ABSTRACT
The castration of stallions is traditionally performed after puberty, at around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we aimed to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in both groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), as well as of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE2). We observed a lack of parallelism between testosterone and estradiol synthesis after birth and during puberty in both groups. The extra-gonadal synthesis of steroids was observed around the 28-month mark, regardless of the castration age. We found the expression of estrogen receptor (ESR1) in cartilage and bone, whereas androgen receptor (AR) expression appeared to be restricted to bone. Nevertheless, with respect to osteoarticular metabolism, steroid hormone deprivation resulting from early castration had no discernable impact on the levels of biomarkers related to bone and cartilage metabolism, nor on those associated with OA and inflammation. Consequently, our research demonstrated that early castration does not disrupt bone and cartilage homeostasis.
Subject(s)
Osteoarthritis , Sexual Maturation , Animals , Male , Horses , Orchiectomy , Castration , Testosterone/pharmacology , Estradiol/pharmacology , Inflammation , BiomarkersABSTRACT
BACKGROUND: Hypertension is the most frequent chronic pathology in France and in the world. It is one of the main modifiable cardiovascular risk factors. In France, 50% of treated hypertensives are uncontrolled and only 30% of treated patients are fully adherent to their antihypertensive treatment. Poor adherence to drug treatments is considered as one of the main causes of non-control of hypertension. Since 2018, a new profession has entered the French healthcare system: advanced practice nurses (APN). They have many broad-based skills, at the interface of nursing and medical exercises. The purpose of this study is to assess the impact of an APN intervention versus usual care on hypertension control. METHODS: The study will take place at the Hôtel-Dieu University Hospital, Paris, France, as prospective, open-label, controlled, randomized 1-to-1, monocentric, and superiority trial. The participants will be recruited during day hospitalization for cardiovascular assessment in the context of their hypertension management. Patients will be divided into two groups: a "usual care" group which will continue traditional follow-up (day hospitalization followed by consultation with a medical doctor (MD) within approximately 2-12 months) and an "intervention" group which will meet an APN between the day hospitalization and the MD consultation. Participants will be monitored until 12 months after the day hospitalization, depending on their last follow-up study appointment (MD consultation). The primary outcome is the rate of controlled BP (BP < 140/90 mmHg in office BP measurement) in each group. The hypothesis formulated is that an individual APN intervention, included in usual hypertension management, improves hypertension control. DISCUSSION: This innovative study will be the first in France where APNs are beginning to be established in the healthcare system. It will provide an objective look at this new profession and the impact it can have in the framework of global management of hypertension. TRIAL REGISTRATION: ClinicalTrials.gov NCT0448249. Registered on June 24, 2020.
Subject(s)
Hypertension , Humans , Follow-Up Studies , Prospective Studies , Hypertension/diagnosis , Hypertension/drug therapy , Antihypertensive Agents/adverse effects , Referral and Consultation , Treatment Outcome , Randomized Controlled Trials as TopicABSTRACT
Equine arteritis virus (EAV) is an Alphaarterivirus (family Arteriviridae, order Nidovirales) that frequently causes an influenza-like illness in adult horses, but can also cause the abortions in mares and death of newborn foals. Once primary infection has been established, EAV can persist in the reproductive tract of some stallions. However, the mechanisms enabling this persistence, which depends on testosterone, remain largely unknown. We aimed to establish an in vitro model of non-cytopathic EAV infection to study viral persistence. In this work, we infected several cell lines originating from the male reproductive tract of different species. EAV infection was fully cytopathic for 92BR (donkey cells) and DDT1 MF-2 (hamster cells) cells, and less cytopathic for PC-3 cells (human cells); ST cells (porcine cells) seemed to eliminate the virus; LNCaP (human cells) and GC-1 spg (murine cells) cells were not permissive to EAV infection; finally, TM3 cells (murine cells) were permissive to EAV infection without any overt cytopathic effects. Infected TM3 cells can be maintained at least 7 days in culture without any subculture. They can also be subcultured over 39 days (subculturing them at 1:2 the first time at 5 dpi and then every 2-3 days), but in this case, the percentage of infected cells remains low. Infected TM3 cells may therefore provide a new model to study the host-pathogen interactions and to help determine the mechanisms involved in EAV persistence in stallion reproductive tract.
