Exploring the impact of Ecuador's policies on the right to health of Venezuelan migrants during the COVID-19 pandemic: a scoping review.

Venezuela's ongoing economic and political crisis has forced >6 million people to emigrate from the country since 2014. In the Andean region, Ecuador is one of the main host countries for Venezuelan migrants and refugees. During the coronavirus disease 2019 (COVID-19) pandemic, specific measures were implemented in the country to control the spread of the disease and its associated impacts. In this context, we conducted a scoping review to understand how policies implemented by the Ecuadorian government during the pandemic impacted Venezuelan migrants' right to health. The literature search focused on scientific and grey publications between 2018 and 2022 in electronic databases and institutional websites, complemented by snowball sampling and expert advice. Our thematic analysis revealed discrepancies between the rights granted to migrants in Ecuador's legal framework and their practical implementation during the pandemic, with several instances of policy and programmatic infringement. The disruption of services further complicated migrant's options for regularization. Some measures, like border closures, negatively impacted migrants' health, including increased exposure to abuse and violence. While migrants were included in the country's COVID-19 vaccination plan, they were excluded from other national aid programmes. There are indications of an increase in xenophobia and discrimination stigmatizing migrants as 'disease carriers' and 'resource takers', resulting in a prioritization of services for the Ecuadorian population. We found limited research on the emergent topic of migrants' vulnerability and related health system challenges. Future research should include working in border zones, consider socioeconomic factors and further explore the poor implementation of Ecuador's legal framework towards upholding migrants' right to health.

Stiffening colloidal gels by solid inclusions.

The elastic properties of a soft matter material can be greatly altered by the presence of solid inclusions whose microscopic properties, such as their size and interactions, can have a dramatic effect. In order to shed light on these effects we use extensive rheology computer simulations to investigate colloidal gels with solid inclusions of different sizes. We show that the elastic properties vary in a highly non-trivial way as a consequence of the interactions between the gel backbone and the inclusions. In particular, we show that the key aspects are the presence of the gel backbone and its mechanical alteration originating from the inclusions. To confirm our observations and their generality, we performed experiments on an emulsion that presents strong analogies with colloidal gels and confirms the trends observed in the simulations.

Multi-component colloidal gels: interplay between structure and mechanical properties.

We present a detailed numerical study of multi-component colloidal gels interacting sterically and obtained by arrested phase separation. Under deformation, we found that the interplay between the different intertwined networks is key. Increasing the number of components leads to softer solids that can accommodate progressively larger strains before yielding. The simulations highlight how this is the direct consequence of the purely repulsive interactions between the different components, which end up enhancing the linear response of the material. Our work provides new insight into mechanisms at play for controlling the material properties and opens a road to new design principles for soft composite solids.

Secreted Phospholipase A2-IIA Modulates Transdifferentiation of Cardiac Fibroblast through EGFR Transactivation: An Inflammation-Fibrosis Link.

Secreted phospholipase A2-IIA (sPLA2-IIA) is a pro-inflammatory protein associated with cardiovascular disorders, whose functions and underlying mechanisms in cardiac remodelling are still under investigation. We herein study the role of sPLA2-IIA in cardiac fibroblast (CFs)-to-myofibroblast differentiation and fibrosis, two major features involved in cardiac remodelling, and also explore potential mechanisms involved. In a mice model of dilated cardiomyopathy (DCM) after autoimmune myocarditis, serum and cardiac sPLA2-IIA protein expression were found to be increased, together with elevated cardiac levels of the cross-linking enzyme lysyl oxidase (LOX) and reactive oxygen species (ROS) accumulation. Exogenous sPLA2-IIA treatment induced proliferation and differentiation of adult rat CFs. Molecular studies demonstrated that sPLA2-IIA promoted Src phosphorylation, shedding of the membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) ectodomain and EGFR phosphorylation, which triggered phosphorylation of ERK, P70S6K and rS6. This was also accompanied by an up-regulated expression of the bone morphogenic protein (BMP)-1, LOX and collagen I. ROS accumulation were also found to be increased in sPLA2-IIA-treated CFs. The presence of inhibitors of the Src/ADAMs-dependent HB-EGF shedding/EGFR pathway abolished the CF phenotype induced by sPLA2-IIA. In conclusion, sPLA2-IIA may promote myofibroblast differentiation through its ability to modulate EGFR transactivation and signalling as key mechanisms that underlie its biological and pro-fibrotic effects.

Anisotropic viscoelastic phase separation in polydisperse hard rods leads to nonsticky gelation.

