ABSTRACT
Summary: The objective of our study was to evaluate the association between the previously described asthma risk factors and the prevalence of asthma in a population of Brazilian adults. A population-based cross-sectional study was conducted using data collected from 7891 patients. All patients in the database > 18 years of age were included. The following variables were collected from the health plan database: age, body mass index, smoking status, alcohol consumption, sedentary lifestyle, heart disease, hypertension, diabetes, and asthma diagnosis. The frequency of the collected variables was compared between patients with or without an asthma diagnosis, and logistic regression was performed. Of our total sample (7891 patients), 150 (1.9%) had asthma. The mean age of patients with asthma was 39.4 years. 1.4% of normal weight patients had the diagnosis of asthma, while 2.4% of overweight and 2.2% of obese patients had the diagnosis. Multivariate analysis demonstrated that a sedentary lifestyle and overweight and obesity were independently associated with asthma prevalence Odds Ratio (OR) (95% confidence interval): (1.61 (1.16-2.22) and 1.25 (1.03-1.52) respectively). Our data provide evidence that some clinical characteristics, such as sedentarism, overweight, and obesity, may be related to the prevalence of asthma in an adult population in southeastern Brazil. Such factors could be modified and better understood through multidisciplinary research and health programs that evaluate the risk factors for asthma in large populations.
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Dental care-related fear and anxiety (DFA) is prevalent, affects oral health care utilization, and is related to poor oral health and decreased quality of life. In addition to learned and cultural factors, genetics is hypothesized to contribute to DFA. Therefore, we performed a genome-wide association study to identify genetic variants contributing to DFA. Adult and adolescent participants were from 4 cohorts (3 from the US-based Center for Oral Health Research in Appalachia, n = 1,144, 1,164, and 535, and the UK-based Avon Longitudinal Study of Parents and Children [ALSPAC], n = 2,078). Two self-report instruments were used to assess DFA: the Dental Fear Survey (US cohorts) and Corah's Dental Anxiety Scale (ALSPAC). Genome-wide scans were performed for the DFA total scores and subscale scores (avoidance, physiological arousal, fear of dental treatment-specific stimuli), adjusting for age, sex, educational attainment, recruitment site, and genetic ancestry. Results across cohorts were combined using meta-analysis. Heritability estimates for DFA total and subscale scores were similar across cohorts and ranged from 23% to 59%. The meta-analysis revealed 3 significant (P < 5E-8) associations between genetic loci and 2 DFA subscales: physiological arousal and avoidance. Nearby genes included NTSR1 (P = 3.05E-8), DMRTA1 (P = 4.40E-8), and FAM84A (P = 7.72E-9). Of these, NTSR1, which was associated with the avoidance subscale, mediates neurotensin function, and its deficiency may lead to altered fear memory in mice. Gene enrichment analyses indicated that loci associated with the DFA total score and physiological arousal subscale score were enriched for genes associated with severe and persistent mental health (e.g., schizophrenia) and neurocognitive (e.g., autism) disorders. Heritability analysis indicated that DFA is partly explained by genetic factors, and our association results suggested shared genetic underpinnings with other psychological conditions.
Subject(s)
Dental Anxiety , Quality of Life , Dental Anxiety/genetics , Dental Anxiety/psychology , Genome-Wide Association Study , Longitudinal Studies , Neurotensin , Humans , Adolescent , AdultABSTRACT
Introducción Diversos estudios han demostrado que los cambios en el gen RA pueden estar asociados a un fenotipo de enfermedad más agresivo e incluso al cáncer de próstata resistente a la castración. Por este motivo, hemos investigado las alteraciones citogénicas y moleculares asociadas al RA.Materiales y métodos Para evaluar la metilación del RA, realizamos un análisis citogenético-molecular mediante hibridación fluorescente in situ que utiliza sondas específicas para el gen del RA (Xq11.12) y el centrómero del cromosoma X. Respecto a la actividad del RA, realizamos un análisis cualitativo de la actividad del receptor de andrógenos humano. Para analizar la expresión del RA en las líneas celulares PC3 y LNCaP, utilizamos ensayos de qPCR.ResultadosEn el ensayo qPCR, encontramos una regulación a la baja del RA en la línea celular PC3 en comparación con la LNCaP. Hallamos la presencia de polisomía del cromosoma X en las líneas celulares PC-3 y LNCaP mediante el ensayo FISH. En el ensayo HUMARA-Q encontramos la presencia de dos cromosomas X/célula y actividad en ambos RA de la línea celular PC-3. En las células LNCaP hallamos la presencia de dos cromosomas X/célula y la metilación de solo un RA.Conclusión El fenotipo del cáncer de próstata resistente a la castración representa un gran desafio en el tratamiento urológico. Estos cromosomas X y las alteraciones ligadas al RA pueden contribuir a una mejor comprensión de la enfermedad; sin embargo, deben realizarse más estudios para arrojar más luz sobre el papel del RA en el fenotipo del cáncer de próstata resistente a la castración (AU)
