A Randomized Clinical Trial of Insulin Glargine and Aspart,Compared to NPH and Regular Insulin in Children with Type 1 Diabetes Mellitus

Objective

Appropriate treatment of patients with Type 1 diabetes mellitus (T1DM) is necessary to avoid further complications. This study was performed to compare the efficacy of insulin Glargine and Aspart with NPH insulin and regular insulin regimen in a group of children with T1DM.

Methods

Forty patients with T1DM were enrolled in this study. During run-in, all subjects were treated with conventional therapy consisting of twice-daily NPH and thrice-daily regular. Following randomization, 20 subjects received Glargine and Aspart and 20 subjects received NPH and Regular insulin.

Findings

Mean HbA1c was 8.8% and 8.6% at first and 8.4% and 8.2% at the end of study for subjects randomized initially to Glargine and Aspart and for those randomized to NPH and Regular, respectively (P>0.05). Mean fasting blood glucose (FBS) of the subjects randomized initially to Glargine and Aspart was 217±101 mg/dL, with no significant difference to 196±75 mg/dL for those randomized to NPH and Regular (P=0.48). This was also true at the end of the study. The difference in total cholesterol and triglyceride between the two groups in the beginning of study and at the end did not show any significance.

Conclusion

The current study showed no significant difference in glycemic control [Glycated hemoglobin (HbA1c) and FBS] and lipid profile (total cholesterol and triglyceride) between two regimes.     

Influence of nitrogen/phosphorus-doped carbon dots on polyamide thin film membranes for water vapor/N2 mixture gas separation

Nanoparticles have been attracting attention because they can significantly improve the performance of membranes when added in small amounts. In this study, the effect of polyamide membranes incorporating hydrophilic nitrogen/phosphorus-doped carbon dots (NP-CDs) to enhance water vapor/N₂ separation has been investigated. NP-CD nanoparticles with many hydrophilic functional groups are synthesized from chitosan by a one-pot green method and introduced to the surface of the polysulfone (PSf) substrates by interfacial polymerization reaction. The mean particle diameter of NP-CDs, estimated from transmission electron microscopy images, is 2.6 nm. By adding NP-CDs (0–1.5 wt%) to the polyamide layer, the contact angles of the membranes dramatically decreased from 65° (PSf) to <9° (thin film nanocomposite (TFN)), which means that the TFN membranes become significantly hydrophilic. From the water vapor separation results, the addition of NP-CDs in the polyamide layer improves the water vapor permeance from 1511 (thin film composite (TFC) without nanoparticles) to 2448 GPU (TFN with 1.0 wt% NP-CD loading, CD-TFN(1.0)) and the water vapor/N₂ selectivity from 73 (TFC) to 854 (CD-TFN(1.0)). To our knowledge, this is the first study of highly functionalized NP-CD-incorporated polyamide membranes to enhance water vapor separation.

Nanoparticles have been attracting attention because they can significantly improve the performance of membranes when added in small amounts.     

Usefulness of Serum Brain Natriuretic Peptide Level for Screening Hemodynamically Significant Patent Ductus Arteriosus in Preterm Neonates

Objective:

We studied usefulness of serum B-type natriuretic peptide level as a screening tool for detecting hemodynamically significant patent ductus arteriosus in the preterm neonates.

Methods:

Sixty admitted preterm neonates with gestational age ≤34 weeks, birth weight ≤2500 gr, and age of >3 days have been enrolled in this study. We measured serum B-type natriuretic peptide levels at the beginning and after completion of drug therapy for ductus occlusion.

Findings:

Mean±SD gestational age and weight was 31±1.9 weeks and 1680±350 gr, respectively. The peptide levels in the neonates with significant duct (n=13) were significantly higher than in those with insignificant duct (n=17) or no duct (n=30) (1667±821 pg/ml versus 667±666 and 309±171, respectively). The peptide level dropped significantly after ibuprofen administration in the neonates with significant PDA (n=13), (1667±1165 pg/ml to 429±386).

