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- A Computational Physiology Approach to Personalized Treatment Models: The Beneficial Effects of Slow Breathing on the Human Cardiovascular System. [JOURNAL ARTICLE]
- Am J Physiol Heart Circ Physiol 2014 Jul 25.
Heart rate variability biofeedback intervention involves slow breathing at a rate of ~6 breaths per min (resonance breathing) to maximize respiratory and baroreflex effects on heart period oscillations. This intervention has wide-ranging clinical benefits and is gaining empirical support as an adjunct therapy for biobehavioral disorders, including asthma and depression. Yet, little is known about the system-level cardiovascular changes that occur during resonance breathing or the extent to which individuals differ in cardiovascular benefit. This study used a computational physiology approach to dynamically model the human cardiovascular system at rest and during resonance breathing. Noninvasive measurements of heart period, beat-to-beat systolic and diastolic blood pressure, and respiration period were obtained from 24 healthy young men and women. A model with respiration as input was parameterized to better understand how the cardiovascular processes that control variability in heart period and blood pressure change from rest to resonance breathing. The cost function used in model calibration corresponded to the difference between the experimental data and model outputs. A good match was observed between the data and model outputs (heart period, blood pressure, and corresponding power spectral densities). Significant improvements in several modeled cardiovascular functions (e.g., blood flow to internal organs, sensitivity of the sympathetic component of the baroreflex, ventricular elastance) were observed during resonance breathing. Individual differences in the magnitude and nature of these dynamic responses suggest that computational physiology may be clinically useful for tailoring heart rate variability biofeedback interventions for the needs of individual patients.
- Allaitement maternel : les bénéfices pour la santé de l'enfant et de sa mère. [JOURNAL ARTICLE]
- Arch Pediatr 2013 Nov.:S29-S48.
The prevalence of breastfeeding in France is one of the lowest in Europe: 65% of infants born in France in 2010 were breastfed when leaving the maternity ward. Exclusive breastfeeding allows normal growth until at least 6 months of age, and can be prolonged until the age of 2 years or more, provided that complementary feeding is started after 6 months. Breast milk contains hormones, growth factors, cytokines, immunocompetent cells, etc., and has many biological properties. The composition of breast milk is influenced by gestational and postnatal age, as well as by the moment of the feed. Breastfeeding is associated with slightly enhanced performance on tests of cognitive development. Exclusive breastfeeding for at least 3 months is associated with a lower incidence and severity of diarrhoea, otitis media and respiratory infection. Exclusive breastfeeding for at least 4 months is associated with a lower incidence of allergic disease (asthma, atopic dermatitis) during the first 2 to 3 years of life in at-risk infants (infants with at least one first-degree relative presenting with allergy). Breastfeeding is also associated with a lower incidence of obesity during childhood and adolescence, as well as with a lower blood pressure and cholesterolemia in adulthood. However, no beneficial effect of breastfeeding on cardiovascular morbidity and mortality has been shown. Maternal infection with hepatitis B and C virus is not a contraindication to breastfeeding, as opposed to HIV infection and galactosemia. A supplementation with vitamin D and K is necessary in the breastfed infant. Very few medications contraindicate breastfeeding. Premature babies can be breastfed and/or receive mother's milk and/or bank milk, provided they receive energy, protein and mineral supplements. Return to prepregnancy weight is earlier in breastfeeding mothers during the 6 months following delivery. Breastfeeding is also associated with a decreased risk of breast and ovarian cancer in the premenopausal period, and of osteoporosis in the postmenopausal period.
- Bidirectional Cross-Regulation between the Endothelial Nitric Oxide Synthase and β-Catenin Signaling Pathways. [JOURNAL ARTICLE]
- Cardiovasc Res 2014 Jul 25.
β-catenin has been shown to be regulated by inducible nitric oxide synthase (NOS) in endothelial cells. We investigated here whether β-catenin interacts with and regulates endothelial NOS (eNOS) and whether eNOS activation promotes β-catenin signaling.We identified β-catenin as a novel eNOS binding protein in human umbilical vein endothelial cells (HUVECs) by mass spectroscopy and western blot analyses of β-catenin and eNOS immunoprecipitates. This was confirmed by in situ proximity ligation assay. eNOS activity, assessed by cGMP production and eNOS phosphorylation (Ser1177), was enhanced in β-catenin(-/-) mouse pulmonary endothelial cells (MPECs) relative to wild type MPECs. eNOS activation (using adenosine, salbutamol, thrombin or histamine), or application of an NO donor (spermine NONOate) or cGMP-analogue (8-bromo-cGMP) caused nuclear translocation of β-catenin in HUVEC as shown by western blotting of nuclear extracts. Exposure to spermine NONOate, 8-bromo-cGMP or sildenafil (a phosphodiesterase type 5 inhibitor) also increased the expression of β-catenin-dependent transcripts, IL-8 and cyclin D1. Stimulation of wild type MPECs with basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), spermine NONOate, 8-bromo-cGMP or sildenafil increased tube length relative to controls in an angiogenesis assay. These responses were abrogated in β-catenin(-/-) MPECs, with the exception of that to bFGF which is NO-independent. In C57BL/6 mice, subcutaneous VEGF-supplemented Matrigel plugs containing β-catenin(-/-) MPECs exhibited reduced angiogenesis compared to plugs containing wild type MPECs. Angiogenesis was not altered in bFGF-supplemented Matrigel.These data reveal bidirectional cross talk and regulation between the NO-cGMP and β-catenin signaling pathways.
