Intrinsic Moment of Inertia of Membranes as bounds for the mass gap of Yang-Mills Theories

We obtain the precise condition on the potentials of Yang-Mills theories in 0+1 dimensions and D0 brane quantum mechanics ensuring the discretness of the spectrum. It is given in terms of a moment of inertia of the membrane. From it we obtain a bound for the mass gap of any D+1 Yang-Mills theory in the slow-mode regime. In particular we analyze the physical case D=3. The quantum mechanical behavior of the theories, concerning its spectrum, is determined by harmonic oscillators with frequencies given by the inertial tensor of the membrane. We find a class of quantum mechanic potential polynomials of any degree, with classical instabilities that at quantum level have purely discrete spectrum.Comment: 12pages, Latex, minor changes, more explanatory comment

A computerized analysis of the entire retinal ganglion cell population and its spatial distribution in adult rats

AbstractIn adult albino (SD) and pigmented (PVG) rats the entire population of retinal ganglion cells (RGCs) was quantified and their spatial distribution analyzed using a computerized technique. RGCs were back-labelled from the optic nerves (ON) or the superior colliculi (SCi) with Fluorogold (FG). Numbers of RGCs labelled from the ON [SD: 82,818±3,949, n=27; PVG: 89,241±3,576, n=6) were comparable to those labelled from the SCi [SD: 81,486±4,340, n=37; PVG: 87,229±3,199; n=59]. Detailed methodology to provide cell density information at small scales demonstrated the presence of a horizontal region in the dorsal retina with highest densities, resembling a visual streak

Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome

The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects

Tracing the retina to analyze the integrity and phagocytic capacity of the retinal pigment epithelium

We have developed a new technique to study the integrity, morphology and functionality of the retinal neurons and the retinal pigment epithelium (RPE). Young and old control albino (Sprague-Dawley) and pigmented (Piebald Virol Glaxo) rats, and dystrophic albino (P23H-1) and pigmented (Royal College of Surgeons) rats received a single intravitreal injection of 3% Fluorogold (FG) and their retinas were analyzed from 5 minutes to 30 days later. Retinas were imaged in vivo with SD-OCT and ex vivo in flat-mounts and in cross-sections. Fifteen minutes and 24 hours after intravitreal administration of FG retinal neurons and the RPE, but no glial cells, were labeled with FG-filled vesicles. The tracer reached the RPE 15 minutes after FG administration, and this labeling remained up to 30 days. Tracing for 15 minutes or 24 hours did not cause oxidative stress. Intraretinal tracing delineated the pathological retinal remodelling occurring in the dystrophic strains. The RPE of the P23H-1 strain was highly altered in aged animals, while the RPE of the RCS strain, which is unable to phagocytose, did not accumulate the tracer even at young ages when the retinal neural circuit is still preserved. In both dystrophic strains, the RPE cells were pleomorphic and polymegathic

Análisis comparativo de la atención de pacientes con enfermedad neurológica en el servicio de urgencias hospitalario durante el periodo de confinamiento por COVID-19

El nuevo coronavirus (SARS-CoV-2) fue identificado por primera vez en la ciudad china de Wuhan, en diciembre de 2019. Desde entonces el virus se ha propagado a más de 200 países. El 30 de enero de 2020 el brote fue declarado “Emergencia de salud pública de importancia internacional” por la Organización Mundial de la Salud, y el 11 de marzo elevado a “Pandemia internacional”1. El primer diagnóstico en España se registró el 31 de enero, pero no fue hasta marzo cuando los casos comenzaron a crecer exponencialmente. El 14 de marzo el Gobierno de España declaraba el estado de alarma por el que limitaba la libre circulación de personas, entre otras medidas. En Aragón esta limitación estuvo vigente hasta el 4 de mayo, cuando dio comienzo el proceso de desescalada. A fecha de 16 de junio de 2020 se han confirmado en España 244.328 diagnósticos por test de reacción en cadena de polimerasa (PCR)2. En nuestro hospital, a medida que aumentaba la carga asistencial de enfermedad respiratoria en el servicio de urgencias hospitalarias (SUH), se percibía un descenso del resto de enfermedades, incluida la neurológica y, particularmente, la enfermedad cerebrovascular aguda, como se ha reportado en otros estudios3. A nivel mundial, las enfermedades neurológicas representan la causa principal de años de vida perdidos ajustados por discapacidad y la segunda causa de muerte4. En España, la mortalidad por causa neurológica representa el 19% del total anual. Esta cifra se ha incrementado en los últimos 10 años en un 18, 5%. En el caso de Aragón, las enfermedades neurológicas causan el 20, 6% de las muertes5..