Introduction Several studies have already shown that changes in the AR gene may be associated with a more aggressive disease phenotype and even castration-resistant prostate cancer. Thus, we investigated cytogenetic and molecular alterations linked to AR.Materials and methods To evaluate AR methylation, we performed a cytogenetic-molecular analysis using fluorescence in situ hybridization that uses specific probes for the AR gene (Xq11.12) and the X chromosome centromere. For AR activity, we performed a qualitative analysis of human androgen receptor activity. To analyze the expression of AR in PC3 and LNCaP cell lines, we used qPCR assays.ResultsIn the qPCR assay, we found downregulation of AR in the PC3 cell line compared with the LNCaP. We found the presence of X chromosome polysomy in PC-3 and LNCaP cell lines by FISH assay. In the HUMARA-Q assay, we found two X chromosomes/cell and the activity of both AR in the PC-3 cell line. In LNCaP cells, we found two X chromosomes/cell and methylation of only one AR.Conclusion Castration-resistant prostate cancer phenotype represents a significant challenge in the setting of urological management. The X chromosomes and AR-linked alterations may contribute to a better understanding of the disease. However, further studies should be performed in an attempt to elucidate as much as possible the role of AR in the castration-resistant prostate cancer phenotype (AU)
Subject(s)
Humans , Male , Prostatic Neoplasms, Castration-Resistant/genetics , Cell Line, Tumor , In Situ Hybridization, Fluorescence , PhenotypeABSTRACT
INTRODUCTION: Several studies have already shown that changes in the AR gene may be associated with a more aggressive disease phenotype and even castration-resistant prostate cancer. Thus, we investigated cytogenetic and molecular alterations linked to AR. MATERIALS AND METHODS: To evaluate AR methylation, we performed a cytogenetic-molecular analysis using fluorescence in situ hybridization that uses specific probes for the AR gene (Xq11.12) and the X chromosome centromere. For AR activity, we performed a qualitative analysis of human androgen receptor activity. To analyze the expression of AR in PC3 and LNCaP cell lines, we used qPCR assays. RESULTS: In the qPCR assay, we found downregulation of AR in the PC3 cell line compared with the LNCaP. We found the presence of X chromosome polysomy in PC-3 and LNCaP cell lines by FISH assay. In the HUMARA-Q assay, we found two X chromosomes/cell and the activity of both AR in the PC-3 cell line. In LNCaP cells, we found two X chromosomes/cell and methylation of only one AR. CONCLUSION: Castration-resistant prostate cancer phenotype represents a significant challenge in the setting of urological management. The X chromosomes and AR-linked alterations may contribute to a better understanding of the disease. However, further studies should be performed in an attempt to elucidate as much as possible the role of AR in the castration-resistant prostate cancer phenotype.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Castration , Cell Line, Tumor , Humans , In Situ Hybridization, Fluorescence , Male , Phenotype , Prostatic Neoplasms, Castration-Resistant/geneticsABSTRACT
Previous research has shown that the brown seaweed Ascophyllum nodosum (ASCO) has antimicrobial and antioxidant properties and also increases milk I concentration. We aimed to investigate the effects of supplementing ASCO meal or monensin (MON) on ruminal fermentation, diversity and relative abundance of ruminal bacterial taxa, metabolism of I and As, and blood concentrations of thyroid hormones, antioxidant enzymes, and cortisol in lactating dairy cows. Five multiparous ruminally cannulated Jersey cows averaging (mean ± standard deviation) 102 ± 15 d in milk and 450 ± 33 kg of body weight at the beginning of the study were used in a Latin square design with 28-d periods (21 d for diet adaptation and 7 d for data and sample collection). Cows were fed ad libitum a basal diet containing (dry matter basis) 65% forage as haylage and corn silage and 35% concentrate and were randomly assigned to 1 of the following 5 dietary treatments: 0, 57, 113, or 170 g/d of ASCO meal, or 300 mg/d of MON. Supplements were placed directly into the rumen once daily after the morning feeding. Diets had no effect on ruminal pH and NH3-N concentration, which averaged 6.02 and 6.86 mg/dL, respectively. Total volatile fatty acid concentration decreased linearly in cows fed incremental amounts of ASCO meal. Supplementation with ASCO meal did not change the ruminal molar proportions of volatile fatty acids apart from butyrate, which responded quadratically with the lowest values observed at 56 and 113 g/d of ASCO supplementation. Compared with the control diet or diets containing ASCO meal, cows fed MON showed greater molar proportion of propionate. Diets did not affect the α diversity indices Shannon, Simpson, and Fisher for ruminal bacteria. However, feeding incremental levels of ASCO meal linearly decreased the relative abundance of Tenericutes in ruminal fluid. Monensin increased the relative abundance of the CAG:352 bacterial genus in ruminal fluid compared with the control diet. Linear increases in response to ASCO meal supplementation were observed for the concentrations and output of I in serum, milk, urine, and feces. Fecal excretion of As increased linearly in cows fed varying amounts of ASCO meal, but ASCO did not affect the concentration and secretion of As in milk. The plasma activities of the antioxidant enzymes and the serum concentrations of thyroid hormones did not change. In contrast, circulating cortisol decreased linearly in diets containing ASCO meal. The apparent total-tract digestibilities of dry matter, organic matter, and crude protein increased linearly with ASCO meal, but those of neutral and acid detergent fiber were not affected. In summary, feeding incremental amounts of ASCO meal decreased serum cortisol concentration, and increased I concentrations and output in serum, milk, feces, and urine.
