Accumulation of lipid-laden macrophages within the arterial neointima is a critical step in atherosclerotic plaque formation. Here, we show that reduced levels of the cellular plasticity factor ZEB1 ...in macrophages increase atherosclerotic plaque formation and the chance of cardiovascular events. Compared to control counterparts (Zeb1
/Apoe
), male mice with Zeb1 ablation in their myeloid cells (Zeb1
/Apoe
) have larger atherosclerotic plaques and higher lipid accumulation in their macrophages due to delayed lipid traffic and deficient cholesterol efflux. Zeb1
/Apoe
mice display more pronounced systemic metabolic alterations than Zeb1
/Apoe
mice, with higher serum levels of low-density lipoproteins and inflammatory cytokines and larger ectopic fat deposits. Higher lipid accumulation in Zeb1
macrophages is reverted by the exogenous expression of Zeb1 through macrophage-targeted nanoparticles. In vivo administration of these nanoparticles reduces atherosclerotic plaque formation in Zeb1
/Apoe
mice. Finally, low ZEB1 expression in human endarterectomies is associated with plaque rupture and cardiovascular events. These results set ZEB1 in macrophages as a potential target in the treatment of atherosclerosis.
Wastewater treatment process design involves the optimization of multiple conflicting objectives. The detection of different equivalent solutions in terms of objective values is crucial for designers ...in order to efficiently switch to the new optimal operation policies if changes in the process conditions or new constraints occur. In this work, the dynamic multi-objective optimization of a municipal wastewater treatment plant model is carried out. The aim is to simultaneously optimize an economic cost term and an effluent quality index. The selected process variables for the optimization are (1) an aeration factor in the aerated tank previous to the clarifier, and (2) an internal recycle flow rate. Their time profiles are approximated using the control vector parameterization technique. To solve the multi-objective problem and find the Pareto front, the NSGA-II algorithm has been used. The simulation of different realistic scenarios which impose operational constraints (e.g., maintenance operations) reveals that, indeed, multiple solutions exist at least in some areas of the Pareto front. It is observed that different control profiles can produce nearly identical results in terms of Pareto solutions. The a priori knowledge of these equivalent solutions for different scenarios provides the decision makers with alternative choices to be adapted to their organizations policies when events altering decision variables bounds or adding new constraints to the process model occur.
The early stages of the COVID-19 pandemic presented the characteristics of a traumatic event that could trigger post-traumatic stress disorder. Emergency Medical Services workers are already a ...high-risk group due to their professional development. The research project aimed to analyse the impact of the COVID-19 pandemic on EMS professionals in terms of their mental health. For this purpose, we present a descriptive crosssectional study with survey methodology. A total of 317 EMS workers (doctors, nurses, and emergency medical technicians) were recruited voluntarily. Psychological distress, post-traumatic stress disorder, and insomnia were assessed. The instruments were the General Health Questionnaire-12 (GHQ-12), the Davidson Trauma Scale (DTS-8), and the Athens Insomnia Scale (AIS-8). We found that 36% of respondents had psychological distress, 30.9% potentially had PTSD, and 60.9% experienced insomnia. Years of work experience were found to be positively correlated, albeit with low effect, with the PTSD score (r = 0.133). Finally, it can be stated that the COVID-19 pandemic has been a traumatic event for EMS workers. The number of professionals presenting psychological distress, possible PTSD, or insomnia increased dramatically during the early phases of the pandemic. This study highlights the need for mental health disorder prevention programmes for EMS workers in the face of a pandemic.
Studies on teachers' knowledge about attention deficit/hyperactivity disorder (ADHD) are not abundant in the literature. The little research done indicates low or moderate scores.
To examine the ...knowledge of Childhood, Primary, and Secondary Education teachers on ADHD, as well as to study possible differences attributable to the previous training, the experience in the disorder and other sociodemographic variables.
A sample of 130 teachers from the Region of Murcia (Spain) was administered a knowledge questionnaire about ADHD and sociodemographic variables were recorded.
The teachers answered correctly to more than half of the items in the questionnaire (63,9%). The Symptoms/Diagnostic scale reached the highest percentage of correct answers (69,1%) and the Etiology scale the lowest (32%). The female teachers showed superior knowledge to the male teachers in all dimensions of the questionnaire. Those teachers who had received training on the disorder presented a higher level of knowledge. In addition, teachers who had previous professional experience showed superior knowledge than those without such experience. According to the teaching specialty, no statistically significant differences were obtained almost in any of the dimensions of the questionnaire. The age group that showed a higher level of knowledge about ADHD was 27-32 years old.