Conclusion:

At a cutoff point of 450 pg/ml, B-type natriuretic peptide level had a sensitivity of 92% and specificity of 87%, the negative predictive value of 98.5%, the positive likelihood ratio of 6.92 and the negative likelihood ratio of 0.089 for detecting significant patent duct. Levels below this can eliminate the need for echocardiography.     

Task-specific stability in muscle activation space during unintentional movements

We used robot-generated perturbations applied during position-holding tasks to explore stability of induced unintentional movements in a multidimensional space of muscle activations. Healthy subjects held the handle of a robot against a constant bias force and were instructed not to interfere with hand movements produced by changes in the external force. Transient force changes were applied leading to handle displacement away from the initial position and then back toward the initial position. Intertrial variance in the space of muscle modes (eigenvectors in the muscle activations space) was quantified within two subspaces, corresponding to unchanged handle coordinate and to changes in the handle coordinate. Most variance was confined to the former subspace in each of the three phases of movement, the initial steady state, the intermediate position, and the final steady state. The same result was found when the changes in muscle activation were analyzed between the initial and final steady states. Changes in the dwell time between the perturbation force application and removal led to different final hand locations undershooting the initial position. The magnitude of the undershot scaled with the dwell time, while the structure of variance in the muscle activation space did not depend on the dwell time. We conclude that stability of the hand coordinate is ensured during both intentional and unintentional actions via similar mechanisms. Relative equifinality in the external space after transient perturbations may be associated with varying states in the redundant space of muscle activations. The results fit a hierarchical scheme for the control of voluntary movements with referent configurations and redundant mapping between the levels of the hierarchy.     

A comparative study of different electrodeposited NiCo2O4 microspheres anchored on a reduced graphene oxide platform: electrochemical sensor for anti-depressant drug venlafaxine

Two different fabrication methods were performed and compared for preparation of binary metallic oxide microstructures supported on a reduced graphene oxide (rGO) modified graphite electrode. Nickel–Cobalt oxide microspheres (NiCo₂O₄ MSs) were prepared by two different deposition methods: wet chemical and in situ-electrical deposited methods. Different characterization methods were conducted, including cyclic voltammetry (CV), scanning emission microscopy (SEM), electrochemical impedance spectroscopy (EIS) and Raman spectroscopy. The deposition methods of NiCo₂O₄ MSs were found to affect the electrochemical behavior of the modified electrodes towards the oxidation of venlafaxine (VEN), an anti-depressant drug. The fabricated electrode showed linearity over the range 5–500 nmol L⁻¹ and an excellent sensitivity with a limit of detection (LOD) and limit of quantitation (LOQ) of 3.4 and 10.3 nmol L⁻¹, respectively. It was revealed that the wet-NiCo₂O₄@rGO modified electrode prepared by the wet chemical method showed an improved electrochemical behavior for determination of VEN in pharmaceuticals and human plasma with high recovery results in the range of 96.7–98.6% and 96.0–100.7%, respectively without any interference from the co-existing components.

Different electrodeposited NiCo₂O₄ microspheres supported on a reduced graphene oxide platform for electrochemical sensing of venlafaxine.     

