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BACKGROUND: Social inequalities in adult mortality have been reported across diverse populations, but there is no large-scale prospective evidence from Mexico. We aimed to quantify social, including educational, inequalities in mortality among adults in Mexico City. METHODS: The Mexico City Prospective Study recruited 150â000 adults aged 35 years and older from two districts of Mexico City between 1998 and 2004. Participants were followed up until Jan 1, 2021 for cause-specific mortality. Cox regression analysis yielded rate ratios (RRs) for death at ages 35-74 years associated with education and examined, in exploratory analyses, the mediating effects of lifestyle and related risk factors. FINDINGS: Among 143â478 participants aged 35-74 years, there was a strong inverse association of education with premature death. Compared with participants with tertiary education, after adjustment for age and sex, those with no education had about twice the mortality rate (RR 1·84; 95% CI 1·71-1·98), equivalent to approximately 6 years lower life expectancy, with an RR of 1·78 (1·67-1·90) among participants with incomplete primary, 1·62 (1·53-1·72) with complete primary, and 1·34 (1·25-1·42) with secondary education. Education was most strongly associated with death from renal disease and acute diabetic crises (RR 3·65; 95% CI 3·05-4·38 for no education vs tertiary education) and from infectious diseases (2·67; 2·00-3·56), but there was an apparent higher rate of death from all specific causes studied with lower education, with the exception of cancer for which there was little association. Lifestyle factors (ie, smoking, alcohol drinking, and leisure time physical activity) and related physiological correlates (ie, adiposity, diabetes, and blood pressure) accounted for about four-fifths of the association of education with premature mortality. INTERPRETATION: In this Mexican population there were marked educational inequalities in premature adult mortality, which appeared to largely be accounted for by lifestyle and related risk factors. Effective interventions to reduce these risk factors could reduce inequalities and have a major impact on premature mortality. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council Population Health Research Unit.
Subject(s)
Mortality, Premature , Adult , Humans , Prospective Studies , Cause of Death , Mexico/epidemiology , Educational StatusABSTRACT
INTRODUCTION: Although higher risks of infectious diseases among individuals with diabetes have long been recognized, the magnitude of these risks is poorly described, particularly in lower income settings. This study sought to assess the risk of death from infection associated with diabetes in Mexico. RESEARCH DESIGN AND METHODS: Between 1998 and 2004, a total of 159 755 adults ≥35 years were recruited from Mexico City and followed up until January 2021 for cause-specific mortality. Cox regression yielded adjusted rate ratios (RR) for death due to infection associated with previously diagnosed and undiagnosed (HbA1c ≥6.5%) diabetes and, among participants with previously diagnosed diabetes, with duration of diabetes and with HbA1c. RESULTS: Among 130 997 participants aged 35-74 and without other prior chronic diseases at recruitment, 12.3% had previously diagnosed diabetes, with a mean (SD) HbA1c of 9.1% (2.5%), and 4.9% had undiagnosed diabetes. During 2.1 million person-years of follow-up, 2030 deaths due to infectious causes were recorded at ages 35-74. Previously diagnosed diabetes was associated with an RR for death from infection of 4.48 (95% CI 4.05-4.95), compared with participants without diabetes, with notably strong associations with death from urinary tract (9.68 (7.07-13.3)) and skin, bone and connective tissue (9.19 (5.92-14.3)) infections and septicemia (8.37 (5.97-11.7)). In those with previously diagnosed diabetes, longer diabetes duration (1.03 (1.02-1.05) per 1 year) and higher HbA1c (1.12 (1.08-1.15) per 1.0%) were independently associated with higher risk of death due to infection. Even among participants with undiagnosed diabetes, the risk of death due to infection was nearly treble the risk of those without diabetes (2.69 (2.31-3.13)). CONCLUSIONS: In this study of Mexican adults, diabetes was common, frequently poorly controlled, and associated with much higher risks of death due to infection than observed previously, accounting for approximately one-third of all premature mortality due to infection.