Subject(s)
Arterivirus Infections , Equartevirus , Horse Diseases , Cricetinae , Pregnancy , Male , Horses , Animals , Humans , Female , Mice , Swine , Host-Pathogen Interactions , Genitalia , Cell Line , Arterivirus Infections/veterinaryABSTRACT
Although it is well established that testis produces estrogens, their precise effect is not fully documented, particularly during the prepubertal period. In a previous in vivo study, we demonstrated that an exposure of prepubertal rats (15-30 days post-partum (dpp)) to 17ß-estradiol (E2) delays the establishment of spermatogenesis. In order to characterize the mechanisms of action and the direct targets of E2 on the immature testis, we developed an organotypic culture model of testicular explants obtained from prepubertal rats (15, 20 and 25 dpp). To determine the involvement of nuclear estrogen receptors (ERs) in the effect of E2, particularly that of ESR1 which is the major ER expressed in the prepubertal testis, a pre-treatment with the full antagonist of this type of ERs (ICI 182.780) was performed. Histological analyses, gene expression studies and hormonal assays were conducted to investigate the effects of E2 on steroidogenesis- and spermatogenesis-related endpoints. Testicular explants from 15 dpp rats were unresponsive to E2 exposure while E2 effects were observed in those obtained from 20 and 25 dpp rats. An E2 exposure of testicular explants obtained from 20 dpp rats seemed to accelerate the establishment of spermatogenesis, whereas an E2 exposure of 25 dpp testicular explants induced a delay of this process. These effects could be related to the E2-induced modulation of steroidogenesis, and involved both ESR1-dependent and -independent mechanisms of action. Overall, this ex vivo study demonstrated differential age- and concentration-related effects of E2 on the testis during the prepubertal period.
Subject(s)
Estradiol , Testis , Male , Rats , Animals , Estradiol/metabolism , Estrogens/pharmacology , Spermatogenesis , Receptors, Estrogen/metabolismABSTRACT
Type 2 diabetes (T2D) induces hyperglycemia, alters hemoglobin (Hb), red blood cell (RBC) deformability and impairs hemorheology. The question remains whether RBC breakdown and intravascular hemolysis (IVH) occur in T2D patients. We characterized RBC-degradation products and vesiculation in a case-control study of 109 T2D patients and 65 control subjects. We quantified heme-related absorbance by spectrophotometry and circulating extracellular vesicles (EV) by flow cytometry and electron microscopy. Heme-related absorbance was increased in T2D vs. control plasma (+57%) and further elevated in obese T2D plasma (+27%). However, large CD235a+ EV were not increased in T2D plasma. EV from T2D plasma, or shed by isolated T2D RBC, were notably smaller in diameter (-27%) and carried heme-related absorbance. In T2D plasma, higher heme-related absorbance (+30%) was associated to peripheral sensory neuropathy, and no other vascular complication. In vitro, T2D RBC-derived EV triggered endothelial stress and thrombin activation in a phosphatidylserine- and heme-dependent fashion. We concluded that T2D was associated with low-grade IVH. Plasma absorbance may constitute a novel biomarker of peripheral neuropathy in T2D, while flow cytometry focusing on large EV may be maladapted to characterize RBC EV in T2D. Moreover, therapeutics limiting IVH or neutralizing RBC breakdown products might bolster vasculoprotection in T2D.
