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CONTEXT: Self-monitoring blood pressure (SMBP) programs are an evidence-based hypertension management intervention facilitated through telehealth. SMBP programs can provide a continuum of care beyond a clinical setting by facilitating hypertension management at home; however, equitable access to SMBP is a concern. OBJECTIVES: To evaluate the implementation of telehealth SMBP programs using an equity lens in 5 federally qualified health centers (FQHCs) in Massachusetts (MA). DESIGN: A prospective case series study. SETTING: Five FQHCs. PARTICIPANTS: The MA Department of Public Health (MDPH) selected 5 FQHCs to implement SMBP programs using telehealth. FQHCs were selected if their patient population experiences inequities due to social determinants of health and has higher rates of cardiovascular disease. Each of the 5 FQHCs reported data on patients enrolled in their SMBP programs totaling 241 patients examined in this study. INTERVENTION: SMBP programs implemented through telehealth. MAIN OUTCOME MEASURE: Systolic blood pressure and diastolic blood pressure. RESULTS: Approximately 53.5% of SMBP participants experienced a decrease in blood pressure. The average blood pressure decreased from 146/87 to 136/81 mm Hg. Among all patients across the 5 FQHCs, the average blood pressure decreased by 10.06/5.34 mm Hg (P < .001). Blood pressure improved in all racial, ethnic, and language subgroups. CONCLUSIONS: Five MA FQHCs successfully implemented equitable telehealth SMBP programs. SMBP participants enrolled in the programs demonstrated notable improvements in their blood pressure at the conclusion of the program. A flexible, pragmatic study design that was adjusted to meet unique patient needs; engaging nonphysician team members, particularly community health workers; adapting health information technology; and partnerships with community-based organizations were critical facilitators to program success.
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Hipertensão , Telemedicina , Humanos , Telemedicina/estatística & dados numéricos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Hipertensão/terapia , Massachusetts , Idoso , Monitorização Ambulatorial da Pressão Arterial/métodos , Monitorização Ambulatorial da Pressão Arterial/estatística & dados numéricos , Adulto , Autocuidado/métodos , Pressão Sanguínea/fisiologiaRESUMO
Atmospheric conditions are expected to become warmer and drier in the future, but little is known about how evaporative demand influences forest structure and function independently from soil moisture availability, and how fast-response variables (such as canopy water potential and stomatal conductance) may mediate longer-term changes in forest structure and function in response to climate change. We used two tropical rainforest sites with different temperatures and vapour pressure deficits (VPD), but nonlimiting soil water supply, to assess the impact of evaporative demand on ecophysiological function and forest structure. Common species between sites allowed us to test the extent to which species composition, relative abundance and intraspecific variability contributed to site-level differences. The highest VPD site had lower midday canopy water potentials, canopy conductance (gc ), annual transpiration, forest stature, and biomass, while the transpiration rate was less sensitive to changes in VPD; it also had different height-diameter allometry (accounting for 51% of the difference in biomass between sites) and higher plot-level wood density. Our findings suggest that increases in VPD, even in the absence of soil water limitation, influence fast-response variables, such as canopy water potentials and gc , potentially leading to longer-term changes in forest stature resulting in reductions in biomass.
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Folhas de Planta , Solo , Solo/química , Folhas de Planta/fisiologia , Floresta Úmida , Pressão de Vapor , Água/fisiologia , Abastecimento de Água , Transpiração Vegetal/fisiologia , Árvores/fisiologiaRESUMO
Empirical knowledge of natural plant extracts is increasingly proving to be a promising field. The effect of Calendula officinalis L. (CO) and Capsicum annum (CA) glycolic extracts (GlExt) have potential that should be further developed in microbial tests. The effect of CO-GlExt and CA-GlExt was evaluated on eight multidrug-resistant clinical strains of Klebsiella pneumoniae and Pseudomonas aeruginosa, as well as collection strains for each bacterial. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract were determined in comparison with 0.12% chlorhexidine. The tests were performed on single species biofilms, at 5 min and 24 h, using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The MIC and MBC of the extract ranged from 1.56 to 50 mg mL-1 for all strains evaluated. Analysis of the MTT assay revealed a strong antimicrobial potential of CA-GlExt, comparable to chlorhexidine. The findings suggest that CA-GlExt is effective against multidrug-resistant strains of K. pneumoniae and P. aeruginosa in planktonic state and biofilms.
