Objectives
To determine the prevalence and factors associated with the use of oral health services in Peruvian children under 12 years of age.
Material and Methods
A secondary analysis of 2019 ...Demographic and Family Health Survey was conducted. The sample consisted of 40,751 children. The main variable was the use of dental services (attended/not attended) in the last 6 months, and the independent variables were gender, age, area of residence, wealth quintile, health insurance coverage, information received on oral health care, age, and educational level of the caregivers. Analyses of absolute and relative frequencies, differences in proportions, and multivariate analysis using generalized linear models were performed.
Results
The dental service utilization prevalence during the last 6 months was 31%. Correlation was found with urban area residents (PRa = 0.945; 95% CI: 0.904–0.988), the Jungle geographical domain (PRa = 0.926; 95% CI: 0.877–0.977), the highest wealth quintile (PRa = 1.323; 95% CI: 1.232–1.421), the higher education level of the caregiver (PRa = 1.375; 95% CI: 1.231–1.536), affiliation with the Public Health Insurance (PRa = 1.112; 95% CI: 1.069–1.158), and the condition of having received information on oral health care (PRa = 2.355; 95% CI: 2.263–2.245) with respect to their baseline variables.
Conclusions
Several socio‐demographic factors were correlated with the use of oral health services in Peruvian children under 12 years of age and the percentage of their use was low. Information on oral health care had a more significant impact on both, the population from the highest wealth quintile and the highest educational attainment.
Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to ...explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles.
We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices.
Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=-0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC).
In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.
Direct evidence for Le Corbusier’s encounters with the writings of nineteenth-century German architect and theorist Gottfried Semper is limited to a few brief early mentions in the archival record, ...and connections between the two men have been mentioned only rarely by historians and others interested in Le Corbusier’s work. In Untangling theThreads of Gottfried Semper’s Legacy in Le Corbusier’s Formative Years, José Miguel Mantilla argues that these connections merit closer attention, given Semper’s stature, even in the early twentieth century, and his impact on many of those from whom Le Corbusier adapted his own ideas. Le Corbusier’s ideas concerning links between artistic style and the spirit or psychology of an era, his belief in architecture’s autonomy in relation to technique and use, and his conversion from the vernacular and medievalist forms emphasized by his mentor Charles L’Eplattenier to Greco-Roman classical ones all seem at least indirectly indebted to Semper’s theories. Mantilla explores the connections between the men, particularly in regard to issues of artistic creation.
At the severe end of the idiopathic constipation spectrum exist patients with chronic idiopathic constipation associated with an enormous megarectosigmoid, among whom few require surgery. We ...performed transanal proximal rectosigmoidectomy, involving preservation of a 5 cm rectal reservoir, to ameliorate inconsistent and unpredictable outcomes and fecal incontinence occurring in some patients operated on with other techniques.
We retrospectively observed patients with chronic idiopathic constipation with megarectosigmoid who underwent transanal proximal rectosigmoidectomy during July 2017–May 2018. We analyzed sex, age, operation indication, complications, functional outcome, and time of follow-up. We statistically compared the dosage of laxative before and after the procedure.
Thirteen patients were included in the study. Median age during surgery was 8 years. In 9 cases, the indication for surgery was chronic intake of a daily high dose of Senna with failed weaning trials, and 4 had persistent fecal impaction with laxative-intolerance and refusal of rectal enemas. No intra/postoperative complications occurred. Currently, all 13 patients have daily voluntary bowel movements and no fecal accidents. Laxative dosage was significantly reduced (p = 0.007). Follow-up ranged 6–16 months.
Preliminary results suggest transanal proximal rectosigmoidectomy as an adequate alternative for patients requiring surgery for chronic idiopathic constipation with megarectosigmoid.
Clinical research.
Level III.
Literature on complex diseases is abundant but not always quantitative. Many molecular pathways are qualitatively well described but this information cannot be used in traditional quantitative ...mathematical models employed in drug development. Tools for analysis of discrete networks are useful to capture the available information in the literature but have not been efficiently integrated by the pharmaceutical industry. We propose an expansion of the usual analysis of discrete networks that facilitates the identification/validation of therapeutic targets.
In this article, we propose a methodology to perform Boolean modeling of Systems Biology/Pharmacology networks by using SPIDDOR (Systems Pharmacology for effIcient Drug Development On R) R package. The resulting models can be used to analyze the dynamics of signaling networks associated to diseases to predict the pathogenesis mechanisms and identify potential therapeutic targets.
The source code is available at https://github.com/SPIDDOR/SPIDDOR .
itzirurzun@alumni.unav.es , itroconiz@unav.es.
Supplementary data are available at Bioinformatics online.
Background and Objective
Mechanistic static and dynamic physiologically based pharmacokinetic models are used in clinical drug development to assess the risk of drug–drug interactions (DDIs). ...Currently, the use of mechanistic static models is restricted to screening DDI risk for an investigational drug, while dynamic physiologically based pharmacokinetic models are used for quantitative predictions of DDIs to support regulatory filing. As physiologically based pharmacokinetic model development by sponsors as well as a review of models by regulators require considerable resources, we explored the possibility of using mechanistic static models to support regulatory filing, using representative cases of successful physiologically based pharmacokinetic submissions to the US Food and Drug Administration under different classes of applications.
