Search

Background: Hypertension (HTN) and diabetes mellitus (DM) are highly prevalent in low- and middle-income countries (LMIC) and a leading cause of morbidity and mortality. Recent evidence on effectiveness of primary care interventions has attracted renewed calls for their implementation. This review aims to synthesize evidence pertaining to primary care interventions on these two diseases, evaluated and tested in LMICs., Methods: Two reviewers conducted an electronic search of three databases (Pubmed, EMBASE and Web of Science) and screened for eligible articles. Interventions covering health promotion, prevention, treatment, or rehabilitation activities at the PHC or community level were included. Studies published in English, French, Portuguese and Spanish, from January 2007 to January 2017, were included. Key extraction variables included the 12 criteria identified by the Template for Intervention Description and Replication (TIDieR) checklist and guide. The Innovative Care for Chronic Conditions Framework (ICCCF) was used to guide analysis and reporting of results., Results: 198 articles were analyzed. The strategies focused on healthcare service organization (76.5%), community level (9.7 %), creating a positive policy environment (3.6%) and strategies covering multiple domains (10.2%). Studies included related to the following topics: description or testing of interventions (n=81; 41.3%), implementation or evaluation projects (n=42; 21.4%), quality improvement initiatives (n=15; 7.7%), screening and prevention efforts (n=26; 13.2%), management of HTN or DM (n=13; 6.6%), integrated health services (n=10; 5.1%), knowledge and attitude surveys (n=5; 2.5%), cost-effective lab tests (n=2; 1%) and policy making efforts (n=2; 1%). Most studies reported interventions by non-specialists (n=86; 43.4%) and multidisciplinary teams (n=49; 25.5%)., Conclusion: Only 198 articles were found over a 10 year period which demonstrates the limited published research on highly prevalent diseases in LMIC. This review shows the variety and complexity of approaches that have been tested to address HTN and DM in LMICs and highlights the elements of interventions needed to be addressed in order to strengthen delivery of care. Most studies reported little information regarding implementation processes to allow replication. Given the need for multi-component complex interventions, study designs and evaluation techniques will need to be adapted by including process evaluations versus simply effectiveness or outcome evaluations.

Introduction: There is an increasing commitment in the African Region towards diabetes care, following acknowledgement that it is an important public health issue which needs to be addressed in order to improve population health. We conducted a situational analysis of diabetes care in Guinea Bissau in order to identify the main issues faced in the management of the disease in this country., Methods: The study design was qualitative and data collection was done using semi directive interviews and focus groups with participants involved in primary diabetes care and management in Guinea Bissau (health care professionals, non-governmental organization staff, traditional healers) and patients. The data was analyzed using the five-phase approach of the thematic analysis framework., Results: The major themes identified included: the lack of specialists and properly trained healthcare personnel; no standardized care protocol for diagnosis, treatment, follow up and proper management for diabetic patients; resources poor primary health care settings; no validated epidemiological dataset on prevalence and the lack of awareness about diabetes (in general population and also in medical staff)., Conclusion: This first situational analysis can serve as a baseline to develop an action plan to address the main issues identified., Competing Interests: The authors declare no competing interest., (© Jorge César Correia et al.)

Type 2 diabetes is a potentially reversible disease. Patient education encompasses a deep investment of the health care providers, who with the aid of pedagogic tools, help the pa tient commit to this path. This facilitates the learning of uncommon knowledge and skills required. Whether or not it leads to a complete remission of the disease may not be the main purpose. The main goal lies in the patient's motivation to learn and change on a long term basis.

In the word obesity, a clinical concept of chronic systemic disease pairs up with pejorative individual or social representations. Being obese is also facing situations of disability, organ failure, uncertainty of the fate and stigmatization. A care concept inspired by rehabilitation and therapeutic patient education could offer a new way and other purposes to the treatment of obesity. Restoring functions, learning how to adapt and change their environment, obese people may live better today, out of their isolation and develop partners in their projects of life and health. Rehabilitation of an obese patient is much more than weight loss!

Background: Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species., Methods: Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species., Results: Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001)., Conclusions: These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.

This article presents an approach of obesity centered on patients' experience. How is obesity defined by these latter? Is it considered as a disease? Is it apprehended by them as an element to fight or as a potentially meaningful event? Has the sick person the feeling to suffer from obesity or to have resources to face it? At the crossroads of three human sciences (sociology, anthropology and education), this approach aims to enrich and increase the efficiency of therapeutic patient education for obese patients. Extended experience narration extracts are presented in this article, obtained from research interviews. They show the importance of taking into account the "subjective experience" of the disease when accompanying persons affected by obesity.

