Access and utilisation of primary health care services comparing urban and rural areas of Riyadh Providence, Kingdom of Saudi Arabia

The Kingdom of Saudi Arabia (KSA) has seen an increase in chronic diseases. International evidence suggests that early intervention is the best approach to reduce the burden of chronic disease. However, the limited research available suggests that health care access remains unequal, with rural populations having the poorest access to and utilisation of primary health care centres and, consequently, the poorest health outcomes. This study aimed to examine the factors influencing the access to and utilisation of primary health care centres in urban and rural areas of Riyadh province of the KSA

Genetic and phenotypic characterization of NKX6‐2‐related spastic ataxia and hypomyelination

Background and purpose Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi‐allelic mutations in NKX6‐2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. Methods Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6‐2 mutations in a multicentre setting is described. Then, all reported NKX6‐2 mutations and those identified in this study were combined and an in‐depth analysis of NKX6‐2‐related disease spectrum was provided. Results Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6‐2 were identified, evidencing a high NKX6‐2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6‐2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. Conclusions NKX6‐2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6‐2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels

Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Background:The molecular drivers of early sporadic Parkinson’s disease (PD) remain unclear, and the presence of widespread end stage pathology in late disease masks the distinction between primary or causal disease-specific events and late secondary consequences in stressed or dying cells. However, early and mid-stage Parkinson’s brains (Braak stages 3 and 4) exhibit alpha-synuclein inclusions and neuronal loss along a regional gradient of severity, from unaffected-mild-moderate-severe. Here, we exploited this spatial pathological gradient to investigate the molecular drivers of sporadic PD. Methods: We combined high precision tissue sampling with unbiased large-scale profiling of protein expression across 9 brain regions in Braak stage 3 and 4 PD brains, and controls, and verified these results using targeted proteomic and functional analyses. Results: We demonstrate that the spatio-temporal pathology gradient in early-mid PD brains is mirrored by a biochemical gradient of a changing proteome. Importantly, we identify two key events that occur early in the disease, prior to the occurrence of alpha-synuclein inclusions and neuronal loss: (i) a metabolic switch in the utilisation of energy substrates and energy production in the brain, and (ii) perturbation of the mitochondrial redox state. These changes may contribute to the regional vulnerability of developing alpha-synuclein pathology. Later in the disease, mitochondrial function is affected more severely, whilst mitochondrial metabolism, fatty acid oxidation, and mitochondrial respiration are affected across all brain regions. Conclusions: Our study provides an in-depth regional profile of the proteome at different stages of PD, and highlights that mitochondrial dysfunction is detectable prior to neuronal loss, and alpha-synuclein fibril deposition, suggesting that mitochondrial dysfunction is one of the key drivers of early disease

Evaluation of Smart Chromatic Technology for a Single-Shade Dental Polymer Resin: An In Vitro Study

The aim of the study was to assess the color matching ability and color stability of a single-shade resin-based composite (Omnichroma—OM) in comparison to a conventional dental composite. One hundred and sixty lower molar acrylic teeth in four different shades (B1, B2, A3, and C3) were prepared with class I cavities. Eighty teeth were divided into two groups based on the two resin composite materials (OM and Filtek Z-350 (FT)) for cavity restoration. Three groups were included in the color matching assessment, namely Gp 1-FT, Gp 2-OM-light cured (C), and Gp 3-OM-uncured (UC) groups. The color assessment was performed prior to cavity restoration and after cavity filling and before and after light curing to detect color matching. The 80 remaining teeth were restored with OM (n = 40) and FT (n = 40); half (n = 40) were submerged in coffee and the other half (n = 40) were submerged in cola for 2 weeks. The color stability was assessed by calculating material color (spectrophotometry) changes (∆E) before and after staining in immersion medium. The means and standard deviations of the ∆E values relating to color matching and color stability (stain resistance) among the study groups were analyzed using ANOVA and Tukey’s post hoc test. FT showed significantly better color matching (lower ΔE) in comparison to OM-UC specimens for shades B1, B2, and A3 (p < 0.01). Regarding the color stability in cola, the FT samples showed significantly lower ΔE values (indicating better color stability) compared to OM samples for all four shades (p < 0.01). The ΔE values of OM and FT samples in coffee were comparable (p > 0.01), showing comparable color stability. The color matching ability of the single-shade resin composite (OM) was influenced by the tooth color. The conventional resin composite showed better color matching than the single-shade composite (OM). The color stability of the single-shade resin composite (OM) was dependent on the staining medium. The OM composite showed more compromised color stability than the conventional resin composite in cola and comparable color stability to conventional resin composite in coffee

