279 research outputs found
Relationship between Mediterranean Diet Adherence and Saliva Composition
Dietary polyphenol exposure is known to change protein saliva composition in rodents, but less is known in humans. The present study aimed to assess the relationship between saliva protein composition and adherence to Mediterranean Diet (MD) and polyphenol intake levels. Participants were assessed for their dietary habits, which were converted in Mediterranean adherence level, according to Mediterranean Diet Adherence Score (MEDAS) score. Total polyphenol and total flavanol intakes were extrapolated from dietary data, using Phenol explorer database. Whole saliva was collected, and proteins were separated by SDS-PAGE. Salivary S-type cystatins were highly expressed in the group with medium adherence to MD, being positively correlated with wine intake in overweight individuals. The association between salivary amylase and MD adherence also depended on Body Mass Index (BMI), with a positive association only in normal weight individuals. Polyphenol intake was positively associated with S-type cystatins levels, particularly when flavanols were considered separately. These results show that saliva relationship with MD adherence depend on BMI, suggesting that normal weight and overweight individuals may have different salivary responses to diet. Moreover, these results reinforce the link between saliva and dietary polyphenols (flavanols) levels, leading to the hypothesis that salivary proteome can have a role in polyphenol-rich foods acceptance
Cardiospondylocarpofacial syndrome as a distinct hereditary connective tissue disorder: novel missense variant in MAP3K7 in two unrelated patients
CDKL5 deficiency disorder is a rare X-linked condition that
results in early onset of impairedmotor and cognitive skills such
as motor rigidity, stereotypical hand movements and deficient
language acquisition aswell as recurrent seizures. It is caused by
mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene,
which encodes a serine/threonine kinase involved in important
neuronal processes such as cell signaling and neuron morphogenesis.FCT: UID/Multi/04326/2019 (CCMAR)info:eu-repo/semantics/publishedVersio
Cost effectiveness of palivizumab in Spain: an analysis using observational data
Objectives: To assess the cost effectiveness of palivizumab for prevention of severe respiratory syncytial virus (RSV) disease in high-risk infants in Spain, incorporating country-specific observational hospitalisation data. Methods: An existing decision tree model, designed using data from a large international clinical trial of palivizumab versus no prophylaxis, was updated to include Spanish observational hospitalisation data. The analysis was performed for preterm children born at or before 32 weeks gestational age, who are at high risk of developing severe RSV disease requiring hospitalisation. Data sources included published literature, official price/tariff lists and national population statistics. The primary perspective of the study was that of the Spanish National Health Service in 2006. Results: The base-case analysis included the direct medical costs associated with palivizumab prophylaxis and hospital care for RSV infections. Use of palivizumab produces an undiscounted incremental cost-effectiveness ratio (ICER) of €6,142 per quality-adjusted life-year (QALY), and a discounted ICER of €12,814/QALY. Conclusion: Palivizumab provides a cost-effective method of prophylaxis against severe RSV disease requiring hospitalisation among preterm infants in Spain
Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma
Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors participate in the coordination of the cell’s energy requirement and in the mitochondrial oxidative phosphorylation enzyme (OXPHOS) biosynthesis, affecting reactive oxygen species (ROS) generation and induction of apoptosis. Although activation of mtGR and mtER is known to trigger anti-inflammatory signals, little information exists on the presence of these receptors in lung tissue and their role in respiratory physiology and disease. Using a mouse model of allergic airway inflammation disease and applying confocal microscopy, subcellular fractionation, and Western blot analysis we showed mitochondrial localization of GRα and ERβ in lung tissue. Allergic airway inflammation caused reduction in mtGRα, mtERβ, and OXPHOS enzyme biosynthesis in lung cells mitochondria and particularly in bronchial epithelial cells mitochondria, which was accompanied by decrease in lung mitochondrial mass and induction of apoptosis. Confirmation and validation of the reduction of the mitochondrial receptors in lung epithelial cells in human asthma was achieved by analyzing autopsies from fatal asthma cases. The presence of the mitochondrial GRα and ERβ in lung tissue cells and especially their reduction in bronchial epithelial cells during allergic airway inflammation suggests a crucial role of these receptors in the regulation of mitochondrial function in asthma, implicating their involvement in the pathophysiology of the disease
Impact of Palivizumab on RSV Hospitalizations for Children with Hemodynamically Significant Congenital Heart Disease
The objective of this study was to evaluate the impact of palivizumab prophylaxis on respiratory syncytial virus (RSV) hospitalizations among children with hemodynamically significant congenital heart disease (CHD). In 2003, the American Academy of Pediatrics (AAP) revised the bronchiolitis policy statement and recommended the use of palivizumab in children <24 months old with hemodynamically significant CHD (HS-CHD). California statewide hospital discharge data from years 2000–2002 (pre-AAP policy revision) were compared to those from years 2004–2006 (post-AAP policy revision). Hospitalizations due to RSV bronchiolitis for children <2 years of age were identified by IDC-9 CM codes 4661.1, 480.1, and 079.6 as the Principal Diagnosis. Children with CHD and children with HS-CHD were identified by the codiagnoses. The overall RSV hospitalization rate was 71 per 10,000 children <2 years of age. Of all RSV hospitalizations, 3.0% were among children with CHD, and 0.50% among children with HS-CHD. HS-CHD patients accounted for 0.56% of RSV hospitalizations in 2000–2002, compared to 0.46% RSV hospitalizations in 2004–2006. That represents a 19% reduction in RSV hospitalizations among HS-CHD patients after 2003. The 19% decrease in RSV hospitalizations equates to seven fewer hospitalizations (76 hospital days) per year among HS-CHD patients. We conclude that, since the recommendation of palivizumab for children with HS-CHD in 2003, the impact on RSV hospitalizations in California among HS-CHD patients has been limited. Considering the high cost of palivizumab administration, the cost-benefit of RSV prophylaxis with palivizumab warrants further investigation
Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.