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Calendula , Capsicum , Antibacterianos/farmacologia , Pseudomonas aeruginosa , Klebsiella pneumoniae , Glicóis/farmacologia , Clorexidina/farmacologia , Plâncton , Biofilmes , Mentol/farmacologia , Cânfora/farmacologia , Extratos Vegetais/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVE: Antibodies against neuronal N-methyl-D-aspartate receptors (NMDARs) in patients with anti-NMDAR encephalitis alter neuronal synaptic function and plasticity, but the effects on other cells of the nervous system are unknown. METHODS: Cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis (preabsorbed or not with GluN1) and a human NMDAR-specific monoclonal antibody (SSM5) derived from plasma cells of a patient, along the corresponding controls, were used in the studies. To evaluate the activity of oligodendrocyte NMDARs and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in vitro after exposure to patients' CSF antibodies or SSM5, we used a functional assay based on cytosolic Ca2+ imaging. Expression of the glucose transporter (GLUT1) in oligodendrocytes was assessed by immunocytochemistry. RESULTS: NMDAR agonist responses were robustly reduced after preincubation of oligodendrocytes with patients' CSF or SSM5 but remained largely unaltered with the corresponding controls. These effects were NMDAR specific, as patients' CSF did not alter responses to AMPA receptor agonists and was abrogated by preabsorption of CSF with HEK cells expressing GluN1 subunit. Patients' CSF also reduced oligodendrocyte expression of glucose transporter GLUT1 induced by NMDAR activity. INTERPRETATION: Antibodies from patients with anti-NMDAR encephalitis specifically alter the function of NMDARs in oligodendrocytes, causing a decrease of expression of GLUT1. Considering that normal GLUT1 expression in oligodendrocytes and myelin is needed to metabolically support axonal function, the findings suggest a link between antibody-mediated dysfunction of NMDARs in oligodendrocytes and the white matter alterations reported in patients with this disorder. ANN NEUROL 2020;87:670-676.
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Encefalite Antirreceptor de N-Metil-D-Aspartato/metabolismo , Autoanticorpos/imunologia , Oligodendroglia/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Adolescente , Adulto , Animais , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/farmacologia , Autoantígenos/imunologia , Células Cultivadas , Criança , Feminino , Transportador de Glucose Tipo 1/biossíntese , Humanos , Masculino , Oligodendroglia/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/imunologia , Adulto JovemRESUMO
In vivo positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChRs) is a promising tool for the imaging evaluation of neurologic and neurodegenerative diseases. However, the role of α7 nAChRs after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. In vivo and ex vivo evaluation of α7 nAChRs expression after transient middle cerebral artery occlusion (MCAO) was carried out using PET imaging with [11 C]NS14492 and immunohistochemistry (IHC). Pharmacological activation of α7 receptors was evaluated with magnetic resonance imaging (MRI), [18 F]DPA-714 PET, IHC, real time polymerase chain reaction (qPCR) and neurofunctional studies. In the ischemic territory, [11 C]NS14492 signal and IHC showed an expression increase of α7 receptors in microglia and astrocytes after cerebral ischemia. The role played by α7 receptors on neuroinflammation was supported by the decrease of [18 F]DPA-714 binding in ischemic rats treated with the α7 agonist PHA 568487 at day 7 after MCAO. Moreover, compared with non-treated MCAO rats, PHA-treated ischemic rats showed a significant reduction of the cerebral infarct volumes and an improvement of the neurologic outcome. PHA treatment significantly reduced the expression of leukocyte infiltration molecules in MCAO rats and in endothelial cells after in vitro ischemia. Despite that, the activation of α7 nAChR had no influence to the blood brain barrier (BBB) permeability measured by MRI. Taken together, these results suggest that the nicotinic α7 nAChRs play a key role in the inflammatory reaction and the leukocyte recruitment following cerebral ischemia in rats.
