Exposure to Low-Intensity Blast Increases Clearance of Brain Amyloid Beta.

The long-term effects of exposure to blast overpressure are an important health concern in military personnel. Increase in amyloid beta (Aß) has been documented after non-blast traumatic brain injury (TBI) and may contribute to neuropathology and an increased risk for Alzheimer's disease. We have shown that Aß levels decrease following exposure to a low-intensity blast overpressure event. To further explore this observation, we examined the effects of a single 37 kPa (5.4 psi) blast exposure on brain Aß levels, production, and clearance mechanisms in the acute (24 h) and delayed (28 days) phases post-blast exposure in an experimental rat model. Aß and, notably, the highly neurotoxic detergent soluble Aß42 form, was reduced at 24 h but not 28 days after blast exposure. This reduction was not associated with changes in the levels of Aß oligomers, expression levels of amyloid precursor protein (APP), or increase in enzymes involved in the amyloidogenic cleavage of APP, the ß- and ϒ-secretases BACE1 and presenilin-1, respectively. The levels of ADAM17 α-secretase (also known as tumor necrosis factor α-converting enzyme) decreased, concomitant with the reduction in brain Aß. Additionally, significant increases in brain levels of the endothelial transporter, low-density related protein 1 (LRP1), and enhancement in co-localization of aquaporin-4 (AQP4) to perivascular astrocytic end-feet were observed 24 h after blast exposure. These findings suggest that exposure to low-intensity blast may enhance endothelial clearance of Aß by LRP1-mediated transcytosis and alter AQP4-aided glymphatic clearance. Collectively, the data demonstrate that low-intensity blast alters enzymatic, transvascular, and perivascular clearance of Aß.

The Neurovascular Unit as a Locus of Injury in Low-Level Blast-Induced Neurotrauma.

Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood-brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury.

Metabotropic Glutamate Receptor 2 Expression Is Chronically Elevated in Male Rats With Post-Traumatic Stress Disorder Related Behavioral Traits Following Repetitive Low-Level Blast Exposure.

Many military veterans who experienced blast-related traumatic brain injuries in the conflicts in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. We previously reported that a group II metabotropic receptor (mGluR2/3) antagonist reversed blast-induced behavioral traits. In this report, we explored mGluR2/3 expression following blast exposure in male rats. Western blotting revealed that mGluR2 protein (but not mGluR3) was increased in all brain regions studied (anterior cortex, hippocampus, and amygdala) at 43 or 52 weeks after blast exposure but not at 2 weeks or 6 weeks. mGluR2 RNA was elevated at 52 weeks while mGluR3 was not. Immunohistochemical staining revealed no changes in the principally presynaptic localization of mGluR2 by blast exposure. Administering the mGluR2/3 antagonist LY341495 after behavioral traits had emerged rapidly reversed blast-induced effects on novel object recognition and cued fear responses 10 months following blast exposure. These studies support alterations in mGluR2 receptors as a key pathophysiological event following blast exposure and provide further support for group II metabotropic receptors as therapeutic targets in the neurobehavioral effects that follow blast injury.

Core-shell chitosan/Porphyridium-exopolysaccharide microgels: Synthesis, properties, and biological evaluation.

Advanced materials used in the biomedicine field comprises a diverse group of organic molecules, including polymers, polysaccharides, and proteins. A significant trend in this area is the design of new micro/nano gels whose small size, physical stability, biocompatibility, and bioactivity could lead to new applications. Herein a new synthesis route is described to obtain core-shell microgels based on chitosan and Porphyridium exopolysaccharides (EPS) crosslinked with sodium tripolyphosphate (TPP). First, the synthesis of EPS-chitosan gels through ionic interactions was explored, leading to the formation of unstable gels. Alternatively, the use of TTP as crosslinker agent led to stable core-shell structures. The influence of reaction temperature, sonication time, and exopolysaccharide concentration, pH and TPP concentration were determined as a function of particle size and polydispersity index (PDI). The obtained EPS-chitosan gels were characterized by TEM, TGA, and FTIR; followed by the assessment of protein load capacity, stability upon freezing, cytotoxicity, and mucoadhesivity. Experimentation revealed that the core-shell particles size ranges 100-300 nm, have a 52 % loading capacity for BSA and a < 90 % mucoadhesivity, and no toxic effects in mammalian cell cultures. The potential application of the obtained microgels in the biomedical field is discussed.