The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition
Targeted therapy against Bcl-2-related proteins in breast cancer cells
INTRODUCTION: Bcl-2 and Bcl-xL confer resistance to apoptosis, thereby reducing the effectiveness of chemotherapy. We examined the relationship between the expression of Bcl-2 and Bcl-xL and chemosensitivity of breast cancer cells, with the aim of developing specific targeted therapy. METHODS: Four human breast cancer cell lines were examined, and the effects of antisense (AS) Bcl-2 and AS Bcl-xL phosphorothioate oligodeoxynucleotides (ODNs) on chemosensitivity were tested in vitro and in vivo. Chemosensitivity was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, and the antitumor effect was assessed in vivo by the success of xenograft transplantation into athymic mice. RESULTS: Treatment with AS Bcl-2 and Bcl-xL ODNs resulted in a sequence-specific decrease in protein expression, compared with controls. Treatment of BT-474, ZR-75-1, and MDA-MB-231 cells with AS Bcl-2 increased chemosensitivity to doxorubicin (DOX), mitomycin C (MMC), paclitaxel (TXL), and docetaxel (TXT). Transfection of the Bcl-2 gene into MDA-MB-453 cells decreased sensitivity to DOX and MMC. Treatment of MDA-MB-231, BT-474, and ZR-75-1 cells with AS Bcl-xL increased chemosensitivity to DOX, MMC and taxanes to a smaller extent than AS Bcl-2. This occurred in the setting of increased Bax and cleaved poly(ADP-ribose) polymerase, as well as decreased Bcl-2 and pAkt. AS Bcl-2 ODNs induced splenomegaly in association with increased serum IL-12, which was attenuated by methylation of the CpG motifs of AS Bcl-2; however, methylated CpG failed to negate the increased antitumor effect of AS Bcl-2. Bcl-2 and Bcl-xL, to a smaller extent, are major determinants of chemosensitivity in breast cancer cells. CONCLUSION: Targeted therapy against Bcl-2 protein with the use of AS ODNs might enhance the effects of chemotherapy in patients with breast cancer
A Simple Stochastic Model with Environmental Transmission Explains Multi-Year Periodicity in Outbreaks of Avian Flu
Avian influenza virus reveals persistent and recurrent outbreaks in North American wild waterfowl, and exhibits major outbreaks at 2–8 years intervals in duck populations. The standard susceptible-infected- recovered (SIR) framework, which includes seasonal migration and reproduction, but lacks environmental transmission, is unable to reproduce the multi-periodic patterns of avian influenza epidemics. In this paper, we argue that a fully stochastic theory based on environmental transmission provides a simple, plausible explanation for the phenomenon of multi-year periodic outbreaks of avian flu. Our theory predicts complex fluctuations with a dominant period of 2 to 8 years which essentially depends on the intensity of environmental transmission. A wavelet analysis of the observed data supports this prediction. Furthermore, using master equations and van Kampen system-size expansion techniques, we provide an analytical expression for the spectrum of stochastic fluctuations, revealing how the outbreak period varies with the environmental transmission
Brazilian adolescents' knowledge and beliefs about abortion methods: A school-based internet inquiry
Background: Internet surveys that draw from traditionally generated samples provide the unique conditions to engage adolescents in exploration of sensitive health topics.Methods: We examined awareness of unwanted pregnancy, abortion behaviour, methods, and attitudes toward specific legal indications for abortion via a school-based internet survey among 378 adolescents aged 12-21 years in three Rio de Janeiro public schools.Results: Forty-five percent knew peers who had undergone an abortion. Most students (66.0%) did not disclose abortion method knowledge. However, girls (aOR 4.2, 95% CI 2.4-7.2), those who had experienced their sexual debut (aOR1.76, 95% CI 1.1-3.0), and those attending a prestigious magnet school (aOR 2.7 95% CI 1.4-6.3) were more likely to report methods. Most abortion methods (79.3%) reported were ineffective, obsolete, and/or unsafe. Herbs (e.g. marijuana tea), over-the-counter medications, surgical procedures, foreign objects and blunt trauma were reported. Most techniques (85.2%) were perceived to be dangerous, including methods recommended by the World Health Organization. A majority (61.4%) supported Brazil's existing law permitting abortion in the case of rape. There was no association between gender, age, sexual debut, parental education or socioeconomic status and attitudes toward legal abortion. However, students at the magnet school supported twice as many legal indications (2.7, SE.27) suggesting a likely role of peers and/or educators in shaping abortion views.Conclusions: Abortion knowledge and attitudes are not driven simply by age, religion or class, but rather a complex interplay that includes both social spaces and gender. Prevention of abortion morbidity and mortality among adolescents requires comprehensive sexuality and reproductive health education that includes factual distinctions between safe and unsafe abortion methods
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