Subject(s)
Communicable Diseases , Diabetes Mellitus , Adult , Humans , Mexico/epidemiology , Glycated Hemoglobin , Diabetes Mellitus/epidemiology , Time Factors , Communicable Diseases/epidemiologyABSTRACT
Background Body-mass index is the sum of fat mass index (FMI) and lean mass index (LMI), which vary by age, sex, and impact on disease outcomes. We investigated the separate and joint relevance of FMI and LMI with vascular-metabolic causes of death in Mexican adults. Methods and Results A total of 113 025 adults aged 35 to 74 years and free from diabetes or other chronic diseases when recruited into the Mexico City Prospective Study were followed for 19 years. Cox models estimated sex-specific death rate ratios from vascular-metabolic causes after adjustment for confounders and exclusion of the first 5 years of follow-up. To account for the strong correlation between FMI and LMI, additional models estimated rate ratios associated with "residual FMI" and "residual LMI" (ie, the residuals from linear regression analyses of FMI on LMI, or vice versa). In both sexes, higher FMI and LMI were associated with higher risks of vascular-metabolic mortality. For a given (ie, fixed) level of LMI, the rate ratio (95% CI) for vascular-metabolic mortality per 1 kg/m2 higher residual FMI strengthened and was higher in women (1.52 [1.38-1.68]) than in men (1.19 [1.13-1.25]). By contrast, for a given level of FMI, higher residual LMI was inversely associated with vascular-metabolic mortality (rate ratio per 1 kg/m2 0.67 [0.56-0.80] in women and 0.94 [0.90-0.98] in men). Conclusions In this study, higher residual FMI was more strongly associated with vascular-metabolic mortality in women than in men. Conversely, higher residual LMI was inversely associated with vascular-metabolic mortality, particularly in women.
Subject(s)
Body Composition , Adult , Male , Humans , Female , Prospective Studies , Mexico/epidemiology , Body Mass Index , Chronic DiseaseABSTRACT
Introduction: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop coronavirus disease 2019 (COVID-19). Risk factors associated with death vary among countries with different ethnic backgrounds. We aimed to describe the factors associated with death in Mexicans with confirmed COVID-19. Material and methods: We analysed the Mexican Ministry of Health's official database on people tested for SARS-CoV-2 infection by real-time reverse transcriptase-polymerase chain reaction (rtRT-PCR) of nasopharyngeal fluids. Bivariate analyses were performed to select characteristics potentially associated with death, to integrate a Cox-proportional hazards model. Results: As of May 18, 2020, a total of 177,133 persons (90,586 men and 86,551 women) in Mexico received rtRT-PCR testing for SARS-CoV-2. There were 5332 deaths among the 51,633 rtRT-PCR-confirmed cases (10.33%, 95% CI: 10.07-10.59%). The median time (interquartile range, IQR) from symptoms onset to death was 9 days (5-13 days), and from hospital admission to death 4 days (2-8 days). The analysis by age groups revealed that the significant risk of death started gradually at the age of 40 years. Independent death risk factors were obesity, hypertension, male sex, indigenous ethnicity, diabetes, chronic kidney disease, immunosuppression, chronic obstructive pulmonary disease, age > 40 years, and the need for invasive mechanical ventilation (IMV). Only 1959 (3.8%) cases received IMV, of whom 1893 were admitted to the intensive care unit (96.6% of those who received IMV). Conclusions: In Mexico, highly prevalent chronic diseases are risk factors for death among persons with COVID-19. Indigenous ethnicity is a poorly studied factor that needs more investigation.
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Barriers to mental healthcare services are reported among military service members. However, little is known about these barriers among the spouses of military personnel, who face unique stressors and may subsequently be at high-need for mental health services. Understanding barriers to care among this vulnerable population may help improve access to psychological services. The current study utilized data from the Millennium Cohort Family Study. Participants were referred by their military spouses or through targeted mailers. Participants completed self-report measures of mood, psychosocial functioning, and perceived barriers to mental healthcare via web- or paper-based surveys. A factor analysis was conducted to identify subscales of the barriers to mental healthcare measure, and logistic regressions were conducted adjusting for relevant sociodemographic variables, to determine psychosocial factors associated with likelihood of reporting barriers to mental healthcare. The sample comprised 9,666 military spouses (86% female; Mage: 27.73 ± 5.09; 29.2% racial/ethnic minority; 19.5% with prior/current military service). Logistic factors were the most frequently reported barrier to care (63%), followed by negative beliefs about mental healthcare (52%), fear of social/occupational consequences (35%), and internalized stigma (32%). Spouses with prior or current military service themselves and individuals with a psychiatric condition were most likely to report barriers to mental healthcare. A preponderance of military spouses reported barriers to mental healthcare services. Prospective data are needed to elucidate the associations between barriers to care and mental healthcare utilization. Efforts may be warranted to improve access to mental healthcare among the spouses of military personnel. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Subject(s)
Mental Health Services , Military Personnel , Ethnicity , Female , Humans , Male , Military Personnel/psychology , Minority Groups , Prospective Studies , Spouses/psychologyABSTRACT
Plant extracts are known for their high content and diversity of polyphenols, which can improve fish oxidative status. A growth trial with Senegalese sole postlarvae (45 days after hatching) fed with one of four experimental diets-control (CTRL), and supplemented with curcumin (CC), green tea (GT), and grape seed (GS) extracts-was performed to assess if supplementation could improve growth performance and oxidative status. At the end of the growth trial, postlarvae were submitted to a thermal stress to assess their robustness. Sole growth was improved by CC and GS diets when compared to those fed the CTRL. CC and CTRL postlarvae presented the lowest oxidative damage (lipid peroxidation and protein carbonylation values). Stress-related biomarkers (heat shock protein 70 and glutathione-S-transferase) decreased in CC fish compared to those fed the CTRL diet, which might be due to a direct antioxidant capacity. In contrast, oxidative damage increased in GT and GS sole reared in standard conditions. However, after a thermal stress, GT and GS diets prevented the increase of protein carbonylation content and the decrease of antioxidant glutathione, depending on exposure time. Overall, dietary supplementation with natural extracts modulated oxidative status and stress response after a short/long-term exposure to temperature.
