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1.
Nat Commun ; 14(1): 4174, 2023 07 13.
Article in English | MEDLINE | ID: mdl-37443074

ABSTRACT

Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , BNT162 Vaccine , SARS-CoV-2 , COVID-19/prevention & control , Vaccination , Immunoglobulin Fc Fragments , Antibodies, Neutralizing , Antibodies, Viral
2.
J Affect Disord ; 319: 352-360, 2022 12 15.
Article in English | MEDLINE | ID: mdl-36167243

ABSTRACT

BACKGROUND: We use the Global Multidimensional Poverty Index (MPI) to explore how different dimensions of poverty more directly linked to young people are associated with depressive symptoms among South African youth. METHODS: Data came from the 2017 wave of the nationally-representative National Income Dynamics Study (NIDS) in South Africa. We focused on a sample of 15-24-year-olds whose depressive symptoms were assessed using an adapted version of the 10-item Centre for Epidemiological Studies Depression Scale. We examine how individual dimensions and indicators of the MPI relate to depression, in comparison to more conventional measures, including household income, subjective social standing, overcrowding and personal assets. Cross-sectional analyses were adjusted for clustering to account for sampling design. RESULTS: The MPI index was not associated with probable depression (OR = 1.02, 95 % CI 0.81-1.29). Only lack of access to the labour market emerged as a key individual dimension associated with probable depression (OR = 5.29, 95 % CI 1.70-16.47), a relationship driven by an increased odds for those not in employment, education or training. Lack of household assets, living in an informal dwelling and lower perceived social standing were also associated with increased odds for depression. No gender differences were noted. LIMITATIONS: The study is cross-sectional and not suitable to examine the causal nature of the association between multidimensional poverty and depression. CONCLUSIONS: Poverty dimensions that measure youth's access to employment or training have a strong association with depression. Further research is needed to assess whether improved access to employment or training contributes to improving mental health among young South Africans.


Subject(s)
Depression , Poverty , Adolescent , Humans , Cross-Sectional Studies , Depression/epidemiology , Depression/psychology , South Africa/epidemiology , Poverty/psychology , Income
3.
bioRxiv ; 2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35923313

ABSTRACT

Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.

4.
Glob Public Health ; 17(3): 377-390, 2022 03.
Article in English | MEDLINE | ID: mdl-33427084

ABSTRACT

The pursuit of health equity is foundational to the global health enterprise. But while moral concerns over health inequities can galvanise political commitment, how such concerns can or should translate into practice remains less clear. This paper reviews evolving ways that equity goals have featured in key World Health Organization (WHO)-related policy documents, before discussing the heuristic value and empirical traction that the concept of equity can bring to the health system strengthening (HSS) agenda. We argue that while health equity is often presented as the overarching goal of HSS, in practice this is typically circumscribed to the provision of healthcare services. Although healthcare equity is important, we suggest that this narrow focus risks losing sight of the structural political, social and economic drivers of health and health inequities, as well as the broader contexts of care and complex socio-political mechanisms through which health systems are strengthened. Drawing on new lines of empirical inquiry, we propose that broadening the equity lens for HSS -offers exciting opportunities to put health systems at the heart of a more ambitious equity agenda in global health.


Subject(s)
Health Equity , Global Health , Government Programs , Health Policy , Humans , Policy , World Health Organization
5.
Soc Sci Med ; 292: 114631, 2022 01.
Article in English | MEDLINE | ID: mdl-34891031

ABSTRACT

This study examines the longitudinal impact of the South African Child Support Grant (CSG) on risk for depression and life satisfaction among young people (15-19 years). We analysed data from the last three waves of the National Income Dynamics Study (NIDS), a nationally representative panel survey that took place every two years from 2008 to 2017. We used an instrumental variable (IV) approach that exploits multiple changes in age eligibility from 1998 to 2012. Depressive symptoms were assessed using an 8-item version of the Centre for Epidemiological Studies Depression Scale; participants who scored above 8 were considered at risk for depression. Life satisfaction was rated on a scale of 1 ('very dissatisfied') to 10 ('very satisfied'); participants who scored 8 or above were classified as satisfied. We also examined impacts on educational deficit (≥2 years behind) and not being in education, employment or training (NEET) as secondary outcomes, as these are also important for mental health. Age eligibility strongly predicted CSG receipt at Wave 3. In instrumental variable models, CSG receipt did not influence the risk for depression (ß = 0.10, SE = 0.10, p = 0.316), nor life satisfaction (ß = -0.07, SE = 0.09, p = 0.420) at Wave 3, nor at Waves 4 or 5. Some improvements in educational deficit were observed at Wave 3 among CSG beneficiaries compared to non-beneficiaries. These results were robust to multiple specifications. CSG receipt did not improve the psychological wellbeing of adolescents and young adults, nor did it improve their education or employment outcomes. Our findings highlight the need to identify alternative social policies that address the root causes of youth social disadvantage, in conjunction with targeted approaches to improve the mental health of young South Africans living in poverty.


