Colony stimulating factor 1 receptor (Csf1r) expressing cell ablation in mafia (macrophage-specific Fas-induced apoptosis) mice alters monocyte landscape and atherosclerotic lesion characteristics.

Macrophage infiltration and accumulation in the atherosclerotic lesion are associated with plaque progression and instability. Depletion of macrophages from the lesion might provide valuable insights into plaque stabilization processes. Therefore, we assessed the effects of systemic and local macrophage depletion on atherogenesis. To deplete monocytes/macrophages we used atherosclerosis-susceptible Apoe- /- mice, bearing a MaFIA (macrophage-Fas-induced-apoptosis) suicide construct under control of the Csf1r (CD115) promotor, where selective apoptosis of Csf1r-expressing cells was induced in a controlled manner, by administration of a drug, AP20187. Systemic induction of apoptosis resulted in a decrease in lesion macrophages and smooth-muscle cells. Plaque size and necrotic core size remained unaffected. Two weeks after the systemic depletion of macrophages, we observed a replenishment of the myeloid compartment. Myelopoiesis was modulated resulting in an expansion of CSF1Rlo myeloid cells in the circulation and a shift from Ly6chi monocytes toward Ly6cint and Ly6clo populations in the spleen. Local apoptosis induction led to a decrease in plaque burden and macrophage content with marginal effects on the circulating myeloid cells. Local, but not systemic depletion of Csf1r+ myeloid cells resulted in decreased plaque burden. Systemic depletion led to CSF1Rlo-monocyte expansion in blood, possibly explaining the lack of effects on plaque development.

Energy Balance and Bone Health: a Nutrient Availability Perspective.

PURPOSE OF REVIEW: Obesity is highly prevalent and is associated with bone fragility and fracture. The changing nutrient availability to bone in obesity is an important facet of bone health. The goal of this article is to summarize current knowledge on the effects of carbohydrate and dietary fat availability on bone, particularly in the context of other tissues. RECENT FINDINGS: The skeleton is a primary site for fatty acid and glucose uptake. The trafficking of carbohydrates and fats into tissues changes with weight loss and periods of weight gain. Exercise acutely influences nutrient uptake into bone and may affect nutrient partitioning to bone. Bone cells secrete hormones that signal to the brain and other tissues information about its energetic state, which may alter whole-body nutrient trafficking. There is a critical need for studies to address the changes that metabolic perturbations have on nutrient availability in bone.

Respiratory and otolaryngological disorders in Down syndrome from one center in Brazil.

Down syndrome (DS) is the most common chromosomal condition. Anatomical and functional variations in the upper and lower airways are component manifestations of the syndrome and increase the risk of various medical problems. The objective of this study was to determine the prevalence of otorhinolaryngological and respiratory diseases in a DS outpatient clinic over a 3-year period. Medical records data from 1207 patients were retrospectively reviewed. Newborn Hearing Screening was positive in 7.1% of patients. Brainstem auditory evoked potential was performed in 1101 children and showed a hearing loss of 19.8% in the first year. It was positive in 21% of 1021 exams. Audiometry was altered in 64 of 994 exams (6.4%), showing a conductive loss in 90%. Adenotonsillectomy was performed in 308 (25.5%) patients, and 169 (14.0%) required serous otitis ventilation tubes. Asthma was observed in 140 (11.6%) patients, and allergic rhinitis in 544 (56.6%). There were hospitalizations for invasive infection in 480 (39.8%) children, and two (0.2%) patients had severe septicemia from pulmonary focus. Five (0.4%) infants had laryngotracheomalacia, and one patient had anomalous right tracheal bronchus. Recognizing the prevalence of respiratory and otorhinolaryngological disorders in patients with DS allows the promotion of optimal follow-up and early treatment, preventing the development of sequelae.

Dual Role of Phenyl Amides from Hempseed on BACE 1, PPARγ, and PGC-1α in N2a-APP Cells.