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Astrócitos/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Receptores Nicotínicos/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/efeitos dos fármacos , Animais , Astrócitos/metabolismo , Compostos Azabicíclicos/farmacologia , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/induzido quimicamente , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Oxidiazóis/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Ratos Sprague-DawleyRESUMO
Due to the increase of bacterial resistance, medicinal alternatives are being explored. Punica granatum L. is an effective herbal extract with broad spectrum of action and bactericidal, antifungal, anthelmintic potential and being able to modulate the immune response. The aim was to evaluate the antimicrobial activity of pomegranate glycolic extract (PGE) against the periodontal pathogen Porphyromonas gingivalis by using Galleria mellonella as in vivo model. Fifteen larvae were used per group. Injection of high concentration (200, 100, and 25 mg/mL) of PGE showed a toxic effect, leading them to death. A suspension of P. gingivalis (106 cells/mL) was inoculated in the left last proleg and PGE (12.5, 6.25, 3.1, and 2.5 mg/mL) were injected into the right proleg. The larvae were then kept at 37°C under the dark. Injection of PGE at any dose statistically improved larvae survival rates. The data were analysed (log-rank test, Mantel-Cox, P < 0.05) and showed that all concentrations of PGE (12.5, 6.25, 3.1, and 2.5 mg/mL) presented higher larval survival rates, with significant statistical difference in relation to control group (P. gingivalis). In conclusion, the PGE had antimicrobial action against P. gingivalis in vivo model using G. mellonella.
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Enhanced efficiency fertilizers (EEFs) can reduce nitrogen (N) losses in temperate agriculture but are less effective in the tropics. We aimed to design a new EEF and evaluate their performance in simple-to-complex tests with tropical soils and crops. We melt-extruded urea at different loadings into biodegradable polymer matrix composites using biodegradable polyhydroxyalkanoate (PHA) or polybutylene adipate-co-terephthalate (PBAT) polymers with urea distributed throughout the pellet. These contrast with commercially coated EEF that have a polymer-coated urea core. We hypothesized that matrix fertilizers would have an intermediate N release rate compared to fast release from urea or slow release from coated EEF. Nitrogen release rates in water and sand-soil columns confirmed that the matrix fertilizer formulations had a more progressive N release than a coated EEF. A more complex picture emerged from testing sorghum [Sorghum bicolor (L.) Moench] grown to maturity in large soil pots, as the different formulations resulted in minor differences in plant N accumulation and grain production. This confirms the need to consider soil interactions, microbial processes, crop physiology, and phenology for evaluating fertilizer performance. Promisingly, crop δ15N signatures emerged as an integrated measure of efficacy, tracking likely N conversions and losses. The three complementary evaluations combine the advantages of standardized high-throughput screening and more resource-intensive and realistic testing in a plant-soil system. We conclude that melt-blended biodegradable polymer matrix fertilizers show promise as EEF because they can be designed toward more abiotically or more microbially driven N release by selecting biopolymer type and N loading rate.