The results point to the need for better training on knowledge and attitudes of teachers towards ADHD that facilitate the early detection of these cases and their specialized care at different educational levels.
Abstract The objectives of this study were to evaluate the survival after 5 years of implants placed using inferior alveolar nerve (IAN) lateralization in cases of mandibular atrophy and to determine ...the incidence of complications. Twenty-seven patients received 74 implants by means of the IAN lateralization technique. Implant survival after 5 years of loading was 98.6%. Eighteen months after surgery, the recovery of sensitivity was complete in 26 cases. Implant placement with IAN lateralization was seen to be a satisfactory and predictable technique. IAN lateralization requires a high level of technical skill, and strict criteria should be applied when prescribing this treatment.
Achondroplasias are the most common genetic forms of dwarfism in humans. They are associated with activating mutations in FGFR3, which signal through the Stat and MAPK pathways in a ...ligand-independent manner to impair chondrocyte proliferation and differentiation. Snail1 has been implicated in chondrocyte differentiation as it represses
Collagen II and
aggrecan transcription in vitro. Here we demonstrate that Snail1 overexpression in the developing bone leads to achondroplasia in mice. Snail1 acts downstream of FGFR3 signaling in chondrocytes, regulating both Stat and MAPK pathways. Moreover, FGFR3 requires Snail1 during bone development and disease as the inhibition of Snail1 abolishes its signaling even through achondroplastic- and thanatophoric-activating FGFR3 forms. Significantly, Snail1 is aberrantly upregulated in thanatophoric versus normal cartilages from stillborns. Thus, Snail activity may likely be considered a target for achondroplasia therapies.
Descending necrotising mediastinitis is one of the most lethal and least frequent forms of mediastinitis. It is a life-threatening infection most frequently originating from an oropharyngeal or ...odontogenic infection.
A retrospective study of 6 patients diagnosed and treated for descending necrotising mediastinitis between 2015 and 2020 is reported.
All patients were male, mean age of 34.83 years; 66% were smokers. 83% had an orocervical infection and 34% had initial mediastinal spread. All patients were treated initially with empirical broad-spectrum antibiotics and surgical drainage, with subsequent admission to the Intensive Care Unit; only one of them required tracheostomy. The mean hospital stay was 27.37 days. After a mean follow-up of 6 months, 100% of the cases had a complete recovery.
Early diagnosis and surgical treatment combined with improved life-support treatment in intensive care units and broad-spectrum antibiotic therapy leads to a decrease in associated mortality.
Thanatophoric dysplasia (TD) is a lethal form of short-limb skeletal dysplasia that is associated with macrocephaly, and variably cloverleaf skull. Two types of TD are clinically recognized, TD1 and ...TD2, mainly distinguished by their radiographic characteristics. The differences between the two are principally observed in the femur, which appears curved in TD1, while it remains straight but with a proximal medial spike in TD2, and are a less severe overall affectation in TD2. Both types of TD are caused by mutations in different functional domains of the FGFR3 gene. However, whereas several mutations in the different domains of FGFR3 cause TD1, the K650E mutation involving the change of a lysine to glutamic acid ("Lys650Glu") has been found in all TD2 cases to date. Here we describe a newborn infant with TD2 associated with brain defects that have either been infrequently observed (encephalocele) or not hitherto described (holoprosencephaly). Based on recent studies, we consider encephaloceles described in TD to be pseudoencephaloceles, since they are secondary to the intracranial pressure generated by severe hydrocephaly and to severe cranial structural anomalies. Finally, to analyze the mechanisms of holoprosencephaly observed in the case described here, we include a concise review on the current understanding of how FGFs and their receptors are expressed in the rostral signaling center (particularly Fgf8). In addition, we evaluated recent observations that FGF ligands and receptors (including FGFR3) act in concert to organize the whole telencephalon activity, rather than independently patterning different areas.
Flavonoids and ascorbic acid have gained especial relevance due to their functional properties. Their level in processed foodstuffs depend not only on the raw material composition but also on the ...processing system employed. The contents of these two nutraceuticals in juice are determined in two lemon varieties. The highest ascorbic acid contents are in Fino lemon juice, irrespective of the system of extraction used. However, a clear technological effect of the extraction system has been found on the levels of the different types of flavonoids.
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