Methods
Drug–drug interaction predictions with mechanistic static models were done for representative cases in the different classes of applications using the same data and modelling workflow as described in the Food and Drug Administration clinical pharmacology reviews. We investigated the hypothesis that the use of unbound average steady-state concentrations of modulators as driver concentrations in the mechanistic static models should lead to the same conclusions as those from physiologically based pharmacokinetic modelling for non-dynamic measures of DDI risk assessment such as the area under the plasma concentration–time curve ratio, provided the same input data are employed for the interacting drugs.
Results
Drug–drug interaction predictions of area under the plasma concentration–time curve ratios using mechanistic static models were mostly comparable to those reported in the Food and Drug Administration reviews using physiologically based pharmacokinetic models for all representative cases in the different classes of applications.
Conclusions
The results reported in this study should encourage the use of models that best fit an intended purpose, limiting the use of physiologically based pharmacokinetic models to those applications that leverage its unique strengths, such as what-if scenario testing to understand the effect of dose staggering, evaluating the role of uptake and efflux transporters, extrapolating DDI effects from studied to unstudied populations, or assessing the impact of DDIs on the exposure of a victim drug with concurrent mechanisms. With this first step, we hope to trigger a scientific discussion on the value of a routine comparison of the two methods for regulatory submissions to potentially create a best practice that could help identify examples where the use of dynamic changes in modulator concentrations could make a difference to DDI risk assessment.
Colombian
strain ST920 was isolated from the sputum of a 68-year-old male patient. This isolate possessed
OXA-72 and
OXA-255-like genes. The assembled genome contained 4,104,098 pb and 38.79% G+C ...content. This is the first case reported of the coproduction (
OXA-72 and
OXA-255-like) of carbapenem-hydrolyzing class D β-lactamases (CHDLs) in
.
The literature on complex diseases is abundant but not always quantitative. This is particularly so for Inflammatory Bowel Disease (IBD), where many molecular pathways are qualitatively well ...described but this information cannot be used in traditional quantitative mathematical models employed in drug development. We propose the elaboration and validation of a logic network for IBD able to capture the information available in the literature that will facilitate the identification/validation of therapeutic targets.
In this article, we propose a logic model for Inflammatory Bowel Disease (IBD) which consists of 43 nodes and 298 qualitative interactions. The model presented is able to describe the pathogenic mechanisms of the disorder and qualitatively describes the characteristic chronic inflammation. A perturbation analysis performed on the IBD network indicates that the model is robust. Also, as described in clinical trials, a simulation of anti-TNFα, anti-IL2 and Granulocyte and Monocyte Apheresis showed a decrease in the Metalloproteinases node (MMPs), which means a decrease in tissue damage. In contrast, as clinical trials have demonstrated, a simulation of anti-IL17 and anti-IFNγ or IL10 overexpression therapy did not show any major change in MMPs expression, as corresponds to a failed therapy. The model proved to be a promising in silico tool for the evaluation of potential therapeutic targets, the identification of new IBD biomarkers, the integration of IBD polymorphisms to anticipate responders and non-responders and can be reduced and transformed in quantitative model/s.
The antiplatelet agent clopidogrel is listed by the FDA as a strong clinical index inhibitor of cytochrome P450 (CYP) 2C8 and weak clinical inhibitor of CYP2B6. Moreover, clopidogrel is a substrate ...of-among others-CYP2C19 and CYP3A4. This work presents the development of a whole-body physiologically based pharmacokinetic (PBPK) model of clopidogrel including the relevant metabolites, clopidogrel carboxylic acid, clopidogrel acyl glucuronide, 2-oxo-clopidogrel, and the active thiol metabolite, with subsequent application for drug-gene interaction (DGI) and drug-drug interaction (DDI) predictions. Model building was performed in PK-Sim
using 66 plasma concentration-time profiles of clopidogrel and its metabolites. The comprehensive parent-metabolite model covers biotransformation via carboxylesterase (CES) 1, CES2, CYP2C19, CYP3A4, and uridine 5'-diphospho-glucuronosyltransferase 2B7. Moreover, CYP2C19 was incorporated for normal, intermediate, and poor metabolizer phenotypes. Good predictive performance of the model was demonstrated for the DGI involving CYP2C19, with 17/19 predicted DGI AUC
and 19/19 predicted DGI C
ratios within 2-fold of their observed values. Furthermore, DDIs involving bupropion, omeprazole, montelukast, pioglitazone, repaglinide, and rifampicin showed 13/13 predicted DDI AUC
and 13/13 predicted DDI C
ratios within 2-fold of their observed ratios. After publication, the model will be made publicly accessible in the Open Systems Pharmacology repository.
Peripheral blood-derived endothelial cells (pBD-ECs) are an attractive tool for cell therapies and tissue engineering, but have been limited by their low isolation yield. We increase pBD-EC yield via ...administration of the chemokine receptor type 4 antagonist AMD3100, as well as via a diluted whole blood incubation (DWBI).
Porcine pBD-ECs were isolated using AMD3100 and DWBI and tested for EC markers, acetylated LDL uptake, growth kinetics, metabolic activity, flow-mediated nitric oxide production and seeded onto titanium tubes implanted into vessels of pigs.
DWBI increased the yield of porcine pBD-ECs 6.6-fold, and AMD3100 increased the yield 4.5-fold. AMD3100-mobilized ECs were phenotypically indistinguishable from nonmobilized ECs. In porcine implants, the cells expressed endothelial nitric oxide synthase, reduced thrombin-antithrombin complex systemically and prevented thrombosis.
Administration of AMD3100 and the DWBI method both increase pBD-EC yield.
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