Subject(s)
Diabetes Mellitus, Type 2 , Peripheral Nerve Injuries , Biomarkers/metabolism , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Erythrocytes/metabolism , Heme/metabolism , Hemoglobins/metabolism , Hemolysis , Humans , Peripheral Nerve Injuries/metabolism , Phosphatidylserines/metabolism , Thrombin/metabolismABSTRACT
Lifestyle recommendations are first-line elements in the management of arterial hypertension. This cross-sectional study aimed to analyze the level to which lifestyle recommendations are used in hypertension management in France, using data from the Esteban study, which was implemented by Santé Publique France, France's public health agency, from 2014 to 2016 on a representative sample of the French population. The study sample comprised 440 adult Esteban participants who were aware they had hypertension and were aged 18-74 years old. The main outcomes were the proportion of participants who received lifestyle recommendations in their hypertension management plan, and the proportion of recommendations according to the three following dimensions: physical activity, weight loss, and changes in diet. Over half (57.0%) of the 440 participants declared they did not receive lifestyle recommendations as part of their hypertension management plan in the year preceding the study. Of these, 39.0% did not receive pharmacological treatment either. Physical activity was recommended to 31.8% of sedentary participants and weight loss to 26.8% of participants with overweight or obesity. One-fifth of the study sample (20.1%) received dietary recommendations. Of these, 69% and 10.7% were advised to limit their salt and alcohol intake, respectively. Lifestyle interventions are too rarely recommended in hypertension management plans in France. Adherence to lifestyle recommendations needs in-depth discussion not only at the time of diagnosis but also throughout follow-up.
Subject(s)
Hypertension , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , Hypertension/therapy , Hypertension/drug therapy , Cross-Sectional Studies , Life Style , Weight Loss , Sodium Chloride, Dietary , France/epidemiologyABSTRACT
Over the past few decades, male fertility has been decreasing worldwide. Many studies attribute this outcome to endocrine disruptors exposure such as bisphenol A (BPA), which is a chemical compound used in plastics synthesis and exhibiting estrogenic activity. In order to assess how the window of exposure modulates the effects of BPA on the testis, prepubertal (15 dpp to 30 dpp) and pubertal (60 dpp to 75 dpp) male Sprague-Dawley rats were exposed to BPA (50 µg/kg bw/day), 17-ß-estradiol (E2) (20 µg/kg bw/day) as a positive control, or to a combination of these compounds. For both periods of exposure, the rats were sacrificed and their testes were collected at 75 dpp. The histological analysis and the quantification of the gene expression of testis cell markers by RT-qPCR confirmed the complete spermatogenesis in all groups for both periods of exposure. However, our results suggest a deleterious effect of BPA on the blood-testis barrier in adults after pubertal exposure as BPA and BPA+E2 treatments induced a decrease in caveolin-1 and connexin-43 gene expression; which are proteins of the junctional complexes. As none of these effects were found after a prepubertal exposure, these results suggested the reversibility of BPA's effects. Caution must be taken when transposing this finding to humans and further studies are needed in this regard. However, from a regulatory perspective, this study emphasizes the importance of taking into account different periods of exposure, as they present different sensitivities to BPA exposure.
Subject(s)
Endocrine Disruptors , Estradiol , Animals , Benzhydryl Compounds/toxicity , Endocrine Disruptors/metabolism , Estradiol/metabolism , Male , Phenols , Rats , Rats, Sprague-Dawley , TestisABSTRACT
Although vitamin D acts in various biological processes, it plays a critical role in the maintenance of bone health, and regulates calcium homeostasis. In humans and rodents, the main tissues involved in vitamin D metabolism are the liver and the kidneys, however it has been shown that the testis has strongly participated in its bioactivation. Indeed, in these different species, enzymes metabolizing vitamin D (CYP27A1, CYP27B1 and CYP2R1) have been demonstrated in this tissue. Moreover, men with hypogonadism have shown a decrease in circulating levels of vitamin D. In equine species, the castration of males is a regular practice to reduce the behavior of stallions deemed too aggressive. Castration is carried out at various ages: in foals during their growth or in adulthood once they have reached their optimum size. Although horses exhibit atypical vitamin D metabolism with low circulating levels of vitamin D, it was suggested that testis may contribute to its activation as has been described in rodents and humans; castration could therefore be likely to affect its metabolism. In this study, blood levels of bioactive form of vitamin D (1 α,25[OH] 2 vitamin D 3 ) were measured before and after castration at different ages: 1 wk, after puberty (2 yr) and at adulthood (6 yr). The gene expression of enzymes involved in vitamin D metabolism has been sought in the testis of different experimental groups. No change in bioactive vitamin D3 levels was observed after castration regardless of the age at the time of surgery. The exceptional status of equine species is confirmed with a low or a lack of testis contribution to vitamin D metabolism, regardless of testicular development. This is demonstrated by a low or a lack of signal from enzymes involved in vitamin D bioactivation. Therefore, horses constitute a unique model in comparative endocrinology.