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Agricultura , Fertilizantes , Nitrogênio , Polímeros , Fertilizantes/análise , Nitrogênio/análise , Agricultura/métodos , Solo/química , Biodegradação Ambiental , SorghumRESUMO
Nontyphoidal Salmonella is one of the major causes of self-limiting diarrheal disease and the most common foodborne pathogen worldwide. It is an important contributor to the burden of foodborne illness in South America, including Peru, where chicken and pork are important vehicles for Salmonella infection. Salmonella infections are underreported, particularly in low- and middle-income countries where concerted action tackling Salmonella along the chicken and pork chains, from primary production to retail, is urgently needed. To support and inform the implementation of new strategies to reduce Salmonella contamination of chicken and pork, this study describes the frequency and distribution of foodborne outbreaks attributed to Salmonella in Peru and evaluates the level of Salmonella in chicken and pork meat sold in markets of three regions of Peru. To that end, we analyzed historical reports of foodborne outbreaks, levels of Salmonella in chicken and pork sold in markets, and the number of mesophiles in the collected meat samples. As a result, the microbiological analysis reveals a widespread contamination of chicken (77.1%) and pork (26.8%) with Salmonella. It also pinpoints Salmonella as the causative agent in nearly half of the outbreaks (47.0%) where the potential origin is identified over a 11-year period with chicken, mayonnaise, and pork being the most likely food vehicles. These results suggest that Salmonella is a major contributor to foodborne illness in Peru and that the monitoring of mesophiles could be a good strategy for surveillance, generating data to support source attribution studies and ultimately evidence-informed policies.
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Galinhas , Doenças Transmitidas por Alimentos , Salmonella , Galinhas/microbiologia , Animais , Peru/epidemiologia , Salmonella/isolamento & purificação , Suínos , Humanos , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Carne/microbiologia , Surtos de Doenças , Microbiologia de Alimentos , Intoxicação Alimentar por Salmonella/epidemiologia , Intoxicação Alimentar por Salmonella/microbiologia , Carne de Porco/microbiologia , Contaminação de Alimentos/análiseRESUMO
Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests.
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Florestas , Herbivoria , Insetos , Nitrogênio , Folhas de Planta , Temperatura , Herbivoria/fisiologia , Animais , Insetos/fisiologia , Folhas de Planta/metabolismo , Nitrogênio/metabolismo , Carbono/metabolismo , Ciclo do Carbono , Fósforo/metabolismo , Ecossistema , Árvores/metabolismoRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has demonstrated that Wastewater Based Epidemiology is a fast and economical alternative for monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the community level in high-income countries. In the present study, wastewater from a city in the Peruvian Highlands, which lacks a wastewater treatment plant, was monitored for one year to assess the relationship between the concentration of SARS-CoV-2 and the reported cases of COVID-19 in the community. Additionally, we compared the relationship between rotavirus (RV), norovirus genogroup II (NoV GGII), and human adenovirus (HAdV) with the number of reported cases of acute gastroenteritis. Before commencing the analysis of the samples, the viral recovery efficacy of three processing methods was determined in spiked wastewater with SARS-CoV-2. This evaluation demonstrated the highest recovery rate with direct analysis (72.2 %), as compared to ultrafiltration (50.8 %) and skimmed milk flocculation (5.6 %). Wastewater monitoring revealed that 72 % (36/50) of the samples tested positive for SARS-CoV-2, with direct analysis yielding the highest detection frequency and quantification of SARS-CoV-2. Furthermore, a strong correlation was observed between the concentration of SARS-CoV-2 in wastewater and the reported cases of COVID-19, mainly when we shift the concentration of SARS-CoV-2 by two weeks, which allows us to anticipate the onset of the fourth and fifth waves of the pandemic in Peru up to two weeks in advance. All samples processed using the skimmed milk flocculation method tested positive and showed high concentrations of RV, NoV GGII, and HAdV. In fact, the highest RV concentrations were detected up to four weeks before outbreaks of acute gastroenteritis reported in children under four years of age. In conclusion, the results of this study suggest that periodic wastewater monitoring is an excellent epidemiological tool for surveillance and can anticipate outbreaks of infectious diseases, such as COVID-19, in low- and middle-income countries.