Subject(s)
Child Custody , Mental Health , Adolescent , Child , Financing, Organized , Humans , Poverty , South Africa/epidemiology , Young Adult
6.
Talanta ; 219: 121184, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-32887102

ABSTRACT

Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is increasingly recognized for its potential in the discovery of novel biomarkers directly from tissue sections. However, there are no MALDI IMS studies as yet on the adipose tissue, a lipid-enriched tissue that plays a pivotal role in the development of obesity-associated disorders. Herein, we aimed at developing an optimized method for analyzing adipose tissue lipid composition under both physiological and pathological conditions by MALDI IMS. Our studies showed an exacerbated lipid delocalization from adipose tissue sections when conventional strategies were applied. However, our optimized method using conductive-tape sampling and 2,5-dihydroxybenzoic acid (DHB) as a matrix, preserved the anatomical organization and minimized lipid diffusion from sample sections. This method enabled the identification of a total of 625 down-regulated and 328 up-regulated m/z values in the adipose tissue from a rat model of extreme obesity as compared to lean animals. Combination of MALDI IMS and liquid chromatography (LC)-MS/MS data identified 44 differentially expressed lipid species between lean and obese animals, including phospholipids and sphingomyelins. Among the lipids identified, SM(d18:0_18:2), PE(P-16:0_20:0), and PC(O-16:0_16:1) showed a differential spatial distribution in the adipose tissue of lean vs. obese animals. In sum, our method provides a valuable new tool for research on adipose tissue that may pave the way for the identification of novel biomarkers of obesity and metabolic disease.


Subject(s)
Phospholipids , Tandem Mass Spectrometry , Adipose Tissue , Animals , Chromatography, Liquid , Rats , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
7.
Hum Reprod ; 34(12): 2495-2512, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31820802

ABSTRACT

STUDY QUESTION: Can kisspeptin treatment induce gonadotrophin responses and ovulation in preclinical models and anovulatory women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Kisspeptin administration in some anovulatory preclinical models and women with PCOS can stimulate reproductive hormone secretion and ovulation, albeit with incomplete efficacy. WHAT IS KNOWN ALREADY: PCOS is a prevalent, heterogeneous endocrine disorder, characterized by ovulatory dysfunction, hyperandrogenism and deregulated gonadotrophin secretion, in need of improved therapeutic options. Kisspeptins (encoded by Kiss1) are master regulators of the reproductive axis, acting mainly at GnRH neurons, with kisspeptins being an essential drive for gonadotrophin-driven ovarian follicular maturation and ovulation. Altered Kiss1 expression has been found in rodent models of PCOS, although the eventual pathophysiological role of kisspeptins in PCOS remains unknown. STUDY DESIGN, SIZE, DURATION: Gonadotrophin and ovarian/ovulatory responses to kisspeptin-54 (KP-54) were evaluated in three preclinical models of PCOS, generated by androgen exposures at different developmental windows, and a pilot exploratory cohort of anovulatory women with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three models of PCOS were generated by exposure of female rats to androgens at different periods of development: PNA (prenatal androgenization; N = 20), NeNA (neonatal androgenization; N = 20) and PWA (post-weaning androgenization; N = 20). At adulthood (postnatal day 100), rats were subjected to daily treatments with a bolus of KP-54 (100 µg/kg, s.c.) or vehicle for 11 days (N = 10 per model and treatment). On Days 1, 4, 7 and 11, LH and FSH responses were assessed at different time-points within 4 h after KP-54 injection, while ovarian responses, in terms of follicular maturation and ovulation, were measured at the end of the treatment. In addition, hormonal (gonadotrophin, estrogen and inhibin B) and ovulatory responses to repeated KP-54 administration, at doses of 6.4-12.8 nmol/kg, s.c. bd for 21 days, were evaluated in a pilot cohort of anovulatory women (N = 12) diagnosed with PCOS, according to the Rotterdam criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Deregulated reproductive indices were detected in all PCOS models: PNA, NeNA and PWA. Yet, anovulation was observed only in NeNA and PWA rats. However, while anovulatory NeNA rats displayed significant LH and FSH responses to KP-54 (P < 0.05), which rescued ovulation, PWA rats showed blunted LH secretion after repeated KP-54 injection and failed to ovulate. In women with PCOS, KP-54 resulted in a small rise in LH (P < 0.05), with an equivalent elevation in serum estradiol levels (P < 0.05). Two women showed growth of a dominant follicle with subsequent ovulation, one woman displayed follicle growth but not ovulation and desensitization was observed in another patient. No follicular response was detected in the other women. LIMITATIONS, REASONS FOR CAUTION: While three different preclinical PCOS models were used in order to capture the heterogeneity of clinical presentations of the syndrome, it must be noted that rat models recapitulate many but not all the features of this condition. Additionally, our pilot study was intended as proof of principle, and the number of participants is low, but the convergent findings in preclinical and clinical studies reinforce the validity of our conclusions. WIDER IMPLICATIONS OF THE FINDINGS: Our first-in-rodent and -human studies demonstrate that KP-54 administration in anovulatory preclinical models and women with PCOS can stimulate reproductive hormone secretion and ovulation, albeit with incomplete efficacy. As our rat models likely reflect the diversity of PCOS phenotypes, our results argue for the need of personalized management of anovulatory dysfunction in women with PCOS, some of whom may benefit from kisspeptin-based treatments. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by research agreements between Ferring Research Institute and the Universities of Cordoba and Edinburgh. K.S. was supported by the Wellcome Trust Scottish Translational Medicine and Therapeutics Initiative (STMTI). Some of this work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1. M.T.-S. is a member of CIBER Fisiopatología de la Obesidad y Nutrición, which is an initiative of Instituto de Salud Carlos III. Dr Mannaerts is an employee of Ferring International PharmaScience Center (Copenhagen, Denmark), and Drs Qi, van Duin and Kohout are employees of the Ferring Research Institute (San Diego, USA). Dr Anderson and Dr Tena-Sempere were recipients of a grant support from the Ferring Research Institute, and Dr Anderson has undertaken consultancy work and received speaker fees outside this study from Merck, IBSA, Roche Diagnostics, NeRRe Therapeutics and Sojournix Inc. Dr Skorupskaite was supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative 102419/Z/13/A. The other authors have no competing interest.


