Blood-brain barrier biomarkers.

The blood-brain barrier (BBB) is a dynamic interface that regulates the exchange of molecules and cells between the brain parenchyma and the peripheral blood. The BBB is mainly composed of endothelial cells, astrocytes and pericytes. The integrity of this structure is essential for maintaining brain and spinal cord homeostasis and protection from injury or disease. However, in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, and multiple sclerosis, the BBB can become compromised thus allowing passage of molecules and cells in and out of the central nervous system parenchyma. These agents, however, can serve as biomarkers of BBB permeability and neuronal damage, and provide valuable information for diagnosis, prognosis and treatment. Herein, we provide an overview of the BBB and changes due to aging, and summarize current knowledge on biomarkers of BBB disruption and neurodegeneration, including permeability, cellular, molecular and imaging biomarkers. We also discuss the challenges and opportunities for developing a biomarker toolkit that can reliably assess the BBB in physiologic and pathophysiologic states.

Expression of Dystrophin Dp71 Splice Variants Is Temporally Regulated During Rodent Brain Development.

Dystrophin Dp71 is the major product of the Duchenne muscular dystrophy (DMD) gene in the brain, and its loss in DMD patients and mouse models leads to cognitive impairments. Dp71 is expressed as a range of proteins generated by alternative splicing of exons 71 to 74 and 78, classified in the main Dp71d and Dp71f groups that contain specific C-terminal ends. However, it is unknown whether each isoform has a specific role in distinct cell types, brain regions, and/or stages of brain development. In the present study, we characterized the expression of Dp71 isoforms during fetal (E10.5, E15.5) and postnatal (P1, P7, P14, P21 and P60) mouse and rat brain development. We finely quantified the expression of several Dp71 transcripts by RT-PCR and cloning assays in samples from whole-brain and distinct brain structures. The following Dp71 transcripts were detected: Dp71d, Dp71d∆71, Dp71d∆74, Dp71d∆71,74, Dp71d∆71-74, Dp71f, Dp71f∆71, Dp71f∆74, Dp71f∆71,74, and Dp71fΔ71-74. We found that the Dp71f isoform is the main transcript expressed at E10.5 (> 80%), while its expression is then progressively reduced and replaced by the expression of isoforms of the Dp71d group from E15.5 to postnatal and adult ages. This major finding was confirmed by third-generation nanopore sequencing. In addition, we found that the level of expression of specific Dp71 isoforms varies as a function of postnatal stages and brain structure. Our results suggest that Dp71 isoforms have different and complementary roles during embryonic and postnatal brain development, likely taking part in a variety of maturation processes in distinct cell types.

Direct interaction between marine cyanobacteria mediated by nanotubes.

Microbial associations and interactions drive and regulate nutrient fluxes in the ocean. However, physical contact between cells of marine cyanobacteria has not been studied thus far. Here, we show a mechanism of direct interaction between the marine cyanobacteria Prochlorococcus and Synechococcus, the intercellular membrane nanotubes. We present evidence of inter- and intra-genus exchange of cytoplasmic material between neighboring and distant cells of cyanobacteria mediated by nanotubes. We visualized and measured these structures in xenic and axenic cultures and in natural samples. We show that nanotubes are produced between living cells, suggesting that this is a relevant system of exchange material in vivo. The discovery of nanotubes acting as exchange bridges in the most abundant photosynthetic organisms in the ocean may have important implications for their interactions with other organisms and their population dynamics.

Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation.

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Interpreter usage and associations with latent tuberculosis infection treatment acceptance and completion in the USA among non-U.S.-born persons, 2012-2017.

BACKGROUND: Latent tuberculosis infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among the non-U.S.-born population are essential for U.S. tuberculosis elimination. We investigated the impact of medical interpreter use on LTBI treatment acceptance and completion among non-U.S.-born persons in a multisite study. METHODS: The Tuberculosis Epidemiologic Studies Consortium was a prospective cohort study that enrolled participants at high risk for LTBI at ten U.S. sites with 18 affiliated clinics from 2012 to 2017. Non-U.S.-born participants with at least one positive tuberculosis infection test result were included in analyses. Characteristics associated with LTBI treatment offer, acceptance, and completion were evaluated using multivariable logistic regression with random intercepts to account for clustering by enrollment site. Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion. We also evaluated whether interpreter usage was associated treatment offer and whether interpreter type was associated with treatment offer, acceptance, or completion. RESULTS: Among 8,761 non-U.S.-born participants, those who used an interpreter during the initial interview had a significantly greater odds of accepting LTBI treatment than those who did not use an interpreter. There was no association between use of an interpreter and a clinician's decision to offer treatment or treatment completion once accepted. Characteristics associated with lower odds of treatment being offered included experiencing homelessness and identifying as Pacific Islander persons. Lower treatment acceptance was observed in Black and Latino persons and lower treatment completion by participants experiencing homelessness. Successful treatment completion was associated with use of shorter rifamycin-based regimens. Interpreter type was not associated with LTBI treatment offer, acceptance, or completion. CONCLUSIONS: We found greater LTBI treatment acceptance was associated with interpreter use among non-U.S.-born individuals.

