Role of ON and OFF Visual Pathways in Rod- and Cone-Driven Flicker Responses

Purpose: To evaluate the effects of various retinal neurotransmitters on temporal resolution, particularly, on the Critical Flicker Fusion Frequency (CFF), which has been previously applied in ophthalmic pathophysiologic research. Methods: A binocular physiologic electroretinogram was performed on adult mice. Animals in the control group were injected in the right eye with 1 & mu;L of phosphate-buffered saline (PBS). Animals in the experimental group were injected in the left eye with 1 & mu;L of PBS and in the right eye with 1 & mu;L of PBS to which different molecules were added: 2-amino-4-phosphonobutyric hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). Initially, rod response was recorded and later the cone response. Results: APB suppressed the rod-driven, but not the cone-driven flicker response. The other agents severely affected the lower flickering frequency response amplitude, in particular, at 3 Hz. The threshold of CFF was lowered from 50 Hz to 40 Hz after applying APB, Glycine, and HEPES. GABA remarkably enhanced rod-driven and cone-driven flicker response at 3 Hz, whereas Glutamate and GABA/Glutamate only did in rod-driven flicker response. Conclusions: Both ON and OFF visual pathways were implied in cone-driven response, but only the ON visual pathway appears to play a relevant role in rod-driven flicker response. Flicker response seems to be enhanced by horizontal cells both in roddriven and cone-driven response. In addition, due to the greater sensitivity of the flicker at low frequencies, it is suggested that pathophysiological studies should be carried out at said frequencies

Effects of global postural reeducation on postural control, dynamic balance, and ankle range of motion in patients with hallux abducto valgus. A randomized controlled trial.

AbstractHallux abducto valgus (HAV) is a common musculoskeletal disorder that has been addressed surgically. Nevertheless, the manual therapy approach may play an important role in the management of this condition. The present study aimed to determine the effectiveness of global postural reeducation (GPR) in subjects with symptomatic mild to moderate HAV in static postural control, dynamic stability, and ankle dorsiflexion range of motion (DFROM). A total of 80 patients with mild to moderate symptomatic HAV were allocated to the intervention group (GPR) or control group (CG) (no treatment) for 8 weeks. Outcome measures were assessed at baseline at 4 and 8 weeks including static postural control (Romberg test), dynamic balance (Star Excursion Balance Test [SEBT]), and ankle DFROM (Weight‐Bearing Lunge Test [WBLT]). No improvements were observed at 4 weeks, but there were improvements at 8 weeks in: static postural control mediolateral displacement (X) of center of pressure (CoP) in both eyes open (EO) and eyes closed (EC): XEO (t(36) = 2.892, p = .006, d = 0.67); XEC (t(68) = 2.280, p = .026, d = 054); and velocity (V) of CoP displacement: VEO (t(68) = 2.380, p = .020, d = 0.57); VEC (t(36) = 2.057, p = .047, d = 0.37). It were also improvements in: WBLT (t(36) = −2.869, p = .007, d = 0.54) and SEBT at three directions (anterior, ANT; posteromedial, PM; and posterolateral, PL): SEBT.ANT (t(36) = −2.292, p = .028, d = 0.23); SEBT.PM (t(36) = −4.075, p < .001, d = 0.43); SEBT.PL (t(62) = −3.506, p = .001, d = 0.34). The present study showed that GPR compared to the CG might be effective in enhancing ankle function including postural control, dynamic balance, and DFROM

Actividad física, ejercicio y deporte en la lucha contra la obesidad infantil y juvenil

El propósito del presente documento es proponer desde el grupo de expertos en ejercicio físico y salud de EXERNET (Red Española de Investigación en Ejercicio Físico y Salud) una serie de recomendaciones sobre la práctica de la actividad física y deportiva que a nivel individual, familiar e institucional ayuden a prevenir y tratar la obesidad infantil y juvenil, basadas en la evidencia científi ca actual

Primera evaluación bimestral bajo ambientes virtuales realizada al ciclo V de la I.E.D. Rafael Bernal Jiménez. “Por la transformación pedagógica"