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Adenovírus Humanos , COVID-19 , Gastroenterite , Norovirus , Rotavirus , Criança , Humanos , Pré-Escolar , SARS-CoV-2 , COVID-19/epidemiologia , Peru/epidemiologia , Águas Residuárias , Gastroenterite/epidemiologia , Surtos de Doenças , GenótipoRESUMO
Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a food and waterborne pathogen with severe public health implications. We report the first-time isolation of this pathogen in the Central Highlands of Peru through standardized culture procedures and polymerase chain reaction (PCR). Escherichia coli strains were cultured from rectal-anal swabs from dairy calves and beef from food markets. The latex agglutination test was used to detect O157 and H7 antigens, and multiplex real-time PCR was carried out to detect virulence-related genes. The STEC O157:H7 strains were isolated from 3.5% (1/28) of beef samples and from 6.0% (3/50) of dairy calves that also carried both eaeA and stx1 genes. Therefore, this pathogen is a potential cause of food/waterborne disease in the region, and its surveillance in both livestock and their products should be improved to characterize the impact of its zoonotic transmission. From 2010 to 2020, E. coli was suspected in 10 outbreaks reported to the Peruvian Ministry of Health. Isolates from future outbreaks should be characterized to assess the burden posed by STEC O157:H7 in Peru.
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Escherichia coli O157 , Microbiologia de Alimentos , Carne Vermelha , Escherichia coli O157/genética , Escherichia coli O157/isolamento & purificação , Escherichia coli O157/patogenicidade , Carne Vermelha/microbiologia , Fezes/microbiologia , Animais , Bovinos , Indústria de Laticínios , Peru , Reação em Cadeia da Polimerase , Testes de Fixação do Látex , Fatores de Virulência/genéticaRESUMO
OBJECTIVES: The purpose of this study was the qualitative and quantitative assessment of the in vitro effect of HIV-1 protease (PR) mutation 82M on replication capacity and susceptibility to the eight clinically available PR inhibitors (PIs). METHODS: The 82M substitution was introduced by site-directed mutagenesis in wild-type subtype B and G strains, as well as reverted back to wild-type in a therapy-failing strain. The recombinant viruses were evaluated for their replication capacity and susceptibility to PIs. RESULTS: The single 82M mutation within a wild-type subtype B or G background did not result in drug resistance. However, the in vitro effect of single PR mutations on PI susceptibility is not always distinguishable from wild-type virus, and particular background mutations and polymorphisms are required to detect significant differences in the drug susceptibility profile. Consequently, reverting the 82M mutation back to wild-type (82I) in a subtype G isolate from a patient that failed therapy with multiple other PR mutations did result in significant increases in susceptibility towards indinavir and lopinavir and minor increases in susceptibility towards amprenavir and atazanavir. The presence of the 82M mutation also slightly decreased viral replication, whether it was in the genetic background of subtype B or subtype G. CONCLUSIONS: Our results suggest that 82M has an impact on PI susceptibility and that this effect is not due to a compensatory effect on the replication capacity. Because 82M is not observed as a polymorphism in any subtype, these observations support the inclusion of 82M in drug resistance interpretation systems and PI mutation lists.
