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Integrazione con inositoli in gravidanze complicate da sindrome metabolica. Effetti sul sistema metabolico e cardiovascolare nell'unità materno-fetale.
La sindrome metabolica (SM), l'obesità e l'ipertensione in gravidanza creano un ambiente intrauterino avverso, che porta ad un'alterazione della programmazione fetale in utero, predisponendo il feto all'insorgenza della malattia in età adulta. Gli inositoli (INO) hanno dimostrato di migliorare la resistenza all'insulina nelle donne con obesità, diabete gestazionale e con SM.
Ipotesi: La somministrazione di INO in gravidanza migliora il profilo metabolico e cardiovascolare materno e della prole riducendo il danno agli organi materni e modulando le vie dell'omeostasi del glucosio placentare, migliorando quindi la salute materna e fetale a breve e lungo termine.
Disegno dello studio: Topi femmine eterozigoti eNOS–/+ con ipertensione moderata sono stati sottoposti ad una dieta ricca di grassi (HFD) per 4 settimane per indurre un fenotipo della SM o alimentati con una dieta regolare per ottenere il fenotipo ipertensivo. Allo stesso modo, i topi wild-type (WT) sono stati nutriti con HFD per 4 settimane per ottenere il modello di obesità murina. Dopo l'accoppiamento con maschi WT, le femmine gravide sono state assegnate casualmente a ricevere INO o acqua come controllo. Al termine della gravidanza (giorno di gestazione 18) sono stati misurati: peso materno, pressione sanguigna sistolica (SBP) ed è stato effettuato il test di tolleranza al glucosio (GTT). Quindi le gravide sono state sacrificate, pesati e raccolti gli organi materni, il sangue, le placente e i feti. I livelli sierici dei biomarcatori, rilevanti per la fibrosi, sono stati misurati mediante un test multiplex di immunoassorbimento enzimatico. L'istologia dei tessuti cardiaci, epatici e renali è stata eseguita per la valutazione del danno d'organo. Le placente di ciascun gruppo di madri sono state genotipizzate per l'allele eNOS ed il sesso per valutare il livello di proteine coinvolte nell'omeostasi del glucosio. In particolare, l'assorbimento del glucosio, la sintesi del glicogeno e la produzione di ATP sono stati misurati mediante Western blot, e l’immagazzinamento del glicogeno mediante test ELISA. Per valutare il danno agli organi materni, i tessuti cardiaci, renali ed epatici sono stati colorati con la tricromia di Masson valutando la deposizione di tessuto connettivo. Il livello sierico di biomarcatori fibrogenici e di collagene è stato misurato tramite ELISA. Un sottogruppo delle madri con SM che ricevevano INO o placebo, è stato lasciato partorire per valutare i profili vascolari e metabolici nella prole sviluppata in un ambiente uterino anormale a causa della SM materna. Nella prole sono stati valutati GTT e SBP a 9-10 settimane di età. Le arterie carotidi sono state isolate per la valutazione delle risposte vascolari alla fenilefrina, in presenza e assenza di un inibitore aspecifico dell'ossido nitrico, del vasodilatatore acetilcolina e del nitroprussiato di sodio.
Risultati: Il trattamento con INO durante la gravidanza ha migliorato i livelli di SBP, glucosio e leptina nelle madri gravide con fenotipo di SM. Inoltre, ha migliorato l'uso del glucosio placentare verso la produzione di energia in modo indipendente dal genere nella prole nata da madri con SM.
Inoltre, il trattamento materno con INO ha ridotto significativamente la fibrosi cardiaca e renale a livello materno indotta dalla SM stabilita prima della gravidanza, riducendo i livelli sierici di TGF-β e collagene di tipo 3 nelle madri con SM. Infine, l'INO ha migliorato la tolleranza al glucosio, la SBP e le risposte vascolari nei figli nati da madri con SM che non hanno ereditato i fattori genetici alterati (eNOS).
Conclusione: Le malattie metaboliche e cardiovascolari in gravidanza hanno gravi conseguenze sulla salute materna e fetale. L'integrazione di inositolo durante la gravidanza è una strategia promettente per contrastare i danni del dismetabolismo sia nella madre che nel feto, mostrando un miglioramento degli esiti metabolici e cardiovascolari a breve e lungo termine.Background: Metabolic syndrome (MS), obesity and hypertension in pregnancy set an adverse intrauterine environment, leading to an altered fetal programming in utero, predisposing the fetus to later onset of adult disease. On this ground, Inositols (INO) are insulin sensitizing agents that have been shown to improve insulin resistance in women with obesity, gestational diabetes and with MS.
