Clinical Pharmacology and Dosing Regimen Optimization of Neonatal Opioid Withdrawal Syndrome Treatments

In this paper, we review the management of neonatal opioid withdrawal syndrome (NOWS) and clinical pharmacology of primary treatment agents in NOWS, including morphine, methadone, buprenorphine, clonidine, and phenobarbital. Pharmacologic treatment strategies in NOWS have been mostly empirical, and heterogeneity in dosing regimens adds to the difficulty of extrapolating study results to broader patient populations. As population pharmacokinetics (PKs) of pharmacologic agents in NOWS become more well-defined and knowledge of patient-specific factors affecting treatment outcomes continue to accumulate, PK/pharmacodynamic modeling and simulation will be powerful tools to aid the design of optimal dosing regimens at the patient level. Although there is an increasing number of clinical trials on the comparative efficacy of treatment agents in NOWS, here, we also draw attention to the importance of optimizing the dosing regimen, which can be arguably equally important at identifying the optimal treatment agent

Pheophorbide b ethyl ester from a chlorella vulgaris dietary supplement

In the title compound, C37H38N4O6, four five-membered nitro­gen-bearing rings are nearly coplanar. Two N atoms in two these five-membered rings have attached H atoms, which contribute to the formation of intra­molecular N—H⋯N hydrogen bonds [N⋯N = 2.713 (5)–3.033 (6) Å]

PHY and MAC, cross-layer optimization and design

This document gives some definitions about PHY and MAC layer displaying its internal architecture and major functions to both layers. And as the same time states some information about cross-layer design, discussing the architecture of the cross-layer, and focusing on major methods of interfacing with giving one example of data transmission and interfacing which is meant to be very useful in this stage. Each researcher may walk through some problems during time of enhancement and optimization for the cross-layer, so here we stated some challenges to solve some problems with concentrating on number of points of classifications for cross-layer solutions

A versatile multiplexed assay to quantify intracellular ROS and cell viability in 3D on-a-chip models

Reactive oxygen species (ROS) have different properties and biological functions. They contribute to cell signaling and, in excessive amounts, to oxidative stress (OS). Although ROS is pivotal in a wide number of physiological systems and pathophysiological processes, direct quantification in vivo is quite challenging and mainly limited to in vitro studies. Even though advanced in vitro cell culture techniques, like on-a-chip culture, have overcome the lack of crucial in vivo-like physiological aspects in 2D culture, the majority of in vitro ROS quantification studies are generally performed in 2D. Here we report the development, application, and validation of a multiplexed assay to quantify ROS and cell viability in organ-on-a-chip models. The assay utilizes three dyes to stain live cells for ROS, dead cells, and DNA. Confocal images were analyzed to quantify ROS probes and determine the number of nuclei and dead cells. We found that, in contrast to what has been reported with 2D cell culture, on-a-chip models are more prone to scavenge ROS rather than accumulate them. The assay is sensitive enough to distinguish between different phenotypes of endothelial cells (ECs) based on the level of OS to detect higher level in tumor than normal cells. Our results indicate that the use of physiologically relevant models and this assay could help unravelling the mechanisms behind OS and ROS accumulation. A further step could be taken in data analysis by implementing AI in the pipeline to also analyze images for morphological changes to have an even broader view of OS mechanism

Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression

Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. Conclusion: This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression

Biocompatible Peptide-Coated Ultrasmall Superparamagnetic Iron Oxide Nanoparticles for In Vivo Contrast-Enhanced Magnetic Resonance Imaging

The biocompatibility and performance of reagents for in vivo contrast-enhanced magnetic resonance imag-ing are essential for their translation to the clinic. The quality of the surface coating of nanoparticle-based MRI contrast agents, such as ultra-small superparamagnetic iron oxide nanoparticles (USPIONs), is criti-cal to ensure high colloidal stability in biological environments, improved magnetic performance and dis-persion in circulatory fluids and tissues. Herein, we report the design of a library of 21 peptides and lig-ands and identify highly stable self-assembled monolayers on the USPIONs surface. A total of 86 differ-ent peptide coated USPIONs are prepared and selected using several stringent criteria, e.g., stability against electrolyte-induced aggregation in physiological conditions, prevention of non-specific binding to cells, absence of cellular toxicity and contrast-enhanced in vivo MRI. The bis-phosphorylated peptide 2PG-S∗VVVT-PEG4-ol provides highest biocompatibility and performance for USPIONs, with no de-tectable toxicity or adhesion to live cells. The 2PG-S∗VVVT-PEG4-ol coated USPIONs show enhanced magnetic resonance properties, r1 (2.4 mM-1.s-1) and r2 (217.8 mM-1.s-1) relaxivities, and greater r2/r1 relaxivity ratios (>90), when compared to commercially available MRI contrast agents. Furthermore, we demonstrate the utility of 2PG-S∗VVVT-PEG4-ol coated USPIONs as a T2 contrast agent for in vivo MRI applica-tions. High contrast enhancement of the liver is achieved as well as detection of liver tumors, with signifi-cant improvement of the contrast-to-noise ratio of tumor-to-liver contrast. It is envisaged that the reported peptide coated USPIONs have the potential to allow for the specific targeting of tumors, and hence early detection of cancer by MRI