Subject(s)
Testis , Vitamin D , Animals , Cholecalciferol/metabolism , Cytochrome P-450 Enzyme System/genetics , Horses/genetics , Humans , Male , RNA, Messenger/metabolismABSTRACT
OBJECTIVES: In recent years, hospital pharmacists have gained more importance in the clinical support of patients. However, most of the studies evaluating the impact of clinical pharmacy have only studied patients' adherence or satisfaction. The aim of this study was to evaluate the direct clinical outcomes of a pharmacist-led educational intervention in patients with chronic disease. METHODS: We conducted a randomised, controlled, parallel, physician-blinded study in a day hospital and a consultation unit of a French teaching hospital over a 1-year period. Patients with hypertension, type 2 diabetes or hypercholesterolaemia who did not reach their therapeutic goals despite drug therapy were eligible. Patients in the intervention group received an intervention from a hospital pharmacist who provided patient education on pathology and drug management. The primary outcome was the proportion of patients reaching their therapeutic goals for blood pressure, glycated haemoglobin level or low-density lipoprotein cholesterol level at the 3-month follow-up consultation. RESULTS: From January to December 2015, 89 patients were included and 73 completed the study. In the intervention group, 61.7% (21/34) of the patients reached their therapeutic goals compared with 33.3% (13/39) in the control group (p=0.015). The intervention was significantly more effective in polypharmacy patients (60.0% (12/20) vs 16.7% (4/24); p=0.005), in those aged >60 years (57.9% (11/19) vs 26.1% (6/23); p=0.037) and in patients with a high education level (68.8% (11/16) vs 29.4% (5/17); p=0.024). CONCLUSION: A single pharmacist-led educational intervention has a clinical impact, doubling the proportion of patients reaching their therapeutic goals at 3 months, especially in polypharmacy patients and those aged >60 years. This study confirms the value of clinical involvement of hospital pharmacists in patient care in a consultation unit and day hospital.
Subject(s)
Diabetes Mellitus, Type 2 , Hypercholesterolemia , Hypertension , Pharmacy Service, Hospital , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Humans , Hypercholesterolemia/drug therapy , Hypercholesterolemia/epidemiology , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Middle Aged , PharmacistsABSTRACT
The aim of this study was to investigate the rapid response pathway and gene and protein expression profiles of the rat testis in response to estradiol (E2) and 1α,25(OH)2 vitamin D3 (1,25-D3), to understand how they mediate their effects on the first spermatogenic wave. To do this, we compared the effects of 1,25-D3 and E2 on 45calcium(Ca2+) uptake and the involvement of estrogen receptors (ESR) in their rapid responses. Additionally, we studied the downstream signal transduction effects of 1,25-D3 and E2 on cyclin A1/B1 and cellular cycle protein expression. As previously observed for 1,25-D3, E2 also increased 45Ca2+ uptake in immature rat testes via voltage-dependent Ca2+ channels, Ca2+-dependent chloride channels and via the activation of protein kinase C, protein kinase A and mitogen-activated protein kinase kinase (MEK). Elevated aromatase expression by testes was observed in the presence of 1,25-D3 and both hormones decreased ESR mRNA expression. Furthermore, 1,25-D3 and E2 diminished cyclin A1 mRNA expression, but E2 did not affect cyclin B1 mRNA levels. Consistent with these findings, the immunocontent of cyclin A1 and B1 in the testes was also increased by 1,25-D3 and E2. 1,25-D3 increased expressions of the p16 and p53 proteins, supporting the anti-proliferative and pro-apoptotic properties of 1,25-D3, while E2 also augmented p16. Data indicate that both hormones trigger rapid responses at the plasma membrane that may control the expression of gene and proteins related to cell cycle regulation, and thereby modulate spermatogenesis.