Subject(s)
Arsenic , Ascophyllum , Iodine , Animals , Antioxidants/metabolism , Arsenic/metabolism , Arsenic/pharmacology , Ascophyllum/metabolism , Bacteria/metabolism , Cattle , Dietary Supplements , Digestion , Fatty Acids, Volatile/metabolism , Female , Hydrocortisone/metabolism , Iodine/metabolism , Lactation , Monensin/metabolism , Monensin/pharmacology , Rumen/metabolismABSTRACT
Despite the proven enhancement of MAPbI3 optoelectronic properties and stability by guanidinium substitution, divergences persist regarding fundamental knowledge on this system. This work shows that GAxMA1-xPbI3 solid solutions have guanidinium content-dependent phase transitions, dielectric permittivities, ionic conductivities, activation energies, and relaxation times.
ABSTRACT
Methylammonium lead iodide (MAPbI3) emerges as a promising halide perovskite material for the next generation of solar cells due to its high efficiency and flexibility in material growth. Despite intensive studies of their optical and electronic properties in the past ten years, there are no reports on dc bias electric field effects on conductivity in a wide temperature range. In this work, we report the combined effects of frequency, temperature, and dc bias electric field on the ac conductivity of MAPbI3. We found that the results of dc bias electric fields are very contrasting in the tetragonal and cubic phases. In the tetragonal phase, sufficiently high dc bias electric fields induce a conductivity peak appearance â¼290 K well evidenced at frequencies higher than 100 kHz. Excluding possible degradation and extrinsic factors, we propose that this peak suggests a ferroelectric-like transition. In the absence of a dc bias electric field, the ac conductivity in the tetragonal phase increases with temperature while decreases with temperature in the cubic phase. Also, ac activation energies for tetragonal and cubic phases were found to be inversely and directly proportional to the dc bias electric field, respectively. This behavior was attributed to the ionic conduction, possibly of MA+and I-ions, for the tetragonal phase. As for the cubic phase, the ac conduction dynamics appear to be metallic-like, which seems to change to a polaronic-controlled charge transport to increased dc bias electric fields.
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Curcumin is an anti-inflammatory and antioxidant compound with potent neuroprotective activity. Due to its poor water solubility, low bioavailability, rapid elimination and the challenges for crossing and transposing the blood-brain barrier (BBB), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with curcumin were successfully produced and functionalized with transferrin, in order to mediate the transport of these particles through the BBB endothelium to the brain. The nanosystems revealed Z-averages under 200 nm, polydispersity index below 0.2 and zeta potential around -30 mV. Curcumin encapsulation around 65 % for SLNs and 80 % for NLCs was accomplished, while the functionalized nanoparticles presented a value around 70-75 %. A stability study revealed these characteristics remained unchanged for at least 3 months. hCMEC/D3 cells viability was firstly analysed by MTT and LDH assays, respectively, and a concentration of 10 µM of curcumin-loaded nanoparticles were then selected for the subsequent permeability assay. The permeability study was conducted using transwell devices with hCMEC/D3 cells monolayers and a 1.5-fold higher permeation of curcumin through the BBB was verified. Both SLNs and NLCs are promising for curcumin brain delivery, protecting the incorporated curcumin and targeting to the brain by the addition of transferrin to the nanoparticles surface.