Objective: To evaluate the clinical, methodological and reporting aspects of systematic reviews and meta-analyses in order to determine the efficacy of therapeutic patient education (TPE)., Methods: A thorough search of the medical and nursing literature recorded in MedLine database from 1999 to August 2009 was conducted using the keywords: patient education, efficacy, diabetes, asthma, COPD, hypertension, cardiology, obesity, rheumatology, and oncology., Results: Thirty five relevant meta-analyses were identified and initially selected for critical analyses (598 studies concerning approximately 61,000 patients). The detailed description of the educative intervention was present in 4% of articles whereas in 23% the interventions were briefly described. In the majority of studies, the educative interventions were only named (49%) or totally absent (24%). The majority of studies reported improvement of patient outcomes due to the TPE (64%), 30% of studies reported no effect of TPE and 6% of the analysed reviews and meta-analyses reported worsening of measured outcomes., Conclusion: Patient education could improve patient outcomes. The high benefit from TPE was shown by articles with detailed description of educational intervention as well as by those who report multidimensional and multidisciplinary educational intervention., Practice Implications: The impact of therapeutic patient education on health outcomes is 50-80%., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

This paper describes a novel tape platform ion sensing methodology specific to the detection of cadmium(II) ions in aqueous solution based on assisted ion transfer reactions across a polarized water/organic gel micro-interface. The tape ion sensors were constructed to incorporate the micro-water/polyvinylchloride-2-nitrophenylethyl ether (PVC-NPOE) gel interfaces referred to as ionodes. The sensors have overall thicknesses less than 300 microm, allowing their packaging in a disposable tape format. The detection methodology is based on the selective assisted transfer of the cadmium ion in aqueous phase by ETH 1062 present in the PVC-NPOE gel layer and was first investigated using cyclic voltammetry. Quantitative analysis of cadmium(II) ions in aqueous solution using the tape sensors was then conducted under stop-flow conditions. Detection limits as low as 20 ppb (178 nM) for Cd(II) ions in very small volumes as low as a single 20 microl droplet without any sample preconcentration was achieved in an analysis time of approximately 20s, which could be easily employed for the direct measurement of Cd(II) ion levels in various field applications. The tape ion sensor can also be used in a flow-cell geometry to preconcentrate Cd(II) ions from aqueous samples and further improve the detection limit.

Therapeutic patient education has been developed over more than 30 years, to better treat chronic patients. The purpose of this article is to summarize its efficiency, based on recent meta-analysis publications. This analysis reflects more than 500 studies concerning ten diseases. It appears that the educative interventions are poorly described and that it is frequent that the control group also received some basic education. Despite these biases, the efficiency of the therapeutic patient education is clearly demonstrated in the majority of the studies (60%), whatever the pathologies or indicators are. Concerning obesity, one can find exactly the same tendency, with consequent and long lasting weight losses.

Myocardial infarction is a frequent, serious and recurrent complication of a chronic disease: atherosclerosis. Therapeutic advances have improved the clinical outcome of affected patients and have shortened the hospital length of stay. However, to decrease the recurrence of cardiovascular events, it is essential to increase adherence to therapeutic projects by improving information given to coronary patients during the short initial hospitalization. This can be achieved by using tools that have been developed for the management of chronic disease: therapeutic education and motivational interviews. Moreover, these information tools have to perform well and have to be used at appropriate times to ensure a positive effect on patients.

Dealing with a long term chronic disease necessarily implies changes of behaviour. In the field of obesity, these behaviours concern habits which are very often firmly fixed in patients' lives. The study of patients' representations is of great interest in the medical field. Representations guide behaviours and therefore build up an important factor which determines the adherence to the treatment. Representations always have a foundation and making them rise up induces a non-judge-mental attitude. The health care provider can help the patient make them evolve. It must be highlighted that health care providers' representations are also important, particularly in the therapeutic relationship. This article proposes a reflection on the obese patients follow-up situation as well as some clinical implications.

