Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients

T2DMis today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DMcomplications, including 367 T2DMpatients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication\u2019s prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P = 0.026), lower limb arteriopathy (P = 0.013), and the major cardiovascular pathologies (P = 0.017). Their cumulative risk was significant (P = 0.01), with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases.The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642\u20138.741).Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients

A maChine and deep Learning Approach to predict pulmoNary hyperteNsIon in newbornS with congenital diaphragmatic Hernia (CLANNISH): Protocol for a retrospective study

Introduction Outcome predictions of patients with congenital diaphragmatic hernia (CDH) still have some limitations in the prenatal estimate of postnatal pulmonary hypertension (PH). We propose applying Machine Learning (ML), and Deep Learning (DL) approaches to fetuses and newborns with CDH to develop forecasting models in prenatal epoch, based on the integrated analysis of clinical data, to provide neonatal PH as the first outcome and, possibly: Favorable response to fetal endoscopic tracheal occlusion (FETO), need for Extracorporeal Membrane Oxygenation (ECMO), survival to ECMO, and death. Moreover, we plan to produce a (semi)automatic fetus lung segmentation system in Magnetic Resonance Imaging (MRI), which will be useful during project implementation but will also be an important tool itself to standardize lung volume measures for CDH fetuses. Methods and analytics Patients with isolated CDH from singleton pregnancies will be enrolled, whose prenatal checks were performed at the Fetal Surgery Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milan, Italy) from the 30th week of gestation. A retrospective data collection of clinical and radiological variables from newborns' and mothers' clinical records will be performed for eligible patients born between 01/01/2012 and 31/12/2020. The native sequences from fetal magnetic resonance imaging (MRI) will be collected. Data from different sources will be integrated and analyzed using ML and DL, and forecasting algorithms will be developed for each outcome. Methods of data augmentation and dimensionality reduction (feature selection and extraction) will be employed to increase sample size and avoid overfitting. A software system for automatic fetal lung volume segmentation in MRI based on the DL 3D U-NET approach will also be developed. Ethics and dissemination This retrospective study received approval from the local ethics committee (Milan Area 2, Italy). The development of predictive models in CDH outcomes will provide a key contribution in disease prediction, early targeted interventions, and personalized management, with an overall improvement in care quality, resource allocation, healthcare, and family savings. Our findings will be validated in a future prospective multicenter cohort study

Sphenofrontal distance on three-dimensional ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation

Objective: To compare the distance between the sphenoid and frontal bones on three-dimensional (3D) ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation. Methods: We acquired 3D volumes of the fetal profile from 80 normal and 30 trisomy-21 fetuses at 16-24 weeks' gestation. We used the multiplanar mode to obtain the mid-sagittal plane and measured the sphenofrontal distance as the shortest distance between the most anterior edge of the sphenoid bone and the lowest edge of the frontal bone. Results: In normal fetuses, the sphenofrontal distance increased linearly with gestational age, from 15.1mm at 16 weeks to 18.2mm at 24 weeks. In fetuses with trisomy 21, the mean sphenofrontal distance delta value was significantly smaller than in normal cases (-3.447mm (95% CI, -5.684 to -1.211mm); P<0.01). The sphenofrontal distance was below the 5th and 1st percentiles of the normal range in 29 (96.7%) and 27 (90.0%) trisomy-21 fetuses, respectively. Conclusions: The sphenofrontal distance is shorter at 16-24 weeks' gestation in fetuses with trisomy 21 than in normal fetuses. A reduction in the growth of the anterior cranial base contributes to the mid-facial hypoplasia observed in fetuses with trisomy 21

Population Physiology: Leveraging Electronic Health Record Data to Understand Human Endocrine Dynamics

Studying physiology and pathophysiology over a broad population for long periods of time is difficult primarily because collecting human physiologic data can be intrusive, dangerous, and expensive. One solution is to use data that have been collected for a different purpose. Electronic health record (EHR) data promise to support the development and testing of mechanistic physiologic models on diverse populations and allow correlation with clinical outcomes, but limitations in the data have thus far thwarted such use. For example, using uncontrolled population-scale EHR data to verify the outcome of time dependent behavior of mechanistic, constructive models can be difficult because: (i) aggregation of the population can obscure or generate a signal, (ii) there is often no control population with a well understood health state, and (iii) diversity in how the population is measured can make the data difficult to fit into conventional analysis techniques. This paper shows that it is possible to use EHR data to test a physiological model for a population and over long time scales. Specifically, a methodology is developed and demonstrated for testing a mechanistic, time-dependent, physiological model of serum glucose dynamics with uncontrolled, population-scale, physiological patient data extracted from an EHR repository. It is shown that there is no observable daily variation the normalized mean glucose for any EHR subpopulations. In contrast, a derived value, daily variation in nonlinear correlation quantified by the time-delayed mutual information (TDMI), did reveal the intuitively expected diurnal variation in glucose levels amongst a random population of humans. Moreover, in a population of continuously (tube) fed patients, there was no observable TDMI-based diurnal signal. These TDMI-based signals, via a glucose insulin model, were then connected with human feeding patterns. In particular, a constructive physiological model was shown to correctly predict the difference between the general uncontrolled population and a subpopulation whose feeding was controlled