Synergistic Interaction Effect of Artemisia cina n-hexane Extract and Tagetes lucida Ethyl Acetate Extract on Haemonchus Contortus.

PURPOSE: We analysed the possible synergistic activity among active extracts from Artemisia cina and Tagetes lucida combinations on Haemonchus contortus, a nematode parasitising sheep. METHODS: The work was carried out in vitro on eggs and infective larvae (L3) of H. contortus. The results were analysed with SAS 9.1, applying the ANOVA and Tukey test, and the lethal concentration (LC) values LC50 and LC90 were determined with regression analysis, employing Proc Probit of SAS 9.1. Additionally, the lethal concentration (LC) was calculated with LC50 and LC90 to determine the synergistic effect. RESULTS: The results demonstrated a high efficacy of the two plants studied on both nematode eggs and L3 larvae as well as of their combinations. The highest egg hatching inhibition was obtained with a 50/50 combination, and the best larvae mortality was obtained with 25% A. cina and 75% T. lucida at 10 mg/mL. Additionally, this combination showed a synergistic effect. CONCLUSION: The two plant species studied here can be applied as natural anthelmintic alternatives due to their high bioactive effect and synergistic response.

Antioxidant and Antifungal Activities and Characterization of Phenolic Compounds Using High-Performance Liquid Chromatography and Mass Spectrometry (HPLC-MS) in Empetrum rubrum Vahl ex Willd.

In searching for compounds with antioxidant and antifungal activity, our study focused on the subshrub species Empetrum rubrum Vahl ex Willd. (Ericaceae). We measured the antioxidant activity of its methanolic extract (MEE) obtained from the aerial parts (leaves and stems) and of its methanolic extract (MEF) obtained from the lyophilized fruits. The antioxidant activity of the MEE and MEF was evaluated in vitro via a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) cationic radical. The results were expressed in gallic acid and Trolox equivalents for the DPPH and ABTS assays, respectively. The antioxidant activities, for the DPPH and ABTS assays, were also evaluated by considering the IC50 values. Concerning the antioxidant activity, the total phenolic content (TPC) in the MEE and MEF was determined using the Folin-Ciocalteu method. Polyphenols contained in the leaves, stems, and fruits of E. rubrum were determined qualitatively by employing high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis. The antifungal activity of the MEE obtained from the aerial parts of E. rubrum was tested against Rhizoctonia solani. The results of IC50 values measured by the DPPH and ABTS methods with MEE were 0.4145 ± 0.0068 mg mL-1 and 0.1088 ± 0.0023 mg mL-1, respectively, and the IC50 values for MEF were 6.4768 ± 0.0218 mg mL-1 and 0.7666 ± 0.0089 mg mL-1 measured by the DPPH and ABTS methods, respectively. The HPLC-MS analysis revealed the presence of anthocyanins, phenolic acids derivatives, and flavonols. In vitro, mycelial growth of this fungus was reduced from 90% to nearly 100% in the presence of MEE. The observed antifungal effect is related to the presence of the abovementioned phenols, detected in the MEE.

A Comparative Analysis of Smartphone and Standard Tools for Touch Perception Assessment Across Multiple Body Sites.

Tactile perception plays an important role in activities of daily living, and it can be impaired in individuals with certain medical conditions. The most common tools used to assess tactile sensation, the Semmes-Weinstein monofilaments and the 128 Hz tuning fork, have poor repeatability and resolution. Long term, we aim to provide a repeatable, high-resolution testing platform that can be used to assess vibrotactile perception through smartphones without the need for an experimenter to be present to conduct the test. We present a smartphone-based vibration perception measurement platform and compare its performance to measurements from standard monofilament and tuning fork tests. We conducted a user study with 36 healthy adults in which we tested each tool on the hand, wrist, and foot, to assess how well our smartphone-based vibration perception thresholds (VPTs) detect known trends obtained from standard tests. The smartphone platform detected statistically significant changes in VPT between the index finger and foot and also between the feet of younger adults and older adults. Our smartphone-based VPT had a moderate correlation to tuning fork-based VPT. Our overarching objective is to develop an accessible smartphone-based platform that can eventually be used to measure disease progression and regression.