Therapeutic patient education is a patient-centred approach, focussed on patients' needs, resources, values and strategies. It allows patients to improve their knowledge and skills not only concerning their illness but also their treatment. It brings a better quality of life, a greater therapeutic compliance and a reduction in complications. The most difficult part of therapeutic patient education occurs when patients must change their behaviour. Motivational interviewing and cognitive-behavioural approaches contribute greatly here and allow both the preparation and support of patients during progressive 'step by step' change. The work on resistance to change is fundamental, and ambivalence when faced with the choice of a new way of life must be measured, discussed and negotiated. Patients become partners and we become 'coaches'. The negotiation of objectives must allow patients to choose their own strategies, which normally should cost them the least possible, psychologically, and bring them the maximum benefit. The efficiency of therapeutic patient education no longer needs to be proved: 80% less amputations over 10 years in diabetic patients; 50% maintenance of weight loss over 5 years, etc. In conclusion, therapeutic education is part of a humanistic medical approach centred on patients; it allows them to be active participants in their own treatment with the aim of improving their quality of life and therapeutic compliance, as well as reducing potential complications. Thus, health care professionals teach, inform, train, negotiate with, motivate and accompany patients in the long-term follow-up of their illness., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Antioxidant redox sensors based on DNA modified carbon screen-printed electrodes were developed. The carbon ink was doped with TiO2 nanoparticles, onto which double-strand DNA was adsorbed. A redox mediator, namely, tris-2,2'-bipyridine ruthenium(II) [Ru(bpy)3(2+)] was electrooxidized on the electrode surface to subsequently oxidize both the adsorbed ds-DNA and the antioxidants in solution. The resulting oxidation damage of the adsorbed ds-DNA was then detected by square wave voltammetry in a second solution containing only Ru(bpy)3Cl2 at a low concentration (microM). A kinetic model was developed to study the protecting role of antioxidants in aqueous solutions. The electrochemical sensor has been applied to evaluate the redox antioxidant capacity of different molecules.

TiO2/ITO modified electrodes were developed to quantitatively photooxidize adsorbed ds-DNA and to study the effect of antioxidants as ds-DNA protecting agents. TiO2 films are used for efficient ds-DNA immobilization, for ds-DNA oxidation through photogenerated hydroxyl radicals, and as electrodes for amperometric sensing. The films, prepared by a sol-gel process, are deposited on ITO glass electrodes. Damages occurring after ds-DNA oxidation by ROS are detected by adding MB as an intercalant probe and by monitoring the electrochemical reduction current of the intercalated redox probe. The MB electrochemical signal is found to be sensitive enough to monitor ds-DNA structure changes, and the electrochemical sensor has been applied to the evaluation of the antioxidant properties of glutathione and gallic acid.

Therapeutic education is a patient centred approach focused on patients' needs, values and strategies. It allows not only to increase patients' knowledge and skills on the disease, but also on their treatments. It brings a better quality of life, an increased therapeutic compliance, and decreases complications. The most difficult part of therapeutic education occurs when patients must change their behaviour. Motivational interviewing techniques are of great support and allow to prepare and support patients in "step by step" progressive changes. It is essential to work on resistance to change. The ambivalence in the choice of a new lifestyle must be measured, discussed and negotiate. Patients become partners and health care providers become coaches. To negotiate objectives must allow patients to choose their own strategies which should cost them minimum psychological efforts and bring them maximum benefits. The efficacy of therapeutic education has not to be proved any more: 80% less of amputations at 10 years in diabetic patients, 50% of stable body weight after weight loss at 5 years, etc. In conclusion, therapeutic education is part of a humanist medicine centred on patients which allow them to take care of their own treatment, in order to improve their quality of life, therapeutic compliance and potential complications. The health care providers teach, train, negotiate, motivate and accompany their patients in the long-term follow-up of their diseases.

The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is an important regulator of cell cycle progression, senescence, and differentiation. Genotoxic stress leads to activation of the tumor suppressor p53 and subsequently to induction of p21 expression. Here we show that the tumor suppressor p53 cooperates with the transcription factor Sp1 in the activation of the p21 promoter, whereas histone deacetylase 1 (HDAC1) counteracts p53-induced transcription from the p21 gene. The p53 protein binds directly to the C terminus of Sp1, a domain which was previously shown to be required for the interaction with HDAC1. Induction of p53 in response to DNA-damaging agents resulted in the formation of p53-Sp1 complexes and simultaneous dissociation of HDAC1 from the C terminus of Sp1. Chromatin immunoprecipitation experiments demonstrated the association of HDAC1 with the p21 gene in proliferating cells. Genotoxic stress led to recruitment of p53, reduced binding of HDAC1, and hyperacetylation of core histones at the p21 promoter. Our findings show that the deacetylase HDAC1 acts as an antagonist of the tumor suppressor p53 in the regulation of the cyclin-dependent kinase inhibitor p21 and provide a basis for understanding the function of histone deacetylase inhibitors as antitumor drugs.