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BACKGROUND: Estimates suggest approximately 2.4% of service members, and 15% of service members who have engaged in recent combat, report misusing pain relievers in the past year. This study explores the extent to which military spouses' obtainment of opioids is associated with their service member partners' obtainment of opioid prescriptions, in addition to other factors such as service member health, state prescribing patterns, and sociodemographic characteristics. METHODS: Data were drawn from the Millennium Cohort Family Study, a large, longitudinal survey of married spouses of service members from all service branches, and archival data analyzed from 2018 to 2020. The dependent variables were spouse long-term opioid therapy and spouse opioid prescriptions that pose a high risk of adverse outcomes. RESULTS: Seven percent of spouse and service member dyads met the criteria for high-risk opioid use, generally because they had purchased a prescription for a ≥90 Morphine Milligram Equivalents daily dose (76.7% for spouses, 72.8% for service members). Strong associations were found between spouse and service member opioid therapies (OR = 5.53 for long-term; OR = 2.20 for high-risk). CONCLUSIONS: Findings suggest that reducing the number of long-term and high-risk opioid prescriptions to service members may subsequently reduce the number of similar prescriptions obtained by their spouses. Reducing the number of service members and spouses at risk for adverse events may prove to be effective in stemming the opioid epidemic and improve the overall health and safety of military spouses and thus, the readiness of the U.S. Armed Forces.
ABSTRACT
Military operations in Iraq and Afghanistan have brought increased attention to posttraumatic stress disorder (PTSD) among service members and, more recently, its impact on spouses. Existing research has demonstrated that PTSD among service members is associated with depression among military spouses. In the current study, we extended these findings by using data from service member-spouse dyads enrolled in the Millennium Cohort Family Study for which the service member had evidence of PTSD (n = 563). Prospective analyses identified the association between PTSD symptom clusters reported by the service member and new-onset depression among military spouses. Over the 3-year study period, 14.4% of these military spouses met the criteria for new-onset depression. In adjusted models, service member ratings of symptoms in the effortful avoidance cluster, odds ratio (OR) = 1.61, 95% CI [1.03, 2.50], predicted an increased risk of new-onset depression among military spouses, whereas reexperiencing symptoms, adjusted OR = 0.57; 95% CI [0.32, 1.01], were marginally protective. These findings suggest that PTSD symptom clusters in service members differentially predict new-onset depression in military spouses, which has implications for treatment provision.
Subject(s)
Depression/epidemiology , Military Family/psychology , Spouses/psychology , Stress Disorders, Post-Traumatic/diagnosis , Adult , Female , Humans , Male , Military Personnel/psychology , Prospective Studies , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Surveys and QuestionnairesABSTRACT
Somatic growth is a balance between protein synthesis and degradation, and it is largely influenced by nutritional clues. Antioxidants levels play a key role in protein turnover by reducing the oxidative damage in the skeletal muscle, and hence promoting growth performance in the long-term. In the present study, Senegalese sole postlarvae (45 days after hatching, DAH) were fed with three experimental diets, a control (CTRL) and two supplemented with natural antioxidants: curcumin (CC) and grape seed (GS). Trial spanned for 25 days and growth performance, muscle cellularity and the expression of muscle growth related genes were assessed at the end of the experiment (70 DAH). The diets CC and GS significantly improved growth performance of fish compared to the CTRL diet. This enhanced growth was associated with larger muscle cross sectional area, with fish fed CC being significantly different from those fed the CTRL. Sole fed the CC diet had the highest number of muscle fibers, indicating that this diet promoted muscle hyperplastic growth. Although the mean fiber diameter did not differ significantly amongst treatments, the proportion of large-sized fibers (>25 µm) was also higher in fish fed the CC diet suggesting increased hypertrophic growth. Such differences in the phenotype were associated with a significant up-regulation of the myogenic differentiation 2 (myod2) and the myomaker (mymk) transcripts involved in myocyte differentiation and fusion, respectively, during larval development. The inclusion of grape seed extract (GS diet) resulted in a significant increase in the expression of myostatin1. These results demonstrate that both diets (CC and GS) can positively modulate muscle development and promote growth in sole postlarvae. This effect is more prominent in CC fed fish, where increased hyperplastic and hypertrophic growth of the muscle was associated with an upregulation of myod2 and mymk genes.