Late chronic local inflammation, synaptic alterations, vascular remodeling and arteriovenous malformations in the brains of male rats exposed to repetitive low-level blast overpressures.

In the course of military operations in modern war theaters, blast exposures are associated with the development of a variety of mental health disorders associated with a post-traumatic stress disorder-related features, including anxiety, impulsivity, insomnia, suicidality, depression, and cognitive decline. Several lines of evidence indicate that acute and chronic cerebral vascular alterations are involved in the development of these blast-induced neuropsychiatric changes. In the present study, we investigated late occurring neuropathological events associated with cerebrovascular alterations in a rat model of repetitive low-level blast-exposures (3 × 74.5 kPa). The observed events included hippocampal hypoperfusion associated with late-onset inflammation, vascular extracellular matrix degeneration, synaptic structural changes and neuronal loss. We also demonstrate that arteriovenous malformations in exposed animals are a direct consequence of blast-induced tissue tears. Overall, our results further identify the cerebral vasculature as a main target for blast-induced damage and support the urgent need to develop early therapeutic approaches for the prevention of blast-induced late-onset neurovascular degenerative processes.

Candimine from Hippeastrum escoipense (Amaryllidaceae): Anti-Trypanosoma cruzi activity and synergistic effect with benznidazole.

BACKGROUND: Chagas disease (CD), caused by Trypanosoma cruzi, represents a health threat to around 20 million people worldwide. Side effects of benznidazole (Bzn) cause 15-20% of patients to discontinue their treatment. Evidence has increased in favor of the use of drug combinations to improve the efficacy and tolerance of the treatment. Natural products are well known to provide structures that could serve as new drugs or scaffolds for CD treatment. Spp of the Amaryllidoideae sub family of Amaryllidaceae family are known by their bioactives alkaloids, which have been reported by their antiparasitic activities. PURPOSE: To evaluate the anti-T. cruzi activity of the isolated alkaloid candimine (Cnd) from Hippeastrum escoipense Slanis & Huaylla; and to assess the combination effect between Cnd and Bzn against different life stages of T. cruzi parasites. METHODS: The chemical profile of H. escoipense alkaloids extract (AE-H. escoipense), including quantitation of Cnd was performed through GC/MS and UPLC-MS/MS techniques. Subsequently, Cnd was isolated using Shephadex LH-20. Then, the AE-H. escoipense and Cnd were tested against T. cruzi, (epimastigotes, trypomastigotes, and amastigotes) by in vitro proliferation and viability assays. The cytotoxicity was evaluated against Vero and HepG2 mammalian cells. The ultrastructural analysis was perform by transmission electron microscopy (TEM) and mitochondrial activity was carried out by MTT assay. Drug combination assay between Cnd and Bzn was evaluated using the Chou-Talalay method. RESULTS: The AE-H. escoipense and Cnd showed high and specific anti-T. cruzi activity, comparable to Bzn. Cnd induces ultrastructural changes in T. cruzi, such as vacuolization, membrane blebs, and increased mitochondrial activity. Regarding the interaction between Cnd and Bzn, it generates synergism in the combinations of 0.25×IC50 in epimastigotes, 2×IC50 in trypomastigotes+amastigotes, and 0.25, 2, and 4×IC50 in amastigotes. CONCLUSION: The synergism between Cnd and Bzn indicates that the combination at the concentration of 4×IC50 could be useful as an effective new therapy against CD in the chronic stage. Thus, Cnd isolated from the leaves of H. escoipense emerges as potential candidate for the development of a new drug for the treatment of CD.

(2R,6R)-Hydroxynorketamine Treatment of Rats Exposed to Repetitive Low-Level Blast Injury.