Spinodal demixing into two phases having very different viscosities leads to viscoelastic networks-i.e., gels-usually as a result of attractive particle interactions. Here, however, we demonstrate demixing in a colloidal system of polydisperse, rod-like clay particles that is driven by particle repulsions instead. One of the phases is a nematic liquid crystal with a highly anisotropic viscosity, allowing flow along the director, but suppressing it in other directions. This phase coexists with a dilute isotropic phase. Real-space analysis and molecular-dynamics simulations both reveal a long-lived network structure that is locally anisotropic, yet macroscopically isotropic. We show that our system exhibits the characteristics of colloidal gelation, leading to nonsticky gels.

The Cyclooxigenase-2 Inhibitor Parecoxib Prevents Epidermal Dysplasia in HPV16-Transgenic Mice: Efficacy and Safety Observations.

Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant efficacy, but also considerable toxicity. This study addresses the chemopreventive effect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16-/-, n = 10, parecoxib-treated); II (HPV16-/- n = 11, untreated); III (HPV16+/-, n = 11, parecoxib-treated) and IV (HPV16+/-, n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/- treated animals (0% versus 64% in HPV16+/- untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/- treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn't modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive effects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.

Long-time anomalous swimmer diffusion in smectic liquid crystals.

The dynamics of self-locomotion of active particles in aligned or liquid crystalline fluids strongly deviates from that in simple isotropic media. We explore the long-time dynamics of a swimmer moving in a three-dimensional smectic liquid crystal and find that the mean-square displacement transverse to the director exhibits a distinct logarithmic tail at long times. The scaling is distinctly different from that in an isotropic or nematic fluid and hints at the subtle but important role of the director fluctuation spectrum in governing the long-time motility of active particles. Our findings are based on a generic hydrodynamic theory and Brownian dynamics computer simulation of a three-dimensional soft mesogen model.

Twisting with a twist: supramolecular helix fluctuations in chiral nematics.

Most theoretical descriptions of lyotropic cholesteric liquid crystals to date focus on homogeneous systems in which the rod concentration, as opposed to the rod orientation, is uniform. In this work, we build upon the Onsager-Straley theory for twisted nematics and study the effect of weak concentration gradients, generated by some external potential, on the cholesteric twist. We apply our theory to chiral nematics of nanohelices in which the supramolecular helix sense is known to spontaneously change sign upon variation of particle concentration, passing through a so-called compensation point at which the mesoscopic twist vanishes. We show that the imposed field offers exquisite control of the handedness and magnitude of the helicoidal director field, even at weak field strengths. Within the same framework we also quantify the director fluctuation spectrum and find evidence for a correlation length diverging at the compensation point.

A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells.

Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA). Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications.

Oleanolic acid controls allergic and inflammatory responses in experimental allergic conjunctivitis.

Pollen is the most common aeroallergen to cause seasonal conjunctivitis. The result of allergen exposure is a strong Th2-mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration. Oleanolic acid (OA) is natural a triterpene that displays strong anti-inflammatory and immunomodulatory properties being an active anti-allergic molecule on hypersensitivity reaction models. However, its effect on inflammatory ocular disorders including conjunctivitis, has not yet been addressed. Hence, using a Ragweed pollen (RWP)-specific allergic conjunctivitis (EAC) mouse model we study here whether OA could modify responses associated to allergic processes. We found that OA treatment restricted mast cell degranulation and infiltration of eosinophils in conjunctival tissue and decreased allergen-specific Igs levels in EAC mice. Th2-type cytokines, secreted phospholipase A2 type-IIA (sPLA2-IIA), and chemokines levels were also significantly diminished in the conjunctiva and serum of OA-treated EAC mice. Moreover, OA treatment also suppressed RWP-specific T-cell proliferation. In vitro studies, on relevant cells of the allergic process, revealed that OA reduced the proliferative and migratory response, as well as the synthesis of proinflammatory mediators on EoL-1 eosinophils and RBL-2H3 mast cells exposed to allergic and/or crucial inflammatory stimuli such as RWP, sPLA2-IIA or eotaxin. Taken together, these findings demonstrate the beneficial activity of OA in ocular allergic processes and may provide a new intervention strategy and potential therapy for allergic diseases.

DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.