Hypothesis: We hypothesized that INO in pregnancy improve maternal and offspring metabolic and cardiovascular profile by reducing maternal end-organ damage and modulating placental glucose homeostasis pathways therefore improving maternal and fetal short and long-term health.
Study design: Female heterozygous for endothelial nitric oxide synthase (eNOS–/+) mice with moderate hypertension were either placed on a high-fat diet (HFD) for 4 weeks to induce a MS phenotype or fed with regular diet to obtain the hypertensive phenotype. Similarly, wild-type (WT) mice were placed on a HFD for 4 weeks to induce a murine obesity model. Female mice were then bred with WT males. On gestational day 1, dams were randomly allocated to receive either INO or plain water as control. To evaluate pregnancy outcomes, pregnant dams were assessed at term (gestational day 18). Maternal weights, systolic blood pressure (SBP), and a glucose tolerance test (GTT) were obtained. Then dams were sacrificed, and maternal organs, blood, placentas, and pups were weighed and collected. Serum levels of biomarkers, relevant to fibrosis pathway, were measured by a multiplex enzyme-linked immunosorbent assay. Cardiac, liver and kidney tissues histology was perfroemd for fibrosis deposition as organ damage. Placentas per each group of dams were processed to obtain offspring genotyped for eNOS allele and gender to evaluate the level of proteins involved in glucose homeostasis. Specifically, glucose uptake (GLUT4 and IR-b), glycogen synthesis (Akt, pAktT-308and GSK3), and ATP production (pPDH) were measured using Western blot, while glycogen storage was measured by ELISA assay.
To evaluate maternal organ damage, cardiac, renal and liver tissues were stained with Masson’s trichrome to assess connective tissue deposition. ELISA was used to measure serum level of fibrogenic and collagen biomarkers.
A subgroup of the previously mentioned MS pregnant dams receiving INO or placebo, were let deliver to evaluate vascular and metabolic profiles in their offspring. The offspring developed in an abnormal uterine environment due to maternal MS underwent a GTT and SBP measurement at 9-10 weeks of age, then were sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine, in the presence and absence of a nonspecific nitric oxide inhibitor, the vasodilator acetylcholine, and sodium nitroprusside were assessed.
Results: INO treatment during pregnancy improved SBP, glucose and leptin levels in pregnant dams with MS phenotype. Moreover, it enhanced placental glucose use toward energy production in a gender-independent manner in offspring born to MS dams.
Moreover, maternal INO treatment significantly decreased maternal cardiac and renal organ fibrosis induced by the MS established before pregnancy by reducing serum levels of TGF-β and collagen-type 3 in MS dams.
Lastly, adult offspring born to dams with MS benefit more of maternal INO treatment if exposed to environmental factors in utero, and less if they inherited the altered genetic factors (eNOS). Indeed, inositol supplementation improved glucose tolerance, SBP, and vascular responses in those mice.
Conclusion: Metabolic and cardiovascular disease in pregnancy have serious consequences on maternal and fetal health. Inositol supplementation during pregnancy is a promising strategy to counteract the damages of dysmetabolism in both the mother and the fetus, acting on different pathways, showing improvement of short and long term metabolic and cardiovascular outcomes
Maternal interventions to improve offspring outcomes in rodent models of diet-induced obesity: a review
Maternal obesity is an adverse factor that affects the intrauterine environment during critical periods of fetal developmental causing adverse lifelong effects on offspring health. Several different interventions have been performed in animal models of obesity to ameliorate maternal conditions and consequently reduce the adverse effects on offspring. Our aim was to critically review studies involving murine models of obesity induced by high fat diet (HFD), assessing maternal outcomes during pregnancy and the related offspring conditions. We carried out a computerized literature search of PubMed and Medline. We identified eight studies that fulfilled the inclusion criteria and have performed interventions in pregnancy with natural, synthetized compounds, and lifestyle modifications. Metabolic profile and lipid metabolism were improved by inositols, resveratrol, germinated brown rice (GBR), and exercise in the mother. The offspring whose mother received resveratrol, adiponectin, GBR, and exercise, showed an improvement in leptin, triglycerides, adiponectin levels, and a decrease in insulin resistance. These experimental studies demonstrate that several interventions in pregnant rodents improve the metabolic profile of both the mother and the offspring. Clinical research could now explore the efficacy and safety of such interventions, interrupting the vicious circle that an obese mother generates a child prone to develop metabolic (and cardiovascular) disease in adult life
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
First-trimester prediction model for placental vascular disorders: an observational prospective study
This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth.
Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0–12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019.
In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy.
The best predictive cut-off for this score was equal to − 2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %.
This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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