Subject(s)
Curcumin , Nanoparticles , Brain , Drug Carriers , Lipids , Particle Size , TransferrinABSTRACT
Tropical forests are experiencing increasing impacts from a multitude of anthropogenic activities such as logging and conversion to agricultural use. These perturbations are expected to have strong impacts on ecological interactions and on the transmission dynamics of infectious diseases. To date, no clear picture of the effects of deforestation on vector-borne disease transmission has emerged. This is associated with the challenge of studying complex systems where many vertebrate hosts and vectors co-exist. To overcome this problem, we focused on an innately simplified system - a small oceanic island (São Tomé, Gulf of Guinea). We analyzed the impacts of human land-use on host-parasite interactions by sampling the bird community (1735 samples from 30 species) in natural and anthropogenic land use at different elevations, and screened individuals for haemosporidian parasites from three genera (Plasmodium, Haemoproteus, Leucocytozoon). Overall, Plasmodium had the highest richness but the lowest prevalence, while Leucocytozoon diversity was the lowest despite having the highest prevalence. Interestingly, co-infections (i.e. intra-host diversity) involved primarily Leucocytozoon lineages (95%). We also found marked differences between bird species and habitats. Some bird species showed low prevalence but harbored high diversity of parasites, while others showed high prevalence but were infected with fewer lineages. These infection dynamics are most likely driven by host specificity of parasites and intrinsic characteristics of hosts. In addition, Plasmodium was more abundant in disturbed habitats and at lower elevations, while Leucocytozoon was more prevalent in forest areas and at higher elevations. These results likely reflect the ecological requirements of their vectors: mosquitoes and black flies, respectively.
Subject(s)
Bird Diseases , Coinfection , Haemosporida , Parasites , Plasmodium , Animals , Bird Diseases/epidemiology , Coinfection/epidemiology , Host Specificity , Humans , Mosquito Vectors , PrevalenceABSTRACT
The treatment with anticancer drugs remains a challenge, as available drugs still entail the risk of deleterious off-target effects. The present study describes folic acid conjugated nanostructured lipid carriers (NLCs) as an effective doxorubicin delivery approach targeted to breast cancer cells. Two distinct NLCs formulations were designed and optimized leading to an encapsulation efficiency over than 65%. Cytotoxic and targeting potential of NLCs were studied in vitro, using MDA-MB-231 cell line. Results showed an enhanced cellular uptake of conjugated NLCs. In vitro release studies, mimicking the path in the body after oral administration, show that all formulations would reach the tumor microenvironment bearing 50% of the encapsulated doxorubicin. Moreover, NLCs demonstrated storage stability at 25 °C for at least 42 days. Overall, results revealed that the developed NLCs enable the possibility of oral administration and are a promising approach for the targeted delivery of doxorubicin to breast cancer cells.
Subject(s)
Antineoplastic Agents , Nanostructures , Doxorubicin , Drug Carriers , Drug Delivery Systems , Lipids , Particle SizeABSTRACT
PURPOSE: Lipid nanoparticles (SLN and NLC) were functionalized with the RVG29 peptide in order to target the brain and increase the neuronal uptake through the nicotinic acetylcholine receptors. These nanosystems were loaded with quercetin to take advantage of its neuroprotective properties mainly for Alzheimer's disease. METHODS: The functionalization of nanoparticles with RVG29 peptide was confirmed by NMR and FTIR. Their morphology was assessed by transmission electron microscopy and nanoparticles size, polydispersity and zeta potential were determined by dynamic light scattering. The in vitro validation tests were conducted in hCMEC/D3 cells, a human blood-brain barrier model and thioflavin T binding assay was conducted to assess the process of amyloid-beta peptide fibrillation typical of Alzheimer's disease. RESULTS: RVG29-nanoparticles displayed spherical morphology and size below 250 nm, which is compatible with brain applications. Zeta potential values were between -20 and -25 mV. Quercetin entrapment efficiency was generally higher than 80% and NLC nanoparticles were able to encapsulate up to 90%. The LDH assay showed that there is no cytotoxicity in hCMEC/D3 cell line and RVG29-nanoparticles clearly increased in 1.5-fold the permeability across the in vitro model of blood-brain barrier after 4 h of incubation compared with non-functionalized nanoparticles. Finally, this nanosystem was capable of inhibiting amyloid-beta aggregation in thioflavin T binding assay, suggesting its great potential for neuroprotection. CONCLUSIONS: RVG29-nanoparticles that simultaneously target the blood-brain barrier and induce neurons protection against amyloid-beta fibrillation proved to be an efficient way of quercetin delivery and a promising strategy for future approaches in Alzheimer's disease. Graphical Abstract.