Aging male symptoms scale (AMS) for health-related quality of life in aging men: translation and adaptation in Malay

The Aging Male Symptoms Scale (AMS) measures health-related quality of life in aging men. The objective of this paper is to describe the translation and validation of the AMS into Bahasa Melayu (BM). The original English version of the AMS was translated into BM by 2 translators to produce BM1 and BM2, and subsequently harmonized to produce BM3. Two other independent translators, blinded to the English version, back-translated BM3 to yield E2 and E3. All versions (BM1, BM2, BM3, E2, E3) were compared with the English version. The BM pre-final version was produced, and pre-tested in 8 participants. Proportion Agreement, Weighted Kappa, Spearman Rank Correlation Coefficient, and verbatim responses were used. The English and the BM versions showed excellent equivalence (weighted Kappa and Spearman Rank Coefficients, ranged from 0.72 to 1.00, and Proportion Agreement values ranged from 75.0% to 100%). In conclusion, the BM version of the AMS was successfully translated and adapted

Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health : the "gut feelings" randomised controlled trial

Background: Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. Methods: “Gut Feelings” was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. Results: A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen’s d = −0.60, 95% confidence interval (CI) = −1.18, −0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = −0.19, 95% CI = −0.75, 0.38; p = 0.51) or synbiotic treatments (d = −0.03, 95% CI = −0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. Conclusion: A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size

Review of Adaptive Cell Selection Techniques in LTE-Advanced Heterogeneous Networks

Poor cell selection is the main challenge in Picocell (PeNB) deployment in Long Term Evolution- (LTE-) Advanced heterogeneous networks (HetNets) because it results in load imbalance and intercell interference. A selection technique based on cell range extension (CRE) has been proposed for LTE-Advanced HetNets to extend the coverage of PeNBs for load balancing. However, poor CRE bias setting in cell selection inhibits the attainment of desired cell splitting gains. By contrast, a cell selection technique based on adaptive bias is a more effective solution to traffic load balancing in terms of increasing data rate compared with static bias-based approaches. This paper reviews the use of adaptive cell selection in LTE-Advanced HetNets by highlighting the importance of cell load estimation. The general performances of different techniques for adaptive CRE-based cell selection are compared. Results reveal that the adaptive CRE bias of the resource block utilization ratio (RBUR) technique exhibits the highest cell-edge throughput. Moreover, more accurate cell load estimation is obtained in the extended RBUR adaptive CRE bias technique through constant bit rate (CBR) traffic, which further improved load balancing as against the estimation based on the number of user equipment (UE). Finally, this paper presents suggestions for future research directions

Mobile station movement direction prediction (MMDP) based handover scanning for mobile WiMAX system

Mobile WiMAX is a broadband technology that is capable of delivering triple play services (voice, data, and video). However, mobility in mobile WiMAX system is still an issue when the mobile station (MS) moves and its connection is handed over between base stations (BSs). In the handover process, scanning is one of the required phases to find the target BS. During the handover scanning process, the MS must synchronize with all the advertised neighbour BSs (nBSs) to select the best BS candidate for the incoming handover action. Without terminating the connection between the SBS and MS, the SBS will schedule the scanning intervals and sleep-intervals (also called interleaving interval) to MS for the handover scanning. However, during the scanning interval period, all the coming transmissions will be paused. Therefore, the redundant or unnecessary scanning of neighbouring BS cause delay and MAC overhead which may affect real-time applications. In this paper, the MS movement direction prediction (MMDP) based handover scanning scheme is introduced to overcome the mobile WiMAX handover scanning issue. It based on dividing the BS coverage area is into zones and sectors. According to the signal quality; there are three zones, no handover (No-HO), low handover (Low-HO) and high handover (High-HO) zones respectively and six sectors. In this scheme, only two BSs can become candidates; the two that the MS moves toward them will be chosen as the candidate for the handover scanning purpose. Hence, the handover scanning process repetition will be reduced with these two shortlisted BS candidates instead of scanning all nBSs. Thus, MMDP will reduce scanning delay and the number of exchange messages during the handover scanning comparing to the conventional scanning scheme. Although, the MMDP may need an extra computational time, the prediction and scanning process will be finished before the MS reach the High-HO zone, which mean the end-user’s running application will be affected. Simulation results show that the proposed MMDP scheme reduces the total handover scanning delay and scanning interval duration by 25 and 50 % respectively. Also, the size of scanning message is reduced, which leads to reduced signalling overhead