Periosteal PTHrP regulates cortical bone modeling during linear growth in mice

The modeling of long bone surfaces during linear growth is a key developmental process, but its regulation is poorly understood. We report here that parathyroid hormone‐related peptide (PTHrP) expressed in the fibrous layer of the periosteum (PO) drives the osteoclastic (OC) resorption that models the metaphyseal–diaphyseal junction (MDJ) in the proximal tibia and fibula during linear growth. PTHrP was conditionally deleted (cKO) in the PO via Scleraxis gene targeting (Scx‐Cre). In the lateral tibia, cKO of PTHrP led to a failure of modeling, such that the normal concave MDJ was replaced by a mound‐like deformity. This was accompanied by a failure to induce receptor activator of NF‐kB ligand (RANKL) and a 75% reduction in OC number (P ≤ 0.001) on the cortical surface. The MDJ also displayed a curious threefold increase in endocortical osteoblast mineral apposition rate (P ≤ 0.001) and a thickened cortex, suggesting some form of coupling of endocortical bone formation to events on the PO surface. Because it fuses distally, the fibula is modeled only proximally and does so at an extraordinary rate, with an anteromedial cortex in CD‐1 mice that was so moth‐eaten that a clear PO surface could not be identified. The cKO fibula displayed a remarkable phenotype, with a misshapen club‐like metaphysis and an enlargement in the 3D size of the entire bone, manifest as a 40–45% increase in the PO circumference at the MDJ (P ≤ 0.001) as well as the mid‐diaphysis (P ≤ 0.001). These tibial and fibular phenotypes were reproduced in a Scx‐Cre‐driven RANKL cKO mouse. We conclude that PTHrP in the fibrous PO mediates the modeling of the MDJ of long bones during linear growth, and that in a highly susceptible system such as the fibula this surface modeling defines the size and shape of the entire bone.     

Modulation of JNK-1/ β-catenin signaling by Lactobacillus casei,inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice

Colon cancer is a complex disease that involves numerous genetic alterations that change the normal colonic mucosa into invasive adenocarcinoma. In the current study, the protective effects of inulin (prebiotic), Lactobacillus casei (L. casei, probiotic) and their combination (synbiotic) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male Swiss mice were evaluated. Animals were divided into: Control group, DMH-treated group, DMH plus inulin, DMH plus L. casei and DMH plus inulin plus L. casei-treated groups. Fecal microbiome analysis, biochemical measurements, histopathological examination of the colon tissues, immunostaining and Western blotting analysis of β-catenin, GSK3β and JNK-1 were performed. The prebiotic-, probiotic- and synbiotic-treated groups showed decreased levels of carcinoembryonic antigen and a lower number of aberrant crypt foci compared to the DMH-treated group with the synbiotic group exhibiting a superior effect. Furthermore, all treatments showed a body weight-reducing effect. Administration of inulin, L. casei or their combination increased the expression level of phospho-JNK-1 while they decreased the expression level of β-catenin and phospho-GSK3β. Remarkably, L. casei treatment resulted in enrichment of certain beneficial bacterial genera i.e. Akkermansia and Turicibacter. Therefore, administration of L. casei and inulin as a synbiotic combination protects against colon cancer in mice.

The lactobacillus casei and inulin modulate the expression of JNK-1, GSK3β and β-catenin proteins and enrich the beneficial bacteria to protect from colon cancer in mice.     

High Frequency of Acquired ADAMTS13 Deficiency After Hemolysis in Hemiscorpius Lepturus (Scorpion) Stung Children

Objective

To estimate the frequency of acquired ADAMTS13 deficiency in severe cases of Hemiscorpius lepturus stung patients and the frequency of acute kidney injury (AKI) in these patients.

Methods

Sixty scorpion stung children who were referred with severe hemolysis and hemoglobinuria were studied. None of them had received blood products and no one had a past medical history of renal failure.

Results

Plasma levels of ADAMTS13 and ADAMTS13 antibody (IgG) were measured using ELISA. ADAMTS13 was decreased in 91.7 % of patients and the anti-ADAMTS13 antibody (Ab) was increased in 98.3 %. ADAMTS13 decreased in all of the patients with acute kidney injury and none of those with normal levels of ADAMTS13 developed renal failure; all patients with AKI had also increased levels of ADAMTS13Ab. Acute kidney injury was found in 23.3 % and had significant association with severe anemia, thrombocytopenia, pyuria, hematuria and considerable proteinuria (p?<?0.001). Disseminated intravascular coagulation (DIC) and Hemolytic uremic syndrome (HUS) developed in 6.7 % and 10 % respectively.

Conclusions

The index findings demonstrate that Hemiscorpius lepturus sting is usually associated with ADAMTS13 deficiency, and increased ADAMTS13 autoantibody. These combined mechanisms may contribute to scorpion sting-induced coagulopathies and may predispose patients to develop DIC and HUS.