BACKGROUND: The natural triterpenes, erythrodiol and uvaol, exert anti-inflammatory, vasorelaxing and anti-proliferative effects. Angiotensin II is a well-known profibrotic and proliferative agent that participates in the cardiac remodeling associated with different pathological situations through the stimulation and proliferation of cardiac fibroblasts. Therefore, the aim of the study was to investigate the preventive effects of the natural triterpenes erythrodiol and uvaol on the proliferation and collagen production induced by angiotensin II in cardiac myofibroblasts. Their actions on cardiac hypertrophy triggered by angiotensin II were also studied. METHODOLOGY/PRINCIPAL FINDINGS: The effect of erythrodiol and uvaol on angiotensin II-induced proliferation was evaluated in cardiac myofibroblasts from adult rats in the presence or the absence of the inhibitors of PPAR-γ, GW9662 or JNK, SP600125. The effect on collagen levels induced by angiotensin II was evaluated in cardiac myofibroblasts and mouse heart. The presence of low doses of both triterpenes reduced the proliferation of cardiac myofibroblasts induced by angiotensin II. Pretreatment with GW9662 reversed the effect elicited by both triterpenes while SP600125 did not modify it. Both triterpenes at high doses produced an increase in annexing-V binding in the presence or absence of angiotensin II, which was reduced by either SP600125 or GW9662. Erythrodiol and uvaol decreased collagen I and galectin 3 levels induced by angiotensin II in cardiac myofribroblasts. Finally, cardiac hypertrophy, ventricular remodeling, fibrosis, and increases in myocyte area and brain natriuretic peptide levels observed in angiotensin II-infused mice were reduced in triterpene-treated animals. CONCLUSIONS/SIGNIFICANCE: Erythrodiol and uvaol reduce cardiac hypertrophy and left ventricle remodeling induced by angiotensin II in mice by diminishing fibrosis and myocyte area. They also modulate growth and survival of cardiac myofibroblasts. They inhibit the angiotensin II-induced proliferation in a PPAR-γ-dependent manner, while at high doses they activate pathways of programmed cell death that are dependent on JNK and PPAR-γ.

Secreted phospholipase A2-IIA-induced a phenotype of activated microglia in BV-2 cells requires epidermal growth factor receptor transactivation and proHB-EGF shedding.

BACKGROUND: Activation of microglia, the primary component of the innate immune response in the brain, is a hallmark of neuroinflammation in neurodegenerative disorders, including Alzheimer's disease (AD) and other pathological conditions such as stroke or CNS infection. In response to a variety of insults, microglial cells produce high levels of inflammatory cytokines that are often involved in neuronal injury, and play an important role in the recognition, engulfment, and clearance of apoptotic cells and/or invading microbes. Secreted phospholipase A2-IIA (sPLA2-IIA), an enzyme that interacts with cells involved in the systemic immune/inflammatory response, has been found up-regulated in the cerebrospinal fluid and brain of AD patients. However, despite several approaches, its functions in mediating CNS inflammation remain unknown. In the present study, the role of sPLA2-IIA was examined by investigating its direct effects on microglial cells. METHODS: Primary and immortalized microglial cells were stimulated by sPLA2-IIA in order to characterize the cytokine-like actions of the phospholipase. The hallmarks of activated microglia analyzed include: mitogenic response, phagocytic capabilities and induction of inflammatory mediators. In addition, we studied several of the potential molecular mechanisms involved in those events. RESULTS: The direct exposure of microglial cells to sPLA2-IIA stimulated, in a time- and dose-dependent manner, their phagocytic and proliferative capabilities. sPLA2-IIA also triggered the synthesis of the inflammatory proteins COX-2 and TNFα. In addition, EGFR phosphorylation and shedding of the membrane-anchored heparin-binding EGF-like growth factor (pro-HB-EGF) ectodomain, as well as a rapid activation/phosphorylation of the classical survival proteins ERK, P70S6K and rS6 were induced upon sPLA2-IIA treatment. We further demonstrated that the presence of an EGFR inhibitor (AG1478), a matrix metalloproteinase inhibitor (GM6001), an ADAM inhibitor (TAPI-1), and a HB-EGF neutralizing antibody abrogated the phenotype of activated microglia induced by the sPLA2-IIA. CONCLUSION: These results support the hypothesis that sPLA2-IIA may act as a potent modulator of microglial functions through its ability to induce EGFR transactivation and HB-EGF release. Accordingly, pharmacological modulation of EGFR might be a useful tool for treating neuroinflammatory diseases characterized by sPLA2-IIA accumulation.

Mitochondria determine the differentiation potential of cardiac mesoangioblasts.