Cell-free DNA testing in the maternal blood in high-risk pregnancies after first-trimester combined screening

Objective: The objective of this study was to investigate a strategy for clinical implementation of cell-free DNA (cfDNA) testing in high-risk pregnancies after first-trimester combined screening. Methods: In 259 singleton pregnancies undergoing invasive testing after first-trimester combined screening, a maternal blood sample was sent to the laboratory Natera for cfDNA testing using a single-nucleotide polymorphism-based methodology. Results: The cfDNA test provided a result in 249 (96.1%) pregnancies and, among these, identified as being at high risk 35 of 36 cases of trisomy 21, 13 of 13 with trisomy 18, five of five with trisomy 13 and three of four with sex chromosome aneuploidies. A policy of performing an invasive test in women with a combined risk of 651 in 10 or NT 654mm and offering cfDNA testing to the remaining cases would detect all cases of trisomy 21, 18 or 13, 80% of sex aneuploidies and 62.5% of other defects and would avoid an invasive procedure in 82.4% of euploid fetuses. Conclusion: In high-risk pregnancies after combined screening, a policy of selecting a subgroup for invasive testing and another for cfDNA testing would substantially reduce the number of invasive procedures and retain the ability to diagnose most of the observed aneuploidies

Maternal Subcutaneous and Visceral Adipose Ultrasound Thickness in Women with Gestational Diabetes Mellitus at 24-28 Weeks&apos; Gestation

BACKGROUND: Preeclampsia is a major pregnancy complication with adverse short- and long-term implications for both the mother and baby. Screening for preeclampsia at 11-13 weeks' gestation by a combination of maternal demographic characteristics and medical history with measurements of biomarkers can identify about 75% of women that develop preterm-preeclampsia with delivery at <37 weeks' gestation and 90% of those with early-preeclampsia at <32 weeks, at a screen positive rate of 10%. A recent trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) has reported that in women identified by first-trimester screening as being at high-risk for preeclampsia, use of aspirin (150 mg/day from the first to the third trimester), compared to placebo, reduced the incidence of preterm-preeclampsia, which was the primary outcome, by 62% (95% confidence interval, 26-80%) and the incidence of early-preeclampsia by 89% (95% confidence interval, 53-97%). The surprising finding of the trial was that despite the reduction in preeclampsia the incidence of admission to the neonatal intensive care unit, which was one of the secondary outcomes, was not significantly affected (odds ratio 0.93, 95% confidence interval, 0.62-1.40). OBJECTIVE: To examine the effect of prophylactic use of aspirin during pregnancy in women at high-risk of preeclampsia on length of stay in the neonatal intensive care unit. STUDY DESIGN: This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial to assess evidence of differences in the effect of aspirin on length of stay in neonatal intensive care. Bootstrapping was used for the comparison of mean length of stay between the aspirin and placebo groups. Logistic-regression was used to assess treatment effects on stay in the neonatal intensive care unit. RESULTS: In the trial there were 1620 participants and 1571 neonates were liveborn. The total length of stay in neonatal intensive care was substantially longer in the placebo than aspirin group (1696 vs. 531 days). This is a reflection of significantly shorter mean lengths of stay in babies admitted to the neonatal intensive care unit from the aspirin than the placebo group (11.1 vs. 31.4 days; a reduction of 20.3 days (95% confidence interval, 7.0-38.6; p=0.008). Neonatal intensive care of babies born at <32 weeks' gestation contributed 1856 (83.3%) of the total of 2227 days in intensive care across both treatment arms. These occurred in 9 (1.2%) of the 777 livebirths in the aspirin group and in 23 (2.9%) of 794 in the placebo group (odds ratio 0.42; 95% confidence interval, 0.19-0.93; p=0.033). Overall, in the whole population, including zero lengths of stay for those that were not admitted to the neonatal intensive care unit, the mean length of stay was longer in the placebo than aspirin group (2.06 vs 0.66 days; reduction of 1.4 days (95% confidence interval, 0.45-2.81; p=0.014). This corresponds to a reduction in length of stay of 68% (95% confidence interval, 20-86%). CONCLUSIONS: In pregnancies at high-risk of preeclampsia administration of aspirin reduces the length of stay in the neonatal intensive care unit by about 70%. This reduction could essentially be attributed to a decrease in the rate of births at <32 weeks' gestation, mainly because of prevention of early preeclampsia. The findings have implications for both short- and long-term healthcare costs as well as infant survival and handicap