Subject(s)
Alzheimer Disease/drug therapy , Antigens, Viral/metabolism , Brain/metabolism , Lipids/chemistry , Neuroprotective Agents/metabolism , Peptide Fragments/metabolism , Quercetin/metabolism , Viral Envelope Proteins/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Antigens, Viral/chemistry , Blood-Brain Barrier/metabolism , Brain/drug effects , Brain/pathology , Capillary Permeability , Cell Line , Drug Compounding , Humans , Liposomes , Nanoparticles , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/chemistry , Peptide Fragments/chemistry , Protein Aggregates , Protein Aggregation, Pathological , Quercetin/administration & dosage , Quercetin/chemistry , Receptors, Nicotinic/metabolism , Tissue Distribution , Viral Envelope Proteins/chemistryABSTRACT
Quercetin was encapsulated in lipid nanoparticles (SLN and NLC) to take advantage of its neuroprotective properties in Alzheimer's disease. The nanoparticles were functionalized with transferrin to facilitate the passage across the blood-brain barrier through the transferrin receptors overexpressed in brain endothelial cells. NMR and FTIR confirmed the functionalization of the nanoparticles with transferrin. TEM results showed all nanoparticles presented spherical morphology. Nanoparticles exhibited size around 200 nm and zeta potential values higher than -30 mV. Quercetin entrapment efficiency was around 80-90%. LDH cytotoxicity assays in hCMEC/D3 cell line demonstrated that even for the highest concentration (30 µM) nanoparticles did not reveal cytotoxicity after 4 h of incubation. Permeability studies across hCMEC/D3 cell monolayers showed NLC permeate more the blood-brain barrier, while amyloid-beta studies demonstrated NLC-transferrin have the capacity to inhibit fibril formation. Nanoparticles seem to be suitable for brain applications, mainly for Alzheimer's disease due to inhibition of amyloid-beta aggregation.
Subject(s)
Alzheimer Disease/drug therapy , Drug Delivery Systems/methods , Nanoparticles/chemistry , Quercetin/administration & dosage , Amyloid beta-Peptides , Blood-Brain Barrier/metabolism , Brain/metabolism , Cell Line , Cell Survival , Drug Carriers/chemistry , Endothelial Cells/metabolism , Humans , Lipids/chemistry , Particle Size , Quercetin/metabolism , Transferrin/chemistryABSTRACT
This work describes the application of an experimental design in optimizing the decomposition and spectrometer operational conditions for analysis of fish feeds. The content of 22 elements (six macroelements, four microelements and eleven trace elements) in feeds for fishes (ornamental and for human consumption) was determined by inductively coupled plasma (ICP)-based methods. Limits of quantification were obtained and the values ranged between 0.02â¯mgâ¯kg-1 (Cd) and 76â¯mgâ¯kg-1 (Al). Evaluation of the methods was achieved through analysis of standard reference material, Oyster Tissue (NIST 1566b) and Tea (NCS DC 73351). Element concentrations in feed samples for ornamental fish ranged from <0.02â¯mgâ¯kg-1 (Cd) to 2.79% (P) and for fish breeding for human consumption from <0.02â¯mgâ¯kg-1 (Cd) to 2.00% (Ca). The concentrations of the elements obtained in the analyzed fish feeds were within the limits established by Brazilian and American legislation for regulated elements.
Subject(s)
Animal Feed/analysis , Fishes , Mass Spectrometry/methods , Minerals/analysis , Animals , Aquaculture , Brazil , Humans , Limit of Detection , Phosphorus/analysis , Trace Elements/analysisABSTRACT
This study aimed to evaluate viral and bacterial contamination from typical Brazilian cheeses, such as Minas (fresh) and Prato (ripened), commercially obtained in the Greater Metropolitan Region of the State of Rio de Janeiro, Brazil. Minas [30], Prato [30] and sliced Prato [30] cheese samples were investigated for norovirus genogroup I and II (NoV GI-II) and human adenovirus (HAdV) by direct nucleic acid extraction using TRIzol and amplification by TaqMan based quantitative polymerase chain reaction. Listeria monocytogenes, Salmonella spp., coagulase-positive staphylococci (CPS) and fecal coliforms were also assessed by using standard counting methods. NoV GI and GII were detected in one sample (1.1%) each and HAdV in nine samples (10.0%) while bacteriological analysis revealed five samples (5.5%) contaminated with L. monocytogenes, 27 (30.0%) with fecal coliforms and 10 (11.1%) with CPS. Salmonella spp. was not detected in any sample. Viruses were detected in 11 samples (12.2%), of which 9 met the microbiological criteria used to evaluate the microbiological quality of the cheeses, stressing the importance of considering virological parameters for monitoring this food matrix.