ABSTRACT
Immunostimulants are key molecules in aquaculture since they heighten defensive responses and protection against pathogens. The present study investigated the treatment of Senegalese sole larvae with a whole-cell crude extract of the microalgae Nannochloropsis gaditana (Nanno) and programming of growth and the immune system. Larvae at hatch were treated with the Nanno extracts for 2 h and thereafter were cultivated for 32 days post-hatch (dph) in parallel with an untreated control group (CN). Dry weight and length at 21 days post-hatch (dph) were higher in post-larvae of the Nanno than CN group. These differences in weight were later confirmed at 32 dph. To evaluate changes in the immune response associated with Nanno-programming treatments, the Nanno and CN post-larvae were supplied with two bioactive compounds yeast ß-glucan (Y) and a microalga extract from the diatom Phaeodactylum tricornutum (MAe). The bioactive treatments were administrated to the treatment groups through the live prey (artemia metanauplii, 200 artemia mL-1) enriched for 30 min with MAe or Y (at 2 mg mL-1 SW) or untreated prey in the case of the negative control (SW). The effect of the treatments was assessed by monitoring gene expression, enzyme activity and mortality over 48 h. The post-larvae sole supplied with the bioactive compounds Y and MAe had increased mortality at 48 h compared to the SW group. Moreover, mortality was higher in Nanno-programmed than CN post-larvae. Lysozyme and total anti-protease enzymatic activities at 6 and 24 h after the start of the trial were significantly higher in the Nanno and MAe supplied post-larvae compared to their corresponding control (CN and SW, respectively). Immune gene transcripts revealed that il1b, cxc10 and mx mRNAs were significantly different between Nanno and CN post-larvae at 6 and 24 h. Moreover, the expression of il1b, tnfa, cxc10, irf3, irf7 and mx was modified by bioactive treatments but with temporal differences. At 48 h after bioactive treatments, Y and SW post-larvae were challenged with the lymphocystis disease virus (LCDV). No difference existed in viral copy number between programming or bioactive treatment groups at 3, 6 and 24 h after LCDV challenge although the total number of copies reduced with time. Gene expression profiles in the LCDV-challenged group indicated that post-larvae triggered a wide defensive response compared to SWC 24 h after challenge, which was modulated by programming and bioactive compound treatments. Cluster analysis of expressed genes separated the SW and Y groups indicating long-lasting effects of yeast ß-glucan treatment in larvae. A noteworthy interaction between Nanno-programming and Y-treatment on the regulation of antiviral genes was observed. Overall, the data demonstrate the capacity of microalgal crude extracts to modify sole larval plasticity with long-term effects on larval growth and the immune responses.
Subject(s)
DNA Virus Infections/veterinary , Fish Diseases/drug therapy , Flatfishes/immunology , Iridoviridae/physiology , Microalgae/chemistry , Animals , DNA Virus Infections/drug therapy , DNA Virus Infections/virology , Fish Diseases/virology , Flatfishes/growth & development , Iridoviridae/drug effects , Phytochemicals/administration & dosage , Random Allocation , Stramenopiles/chemistryABSTRACT
INTRODUCTION: The use and misuse of opioids by active service members has been examined in several studies, but little is known about their spouses' opioid use. This study estimates the number of military spouses who received high-risk or long-term opioid prescriptions between 2010 and 2014, and addresses how the Military Health System can help prevent risky prescribing in order to improve military force readiness. MATERIALS AND METHODS: This study used data from the Millennium Cohort Family Study, a nationwide survey of 9,872 spouses of service members with 2 to 5 years of military service, augmented with information from the military's Pharmacy Data Transaction Service about prescriptions for controlled drugs dispensed to these service members' spouses. Our objectives were to estimate the prevalence of opioid prescribing indicative of long-term use (≥60 day supply or at least one extended-release opioid prescription in any 3-month period) and, separately, high-risk use (daily dosage of ≥90 morphine mg equivalent or total dosage of ≥8,190 morphine mg equivalent, or prescriptions from more than three pharmacies, or concurrent prescriptions). For each of these dependent variables, we conducted bivariate analyses and multiple logistic regression models using information about spouses' physical health, sociodemographic characteristics, substance use behaviors, perceived social support, and stresses associated with military stress, among others. Informed consent, including consent to link survey responses to medical and personnel records, was obtained from all participants. The Naval Health Research Center's Institutional Review Board and the Office of Management and Budget approved the study. RESULTS: Spouses were predominantly female (86%), had not served in the military themselves (79%), and were spouses of enlisted (91%) active duty (86%) service members. Almost half (47.6%) of spouses obtained at least one opioid prescription during the 2-year observation window, and 8.5% had received opioid prescriptions that posed risk to their health. About 7% met the criteria for receipt of high-risk opioid prescriptions, 3% obtained opioids from three or more pharmacies during a 3-month period, and 4% of spouses who received any opioids received both long-term and high-risk prescriptions. Adverse childhood experiences, physical pain, and lack of social support were associated with increased odds of obtaining high-risk opioid prescriptions. CONCLUSIONS: Approximately 48% of military spouses had used Military Health System insurance to fill at least one opioid prescription during the 2-year observation period. The Department of Defense has taken measures to minimize high-risk opioid prescribing, including passing prescribing guidelines in 2017, establishing the controlled drug management analysis reporting tool, establishing a pain management education and training program, and more. These efforts should continue to expand as reducing the numbers of service members and spouses at risk for adverse events may be effective in reducing opioid misuse and improve the overall health and safety of military spouses and thus, the readiness of the U.S. Armed Forces.