Evaluation of the Impact of the COVID-19 Lockdown in the Clinical Course of Migraine

Objective: Previous studies have demonstrated that emotional stress, changes in lifestyle habits and infections can worsen the clinical course of migraine. We hypothesize that changes in habits and medical care during coronavirus disease 2019 (COVID-19) lockdown might have worsened the clinical course of migraine. Design: Retrospective survey study collecting online responses from migraine patients followed-up by neurologists at three tertiary hospitals between June and July 2020. Methods: We used a web-based survey that included demographic data, clinical variables related with any headache (frequency) and migraine (subjective worsening, frequency, and intensity), lockdown, and symptoms of post-traumatic stress. Results: The response rate of the survey was 239/324 (73.8%). The final analysis included 222 subjects. Among them, 201/222 (90.5%) were women, aged 42.5 ± 12.0 (mean±SD). Subjective improvement of migraine during lockdown was reported in 31/222 participants (14.0%), while worsening in 105/222 (47.3%) and was associated with changes in migraine triggers such as stress related to going outdoors and intake of specific foods or drinks. Intensity of attacks increased in 67/222 patients (30.2%), and it was associated with the subjective worsening, female sex, recent insomnia, and use of acute medication during a headache. An increase in monthly days with any headache was observed in 105/222 patients (47.3%) and was related to symptoms of post-traumatic stress, older age and living with five or more people. Conclusions: Approximately half the migraine patients reported worsening of their usual pain during the lockdown. Worse clinical course in migraine patients was related to changes in triggers and the emotional impact of the lockdown. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine

Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis.

Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.The authors acknowledge funding from the National Institute of Allergy and Infectious Diseases (M.P.P. and M.N., R01AI114685; M.P.P., 1R21AI127594, R01AI124046; C.R.C., R21AI126296; https://www.niaid.nih.gov/), the Spanish Ministerio de Economí a, Industria y Competitividad (M.N., SAF2015-71444-P; D.G.-P., SAF2016-79957-R; http://www.mineco.gob.es), Subdireccion General de Redes ́ y Centros de Investigacion Cooperativa (RICET, https://www.ricet.es/) (M.N., RD16/0027/0019; D.G.P., RD16/ 0027/0014), and RTI2018-097210-B-I00 (MINCIU-FEDER) to F.G. An ACS MEDI Predoctoral Fellowship for D.M.K. is gratefully acknowledged, as is support from the National Science Foundation for K.F. (CHE-1262734). We thank AstraZeneca, Charles River Laboratories, and GlaxoSmithKline for the provision of the in vitro ADME and physicochemical properties data. The use of JChem/ChemAxon software is acknowledged

Early life risk factors and their cumulative effects as predictors of overweight in Spanish children

Objectives: To explore early life risk factors of overweight/obesity at age 6 years and their cumulative effects on overweight/obesity at ages 2, 4 and 6 years. Methods: Altogether 1031 Spanish children were evaluated at birth and during a 6-year follow-up. Early life risk factors included: parental overweight/obesity, parental origin/ethnicity, maternal smoking during pregnancy, gestational weight gain, gestational age, birth weight, caesarean section, breastfeeding practices and rapid infant weight gain collected via hospital records. Cumulative effects were assessed by adding up those early risk factors that significantly increased the risk of overweight/obesity. We conducted binary logistic regression models. Results: Rapid infant weight gain (OR 2.29, 99% CI 1.54–3.42), maternal overweight/obesity (OR 1.93, 99% CI 1.27–2.92), paternal overweight/obesity (OR 2.17, 99% CI 1.44–3.28), Latin American/Roma origin (OR 3.20, 99% CI 1.60–6.39) and smoking during pregnancy (OR 1.61, 99% CI 1.01–2.59) remained significant after adjusting for confounders. A higher number of early life risk factors accumulated was associated with overweight/obesity at age 6 years but not at age 2 and 4 years. Conclusions: Rapid infant weight gain, parental overweight/obesity, maternal smoking and origin/ethnicity predict childhood overweight/obesity and present cumulative effects. Monitoring children with rapid weight gain and supporting a healthy parental weight are important for childhood obesity prevention