Levels of DNA Adducts in the Blood and Follicular Fluid of Women Undergoing In Vitro Fertilization Treatment and Its Correlation with the Pregnancy Outcome

This study is designed to investigate the impact of DNA damage on pregnancy and fertilization rate outcome in a sub-sample of women undergoing IVF treatment. Blood and follicular fluid samples (n = 60) were analyzed for DNA adducts. While no BPDE-DNA adducts were detected, other unknown lipophilic adducts were seen in blood and follicular fluid. Women who failed to achieve pregnancy had higher DNA adducts in follicular fluid than those who succeeded (p < 0.05). Follicular fluid cotinine levels were associated with DNA adduct levels in blood and follicular fluid (p < 0.05). Evaluation of DNA damage resulting from oxidative stress could have a role in predicting IVF success rate. © 2009 Springer Science+Business Media, LLC

A Selective Gas Chromatography–Tandem Mass Spectrometry Method for Quantitation of Ethylene and Diethylene Glycol in Paediatric Syrups

Ethylene Glycol (EG) and diethylene Glycol (DEG) are two contaminants known to cause various human health problems. These glycols might be present in drug syrups that are based on glycerol, sorbitol, or polyethylene glycol. In late 2022, several batches of cough, antipyretics, and antihistamine syrups were reported to contain toxic levels of EG and DEG in multiple countries; this incident concerned the World Health Organization (WHO). From an analytical perspective, several methods of glycols analysis in pharmaceuticals have been reported in the literature, with the majority being dedicated to raw material analysis. This study aims to develop a selective method capable of evaluating a wide range of paediatric syrups in order to assess the safety of commercially available paediatric syrups currently distributed in the local market. This research introduces a method for determining glycols utilizing gas chromatography-tandem mass spectrometry (GC–MS/MS), which offers significantly higher selectivity than conventional single quadrupole gas chromatography-mass spectrometry (GC–MS). The developed method meets the current International Council for Harmonisation (ICH) guidelines for validation. The absence of any interfering peaks in both the unspiked sample of promethazine syrup and the reference standard solutions proved the method's selectivity. Furthermore, 2,2,2-trichloroethanol was used as an internal standard, and a new GC–MS/MS method was developed to analyze it. The calibration curves for EG and DEG were linear within the selected concentration range of 1–10 μg/mL. The detection limit for both EG and DEG was 400 ng/mL, while the quantification limit was 1 μg/mL. Recovery values for both EG and DEG met the accuracy acceptance criterion. Thus, the developed method proved to be efficient and accurate for determining EG and DEG levels in suspected contaminated syrups

Argus II retinal prosthesis for retinitis pigmentosa in the Middle East: The 2015 Pan-American Association of Ophthalmology Gradle Lecture

Background: To describe the outcomes of patients with retinitis pigmentosa (RP) who received the Argus II Retinal Prosthesis System. Methods: This retrospective, interventional case series evaluated 10 consecutive patients who received the Argus II retinal implant and underwent visual function tests with the system on and system off. The main outcome measures were safety (the number, seriousness, and relatedness of adverse events), and visual function measured by computer-based objective tests, including square localization (SL) and direction of motion (DOM). Secondary measures included functional vision performance, including orientation and mobility (O&amp;M) tasks. Results: There were no intraoperative complications and all prostheses remained implanted at the end of follow up. The mean patient age was 41.3&nbsp;years; mean duration of the implant in vivo was 2.1&nbsp;years. One patient had a suture exposure over the coil suture tab and over the inferior case suture tab at 2&nbsp;years postoperatively, which was managed successfully. One patient developed mild vitreous hemorrhage that resolved spontaneously. One patient developed high intraocular pressure postoperatively due to a tight scleral band (SB) that was managed successfully. Patients performed significantly better with the Argus II system on than off on all tasks. Conclusion: Patients who received the Argus II had a safety profile out to 4&nbsp;years post-implantation that was markedly better than that observed in the pre-approval phase of the Argus II. In this population of RP patients, the Argus II retinal prosthesis provided useful visual function over several years that likely translates into improved quality of life. Trial Registration: clinicaltrials.gov identifier, NCT00407602