Subject(s)
Analgesics, Opioid , Analgesics, Opioid/therapeutic use , Cohort Studies , Female , Humans , Male , Opioid-Related Disorders/drug therapy , Practice Patterns, Physicians' , SpousesABSTRACT
The hatching enzymes or choriolysins are key proteases in fish life cycle controlling the release of larvae to surrounding environment that have been suggested as target for novel biotechnological uses. Due to the large amounts of eggs released by the flatfish Solea senegalensis, during the spawning season, the hatching liquid properties and choriolysin-encoding genes were investigated in this species. A genomic analysis identified four putative genes referred to as SseHCEa, SseHCEb, SseLCE and SseHE. The phylogenetic analysis classified these paralogs into two clades, the clade I containing SseHCE paralogs and the clade II containing two well-supported subclades named as HE and LCE. The two SseHCE paralogs were intron-less and both genes were tandemly arrayed very close in the genome. The synteny and gene rearrangement identified in the flatfish lineage indicated that the duplication of these two paralogs occurred recently and they are under divergent evolution. The genes SseHE and SseLCE were structured in 8 exons and 7 introns and the synteny was conserved in teleosts. Expression studies confirmed that the four genes were expressed in the hatching gland cells and they migrate co-ordinately from the head to around the yolk sac close to the hatch with specific temporal and intensity expression profiles. Although the mRNA levels of the four genes peaked in the hours previous to larval hatching, the SseHCE and SseLCE paralogs kept a longer expression than SseHE after hatching. These expression patterns were consistent even when larvae were incubated at different temperatures that modified hatching times. The analysis of hatching-liquid using SDS-PAGE and zymography analyses of hatching liquid identified a major band of expected choriolysin size. The optimal pH for protease activity was 8.5 and inhibition assays using EDTA demonstrated that most of the activity in the hatching liquid was due to metalloproteases with Ca2+ ions acting as the most effective metal to restore the activity. All these data provide new clues about the choriolysin evolution and function in flatfish with impact in the aquaculture and the blue cosmetic industry.
Subject(s)
Evolution, Molecular , Flatfishes/metabolism , Metalloendopeptidases , Animals , Flatfishes/genetics , Gene Expression Regulation, Developmental , Larva/genetics , Metalloendopeptidases/classification , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism , Phylogeny , RNA, Messenger/geneticsABSTRACT
Pseudo-albinism is a pigmentation disorder observed in flatfish aquaculture with a complex, multi-factor aetiology. We tested the hypothesis that pigmentation abnormalities are an overt signal of more generalised modifications in tissue structure and function, using as a model the Senegalese sole and two important innate immune barriers, the skin and intestine, and their microbiomes. Stereological analyses in pseudo-albino sole revealed a significantly increased mucous cell number in skin (P < 0.001) and a significantly thicker muscle layer and lamina propria in gut (P < 0.001). RNA-seq transcriptome analysis of the skin and gut identified 573 differentially expressed transcripts (DETs, FDR < 0.05) between pseudo-albino and pigmented soles (one pool/tissue from 4 individuals/phenotype). DETs were mainly linked to pigment production, skin structure and regeneration and smooth muscle contraction. The microbiome (16 S rRNA analysis) was highly diverse in pigmented and pseudo-albino skin but in gut had low complexity and diverged between the two pigmentation phenotypes. Quantitative PCR revealed significantly lower loads of Mycoplasma (P < 0.05) and Vibrio bacteria (P < 0.01) in pseudo-albino compared to the control. The study revealed that pseudo-albinism in addition to pigmentation changes was associated with generalised changes in the skin and gut structure and a modification in the gut microbiome.