- Airway smooth muscle in asthma: Linking contraction and mechanotransduction to disease pathogenesis and remodelling. [JOURNAL ARTICLE]
- Pulm Pharmacol Ther 2014 Jul 22.
Asthma is an obstructive airway disease, with a heterogeneous and multifactorial pathogenesis. Although generally considered to be a disease principally driven by chronic inflammation, it is becoming increasingly recognised that the immune component of the pathology poorly correlates with the clinical symptoms of asthma, thus highlighting a potentially central role for non-immune cells. In this context airway smooth muscle (ASM) may be a key player, as it comprises a significant proportion of the airway wall and is the ultimate effector of acute airway narrowing. Historically, the contribution of ASM to asthma pathogenesis has been contentious, yet emerging evidence suggests that ASM contractile activation imparts chronic effects that extend well beyond the temporary effects of bronchoconstriction. In this review article we describe the effects that ASM contraction, in combination with cellular mechanotransduction and novel contraction-inflammation synergies, contribute to asthma pathogenesis. Specific emphasis will be placed on the effects that ASM contraction exerts on the mechanical properties of the airway wall, as well as novel mechanisms by which ASM contraction may contribute to more established features of asthma such as airway wall remodelling.
- Inhaler reminders improve adherence with controller treatment in primary care patients with asthma. [JOURNAL ARTICLE]
- J Allergy Clin Immunol 2014 Jul 18.
Poor adherence contributes to uncontrolled asthma. Pragmatic adherence interventions for primary care settings are lacking.To test the effectiveness of 2 brief general practitioner (GP)-delivered interventions for improving adherence and asthma control.In a 6-month cluster randomized 2 × 2 factorial controlled trial, with GP as unit of cluster, we compared inhaler reminders and feedback (IRF) and/or personalized adherence discussions (PADs) with active usual care alone; all GPs received action plan and inhaler technique training. GPs enrolled patients prescribed combination controller inhalers, with suboptimal Asthma Control Test (ACT) scores (ACT score ≤19). Inhaler monitors recorded fluticasone propionate/salmeterol adherence (covertly for non-IRF groups) and, in IRF groups, provided twice-daily reminders for missed doses, and adherence feedback. PAD GPs received communication training regarding adherence. Outcomes collected every 2 months included ACT scores (primary outcome) and severe exacerbations. Intention-to-treat mixed-model analysis incorporated cluster effect and repeated measures.A total of 43 GPs enrolled 143 patients with moderate-severe asthma (mean age, 40.3 ± 15.2 years; ACT score, 14.6 ± 3.8; fluticasone propionate dose, 718 ± 470 μg). Over 6 months, adherence was significantly higher in the IRF group than in non-IRF groups (73% ± 26% vs 46% ± 28% of prescribed daily doses; P < .0001), but not between PAD and non-PAD groups. Asthma control improved overall (mean change in ACT score, 4.5 ± 4.9; P < .0001), with no significant difference among groups (P = .14). Severe exacerbations were experienced by 11% of the patients in IRF groups and 28% of the patients in non-IRF groups (P = .013; after adjustment for exacerbation history; P = .06).Inhaler reminders offer an effective strategy for improving adherence in primary care compared with a behavioral intervention or usual care, although this may not be reflected in differences in day-to-day asthma control.
- Are chronic diseases related to height? Results from the Portuguese National Health Interview Survey. [JOURNAL ARTICLE]
- Econ Hum Biol 2014 Jul 8.:56-66.
This paper analyze the association between height and chronic diseases in Portugal and the extent to which this relationship is mediated by education. The sample upon which the analysis is based comprised those participants in the 2005/2006 Portuguese National Health Interview Survey (n=28,433) aged 25-79. Logistic regressions measured the association of height with ten chronic diseases, adjusting for age, lifestyle, education, and other socioeconomic factors. Among women, an additional centimeter in stature significantly decreased the prevalence of asthma, chronic pain, and acute cardiac disease, by 0.057, 0.221, and 0.033 percentage points, respectively. Also, mental disorders were significantly less prevalent in the last quartile of height. Among men, an additional centimeter in height was associated with a 0.074 lower prevalence of asthma, and men in the last quartile of height were significantly less at risk of acute cardiovascular disease. There was no significant association between height and the risk of diabetes, high blood pressure, cancer, and pulmonary diseases. As for the impact of education, women with a tertiary level were on average 5.3cm taller than those with no schooling; among men, the difference was almost 9cm. Adjusting for education reduced the height-related excess risk of ill health by 36% on average among men, and by 7% among women. The analysis indicates that there is a significant association of height with several chronic conditions, and that education plays a mediating role in the height-health connection. By emphasizing the role of height and education as determinants of chronic conditions, this paper also highlights the role of conditions related to childhood health and socioeconomic background.