Subject(s)
Kisspeptins/therapeutic use , Ovulation/drug effects , Polycystic Ovary Syndrome/drug therapy , Adult , Animals , Disease Models, Animal , Female , Follicle Stimulating Hormone/blood , Humans , Kisspeptins/pharmacology , Luteinizing Hormone/blood , Pilot Projects , Polycystic Ovary Syndrome/blood , Rats, Wistar , Young Adult
8.
Mol Immunol ; 103: 63-70, 2018 11.
Article in English | MEDLINE | ID: mdl-30205305

ABSTRACT

The Surface Immunogenic Protein (SIP) of Group B Streptococcus (GBS) had been described as a good target for vaccine development. To date, SIP has been reported as a highly conserved protein, and in a mouse model it induces protection against lethal GBS challenge. Also, similar effects have been described by intranasal immunization with a SIP-based vaccine. In this study, we show the immune response induced by an oral SIP-based vaccine formulated on alum in a mouse model. Our vaccine can reduce vaginal GBS colonization and induce specific SIP-antibodies with opsonophagocytosis activities against GBS. Moreover, we observed the activation of T-cells producing IFN-γ, TNF-α, IL-10, IL-2, and increased expression of the transcription factor T-bet, suggesting a Th1-type humoral response. The oral SIP-based vaccine is a novel alternative in the development of a vaccine against GBS.


Subject(s)
Antigens, Bacterial/immunology , Streptococcal Infections/immunology , Streptococcus agalactiae/immunology , Vaccines/immunology , Vagina/immunology , Administration, Oral , Alum Compounds/administration & dosage , Alum Compounds/chemistry , Animals , Antibodies, Bacterial/immunology , Antigens, Bacterial/chemistry , Female , HL-60 Cells , Humans , Mice, Inbred C57BL , Streptococcal Infections/microbiology , Streptococcal Infections/prevention & control , Streptococcus agalactiae/drug effects , Streptococcus agalactiae/physiology , Vaccination/methods , Vaccines/administration & dosage , Vaccines/chemistry , Vagina/drug effects , Vagina/microbiology
9.
Hum Reprod Update ; 23(6): 737-763, 2017 11 01.
Article in English | MEDLINE | ID: mdl-28961976

