Thalamocortical interactions shape hierarchical neural variability during stimulus perception.

The brain is organized hierarchically to process sensory signals. But, how do functional connections within and across areas contribute to this hierarchical order? We addressed this problem in the thalamocortical network, while monkeys detected vibrotactile stimulus. During this task, we quantified neural variability and directed functional connectivity in simultaneously recorded neurons sharing the cutaneous receptive field within and across VPL and areas 3b and 1. Before stimulus onset, VPL and area 3b exhibited similar fast dynamics while area 1 showed slower timescales. During the stimulus presence, inter-trial neural variability increased along the network VPL-3b-1 while VPL established two main feedforward pathways with areas 3b and 1 to process the stimulus. This lower variability of VPL and area 3b was found to regulate feedforward thalamocortical pathways. Instead, intra-cortical interactions were only anticipated by higher intrinsic timescales in area 1. Overall, our results provide evidence of hierarchical functional roles along the thalamocortical network.

Orthogonality of sensory and contextual categorical dynamics embedded in a continuum of responses from the second somatosensory cortex.

How does the brain simultaneously process signals that bring complementary information, like raw sensory signals and their transformed counterparts, without any disruptive interference? Contemporary research underscores the brain's adeptness in using decorrelated responses to reduce such interference. Both neurophysiological findings and artificial neural networks support the notion of orthogonal representation for signal differentiation and parallel processing. Yet, where, and how raw sensory signals are transformed into more abstract representations remains unclear. Using a temporal pattern discrimination task in trained monkeys, we revealed that the second somatosensory cortex (S2) efficiently segregates faithful and transformed neural responses into orthogonal subspaces. Importantly, S2 population encoding for transformed signals, but not for faithful ones, disappeared during a nondemanding version of this task, which suggests that signal transformation and their decoding from downstream areas are only active on-demand. A mechanistic computation model points to gain modulation as a possible biological mechanism for the observed context-dependent computation. Furthermore, individual neural activities that underlie the orthogonal population representations exhibited a continuum of responses, with no well-determined clusters. These findings advocate that the brain, while employing a continuum of heterogeneous neural responses, splits population signals into orthogonal subspaces in a context-dependent fashion to enhance robustness, performance, and improve coding efficiency.

Distinct neural mechanisms for heading retrieval and context recognition in the hippocampus during spatial reorientation.

Reorientation, the process of regaining one's bearings after becoming lost, requires identification of a spatial context (context recognition) and recovery of facing direction within that context (heading retrieval). We previously showed that these processes rely on the use of features and geometry, respectively. Here, we examine reorientation behavior in a task that creates contextual ambiguity over a long timescale to demonstrate that male mice learn to combine both featural and geometric cues to recover heading. At the neural level, most CA1 neurons persistently align to geometry, and this alignment predicts heading behavior. However, a small subset of cells remaps coherently in a context-sensitive manner, which serves to predict context. Efficient heading retrieval and context recognition correlate with rate changes reflecting integration of featural and geometric information in the active ensemble. These data illustrate how context recognition and heading retrieval are coded in CA1 and how these processes change with experience.

The Mitragyna speciosa (kratom) alkaloid mitragynine: Analysis of adrenergic α2 receptor activity in vitro and in vivo.

Mitragynine, an alkaloid present in the leaves of Mitragyna speciosa (kratom), has a complex pharmacology that includes low efficacy agonism at µ-opioid receptors (MORs). This study examined the activity of mitragynine at adrenergic α2 receptors (Aα2Rs) in vitro and in vivo. Mitragynine displaced a radiolabeled Aα2R antagonist ([3H]RX821002) from human Aα2ARs in vitro with lower affinity (Ki = 1260 nM) than the agonists (-)-epinephrine (Ki = 263 nM) or lofexidine (Ki = 7.42 nM). Mitragynine did not significantly stimulate [35S]GTPγS binding at Aα2ARs in vitro, but in rats trained to discriminate 32 mg/kg mitragynine from vehicle (intraperitoneally administered; i.p.), mitragynine exerted an Aα2R agonist-like effect. Both α2R antagonists (atipamezole and yohimbine) and MOR antagonists (naloxone and naltrexone) produced rightward shifts in mitragynine discrimination dose-effect function and Aα2R agonists lofexidine and clonidine produced leftward shifts. In the mitragynine trained rats, Aα2R agonists also produced leftward shifts in discrimination dose-effect functions for morphine and fentanyl. In a separate rat cohort trained to discriminate 3.2 mg/kg i.p. morphine from vehicle, naltrexone produced a rightward shift, but neither an Aα2R agonist or antagonist affected morphine discrimination. In a hypothermia assay, both lofexidine and clonidine produced marked effects antagonized by yohimbine. Mitragynine did not produce hypothermia. Together, these data demonstrate that mitragynine acts in vivo like an Aα2R agonist, although its failure to induce hypothermia or stimulate [35S]GTPγS binding in vitro, suggests that mitragynine maybe a low efficacy Aα2R agonist.