Histone deacetylase 1 (HDAC1) is a major regulator of chromatin structure and gene expression. Tight control of HDAC1 expression is essential for normal cell cycle progression of mammalian cells. HDAC1 mRNA levels are regulated by growth factors and by changes in intracellular deacetylase activity levels. Stimulation of the mitogen-activated protein kinase cascade by anisomycin or growth factors, together with inhibition of deacetylases by trichostatin A (TSA), leads to stable histone H3 phosphoacetylation and strongly induced HDAC1 expression. In contrast, activation of the nucleosomal response by anisomycin alone results only in transient phosphoacetylation of histone H3 without affecting HDAC1 mRNA levels. The transcriptional induction of the HDAC1 gene by anisomycin and TSA is efficiently blocked by H89, an inhibitor of the nucleosomal response. Detailed studies of the kinetics of histone acetylation and phosphorylation show that the two modifications are synergistic and essential for induced HDAC1 transcription. Activation of the HDAC1 gene by anisomycin together with TSA or by growth factors is accompanied by phosphoacetylation of HDAC1 promoter-associated histone H3. Our results present evidence for a precise regulatory mechanism which allows induction of the HDAC1 gene in response to proliferation signals and modulation of HDAC1 expression dependent on intracellular deacetylase levels.

This paper presents a novel technique based on plasma etching for the mass production of polymer microchip devices. The method consists of the patterning of a photo-resist by a high resolution printer on a foil composed of three layers (5 microm copper/50 microm polyimide/5 microm copper). After this step, both copper layers are chemically etched in order to serve as a contact mask on the polyimide surface so as to produce the desired microstructure pattern. The foil is placed into a reactive plasma chamber in order to etch the exposed polyimide by means of an oxidizing plasma. The method enables holes, lines or larger areas to be etched, thereby generating either microholes, microchannels or electrodes in the plastic material. The copper can then be chemically removed or further patterned to produce conductive pads which are further electroplated with gold. The microchannel is then covered with a polyethylene terephthalate/polyethylene (PET/PE) lamination. The strength of this technology is that access holes for the fluid inlet and outlet, as well as gold coated electrodes can be fabricated without post-processing in a batch process. Demonstration of the application of such microelectrochemical systems is shown here by voltammetric detection inside a 60 nL microchannel, which presents the special feature of linear depletion of the analytes in the direction parallel to the microchannel.

Histone deacetylases (HDACs) modulate chromatin structure and transcription, but little is known about their function in mammalian development. HDAC1 was implicated previously in the repression of genes required for cell proliferation and differentiation. Here we show that targeted disruption of both HDAC1 alleles results in embryonic lethality before E10.5 due to severe proliferation defects and retardation in development. HDAC1-deficient embryonic stem cells show reduced proliferation rates, which correlate with decreased cyclin-associated kinase activities and elevated levels of the cyclin-dependent kinase inhibitors p21(WAF1/CIP1) and p27(KIP1). Similarly, expression of p21 and p27 is up-regulated in HDAC1-null embryos. In addition, loss of HDAC1 leads to significantly reduced overall deacetylase activity, hyperacetylation of a subset of histones H3 and H4 and concomitant changes in other histone modifications. The expression of HDAC2 and HDAC3 is induced in HDAC1-deficient cells, but cannot compensate for loss of the enzyme, suggesting a unique function for HDAC1. Our study provides the first evidence that a histone deacetylase is essential for unrestricted cell proliferation by repressing the expression of selective cell cycle inhibitors.

The members of the Sp1 transcription factor family can act as both negative and positive regulators of gene expression. Here we show that Sp1 can be a target for histone deacetylase 1 (HDAC1)-mediated transcriptional repression. The histone deacetylase inhibitor trichostatin A activates the chromosomally integrated murine thymidine kinase promoter in an Sp1-dependent manner. Coimmunoprecipitation experiments with Swiss 3T3 fibroblasts and 293 cells demonstrate that Sp1 and HDAC1 can be part of the same complex. The interaction between Sp1 and HDAC1 is direct and requires the carboxy-terminal domain of Sp1. Previously we have shown that the C terminus of Sp1 is necessary for the interaction with the transcription factor E2F1 (J. Karlseder, H. Rotheneder, and E. Wintersberger, Mol. Cell. Biol. 16:1659-1667, 1996). Coexpression of E2F1 interferes with HDAC1 binding to Sp1 and abolishes Sp1-mediated transcriptional repression. Our results indicate that one component of Sp1-dependent gene regulation involves competition between the transcriptional repressor HDAC1 and the transactivating factor E2F1.