ABSTRACT

BACKGROUND: Puberty is a complex developmental event, controlled by sophisticated regulatory networks that integrate peripheral and internal cues and impinge at the brain centers driving the reproductive axis. The tempo of puberty is genetically determined but is also sensitive to numerous modifiers, from metabolic and sex steroid signals to environmental factors. Recent epidemiological evidence suggests that the onset of puberty is advancing in humans, through as yet unknown mechanisms. In fact, while much knowledge has been gleaned recently on the mechanisms responsible for the control of mammalian puberty, fundamental questions regarding the intimate molecular and neuroendocrine pathways responsible for the precise timing of puberty and its deviations remain unsolved. OBJECTIVE AND RATIONALE: By combining data from suitable model species and humans, we aim to provide a comprehensive summary of our current understanding of the neuroendocrine mechanisms governing puberty, with particular focus on its central regulatory pathways, underlying molecular basis and mechanisms for metabolic control. SEARCH METHODS: A comprehensive MEDLINE search of articles published mostly from 2003 to 2017 has been carried out. Data from cellular and animal models (including our own results) as well as clinical studies focusing on the pathophysiology of puberty in mammals were considered and cross-referenced with terms related with central neuroendocrine mechanisms, metabolic control and epigenetic/miRNA regulation. OUTCOMES: Studies conducted during the last decade have revealed the essential role of novel central neuroendocrine pathways in the control of puberty, with a prominent role of kisspeptins in the precise regulation of the pubertal activation of GnRH neurosecretory activity. In addition, different transmitters, including neurokinin-B (NKB) and, possibly, melanocortins, have been shown to interplay with kisspeptins in tuning puberty onset. Alike, recent studies have documented the role of epigenetic mechanisms, involving mainly modulation of repressors that target kisspeptins and NKB pathways, as well as microRNAs and the related binding protein, Lin28B, in the central control of puberty. These novel pathways provide the molecular and neuroendocrine basis for the modulation of puberty by different endogenous and environmental cues, including nutritional and metabolic factors, such as leptin, ghrelin and insulin, which are known to play an important role in pubertal timing. WIDER IMPLICATIONS: Despite recent advancements, our understanding of the basis of mammalian puberty remains incomplete. Complete elucidation of the novel neuropeptidergic and molecular mechanisms summarized in this review will not only expand our knowledge of the intimate mechanisms responsible for puberty onset in humans, but might also provide new tools and targets for better prevention and management of pubertal deviations in the clinical setting.


Subject(s)
Mammals/growth & development , Sexual Maturation/physiology , Animals , Epigenesis, Genetic , Humans , Mammals/physiology , Neurosecretory Systems/physiology , Reproduction , Sexual Maturation/genetics , Signal Transduction
10.
Br J Pharmacol ; 173(9): 1541-55, 2016 May.
Article in English | MEDLINE | ID: mdl-26856544

ABSTRACT

BACKGROUND AND PURPOSE: Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension. EXPERIMENTAL APPROACH: Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg · kg(-1) · day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg · kg(-1) · day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg · kg(-1) · day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used. KEY RESULTS: Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-α expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment. CONCLUSIONS AND IMPLICATIONS: COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage.


Subject(s)
Cyclooxygenase 2/metabolism , Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide/pharmacology , Dinoprostone/metabolism , Hypertension/drug therapy , Receptors, Prostaglandin E, EP1 Subtype/metabolism , Vascular Stiffness/drug effects , Animals , Celecoxib/administration & dosage , Celecoxib/chemistry , Celecoxib/pharmacology , Cells, Cultured , Cyclooxygenase 2/deficiency , Cyclooxygenase 2 Inhibitors/pharmacology , Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide/administration & dosage , Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide/chemistry , Dose-Response Relationship, Drug , Humans , Hypertension/metabolism , Male , Mice , Rats , Rats, Inbred SHR , Rats, Wistar , Receptors, Prostaglandin E, EP1 Subtype/antagonists & inhibitors , Structure-Activity Relationship
11.
Clin Infect Dis ; 62(7): 887-895, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-26757804

ABSTRACT

BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.


Subject(s)
Pneumonectomy/statistics & numerical data , Tuberculosis, Multidrug-Resistant/surgery , Tuberculosis, Pulmonary/surgery , Adult , Antitubercular Agents/therapeutic use , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology
12.
Br J Pharmacol ; 172(12): 3028-42, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25653183

ABSTRACT

BACKGROUND AND PURPOSE: Angiotensin II (AngII) and IL-1ß are involved in cardiovascular diseases through the induction of inflammatory pathways. HuR is an adenylate- and uridylate-rich element (ARE)-binding protein involved in the mRNA stabilization of many genes. This study investigated the contribution of HuR to the increased expression of COX-2 induced by AngII and IL-1ß and its consequences on VSMC migration and remodelling. EXPERIMENTAL APPROACH: Rat and human VSMCs were stimulated with AngII (0.1 µM) and/or IL-1ß (10 ng · mL(-1)). Mice were infused with AngII or subjected to carotid artery ligation. mRNA and protein levels were assayed by quantitative PCR, Western blot, immunohistochemistry and immunofluorescence. Cell migration was measured by wound healing and transwell assays. KEY RESULTS: In VSMCs, AngII potentiated COX-2 and tenascin-C expressions and cell migration induced by IL-1ß. This effect of AngII on IL-1ß-induced COX-2 expression was accompanied by increased COX-2 3' untranslated region reporter activity and mRNA stability, mediated through cytoplasmic HuR translocation and COX-2 mRNA binding. These effects were blocked by ERK1/2 and HuR inhibitors. VSMC migration was reduced by blockade of ERK1/2, HuR, COX-2, TXAS, TP and EP receptors. HuR, COX-2, mPGES-1 and TXAS expressions were increased in AngII-infused mouse aortas and in carotid-ligated arteries. AngII-induced tenascin-C expression and vascular remodelling were abolished by celecoxib and by mPGES-1 deletion. CONCLUSIONS AND IMPLICATIONS: The synergistic induction of COX-2 by AngII and IL-1ß in VSMCs involves HuR through an ERK1/2-dependent mechanism. The HuR/COX-2 axis participates in cell migration and vascular damage. HuR might be a novel target to modulate vascular remodelling.


Subject(s)
Angiotensin II/metabolism , Cyclooxygenase 2/genetics , ELAV-Like Protein 1/metabolism , Interleukin-1beta/metabolism , Angiotensin II/administration & dosage , Animals , Aorta/metabolism , Celecoxib/pharmacology , Cell Movement/physiology , Drug Synergism , Gene Expression Regulation/drug effects , Humans , Interleukin-1beta/administration & dosage , Male , Mice , Mice, Inbred C57BL , Muscle, Smooth, Vascular/cytology , RNA Stability , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Tenascin/genetics , Vascular Remodeling/drug effects
13.
Public Health ; 128(10): 911-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25369355

ABSTRACT

OBJECTIVES: Greece and Ireland suffered an economic recession of similar magnitude, but whether their health has deteriorated as a result has not yet been well established. STUDY DESIGN: Based on five waves (2006-2010) of the European Union Statistics of Income and Living Conditions (EU-SILC) survey a (DID) approach was implemented that compared trends in self-rated health in Greece and Ireland before and after the crisis with trends in a 'control' population (Poland) that did not experience a recession and had health trends comparable to both countries before the crisis. METHODS: Logistic regression using a (DID) approach. RESULTS: A simple examination of trends suggests that there was no significant change in health in Greece or Ireland following the onset of the financial crisis. However, DID estimates that incorporated a control population suggest an increase in the prevalence of poor self-rated health in Greece (OR = 1.216; CI = 1.11-1.32). Effects were most pronounced for older individuals and those living in high-density areas, but effects in Greece were overwhelmingly consistent in different population sub-groups. In contrast, DID estimates revealed no effect of the financial crisis on the prevalence of poor self-rated health in Ireland (OR = 0.97; CI = 0.81-1.16). CONCLUSIONS: DID estimates suggest that the financial crisis led to higher prevalence of reporting poor health in Greece but not in Ireland. Although the research design does not allow the authors to directly assess the role of specific policies, contextual factors including policy responses may have contributed to the different effect of the crisis on the health of the two countries.


Subject(s)
Economic Recession , Health Status , Adolescent , Adult , Aged , Female , Greece , Humans , Ireland , Male , Middle Aged , Socioeconomic Factors , Young Adult
15.
Rev Neurol ; 58 Suppl 1: S57-63, 2014 Feb 24.
Article in Spanish | MEDLINE | ID: mdl-25252669

ABSTRACT

INTRODUCTION: In July 2013, the US Food and Drug Administration approved the use of NEBA as the first device for the complementary evaluation of attention deficit hyperactivity disorder (ADHD). It is based on quantitative electroencephalogram (qEEG) and includes the standardised theta/beta ratio, the results of which were consistent with both the medical and psychological clinical evaluation. Likewise, it has proved to be a useful tool for determining whether the ADHD is primary, secondary or comorbid to another pathology. Yet, to date no publications have specified whether it is a total theta/beta ratio or theta/beta-1 and theta/beta-2. Additionally, no data are provided to be able to discriminate between diagnostic subtypes of ADHD. AIMS: To quantify the theta/beta ratios, by means of qEEG, in a sample of patients from the Rio de la Plata area with a main confirmed diagnosis of ADHD, in order to compare the neurophysiological patterns according to the diagnostic subtypes. PATIENTS AND METHODS: We used a randomised stratified sample of 62 subjects of both sexes, with ages between 8 and 17 years, distributed into two groups, depending on the diagnostic subtype: attention deficit subtype of ADHD (n = 31) and the combined subtype of ADHD (n = 31). RESULTS: High theta/beta-1 and theta/beta-2 ratios were confirmed in the Cz region, being higher than the ratios in the C3 and C4 areas. Moderate and statistically significant differences were found between the two subtypes only in the beta-1 band in the occipital regions. The analysis of the interhemispheric coherence suggests an association of the power peak crossed with the diagnostic subtype, which is the fastest peak (10 Hz) for the combined subtype. No important differences are found on analysing the phase spectra or the theta/beta ratios. CONCLUSIONS: Although the scientific literature, especially the NEBA system, highlights the importance of the theta/beta ratio in the differential diagnosis of ADHD in control samples and other neurodevelopmental disorders, a distinction must be made between beta-1 and beta-2.


TITLE: Cociente theta/beta (NEBA) en el diagnostico del trastorno por deficit de atencion/hiperactividad.Introduccion. En julio del año 2013, la Food and Drug Administration estadounidense aprobo el NEBA como el primer dispositivo para la evaluacion complementaria del trastorno por deficit de atencion/hiperactividad (TDAH), basado en el electroencefalograma cuantificado (EEGq) e incluyendo la relacion theta/beta estandarizada, cuyos resultados fueron consistentes con la evaluacion clinica, tanto medica como psicologica, y es una herramienta util para determinar si el TDAH es primario, secundario o comorbido a otro trastorno. Sin embargo, ninguna de las publicaciones, hasta la fecha, especifica si se trata de un cociente theta/beta total, o theta/beta-1 y theta/beta-2, como tampoco se aportan datos para discriminar entre subtipos diagnosticos del TDAH. Objetivo. Cuantificar los cocientes theta/beta, a traves del EEGq, en una muestra de pacientes rioplatenses con diagnostico principal confirmado de TDAH, para comparar el patron neurofisiologico segun el subtipo diagnostico. Pacientes y metodos. Muestra aleatoria estratificada de 62 sujetos de ambos sexos, de 8 a 17 años, distribuidos en dos grupos segun subtipo diagnostico, TDAH subtipo deficit de atencion (n = 31) y TDAH subtipo combinado (n = 31). Resultados. Se confirman cocientes altos theta/beta-1 y theta/beta-2 en la region Cz, mayores a los cocientes en las areas C3 y C4. Se encontraron diferencias moderadas y estadisticamente significativas entre los dos subtipos solo en la banda beta-1 en las regiones occipitales. El analisis de la coherencia interhemisferica sugiere una asociacion del pico de potencia cruzada con el subtipo diagnostico, que para el subtipo combinado es el pico mas rapido (10 Hz). No se encuentran diferencias importantes al analizar los espectros de fase, ni los cocientes theta/alfa. Conclusiones. Si bien la bibliografia cientifica, especificamente el sistema NEBA, plantea la importancia del cociente theta/beta en el diagnostico diferencial del TDAH de muestras controles y otros trastornos del neurodesarrollo, es necesario discriminar entre beta-1 y beta-2.


Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnosis , Beta Rhythm , Theta Rhythm , Adolescent , Algorithms , Attention Deficit Disorder with Hyperactivity/classification , Attention Deficit Disorder with Hyperactivity/physiopathology , Child , Dominance, Cerebral , Female , Humans , Male , Random Allocation , Sampling Studies
16.
Rev. neurol. (Ed. impr.) ; 58(supl.1): 57-63, 24 feb., 2014. tab, graf
Article in Spanish | IBECS | ID: ibc-119463

ABSTRACT

Introducción. En julio del año 2013, la Food and Drug Administration estadounidense aprobó el NEBA como el primer dispositivo para la evaluación complementaria del trastorno por déficit de atención/hiperactividad (TDAH), basado en el electroencefalograma cuantificado (EEGq) e incluyendo la relación theta/beta estandarizada, cuyos resultados fueron consistentes con la evaluación clínica, tanto médica como psicológica, y es una herramienta útil para determinar si el TDAH es primario, secundario o comórbido a otro trastorno. Sin embargo, ninguna de las publicaciones, hasta la fecha, especifica si se trata de un cociente theta/beta total, o theta/beta-1 y theta/beta-2, como tampoco se aportan datos para discriminar entre subtipos diagnósticos del TDAH. Objetivo. Cuantificar los cocientes theta/beta, a través del EEGq, en una muestra de pacientes rioplatenses con diagnóstico principal confirmado de TDAH, para comparar el patrón neurofisiológico según el subtipo diagnóstico. Pacientes y métodos. Muestra aleatoria estratificada de 62 sujetos de ambos sexos, de 8 a 17 años, distribuidos en dos grupos según subtipo diagnóstico, TDAH subtipo déficit de atención (n = 31) y TDAH subtipo combinado (n = 31). Resultados. Se confirman cocientes altos theta/beta-1 y theta/beta-2 en la región Cz, mayores a los cocientes en las áreas C3 y C4. Se encontraron diferencias moderadas y estadísticamente significativas entre los dos subtipos sólo en la banda beta-1 en las regiones occipitales. El análisis de la coherencia interhemisférica sugiere una asociación del pico de potencia cruzada con el subtipo diagnóstico, que para el subtipo combinado es el pico más rápido (10 Hz). No se encuentran diferencias importantes al analizar los espectros de fase, ni los cocientes theta/alfa. Conclusiones. Si bien la bibliografía científica, específicamente el sistema NEBA, plantea la importancia del cociente theta/ beta en el diagnóstico diferencial del TDAH de muestras controles y otros trastornos del neurodesarrollo, es necesario discriminar entre beta-1 y beta-2 (AU)