- Modulation of immune responses by immunotherapy in allergic diseases. [REVIEW]
- Curr Opin Pharmacol 2014 Jul 22.:30-37.
Allergen immunotherapy (AIT) has been used for 100 years and until now different immunoregulatory pathways have been shown to take place in its mechanisms of action. It is characterized by administration of the causative allergen and is shown to be clinically efficient even after discontinuation of therapy particularly in allergic respiratory diseases, bee venom allergy, and food allergy. Generation of antigen/allergen-specific peripheral tolerance is the key mechanism during immunotherapy. It is mediated by development of T and B regulatory cells, IgG4 isotype allergen-specific antibodies and the involvement of multiple suppressor factors, which lead to decreased tissue inflammation, early and late phase responses. Describing novel regulatory mechanisms in the process of immune tolerance induction will help to identify treatment modalities not only for allergic disorders, but also for autoimmune diseases, organ transplantation, chronic infections, and cancer.
- Medication monitoring and optimization: a targeted pharmacist program for effective and cost-effective improvement of chronic therapy adherence. [Journal Article]
- J Manag Care Pharm 2014 Aug; 20(8):786-92.
Community pharmacies provide a promising platform for monitoring and improving therapy adherence and providing pharmaceutical care. Structured methods and appropriate software are important tools to increase pharmacist effectiveness and improve health outcomes. In 2006, the Medication Monitoring and Optimization (MeMO) program was introduced in several community pharmacies in the Netherlands. MeMO facilitates targeted and continuous patient-centered pharmaceutical care around chronic medication, such as for osteoporosis, cardiovascular disease, and asthma/chronic obstructive pulmonary disease (COPD).To describe the MeMO program and summarize findings from publications on its effectiveness, patient satisfaction, and cost-effectiveness. In the first part of this article, the MeMO program is extensively described. In the second part, a review of the evidence of effectiveness, cost-effectiveness, and patient satisfaction of the MeMO program is provided. Evidence is based on 5 previously published articles.The MeMO program starts with structured counseling sessions with patients at the initiation and follow-up of chronic therapies. This process is followed by a continuous phase in which patients' therapy adherence is monitored on a monthly basis, using standardized search algorithms in the pharmacy database. When the algorithm detects a patient's discontinuation of therapy, tailored interventions are used to improve adherence and optimize pharmacotherapy. For osteoporosis patients, treatment discontinuation with bisphosphonates after 1 year dropped from 31.7% to 16.1% (P less than 0.001). This program was shown to be cost-effective in patients initiating osteoporotic therapy. Future scenarios with lower drug prices (e.g., from generic prescribing) result in cost savings for the MeMO program. For lipid-lowering drugs, the MeMO program has been shown to lower therapy discontinuation after 1 year from 25.9% to 13.6% (P less than 0.001). By extrapolating these results to patients' lifetimes, the intervention was estimated to be cost-effective, with gains for primary prevention of cardiovascular events, and even cost saving in secondary prevention. Results from the ongoing MeMO asthma/COPD program are promising, showing marked improvements in therapy control and quality of life for asthma and COPD patients. Almost all patients participating in MeMO programs are satisfied with the pharmacy team and have gained knowledge of the effectiveness and administration of their medications and the importance of therapy adherence.The MeMO program is an effective and structured method to improve patients' adherence to chronic medication in the field of osteoporosis, lipid-lowering drugs, and asthma/COPD and is well received by patients. By targeting the program toward nonadherent and high-risk patients, the program showed favorable cost-effectiveness.
- PURLs: Think twice about nebulizers for asthma attacks. [Journal Article]
- J Fam Pract 2014 Jun; 63(6):321-46.
MDIs with spacers are as effective as nebulizers for delivering beta-agonists and less likely to cause adverse effects.
- Hepatotoxicity caused by montelukast in a paediatric patient. [Journal Article]
- Prz Gastroenterol 2014; 9(2):121-3.
Montelukast is a selective and competitive cysteinyl leukotriene receptor antagonist (CystLTRA) which is increasingly used for the treatment of allergic asthma. Recently, hepatotoxicity has been reported with this drug in adult patients, but only one letter to the editor has reported a case of probable montelukast-induced hepatotoxicity in a child. We present a case of a 3.5-year-old boy, receiving treatment with montelukast, who developed hepatocellular injury. The exclusion of other causes of increased activity of aminotransferases (viral, metabolic, autoimmune), improvement after dechallenge, the morphological findings and previous reports of comparable cases support the diagnosis of montelukast-induced liver injury in this boy. Physicians should strictly analyse indications for this drug and be aware of potential drug-induced liver disease caused by this agent. Therefore, the periodical assessment of aminotransferases should be recommended during treatment with this leukotriene modifier.