In Alzheimer's disease (AD) the accumulation of amyloid ß (Aß) plaques in the brain leads to neuroinflammation, neuronal cell dysfunction, and progressive memory loss. Therefore, blocking the formation of Aß plaques has emerged as one of the most promising strategies to develop AD treatments. Hempseed is widely used as a food, and recently its compounds have shown beneficial effects on neuroinflammation. The objective of this study was to investigate whether a fraction rich in phenyl amide compounds, N-trans-caffeoyltyramine (CAFT) and N-trans-coumaroyltyramine (CUMT), can affect gene expression: ß-site amyloid-precursor-protein-cleaving enzyme 1 (BACE 1), peroxisome proliferator-activated receptor gamma (PPAR γ), and PPARγ-coactivator-1α (PGC-1α) in N2a-APP cells. The mRNA levels were measured using RT-qPCR. The ethyl acetate fraction and CAFT were found to reduce BACE1 gene expression and are promissory PPARγ and PGC-1α natural agonists. The results show that hempseed compounds can inhibit the expression of BACE 1, which is involved in the accumulation of Aß plaques and positively affect transcription factors involved in complex and diverse biological functions.

Dy3+ White Light Emission Can Be Finely Controlled by Tuning the First Coordination Sphere of Ga3+/Dy3+ Metallacrown Complexes.

Single lanthanide(III) ion white light emission is in high demand since it provides the advantage of requiring only one chromophore for the control of the color. Herein, a series of Ga3+/Dy3+ metallacrowns (MCs) is presented, demonstrating outstanding white light colorimetric properties with CIE chromaticity coordinates of (0.309, 0.334) and correlated color temperature (CCT) equal to 6670 K for the MC emitting the closest to the standard white color. Experimental data reveal that the CIE coordinates within the studied series of MCs are controlled mainly by the Dy3+-centered emission rather than by the ligand-centered bands, implying that Dy3+ can be tuned as a single ionic white light emitter by a simple modification of the coordination environment.

Ophthalmological abnormalities in Down syndrome among Brazilian patients.

Down syndrome is the most common chromosomal disorder, affecting 1/700 live births. Among the clinical findings, one constant concern is the high prevalence of visual disorders that, if left untreated, can negatively affect child development. The aim of this study was to determine the prevalence of ophthalmological findings among patients who attended an outpatient clinic for patients with Down syndrome in southern Brazil between 2005 and 2016. A cross-sectional study including 1,207 patients medical records were done, which 492 (40.8%) had some ophthalmological disorder. These data were subjected to descriptive analysis using Statistica software. Among the 492 patients with any ophthalmological disease, the need for glasses was found in 434 (36%) patients, keratoconus in 254 (42.1%), congenital cataract in 27 (15.1%), nasolacrimal duct obstruction in 25 (2.0%), strabismus in 22 (1.9%), nystagmus in four (0.3%), and juvenile cataract in two (0.2%). Two young adults with keratoconus underwent corneal transplantation. Although the prevalence of an ophthalmological disease among the present sample (40.8%) was lower than described in the current literature, it still reinforced the importance of routine and early evaluations in infants. These should begin at 6 months of age and be repeated half-year until 2 years old, annually until 7 years old, biennial in adolescents, and triennial in adults and elderly. Our findings of a high frequency of keratoconus support a detailed corneal study in such patients for early detection and treatment.

Gastrointestinal disorders in Down syndrome.

Down syndrome is the most common human chromosomal disorder. Among clinical findings, one constant concern is the high prevalence of gastrointestinal system alterations. The aim of this study was to determine the prevalence of gastrointestinal disorders at a Down syndrome outpatient clinic during a 10-year follow-up period. Data from medical files were retrospectively reviewed from 1,207 patients. Gastrointestinal changes occurred in 612 (50.7%). The most prevalent disorder was chronic intestinal constipation. Intestinal parasite occurred in 22% (mainly giardiasis), gastroesophageal reflux disease in 14%, digestive tract malformations occurred in 5%: 13 cases of duodenal atresia, 8 of imperforate anus, 4 annular pancreases, 2 congenital megacolon, 2 esophageal atresias, 2 esophageal compression by anomalous subclavian and 1 case of duodenal membrane. We had 38/1,207 (3.1%) patients with difficulty in sucking and only three with dysphagia that resolved before the second year of life. Peptic ulcer disease, celiac disease, and biliary lithiasis were less prevalent with 3% each. Awareness of the high prevalence of gastrointestinal disorders promotes outstanding clinical follow-up as well as adequate development and greater quality of life for patients with Down syndrome and their families.

Nutraceutical Extract from Dulse (Palmaria palmata L.) Inhibits Primary Human Neutrophil Activation.

