Effect of 28 days treatment of baricitinib on mechanical allodynia, osteopenia, and loss of nerve fibers in an experimental model of type-1 diabetes mellitus.

BACKGROUND: Type-1 diabetes mellitus (T1DM) is associated with numerous health problems, including peripheral neuropathy, osteoporosis, and bone denervation, all of which diminish quality of life. However, there are relatively few therapies to treat these T1DM-related complications. Recent studies have shown that Janus kinase (JAK) inhibitors reverse aging- and rheumatoid arthritis-induced bone loss and reduce pain associated with peripheral nerve injuries, and rheumatoid arthritis. Thus, we assessed whether a JAK1/JAK2 inhibitor, baricitinib, ameliorates mechanical pain sensitivity (a measure of peripheral neuropathy), osteoporosis, and bone denervation in the femur of mice with T1DM. METHODS: Female ICR mice (13 weeks old) received five daily administrations of streptozotocin (ip, 50 mg/kg) to induce T1DM. At thirty-one weeks of age, mice were treated with baricitinib (po; 40 mg/kg/bid; for 28 days) or vehicle. Mechanical sensitivity was evaluated at 30, 33, and 35 weeks of age on the plantar surface of the right hind paw. At the end of the treatment, mice were sacrificed, and lower extremities were harvested for microcomputed tomography and immunohistochemistry analyses. RESULTS: Mice with T1DM exhibited greater blood glucose levels, hind paw mechanical hypersensitivity, trabecular bone loss, and decreased density of calcitonin gene-related peptide-positive and tyrosine hydroxylase-positive axons within the marrow of the femoral neck compared to control mice. Baricitinib treatment significantly reduced mechanical hypersensitivity and ameliorated sensory and sympathetic denervation at the femoral neck, but it did not reverse trabecular bone loss. CONCLUSIONS: Our findings suggest that baricitinib may represent a new therapeutic alternative to treat T1DM-induced peripheral neuropathy and bone denervation.

Fluorescence microscopy shadow imaging for neuroscience.

Fluorescence microscopy remains one of the single most widely applied experimental approaches in neuroscience and beyond and is continuously evolving to make it easier and more versatile. The success of the approach is based on synergistic developments in imaging technologies and fluorophore labeling strategies that have allowed it to greatly diversify and be used across preparations for addressing structure as well as function. Yet, while targeted labeling strategies are a key strength of fluorescence microscopy, they reciprocally impose general limitations on the possible types of experiments and analyses. One recent development that overcomes some of these limitations is fluorescence microscopy shadow imaging, where membrane-bound cellular structures remain unlabeled while the surrounding extracellular space is made to fluoresce to provide a negative contrast shadow image. When based on super-resolution STED microscopy, the technique in effect provides a positive image of the extracellular space geometry and entire neuropil in the field of view. Other noteworthy advantages include the near elimination of the adverse effects of photobleaching and toxicity in live imaging, exhaustive and homogeneous labeling across the preparation, and the ability to apply and adjust the label intensity on the fly. Shadow imaging is gaining popularity and has been applied on its own or combined with conventional positive labeling to visualize cells and synaptic proteins in their parenchymal context. Here, we highlight the inherent limitations of fluorescence microscopy and conventional labeling and contrast these against the pros and cons of recent shadow imaging approaches. Our aim is to describe the brief history and current trajectory of the shadow imaging technique in the neuroscience field, and to draw attention to its ease of application and versatility.

Engineering paralog-specific PSD-95 recombinant binders as minimally interfering multimodal probes for advanced imaging techniques.

Despite the constant advances in fluorescence imaging techniques, monitoring endogenous proteins still constitutes a major challenge in particular when considering dynamics studies or super-resolution imaging. We have recently evolved specific protein-based binders for PSD-95, the main postsynaptic scaffold proteins at excitatory synapses. Since the synthetic recombinant binders recognize epitopes not directly involved in the target protein activity, we consider them here as tools to develop endogenous PSD-95 imaging probes. After confirming their lack of impact on PSD-95 function, we validated their use as intrabody fluorescent probes. We further engineered the probes and demonstrated their usefulness in different super-resolution imaging modalities (STED, PALM, and DNA-PAINT) in both live and fixed neurons. Finally, we exploited the binders to enrich at the synapse genetically encoded calcium reporters. Overall, we demonstrate that these evolved binders constitute a robust and efficient platform to selectively target and monitor endogenous PSD-95 using various fluorescence imaging techniques.

