Networks of Care: An Approach to Improving Maternal and Newborn Health.

The Networks of Care approach has the potential to harmonize existing strategies and optimize health systems functions for maternal and newborn health, thereby strengthening the quality of care and ultimately improving outcomes

User needs elicitation via analytic hierarchy process (AHP). A case study on a Computed Tomography (CT) scanner

Background: The rigorous elicitation of user needs is a crucial step for both medical device design and purchasing. However, user needs elicitation is often based on qualitative methods whose findings can be difficult to integrate into medical decision-making. This paper describes the application of AHP to elicit user needs for a new CT scanner for use in a public hospital. Methods: AHP was used to design a hierarchy of 12 needs for a new CT scanner, grouped into 4 homogenous categories, and to prepare a paper questionnaire to investigate the relative priorities of these. The questionnaire was completed by 5 senior clinicians working in a variety of clinical specialisations and departments in the same Italian public hospital. Results: Although safety and performance were considered the most important issues, user needs changed according to clinical scenario. For elective surgery, the five most important needs were: spatial resolution, processing software, radiation dose, patient monitoring, and contrast medium. For emergency, the top five most important needs were: patient monitoring, radiation dose, contrast medium control, speed run, spatial resolution. Conclusions: AHP effectively supported user need elicitation, helping to develop an analytic and intelligible framework of decision-making. User needs varied according to working scenario (elective versus emergency medicine) more than clinical specialization. This method should be considered by practitioners involved in decisions about new medical technology, whether that be during device design or before deciding whether to allocate budgets for new medical devices according to clinical functions or according to hospital department

Verification and improvement of flexible mathematical procedures for co-optimizing design and control of fuel cell hybrid vehicles

A study on the usefulness of flexible mathematical tools for determining the optimal architecture of fuel cell hybrid vehicles is presented. Starting from a pre-existing powertrain and control strategies co-optimization tool, the technological (especially in terms of lithium battery type) search domain was first expanded by including an updated battery model. Afterward, the availability of specification independent control strategies was exploited in such a way as to enable two optimization tasks: one relying on previous heuristic control rules and the other based on newly optimized control strategies. The results evidenced negligible differences, in terms of key control variable trends, objective (i.e., fuel economy), and design parameters (i.e., fuel cell system size and battery energy density), thus further proving the tool versatility. Moreover, optimal configurations exhibit appreciable fuel economies and acceleration performance on the WLTP driving cycle, while proposing potentially cost-effective solutions in terms of fuel cell system size. Copyright (c) 2022 The Authors. This is an open access article under the CC BY-NC-ND licens

The role of Store-Operated Cyclic AMP Signalling (SOcAMPS) in cardiac physiology and pathology: an in vitro study on neonatal rat cardiomyocytes.

Background and Aims: Store-Operated Cyclic AMP Signaling (SOcAMPS) represents a recently identified mechanism of cross-talk between Ca2+ and cAMP signals. In this process, depletion of Ca2+ in the endoplasmic reticulum (ER) leads to increases in cAMP levels, independently of cytosolic Ca2+ changes. Expression and functionality of STIM1 (Stromal Interaction Molecule 1), a transmembrane ER Ca2+ sensor protein, is necessary for SOcAMPS to occur. Interestingly, recent reports have demonstrated a critical role for STIM1 in the development of cardiac hypertrophy, a process notoriously controlled both by Ca2+ and cAMP signaling. Here we aimed to evaluate whether SOcAMPS was manifest in neonatal rat cardiomyocytes and its potential role in cardiac cell hypertrophy. Methods: To monitor changes in cAMP levels, real time imaging experiments were performed on neonatal rat cardiomyocytes transiently transfected with an EPAC-based fluorescent probe for [cAMP], EPAC H30. Fura-2 and Fluo-4 were used to monitor cytosolic Ca2+ levels and an ER/SR targeted probe, D1ERcameleon, was used to measure ER [Ca2+]. Long term incubation (48h) of cardiomyocytes with angiotensin II (1 μM) and aldosterone (1 μM) was used to induce "in vitro" cell hypertrophy. Increases in cell size and/or sarcomere alignment were monitored microscopically after labeling with phalloidin-TRITC. Results: To verify the existence of SOcAMPS in neonatal rat cardiomyocytes, cells were stimulated in Ca2+-free Ringer's solutions with the low affinity membrane permeant Ca2+ chelator TPEN (1mM), able to induce a reduction of SR Ca2+ levels ([Ca2+]SR) without affecting cytosolic [Ca2+]. SR Ca2+ measurements demonstrated that under these experimental conditions, 1 mM TPEN led to a reduction in intraluminal [Ca2+] that was 50,5±2,4% (8 exp, 11 cells, p<0.001) of the maximal store depletion. Parallel experiments performed with the EPAC H30 cAMP sensor showed increases in [cAMP] that were 26,5±3% (13 exp, 13 cells, p<0.001) of the maximum delta ratio. In the presence of 5 μM Forskolin (FRSK) the TPEN-induced cAMP augmentation resulted 63,7±3,9% of the maximal response (16 exp, 19 cells, p<0.001). Also depletion of SR by the Ca2+ ionophore ionomycin (10 μM) was found to induce significant cAMP increases both in the absence and presence of FRSK. The participation of STIM1 in the observed phenomenon was proven by the 47 % reduction of the TPEN+FRSK induced [cAMP] signal after transfection of cells with a shRNA against STIM1 (6 exp, p<0,01). To evaluate the putative role of SOcAMPS in cardiac hypertrophy, cAMP measurements were performed on angio+aldo treated cells and compared to control cardiomyocytes. Under these experimental conditions a 20% increase of the TPEN+FRSK induced response was observed in hypertrophic myocytes (16 exp, p<0,01). Conclusions: These data straightforwardly establish, for the first time, the existence of SOcAMPS in the neonatal cardiomyocyte cell model. Also, a significantly increased SOcAMP signalling was shown to exist in hypertrophic cardiomyocytes. Further experiments to ascertain whether a causeand- effect relationship exists between SOcAMPS and cardiac cell hypertrophy are in progress