Palmaria palmata L. (Palmariaceae), commonly known as "dulse", is a red alga that grows on the northern coasts of the Atlantic and Pacific oceans, and is widely used as source of fiber and protein. Dulse is reported to contain anti-inflammatory and antioxidant compounds, albeit no study has investigated these effects in primary human neutrophils. Implication strategies to diminish neutrophil activation have the potential to prevent pathological states. We evaluated the ability of a phenolic dulse extract (DULEXT) to modulate the lipopolysaccharide (LPS)-mediated activation of primary human neutrophils. Intracellular reactive oxygen species (ROS) were measured by fluorescence analysis and nitric oxide (NO) production using the Griess reaction. Inflammatory enzymes and cytokines were detected by ELISA and RT-qPCR. The results show that DULEXT diminished the neutrophil activation related to the down-regulation of TLR4 mRNA expression, deceased gene expression and the LPS-induced release of the chemoattractant mediator IL-8 and the pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α. ROS, NO, and myeloperoxidase (MPO) were also depressed. The data indicated that DULEXT has the potential to disrupt the activation of human primary neutrophils and the derived inflammatory and prooxidant conditions, and suggest a new role for Palmaria palmata L. in the regulation of the pathogenesis of health disorders in which neutrophils play a key role, including atherosclerosis.

Leukocyte Overexpression of Intracellular NAMPT Attenuates Atherosclerosis by Regulating PPARγ-Dependent Monocyte Differentiation and Function.

OBJECTIVE: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) mediates inflammatory and potentially proatherogenic effects, whereas the role of intracellular NAMPT (iNAMPT), the rate limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD)+ generation, in atherogenesis is largely unknown. Here we investigated the effects of iNAMPT overexpression in leukocytes on inflammation and atherosclerosis. APPROACH AND RESULTS: Low-density lipoprotein receptor-deficient mice with hematopoietic overexpression of human iNAMPT (iNAMPThi), on a western type diet, showed attenuated plaque burden with features of lesion stabilization. This anti-atherogenic effect was caused by improved resistance of macrophages to apoptosis by attenuated chemokine (C-C motif) receptor 2-dependent monocyte chemotaxis and by skewing macrophage polarization toward an anti-inflammatory M2 phenotype. The iNAMPThi phenotype was almost fully reversed by treatment with the NAMPT inhibitor FK866, indicating that iNAMPT catalytic activity is instrumental in the atheroprotection. Importantly, iNAMPT overexpression did not induce any increase in eNAMPT, and eNAMPT had no effect on chemokine (C-C motif) receptor 2 expression and promoted an inflammatory M1 phenotype in macrophages. The iNAMPT-mediated effects at least partly involved sirtuin 1-dependent molecular crosstalk of NAMPT and peroxisome proliferator-activated receptor γ. Finally, iNAMPT and peroxisome proliferator-activated receptor γ showed a strong correlation in human atherosclerotic, but not healthy arteries, hinting to a relevance of iNAMPT/peroxisome proliferator-activated receptor γ pathway also in human carotid atherosclerosis. CONCLUSIONS: This study highlights the functional dichotomy of intracellular versus extracellular NAMPT, and unveils a critical role for the iNAMPT-peroxisome proliferator-activated receptor γ axis in atherosclerosis.

Virgin olive oil and its phenol fraction modulate monocyte/macrophage functionality: a potential therapeutic strategy in the treatment of systemic lupus erythematosus.

Monocytes and macrophages are critical effectors and regulators of inflammation and innate immune response, which appear altered in different autoimmune diseases such as systemic lupus erythematosus (SLE). Recent studies suggested that virgin olive oil (VOO) and particularly its phenol compounds might possess preventive effects on different immune-inflammatory diseases, including SLE. Here, we evaluated the effects of VOO (and sunflower oil) on lipopolysaccharide (LPS)-activated peritoneal macrophages from a model of pristane-induced SLE in BALB/c mice, as well as those of the phenol fraction (PF) from VOO on the immune-inflammatory activity and plasticity in monocytes and monocyte-derived macrophages from healthy volunteers. The release of nitrite and inflammatory cytokines was lower in LPS-treated peritoneal macrophages from pristane-SLE mice fed the VOO diet when compared with the sunflower oil diet. PF from VOO similarly decreased the secretion of nitrite and inflammatory cytokines and expression of inducible nitric oxide, PPARγ and Toll-like receptor 4 in LPS-treated human monocytes. PF from VOO also prevented the deregulation of human monocyte subset distribution by LPS and blocked the genetic signature of M1 macrophages while favouring the phenotype of M2 macrophages upon canonical polarisation of naïve human macrophages. For the first time, our study provides several lines of in vivo and in vitro evidence that VOO and PF from VOO target and counteract inflammatory pathways in the monocyte-macrophage lineage of mice with pristane-induced SLE and of healthy subjects, which is a meaningful foundation for further development and application in preclinical and clinical use of PF from VOO in patients with SLE.

