Nasal Drug Delivery Systems: An Overview

Since ancient times, drugs have been administered via the nasal route for therapeutic and recreational purposes. The interest in, and importance, of the systemic effects of drugs administered through the nasal route, have expanded over recent decades. Intra-nasal administration of drugs offers an interesting alternative for achieving systemic therapeutic effects of drugs that are comparable to the parenteral route, which can be inconvenient at times or oral administration, which can result in unacceptably low drug bioavailability. So, it is important to understand the potential and limitations of various nasal drug delivery systems. Therefore, the aim of this review article is to discuss the various pharmaceutical dosage forms that have the potential to be utilised for local or systemic drug administration. It is intuitively expected that this review will help to understand and further to develop suitable intra-nasal formulations to achieve specific therapeutic objectives

Prevalence and risk factors for hypertension and association with ethnicity in Nigeria: results from a national survey.

OBJECTIVE: Non-communicable diseases are now a global priority. We report on the prevalence of hypertension and its risk factors, including ethnicity, in a nationally representative sample of Nigerian adults recruited to a survey of visual impairment. METHODS: multi-stage, stratified, cluster random sample with probability proportional to size procedures was used to obtain a nationally representative sample of 13 591 subjects aged ≥ 40 years. Of these, 13 504 (99.4%) had a blood pressure measurement. RESULTS: The prevalence of hypertension was 44.9% [95% confidence interval (CI): 43.5-46.3% ]. Increasing age, gender, urban residence and body mass index were independent risk factors (p < 0.001). The Kanuri ethnic group had the highest prevalence of hypertension (77.5%, 95% CI: 71.0-84.0%). CONCLUSIONS: The high prevalence of hypertension in Nigeria is a cause for concern and suggests that it is inevitable that the impact of hypertension-related ill health is imminent, with the accompanying financial and societal costs to families and the state of Nigeria

Cancer-Associated noncoding mutations affect RNA G-quadruplex-mediated regulation of gene expression

© 2017 The Author(s). Cancer is a multifactorial disease driven by a combination of genetic and environmental factors. Many cancer driver mutations have been characterised in protein-coding regions of the genome. However, mutations in noncoding regions associated with cancer have been less investigated. G-quadruplex (G4) nucleic acids are four-stranded secondary structures formed in guanine-rich sequences and prevalent in the regulatory regions. In this study, we used published whole cancer genome sequence data to find mutations in cancer patients that overlap potential RNA G4-forming sequences in 5ⲠUTRs. Using RNAfold, we assessed the effect of these mutations on the thermodynamic stability of predicted RNA G4s in the context of full-length 5ⲠUTRs. Of the 217 identified mutations, we found that 33 are predicted to destabilise and 21 predicted to stabilise potential RNA G4s. We experimentally validated the effect of destabilising mutations in the 5ⲠUTRs of BCL2 and CXCL14 and one stabilising mutation in the 5ⲠUTR of TAOK2. These mutations resulted in an increase or a decrease in translation of these mRNAs, respectively. These findings suggest that mutations that modulate the G4 stability in the noncoding regions could act as cancer driver mutations, which present an opportunity for early cancer diagnosis using individual sequencing information.Link_to_subscribed_fulltex

Diversity in the pathway from medical student to specialist in the Netherlands:a retrospective cohort study

Background: Medical specialist workforces are not representative of the society they serve, partially due to loss of diversity in the path from student to specialist. We investigated which demographic characteristics of bachelor students of medicine (BSM) are associated with becoming a physician and (particular type of) medical specialist; and whether this suggests ‘cloning’ (reproduction of sameness) of the existing workforce. Methods: We used a retrospective cohort design, based on Statistics Netherlands data of all first-year BSM in 2002–2004 in The Netherlands (N = 4503). We used logistic regression to analyze the impact of sex, migration background, urbanity of residence, parental income and assets categories, and having healthcare professional parents, on being registered as physician or medical specialist in 2021. We compared our results to the national pool of physicians (N = 76,845) and medical specialists (N = 49,956) to identify cloning patterns based on Essed's cultural cloning theory. Findings: Female students had higher odds of becoming a physician (OR 1.87 [1.53–2.28], p &lt; 0.001). Physicians with a migration background other than Turkish, Moroccan, Surinamese, Dutch Caribbean or Indonesian (TMSDI) had lower odds of becoming a specialist (OR 0.55 [0.43–0.71], p &lt; 0.001). This was not significant for TMSDI physicians (OR 0.74 [0.54–1.03], p = 0.073). We found a cloning pattern with regard to sex and migration background. Nationwide, physicians with a Turkish or Moroccan migration background, and female physicians with other migration backgrounds, are least likely to be a medical specialist. Interpretation: In light of equity in healthcare systems, we recommend that every recruitment body increases the representativeness of their particular specialist workforce. Funding: ODISSEI.</p

Effect of alkali/mixed alkali metal ions on the thermal and spectralcharacteristics of Dy3+:B2O3-PbO-Al2O3-ZnO glasses