Type A acute aortic dissection presenting as a stroke in a young male patient.

A male patient in his 40s with a history of nephrolithiasis and found in the desert after 10 days without oral intake was admitted to the hospital for severe dehydration, acute kidney injury and rhabdomyolysis. He had acute-onset loss of consciousness during hospitalisation with new left-sided hemiparesis and hemineglect. After haemorrhage was excluded, prompt thrombolysis was given. He later had chest pain and became hypotensive. An echocardiogram revealed pericardial effusion and dilation of the ascending aorta with suspected dissection. Magnetic resonance angiography of the brain and neck reported bilateral parieto-occipital areas of stroke in a watershed distribution and dissection of the right internal carotid artery. CT angiography showed type A aortic dissection from the ascending aorta extending into the bilateral common iliac arteries. Thrombolysis was reversed and the patient underwent ascending aorta replacement, resuspension of the aortic valve and aortic arch debranching at outside facility with complete recovery.

Mathematical modeling for operative improvement of the decoloration of Acid Red 27 by a novel microbial consortium of Trametes versicolor and Pseudomonas putida: A multivariate sensitivity analysis.

In this work, it is presented a first approach of a mathematical and kinetic analysis for improving the decoloration and further degradation process of an azo dye named acid red 27 (AR27), by means of a novel microbial consortium formed by the fungus Trametes versicolor and the bacterium Pseudomonas putida. A multivariate analysis was carried out by simulating scenarios with different operating conditions and developing a specific mathematical model based on kinetic equations describing all stages of the biological process, from microbial growth and substrate consuming to decoloration and degradation of intermediate compounds. Additionally, a sensitivity analysis was performed by using a factorial design and the Response Surface Method (RSM), for determining individual and interactive effects of variables like, initial glucose concentration, initial dye concentration and the moment in time for bacterial inoculation, on response variables assessed in terms of the minimum time for: full decoloration of AR27 (R1 = 2.375 days); maximum production of aromatic metabolites (R2 = 1.575 days); and full depletion of aromatic metabolites (R3 = 12.9 days). Using RSM the following conditions improved the biological process, being: an initial glucose concentration of 20 g l-1, an initial AR27 concentration of 0.2 g l-1 and an inoculation moment in time of P. putida at day 1. The mathematical model is a feasible tool for describing AR27 decoloration and its further degradation by the microbial consortium of T. versicolor and P. putida, this model will also work as a mathematical basis for designing novel bio-reaction systems than can operate with the same principle of the described consortium.

Exploring the CO2 photocatalytic evolution onto the CuO (1 1 0) surface: A combined theoretical and experimental study.

A combined theoretical and experimental study was performed to elucidate the photocatalytic potential of tenorite, CuO (1 1 0) and to assess the evolution pathway of carbon dioxide (CO2) evolution pathway. The calculations were performed with density functional theory (DFT) at a DFT + U + J0 and spin polarized level. The CuO was experimentally synthesized and characterized with structural and optical methodologies. The band structure and density of states revealed the rise of band gaps at 1.24 and 1.03 eV with direct and indirect band gap nature, respectively. These values are in accordance with the experimental evidence at 1.28 and 0.96 eV; respectively, which were obtained by UV-Vis DRS. Such a behavior could be related to enhanced photocatalytic activity among copper oxide materials. Experimental evidence such as SEM images and work function measurements were also performed to evaluate the oxide. The redox potential suggests a catalytic character of tenorite (1 1 0) for the CO2 transformation through aldehydes (methanal) intermediate formation. Furthermore, a route through methylene glycol CH2(OH)2 was also explored with the theoretical methodology. The reaction path exhibits an immediate reduction of Image 1 into a •OH radical and an [OH]- anion, in the first step. This •OH radical attacks a double bond (C = O) of Image 2 to form bicarbonate ([Image 3]-) and subsequently, carbonic acid (Image 4). The carbonic acid reacts with other •OH radical to finally form orthocarbonic acid (Image 5).