Complete Genome Sequence of Bacteriophage Loca, Isolated on a Microbacterium foliorum Culture.

Microbacteriophage Loca was extracted from a shopping cart handle swab sample in Stephenville, TX, and isolated on a Microbacterium foliorum NRRL-24224 culture. The 17,475-bp double-stranded DNA genome contains 25 predicted protein-coding genes and has >96% nucleotide identity to bacteriophages Quaker and Livingwater.

Effect of chronic lithium on mechanical sensitivity and trabecular bone loss induced by type-1 diabetes mellitus in mice.

Type-1 diabetes mellitus (T1DM) is a chronic condition characterized by long-term hyperglycemia that results in several complications such as painful peripheral neuropathy, bone deterioration, and increased risk of bone fractures. Lithium, a first-line therapy for bipolar disorder, has become an attractive agent for attenuating peripheral neuropathy and menopause-induced bone loss. Therefore, our aim was to determine the effect of chronic lithium treatment on mechanical hypersensitivity and trabecular bone loss induced by T1DM in mice. T1DM was induced in male C57BL/6J mice by intraperitoneal injection of streptozotocin (STZ, 50 mg/kg/day, for 5 consecutive days). 12 weeks after T1DM-induction, mice received a daily intraperitoneal injection of vehicle, 30 or 60 mg/kg lithium (as LiCl) for 6 weeks. Throughout the treatment period, blood glucose levels and mechanical sensitivity were evaluated every 2 weeks. After lithium treatment, the femur and L5 vertebra were harvested for microcomputed tomography (microCT) analysis. T1DM mice showed significant hyperglycemia, mechanical hypersensitivity, and significant trabecular bone loss as compared with the control group. Chronic lithium treatment did not revert the hindpaw mechanical hypersensitivity nor hyperglycemia associated to T1DM induced by STZ. In contrast, microCT analysis revealed that lithium reverted, in a dose-dependent manner, the loss of trabecular bone associated to T1DM induced by STZ at both the distal femur and L5 vertebra. Lithium treatment by itself did not affect any trabecular bone parameter in non-diabetic mice.

New Red-Emitting Chloride-Sensitive Fluorescent Protein with Biological Uses.

A new chloride-sensitive red fluorescent protein derived from Entacmaea quadricolor is described. We found that mBeRFP exhibited moderate sensitivity to chloride and, via site-directed mutagenesis (S94V and R205Y), we increased the chloride affinity by more than an order of magnitude (kd = 106 ± 6 mM) at physiological pH. In addition, cis-trans isomerization of the chromophore produces a dual emission band with different chloride sensitivities, which allowed us to develop a ratiometric methodology to measure intracellular chloride concentrations.

Bioprotective extracts from Lactobacillus acidophilus CRL641 and Latilactobacillus curvatus CRL705 inhibit a spoilage exopolysaccharide producer in a refrigerated meat system.

The effect of bioprotective extracts (BEs) from Latilactobacillus curvatus CRL705 and Lactobacillus acidophilus CRL641 against Latilactobacillus sakei CRL1407 was evaluated in a refrigerated meat model system under vacuum and aerobic conditions at 4 and 10 °C. As shown by culturing, the BE-1 from L. acidophilus completely inhibited the spoilage strain, while that from Lat. Curvatus CRL705 (BE-2) and its combination with BE-1 exerted a bacteriostatic effect. The antimicrobial activity and exopolysaccharide production correlated with the efficacy of inhibitory treatment while final pH decrease was higher in control samples. When flow cytometry was applied, a lack of correlation with plate counting was found; counts under the detection limit for BE-1 at 21 and 28 days at 4 and 10 °C represented between 64.15 and 73.70% of dead cells. Thus, the concurrence of lactic acid bacteria as biocontrol agents and the use of more accurate tools to prevent the growth of deteriorating species will contribute to the extension of fresh meat shelf-life without quality loss.

Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery.