Many military veterans who experienced blast-related traumatic brain injuries (TBIs) in the conflicts in Iraq and Afghanistan suffer from chronic cognitive and mental health problems, including post-traumatic stress disorder (PTSD). Male rats subjected to repetitive low-level blast exposure develop chronic cognitive and PTSD-related traits that develop in a delayed manner. Ketamine has received attention as a treatment for refractory depression and PTSD. (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] is a ketamine metabolite that exerts rapid antidepressant actions. (2R,6R)-HNK has become of clinical interest because of its favorable side-effect profile, low abuse potential, and oral route of administration. We treated three cohorts of blast-exposed rats with (2R,6R)-HNK, beginning 7-11 months after blast exposure, a time when the behavioral phenotype is established. Each cohort consisted of groups (n = 10-13/group) as follows: 1) Sham-exposed treated with saline, 2) blast-exposed treated with saline, and 3) blast-exposed treated with a single dose of 20 mg/kg of (2R,6R)-HNK. (2R,6R)-HNK rescued blast-induced deficits in novel object recognition (NOR) and anxiety-related features in the elevated zero maze (EZM) in all three cohorts. Exaggerated acoustic startle was reversed in cohort 1, but not in cohort 3. (2R,6R)-HNK effects were still present in the EZM 12 days after administration in cohort 1 and 27 days after administration in NOR testing of cohorts 2 and 3. (2R,6R)-HNK may be beneficial for the neurobehavioral syndromes that follow blast exposure in military veterans. Additional studies will be needed to determine whether higher doses or more extended treatment regimens may be more effective.

Sortilin knock-down alters the expression and distribution of cathepsin D and prosaposin and up-regulates the cation-dependent mannose-6-phosphate receptor in rat epididymal cells.

The selective transport to lysosomes can be mediated by either mannose-6-phosphate receptors (CD-MPR and CI-MPR) or sortilin. In mammalian epididymis, some lysosomal proteins are secreted into the lumen through unknown mechanisms. To investigate the underlying mechanisms of lysosomal protein transport in epididymal cells we studied the expression and distribution of cathepsin D (CatD) and prosaposin (PSAP) in a sortilin knocked down RCE-1 epididymal cell line (RCE-1 KD) in comparison with non-transfected RCE-1 cells. In RCE-1 cells, CatD was found in the perinuclear zone and co-localize with sortilin, whereas in RCE-1 KD cells, the expression, distribution and processing of the enzyme were altered. In turn, PSAP accumulated intracellularly upon sortilin knock-down and redistributed from LAMP-1-positive compartment to a perinuclear location, remaining co-localized with CatD. Interestingly, the sortilin knock-down induced CD-MPR overexpression and a redistribution of the receptor from the perinuclear zone to a dispersed cytoplasmic location, accompanied by an increased co-localization with CatD. The increase in CD-MPR could result from a compensatory response for the proper delivery of CatD to lysosomes in epididymal cells. The intracellular pathway taken by lysosomal proteins could be an approach for addressing further studies to understand the mechanism of exocytosis and therefore the role of these proteins in the epididymis.

Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.

Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding need for therapeutic alternatives to reduce their progression to advanced stages. The stress caused by diseases leads to the activation of protective mechanisms in the cell, including chaperone proteins. The Sigma-1 receptor (Sig-1R) is a ligand-operated chaperone protein that modulates signal transduction during cellular stress processes. Sig-1R interacts with various ligands and proteins to elicit distinct cellular responses, thus, making it a potential target for pharmacological modulation. Furthermore, Sig-1R ligands activate signaling pathways that promote cardioprotection, ameliorate ischemic injury, and drive myofibroblast activation and fibrosis. The role of Sig-1R in diseases has also made it a point of interest in developing clinical trials for pain, neurodegeneration, ischemic stroke, depression in patients with heart failure, and COVID-19. Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage. These basic discoveries could inform clinical trials for heart failure (HF), myocardial hypertrophy, acute kidney injury (AKI), and chronic kidney disease (CKD). Here, we review Sig-1R signaling pathways and the evidence of Sig-1R modulation in preclinical cardiac and renal injury models to support the potential therapeutic use of Sig-1R agonists and antagonists in these diseases.

BCI-838, an orally active mGluR2/3 receptor antagonist pro-drug, rescues learning behavior deficits in the PS19 MAPTP301S mouse model of tauopathy.