Subject(s)
Albinism/genetics , Flatfishes/genetics , Animals , Computational Biology/methods , Flatfishes/metabolism , Gastrointestinal Microbiome/genetics , Gene Expression Profiling/methods , Intestines/microbiology , Metagenomics/methods , Microbiota/genetics , Skin/microbiology , Transcriptome/geneticsABSTRACT
Background: Some reports suggest that body mass index (BMI) is not strongly associated with mortality in Hispanic populations. Objective: To assess the causal relevance of adiposity to mortality in Mexican adults, avoiding reverse causality biases. Design: Prospective study. Setting: 2 Mexico City districts. Participants: 159 755 adults aged 35 years and older at recruitment, followed for up to 14 years. Participants with a hemoglobin A1c level of 7% or greater, diabetes, or other chronic diseases were excluded. Measurements: BMI, waist-to-hip ratio, waist circumference, and cause-specific mortality. Cox regression, adjusted for confounders, yielded mortality hazard ratios (HRs) after at least 5 years of follow-up and before age 75 years. Results: Among 115 400 participants aged 35 to <75 years at recruitment, mean BMI was 28.0 kg/m2 (SD, 4.1 kg/m2) in men and 29.6 kg/m2 (SD, 5.1 kg/m2) in women. The association of BMI at recruitment with all-cause mortality was J-shaped, with the minimum at 25 to <27.5 kg/m2. Above 25 kg/m2, each 5-kg/m2 increase in BMI was associated with a 30% increase in all-cause mortality (HR, 1.30 [95% CI, 1.24 to 1.36]). This association was stronger at ages 40 to <60 years (HR, 1.40 [CI, 1.30 to 1.49]) than at ages 60 to <75 years (HR, 1.24 [CI, 1.17 to 1.31]) but was not materially affected by sex, smoking, or other confounders. The associations of mortality with BMI and waist-to-hip ratio were similarly strong, and each was weakened only slightly by adjustment for the other. Waist circumference was strongly related to mortality and remained so even after adjustment for BMI and hip circumference. Limitation: Analyses were limited to mortality. Conclusion: General, and particularly abdominal, adiposity were strongly associated with mortality in this Mexican population. Primary Funding Source: Mexican Health Ministry, Mexican National Council of Science and Technology, Wellcome Trust, Medical Research Council, and Kidney Research UK.
Subject(s)
Adiposity , Obesity, Abdominal/mortality , Adult , Aged , Body Mass Index , Female , Humans , Male , Mexico/epidemiology , Middle Aged , Obesity, Abdominal/epidemiology , Prospective Studies , Urban Population , Waist Circumference , Waist-Hip RatioABSTRACT
One bottleneck to sustainability of fish aquaculture is the control of infectious diseases. Current trends include the preventive application of immunostimulants and prebiotics such as polysaccharides. The present study investigated how yeast ß-glucan (Y), microalgal polysaccharide-enriched extracts (MAe) and whole Phaeodactylum tricornutum cells (MA) modulated the gut microbiome and stimulated the immune system in Senegalese sole (Solea senegalensis) when administered by oral intubation. Blood, intestine and spleen samples were taken at 3â¯h, 24â¯h, 48â¯h and 7 days after treatment. The short-term response (within 48â¯h after treatment) consisted of up-regulation of il1b and irf7 expression in the gut of the Y treated group. In contrast, administration of MAe decreased expression of tnfa and the chemokine cxc10 in the gut and spleen. Both treatments down-regulated the expression of irf3 with respect to the control group. Lysozyme activity in plasma decreased at 48â¯h only in the MAe-treated soles. Medium-term response consisted of the up-regulation of clec and irf7 expression in the gut of the Y, MAe and MA groups and of il1b mRNAs in the spleen of the MA group compared to the control group. Microbiome analysis using 16S rDNA gene sequencing indicated that the intestine microbiome was dominated by bacteria of the Vibrio genus (>95%). All the treatments decreased the relative proportion of Vibrio in the microbiome and Y and MAe decreased and MA increased diversity. Quantitative PCR confirmed the load of bacteria of the Vibrio genus was significantly decreased and this was most pronounced in Y treated fish. These data indicate that orally administrated insoluble yeast ß-glucans acted locally in the gut modulating the immune response and controlling the Vibrio abundance. In contrast, the MAe slightly reduced the Vibrio load in the intestine and caused a transient systemic anti-inflammatory response. The results indicate that these polysaccharides are a promising source of prebiotics for the sole aquaculture industry.