Effects of immediate-release niacin and dietary fatty acids on acute insulin and lipid status in individuals with metabolic syndrome.

BACKGROUND: The nature of dietary fats profoundly affects postprandial hypertriglyceridemia and glucose homeostasis. Niacin is a potent lipid-lowering agent. However, limited data exist on postprandial triglycerides and glycemic control following co-administration of high-fat meals with a single dose of niacin in subjects with metabolic syndrome (MetS). The aim of the study was to explore whether a fat challenge containing predominantly saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated (LCPUFAs) fatty acids together with a single dose of immediate-release niacin have a relevant role in postprandial insulin and lipid status in subjects with MetS. RESULTS: In a randomized crossover within-subject design, 16 men with MetS were given a single dose of immediate-release niacin (2 g) and ∼15 cal kg-1 body weight meals containing either SFAs, MUFAs, MUFAs plus omega-3 LCPUFAs or no fat. At baseline and hourly over 6 h, plasma glucose, insulin, C-peptide, triglycerides, free fatty acids (FFAs), total cholesterol, and both high- and low-density lipoprotein cholesterol were assessed. Co-administered with niacin, high-fat meals significantly increased the postprandial concentrations of glucose, insulin, C-peptide, triglycerides, FFAs and postprandial indices of ß-cell function. However, postprandial indices of insulin sensitivity were significantly decreased. These effects were significantly attenuated with MUFAs or MUFAs plus omega-3 LCPUFAs when compared with SFAs. CONCLUSION: In the setting of niacin co-administration and compared to dietary SFAs, MUFAs limit the postprandial insulin, triglyceride and FFA excursions, and improve postprandial glucose homeostasis in MetS. © 2017 Society of Chemical Industry.

Hck/Fgr Kinase Deficiency Reduces Plaque Growth and Stability by Blunting Monocyte Recruitment and Intraplaque Motility.

BACKGROUND: Leukocyte migration is critical for the infiltration of monocytes and accumulation of monocyte-derived macrophages in inflammation. Considering that Hck and Fgr are instrumental in this process, their impact on atherosclerosis and on lesion inflammation and stability was evaluated. METHODS AND RESULTS: Hematopoietic Hck/Fgr-deficient, LDLr(-/-) chimeras, obtained by bone marrow transplantation, had smaller but, paradoxically, less stable lesions with reduced macrophage content, overt cap thinning, and necrotic core expansion as the most prominent features. Despite a Ly6C(high)-skewed proinflammatory monocyte phenotype, Hck/Fgr deficiency led to disrupted adhesion of myeloid cells to and transmigration across endothelial monolayers in vitro and atherosclerotic plaques in vivo, as assessed by intravital microscopy, flow cytometry, and histological examination of atherosclerotic arteries. Moreover, Hck/Fgr-deficient macrophages showed blunted podosome formation and mesenchymal migration capacity. In consequence, transmigrated double-knockout macrophages were seen to accumulate in the fibrous cap, potentially promoting its focal erosion, as observed for double-knockout chimeras. CONCLUSIONS: The hematopoietic deficiency of Hck and Fgr led to attenuated atherosclerotic plaque formation by abrogating endothelial adhesion and transmigration; paradoxically, it also promoted plaque instability by causing monocyte subset imbalance and subendothelial accumulation, raising a note of caution regarding src kinase-targeted intervention in plaque inflammation.

Membrane composition and dynamics: a target of bioactive virgin olive oil constituents.