Antisense RNA regulates glutamine synthetase in a heterocyst-forming cyanobacterium.

Glutamine synthetase (GS) is a key enzyme involved in nitrogen assimilation and the maintenance of C/N balance, and it is strictly regulated in all bacteria. In cyanobacteria, GS expression is controlled by nitrogen control A (NtcA) transcription factor, which operates global nitrogen regulation in these photosynthetic organisms. Furthermore, posttranslational regulation of GS is operated by protein-protein interaction with GS inactivating factors (IFs). In this study, we describe an additional regulatory mechanism involving an antisense RNA. In Nostoc sp. PCC 7120, the gifA gene (encoding GS inactivating factor IF7) is transcribed downstream of the GS (glnA) gene, from the opposite strand, and the gifA mRNA extends into the glnA coding sequence in antisense orientation. Therefore, the dual RNA transcript that encodes gifA constitutes two functional regions: a 5' protein-coding region, encoding IF7, and a 3' untranslated region that acts as an antisense to glnA. By increasing the levels of such antisense RNA either in cis or in trans, we demonstrate that the amount of GS activity can be modulated by the presence of the antisense RNA. The tail-to-tail disposition of the glnA and gifA genes observed in many cyanobacterial strains from the Nostocales clade suggests the prevalence of such antisense RNA-mediated regulation of GS in this group of cyanobacteria.

Vasa Previa and the Role of Fetal Fibronectin and Cervical Length Surveillance: A Review.

Vasa previa is a pregnancy complication that occurs when unprotected fetal blood vessels traverse the cervical os, placing the fetus at high risk of exsanguination and fetal death. These fetal vessels may be compromised by fetal movement and compression, leading to poor oxygen distribution and asphyxiation. Diagnostic tools for vasa previa management and preterm labor (PTL) include transvaginal ultrasound, cervical length (CL) surveillance and use of fetal fibronectin (FFN) testing. These tools can prove to be quite useful as they allow for lead time in the prediction of PTL and spontaneous rupture of membranes which can result in devastating outcomes for pregnancies affected by vasa previa. We conducted a literature review on vasa previa management and the usefulness of FFN and CL surveillance in predicting PTL and found 36 related papers. Although there is limited research available to show the impact of FFN and CL surveillance in the management of vasa previa, there is sufficient evidence to support FFN and CL surveillance in predicting the onset of PTL, which can have devastating consequences for the pregnancies affected. It can be extrapolated that these tools, by helping to determine pregnancies at risk for PTL, could improve management and outcomes in patients with vasa previa. Future studies investigating the management of vasa previa with FFN and CL surveillance to reduce the burden of PTL and its associated comorbidities are warranted.

Vancomicina contra metronidazol en infección por Clostridioides difficile leve-moderada de manejo ambulatorio / Vancomycin or metronidazole in the outpatient treatment of mild-moderate Clostridioides difficile infection

INTRODUCCIÓN: En la diarrea asociada a Clostridioides dfficile (DACD) leve-moderada se recomienda tratar con vancomicina por sobre metronidazol, a pesar de su difícil acceso y poca evidencia en el medio ambulatorio. OBJETIVO: Comparar la tasa de cura clínica y recurrencia entre vancomicina y metronidazol en adultos chilenos con primer episodio leve-moderado de DACD de manejo ambulatorio. MÉTODOS: Cohorte retrospectiva entre enero 2015 y diciembre 2020 en centros de una red de salud universitaria de pacientes de ≥ 18 años con DACD tratados ambulatoriamente. RESULTADOS: Se obtuvieron 161 pacientes, 59% mujeres, edad promedio de 53 años (entre 18 y 94 años). De ellos, 109 (67,7%) usaron metronidazol y 52 (32,3%) vancomicina. En el análisis multivariado ajustado por edad y comorbilidades se obtuvo un OR 3,00 (IC 95% 1,12-9,59) para cura clínica y 0,27 (IC 95% 0,06-0,88) para recurrencia a ocho semanas, ambos a favor de vancomicina, sin diferencias en recurrencia a 12 meses, necesidad de hospitalización o mortalidad. CONCLUSIÓN: La terapia con vancomicina comparada contra metronidazol en el tratamiento ambulatorio de la infección leve-moderada por C. dfficile se asocia a mayor cura clínica y menor tasa de recurrencia a corto plazo, sin diferencias en desenlaces a largo plazo.

