathology in cognitively unimpaired subjects.

Se realizó una revisión de la literatura actual para determinar el papel de la uretroplastia en el tratamiento de la estenosis uretral que afecta al 0.6% de los hombres. La etiología de estenosis uretral anterior puede ser por causas iatrogénicas, traumáticas, inflamatorias e idiopáticas. La etiología de estenosis uretral posterior es fractura pélvica. Los síntomas son inespecíficos y pueden incluir síntomas del tracto urinario inferior, así como infecciones. La uretrografía retrógrada es el estudio de elección para el diagnóstico. El tratamiento se clasifica en dos grupos: cirugía abierta (uretroplastia formal) y cirugía transuretral endoscópica. La uretroplastia es un tratamiento duradero y definitivo. En estenosis cortas, < 2 cm, la uretroplastia de escisión y anastomosis primaria es muy satisfactoria, con una tasa de éxito superior al 90% en procedimientos primarios y repetidos. En estenosis > 2 cm, la uretroplastia de ampliación con injerto en posición dorsal o ventral de mucosa oral es la técnica ideal, con resultados exitosos a largo plazo en el 90% de los pacientes. La longitud de la estenosis es el factor pronóstico principal y el criterio mayor empleado para decidir el tipo de tratamiento. La espongiofibrosis es otro factor determinante del tratamiento adecuado y del pronóstico final.

Spodoptera frugiperda is the main pest of maize. One of the alternatives proposed for its control is the implementation of products of botanical origin, such as those derived from Ricinus communis. In this work, the insecticidal and insectistatic activities of methanolic and hydrolyzed methanolic extracts of the aerial parts of R. communis and kaempferol against S. frugiperda are evaluated. The methanolic extract presented a larval mortality rate of 55% and an accumulated mortality rate of 65% starting at 4000 ppm, with LC50 values of 3503 (larvae) and 2851 (accumulated); meanwhile, from a concentration of 1000 ppm, a decrease in pupa weight at 24 h of 20.5 mg was observed when compared to the control. The hydrolyzed methanolic extract presented a larval mortality and accumulated mortality rate of 60% from a concentration of 1000 ppm, and a decrease in pupa weight at 24 h of 35.31 mg was observed, when compared to the control. For the compound kaempferol 3-β-D-glucopyranoside, a larval mortality rate of 65% and an accumulated mortality rate of 80% were observed from 800 ppm, with LC50 values of 525.2 (larvae) and 335.6 ppm (accumulated); meanwhile, at 300 ppm, a decrease in pupa weight of 25.59 mg after 24 h was observed when compared to the control.

BackgroundLimited information is available on the active process of seeking medical help in patients with Alzheimer’s disease (AD) at early stages. The aim of this study was to assess the phenomenon of medical help-seeking in early AD and to identify associated factors.MethodsA multicenter, non-interventional study was conducted including patients of 50–90 years of age with prodromal or mild AD (National Institute on Aging/Alzheimer’s Association criteria), a Mini-Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5–1.0. A multivariate logistic regression analysis was conducted.ResultsA total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years, 50.3% were female, and 87.2% had a CDR-GS score of 0.5. Mean disease duration was 1.4 (1.8) years. Ninety-four (63.1%) patients sought medical help, mostly from neurologists. Patients with help-seeking intentions were mostly female (60.6%) with a CDR-GS score of 0.5 (91.5%) and had a greater awareness of diagnosis, poorer quality of life, more depressive symptoms, and a more severe perception of their condition than their counterparts. Lack of help-seeking intentions was associated with male sex (p = 0.003), fewer years of education (p = 0.005), a low awareness of diagnosis (p = 0.005), and a low emotional consequence of the condition (p = 0.016).ConclusionUnderstanding the phenomenon of active medical help-seeking may facilitate the design of specific strategies to improve the detection of cognitive impairment, especially in patients with a lower level of educational attainment and poor awareness of their condition.

Summary: Background: With the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need. Methods: Safety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.gov NCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n = 110) or blinded pooled placebo (n = 110) between February 10 and August 18, 2021. Findings: The proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n = 1; 1%) compared with placebo (n = 7; 6%), representing an 86% relative risk reduction (p = 0.07). There were no deaths in either arm. Interpretation: In this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia. Funding: The ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.