Tauopathies are a heterogeneous group of neurodegenerative disorders that are clinically and pathologically distinct from Alzheimer's disease (AD) having tau inclusions in neurons and/or glia as their most prominent neuropathological feature. BCI-838 (MGS00210) is a group II metabotropic glutamate receptor (mGluR2/3) antagonist pro-drug. Previously, we reported that orally administered BCI-838 improved learning behavior and reduced anxiety in Dutch (APPE693Q) transgenic mice, a model of the pathological accumulation of Aß oligomers found in AD. Herein, we investigated effects of BCI-838 on PS19 male mice that express the tauopathy mutation MAPTP301S associated with human frontotemporal lobar degeneration (FTLD). These mice develop an aging-related tauopathy without amyloid accumulation. Mice were divided into three experimental groups: (1) non-transgenic wild type mice treated with vehicle, (2) PS19 mice treated with vehicle and (3) PS19 mice treated with 5 mg/kg BCI-838. Groups of 10-13 mice were utilized. Vehicle or BCI-838 was administered by oral gavage for 4 weeks. Behavioral testing consisting of a novel object recognition task was conducted after drug administration. Two studies were performed beginning treatment of mice at 3 or 7 months of age. One month of BCI-838 treatment rescued deficits in recognition memory in PS19 mice whether treatment was begun at 3 or 7 months of age. These studies extend the potential utility of BCI-838 to neurodegenerative conditions that have tauopathy as their underlying basis. They also suggest an mGluR2/3 dependent mechanism as a basis for the behavioral deficits in PS19 mice.

Antiparasitic Activity of Hippeastrum Species and Synergistic Interaction between Montanine and Benznidazole against Trypanosoma cruzi.

BACKGROUND: Hippeastrum species have a wide range of biological properties. In Argentina, this genus comprises ten widely distributed species. PURPOSE: To evaluate the antiparasitic and anticholinesterase activities and chemical profiles of seven Argentinean Hippeastrum species and determine the synergism between the major isolated alkaloid-montanine-and benznidazole in anti-Trypanosoma cruzi activity. METHODS: The antiparasitic activity was evaluated through antiproliferative and viability assays against T. cruzi epimastigotes. Synergism assays were performed using the Chou-Talalay method. AChE and BuChE inhibitory activities were also assessed. The alkaloid composition was obtained using GC-MS analysis. RESULTS: All extracts showed strong growth inhibition of T. cruzi epimastigote proliferation. The extracts from H. aglaiae, H. aulicum, and H. hybrid stand out for their potent and total growth inhibition, which was comparable to benznidazole. The H. reticulatum extract showed strong Acetylcholinesterase (AChE) inhibitory activities, while five species showed moderate Butyrylcholinesterase (BuChE) inhibition. Fifteen alkaloids were identified by means of GC-MS. Regarding the synergism assessment, the highest synergistic effect was obtained from the combination of montanine and benznidazole. CONCLUSION: Hippeastrum species bulb extracts from Argentina were shown to be a good source of antiparasitic alkaloids and cholinesterase inhibitors. The synergism between montanine and benznidazole emerges as a potential combination for future studies to treat Chagas disease.

Progressive Transcriptional Changes in the Amygdala Implicate Neuroinflammation in the Effects of Repetitive Low-Level Blast Exposure in Male Rats.