Observer-Based State Feedback for Enhanced Insulin Control of Type ‘I’ Diabetic Patients

During the past few decades, biomedical modeling techniques have been applied to improve performance of a wide variety of medical systems that require monitoring and control. Diabetes is one of the most important medical problems. This paper focuses on designing a state feedback controller with observer to improve the performance of the insulin control for type ‘I’ diabetic patients. The dynamic model of glucose levels in diabetic patients is a nonlinear model. The system is a typical fourth-order single-input-single-output state space model. Using a linear time invariant controller based on an operating condition is a common method to simplify control design. On the other hand, adaptive control can potentially improve system performance. But it increases control complexity and may create further stability issues. This paper investigates patient models and presents a simplified control scheme using observer-based feedback controllers. By comparing different control schemes, it shows that a properly designed state feedback controller with observer can eliminate the adaptation strategy that the Proportional-Integral-Derivative (PID) controllers need to improve the control performance. Control strategies are simulated and their performance is evaluated in MATLAB and Simulink

Effects of treated wastewater irrigation on the establishment of young grapevines

Irrigation with treated wastewater could produce excessive accumulations within the plant and soil, negatively affecting the yield and production quality. In addition, the presence of biological and chemical contaminants could harm the agricultural environment, as well as the health of farmers and consumers. During this work, the suitability of secondary and tertiary treated wastewater for use in young grapevines was evaluated by studying the effect of the wastewater irrigation on the soil-plant system, crop yield, fruit quality and the presence of inorganic chemical contamination (salts, elements and heavy metals), organic chemical contamination (polycyclic aromatic hydrocarbons) and microbial contamination (E. coli, total coliforms). The results show that tertiary treated wastewater had positive impact on plant growth and yield while secondary treated wastewater had negative impact on fruit safety in comparison with tap water. Sodium levels in soils irrigated with treated wastewater increased at the end of the irrigation period while decreased during the wet season. The total polycyclic aromatic hydrocarbon concentrations in the soils ranged from 363 μg/kg to 374 μg/kg at the end of the experiment for all irrigation treatments applied. The use of tertiary treated wastewater was recommended for the irrigation of young grapevines as an alternative water source secured protection of environment, plant health and fruit quality

Advances in research on the use of biochar in soil for remediation: a review

Purpose: Soil contamination mainly from human activities remains a major environmental problem in the contemporary world. Significant work has been undertaken to position biochar as a readily-available material useful for the management of contaminants in various environmental media notably soil. Here, we review the increasing research on the use of biochar in soil for the remediation of some organic and inorganic contaminants.  Materials and methods: Bibliometric analysis was carried out within the past 10 years to determine the increasing trend in research related to biochar in soil for contaminant remediation. Five exemplar contaminants were reviewed in both laboratory and field-based studies. These included two inorganic (i.e., As and Pb) and three organic classes (i.e., sulfamethoxazole, atrazine, and PAHs). The contaminants were selected based on bibliometric data and as representatives of their various contaminant classes. For example, As and Pb are potentially toxic elements (anionic and cationic, respectively), while sulfamethoxazole, atrazine, and PAHs represent antibiotics, herbicides, and hydrocarbons, respectively.  Results and discussion: The interaction between biochar and contaminants in soil is largely driven by biochar precursor material and pyrolysis temperature as well as some characteristics of the contaminants such as octanol-water partition coefficient (KOW) and polarity. The structural and chemical characteristics of biochar in turn determine the major sorption mechanisms and define biochar’s suitability for contaminant sorption. Based on the reviewed literature, a soil treatment plan is suggested to guide the application of biochar in various soil types (paddy soils, brownfield, and mine soils) at different pH levels (4–5.5) and contaminant concentrations ( 50 mg kg−1).  Conclusions: Research on biochar has grown over the years with significant focus on its properties, and how these affect biochar’s ability to immobilize organic and inorganic contaminants in soil. Few of these studies have been field-based. More studies with greater focus on field-based soil remediation are therefore required to fully understand the behavior of biochar under natural circumstances. Other recommendations are made aimed at stimulating future research in areas where significant knowledge gaps exist

Experimental studies of the kaon-nucleus interaction at low energy with x-ray spectroscopy of kaonic atoms

In the exotic atoms in which one electron is replaced by a negatively charged kaon, the kaon-nucleus hadronic interaction introduces an energy shift and broadening of the low-lying states of the kaonic atoms. The shift and width can be determined with high precision from the atomic x-ray spectroscopy, and this experimental method provides unique information to understand the low energy kaon-nucleus interaction at the production threshold