Analysis of the psychometric properties of the Buss-Perry Aggression Questionnaire (AQ) in Colombian adolescents / Análisis de las propiedades psicométricas del cuestionario de agresividad (AQ) de Buss y Perry en adolescentes colombianos

The psychometric properties of the Buss and Perry AQ questionnaire of aggression, one of the most used questionnaires worldwide to measure aggressive behavior, were examined in a sample of adolescents (n=779 participants) from the cities of Barranquilla (n= 410) and Pereira (n= 369), in Colombia. In total, 752 participants (Mean age of 15.3 years, SD = 1.9; 57,4%. women and 42,6 men) completed the Buss and Perry AQ questionnaire. Subsequently, the univariate and multivariate normality of the items was evaluated, and a confirmatory factor analysis (CFA) was performed on the data set. Likewise, the fit of two models was evaluated, a multidimensional a priori model, and a model with a second-order factor (aggressive behavior), which could explain the variance of the items. Finally, the reliability indices of the questionnaire were identified. The results showed acceptable goodness-of-fit indices (X2/df = 2.29, CFI = .977, IFI = .977, GFI = .984, AGFI = .979, RNI = .984, NFI = .972, RMSEA of .047 [90% CI = .016 - .036] and SRMR = .059) for the second-order one-factor model, as well as acceptable reliability indices (α= .55 - .88). In conclusion, these results show that the scale can be applicable to Colombian preadolescents and adolescents, but warn of the limitations of its use for the non-aggression subscale. Nevertheless, the application of the scale in its original version is suggested to determine its psychometric behavior. (AU)

Las propiedades psicométricas del cuestionario de agresión Buss y Perry AQ, uno de los cuestionarios más utilizados mundialmente para medir la conducta agresiva, fue examinado en una muestra de adolescentes (n=779 participantes) de las ciudades de Barranquilla (n= 410) y Pereira (n= 369), en Colombia. En total, 752 participantes (edad media de 15,3 años, DE = 1,9; 57,4%. mujeres y 42,6 hombres) completaron el cuestionario AQ de Buss y Perry. Posteriormente, se evaluó la normalidad univariante y multivariante de los ítems, y se realizó un análisis factorial confirmatorio (AFC) sobre el conjunto de datos. Asimismo, se evaluó el ajuste de dos modelos, un modelo multidimensional a priori, y un modelo con un factor de segundo orden (conducta agresiva), que podría explicar la varianza de los ítems. Por último, se identificaron los índices de fiabilidad del cuestionario. Los resultados mostraron índices de bondad de ajuste aceptables (X2/df = 2,29, CFI = .977, IFI = .977, GFI = .984, AGFI = .979, RNI = .984, NFI = .972, RMSEA de .047 [90% CI = .016 - .036] y SRMR = .059) para el modelo de un factor de segundo orden, así como índices de fiabilidad aceptables (α= .55 - .88). En conclusión, estos resultados muestran que la escala puede ser aplicable a preadolescentes y adolescentes colombianos, pero advierten de las limitaciones de su uso para la subescala de no agresión. No obstante, se sugiere la aplicación de la escala en su versión original para determinar su comportamiento psicométrico. (AU)

Sex-specific metabolic adaptations in transgenic mice overexpressing cytochrome b5 reductase-3.

Cytochrome b5 reductase 3 (CYB5R3) activates respiratory metabolism in cellular systems and exerts a prolongevity action in transgenic mice overexpressing this enzyme, mimicking some of the beneficial effects of calorie restriction. The aim of our study was to investigate the role of sex on metabolic adaptations elicited by CYB5R3 overexpression, and how key markers related with mitochondrial function are modulated in skeletal muscle, one of the major contributors to resting energy expenditure. Young CYB5R3 transgenic mice did not exhibit the striking adaptations in carbon metabolism previously detected in older animals. CYB5R3 was efficiently overexpressed and targeted to mitochondria in skeletal muscle from transgenic mice regardless sex. Overexpression significantly elevated NADH in both sexes, although differences were not statistically significant for NAD+, and increased the abundance of cytochrome c and the fission protein DRP-1 in females but not in males. Moreover, while mitochondrial biogenesis and function markers (as TFAM, NRF-1 and cleaved SIRT3) were markedly upregulated by CYB5R3 overexpression in females, a downregulation was observed in males. Ultrastructural changes were also highlighted, with an increase in the number of mitochondria per surface unit, and in the size of intermyofibrillar mitochondria in transgenic females compared with their wild-type controls. Our results support that CYB5R3 overexpression upregulates markers consistent with enhanced mitochondrial biogenesis and function, and increases mitochondrial abundance in skeletal muscle, producing most of these potentially beneficial actions in females.

Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.

Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis.

OBJECTIVE: We analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting. METHODS: Our study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+ -related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti-tumor necrosis factor (anti-TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside. RESULTS: Reduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP-ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti-TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status. CONCLUSION: RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti-TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds.

Integrins control epithelial stem cell proliferation in the Drosophila ovary by modulating the Notch pathway.