Chronic mental health problems are common among military veterans who sustained blast-related traumatic brain injuries. The reasons for this association remain unexplained. Male rats exposed to repetitive low-level blast overpressure (BOP) exposures exhibit chronic cognitive and post-traumatic stress disorder (PTSD)-related traits that develop in a delayed fashion. We examined blast-induced alterations on the transcriptome in four brain areas (anterior cortex, hippocampus, amygdala, and cerebellum) across the time frame over which the PTSD-related behavioral phenotype develops. When analyzed at 6 weeks or 12 months after blast exposure, relatively few differentially expressed genes (DEGs) were found. However, longitudinal analysis of amygdala, hippocampus, and anterior cortex between 6 weeks and 12 months revealed blast-specific DEG patterns. Six DEGs (hyaluronan and proteoglycan link protein 1 [Hapln1], glutamate metabotropic receptor 2 [Grm2], purinergic receptor P2y12 [P2ry12], C-C chemokine receptor type 5 [Ccr5], phenazine biosynthesis-like protein domain containing 1 [Pbld1], and cadherin related 23 [Cdh23]) were found altered in all three brain regions in blast-exposed animals. Pathway enrichment analysis using all DEGs or those uniquely changed revealed different transcription patterns in blast versus sham. In particular, the amygdala in blast-exposed animals had a unique set of enriched pathways related to stress responses, oxidative phosphorylation, and mitochondrial dysfunction. Upstream analysis implicated tumor necrosis factor (TNF)α signaling in blast-related effects in amygdala and anterior cortex. Eukaryotic initiating factor eIF4E (EIF4e), an upstream regulator of P2ry12 and Ccr5, was predicted to be activated in the amygdala. Quantitative polymerase chain reaction (qPCR) validated longitudinal changes in two TNFα regulated genes (cathepsin B [Ctsb], Hapln1), P2ry12, and Grm2. These studies have implications for understanding how blast injury damages the brain and implicates inflammation as a potential therapeutic target.

Multimodal Assessment of Bottlenose Dolphin Auditory Nuclei Using 7-Tesla MRI, Immunohistochemistry and Stereology.

The importance of assessing neurochemical processes in the cetacean brain as a tool for monitoring their cognitive health and to indirectly model human neurodegenerative conditions is increasingly evident, although available data are largely semiquantitative. High-resolution MRI for post-mortem brains and stereology allow for quantitative assessments of the cetacean brain. In this study, we scanned two brains of bottlenose dolphins in a 7-Tesla (7T) MR scanner and assessed the connectivity of the inferior colliculi and ventral cochlear nuclei using diffusion tensor imaging (DTI). Serial thick sections were investigated stereologically in one of the dolphins to generate rigorous quantitative estimates of identifiable cell types according to their morphology and expression of molecular markers, yielding reliable cell counts with most coefficients of error <10%. Fibronectin immunoreactivity in the dolphin resembled the pattern in a human chronic traumatic encephalopathy brain, suggesting that neurochemical compensation for insults such as hypoxia may constitute a noxious response in humans, while being physiological in dolphins. These data contribute to a growing body of knowledge on the morphological and neurochemical properties of the dolphin brain and highlight a stereological and neuroimaging workflow that may enable quantitative and translational assessment of pathological processes in the dolphin brain in the future.

Cranioplasty with cryopreserved autologous bone in craniectomized patients due to brain trauma, a current and safe option: Experience of 97 cases.

BACKGROUND: Cranioplasty is the used method in neurosurgery for repairing cranial bone defects. In our environment, the most widely used material is cryopreserved autologous bone (ABCp). OBJECTIVE: A retrospective observational study was proposed in order to analyze complications in patients who underwent decompressive craniectomy for brain trauma, with subsequent cranioplasty with ABCp. METHOD: Patients who underwent cranioplasties with consecutive ABCp performed at our institution over a four-year period (2016-2019) with subsequent follow-up were included, collecting multiple variables in relation to the appearance of complications. RESULTS: 113 cranioplasties were performed, of which 85.8% (n = 97) were performed with ABCp. Mainly with frontotemporoparietal bone defect (94.84%) performed late (> 3 months) in 91.76%. The complication rate was 16.49%, the most significant being the infection of the surgical site (n = 8, 8.24%), the presence of intracranial hematoma (n = 3, 3.09%) and the reabsorption of the autologous bone (n = 2, 2.06%), meriting surgical management in nine of them (9.27%). CONCLUSIONS: ABCp is a valid and safe option, which meets the basic characteristics to consider it the ideal material, with an acceptable rate of complications, biocompatible, with osteogenic potential, adequate protection of the brain and decrease in surgery costs.