The role of Store-Operated Cyclic AMP Signalling (SOcAMPS) in cardiac physiology and pathology

Store-Operated Cyclic AMP Signaling (SOcAMPS) represents a novel signaling mechanism in which depletion of Ca2+ in the endoplasmic reticulum (ER) leads to a STIM1- dependent (Stromal Interaction Molecule 1) increase in cAMP levels, independently of cytosolic Ca2+. Here we aimed to evaluate whether SOcAMPS was manifest in neonatal rat ventricular myocytes (NRVM) and human &quot;iCardiomyocytes&quot; and exploit its potential role in cardiac cell hypertrophy. cAMP levels and ER [Ca2+]were monitored by live cell fluorescence imaging after transfection with the EPAC H30 and D1ER cameleon probes, respectively. The existence of SOcAMPS in NRVM was first assessed by using the low affinity Ca2+ chelator TPEN, able to induce a reduction of SR Ca2+ levels without affecting cytosolic [Ca2+]. TPEN (1mM) was shown to induce significant cAMP increases both in the absence and presence of 5 M Forskolin (FRSK). Depletion of SR by ionomycin (10 M) was found to exert similar effects. Similar data were obtained in human &quot;iCardiomyocytes&quot;. The participation of STIM1 in the observed phenomenon was proven in NRVM by the 47% reduction of the [cAMP] response obtained after shRNA-mediated knockdown of STIM1. Interestingly, a significant increase of the TPEN+FRSK induced response was found after &quot;in vitro&quot; induced cell hypertrophy. These data establish, for the first time, the existence of SOcAMPS in the two cardiac cell models analyzed and suggest a potential role for this new signaling mechanism in cardiac cell hypertrophy

Flavin adenine dinucleotide metabolism in nucleus

Following its uptake from outside, in the cell riboflavin undergoes an ATP-dependent phosphorylation catalyzed by riboflavin kinase (RFK, E.C. 2.7.1.26) to form FMN, most of which is further converted by FAD synthase (FADS, E.C. 2.7.7.2) into FAD, the cofactor for many flavoenzymes involved in several biological processes in different cellular compartments. We previously demonstrated that beside a cytosolic enzyme (i.e. isoform 2 of human FLAD1 gene product) a mitochondrial isoform of FADS exists (isoform 1) (1, 2), presumably responsible for the biogenesis of mitochondrial flavoenzymes. Interestingly, the possibility of unexpected localizations for FADS has arisen (3) and, meanwhile, at least two new isoforms of FADS have been deposited in databases. Among FAD-dependent enzymes, lysine-specific demethylase-1 (E.C. 1.14.11.B1) is a nuclear protein recently shown to regulate cellular energy balance depending on FAD availability (4). These observation prompted us to investigate on the presence of flavin coenzymes in the nucleus and on a possible metabolism of FAD in this organelle. To this aim HPLC analysis of acid-precipitable flavins in nuclei isolated from rat liver were performed. The observation of a time-dependent decrease of FAD suggested us the existence of a hydrolytic activity, as confirmed by spectrofluorimetric measurements revealing an increase in fluorescence due to conversion of FAD into its more fluorescent precursor FMN/riboflavin (5). Immunoblotting experiments performed on rat liver nuclei using a home-made antibody against FADS revealed the enrichment of an immunoreactive band in respect to the other sub-cellular fractions. Confocal microscopy on several mammalian cells confirmed the existence of FADS co-localizing with nuclear markers. 1. Barile et al., Eur J Biochem, 2000, 15, 4888-900. 2. Torchetti et al., Mitochondrion, 2010, 10, 263-73. 3. Lin et al., J Neurol, 2009, 256, 774-82. 4. Hino et al., Nat Commun, 2012, 3, 758. 5. Brizio et al., Eur J Biochem, 1997, 3, 777-85

Genes Involved in Energy Metabolism Are Differentially Expressed During the Day-Night Cycle in Murine Retinal Pigment Epithelium

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