Subject(s)
Calcium , Estradiol , Animals , Cell Membrane , Cholecalciferol , Estradiol/pharmacology , Genomics , Male , Rats , Signal Transduction , TestisABSTRACT
On 15th April 2019, Parisians watched in shock as Notre-Dame de Paris, the iconic cathedral that has towered over their city for almost 900 years, was engulfed in flames. Although flames destroyed the spire and considerably weakened the structure, no human lives were lost. However, as some amounts of lead volatilized and deposited in the surrounding areas, fears of potential intoxication began to rise. We investigated the impact of this fire on the blood lead levels of adults in Paris according to the distance between the cathedral and where they live or work. The geometric mean of blood lead levels of the study population was 1.49µg/dl (95% CI [1.38-1.62]) with a prevalence of blood lead levels≥5.0µg/dL of 5.0%. Despite the early legitimate fears of intoxication, the fire that destroyed a significant part of the Notre-Dame cathedral did not increase the blood lead levels of adults living and working in the vicinity.
Subject(s)
Fires , Lead , Adult , HumansABSTRACT
Home blood pressure monitoring (HBPM) is increasingly being promoted in hypertension guidelines to improve hypertension management. Possessing a HBPM device could improve blood pressure (BP) control and prognostic impact. The aims of this study were to estimate the possession rate of HBPM devices in the French population and in hypertensive adults, and to investigate the determinants of possessing such devices at home. Cross-sectional analyses were performed using data from the Esteban survey, which comprised a representative sample of the French population. Among the 2,054 study participants, 673 had hypertension. Of these, 385 were aware they had it. Weighted logistic regressions were performed to investigate the factors (socioeconomic, clinical, drug treatment, and healthcare visits) associated with possessing a HBPM device. 20.9% of the study sample, 42.1% of those with hypertension, and 54% of those aware of their hypertension, possessed a HBPM device. Female gender (OR = 2.03, 95%CI [1.46; 2.60]), smoking (OR = 2.33, 95%CI [1.51; 3.15]), antihypertensive drugs (OR = 1.75, 95%CI [1.06; 2.44]), general practitioner (GP) visits (OR = 3.28, 95%CI [1.84; 4.68]), and diabetes (OR = 0.41 95% CI [0.14; 0.68]) were associated with possessing a HBPM device among those aware of their hypertension. Over 20% of the study population possessed a HBPM device at home. This proportion rose to one in two in those aware or their hypertension. Among the latter, possessing a device was positively associated with female gender, GP visits, and antihypertensive drug use. Increasing possession of HBPM devices in the hypertensive population could foster better management of the condition.
