A novel pathogenic mutation of the CYP27B1 gene in a patient with vitamin D-dependent rickets type 1: a case report

BACKGROUND: Rickets can occur due to Vitamin D deficiency or defects in its metabolism. Three rare genetic types of rickets with different alterations of genes have been reported, including: Vitamin D dependent rickets type 1, Vitamin D dependent rickets type 2 or also known as Vitamin D resistant rickets and 25 hydroxylase deficiency rickets. Vitamin D dependent rickets type 1 is inherited in an autosomal recessive pattern, and is caused by mutations in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. We report here a new mutation in CYP27B1, which lead to Vitamin D dependent rickets type 1. CASE PRESENTATION: We report on a 13-month-old Arabic Saudi girl with Vitamin D dependent rickets type 1 presented with multiple fractures and classic features of rickets. A whole exome sequencing identified a novel pathogenic missense mutation (CYP27B1:Homozygous c.1510C > T(p.Q504X)) which results in a protein truncating alteration. Both parents are heterozygous carriers of the mutation. Based on data search in Human Gene Mutation Database, 63 CYP27B1 alterations were reported: only 28.6% are protein truncating (5 nonsense, 13 frameshift insertions/deletions, 0 gross deletions), while 61.9% are non-truncating (38 missense, 1 small in-frame insertions/deletion), and 9.5% are possible protein-truncating (5 splice, 1 regulatory). CONCLUSION: The deleterious effect of this alteration, which was the only mutation detected in the CYP27B1 common gene of Vitamin D dependent rickets type 1 in the proband, and its autosomal recessive inheritance fashion, both support a pathogenic nature of this mutation as the cause of Vitamin D dependent rickets type 1

Adaptive multi-polling scheduler for QoS support of video transmission in IEEE 802.11e WLANs

The 802.11E Task Group has been established to enhance quality of service (QoS) provision for time-bounded services in the current IEEE 802.11 medium access control protocol. The QoS is introduced throughout hybrid coordination function controlled channel access (HCCA) for the rigorous QoS provision. In HCCA, the station is allocated a fixed transmission opportunity (TXOP) based on its TSPEC parameters so that it is efficient for constant bit rate streams. However, as the profile of variable bit rate traffics is inconstant, they are liable to experience a higher delay especially in bursty traffic case. In this paper, we present a dynamic TXOP assignment algorithm called adaptive multi-polling TXOP scheduling algorithm (AMTXOP) for supporting the video traffics transmission over IEEE 802.11e wireless networks. This scheme invests a piggybacked information about the size of the subsequent video frames of the uplink streams to assist the hybrid coordinator accurately assign the TXOP according to actual change in the traffic profile. The proposed scheduler is powered by integrating multi-polling scheme to further reduce the delay and polling overhead. Extensive simulation experiments have been carried out to show the efficiency of the AMTXOP over the existing schemes in terms of the packet delay and the channel utilization

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

Highly sensitive label-free in vitro detection of aflatoxin B1 in an aptamer assay using optical planar waveguide operating as a polarization interferometer

This work reports on further development of an optical biosensor for the in vitro detection of mycotoxins (in particular, aflatoxin B1) using a highly sensitive planar waveguide transducer in combination with a highly specific aptamer bioreceptor. This sensor is built on a SiO2–Si3N4–SiO2 optical planar waveguide (OPW) operating as a polarization interferometer (PI), which detects a phase shift between p- and s-components of polarized light propagating through the waveguide caused by the molecular adsorption. The refractive index sensitivity (RIS) of the recently upgraded PI experimental setup has been improved and reached values of around 9600 rad per refractive index unity (RIU), the highest RIS values reported, which enables the detection of low molecular weight analytes such as mycotoxins in very low concentrations. The biosensing tests yielded remarkable results for the detection of aflatoxin B1 in a wide range of concentrations from 1 pg/mL to 1 μg/mL in direct assay with specific DNA-based aptamers

Thermodynamics and Kinetics of Inhibition of Aluminum in Hydrochloric Acid by Date Palm Leaf Extract

The corrosion behavior of commercial aluminum in HCl was investigated by gravimetric method in absence and presence of date palm leaf extract (DPLE) as inhibitor. Corrosion rates in absence of extract ranged from 2.4-8.0 mg/cm2/h in the temperature range 20- 50ºC but decreased down to 0.30-2.6 mg/cm2/h in presence of the inhibitor. Hot-water extract of date palm leaves has shown inhibition efficiency (IE) of 40- 88%at the tested conditions. IE was found to increase with increasing inhibitor concentration from 0.2 to 0.6 g/L and decrease as temperature increased. Data showed that Langmuir adsorption isotherm represents surface coverage versus extract concentration data indicating that inhibition is due to monolayer adsorption of extract components on aluminum surface. Low activation energy and enthalpy values support physical adsorption mechanism. SEM-EDS microanalysis of aluminum surface supported the inhibitive effect of the extract at the metal surface.© JASE

Awareness of hypertension guidelines among family physicians in primary health care