Recently, it was proposed that the thiophene ring is capable of promoting mitochondrial accumulation when linked to fluorescent markers. As a noncharged group, thiophene presents several advantages from a synthetic point of view, making it easier to incorporate such a side moiety into different molecules. Herein, we confirm the general applicability of the thiophene group as a mitochondrial carrier for drugs and fluorescent markers based on a new concept of nonprotonable, noncharged transporter. We implemented this concept in a medicinal chemistry application by developing an antitumor, metabolic chimeric drug based on the pyruvate dehydrogenase kinase (PDHK) inhibitor dichloroacetate (DCA). The promising features of the thiophene moiety as a noncharged carrier for targeting mitochondria may represent a starting point for the design of new metabolism-targeting drugs.

[Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19]. / Mortalidad y factores pronósticos asociados en pacientes ancianos y muy ancianos hospitalizados con infección respiratoria COVID-19.

INTRODUCTION: Elderly patients with COVID-19 has a worse clinical evolution, being more susceptible to develop serious manifestations. The differences between the elderly and very elderly population, mortality and associated prognostic factors of SARS-CoV-2 infection have not been enough studied yet. METHODS: An observational study of 416 elderly patients admitted consecutively to Hospital General Universitario de Ciudad Real for COVID-19 respiratory infection from March 1st to April 30th, 2020. Data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions and clinical outcomes during the hospitalization and after discharge, until June 15, 2020 with the aim of analyzing mortality, and associated prognostic factors. RESULTS: The mean age was 84.43±5.74 years old; elderly patients (75-84 years) were 50.2% of the sample and very elderly (≥85 years) the remaining 49.8%. In Cox regression model, mortality rate was higher in very elderly group (HR = 2.58; 95% CI: 1.23-5.38; P = .01), hypertensive (HR = 3, 45; 95% CI: 1.13-10.5; P = .03) and chronic kidney disease patients (HR = 3.86; 95% CI: 1.3-11.43; P = .02). In contrast, calcium antagonists (HR = 0.27; 95% CI: 0.12-0.62; P = .002) and anticoagulant therapy during hospitalization (HR = 0.26; 95% CI: 0.08 0, 83; P = .02) were associated with a longer time free of mortality. CONCLUSIONS: Mortality rate was higher in very eldery patients compared with eldery; and in hypertensive and chronic kidney disease patients. Anticoagulation therapy and calcium chanel bloquers treatment during hospitalization were associated with a higher survival in the short-term follow-up in patients hospitalized with COVID-19.

Chronic administration of Cl-amidine, a pan-peptidylarginine deiminase inhibitor, does not reverse bone loss in two different murine models of osteoporosis.

Recent in vitro studies have shown a role for the peptidyl-arginine deiminases (PADs) in bone resorption. However, it is unknown whether these enzymes are involved in bone loss in vivo. Thus, we evaluated the antiresorptive effect of a pan-PAD inhibitor in two murine models of osteoporosis: (a) primary osteoporosis induced by ovariectomy (OVX); and (b) secondary osteoporosis associated to Type-1 diabetes induced by streptozotocin (STZ, 50 mg/kg, i.p., five daily administrations). Five weeks after OVX and 15 weeks after injections of STZ, mice received daily administrations of Cl-amidine (3 or 10 mg/kg, i.p.) or vehicle for 30 consecutive days. At the end of the treatment, femur and vertebra were harvested for microCT analysis. Blood samples were collected for determination of antibodies against cyclic citrullinated peptides (anti-CCP) by enzyme-linked immunosorbent assay. Serum levels of anti-CCP antibodies from diabetic mice were not significantly different compared to control mice. However, a significant loss of both trabecular bone at the femoral neck and cortical bone at the femoral diaphysis was found in diabetic mice, and Cl-amidine did not reverse the diabetes-induced bone loss. Mice with OVX had significantly lower serum levels of anti-CCP compared to mice with sham surgery. OVX resulted in significant loss of both trabecular bone at the L5 vertebra and distal femoral metaphysis. Cl-amidine did not block the OVX-induced bone loss. Our results suggest that chronic treatment with Cl-amidine at the doses and period of time administered is not long enough to inhibit bone loss in two different murine models of osteoporosis.

Medium-long term mortality and change in functional status in elderly patients with pacemaker.

Background: Nowadays, 49% of patients with pacemakers are older than 80 years old. Nevertheless, mortality and change in functional status after pacemaker implantation are not well documented in elderly patients. Objective: We designed a prospective study to analyze cardiovascular mortality and change in functional status of elderly patients, medium-long term after pacemaker implantation. Methods: Observational study including pacemaker implants in individual older than 70 years old in a single center university hospital between 2012 and 2014. Analysis testing for an association between pacemaker system, medium-long term mortality and functional status after implantation were undertaken. Results: 60% of patients were older than 80 years old. Third-degree atrio-ventricular block (44.3%) and slow ventricular response atrial fibrillation (16.7%) were the most frequent electrocardiogram abnormalities, while bicameral DDD was the sort of pacing our department used the most (38.6%) (VVI in octogenarian patients, 38.7%). Long-term mortality was significantly higher in ventricular devices, especially in octogenarian patients (p = 0.001 respectively). Single-chamber VVI pacing acted as independent predictors of all-cause mortality in these individuals (p = 0.001). We found no significant improvement in Barthel index and functional status in this subgroup of patients, 3 years after pacing. Conclusion: Long-term mortality in individuals older than 80 years old with pacemaker implantation, was significantly higher comparing with general population, especially in ventricular devices. No significant improvement in functional status was detected in this subgroup of patients.

Antecedentes: Aproximadamente un 49% de los implantes se efectúan a individuos mayores de 80 años; sin embargo, la evidencia científica sobre mortalidad y cambio en la situación funcional de estos pacientes es muy pobre. Objetivo: Diseñamos un estudio prospectivo para analizar la morbimortalidad cardiovascular y la variación de su grado funcional a medio plazo en pacientes ancianos con electroestimulación permanente. Método: Estudio observacional prospectivo, que incluye 308 pacientes ancianos sometidos a implante de marcapasos en un hospital terciario entre 2012 y 2014. Como variables principales se evaluaron eventos cardiovasculares, mortalidad y grado funcional, con una media de seguimiento de 3.5 años. Resultados: El 60% de los pacientes incluidos en nuestro estudio tenían una edad superior a 80 años, y la indicación más frecuente fue el bloqueo auriculoventricular completo (44.3%), seguido de la fibrilación auricular lenta o bloqueada (16.7%). El modo de estimulación más frecuente en la muestra general fue el DDD (38.6%) (VVI en pacientes octogenarios, 38.7%). En el seguimiento, la mortalidad a largo plazo fue mayor en dispositivos ventriculares, especialmente en octogenarios (p = 0.001). El modo de estimulación ventricular (VVI) fue predictor independiente de mortalidad. A largo plazo, no se observó mejoría del índice de Barthel ni del grado funcional tras el implante del marcapasos. Conclusiones: La morbimortalidad cardiovascular en pacientes octogenarios portadores de marcapasos resulta superior a la de la población general, especialmente en dispositivos monocamerales. La electroestimulación permanente no se asocia con mejoría del grado funcional a medio-largo plazo en estos pacientes.

Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules.

Designing highly specific modulators of protein-protein interactions (PPIs) is especially challenging in the context of multiple paralogs and conserved interaction surfaces. In this case, direct generation of selective and competitive inhibitors is hindered by high similarity within the evolutionary-related protein interfaces. We report here a strategy that uses a semi-rational approach to separate the modulator design into two functional parts. We first achieve specificity toward a region outside of the interface by using phage display selection coupled with molecular and cellular validation. Highly selective competition is then generated by appending the more degenerate interaction peptide to contact the target interface. We apply this approach to specifically bind a single PDZ domain within the postsynaptic protein PSD-95 over highly similar PDZ domains in PSD-93, SAP-97 and SAP-102. Our work provides a paralog-selective and domain specific inhibitor of PSD-95, and describes a method to efficiently target other conserved PPI modules.

Morbimortalidad cardiovascular y variación del grado funcional en pacientes ancianos portadores de marcapasos / Medium-long term mortality and change in functional status in elderly patients with pacemaker