Subject(s)
Diatoms/chemistry , Flatfishes/immunology , Gastrointestinal Microbiome/drug effects , Immunity, Innate/drug effects , Prebiotics/administration & dosage , Yeast, Dried/metabolism , beta-Glucans/metabolism , Animal Feed/analysis , Animals , Diet/veterinary , Flatfishes/microbiology , Microalgae/chemistry , Random Allocation , Yeast, Dried/administration & dosage , beta-Glucans/administration & dosageABSTRACT
The horizontal transmission of lymphocystis disease virus (LCDV) through contaminated water and feed (using artemia as vehicle) and the associated immune gene expression profiles in Senegalese sole post-larvae were investigated. All specimens analyzed were positive for LCDV DNA detection at 1-day post-challenge (1 dpc) with the highest viral levels in specimens infected through the immersion route. However, the percentage of LCDV-positive animals and number of viral DNA copies dropped progressively at 2 and 7 dpc. The histological analysis identified structural changes in the skin, muscle and gills of sole post-larvae LCDV-challenged by immersion. In situ hybridization confirmed a wide distribution of LCDV in the skin, gut, surrounding vessels in trunk muscle and head kidney in the immersion route, while the signals were restricted to the liver and lamina propria in the feeding treatment. Expression analysis using a set of 22 genes related to innate immune defense system demonstrated clear differences in the time-course response to LCDV as function of the infection route. Most antiviral defense genes, the proinflammatory cytokines, the complement c3, g-type lysozyme and T-cell markers cd4 and cd8a were rapidly induced in the feeding-infected post-larvae, and they were remained activated at 2 dpc. In contrast, in the immersion-infected post-larvae the induction of most defensive genes was delayed, with a low intensity at 2 dpc. All these data demonstrate that LCDV can horizontally infect Senegalese sole post-larvae through the water or feed although with different patterns of histopathological disorders, virus distribution and route-specific expression profiles.
Subject(s)
Fish Diseases/immunology , Fish Proteins/genetics , Flatfishes , Iridoviridae/physiology , Transcriptome/immunology , Viral Load , Animals , DNA Virus Infections/immunology , DNA Virus Infections/veterinary , Fish Proteins/metabolism , Tissue DistributionABSTRACT
The microalgae are an important source of bioactive molecules including ß-glucans that can be used as immunostimulants in aquaculture. In the present study, the antioxidant capacity, cytotoxicity and immunomodulatory activity of a chrysolaminarin-enriched extract obtained from the diatom Phaeodactylum tricornutum was evaluated. The extract showed a higher total antioxidant activity as determined by ORAC and FRAP assays and a lower DPPH scavenging activity than particulate yeast-ß-glucan. The cytotoxicity test indicated that extract concentrations higher than 0.01% w/v could impair cell viability of human dermal fibroblasts. To evaluate the immunomodulatory activity, juvenile soles were intraperitoneally injected with the chrysolaminarin-enriched extract suspended in coconut oil (1 mg/fish) followed by a reinjection at 7 days. A sham group injected with the carrier solution was maintained as a negative control. Cumulated mortality of fish injected with the chrysolaminarin-enriched extract was 29.4% after six days and no mortality was recorded after extract reinjection. Expression analyses of fifteen genes related to the innate immune system in kidney, spleen and intestine showed temporal and organ-specific responses. A rapid (2 days post-injection; dpi) and strong induction of the pro-inflammatory il1b and the antimicrobial peptide hamp1 in the three immunological organs, the hsp90aa in kidney and spleen, irf3 in intestine and c3 in spleen was observed indicating a potent inflammatory response. The recovery of steady-state levels for all activated genes at 5 dpi, and the down-regulation of c-lectin receptor as well as some interferon-related genes (ifn1, irf1, irf3, irf8, irf9 and mx) in kidney and cxc10 in spleen indicated that the soles were able to activate a homeostatic response against the ß-glucan insult. The reinjection of the chrysolaminarin-enriched extract did not activate a new inflammatory response but reduced the mRNA levels of hsp90aa and irf3 indicating that soles developed some resistance to ß-glucans. Overall, these results reveal this enriched extract as a novel and potent source of ß-glucans with antioxidant and immunomodulatory capacity suitable for immunostimulation in aquaculture.
Subject(s)
Adjuvants, Immunologic/pharmacology , Antioxidants/pharmacology , Diatoms/chemistry , Fish Diseases/immunology , Flatfishes , Immunity, Innate/drug effects , Animals , Fish Diseases/genetics , Gene Expression Profiling/veterinary , Immunity, Innate/genetics , Injections, Intraperitoneal/veterinary , Microalgae/chemistryABSTRACT
The apolipoprotein E (ApoE) is a key component of several lipoproteins involved in lipid homeostasis. In this study, two cDNA sequences encoding ApoE (referred to as apoEa and apoEb) were characterized in the flatfish Solea senegalensis. The predicted peptides contained conserved structural blocks related with their capacity for lipid binding and lipoprotein receptor interaction. At genomic level, both genes contained five exons and four introns and they were organized into two tandem arrays with apoA-IV gene copies. The phylogenetic analysis clearly separated them into two well-supported clusters that matched with their organization in the genome of teleosts. Whole-mount in situ hybridization located the apoEa signal in the yolk syncytial layer (YSL) of lecitothrophic larval stages (0dph) and in the anterior intestine of exotrophic larvae and benthic fish. In the case of apoEb, hybridization signals were located in the YSL, tail bud, eyes and mouth at 0dph and in the otic vesicle, hindbrain, eyes, pharynx, mouth, heart and intestine at 1dph. In exotrophic larvae, apoEb was ubiquitously expressed in several tissues such as taste buds, brain, mouth, nostril, gills, intestine, liver and around the neuromasts and eyes. Quantification of mRNA levels in pools of whole larvae confirmed distinct expression patterns with a significant reduction of apoEa and an increase of apoEb mRNA levels throughout larval development. Moreover, only apoEa transcripts increased in response to food supply suggesting that this paralog mostly participates in the absorption and transport of dietary lipids and the apoEb in the redistribution of endogenous lipids as well as in neural tissue regeneration.
