Electric fields have been highlighted as a smart reagent in nature's enzymatic machinery, as they can directly trigger or accelerate chemical processes with stereo- and regio-specificity. In ...enzymatic catalysis, controlled mass transport of chemical species is also key in facilitating the availability of reactants in the active reaction site. However, recent progress in developing a clean catalysis that profits from oriented electric fields is limited to theoretical and experimental studies at the single molecule level, where both the control over mass transport and scalability cannot be tested. Here, we quantify the electrostatic catalysis of a prototypical Huisgen cycloaddition in a large-area electrode surface and directly compare its performance to the conventional Cu(I) catalysis. Our custom-built microfluidic cell enhances reagent transport towards the electrified reactive interface. This continuous-flow microfluidic electrostatic reactor is an example of an electric-field driven platform where clean large-scale electrostatic catalytic processes can be efficiently implemented and regulated.
Abstract Introduction The available information on the cost of illness of Borderline Personality Disorder (BPD) is overtly insufficient for policy planning. Our aim was to estimate the costs of ...illness for BPD in Catalonia (Spain) for 2006. Methods This is a multilevel cross-design synthesis study combining a qualitative nominal approach, quantitative ‘top-down’ analysis of multiple health databases, and ‘bottom-up’ data of local surveys. Both direct and indirect costs have been estimated from a governmental and societal perspective. Results Estimated year-prevalence of BPD was 0.7% (41,921 cases), but only 9.6% of these cases were treated in the mental health system (4033 cases). The baseline of the total cost of BPD in Catalonia was 45.6 million €, of which 15.8 million € (34.7%) were direct costs related to mental health care. The cost distribution was 0.4% in primary care; 4% in outpatient mental health care; 4.7% in hospitalisation; 0.7% in emergency care; and 24.9% in pharmacotherapy. Additionally, the cost of drug addiction treatment for persons with BPD was 11.2%; costs associated with sheltered employment were 23.9% and those of crime and justice were 9.7%. Indirect costs – including temporary sick leave and premature death (suicide) – represented 20.5% of total costs. The average annual cost per patient was 11,308 €. Conclusions An under-reporting of BPD was identified by the experts in all health databases and official registries. Most of the BPD costs were not related to mental health care. Amongst the direct cost categories, pharmacotherapy had the largest proportion despite the lack of specificity for BPD. This distribution of costs reinforces the idea of BPD complexity related to an inadequate and inefficient use of health resources.
Aging can be viewed as a quasi-programmed phenomenon driven by the overactivation of the nutrient-sensing mTOR gerogene. mTOR-driven aging can be triggered or accelerated by a decline or loss of ...responsiveness to activation of the energy-sensing protein AMPK, a critical gerosuppressor of mTOR. The occurrence of age-related diseases, therefore, reflects the synergistic interaction between our evolutionary path to sedentarism, which chronically increases a number of mTOR activating gero-promoters (e.g., food, growth factors, cytokines and insulin) and the "defective design" of central metabolic integrators such as mTOR and AMPK. Our laboratories at the Bioactive Food Component Platform in Spain have initiated a systematic approach to molecularly elucidate and clinically explore whether the "xenohormesis hypothesis," which states that stress-induced synthesis of plant polyphenols and many other phytochemicals provides an environmental chemical signature that upregulates stress-resistance pathways in plant consumers, can be explained in terms of the reactivity of the AMPK/mTOR-axis to so-called xenohormetins. Here, we explore the AMPK/mTOR-xenohormetic nature of complex polyphenols naturally present in extra virgin olive oil (EVOO), a pivotal component of the Mediterranean style diet that has been repeatedly associated with a reduction in age-related morbid conditions and longer life expectancy. Using crude EVOO phenolic extracts highly enriched in the secoiridoids oleuropein aglycon and decarboxymethyl oleuropein aglycon, we show for the first time that (1) the anticancer activity of EVOO secoiridoids is related to the activation of anti-aging/cellular stress-like gene signatures, including endoplasmic reticulum (ER) stress and the unfolded protein response, spermidine and polyamine metabolism, sirtuin-1 (SIRT1) and NRF2 signaling; (2) EVOO secoiridoids activate AMPK and suppress crucial genes involved in the Warburg effect and the self-renewal capacity of "immortal" cancer stem cells; (3) EVOO secoiridoids prevent age-related changes in the cell size, morphological heterogeneity, arrayed cell arrangement and senescence-associated β-galactosidase staining of normal diploid human fibroblasts at the end of their proliferative lifespans. EVOO secoiridoids, which provide an effective defense against plant attack by herbivores and pathogens, are bona fide xenohormetins that are able to activate the gerosuppressor AMPK and trigger numerous resveratrol-like anti-aging transcriptomic signatures. As such, EVOO secoiridoids constitute a new family of plant-produced gerosuppressant agents that molecularly "repair" the aimless (and harmful) AMPK/mTOR-driven quasi-program that leads to aging and aging-related diseases, including cancer.
Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single ...dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti‐inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I‐converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti‐inflammatory, and endothelium‐dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks.