The endogenous synthesis of lipids, which requires suitable dietary raw materials, is critical for the formation of membrane bilayers. In eukaryotic cells, phospholipids are the predominant membrane lipids and consist of hydrophobic acyl chains attached to a hydrophilic head group. The relative balance between saturated, monounsaturated, and polyunsaturated acyl chains is required for the organization and normal function of membranes. Virgin olive oil is the richest natural dietary source of the monounsaturated lipid oleic acid and is one of the key components of the healthy Mediterranean diet. Virgin olive oil also contains a unique constellation of many other lipophilic and amphipathic constituents whose health benefits are still being discovered. The focus of this review is the latest evidence regarding the impact of oleic acid and the minor constituents of virgin olive oil on the arrangement and behavior of lipid bilayers. We highlight the relevance of these interactions to the potential use of virgin olive oil in preserving the functional properties of membranes to maintain health and in modulating membrane functions that can be altered in several pathologies. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.

Hematopoietic G-protein-coupled receptor kinase 2 deficiency decreases atherosclerotic lesion formation in LDL receptor-knockout mice.

Leukocyte chemotaxis is deemed instrumental in initiation and progression of atherosclerosis. It is mediated by G-protein-coupled receptors (e.g., CCR2 and CCR5), the activity of which is controlled by G-protein-coupled receptor kinases (GRKs). In this study, we analyzed the effect of hematopoietic deficiency of a potent regulator kinase of chemotaxis (GRK2) on atherogenesis. LDL receptor-deficient (LDLr(-/-)) mice with heterozygous hematopoietic GRK2 deficiency, generated by bone marrow transplantation (n=15), displayed a dramatic attenuation of plaque development, with 79% reduction in necrotic core and increased macrophage content. Circulating monocytes decreased and granulocytes increased in GRK2(+/-) chimeras, which could be attributed to diminished granulocyte colony-forming units in bone marrow. Collectively, these data pointed to myeloid cells as major mediators of the impaired atherogenic response in GRK2(+/-) chimeras. LDLr(-/-) mice with macrophage/granulocyte-specific GRK2 deficiency (LysM-Cre GRK2(flox/flox); n=8) failed to mimic the aforementioned phenotype, acquitting these cells as major responsible subsets for GRK2 deficiency-associated atheroprotection. To conclude, even partial hematopoietic GRK2 deficiency prevents atherosclerotic lesion progression beyond the fatty streak stage, identifying hematopoietic GRK2 as a potential target for intervention in atherosclerosis.

Sex-specific effects of Fat-1 transgene on bone material properties, size, and shape in mice.

Western diets are becoming increasingly common around the world. Western diets have high omega 6 (ω-6) and omega 3 (ω-3) fatty acids and are linked to bone loss in humans and animals. Dietary fats are not created equal; therefore, it is vital to understand the effects of specific dietary fats on bone. We aimed to determine how altering the endogenous ratios of ω-6:ω-3 fatty acids impacts bone accrual, strength, and fracture toughness. To accomplish this, we used the Fat-1 transgenic mice, which carry a gene responsible for encoding a ω-3 fatty acid desaturase that converts ω-6 to ω-3 fatty acids. Male and female Fat-1 positive mice (Fat-1) and Fat-1 negative littermates (WT) were given either a high-fat diet (HFD) or low-fat diet (LFD) at 4 wk of age for 16 wk. The Fat-1 transgene reduced fracture toughness in males. Additionally, male BMD, measured from DXA, decreased over the diet duration for HFD mice. In males, neither HFD feeding nor the presence of the Fat-1 transgene impacted cortical geometry, trabecular architecture, or whole-bone flexural properties, as detected by main group effects. In females, Fat-1-LFD mice experienced increases in BMD compared to WT-LFD mice; however, cortical area, distal femur trabecular thickness, and cortical stiffness were reduced in Fat-1 mice compared to pooled WT controls. However, reductions in stiffness were caused by a decrease in bone size and were not driven by changes in material properties. Together, these results demonstrate that the endogenous ω-6:ω-3 fatty acid ratio influences bone material properties in a sex-dependent manner. In addition, Fat-1 mediated fatty acid conversion was not able to mitigate the adverse effects of HFD on bone strength and accrual.

Epidemiological Overview of Overweight and Obesity Related to Eating Habits, Physical Activity and the Concurrent Presence of Depression and Anxiety in Adolescents from High Schools in Mexico City: A Cross-Sectional Study.