Thermal and spectroscopic features of 50 B2O3–10 PbO–10 Al2O3–10 ZnO–(x) Li2O–(y) Na2O–(z) K2O–1.0 Dy2O3 (mol %) (x = 19, y = 0, and z = 0; x = 0, y = 19, and z = 0; x = 0, y = 0, and z = 19; x = 9.5, y = 9.5, and z = 0; x = 9.5, y = 0, and z = 9.5; x = 0, y = 9.5, and z = 9.5) glasses, that were fabricated by utilizing melt-quenching approach, are investigated by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), optical absorption, photoluminescence excitation (PLE), photoluminescence (PL), and PL decay lifetimes. PL spectra for all the Dy3 +-doped samples show emission bands at 453 nm (blue), 482 nm (blue), 573 nm (yellow), 662 nm (red), and 752 nm (red) corresponding to the 4I15/2 → 6H15/2, 4F9/2 → 6H15/2, 4F9/2 → 6H13/2, 4F9/2 → 6H11/2, and 4F9/2 → 6H9/2 transitions, respectively, upon excitation at 350 nm. Here, Dy3 +: Li–Na glass shows the highest PL intensity for all identified emissions. The yellow-to-blue (Y/B) emission intensity ratio (varied within the range 1.257–1.376), CIE chromaticity coordinates (x,y) (slight variation between (0.3410, 0.3802) and (0.3495, 0.3872), and correlated color temperatures (CCTs) (changed from 4953 K to 5212 K) are calculated following the PL spectra. Dy3 +: 4F9/2 decay curves show non-exponential behavior and are fitted by the Inokuti-Hirayama (I–H) model, where S = 6 shows best fit, indicating dipole-dipole (d-d) interactions for Dy3 + excited (donor) and ground state (acceptor) ions

Preface

AimThis was a one-year follow-up of families referred to support services after the parents visited the emergency department due to intimate partner violence, substance abuse or a suicide attempt. Its aim was to evaluate the well-being of any children. MethodsData on families identified a year earlier by the Amsterdam protocol were gathered from child protective services and parent and child self-reports in two Dutch regions from 2012-2015. ResultsWe included 399 children (52%) boys with a median age of eight years (range 1-18) in the study using child protective services data. Of the 101 families who participated in the first measurement, 67 responded one year after the parent's emergency department visit. The results showed that 20% of the children had no or minor problems, voluntary support services were involved in 60% of cases and child protective services were involved in 20%. Compared to their first assessment a year earlier, the children's psychosocial problems had not increased, but this could have been an underestimation due to selective responses. ConclusionThe Amsterdam protocol was valuable in referring families to voluntary support services, but given the ongoing problems in some families, professionals need to carefully monitor whether support services are sufficiently effectiv

RBF-TSS: Identification of Transcription Start Site in Human Using Radial Basis Functions Network and Oligonucleotide Positional Frequencies

Accurate identification of promoter regions and transcription start sites (TSS) in genomic DNA allows for a more complete understanding of the structure of genes and gene regulation within a given genome. Many recently published methods have achieved high identification accuracy of TSS. However, models providing more accurate modeling of promoters and TSS are needed. A novel identification method for identifying transcription start sites that improves the accuracy of TSS recognition for recently published methods is proposed. This method incorporates a metric feature based on oligonucleotide positional frequencies, taking into account the nature of promoters. A radial basis function neural network for identifying transcription start sites (RBF-TSS) is proposed and employed as a classification algorithm. Using non-overlapping chunks (windows) of size 50 and 500 on the human genome, the proposed method achieves an area under the Receiver Operator Characteristic curve (auROC) of 94.75% and 95.08% respectively, providing increased performance over existing TSS prediction methods

A Modified Random Phase Approximation of Polyelectrolyte Solutions

We compute the phase diagram of salt-free polyelectrolyte solutions using a modified Debye-Huckel Approach. We introduce the chain connectivity via the Random Phase Approximation with two important modifications. We modify the electrostatic potential at short distances to include a bound on the electrostatic attractions at the distance of closest approach between charges. This modification is shown to act as a hard core in the phase diagram of electrolyte solutions. We also introduce a cut-off on the integration of the modes of wave length smaller than the size over which the chains are strongly perturbed by the electrostatic interactions. This cut-off is shown to be essential to predict physical phase diagram in long chain solutions

Wnt antagonist secreted frizzled-related protein 4 upregulates adipogenic differentiation in human adipose tissue-derived mesenchymal stem cells

With more than 1.4 billion overweight or obese adults worldwide, obesity and progression of the metabolic syndrome are major health and economic challenges. To address mechanisms of obesity, adipose tissue-derived mesenchymal stem cells (ADSCs) are being studied to detail the molecular mechanisms involved in adipogenic differentiation. Activation of the Wnt signalling pathway has inhibited adipogenesis from precursor cells. In our study, we examined this anti-adipogenic effect in further detail stimulating Wnt with lithium chloride (LiCl) and 6-bromo indirubin 3'oxime (BIO). We also examined the effect of Wnt inhibition using secreted frizzled-related protein 4 (sFRP4), which we have previously shown to be pro-apoptotic, anti-angiogenic, and anti-tumorigenic. Wnt stimulation in LiCl and BIOtreated ADSCs resulted in a significant reduction (2.7-fold and 12-fold respectively) in lipid accumulation as measured by Oil red O staining while Wnt inhibition with sFRP4 induced a 1.5-fold increase in lipid accumulation. Furthermore, there was significant 1.2-fold increase in peroxisome proliferator-activated receptor gamma (PPAR ?) and CCAAT/enhancer binding protein alpha (C/EBPa), and 1.3-fold increase in acetyl CoA carboxylase protein levels. In contrast, the expression of adipogenic proteins (PPAR?, C/EBPa, and acetyl CoA carboxylase) were decreased significantly with LiCl (by 1.6, 2.6, and 1.9-fold respectively) and BIO (by 7, 17, and 5.6-fold respectively) treatments. These investigations demonstrate interplay between Wnt antagonism and Wnt activation during adipogenesis and indicate pathways for therapeutic intervention to control this process