Subject(s)
Apolipoproteins E/genetics , Flatfishes/genetics , Amino Acid Sequence/genetics , Animals , Apolipoproteins E/metabolism , Conserved Sequence/genetics , Flatfishes/embryology , Gene Expression Profiling/methods , Gene Expression Regulation, Developmental/genetics , Genome , Genomics , In Situ Hybridization , Larva/genetics , Phylogeny , RNA, Messenger/geneticsABSTRACT
BACKGROUND: The identification of DNA methyltransferases (Dnmt) expression patterns during development and their regulation is important to understand the epigenetic mechanisms that modulate larval plasticity in marine fish. In this study, dnmt1 and dnmt3 paralogs were identified in the flatfish Solea senegalensis and expression patterns in early developmental stages and juveniles were determined. Additionally, the regulation of Dnmt transcription by a specific inhibitor (5-aza-2'-deoxycytidine) and temperature was evaluated. RESULTS: Five paralog genes of dnmt3, namely dnmt3aa, dnmt3ab, dnmt3ba, dnmt3bb.1 and dnmt3bb.2 and one gene for dnmt1 were identified. Phylogenetic analysis revealed that the dnmt gene family was highly conserved in teleosts and three fish-specific genes, dnmt3aa, dnmt3ba and dnmt3bb.2 have evolved. The spatio-temporal expression patterns of four dnmts (dnmt1, dnmt3aa, dnmt3ab and dnmt3bb.1) were different in early larval stages although all of them reduced expression with the age and were detected in neural organs and dnmt3aa appeared specific to somites. In juveniles, the four dnmt genes were expressed in brain and hematopoietic tissues such as kidney, spleen and gills. Treatment of sole embryos with 5-aza-2'-deoxycytidine down-regulated dntm1 and up-regulated dntm3aa. Moreover, in lecithotrophic larval stages, dnmt3aa and dnmt3ab were temperature sensitive and their expression was higher in larvae incubated at 16 °C relative to 20 °C. CONCLUSION: Five dnmt3 and one dnmt1 paralog were identified in sole and their distinct developmental and tissue-specific expression patterns indicate that they may have different roles during development. The inhibitor 5-aza-2'-deoxycytidine modified the transcript abundance of dntm1 and dntm3aa in embryos, which suggests that a regulatory feedback mechanism exists for these genes. The impact of thermal regime on expression levels of dnmt3aa and dnmt3ab in lecithotrophic larval stages suggests that these paralogs might be involved in thermal programing.
Subject(s)
Fish Proteins/genetics , Flatfishes/genetics , Gene Expression Regulation, Developmental/genetics , Methyltransferases/genetics , Animals , DNA Methylation , Enzyme Inhibitors/pharmacology , Flatfishes/classification , Flatfishes/embryology , Flatfishes/growth & development , Gene Expression Profiling , Gene Expression Regulation, Developmental/drug effects , Methyltransferases/antagonists & inhibitors , Methyltransferases/chemistry , Phylogeny , Sequence Homology, Amino Acid , TemperatureABSTRACT
In the present study, the pathogenesis of lymphocystis disease virus (LCDV) and the immune gene expression patterns associated with this viral infection were determined in the flatfish Senegalese sole. The results indicate that LCDV spreads rapidly from the peritoneal cavity through the bloodstream to reach target organs such as kidney, gut, liver, and skin/fin. The viral load was highest in kidney and reduced progressively thorough the experiment in spite of the viral major capsid protein gene was transcribed. The LCDV injection activated a similar set of differentially expressed transcripts in kidney and intestine although with some differences in the intensity and time-course response. This set included antiviral-related transcripts (including the mx and interferon-related factors irf1, irf2, irf3, irf7, irf8, irf9, irf10), cytokines (il1b, il6, il8, il12 and tnfa) and their receptors (il1r, il8r, il10r, il15ra, il17r), chemokines (CXC-type, CC-type and IL-8), prostaglandins (cox-2), g-type lysozymes, hepcidin, complement fractions (c2, c4-1 and c4-2) and the antigen differentiation factors cd4, cd8a, and cd8b. The expression profile observed indicated that the host triggered a systemic defensive response including inflammation able to cope with the viral challenge.