Overweight and obesity in adolescents has become a serious public health problem worldwide and Mexico City is no exception. Therefore, the objective of this study was to investigate the epidemiological panorama of overweight and obesity related to eating habits, physical activity and the concurrent presence of depression and anxiety in adolescents from high schools in Mexico City. Anthropometric measurements were taken from 2710 adolescents from 33 participating high schools. Likewise, a previously validated eating habit and physical activity questionnaire was administered, which consisted of four different sections, where each of the sections focused on key aspects of the participants' lifestyle: (1) eating habits, (2) intake of non-recommended foods, (3) food and company environment, and (4) physical activity. Moreover, the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression was applied. In this study, a high prevalence of overweight and obesity (26.5% overweight and 20.0% obese) was found in adolescents from high schools in Mexico City. Only 13.14% of participants had adequate eating habits and 18.19% physical activity habits. An association was found between having inadequate eating habits and obesity in adolescent women (OR = 1.95; CI 1.009-3.76). Additionally, associations were observed between depression symptoms and obesity (OR = 5.68, CI 1.36-32.81; p = 0.01), while anxiety was associated with underweight and obesity adjusted by other dietary habits and psychological factors. Therefore, it is important to identify adolescents with overweight or obesity and establish prevention strategies for weight control in this age group, promoting healthy eating, physical activity and education in mental health.

Inclusion of chia seeds (Salvia hispanica L.) and pumpkin seeds (Cucurbita moschata) in dairy sheep diets.

Chia (Salvia hispanica L.) seed (CS) and Pumpkin (Cucurbita moschata) seed (PS) are used in ruminant diets as energy sources. The current experiment studied the impact of dietary inclusion of CS and PS on nutrient intake and digestibility, milk yield, and milk composition of dairy sheep. Twelve primiparous Texel × Suffolk ewes [70 ± 5 days in milk (DIM); 0.320 ± 0.029 kg milk yield] were distributed in a 4 × 3 Latin square design and fed either a butter-based control diet [CON; 13 g/kg dry matter] or two diets with 61 g/kg DM of either CS or PS. Dietary inclusion of CS and PS did not alter live weight (p >0.1) and DM intake (p >0.1). However, compared to the CON, dietary inclusion of both CS and PS increased the digestibility of neutral detergent fiber (p <0.001) and acid detergent lignin (p < 0.001). Milk production (p = 0.001), fat-corrected milk (p < 0.001), and feed efficiency (p < 0.001) were enhanced with PS, while the highest milk protein yield (p < 0.05) and lactose yield (p < 0.001) were for CS-fed ewes. Compared to the CON diet, the ingestion of either CS and/or PS decreased (p < 0.001) the C16:0 in milk. Moreover, both CS and PS tended to enhance the content of C18:3n6 (p > 0.05) and C18:3n3 (p > 0.05). Overall short-term feeding of CS and/or PS (up to 6.1% DM of diet) not only maintains the production performance and digestibility of nutrients but also positively modifies the milk FA composition.

p38 MAPK protects human monocytes from postprandial triglyceride-rich lipoprotein-induced toxicity.

Postprandial triglyceride (TG)-rich lipoproteins (TRLs) transport dietary fatty acids through the circulatory system to satisfy the energy and structural needs of the tissues. However, fatty acids are also able to modulate gene expression and/or induce cell death. We investigated the underlying mechanism by which postprandial TRLs of different fatty acid compositions can induce cell death in human monocytes. Three types of dietary fat [refined olive oil (ROO), high-palmitic sunflower oil (HPSO), and butter] with progressively increasing SFA:MUFA ratios (0.18, 0.41, and 2.08, respectively) were used as a source of postprandial TRLs (TRL-ROO, TRL-HPSO, and TRL-BUTTER) from healthy men. The monocytic cell line THP-1 was used as a model for this study. We demonstrated that postprandial TRLs increased intracellular lipid accumulation (31-106%), reactive oxygen species production (268-349%), DNA damage (133-1467%), poly(ADP-ribose) polymerase 1 (800-1710%) and caspase-3 (696-1244%) activities, and phosphorylation of c-Jun NH2-terminal kinase (JNK) (54 kDa, 141-288%) and p38 (24-92%). These effects were significantly greater with TRL-BUTTER, and TRL-ROO did not induce DNA damage, DNA fragmentation, or p38 phosphorylation. In addition, blockade of p38, but not of JNK, significantly decreased intracellular lipid accumulation and increased cell death in postprandial TRL-treated cells. These results suggest that in human monocytes, p38 is involved in survival signaling pathways that protect against the lipid-mediated cytotoxicity induced by postprandial TRLs that are abundant in saturated fatty acids.