Proliferation and cell cycle progression of eukaryotic cells are closely linked to changes in chromatin structure and gene expression. By reversible histone acetylation the cell is able to modulate chromatin condensation and accessibility of specific regions within the chromatin. Here, we examined histone H4 acetylation patterns during growth induction of the murine interleukin-2 dependent T cell line B6.1. In order to detect acetylation on each of the four potential target residues we produced a set of antibodies recognizing specifically acetylated lysine 5, 8, 12 and 16 in the N-terminal tail of histone H4. Acetylation was generally low in resting T cells, but increased after stimulation with a specific kinetics for each lysine. Lysine 16 was acetylated during the G1 phase and deacetylated during S phase. H4 acetylation on lysine 5, 8 and 12, in contrast, was induced before cells started to replicate, and persisted until cells entered mitosis. Treatment of resting B6.1 cells with the specific deacetylase inhibitor trichostatin A (TSA) led to H4 hyperacetylation at all four lysine residues indicating that the histone modification can occur in the absence of replication. After release from TSA treatment normal H4 acetylation levels were reestablished by extremely rapid deacetylation of lysines 5, 8, 12 and 16. The deacetylation step was 60-100 times faster than TSA induced acetylation and equally efficient in resting and exponentially growing T cells. Our results indicate the presence of cell cycle regulated lysine specific acetylating and deacetylating activities in mouse T cells.

The avian erythroblastosis virus (AEV) oncoprotein v-ErbA represents a mutated, oncogenic thyroid hormone receptor alpha (c-ErbA/ TRalpha). v-ErbA cooperates with the stem cell factor-activated, endogenous receptor tyrosine kinase c-Kit to induce self-renewal and to arrest differentiation of primary avian erythroblasts, the AEV transformation target cells. In this cooperation, v-ErbA substitutes for endogenous steroid hormone receptor function required for sustained proliferation of non-transformed erythroid progenitors. In this paper, we propose a novel concept of how v-ErbA transforms erythroblasts. Using culture media strictly depleted from thyroid hormone (T3) and retinoids, the ligands for c-ErbA/TRalpha and its co-receptor RXR, we show that overexpressed, unliganded c-ErbA/ TRalpha closely resembles v-ErbA in its activity on primary erythroblasts. In cooperation with ligand-activated c-Kit, c-ErbA/ TRalpha causes steroid-independent, long-term proliferation and tightly blocks differentiation. Activation of c-ErbA/ TRalpha by physiological T3 levels causes the loss of self-renewal capacity and induces synchronous, terminal differentiation under otherwise identical conditions. This T3-induced switch in erythroid progenitor development is correlated with a decrease of c-ErbA-associated histone deacetylase activity. Our results suggest that the crucial role of the mutations activating v-erbA as an oncogene is to 'freeze' c-ErbA/ TRalpha in its non-liganded, repressive conformation and to facilitate its overexpression.

Reversible acetylation of core histones plays an important role in transcriptional regulation, cell cycle progression, and developmental events. The acetylation state of histones is controlled by the activities of acetylating and deacetylating enzymes. By using differential mRNA display, we have identified a mouse histone deacetylase gene, HD1, as an interleukin-2-inducible gene in murine T cells. Sequence alignments revealed that murine HD1 is highly homologous to the yeast RPD3 pleiotropic transcriptional regulator. Indirect immunofluorescence microscopy proved that mouse HD1 is a nuclear protein. When expressed in yeast, murine HD1 was also detected in the nucleus, although it failed to complement the rpd3delta deletion phenotype. HD1 mRNA expression was low in G0 mouse cells but increased when the cells crossed the G1/S boundary after growth stimulation. Immunoprecipitation experiments and functional in vitro assays showed that HD1 protein is associated with histone deacetylase activity. Both HD1 protein levels and total histone deacetylase activity increased upon interleukin-2 stimulation of resting B6.1 cells. When coexpressed with a luciferase reporter construct, HD1 acted as a negative regulator of the Rous sarcoma virus enhancer/promoter. HD1 overexpression in stably transfected Swiss 3T3 cells caused a severe delay during the G2/M phases of the cell cycle. Our results indicate that balanced histone acetylation/deacetylation is crucial for normal cell cycle progression of mammalian cells.