Introduction. In July 2013, the US Food and Drug Administration approved the use of NEBA as the first device for the complementary evaluation of attention deficit hyperactivity disorder (ADHD). It is based on quantitative electroencephalogram (qEEG) and includes the standardised theta/beta ratio, the results of which were consistent with both the medical and psychological clinical evaluation. Likewise, it has proved to be a useful tool for determining whether the ADHD is primary, secondary or comorbid to another pathology. Yet, to date no publications have specified whether it is a total theta/beta ratio or theta/beta-1 and theta/beta-2. Additionally, no data are provided to be able to discriminate between diagnostic subtypes of ADHD. Aims. To quantify the theta/beta ratios, by means of qEEG, in a sample of patients from the Rio de la Plata area with a main confirmed diagnosis of ADHD, in order to compare the neurophysiological patterns according to the diagnostic subtypes. Patients and methods. We used a randomised stratified sample of 62 subjects of both sexes, with ages between 8 and 17 years, distributed into two groups, depending on the diagnostic subtype: attention deficit subtype of ADHD (n = 31) and the combined subtype of ADHD (n = 31). Results. High theta/beta-1 and theta/beta-2 ratios were confirmed in the Cz region, being higher than the ratios in the C3 and C4 areas. Moderate and statistically significant differences were found between the two subtypes only in the beta-1 band in the occipital regions. The analysis of the interhemispheric coherence suggests an association of the power peak crossed with the diagnostic subtype, which is the fastest peak (10 Hz) for the combined subtype. No important differences are found on analysing the phase spectra or the theta/beta ratios. Conclusions. Although the scientific literature, especially the NEBA system, highlights the importance of the theta/beta ratio in the differential diagnosis of ADHD in control samples and other neurodevelopmental disorders, a distinction must be made between beta-1 and beta-2 (AU)


Subject(s)
Humans , Male , Female , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnosis , Electroencephalography/methods , Diagnosis, Differential , Neuropsychological Tests
17.
Int J Obes (Lond) ; 38(1): 97-105, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23649471

ABSTRACT

OBJECTIVE: There has been an increase in overweight among women in low- and middle-income countries but whether these trends differ for women in different occupations is unknown. We examined trends by occupational class among women from 33 low- and middle-income countries in four regions. DESIGN: Cross-national study with repeated cross-sectional demographic health surveys. SUBJECTS: Height and weight were assessed at least twice between 1992 and 2009 in 248,925 women aged 25-49 years. Interviews were conducted to assess occupational class, age, place of residence, educational level, household wealth index, parity, age at first birth and breastfeeding. We used logistic and linear regression analyses to assess the annual percent change in overweight (body mass index >25 kg m(-2)) by occupational class. RESULTS: The prevalence of overweight ranged from 2.2% in Nepal in 1992-1997 to 75% in Egypt in 2004-2009. In all the four regions, women working in agriculture had consistently lower prevalence of overweight, while women from professional, technical, managerial as well as clerical occupational classes had higher prevalence. Although the prevalence of overweight increased in all the occupational classes in most regions, women working in agriculture and production experienced the largest increase in overweight over the study period, while women in higher occupational classes experienced smaller increases. To illustrate, overweight increased annually by 0.5% in Latin America and the Caribbean and by 0.7% in Sub-Saharan Africa among women from professional, technical and managerial classes, as compared with 2.8% and 3.7%, respectively, among women in agriculture. CONCLUSION: The prevalence of overweight has increased in most low- and middle-income countries, but women working in agriculture and production have experienced larger increases than women in higher occupational classes.


Subject(s)
Motor Activity , Occupations/statistics & numerical data , Overweight/epidemiology , Sedentary Behavior , Adult , Africa/epidemiology , Asia/epidemiology , Body Height , Body Mass Index , Body Weight , Caribbean Region/epidemiology , Cross-Sectional Studies , Educational Status , Female , Health Education , Humans , Income , Latin America/epidemiology , Logistic Models , Middle Aged , Needs Assessment , Overweight/prevention & control , Parity , Prevalence , Socioeconomic Factors
18.
Obes Rev ; 14(10): 806-17, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23782957

ABSTRACT

This study examined trends in overweight among women of reproductive age by educational level in 33 low- and middle-income countries, and estimated the contribution of parity, age at first birth and breastfeeding to these trends. We used repeated cross-sectional Demographic Health Surveys of 255,828 women aged 25-49 years interviewed between 1992 and 2009. We applied logistic regression to model overweight (>25 kg m(-2) ) as a function of education, reproductive variables and time period by country and region. The prevalence of overweight ranged from 3.4% in South and Southeast Asia to 73.7% in North Africa West/Central Asia during the study period. The association between education and overweight differed across regions. In North Africa West/Central Asia and Latin American, lower education was associated with higher overweight prevalence, while the inverse was true in South/Southeast Asia and Sub-Saharan Africa. In all regions, there was a consistent pattern of increasing overweight trends across all educational groups. Older age at first birth, longer breastfeeding and lower parity were associated with less overweight, for differences by educational level in overweight prevalence and trends.