ANTECEDENTES: La craneoplastia es el método utilizado en neurocirugía para reparar los defectos óseos craneanos. En nuestro medio, el material utilizado mayormente es el hueso autólogo criopreservado (HACp). OBJETIVO: Realizamos un estudio retrospectivo observacional para analizar las complicaciones en pacientes sometidos a craniectomía descompresiva por trauma craneoencefálico y realización de craneoplastia con HACp. MÉTODO: Se incluyeron pacientes que fueron sometidos a craneoplastias con HACp consecutivas realizadas en un periodo de 4 años (2016-2019) con seguimiento posterior, recabando múltiples variables en relación con la aparición de complicaciones. RESULTADOS: Se realizaron 113 craneoplastias, de las cuales el 85.8% (n = 97) fueron realizadas con HACp, principalmente con defecto óseo frontotemporoparietal (94.84%), realizadas de forma tardía (> 3 meses) en el 91.76%. El índice de complicaciones fue del 16.49%, siendo las más significativas la infección del sitio quirúrgico (n = 8, 8.24%), la presencia de hematoma endocraneano (n = 3, 3.09%) y la reabsorción del hueso autólogo (n = 2, 2.06%), ameritando manejo quirúrgico en nueve ocasiones (9.27%). CONCLUSIONES: El HACp es una opción válida y segura, la cual cumple con las características para considerarlo el material ideal, con un aceptable índice de complicaciones, biocompatible, con potencial osteogénico, adecuada protección encefálica y disminución de los costos de la cirugía.

Factores psicológicos protectores y desestabilizadores en pacientes con cardiopatía isquémica / Protective and destabilizing psychological factors in patients with ischemic heart disease / Fatores psicológicos protetores e desestabilizadores em pacientes com doença isquêmica do coração

RESUMEN En el estudio actual de las patologías cardíacas se consideran cada vez más los factores psicológicos por el papel relevante que poseen en la evolución de estas enfermedades. El objetivo de este trabajo fue determinar los principales factores psicológicos protectores y desestabilizadores que se manifiestan en los pacientes con cardiopatía isquémica. Para ello se realizó un estudio descriptivo de corte transversal, en los pacientes con cardiopatía isquémica atendidos en el servicio de cardiología del Hospital Clínico Quirúrgico "Celia Sánchez Manduley", del municipio Manzanillo, en el período octubre- diciembre del 2019. El universo estuvo constituido por 60 pacientes con cardiopatía isquémica. En el estudio el 78,33% de los pacientes tenían más de 60 años, 40 pacientes eran hombres y el 75% pertenecía a la zona urbana. Los principales factores psicológicos protectores presentes fueron el apoyo social reportado por todos los participantes y el cumplimiento terapéutico en el 91,67% de la población estudiada. Dentro de los factores psicológicos desestabilizadores el de mayor reporte fue la ansiedad presente en el 66,66% de los pacientes incluidos en el estudio. Se deben tomar en cuenta tanto los factores psicológicos protectores para poder potenciarlos y generar un mejor estado general del paciente, como los factores psicológicos desestabilizadores que generan descompensación y deben ser atendidos con intencionalidad una vez identificados.

ABSTRACT In the current study of cardiac pathologies, psychological factors are increasingly considered due to the relevant role they have in the evolution of these diseases. The objective of this work was to determine the main protective and destabilizing psychological factors that manifest themselves in patients with ischemic heart disease. To this end, a descriptive cross-sectional study was carried out in patients with ischemic heart disease treated in the cardiology service of the "Celia Sánchez Manduley" Clinical Surgical Hospital, in the municipality of Manzanillo, in the period October-December 2019.The universe consisted of 60 patients with ischemic heart disease. In the study, 78.33% of the patients were over 60 years old, 40 patients were men and 75% belonged to the urban area. The main protective psychological factors present were social support reported by all participants and therapeutic compliance in 91.67% of the studied population. Among the destabilizing psychological factors, the one with the highest report was the anxiety present in 66.66% of the patients included in the study. Both the protective psychological factors must be taken into account in order to enhance them and generate a better general condition of the patient, as well as the destabilizing psychological factors that generate decompensation and must be addressed with intentionality once identified.