Subject(s)
Adenoviridae/isolation & purification , Bacteria/classification , Bacteria/isolation & purification , Cheese/microbiology , Cheese/virology , Norovirus/isolation & purification , Adenoviridae/classification , Adenoviridae/genetics , Bacterial Load , Brazil , DNA, Viral/genetics , DNA, Viral/isolation & purification , Food Contamination , Humans , Norovirus/classification , Norovirus/genetics , RNA, Viral/genetics , RNA, Viral/isolation & purification , Real-Time Polymerase Chain ReactionABSTRACT
An adapted methodology for obtaining lipid nanoparticles that only uses the microwave reactor in the synthesis process was developed. The method has the following features: one-pot, one-step, fast, practical, economical, safe, readiness of scaling-up, lack of organic solvents and production of nanoparticles with low polydispersity index (PDI) (below 0.3). This new method was applied for the development of nanostructured lipid carriers (NLC) loaded with a hydrophilic drug, the antiretroviral agent zidovudine (AZT). The aim of the present work was to develop, evaluate and compare optimized NLC formulations produced by two different methods - hot ultrasonication and microwave-assisted method. The development and optimization of the NLC formulations were supported by a Quality by Design (QbD) approach. All formulations were physicochemically characterized by the same parameters. The optimized formulations presented a suitable profile for oral administration (particle size between 100 and 300â¯nm, PDIâ¯<â¯0.3 and negative zeta potential >-20â¯mV). Furthermore, the morphologies assessed by TEM showed spherical shape and confirmed the results obtained by DLS. Both AZT loaded formulations were physically stable for at least 45â¯days and non-toxic on Jurkat T cells. Drug release studies showed a controlled release of AZT under gastric and plasma-simulated conditions.
Subject(s)
Anti-HIV Agents/chemistry , Drug Carriers/chemistry , Microwaves , Nanostructures/chemistry , Zidovudine/chemistry , Anti-HIV Agents/administration & dosage , Cell Survival/drug effects , Diglycerides/administration & dosage , Diglycerides/chemistry , Drug Carriers/administration & dosage , Drug Compounding , Drug Liberation , Drug Stability , Emulsions , Humans , Jurkat Cells , Nanostructures/administration & dosage , Sonication , Triglycerides/administration & dosage , Triglycerides/chemistry , Zidovudine/administration & dosageABSTRACT
The population of Brazil is highly admixed, with each individual showing variable levels of Amerindian, European and African ancestry, which may interfere in the genetic susceptibility of known risk loci to nonsyndromic cleft lip with or without cleft palate (NSCL±P). Here, we investigated 5 reported genome-wide loci for NSCL±P in an ancestry-structured case-control study containing 1697 Brazilian participants (831 NSCL±P and 866 healthy controls). SNPs rs7552 in 2q24.2, rs8049367 in 16p13.3, rs1880646, rs7406226, rs9891446 in 17p13, rs1588366 in 17q23.2 and rs73039426 in 19q13.11 were genotyped using TaqMan allelic discrimination assays and genomic ancestry was estimated using a panel of 40 biallelic short insertion/deletion polymorphic markers informative of the Brazilian population. Logistic regression analysis of the single-markers revealed rs7552 in 2p24.2 as a susceptibility risk marker for NSCL±P, yielding an odds ratio (OR) of 1.71 (95% confidence interval (CI): 1.31-2.24, P = 9 × 10-6 ) in the homozygous state. Several SNP-SNP interactions containing rs7552 reached significance after adjustment for multiple tests (both Bonferroni assumption and 1000 permutation test), with the most significant interaction involving the 3-loci among rs7552, rs9891446 and rs73039426 (P = 6.1 × 10-9 and p1000 permutation = 0.001). Our study is the first to support the association of rs7552 in 2p24.2 with NSCL±P in the highly admixed Brazilian population.