Migration of Information and Communication Technologies (ICT) towards Learning and Knowledge Technologies (tac for its meaning in Spanish) and even more, towards Empowerment and Participation Technologies (tep for its meaning in Spanish), are generating radical changes in traditional school learning processes. Therefore, the article presents the results obtained in the design, planning and implementation of the first Bimonthly Virtual Assessment for the 5th cycle in the Educational District Institution (IED) Rafael Bernal Jiménez, in order to encourage the use of ict and a responsable and self-regulated training for learning processes through the Virtual Classroom Casquete de Esfera Perforada (http://casquetedeesferaperforada. com/plataforma2/).La migración de las tecnologías de la información y la comunicación (tic) hacia las tecnologías para el aprendizaje y el conocimiento (tac) y, aún más, hacia las tecnologías para el empoderamiento y la participación (tep) está generando cambios radicales en los procesos de aprendizaje escolar tradicional. Este artículo presenta los resultados obtenidos en el diseño, planeación e implementación de la primera evaluación virtual bimestral del ciclo V, en la Institución Educativa Distrital Rafael Bernal Jiménez, con el fin de incentivar el uso de las tic y la formación autorregulada y responsable en los procesos de aprendizaje, a través del aula virtual Casquete de Esfera Perforada (http://casquetedeesferaperforada.com/plataforma2/)

Experimental archeology at Cuevas de la Araña (Málaga, Spain)

En este trabajo abordamos las actividades de Arqueología Experimental desarrolladas en las Cuevas de La Araña. Éstas, cubren los campos más significativos de la Arqueología y sus protocolos -de campo y laboratorio-, así como la reproducción de los procesos tecnológicos con que se tuvieron que enfrentar los grupos prehistóricos para su supervivencia, desde el Paleolítico Inferior hasta el Calcolítico. Con la reproducción de las diversas tecnologías se obtiene una información más directa, y se aprecia mejor las dificultades inherentes a cada una de ellas, obteniéndose una visión más ajustada de la propia evolución tecnológica, y los avances conseguidos en cada periodo culturalThe following paper addresses a series ofexperimental archeology activities performed at the Archeological Site ofLa Araña. They cover the most significant aspects ofArcheology and its protocols -includingfield and laboratory work-as well as the replication of technological processes prehistoric groups had to face for their survival, from the Lower Paleolithic to the Chalcolithic. With the reenactment of the various technologies more immediate information is obtained, and the difficulties inherent to each of them are better appreciated, building a more accurate perspective of the technological evolution itself, andthe advances achieved in each cultural perio

Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina

PurposeThe aim of this study was to investigate, the neuroprotective effects of a new Gramine derivative named: ITH12657, in a model of retinal excitotoxicity induced by intravitreal injection of NMDA.MethodsAdult Sprague Dawley rats received an intravitreal injection of 100 mM NMDA in their left eye and were treated daily with subcutaneous injections of ITH12657 or vehicle. The best dose–response, therapeutic window study, and optimal treatment duration of ITH12657 were studied. Based on the best survival of Brn3a + RGCs obtained from the above-mentioned studies, the protective effects of ITH12657 were studied in vivo (retinal thickness and full-field Electroretinography), and ex vivo by quantifying the surviving population of Brn3a + RGCs, αRGCs and their subtypes α-ONsRGCs, α-ONtRGCs, and α-OFFRGCs.ResultsAdministration of 10 mg/kg ITH12657, starting 12 h before NMDA injection and dispensed for 3 days, resulted in the best significant protection of Brn3a + RGCs against NMDA-induced excitotoxicity. In vivo, ITH12657-treated rats showed significant preservation of retinal thickness and functional protection against NMDA-induced retinal excitotoxicity. Ex vivo results showed that ITH12657 afforded a significant protection against NMDA-induced excitotoxicity for the populations of Brn3a + RGC, αRGC, and αONs-RGC, but not for the population of αOFF-RGC, while the population of α-ONtRGC was fully resistant to NMDA-induced excitotoxicity.ConclusionSubcutaneous administration of ITH12657 at 10 mg/kg, initiated 12 h before NMDA-induced retinal injury and continued for 3 days, resulted in the best protection of Brn3a + RGCs, αRGC, and αONs-RGC against excitotoxicity-induced RGC death. The population of αOFF-RGCs was extremely sensitive while α-ONtRGCs were fully resistant to NMDA-induced excitotoxicity

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study

Background: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. Methods: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero ([removed]2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. Findings: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16–0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26–0·57; p[removed]11 página