RESUMO No presente estudo das patologias cardíacas, fatores psicológicos são cada vez mais considerados devido ao papel relevante que têm na evolução dessas doenças. O objetivo deste trabalho foi determinar os principais fatores psicológicos protetores e desestabilizadores que se manifestam em pacientes com doença isquêmica do coração. Para isso, foi realizado um estudo transversal descritivo em pacientes com doença isquêmica do coração tratada no serviço de cardiologia do Hospital Cirúrgico Clínico "Celia Sánchez Manduley", no município de Manzanillo, no período de outubro a dezembro de 2019.O universo era composto por 60 pacientes com doença isquêmica do coração. No estudo, 78,33% dos pacientes tinham mais de 60 anos, 40 eram homens e 75% pertenciam à área urbana. Os principais fatores psicológicos protetores presentes foram o apoio social relatado por todos os participantes e o cumprimento terapêutico em 91,67% da população estudada. Entre os fatores psicológicos desestabilizadores, o com maior relato foi a ansiedade presente em 66,66% dos pacientes incluídos no estudo. Tanto os fatores psicológicos protetores devem ser levados em conta para melhorantá-los e gerar uma melhor condição geral do paciente, bem como os fatores psicológicos desestabilizadores que geram descompensação e devem ser tratados com intencionalidade uma vez identificados.

A comprehensive approach to complementary and alternative medicine usage among patients from a vascular department.

INTRODUCTION: Use of complementary and alternative medicine (CAM) therapies had been described in patients with disabling, chronic and painful conditions; these characteristics define the majority of vascular surgery (VS) entities. A lack of disclosure about CAM use from patients has been universally cited and may impact effective patient-doctor communication. Our primary objective was to describe CAM use, modalities, perceived benefits, safety, and associated factors among adult patients attending a VS outpatient clinic; we additionally explored patient's attitudes about CAM disclosure with their primary vascular surgeon. METHODS: This cross-sectional study invited 223 consecutive outpatients to an interview where the ICAM-Q (International Complementary and Alternative Medicine Questionnaire) and the PDRQ-9 (Patient-Doctor Relationship Questionnaire-9 items) were applied. In addition, sociodemographics, vascular disease and treatment-related information, comorbidity, and disease severity characteristics were obtained. Appropriated statistics was used; multiple logistic regression analysis identified factors associated to CAM use. All statistical tests were two-sided, and a p value ≤ 0.05 was considered significant. IRB approval was obtained. RESULTS: Patients recruited were primary females (69%) and had a median age of 65 years (54-75). Most frequent vascular diagnoses were chronic venous insufficiency (36.2%) and peripheral artery disease (26%). There were 104 (46.6%) patients who referred CAM use, primarily self-helped practices (96%), and use of herbal, vitamins, or homeopathic medicines (23.7%). Overall, the majority of the patients perceived CAM modalities helpful and 94.6% denied any adverse event. Female sex (OR: 1.768, 95% CI: 0.997-3.135, p = 0.051) and hospitalization during the previous year (OR: 3.173, 95% CI: 1.492-6.748, p = 0.003) were associated to CAM use. The majority of the patients (77%) agreed about CAM disclosure with their primary vascular surgeon; meanwhile, among CAM users, up to 54.9% did not disclose it, and their main reasons were "Doctor didn't ask" (32%) and "I consider it unnecessary" (16%). The patient-doctor relationship was rated by the patients with high scores. CONCLUSIONS: CAM use is frequent and perceived as safe and beneficial among VS outpatients; nonetheless, patients do not disclose CAM use with their primary vascular surgeons, and a wide range of reasons are given by the patients that prevent effective and open communication.

Engagement of vascular early response genes typifies mild cognitive impairment.

INTRODUCTION: Molecular responses in the brains of persons with mild cognitive impairment (MCI), the earliest transitional state between normal aging and early Alzheimer's disease (AD), are poorly understood. METHODS: We examined AD-related neuropathology and transcriptome changes in the neocortex of individuals with MCI relative to controls and temporal responses to the mild hypoxia in mouse brains. RESULTS: Subsets of vascular early response to hypoxia genes were upregulated in MCI prior to the buildup of AD neuropathology. Early activation of pro-angiogenic hypoxia-inducible factor signaling in response to mild hypoxia was detected in mouse brains similar to those that were altered in MCI. Protracted responses to hypoxia were characterized by activation of phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt)-the mammalian target of rapamycin (mTOR) pathways in brain microvessel isolates. DISCUSSION: These findings suggest that cerebrovascular remodeling is an important antecedent to the development of dementia and a component of the homeostatic response to reduced oxygen tension in aging prior to the onset of AD.