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Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Inibidores da Protease de HIV/farmacologia , Protease de HIV/genética , Protease de HIV/metabolismo , HIV-1/efeitos dos fármacos , Mutação de Sentido Incorreto , Substituição de Aminoácidos , HIV-1/enzimologia , HIV-1/genética , Humanos , Testes de Sensibilidade Microbiana , Mutagênese Sítio-Dirigida , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Wearables and their benefits for the safety and well-being of users have been widely studied and have had an enormous impact on the general development of these kinds of devices. Yet, the extent of research into the use and impact of wearable devices in the underwater environment is comparatively low. In the past 15 years, there has been an increased interest in research into wearables that are used underwater, as the use of such wearables has steadily grown over time. However, there has so far been no clear indication in the literature about the direction in which efforts for the design and construction of underwater wearable devices are developing. Therefore, the analysis presented in this scoping review establishes a good and powerful basis for the further development and orientation of current underwater wearables within the field. OBJECTIVE: In this scoping review, we targeted wearable devices for underwater use to make a comprehensive map of their capabilities and features and discuss the general direction of the development of underwater wearables and the orientation of research into novel prototypes of these kinds of devices. METHODS: In September 2021, we conducted an extensive search for existing literature on 4 databases and for grey literature to identify developed prototypes and early-stage products that were described and tested in water, could be worn and interacted with (eg, displays, buttons, etc), and were fully functional without external equipment. The studies were written in English, came from peer-reviewed academic sources, and were published between 2005 and 2021. We reviewed each title and abstract. The data extraction process was carried out by one author and verified by another author. RESULTS: In total, 36 relevant studies were included. Among these, 4 different categories were identified; 18 studies dealt primarily with safety devices, 9 dealt with underwater communication devices, 7 dealt with head-up displays, and 2 dealt with underwater human-computer interaction approaches. Although the safety devices seemed to have gained the most interest at the time of this study, a clear trend toward underwater communication wearables was identified. CONCLUSIONS: This review sought to provide a first insight into the possibilities and challenges of the technologies that have been used in and for wearable devices that are meant for use in the underwater environment. Among these, underwater communication technologies have had the most significant influence on future developments. Moreover, a topic that has not received enough attention but should be further addressed is human-computer interaction. By developing underwater wearables that cover 2 or more of the technology categories that we identified, the extent of the benefits of such devices can be significantly increased in the future.
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Mergulho , Dispositivos Eletrônicos Vestíveis , Humanos , TecnologiaRESUMO
Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promising drug with promyelinating properties. Clemastine penetrates the blood brain barrier efficiently and promotes remyelination in different animal models of neurodegeneration including multiple sclerosis, ischemia and Alzheimer's disease. However, its role in myelination during development is unknown. We showed that clemastine treatment during development increased oligodendrocyte differentiation in both white and gray matter. However, despite the increase in the number of oligodendrocytes, conduction velocity of myelinated fibers of corpus callosum decreased in clemastine treated mice. Confocal and electron microscopy showed a reduction in the number of myelinated axons and nodes of Ranvier and a reduction of myelin thickness in corpus callosum. To understand the mechanisms leading to myelin formation impairment in the presence of an excess of myelinating oligodendrocytes, we focused on microglial cells that also express muscarinic M1 receptors. Importantly, the population of CD11c+ microglia cells, necessary for myelination, as well as the levels of insulin growth factor-1 decrease in clemastine-treated mice. Altogether, these data suggest that clemastine impact on myelin development is more complex than previously thought and could be dependent on microglia-oligodendrocyte crosstalk. Further studies are needed to clarify the role of microglia cells on developmental myelination.
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Transcription factor aryl hydrocarbon receptor (AHR) has emerged as one of the main regulators involved both in different homeostatic cell functions and tumor progression. Being a member of the family of basic-helix-loop-helix (bHLH) transcriptional regulators, this intracellular receptor has become a key member in differentiation, pluripotency, chromatin dynamics and cell reprogramming processes, with plenty of new targets identified in the last decade. Besides this role in tissue homeostasis, one enthralling feature of AHR is its capacity of acting as an oncogene or tumor suppressor depending on the specific organ, tissue and cell type. Together with its well-known modulation of cell adhesion and migration in a cell-type specific manner in epithelial-mesenchymal transition (EMT), this duality has also contributed to the arise of its clinical interest, highlighting a new potential as therapeutic tool, diagnosis and prognosis marker. Therefore, a deregulation of AHR-controlled pathways may have a causal role in contributing to physiological and homeostatic failures, tumor progression and dissemination. With that firmly in mind, this review will address the remarkable capability of AHR to exert a different function influenced by the phenotype of the target cell and its potential consequences.