Resumen Antecedentes: Aproximadamente un 49% de los implantes se efectúan a individuos mayores de 80 años; sin embargo, la evidencia científica sobre mortalidad y cambio en la situación funcional de estos pacientes es muy pobre. Objetivo: Diseñamos un estudio prospectivo para analizar la morbimortalidad cardiovascular y la variación de su grado funcional a medio plazo en pacientes ancianos con electroestimulación permanente. Método: Estudio observacional prospectivo, que incluye 308 pacientes ancianos sometidos a implante de marcapasos en un hospital terciario entre 2012 y 2014. Como variables principales se evaluaron eventos cardiovasculares, mortalidad y grado funcional, con una media de seguimiento de 3.5 años. Resultados: El 60% de los pacientes incluidos en nuestro estudio tenían una edad superior a 80 años, y la indicación más frecuente fue el bloqueo auriculoventricular completo (44.3%), seguido de la fibrilación auricular lenta o bloqueada (16.7%). El modo de estimulación más frecuente en la muestra general fue el DDD (38.6%) (VVI en pacientes octogenarios, 38.7%). En el seguimiento, la mortalidad a largo plazo fue mayor en dispositivos ventriculares, especialmente en octogenarios (p = 0.001). El modo de estimulación ventricular (VVI) fue predictor independiente de mortalidad. A largo plazo, no se observó mejoría del índice de Barthel ni del grado funcional tras el implante del marcapasos. Conclusiones: La morbimortalidad cardiovascular en pacientes octogenarios portadores de marcapasos resulta superior a la de la población general, especialmente en dispositivos monocamerales. La electroestimulación permanente no se asocia con mejoría del grado funcional a medio-largo plazo en estos pacientes.

Abstract Background: Nowadays, 49% of patients with pacemakers are older than 80 years old. Nevertheless, mortality and change in functional status after pacemaker implantation are not well documented in elderly patients. Objective: We designed a prospective study to analyze cardiovascular mortality and change in functional status of elderly patients, medium-long term after pacemaker implantation. Methods: Observational study including pacemaker implants in individual older than 70 years old in a single center university hospital between 2012 and 2014. Analysis testing for an association between pacemaker system, medium-long term mortality and functional status after implantation were undertaken. Results: 60% of patients were older than 80 years old. Third-degree atrio-ventricular block (44.3%) and slow ventricular response atrial fibrillation (16.7%) were the most frequent electrocardiogram abnormalities, while bicameral DDD was the sort of pacing our department used the most (38.6%) (VVI in octogenarian patients, 38.7%). Long-term mortality was significantly higher in ventricular devices, especially in octogenarian patients (p = 0.001 respectively). Single-chamber VVI pacing acted as independent predictors of all-cause mortality in these individuals (p = 0.001). We found no significant improvement in Barthel index and functional status in this subgroup of patients, 3 years after pacing. Conclusion: Long-term mortality in individuals older than 80 years old with pacemaker implantation, was significantly higher comparing with general population, especially in ventricular devices. No significant improvement in functional status was detected in this subgroup of patients.

New Thiol-Sensitive Dye Application for Measuring Oxidative Stress in Cell Cultures.

A xanthene derivative, Granada Green dinitrobenzene sulfonate (GGDNBS), has been synthesized to assay cellular oxidative stress based on changes in the concentration of biothiols. The dye is able to react with biological thiols by a thiolysis reaction that promotes a change in fluorescence intensity. To demonstrate the usefulness of GGDNBS for in vivo oxidative stress measurements, 661 W photoreceptor-derived cells were exposed to light to induce ROS generation, and changes in GGDNBS fluorescence were measured. In these cells, GGDNBS fluorescence was correlated with the biothiol levels measured by an enzymatic method. Therefore, GGDNBS allows us to monitor changes in the levels of biothiols associated with ROS generation via single-cell bioimaging.

Medium-long-term mortality and change in functional status in elderly patients with pacemaker.

Background: Nowadays, 49% of patients with pacemakers are older than 80 years old. Nevertheless, mortality and change in functional status after pacemaker implantation are not well documented in elderly patients. Objective: We designed a prospective study to analyze the cardiovascular mortality and change in functional status of elderly patients, medium-long term after pacemaker implantation. Methods: An observational study including pacemaker implants in individual older than 70 years old in a single-center university hospital between 2012 and 2014. Analysis testing for an association between pacemaker system, medium-long-term mortality, and functional status after implantation was undertaken. Results: About 60% of patients were older than 80 years old. The third-degree atrioventricular blockage (44.3%) and slow ventricular response atrial fibrillation (16.7%) were the most frequent electrocardiogram abnormalities, while bicameral DDD was the sort of pacing our department used the most (38.6%) (VVI in octogenarian patients, 38.7%). Long-term mortality was significantly higher in ventricular devices, especially in octogenarian patients (p = 0.001). Single-chamber VVI pacing acted as independent predictors of all-cause mortality in these individuals (p = 0.001). We found no significant improvement in Barthel Index and functional status in this subgroup of patients, 3 years after pacing. Conclusions: Long-term mortality in individuals older than 80 years old with pacemaker implantation was significantly higher comparing with general population, especially in ventricular devices. No significant improvement in functional status was detected in this subgroup of patients.