Subject(s)
Blood Pressure Monitoring, Ambulatory , Hypertension , Adult , Antihypertensive Agents/therapeutic use , Blood Pressure , Cross-Sectional Studies , Female , France/epidemiology , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiologyABSTRACT
BACKGROUND: Healthy lifestyle factors are widely recommended for hypertension prevention and control. Nevertheless, little is known about their combined impact on hypertension, in the general population. Our aim was to compute a Healthy Lifestyle Index (HLI) comprising the main non-pharmacological measures usually recommended to improve hypertension prevention: normal weight, regular physical activity, limited alcohol consumption, adoption of a healthy diet; to evaluate their combined impact on hypertension incidence. METHODS: We prospectively followed the incidence of hypertension among 80,426 French adults participating in the NutriNet-Santé cohort study. Self-reported dietary, socio-demographic, lifestyle and health data were assessed at baseline and yearly using a dedicated website; the association between HLI and hypertension risk was assessed by multivariable Cox proportional hazards models adjusted for age, sex, family history of hypertension, socio-demographic and lifestyle factors. Hypothetical Population Attributable Risks associated to each factor were estimated. RESULTS: During a median follow-up of 3.5 years (IQR: 1.5-5.3), 2413 incident cases of hypertension were identified. Compared with no or one healthy lifestyle factor, the hazard ratios (HR) for hypertension were 0.76 (95% CI, 0.67-0.85) for two factors, 0.47 (95% CI, 0.42-0.53) for three factors and 0.35 (95% CI, 0.30-0.41) for all healthy lifestyle factors (p-trend <0.0001). Compared with adhering to 0, 1, 2 or 3 healthy lifestyles, adhering to all of them was found associated with a reduction of the hypertension risk of half (HR = 0.55 (95% CI, 0.46-0.65)). CONCLUSION: Active promotion of healthy lifestyle factors at population level is a key leverage to fight the hypertension epidemic.
Subject(s)
Healthy Lifestyle , Hypertension/prevention & control , Risk Reduction Behavior , Adult , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Alcohol Drinking/prevention & control , Diet, Healthy , Exercise , Female , France/epidemiology , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/physiopathology , Incidence , Male , Middle Aged , Nutritive Value , Prospective Studies , Protective Factors , Risk Assessment , Risk Factors , Time FactorsABSTRACT
INTRODUCTION: Recommendations about lipid parameters varied from different guidelines. Aortic stiffness is a marker of vascular aging and may reflect occurrence of cardiovascular diseases. Aortic pulse wave velocity (PWV), a marker of aortic stiffness, can be measured by applanation tonometry. The purpose of our study was to test the associations between lipid parameters and aortic stiffness. METHODS: A cross-sectional study was conducted from 2012 to 2017, 603 participants were included: 517 patients and 86 'healthy' individuals used to calculate the theoretical PWV. Lipid parameters, including total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, total cholesterol/HDL ratio, triglycerides/HDL ratio and LDL/HDL ratio were measured. Theoretical PWV can be calculated according to age, sex, mean blood pressure and heart rate, allowing to form an individual PWV index [(measured PWVâ-âtheoretical PWV)/theoretical PWV]. PWV index [(measured PWVâ-â theoretical PWV)/theoretical PWV] greater than 0 defined aortic stiffness. RESULTS: In multiple linear regression analyses, total cholesterol (Pâ=â0.03), LDL (Pâ=â0.04), non-HDL (Pâ=â0.03), total cholesterol/HDL (Pâ=â0.01) and LDL/HDL (Pâ=â0.03) were significantly correlated with PWV. In multiple logistic regression analyses, non-HDL [ORâ=â1.12 (1.04-1.20), Pâ=â0.01, R value: 0.224], total cholesterol/HDL [ORâ=â1.12 (1.02-1.22), Pâ=â0.03, R value: 0.219] and total cholesterol [ORâ=â1.11 (1.01-1.23), Pâ=â0.03, R value: 0.209] were significantly associated with aortic stiffness. CONCLUSION: Non-HDL, total cholesterol and total cholesterol/HDL were significantly associated with aortic stiffness than others and especially individually lipid parameters. This result should be considered in future clinical lipid-lowering trials.