Quality of life in Down syndrome in Brazil: a cross-sectional study.

BACKGROUND: Down syndrome is the most commonly genetic cause of developmental delay and intellectual disability, affecting 1:700 live births. It is associated with heart disease and recurrent infections, among other complications that greatly impair the patient's quality of life. OBJECTIVE: To evaluate the major factors associated with quality of life in a cohort of patients with Down syndrome. METHODS: We assessed 1,187 patients with Down syndrome, older than 4 years old, with an adaptation of the Personal Outcomes Scale validated for Portuguese language, interviewing patients, parents, and caregivers. RESULTS: A bad quality of life was reported in 56.4% of the sample. The main factors associated with better quality of life were female sex, first medical visit before 4 months old, higher parental education, a professionally active mother, and prenatal care. The main factors associated with worse quality of life were family history of alcohol abuse and psychiatric disorders and comorbidity with autism and epilepsy. CONCLUSION: Clinical comorbidities such as autism and epilepsy carry a heavy burden among patients with Down syndrome, while factors related to family support, such as employment status and educational background of the parents, enhance quality of life. The factors associated with quality of life among patients with Down syndrome should be adequately evaluated in medical consultation and targeted in public health policies.

ANTECEDENTES: A síndrome de Down é a mais comum causa identificável de atraso de desenvolvimento e deficiência intelectual, afetando 1 a cada 700 nascidos vivos. Está associada a cardiopatias, infecções recorrentes e outras complicações que impactam significativamente a qualidade de vida dos pacientes. OBJETIVO: Avaliar os principais fatores associados a qualidade de vida em uma coorte de pacientes com Síndrome de Down. MéTODOS: Avaliamos 1.187 pacientes com síndrome de Down com mais de 4 anos de idade utilizando uma adaptação da versão validada para o português da Escala Pessoal de Resultados, entrevistando pacientes, pais e cuidadores. RESULTADOS: Uma má qualidade de vida foi encontrada em 56.4% da amostra. Os principais fatores associados à melhor qualidade de vida foram sexo feminino, primeira consulta médica antes dos 4 meses de idade, maior nível educacional dos pais, mãe profissionalmente ativa e atenção pré-natal. Os principais fatores associados à pior qualidade de vida foram o histórico familiar de abuso de álcool e distúrbios psiquiátricos, além de comorbidade com autismo e epilepsia. CONCLUSãO: As comorbidades clínicas como autismo e epilepsia levam a um maior impacto entre os pacientes com síndrome de Down, enquanto fatores relacionados ao apoio familiar, como situação profissional e formação educacional dos pais, estão associados à melhor qualidade de vida. Os fatores associados à qualidade de vida de pacientes com síndrome de Down devem ser adequadamente avaliados em consulta médica e alvo de políticas públicas de saúde.

Proteomic analysis of postprandial high-density lipoproteins in healthy subjects.

The relationship between the functionality and composition of high-density lipoproteins (HDL) is yet not fully studied, and little is known about the influence of the diet in HDL proteome. Therefore, the aim of this research was to elucidate the HDL proteome associated to postprandial hyperlipidemia. Male volunteers were recruited for an interventional study with high fatty acid-based meals. Blood samples were collected before the intake (baseline), and 2-3 (postprandial peak) and 5-6 (postprandial post peak) hours later. HDL were purified and the protein composition was quantified by LC-MS/MS. Statistical analysis was performed by lineal models (amica) and by ANOVA and multi-t-test of the different conditions (MetaboAnalyst). Additionally, a clustering of the expression profiles of each protein was done with coseq R package (RStudio). Initially, 320 proteins were identified but only 119 remained after the filtering. APOM, APOE, APOB, and APOA2, proteins previously identified in the HDL proteome, were the only proteins with a statistically significant altered expression in postprandial hyperlipidemia when compared to baseline (p values <0.05 and logFC >1). In conclusion, we have been able to describe several behaviors of the whole HDL proteome during the postprandial hyperlipidemic metabolism.