Objetivo: Aproximadamente un 49% de los implantes se efectúan a individuos mayores de 80 años; sin embargo, la evidencia científica sobre mortalidad y cambio en la situación funcional de estos pacientes es muy pobre. Diseñamos un estudio prospectivo para analizar la morbimortalidad cardiovascular y la variación de su grado funcional a medio plazo en pacientes ancianos con electroestimulación permanente. Método: Estudio observacional prospectivo, que incluye 308 pacientes ancianos sometidos a implante de marcapasos en un hospital terciario entre 2012 y 2014. Como variables principales se evaluaron eventos cardiovasculares, mortalidad y grado funcional, con una media de seguimiento de 3.5 años. Resultados: El 60% de los pacientes incluidos en nuestro estudio tenían una edad superior a 80 años, y la indicación más frecuente fue el bloqueo auriculoventricular completo (44.3%), seguido de la fibrilación auricular lenta o bloqueada (16.7%). El modo de estimulación más frecuente fue el DDD (38.6%). En el seguimiento, la mortalidad a largo plazo fue mayor en dispositivos ventriculares, especialmente en octogenarios (p = 0.001). El modo de estimulación VVI fue predictor independiente de mortalidad. A largo plazo, no se observó mejoría del grado funcional tras el implante del marcapasos. Conclusiones: La morbimortalidad cardiovascular en pacientes octogenarios portadores de marcapasos resulta superior a la de la población general, especialmente en dispositivos monocamerales. La electroestimulación permanente no se asocia con mejoría del grado funcional a medio-largo plazo en estos pacientes.

Versatile synthesis and enlargement of functionalized distorted heptagon-containing nanographenes.

Highly distorted polycyclic aromatic hydrocarbons (PAHs) are predicted to be attractive goals in nanoscience owing to the new properties they can exhibit. We have shown that a variety of functionalized distorted heptagon-containing nanographenes can be easily prepared from simple building blocks by a sequence of Co-catalyzed cyclotrimerization and cyclodehydrogenation reactions. The versatility of this strategy allows easy subsequent enlargement of these nanostructures by Ni-catalyzed cross-coupling and final cyclodehydrogenation reactions. Soluble extended distorted nanographenes 1 and 2 containing heptagon and an edge-shared pentagon-heptagon combination have been synthesized. High distortion of the polycyclic backbone of 2 caused by non-hexagonal rings and a helicene moiety was confirmed by X-ray crystallography. Experimental data reveal promising optical and electronic properties for distorted PAHs with long fluorescence lifetimes (up to 14.5 ns) and low band gaps (down to 2.27 eV). This straightforward and versatile synthetic strategy, the observed long fluorescence lifetimes and the small optical and electrochemical band gaps for the presented compounds may promote the future implementation of distorted graphene molecules in electronic devices.

High-fat diet exacerbates pain-like behaviors and periarticular bone loss in mice with CFA-induced knee arthritis.

OBJECTIVE: Our aim was to quantify nociceptive spontaneous behaviors, knee edema, proinflammatory cytokines, bone density, and microarchitecture in high-fat diet (HFD)-fed mice with unilateral knee arthritis. METHODS: ICR male mice were fed either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD mice received intra-articular injections either with Complete Freund's Adjuvant (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous pain-like behaviors and knee edema were assessed for 26 days. At day 26 post-first CFA injection, serum levels of IL-1ß, IL-6, and RANKL were measured by ELISA, and microcomputed tomography analysis of knee joints was performed. RESULTS: HFD-fed mice injected with CFA showed greater spontaneous pain-like behaviors of the affected extremity as well as a decrease in the weight-bearing index compared to SD-fed mice injected with CFA. Knee edema was not significantly different between diets. HFD significantly exacerbated arthritis-induced bone loss at the distal femoral metaphysis but had no effect on femoral diaphyseal cortical bone. HFD did not modify serum levels of proinflammatory cytokines. CONCLUSIONS: HFD exacerbates pain-like behaviors and significantly increases the magnitude of periarticular trabecular bone loss in a murine model of unilateral arthritis.

[Not Available]. / Diseño de un programa de educación nutricional destinado a mujeres saharauis residentes en los campamentos de Tinduf (Argelia).