Subject(s)
Lipids/blood , Vascular Stiffness , Aged , Aorta/physiopathology , Cardiovascular Diseases/physiopathology , Case-Control Studies , Cross-Sectional Studies , Female , Heart Rate , Humans , Lipid Metabolism , Male , Middle Aged , Pulse Wave Analysis , Triglycerides/bloodABSTRACT
PREVALENCE OF HYPERTENSION LESS FREQUENT IN WOMEN BEFORE MENOPAUSE: In adults, up to the age of 50-60, hypertension is an uncommon disease, less frequent in women than in men. The literature review does not determine whether this difference is related to a protective effect of endogenous estrogens on the risk of high blood pressure, to genetic or immuno-enzymatic differences related to sex but of non-hormonal origin or to a large number of confounding variables (salt consumption, alcohol consumption, fruit and vegetable consumption, body mass index, psycho-socio-economic factors, sedentary lifestyle). PREVALENCE OF HYPERTENSION INCREASES AT MENOPAUSE: After menopause, the risk of hypertension in women increases and quickly reaches that of men, even exceeding it from the seventh decade onwards. The factors that make hypertension more frequent after the seventh decade in women are related to differences in cardiovascular risk and life expectancy between men and women, as well as a likely surviving effect in older men. The mechanisms by which estrogen-progestin deficiency increases the risk of hypertension have been extensively studied. These mechanisms are obviously numerous. However, it has not been clearly demonstrated that hormone replacement therapy during menopause reduces blood pressure levels. It should be noted that the route of administration, the choice of molecules, the respect of the intervention window and the dosage seem to modulate the potential vascular effects.
Subject(s)
Hypertension/epidemiology , Menopause , Sex Factors , Age Factors , Alcohol Drinking/adverse effects , Body Mass Index , Diet , Estrogens/physiology , Female , Fruit , Humans , Hypertension/etiology , Male , Middle Aged , Prevalence , Socioeconomic Factors , Sodium Chloride, Dietary/adverse effects , VegetablesABSTRACT
BACKGROUND: Cardiovascular disease, such as coronary heart disease (CHD), are the main cause of mortality and morbidity worldwide. CHD is not entirely predicted by classic risk factors; however, they are preventable. Facing this major problem, the development of novel methods for CHD risk prediction is of practical interest. The purpose of our study was to construct an artificial neural networks (ANNs)-based diagnostic model for CHD risk using a complex of clinical and haemodynamics factors of this disease and aortic pulse wave velocity (PWV) index. METHODS: A total of 437 patients were included from 2012 to 2017: 99 CHD and 338 non-CHD patients. Theoretical PWV was calculated, on 93 patients free of hypertension, diabetes and CHD, according to age, blood pressure, sex and heart rate. The results were expressed as an index [(measured PWVâ-âtheoretical PWV)/theoretical PWV] for each patient. The original database for ANNs included clinical, haemodynamic and laboratory characteristics. Multilayered perceptron ANNs architecture were applied. The performance of prediction was evaluated by accuracy values based on standard definitions. RESULTS: By changing the types of ANNs and the number of input factors applied, we created models that demonstrated 0.63-0.93 accuracy. The best accuracy was obtained with ANNs topology of multilayer perceptron with three hidden layers for models, parameters included by both biological factors, carotid plaque and PWV index. CONCLUSION: ANNs models including a PWV index could be used as promising approaches for predicting CHD risk without the need for invasive diagnostic methods and may help in the clinical decision.
Subject(s)
Coronary Disease/diagnosis , Diagnosis, Computer-Assisted , Neural Networks, Computer , Pulse Wave Analysis , HumansABSTRACT
With increasing life expectancies worldwide, it is an important public health issue to identify factors that influence the quality of aging. We aimed to investigate the individual and combined roles of lifestyle factors at midlife for healthy aging (HA). We analyzed data from 2203 participants of the French ”Supplémentation en Vitamines et Minéraux Antioxydants” (SU.VI.MAX) cohort aged 45â»60 years at baseline (1994â»1995), and assessed the combined impact of lifestyle factors (weight, smoking status, physical activity, alcohol consumption, and diet) on HA (absence of chronic diseases and function-limiting pain, good physical and cognitive functioning, functional independence, no depressive symptoms, and good social and self-perceived health) with a five-component healthy lifestyle index (HLI). Relative risks (RR) and 95% confidence intervals (CIs) were estimated using a robust-error-variance Poisson regression. Approximately 39% of our sample aged healthily. After adjustment for potential confounders, a one-point increase in HLI was related to an 11% higher probability of HA (95% CI = 6%, 16%; p < 0.001). The proportions of HA attributable to specific factors based on the “population attributable risk” concept were 7.6%, 6.0%, 7.8%, and 16.5% for body mass index (BMI), physical activity, diet quality, and smoking status, respectively. This study highlights the importance of healthy lifestyle habits at midlife for the promotion of good overall health during aging.