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The liver is among the few organs having the ability to self-regenerate in response to a severe damage compromising its functionality. The Aryl hydrocarbon receptor (Ahr) is a transcription factor relevant for the detoxification of xenobiotics but also largely important for liver development and homeostasis. Hence, liver cell differentiation is developmentally modulated by Ahr through the controlled expression of pluripotency and stemness-inducing genes. Here, 2/3 partial hepatectomy (PH) was used as a clinically relevant approach to induce liver regeneration in Ahr-expressing (Ahr+/+) and Ahr-null (Ahr-/-) mice. Ahr expression and activity were early induced after 2/3 PH to be gradually downmodulated latter during regeneration. Ahr-/- mice triggered liver regeneration much faster than AhR+/+ animals, although both reached full regeneration at the latest times. At initial stages after PHx, earlier regenerating Ahr-/- livers had upregulation of cell proliferation markers and increased activation of signalling pathways related to stemness such as Hippo-YAP and Wnt/ß-catenin, concomitantly with the induction of pro-inflammatory cytokines TNFa, IL6 and p65. These phenotypes, together with the improved metabolic adaptation of Ahr-/- mice after PHx and their induced sustained cell proliferation, could likely result from the expansion of undifferentiated stem cells residing in the liver expressing OCT4, SOX2, KLF4 and NANOG. We propose that Ahr needs to be induced early during regeneration to fine-tune liver regrowth to physiological values. Since Ahr deficiency did not result in liver overgrowth, its transient pharmacological inhibition could serve to improve liver regeneration in hepatectomized and transplanted patients and in those exposed to damaging liver toxins and carcinogens.
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Regeneração Hepática , Receptores de Hidrocarboneto Arílico , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Diferenciação Celular , Hepatectomia , Fígado/metabolismo , Fígado/cirurgia , Camundongos , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismoRESUMO
Aging impairs organismal homeostasis leading to multiple pathologies. Yet, the mechanisms and molecular intermediates involved are largely unknown. Here, we report that aged aryl hydrocarbon receptor-null mice (AhR-/-) had exacerbated cellular senescence and more liver progenitor cells. Senescence-associated markers ß-galactosidase (SA-ß-Gal), p16Ink4a and p21Cip1 and genes encoding senescence-associated secretory phenotype (SASP) factors TNF and IL1 were overexpressed in aged AhR-/- livers. Chromatin immunoprecipitation showed that AhR binding to those gene promoters repressed their expression, thus adjusting physiological levels in AhR+/+ livers. MCP-2, MMP12 and FGF secreted by senescent cells were overproduced in aged AhR-null livers. Supporting the relationship between senescence and stemness, liver progenitor cells were overrepresented in AhR-/- mice, probably contributing to increased hepatocarcinoma burden. These AhR roles are not liver-specific since adult and embryonic AhR-null fibroblasts underwent senescence in culture, overexpressing SA-ß-Gal, p16Ink4a and p21Cip1. Notably, depletion of senescent cells with the senolytic agent navitoclax restored expression of senescent markers in AhR-/- fibroblasts, whereas senescence induction by palbociclib induced an AhR-null-like phenotype in AhR+/+ fibroblasts. AhR levels were downregulated by senescence in mouse lungs but restored upon depletion of p16Ink4a-expressing senescent cells. Thus, AhR restricts age-induced senescence associated to a differentiated phenotype eventually inducing resistance to liver tumorigenesis.