Subject(s)
Birth Order , Breast Feeding , Developing Countries , Overweight/epidemiology , Parity/physiology , Adult , Asia/epidemiology , Body Mass Index , Cross-Sectional Studies , Educational Status , Female , Health Surveys , Humans , Logistic Models , Middle Aged , Pregnancy , Prevalence , Reproduction/physiology
19.
Rev. Soc. Psiquiatr. Neurol. Infanc. Adolesc ; 22(3): 232-274, dic. 2011. ilus, tab
Article in Spanish | LILACS | ID: lil-677221

ABSTRACT

Por iniciativa de tres instituciones: Liga Chilena contra la Epilepsia (LICHE), Sociedad de Epileptología de Chile (SOCEPCHI) y Sociedad de Psiquiatría y Neurología de la Infancia y Adolescencia (SOPNIA) de Chile, se constituye un comité de trabajo que convoca a un consenso de uso de fármacos antiepilépticos (FAEs) en un grupo de 16 Síndromes electro-clínicos y otras Epilepsias en niños y adolescentes. Cuarenta y dos médicos neuropediatras especialistas en Epilepsias de todas las regiones de Chile, participaron en la discusión y realizaron una propuesta de tratamiento farmacológico para cada cuadro. El comité de trabajo realizó un análisis exhaustivo y discusión de los documentos, para finalmente concluir en una recomendación de tratamiento para cada cuadro. Este consenso es una guía práctica de orientación para ayudar a las decisiones de tratamiento en situaciones clínicas concretas. Su objetivo final es ofrecer una mejor calidad de atención a los niños y adolescentes con epilepsias, a través de decisiones fundadas que contribuyan a disminuir la variabilidad de las decisiones terapéuticas.


Committed by three institutions: Liga Chilena contra la Epilepsia (LICHE), Sociedad de Epileptología de Chile (SOCEPCHI) y Sociedad de Psiquiatría y Neurología de la Infancia y Adolescencia (SOPNIA) de Chile, a 6-member working committee called for a meeting of 42 Chilean pediatric epileptologists from all over the country, with the aim of reaching a consensus on the use of antiepileptic drugs in 16 selected children and adolescents electro-clinical syndromes and epilepsies. These treatment proposals were analyzed and fully discussed by the working committee, ending in an antiepileptic drug treatment recommendation guideline for each condition. This consensus is a practical guideline to be used in specific clinical situations, which aims to support treatment decision making. Its main purpose is to offer the best evidence based treatments to our children and adolescents patients with epilepsy, thus contributing to diminish variability in therapeutic decisions.


Subject(s)
Humans , Adolescent , Child , Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Chile , Consensus
20.
J Epidemiol Community Health ; 65(11): 980-5, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21296902

ABSTRACT

BACKGROUND: To investigate the association between childhood and adulthood socioeconomic position and the hospital-based incidence of hip fractures, and the contribution of health behaviours to these socioeconomic disparities. METHODS: Baseline (1991) information about socioeconomic position in childhood and adulthood, behavioural factors (alcohol consumption, smoking, physical inactivity, coffee consumption) and body height of 25-74-year-old participants (n=18 810) were linked to hospital admissions for hip fractures (ICD9 code 820-821) over a follow-up period of almost 13 years. RESULTS: During follow-up 192 hip fractures resulted in hospital admission. Childhood socioeconomic position was not associated with the incidence of hip fractures. Adjusted for body height, a lower educational level and being in a lower income proxy group were associated with an increased probability of hip fractures (HR=1.88, 95% CI 1.00 to 3.53 in the lowest education group; HR=2.39, 95% 1.46 to 3.92 in the lowest income group). Very excessive alcohol consumption, smoking and physical inactivity were associated with an increased probability of hip fractures, and contributed (10-31%) to socioeconomic disparities in hip fractures. CONCLUSIONS: The higher prevalence of unhealthy behaviour in lower socioeconomic groups in adulthood contributes moderately to socioeconomic disparities in incidence of hip fractures later in life.


Subject(s)
Health Behavior , Hip Fractures/epidemiology , Hospitalization/trends , Social Class , Adult , Aged , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Netherlands/epidemiology , Prospective Studies , Surveys and Questionnaires
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