BACKGROUND: Recommended treatment against mild cases of Clostridioides difficile associated diarrhea is vancomycin despite the difficulties of access compared to metronidazole. AIM: To compare the effectiveness of vancomycin and metronidazole in Chilean adults with first mild-moderate episode of Clostridiodes difficile infection (CDI). METHODS: Retrospective cohort of patients with CDI between January 2015 and December 2020 treated in centers of a university health network. The patients were adults treated for C. difficile infection on an outpatient basis. Recurrent and severe cases were excluded. Outcomes included clinical cure and recurrence rate. RESULTS: Data from 161 patients was recovered. Fifty-nine percent were women and average age was 53 (18-94). One hundred and nine patients were treated with metronidazole (67.7%) and 52 (32.3%) used vancomycin. Multivariate analysis adjusted by age and comorbidities showed an Odds Ratio of 3.00 (IC 95% 1.12-9.59) for clinical cure and 0.27 (IC 95% 0.06-0.88) for 8-week recurrence rate, both in favor of vancomycin, without differences in 12-month recurrence rate, hospitalization rate nor mortality. CONCLUSIONS: Vancomycin is associated with better short-term outcomes in the treatment of outpatient mild-moderate first episode C. difficile infection, without differences in long term recurrence or mortality when compared with metronidazole.

Eco-Design and Characterization of Sustainable Lightweight Gypsum Composites for Panel Manufacturing including End-of-Life Tyre Wastes.

The incorporation of rubber recycled aggregates from end-of-life tyres (ELT) in the manufacturing process of sustainable building materials has gained great interest in recent decades as a result of the large volume of this waste being generated annually. In this work, the objective is to make a contribution towards the circularity of construction products by carrying out a physico-mechanical characterisation of new gypsum composites made with the incorporation of these recycled rubber aggregates. To this end, up to 30% by volume of the original raw material has been substituted, analysing the mechanical resistance to bending and compression. Although lower than those of traditional gypsum material, both properties exceed the limits set at 1 and 2 MPa, respectively, by the current regulations. In addition, water absorption by capillarity significantly decreases, and thermal conductivity is reduced by more than 35% with respect to the reference material. Finally, in order to provide the research with a practical application, a prefabricated plate design has been proposed that incorporates the gypsum materials studied and an agglomerated rubber band that increases the thermal resistance and improves the efficiency of the designed construction system. In this way, this research reflects the potential of these novel building materials and explores new avenues for their application in building construction.

Low-Cost EEG Multi-Subject Recording Platform for the Assessment of Students' Attention and the Estimation of Academic Performance in Secondary School.

The level of student attention in class greatly affects their academic performance. Teachers typically rely on visual inspection to react to students' attention in time, but this subjective method leads to inconsistencies across classes. Online education exacerbates the issue as students can turn off cameras and microphones to keep their own privacy. To address this, we present a novel, low-cost EEG-based platform for assessing students' attention and estimating their academic performance. In a study involving 34 secondary school students (aged 14 to 16), participants watched an academic video and answered evaluation questions while their EEG activity was recorded using a commercial headset. The results demonstrate a significant correlation (0.53, p-value = 0.003) between the power spectral density (PSD) of the EEG beta band (12-30 Hz) and students' academic performance. Additionally, there was a notable difference in PSD-beta between high and low academic performers. These findings encourage the use of PSD-beta for the immediate and objective assessment of both the student attention and the subsequent academic performance. The platform offers valuable and objective feedback to teachers, enhancing the effectiveness of both face-to-face and online teaching and learning environments.

One-Pot Solvothermal Synthetic Route of a Zinc Oxide Nanoparticle-Decorated Reduced Graphene Oxide Nanocomposite: An Advanced Material with a Novel Anticancer Theranostic Approach.

This study focuses on a one-pot solvothermal synthetic route for the preparation of uniformly decorated zinc oxide nanoparticles on the surface of reduced graphene oxide (rGO/ZnO-NC) by using Andrographis paniculata leaf aqueous extract as an eco-friendly reducing agent. After characterizing the samples by different physical and chemical techniques, the anticancer activity of the synthesized rGO/ZnO-NC was examined on two human cancerous cell lines (HCT116 and A549) and one normal cell line (hMSCs). The MTT assays revealed that rGO/ZnO-NC exhibited dose-dependent cytotoxicity at a maximum concentration range of 10 ppm and the viability of the cells was drastically decreased to 95-96%. Measurement of reactive oxygen species (ROS) generation and Annexin V-FTIC staining assay revealed that rGO/ZnO-NC induced apoptosis in HCT116 and A549 cell lines. Thus, this study shows that the green-synthesized rGO/ZnO-NC has great potential in developing an efficacious novel therapeutic agent for cancers.