An understanding of cardiac progenitor cell biology would facilitate their therapeutic potential for cardiomyocyte restoration and functional heart repair. Our previous studies identified cardiac mesoangioblasts as precommitted progenitor cells from the postnatal heart, which can be expanded in vitro and efficiently differentiated in vitro and in vivo to contribute new myocardium after injury.Based on their proliferation potential in culture, we show here that two populations of mesoangioblasts can be isolated from explant cultures of mouse and human heart.Although both populations express similar surface markers, together with a panel of instructive cardiac transcription factors, they differ significantly in their cellular content of mitochondria. Slow dividing (SD) cells, containing many mitochondria, can be efficiently differentiated with 5-azacytidine (5-aza) to generate cardiomyocytes expressing mature structural markers. In contrast, fast dividing (FD) mesoangioblasts, which contain decreased quantities of mitochondria, do not respond to 5-aza treatment.Notably, increasing mitochondrial numbers using pharmacological nitric oxide (NO) donors reverses the differentiation block in FD mesoangioblasts and leads to a progressive maturation to cardiomyocytes; conversely decreasing mitochondrial content, using respiratory chain inhibitors and chloramphenicol, perturbs cardiomyocyte differentiation in SD populations. Furthermore, isolated cardiac mesoangioblasts from aged mouse and human hearts are found to be almost exclusively mitochondria low FD populations, which are permissive for cardiomyocyte differentiation only after NO treatment. Taken together,this study illustrates a key role for mitochondria in cardiac mesoangioblast differentiation and raises the interesting possibility that treatments, which increase cellular mitochondrial content, may have utility for cardiac stem cell therapy.

Factores de riesgo modulados por los padres de familia o encargados, que influyen en la presencia de caries de la temprana infancia en niños y niñas de 3 a 5 años que asisten a las clínicas de odontopediatría de la Facultad de Odontología de la Universidad de El Salvador / Risk factors modulated by parents or guardians, which influence the presence of early childhood caries in boys and girls aged 3 to 5 years old who attend the pediatric dentistry clinics of the Faculty of Dentistry of the University of El Salvador

La presente investigación tenía como objetivo conocer la modulación que los padres de familia o encargados ejercen sobre los factores de riesgo que influyen en la presencia de Caries de la Temprana Infancia en niños y niñas de 3 a 5 años que asisten a la Clínica de Odontopediatría de la Facultad de Odontología de la Universidad de El Salvador, durante los meses de Abril y Mayo del 2010, en el turno clínico de 7 a 9 a.m. El universo de estudio fueron 37 niños, de los cuales se identificó tanto la edad y el género en que dicha patología es más predominante; así como también la cantidad de niños afectados por dicha enfermedad. De 37 niños examinados, 30 presentaron CTI, determinando que la prevalencia de dicha enfermedad en la población representó el 81.10%. De los cuales, la edad más afectada fue el grupo de 3 a 4 años con un porcentaje de 51.4%; con una prevalencia del género masculino, siempre en este mismo rango de edad, con un 27%; entre los factores de riesgo más influyentes modulados por los padres de familia o encargados se concluyó que la ingesta de leche materna representó el 89.2%; el consumo de leche por medio de la pacha fue de 73%; sumado al mal hábito de que los padres permitieran que el niño se durmiera tomando pacha o leche materna con un 89.2%; el consumo de golosinas en un100% de la población, y la contaminación cruzada por medio del beso en la boca o mano del niño con un 62.2%; siendo estos resultados los más representativos de la investigación.

The objective of the present investigation was to know the modulation that parents or guardians exert on the risk factors that influence the presence of Early Childhood Caries in boys and girls from 3 to 5 years old who attend the Pediatric Dentistry Clinic of the Faculty of Dentistry of the University of El Salvador, during the months of April and May 2010, in the clinical shift from 7 to 9 am The universe of study was 37 children, of which both age and gender were identified in that said pathology is more prevalent; as well as the number of children affected by this disease. Of 37 children examined, 30 presented ICC, determining that the prevalence of this disease in the population represented 81.10%. Of which, the most affected age was the group of 3 to 4 years with a percentage of 51.4%; with a prevalence of the male gender, always in this same age range, with 27%; Among the most influential risk factors modulated by parents or guardians, it was concluded that the intake of breast milk represented 89.2%; the consumption of milk through the pacha was 73%; added to the bad habit of parents allowing the child to fall asleep drinking pacha or breast milk with 89.2%; the consumption of sweets in 100% of the population, and cross contamination through kissing on the child's mouth or hand with 62.2%; these results being the most representative of the research.