Subject(s)
Cleft Lip/complications , Cleft Lip/genetics , Cleft Palate/complications , Cleft Palate/genetics , Genetic Loci , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Adolescent , Brazil , Epistasis, Genetic , Humans , Multifactor Dimensionality ReductionABSTRACT
We aimed to compare the effects of ground (GC) or cracked corn (CC), with or without flaxseed oil (FSO), on milk yield, milk and plasma fatty acid (FA) profile, and nutrient digestibility in Jersey cows fed diets formulated to contain similar starch concentrations. Twelve multiparous organic-certified Jersey cows averaging (mean ± standard deviation) 455 ± 41.9 kg of body weight and 152 ± 34 d in milk and 4 primiparous organic-certified Jersey cows averaging (mean ± standard deviation) 356 ± 2.41 kg of body weight and 174 ± 30 d in milk in the beginning of the experiment were used. Cows were randomly assigned to treatment sequences in a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Each period lasted 24 d with 18 d for diet adaptation and 6 d for data and sample collection. Treatments were fed as total mixed rations consisting of (dry matter basis): (1) 0% FSO + 27.1% GC, (2) 0% FSO + 28.3% CC, (3) 3% FSO + 27.1% GC, and (4) 3% FSO + 28.3% CC. All cows were offered 55% of the total diet dry matter as mixed grass-legume baleage and treatments averaged 20% starch. Significant FSO × corn grain particle size interactions were observed for some variables including milk concentration of lactose and proportions of cis-9,cis-12,cis-15 18:3 in milk and plasma. The proportion of cis-9,cis-12,cis-15 18:3 in milk and plasma decreased slightly when comparing GC versus CC in 0% FSO cows, but a larger reduction was observed in 3% FSO cows. Dry matter intake did not differ and averaged 16.1 kg/d across diets. Feeding 3% FSO increased yields of milk and milk fat and lactose and feed and milk N efficiencies, but decreased fat, true protein, and MUN concentrations and apparent total-tract digestibility of fiber. The Σ branched-chain, Σ<16C, Σ16C, and Σn-6 FA decreased, whereas Σ18C, Σcis-18:1, and Σtrans-18:1 FA increased in 3% versus 0% FSO cows. No effect of corn particle size was observed for production and milk components. However, the apparent total-tract digestibility of starch was greater in GC than CC cows. Compared with CC, GC increased Σ branched-chain, Σ<16C, Σ16C, Σn-6 FA, and decreased Σ18C and Σ cis-18:1 FA in milk fat. Overall, results of this study are more directly applicable to dairy cows fed low starch, mixed grass-legume baleage-based diets.
Subject(s)
Animal Feed/analysis , Cattle/physiology , Digestion , Linseed Oil/chemistry , Milk/chemistry , Milk/metabolism , Zea mays/chemistry , Animals , Diet/veterinary , Fatty Acids/analysis , Fatty Acids/blood , Female , Lactation , Particle Size , Random Allocation , Starch/metabolismABSTRACT
OBJECTIVE: Preterm birth (PTB) is associated with excess maternal cardiovascular disease risk. We considered that women with PTB and placental evidence of maternal malperfusion would be particularly affected. DESIGN: Pregnancy cohort study. SETTING: Pittsburgh, PA, USA. POPULATION: Women with PTB (n = 115) and term births (n = 210) evaluated 4-12 years after pregnancy. METHODS: Cardiometabolic risk markers were compared in women with prior PTB versus term births; pre-eclampsia and growth restriction cases were excluded. Placental evidence of maternal vascular malperfusion (vasculopathy, infarct, advanced villous maturation, perivillous fibrin, intervillous fibrin deposition), acute infection/inflammation (chorioamnionitis, funisitis, deciduitus) and villitis of unknown aetiology (chronic inflammation) was used to classify PTBs. MAIN OUTCOME MEASURES: Carotid artery intima-media thickness (IMT), fasting lipids, blood pressure (BP) and inflammatory markers measured after delivery. RESULTS: Women with PTB and malperfusion lesions had higher total cholesterol (+13.5 mg/dl) and systolic BP (+4.0 mmHg) at follow up compared with women with term births, accounting for age, race, pre-pregnancy BMI, and smoking (P < 0.05). Women with PTB and malperfusion accompanied by inflammatory lesions had the most atherogenic profile after pregnancy (cholesterol +18.7, apolipoprotein B + 12.7 mg/dl; all P < 0.05), adjusted for pre-pregnancy features. Carotid IMT was higher in this group (+0.037 cm, P = 0.031) accounting for pre-pregnancy factors; differences were attenuated after adjusting for BP and atherogenic lipids at follow up (+0.027, P = 0.095). CONCLUSION: PTBs with placental malperfusion were associated with an excess maternal cardiometabolic risk burden in the decade after pregnancy. The placenta may offer insight into subtypes of PTB related to maternal cardiovascular disease. TWEETABLE ABSTRACT: Preterm births with placental malperfusion may mark women at higher cardiovascular disease risk.