Synthesis and Characterization of Innovative Microgels Based on Polyacrylic Acid and Microalgae Cell Wall and Their Potential as Antigen Delivery Vehicles.

In this study, hybrid polyacrylic acid and Schizochytrium sp. microalgae (PAA/Schizo) microgels were synthesized by inverse emulsion assisted by ultrasound using the cell wall fraction as crosslinker. Physicochemical characterization of PAA/Schizo microgels revealed polymeric spherical particles (288 ± 39 nm) and were deemed stable and negatively charged. The produced microgels are not inherently toxic as cell viability was sustained above 80% when mice splenocytes were exposed to concentrations ranging 10-900 µg/mL. PAA/Schizo microgels were evaluated as antigen delivery nanovehicle by adsorbing bovine serum albumin (BSA); with a loading efficiency of 72% and loading capacity of 362 µg/mg. Overall, intranasally-immunized BALB/c mice showed null IgG or IgA responses against PAA/Schizo microgel-BSA, whereas soluble BSA induced significant humoral responses in systemic and mucosal compartments. Splenocytes proliferation assay upon BSA stimulus revealed positive CD4+ T cells-proliferation response in PAA/Schizo microgels-BSA group. Thus, PAA/Schizo microgels constitute functional antigen delivery vehicles of simple and ecofriendly synthesis. Moreover, the use of cell wall fraction as cross-linker agent provides an alternative use for the generation of high-value products using residual algae biomass from the oil industry. Our data suggests that the PAA/Schizo microgels are potential antigen delivery vehicles for immunotherapy development.

Factores psicológicos protectores y desestabilizadores en pacientes concardiopatía isquémica / Protective and destabilizing psychological factors in patients with ischemic heart disease

En el estudio actual de las patologías cardíacas se consideran cada vez más los factores psicológicos por el papel relevante que poseen en la evolución de estas enfermedades. El objetivo de este trabajo fue determinar los principales factores psicológicos protectores y desestabilizadores que se manifiestan en los pacientes con cardiopatía isquémica. Para ello se realizó un estudio descriptivo de corte transversal, en los pacientes con cardiopatía isquémica atendidos en el servicio de cardiología del Hospital Clínico Quirúrgico Celia Sánchez Manduley, del municipio Manzanillo, en el período octubre- diciembre del 2019. El universo estuvo constituido por 60 pacientes con cardiopatía isquémica. En el estudio el 78,33 por ciento de los pacientes tenían más de 60 años, 40 pacientes eran hombres y el 75 por ciento pertenecía a la zona urbana. Los principales factores psicológicos protectores presentes fueron el apoyo social reportado por todos los participantes y el cumplimiento terapéutico en el 91,67 por ciento de la población estudiada. Dentro de los factores psicológicos desestabilizadores el de mayor reporte fue la ansiedad presente en el 66,66 por ciento de los pacientes incluidos en el estudio. Se deben tomar en cuenta tanto los factores psicológicos protectores para poder potenciarlos y generar un mejor estado general del paciente, como los factores psicológicos desestabilizadores que generan descompensación y deben ser atendidos con intencionalidad una vez identificados(AU)

In the current study of cardiac pathologies, psychological factors are increasingly considered due to the relevant role they have in the evolution of these diseases. The objective of this work was to determine the main protective and destabilizingpsychological factors that manifest themselves in patients with ischemic heart disease. To this end, a descriptive cross-sectional study was carried out in patients with ischemic heart disease treated in the cardiology service of the Celia Sánchez Manduley Clinical Surgical Hospital, in the municipality of Manzanillo, in the period October-December 2019.The universe consisted of 60 patients with ischemic heartdisease. In the study, 78.33 percent of the patients were over 60 years old, 40 patients were men and 75 percent belonged to the urban area. The main protective psychological factors present were social support reported by all participants and therapeutic compliance in 91.67 percent of the studied population. Among the destabilizing psychological factors, the one with the highest report was the anxiety present in 66.66 percent of the patients included in the study. Both the protective psychological factors must be taken into account in order to enhance them and generate a better general condition of the patient, as well as the destabilizing psychological factors that generate decompensation and must beaddressed with intentionality once identified(EU)