Introducción: la población saharaui residente en los campamentos de Tinduf (Argelia) se considera vulnerable desde el punto de vista nutricional.Objetivos: evaluar los hábitos dietéticos de un grupo de mujeres emigrantes saharauis con el fin de obtener datos para diseñar un programa de educación nutricional (EN) destinado a mujeres residentes en los campamentos. Métodos: la información sobre hábitos dietéticos se registró a través de historias dietéticas. Los resultados de ingesta de macro y micronutrientes se compararon con los rangos aceptables de distribución y los requerimientos medios estimados. También se recogieron datos demográficos, socioeconómicos y sobre salud. Análisis estadístico: SPSS vs 22.0. A partir de los datos obtenidos y de la revisión de los programas de salud llevados a cabo en campamentos y de otros programas de EN se diseñó un programa específico. Resultados: la alimentación en campamentos se caracterizó por ser deficitaria en energía y por un bajo consumo de fibra (6,1 [2,8] g/día), de ácidos grasos monoinsaturados (6,9 [2,9]% del valor calórico total) y de la mayoría de los micronutrientes. El aumento en la disponibilidad de alimentos tras emigrar a España incrementó la ingesta calórica, pero la dieta siguió siendo inadecuada. El programa de EN diseñado se basó en la formación de formadoras. En este manuscrito se proporciona información detallada sobre la organización y el material a emplear en esta intervención educativa. Discusión y conclusión: la alimentación de las mujeres saharauis en campamentos y tras emigrar a España fue inadecuada, lo que corrobora que la aculturación puede estar asociada a cambios no saludables. Cabe esperar que el programa de EN diseñado contribuya a mejorar su bienestar nutricional.

New Dual Fluorescent Probe for Simultaneous Biothiol and Phosphate Bioimaging.

The simultaneous detection of relevant metabolites in living organisms by using one molecule introduces an approach to understanding the relationships between these metabolites in healthy and deregulated cells. Fluorescent probes of low toxicity are remarkable tools for this type of analysis of biological systems in vivo. As a proof of concept, different naturally occurring compounds, such as biothiols and phosphate anions, were the focus for this work. The 2,4-dinitrobenzenesulfinate (DNBS) derivative of 9-[1-(4-tert-butyl-2-methoxyphenyl)]-6-hydroxy-3H-xanthen-3-one (Granada Green; GG) were designed and synthesized. This new sulfinyl xanthene derivative can act as a dual sensor for the aforementioned analytes simultaneously. The mechanism of action of this derivative implies thiolysis of the sulfinyl group of the weakly fluorescent DNBS-GG by biological thiols at near-neutral pH values, thus releasing the fluorescent GG moiety, which simultaneously responds to phosphate anions through its fluorescence-decay time. The new dual probe was tested in solution by using steady-state and time-resolved fluorescence and intracellularly by using fluorescence-lifetime imaging microscopy (FLIM) in human epithelioid cervix carcinoma (HeLa) cells.

Comparative assessment of button cells using a normalized index for potential pollution by heavy metals.

Many household batteries worldwide still end up in landfills or are incinerated due to inefficient collection and recycling schemes. Toxic heavy metals from improperly discarded button cells pose a serious risk to human health and the environment, as they can pollute air, soil and water. This paper analyses a series of button cells selected from batteries available on the retail market, and compares their polluting potential. A total of 64 batteries were subjected to chemical analyses of 19 elements - including metals and metalloids - , and energy density measurements. The samples were from four different brands of each of the four most common button cell technologies (alkaline, zinc-air, silver oxide and lithium). An energy-normalized index - the Weighted Potential Pollution Index (WPPI) - was proposed to compare the polluting potential of the different batteries. The higher the battery WPPI score, the greater the content in toxic elements and the lower the energy output. The results of the chemical composition and energy density varied depending on the construction technology of the button cells. However, significant differences in both variables were also found when comparing different brands within the same technology. The differences in WPPI values confirmed the existence of a significant margin to reduce the environmental impact of discarded button cells simply by avoiding the most polluting options. The choice of the battery with the most favourable WPPI produced a reduction in potential pollution of 3-53% for silver oxide batteries, 4-39% for alkaline, 20-28% for zinc-air and 12-26% for lithium. Comparative potential pollution could be assessed when selecting batteries using an energy-normalized index such as WPPI to reduce the environmental impact of improperly disposed button cells.