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Inibidor p16 de Quinase Dependente de Ciclina , Receptores de Hidrocarboneto Arílico , Envelhecimento/metabolismo , Animais , Senescência Celular/fisiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Fibroblastos/metabolismo , Fígado/metabolismo , Camundongos , Receptores de Hidrocarboneto Arílico/genéticaRESUMO
Taenia solium is an important cause of acquired epilepsy worldwide and remains endemic in Asia, Africa, and Latin America. Transmission of this parasite is still poorly understood despite the design of infection experiments to improve our knowledge of the disease, with estimates for critical epidemiological parameters, such as the probability of human-to-pig infection after exposure to eggs, still lacking. In this paper, a systematic review was carried out and eight pig infection experiments were analyzed to describe the probability of developing cysts. These experiments included different pathways of inoculation: with ingestion of proglottids, eggs, and beetles that ingested eggs, and direct injection of activated oncospheres into the carotid artery. In these experiments, different infective doses were used, and the numbers of viable and degenerated cysts in the body and brain of each pig were registered. Five alternative dose-response models (exponential, logistic, log-logistic, and exact and approximate beta-Poisson) were assessed for their accuracy in describing the observed probabilities of cyst development as a function of the inoculation dose. Dose-response models were developed separately for the presence of three types of cysts (any, viable only, and cysts in the brain) and considered for each of the four inoculation methods ("Proglottids", "Eggs", "Beetles" and "Carotid"). The exact beta-Poisson model best fit the data for the three types of cysts and all relevant exposure pathways. However, observations for some exposure pathways were too scarce to reliably define a dose-response curve with any model. A wide enough range of doses and sufficient sample sizes was only found for the "Eggs" pathway and a merged "Oral" pathway combining the "Proglottids", "Eggs" and "Beetles" pathways. Estimated parameter values from this model suggest that a low infective dose is sufficient to result in a 50% probability for the development of any cyst or for viable cyst infections. Although this is a preliminary model reliant on a limited dataset, the parameters described in this manuscript should contribute to the design of future experimental infections related to T. solium transmission, as well as the parameterization of simulation models of transmission aimed at informing control.
Assuntos
Besouros , Cisticercose , Cistos , Doenças dos Suínos , Taenia solium , Animais , Cisticercose/epidemiologia , Suínos , Doenças dos Suínos/epidemiologiaRESUMO
Howler monkeys are among the most studied primates in the Neotropics, however, behavioral studies including estimation of food availability in Andean forests are scarce. During 12 months we studied habitat use, behavior, and feeding ecology of two groups of red howler monkeys (Alouatta seniculus) in an isolated fragment in the Colombian Andes. We used a combination of focal animal and instantaneous sampling. We estimated fruit production (FP) using phenology transects, and calculated young leaf abundance by observing marked trees. The home range area used by each group was 10.5 and 16.7 ha and daily distances traveled were 431 ± 228 and 458 ± 259 m, respectively. We found that both groups spent most of their time resting (62-64%). Resting time did not increase with leaf consumption as expected using a strategy of energy minimization. We did not find a relationship between daily distances traveled and leaf consumption. However, howlers consumed fruits according to their availability, and the production of young leaves did not predict feeding time on this resource. Overall, our results are similar to those found on other forest types. We found that despite limited FP in Andean forests, this did not lead to a higher intake of leaves, longer resting periods, or shorter traveling distances for red howlers.
Assuntos
Ciclos de Atividade , Alouatta/psicologia , Ecossistema , Comportamento Alimentar , Territorialidade , Animais , Colômbia , Feminino , Frutas/crescimento & desenvolvimento , Masculino , Folhas de Planta/crescimento & desenvolvimento , Densidade Demográfica , Árvores/fisiologiaRESUMO
Functional Analytic Psychotherapy (FAP) offers a radically behavioral and transdiagnostic conception of the formation of the "self" and the appearance of a diversity of psychological problems. This study examined the extent to which a wide variety of psychological disorders (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility/aggressiveness, phobic anxiety, paranoid ideation, and psychoticism) and a global index of psychopathological severity may in fact be linked to problems of the "self" according to the FAP conception. Two questionnaires, one related to self-experience according to FAP and the other to find the scores on several different psychopathology scales, were administered to 280 adult Spaniards for this purpose. The results confirmed the transdiagnostic nature of the "self"-experience. There are significant and strong correlations between all the psychopathology scales studied and self-experience. Linear regression analyses also show that, along with age and gender, in some cases, the score on self-experience predicts each and every one of the psychopathological variables studied, in addition to the Global Severity Index. These results are discussed and related to the transdiagnostic approach to psychopathology.