Subject(s)
Diet, Healthy , Healthy Aging , Risk Reduction Behavior , Age Factors , Alcohol Drinking/adverse effects , Antioxidants/administration & dosage , Body Mass Index , Body Weight , Chi-Square Distribution , Dietary Supplements , Exercise , Female , France , Health Status , Humans , Life Expectancy , Linear Models , Male , Mental Health , Middle Aged , Minerals/administration & dosage , Odds Ratio , Protective Factors , Randomized Controlled Trials as Topic , Risk Factors , Sedentary Behavior , Smoking/adverse effects , Smoking CessationABSTRACT
We investigated the acute effect of low concentrations of BPA on calcium influx and the mechanism of action of BPA in this rapid response in the rat testis. BPA increased calcium influx at 1 pM and 1â¯nM at 300â¯s of incubation, in a similar manner to that of estradiol. At 1 pM, BPA stimulated calcium influx independently of classical estrogen receptors, consistent with a G-protein coupled receptor. This effect also involves the modulation of ionic channels, such as K+, TRPV1 and Cl- channels. Furthermore, BPA is able to modulate calcium from intracellular storages by inhibiting SERCA and activating IP3 receptor/Ca2+ channels at the endoplasmic reticulum and activate kinase proteins, such as PKA and PKC. The rapid responses of BPA on calcium influx could, in turn, trigger a cross talk by MEK and p38MAPK activation and also mediate genomic responses.
Subject(s)
Benzhydryl Compounds/toxicity , Calcium/metabolism , Endocrine Disruptors/toxicity , Phenols/toxicity , Testis/drug effects , Animals , Ion Channels/metabolism , Male , Membrane Transport Proteins/metabolism , Rats, Wistar , Signal Transduction/drug effects , Testis/metabolism , Type C Phospholipases/metabolismABSTRACT
PURPOSE: Metabolic syndrome (MetS), a multicomponent condition, is a cardiovascular disease predictor. Although exposure to agricultural pesticides has been suggested as a potential contributor to the rising rates of obesity, type 2 diabetes, and other features of metabolic disorders, no studies have focused on the association between consumption of organic food (produced without synthetic pesticides) and MetS. We aimed to investigate the cross-sectional association between organic food consumption and MetS in French adults to determine whether it would be worth conducting further studies, particularly large prospective and randomised trials. METHODS: A total of 8174 participants from the NutriNet-Santé study who attended a clinical visit and completed an organic food frequency questionnaire were included in this cross-sectional analysis. We evaluated the association between the proportion of organic food in the diet (overall and by food group) and MetS using Poisson regression models while adjusting for potential confounders. RESULTS: Higher organic food consumption was negatively associated with the prevalence of MetS: adjusted prevalence ratio was 0.69 (95% CI 0.61, 0.78) when comparing the third tertile of proportion of organic food in the diet with the first one (p value <0.0001). Higher consumption of organic plant-based foods was also related to a lower probability of having MetS. In addition, when stratifying by lifestyle factors (nutritional quality of the diet, smoking status, and physical activity), a significant negative association was detected in each subgroup (p values <0.05), except among smokers. CONCLUSIONS: Our results showed that a higher organic food consumption was associated with a lower probability of having MetS. Additional prospective studies and randomised trials are required to ascertain the relationship between organic food consumption and metabolic disorders.