Subject(s)
Cardiovascular Diseases/etiology , Placenta/blood supply , Premature Birth/physiopathology , Reperfusion Injury/complications , Adult , Blood Pressure , Carotid Intima-Media Thickness , Female , Humans , Postpartum Period , Pregnancy , Premature Birth/etiology , Prospective Studies , Risk FactorsABSTRACT
The objective of this study was to compare the effects of ground corn or liquid molasses fed as the sole supplemental nonstructural carbohydrate (NSC) source on production performance, milk fatty acid (FA) profile, grazing behavior, and N metabolism in grazing dairy cows. A strip-grazing management system was used, with cows offered a new strip of fresh herbage after each milking, resulting in approximately 16 h of access to pasture daily. Animals were fed a diet formulated to yield an 86:14 forage-to-concentrate ratio consisting [dry matter (DM) basis] of 74% mixed grass-legume herbage, 12% mixed-mostly legume baleage, 12% NSC source, and 2% mineral-vitamin premix. Twenty Jersey cows averaging (mean ± standard deviation) 121 ± 73 d in milk in the beginning of the study were randomly assigned to 1 of 2 herbage supplementation treatments: (1) baleage plus ground corn (B+GC) or (2) baleage + liquid molasses (B+LM). Both NSC sources were fed at a flat rate of 1.6 kg of DM/cow daily. The study lasted from June to September for a total of 15 wk with data and sample collection conducted in wk 3, 7, 12, and 15. Milk samples for FA analysis were collected in wk 2, 4, 6, 8, 9, 11, and 13. Data were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC) for a randomized complete block design with repeated measures over time. Treatment × week interactions were observed for supplement DM intake, milk urea N, bite rate, urinary excretion of uric acid, and milk FA (e.g., 17:0, 18:0, cis-9,trans-11 18:2). Supplement DM intake was greatest in cows fed B+LM in wk 7, 12, and 15. Compared with cows fed B+GC, those fed B+LM had lower concentrations of milk urea N in wk 7 and 15. Milk yield, concentrations and yields of milk components, and plasma concentrations of essential AA, except Met, which was lowest with feeding B+LM, were not affected by supplementation. The plasma concentration of urea N was lowest with feeding B+LM. Cows fed B+GC spent more time grazing than those fed B+LM. Feeding B+GC increased cis-9 18:1 FA and most trans-18:1 FA in milk, whereas B+LM increased Σ odd-chain FA, Σ n-3 FA, and the trans-11 18:1 to trans-10 18:1 ratio, and decreased the n-6 to n-3 ratio. Based on current results, B+LM can entirely replace B+GC without negatively affecting milk yield or yields and concentrations of milk fat and true protein, while decreasing milk urea N, plasma urea N, and the milk trans-11 18:1 to trans-10 18:1 ratio, and increasing Σ n-3 FA.
Subject(s)
Animal Feed , Dietary Carbohydrates/administration & dosage , Fatty Acids/analysis , Milk/chemistry , Molasses , Zea mays , Animals , Cattle , Diet/veterinary , Dietary Carbohydrates/metabolism , Female , Lactation , Milk/metabolism , Random AllocationABSTRACT
Previous research has shown that cows fed ≥24% of the diet dry matter (DM) as field peas decreased milk yield as well as concentration and yield of milk protein, possibly due to reduced DM intake and limited supply of Lys and Met. Twelve multiparous and 4 primiparous lactating Holstein cows were randomly assigned to 1 of 4 diets in a replicated 4 × 4 Latin square design. The diets contained (DM basis) 34.8% corn silage, 15.2% grass-legume silage, 5.9% roasted soybean, 2.4% mineral-vitamin premix, 2.0% alfalfa pellets, and either (1) 36% ground corn, 2.4% soybean meal, and 1.3% urea (UR), (2) 29.7% ground corn, 9.8% soybean meal, 0.13% ruminally protected (RP) Lys, and 0.07% RP-Met (CSBAA), (3) 25% ground field peas, 12.3% ground corn, and 2.4% soybean meal (FP), or (4) FP supplemented with 0.15% RP-Lys and 0.05% RP-Met (FPAA). Our objective was to test the effects of FP versus UR, FPAA versus CSBAA, and FPAA versus FP on milk yield and composition, N utilization, nutrient digestibility, ruminal fermentation profile, and plasma concentration of AA. Milk yield did not differ across diets. Compared with cows fed UR, those fed FP had greater DM intake, concentration and yield of milk true protein, apparent total-tract digestibility of fiber, urinary excretion of purine derivatives, and concentrations of total volatile fatty acids in the rumen and Lys in plasma, and less milk urea N and ruminal NH3-N. The concentration of milk urea N, as well as the concentration and yield of milk fat increased in cows fed FPAA versus CSBAA. Moreover, cows fed FPAA had greater ruminal concentration of total volatile fatty acids, increased proportions of acetate and isobutyrate, and decreased proportions of propionate and valerate than those fed CSBAA. The plasma concentrations of His, Leu, and Phe decreased, whereas plasma Met increased and plasma Lys tended to increase in cows fed FPAA versus CSBAA. Concentration of milk true protein, but not yield, was increased in cows fed FPAA versus FP. However, cows fed FPAA showed decreased concentrations of His and Leu in plasma compared with those fed FP. Overall, compared with the CSBAA diet, feeding FPAA did not negatively affect milk yield and milk protein synthesis. Furthermore, RP-Lys and RP-Met supplementation of the FP diet did not improve milk yield or milk protein synthesis, but decreased urinary urea N excretion.