Abstract Background Collaborative care programmes lead to better outcomes in the management of depression. A programme of this nature has demonstrated its effectiveness in primary care in Spain. Our ...objective was to evaluate the cost-effectiveness of this programme compared to usual care. Methods A bottom-up cost-effectiveness analysis was conducted within a randomized controlled trial (2007–2010). The intervention consisted of a collaborative care programme with clinical, educational and organizational procedures. Outcomes were monitored over a 12 months period. Primary outcomes were incremental cost-effectiveness ratios (ICER): mean differences in costs divided by quality-adjusted life years (QALY) and mean differences in costs divided by depression-free days (DFD). Analyses were performed from a healthcare system perspective (considering healthcare costs) and from a society perspective (including healthcare costs plus loss of productivity costs). Results Three hundred and thirty-eight adult patients with major depression were assessed at baseline. Only patients with complete data were included in the primary analysis (166 in the intervention group and 126 in the control group). From a healthcare perspective, the average incremental cost of the programme compared to usual care was €182.53 ( p <0.001). Incremental effectiveness was 0.045 QALY ( p =0.017) and 40.09 DFD ( p =0.011). ICERs were €4,056/QALY and €4.55/DFD. These estimates and their uncertainty are graphically represented in the cost-effectiveness plane. Limitations The amount of 13.6% of patients with incomplete data may have introduced a bias. Available data about non-healthcare costs were limited, although they may represent most of the total cost of depression. Conclusions The intervention yields better outcomes than usual care with a modest increase in costs, resulting in favourable ICERs. This supports the recommendation for its implementation.
Abstract To analyze the role of parabrachial complex (PBc) in the modulation of cardiorespiratory response evoked from the hypothalamic defense area (HDA), cardiorespiratory changes were analyzed in ...spontaneously breathing anesthetised rats in response to electrical stimulation of the HDA (1 ms pulses, 30–50 μA, 100 Hz for 5 s) before and after the microinjection of muscimol (50 nl, 0.25 nmol, 5 s) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate ( p < 0.001) due to a decrease in expiratory time ( p < 0.01). The respiratory response was accompanied by a pressor ( p < 0.001) and a tachycardic ( p < 0.001) response. Muscimol microinjection within the lateral parabrachial region (lPB) abolished the respiratory response to HDA stimulation ( p < 0.01) and decreased the pressor response ( p < 0.05). Muscimol within the medial parabrachial region and Kölliker-Fuse (mPB-KF) decreased the magnitude of the pressor ( p < 0.01) and tachycardic ( p < 0.05) responses to HDA stimulation. The respiratory response persisted unchanged. Finally, extracellular recording of putative neurons from these regions were obtained during HDA stimulation to confirm functional interaction between HDA and parabrachial regions. 105 pontine cells were recorded during HDA stimulation, 57 from the lPB and 48 from the mPB-KF. In mPB-KF 34/48 (71%) and in lPB 38/57 (67%) cells were influenced from HDA. The results indicate that neurons from different regions of the PBc have an important function in mediating the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.
Objective
Multidisciplinary treatments of fibromyalgia (FM) have demonstrated efficacy. Nevertheless, they have been criticized for not maintaining their benefits and for not being studied for ...specific populations. Our objectives were to determine the efficacy of a multidisciplinary treatment for FM adapted for patients with low educational levels and to determine the maintenance of its therapeutic benefits during a long‐term followup period.
Methods
Inclusion criteria consisted of female sex, a diagnosis of FM (using American College of Rheumatology criteria), age between 18 and 60 years, and between 3 and 8 years of schooling. Patients were randomly assigned to 1 of the 2 treatment conditions: conventional pharmacologic treatment or multidisciplinary treatment. Outcome measures were functionality, sleep disturbances, pain intensity, catastrophizing, and psychological distress. Analysis was by intent‐to‐treat and missing data were replaced following the baseline observation carried forward method.
Results
One hundred fifty‐five participants were recruited. No statistically significant differences regarding pretreatment measures were found between the 2 experimental groups. Overall statistics comparison showed a significant difference between the 2 groups in all of the variables studied (P < 0.0001). Mixed linear model analysis demonstrated the superiority of the multidisciplinary treatment in all of the studied variables at posttreatment. The differences were maintained at 12‐month followup in sleep disturbances (P < 0.0001), catastrophizing (P < 0.0001), and psychological distress (P < 0.01).
Conclusion
Multidisciplinary treatment adapted for individuals with low educational levels is effective in reducing key symptoms of FM. Some improvements were maintained 1 year after completing the multidisciplinary treatment.
Abstract Objective Borderline personality disorder (BPD) is a common personality disorder, with a population prevalence of 1.4–5.9%, although the epidemiology of this disorder in primary care is ...insufficiently known. Our objective was to determine the registered prevalence of BPD in primary care databases and to study the demographic and clinical characteristics of these patients. Methods We performed a cross-sectional study of the computerized databases of primary care clinical records. The target population consisted of all adults (≥ 16 years old) registered in the Catalan Health Institute (n = 4,764,729). Results The prevalence of recorded BPD was 0.017%, and was higher in patients with other mental disorders, particularly substance-abuse disorders (0.161%). These patients had twice as many appointments with the general practitioner as the general population (8.1 vs. 4.4). Conclusion The number of diagnoses of BPD recorded in primary care is extremely low, which contrasts with the available population-based data.
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