Cell proliferation and differentiation show a remarkable inverse relationship. The temporal coupling between cell cycle withdrawal and differentiation of stem cells (SCs) is crucial for epithelial tissue growth, homeostasis and regeneration. Proliferation vs. differentiation SC decisions are often controlled by the surrounding microenvironment, of which the basement membrane (BM; a specialized form of extracellular matrix surrounding cells and tissues), is one of its main constituents. Years of research have shown that integrin-mediated SC-BM interactions regulate many aspects of SC biology, including the proliferation-to-differentiation switch. However, these studies have also demonstrated that the SC responses to interactions with the BM are extremely diverse and depend on the cell type and state and on the repertoire of BM components and integrins involved. Here, we show that eliminating integrins from the follicle stem cells (FSCs) of the Drosophila ovary and their undifferentiated progeny increases their proliferation capacity. This results in an excess of various differentiated follicle cell types, demonstrating that cell fate determination can occur in the absence of integrins. Because these phenotypes are similar to those found in ovaries with decreased laminin levels, our results point to a role for the integrin-mediated cell-BM interactions in the control of epithelial cell division and subsequent differentiation. Finally, we show that integrins regulate proliferation by restraining the activity of the Notch/Delta pathway during early oogenesis. Our work increases our knowledge of the effects of cell-BM interactions in different SC types and should help improve our understanding of the biology of SCs and exploit their therapeutic potential.

Visualization and Quantification of Drosophila Larval Ovaries.

The morphogenesis of the ovarian germline stem cell (GSC) niche during larval stages in Drosophila provides the initial cellular and molecular basis for female gamete production in the adult. During larval instars, the Drosophila female gonad matures gradually from a round structure enclosing primordial germ cells (PGCs) and somatic cells into a functional organ containing GSC populations in their niches that later in adult stages support oogenesis. In this chapter, we describe a technique for dissecting, staining, and analyzing gonads from female Drosophila larvae and early pupae, offering the possibility of a direct view of the morphogenesis of an ovarian niche.

Native Fauna of Tardigrades from Two Natural Areas of the Argentina Republic.

Understanding and preserving biodiversity in natural habitats is crucial due to their rapid degradation and destruction. The meiofauna of natural areas is less well known than the macroscopic life. Tardigrades are common in limno-terrestrial meiofauna and can indicate environmental conditions. In this study, we expand our understanding of the taxonomy and ecology of tardigrade communities in two natural reserves in Argentina by examining the environmental factors that can affect them and the species that could be used as indicators. In 2018, sampling occurred in the Parque Luro Provincial Reserve (province of La Pampa) and the Poligono A Municipal Ecological Reserve (province of Salta). Samples were taken from epiphytic communities that grow on the bark of trees. Various environmental and microhabitat factors were taken into account. In the province of La Pampa, there were 1326 specimens of five species, and in the province of Salta, there were 212 specimens of nine species. The tardigrade communities in Salta exhibited statistically higher diversity than those in La Pampa. Temperature and moisture affected the tardigrade community of Parque Luro Provincial Reserve, while the microhabitat thickness affected those of Poligono A Municipal Ecological Reserve. The species turnover shaped the community of Salta, while nesting shaped the community of La Pampa.

Distrofia muscular de Duchenne, una causa infrecuente de miocardiopatía dilatada / Duchenne muscular dystrophy, a rare cause of dilated cardiomyopathy

Neuromuscular diseases represent a rare cause of dilated myocardiopathy, among them Duchenne muscular dystrophy is the most common. Transthoracic echocardiography and cardiac magnetic resonance imaging can assess cardiac involvement early. The case of a patient diagnosed with Duchenne muscular dystrophy who develops cardiac involvement during cardiology follow-up is presented below.

Astrocytes as a Therapeutic Target in Alzheimer's Disease-Comprehensive Review and Recent Developments.

Alzheimer's disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate in several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress and lipid metabolism (along with a critical role in apolipoprotein E function). Current evidence shows that astrocytes have both neuroprotective and neurotoxic effects depending on the disease stage and microenvironmental factors. Furthermore, astrocytes appear to be affected by the presence of amyloid-beta (Aß), with alterations in calcium levels, gliotransmission and proinflammatory activity via RAGE-NF-κB pathway. In addition, astrocytes play an important role in the metabolism of tau and clearance of Aß through the glymphatic system. In this review, we will discuss novel pharmacological and non-pharmacological treatments focused on astrocytes as therapeutic targets for AD. These interventions include effects on anti-inflammatory/antioxidant systems, glutamate activity, lipid metabolism, neurovascular coupling and glymphatic system, calcium dysregulation, and in the release of peptides which affects glial and neuronal function. According to the AD stage, these therapies may be of benefit in either preventing or delaying the progression of the disease.