Background: Only 14% of patients on treatment achieve the recommended blood pressure target. Guidelines aim to assist clinicians in the management of patients with hypertension.Objectives: The primary purpose of the study was to survey family physicians(FPs) in Kuwait about their awareness, and to understand better their reasons for not implementing specific guidance within the WHO/ISH guidelines.Methods: This study is a cross-sectional survey that was carried out in the five health regions of Kuwait. All PHC physicians who were currently working as FPs were asked to participate in the study. Data were collected using a structured questionnaire of clinically oriented questions formulated on the basis of the 1999 World Health Organization/International Society of Hypertension (WHO/ISH), as standard reference.Results: The study revealed that 49.1% and 42.1% of FPs were very familiar or somewhat familiar with the guidelines respectively, 92.1% were in agreement, and 79.8% indicated that they always or usually follow these guidelines when treating patients. Regarding the correct choice of the guideline statements, only 8.8% of the FPs choose correctly less than ten of the 20 statements, 64% choose 10 to less than 15, and only 27.2% choose > 15 statements. When asked about perceived patient barriers to blood pressure control, 84.0% of the respondents ranked overcrowded clinics as important or most important barrier to blood pressure control while, 87.4% considered lack of patient knowledge as important or most important barrier. Non availability of the drugs in the clinic was considered by 88.4% of the physicians, and poor adherence to antihypertensive drugs by 90.1%.Conclusion: There is a need to establish nationwide educational and quality monitoring programs to facilitate the correct implementation of hypertension guidelines in PHC clinical practices in Kuwait.Keywords:  Family physicians; Awareness; Hypertension; Guideline

Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance

INTRODUCTION: The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by profiling a large cohort of breast tumours in tissue microarrays (TMAs) using immunohistochemistry (IHC). METHODS: We included 4, 125 patients enrolled in the SEARCH population-based study with tumours represented in TMAs and classified into molecular subtype according to a validated IHC-based five-marker scheme. IHC was used to detect CD44/CD24, ALDH1A1, aldehyde dehydrogenase family 1 member A3 (ALDH1A3) and integrin alpha-6 (ITGA6). A 'Total CSC' score representing expression of all four CSC markers was also investigated. Association with breast cancer specific survival (BCSS) at 10 years was assessed using a Cox proportional-hazards model. This study was complied with REMARK criteria. RESULTS: In ER negative cases, multivariate analysis showed that ITGA6 was an independent prognostic factor with a time-dependent effect restricted to the first two years of follow-up (hazard ratio (HR) for 0 to 2 years follow-up, 2.4; 95% confidence interval (95% CI), 1.2 to 4.8; P = 0.009). The composite 'Total CSC' score carried independent prognostic significance in ER negative cases for the first four years of follow-up (HR for 0 to 4 years follow-up, 1.3; 95% CI, 1.1 to 1.6; P = 0.006). CONCLUSIONS: Breast CSC markers do not identify identical subpopulations in primary tumours. Both ITGA6 and a composite Total CSC score show independent prognostic significance in ER negative disease. The use of multiple markers to identify tumours enriched for CSCs has the greatest prognostic value. In the absence of more specific markers, we propose that the effective translation of the CSC hypothesis into patient benefit will necessitate the use of a panel of markers to robustly identify tumours enriched for CSCs

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Exploring the Current Tools in Cardiovascular Risk Assessment in the Middle East and the Need for Region-Specific Models - A Scoping Review

Gamilah Abdulkarem Al-ezzi,1,2 Adliah Mhd Ali,1 Mohammed Abdullah Kubas,3,4 Adyani Md Redzuan1 1Centre for Quality Management of Medicines (QMM), Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Faculty of Pharmacy, Sana’a University, Sana’a, Yemen; 3Faculty of Pharmacy, Lebanese International University (LIU), Sana’a, Yemen; 4Clinical Pharmacist Specialist, University of Science and Technology Hospital (USTH), Sana’a, YemenCorrespondence: Adyani Md Redzuan, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia, Tel +60392897264, Email [email protected]: Cardiovascular diseases (CVDs) are a major contributor to premature mortality, disability, and reduced quality of life globally. Assessing CVD risks is central to primary prevention, prompting the development of numerous tools to predict CVD risks for the general population. However, it is unclear which tools are recommended in clinical practice in the Middle East region.Aim: This scoping review aims to identify, review, and summarize the available literature on CVD risk assessment tools recommended for the general population in the Middle East region.Methods: The scoping review synthesized the literature on CVD risk assessment tools recommended for the general population in the Middle East region. It followed PRISMA-ScR guidelines, covering searches in the Web of Science (WOS), Medline, and Scopus databases. English-language articles published between 2015 and 2024 that focused on the primary prevention of CVDs in sixteen Middle Eastern countries were included.Results: Seventeen articles met the inclusion criteria. The studies were distributed over Cyprus (n=1), Iran (n=7), Saudi Arabia (n=4), Qatar (n=1), the United Arab Emirates (n=3), and Egypt (n=1). Various tools are recommended in these countries, including validated Western tools such as ACC/AHA Pooled-Cohort Equations (PCE), Systematic Coronary Risk Evaluation 2 (SCORE 2), World Health Organization charts (WHO/ ISH) for the Eastern Mediterranean region (EMR), Cardiovascular Disease Risk Algorithm (QRISK3), and PREDICT. Some studies in Iran, Saudi Arabia, the United Arab Emirates, and Egypt focused on developing new CVD risk tools tailored for national use.Conclusion: Current studies on CVD risk assessment are limited and have been conducted in six Middle Eastern countries. These studies recommend various tools, including both validated Western models and locally developed frameworks. However, the limitations of existing tools and the gaps in current research underscore the need for further studies to develop or recalibrate models that account for country-specific CVD risk factors across the region.Keywords: CVD risk assessment tools, general population, Middle East region, primary prevention, scoping revie

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy