NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin.

Angiogenesis relies on the ability of endothelial cells (ECs) to migrate over the extracellular matrix via integrin receptors to respond to an angiogenic stimulus. Of the two neuropilin (NRP) orthologs to be identified, both have been reported to be expressed on normal blood and lymphatic ECs, and to play roles in the formation of blood and lymphatic vascular networks during angiogenesis. Whilst the role of NRP1 and its interactions with integrins during angiogenesis has been widely studied, the role of NRP2 in ECs is poorly understood. Here we demonstrate that NRP2 promotes Rac-1 mediated EC adhesion and migration over fibronectin (FN) matrices in a mechanistically distinct fashion to NRP1, showing no dependence on β3 integrin (ITGB3) expression, or VEGF stimulation. Furthermore, we highlight evidence of a regulatory crosstalk between NRP2 and α5 integrin (ITGA5) in ECs, with NRP2 depletion eliciting an upregulation of ITGA5 expression and disruptions in ITGA5 cellular organization. Finally, we propose a mechanism whereby NRP2 promotes ITGA5 recycling in ECs; NRP2 depleted ECs were found to exhibit reduced levels of total ITGA5 subunit recycling compared to wild-type (WT) ECs. Our findings expose NRP2 as a novel angiogenic player by promoting ITGA5-mediated EC adhesion and migration on FN

Physicians’ attitudes, beliefs and barriers to a pulmonary rehabilitation for COPD patients in Saudi Arabia: a cross-sectional study

This study aimed to assess physicians’ attitudes toward delivering pulmonary rehabilitation (PR) to chronic obstructive pulmonary disease (COPD) patients and identify factors and barriers that might influence referral decisions. Between September 2021 and January 2022, a cross-sectional online survey was distributed to all physicians in Saudi Arabia. A total of 502 physicians completed the online survey, of which 62.0% (n = 312) were male. General physicians accounted for 51.2%, while internal-medicine specialists and pulmonologists accounted for 26.9% and 6.6%, respectively. Only 146 (29%) physicians had referred COPD patients to a PR program. The difference in referral rates between all specialties (p = 0.011) was statistically significant. Physicians with more years of experience were more likely to refer COPD patients to PR (p < 0.001). Moreover, a home-based PR program was preferred by 379 physicians (75.5%), and 448 (89.2%) perceived smoking cessation as an essential component of PR. Availability of PR centers (69%) was the most common barrier for not referring patients to PR. The overall referral rate was low among all physicians, owing to a lack of PR centers and trained staff. Home-based delivery was the preferred method of delivering PR, with smoking cessation as an essential component

Perception and clinical practice regarding mucus clearance devices with chronic obstructive pulmonary disease: a cross-sectional study of healthcare providers in Saudi Arabia

OBJECTIVES: Clearing secretions from the airway can be difficult for people with chronic obstructive pulmonary disease (COPD). Mucus clearance devices (MCDs) are an option in disease management to help with this, but healthcare provider awareness and knowledge about them as well as current clinical practice in Saudi Arabia are not known. DESIGN: A cross-sectional online survey consisting of four themes; demographics, awareness, recommendations and clinical practice, for MCDs with COPD patients. SETTING: Saudi Arabia. PARTICIPANTS: 1188 healthcare providers including general practitioners, family physicians, pulmonologists, nursing staff, respiratory therapists and physiotherapists. PRIMARY OUTCOME MEASURES: Healthcare providers' level of awareness about MCDs, and the identification of current clinical practices of COPD care in Saudi Arabia. RESULTS: 1188 healthcare providers (44.4% female) completed the survey. Regarding devices, 54.2% were aware of the Flutter, 23.8% the Acapella and 5.4% the positive expiratory pressure mask. 40.7% of the respondents identified the Acapella, and 22.3% the Flutter as first choice for COPD management. 75% would usually or always consider their use in COPD patients reporting daily difficulty clearing mucus, whereas 55.9% would sometimes or usually consider the use of MCDs with COPD patients who produced and were able to clear mucus with cough. In clinical practice, 380 (32%) of the respondents would prescribe MCDs, 378 (31.8%) would give MCDs without prescriptions, 314 (26.4%) would not provide them at all and 116 (9.8%) would only advise patients about them. CONCLUSION: Healthcare providers are aware of the existence of MCDs and their benefits for sputum clearance and believe that MCDs are beneficial for sputum clearance in some COPD patients. TRIAL REGISTRATION NUMBER: ISRCTN44651852

Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G &gt; A). Two missense mutations were identified with a PKD1 (c.1758A &gt; C and c.9774T &gt; G), and one patient had a PKD2 mutation (c.1445T &gt; G). Three detected variants were novel, identified at PKD1 (c.1758A &gt; C), PKD2L2 (c.1364A &gt; T), and TSC2 (deletion of a'a at the 3'UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C &gt; T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3'UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein-protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended

External Vs Internal e-Referrals: Results from a Nationwide Epidemiological Study Utilizing Secondary Collected Data

Nawfal A Aljerian,1,2 Abdullah A Alharbi,3 Hani A Alghamdi,4 Meshary S Binhotan,5,6 Reem S AlOmar,7 Ali K Alsultan,1 Mohammed S Arafat,1 Abdulrahman Aldhabib,1 Mohammed K Alabdulaali1 1Medical Referrals Centre, Ministry of Health, Riyadh, Kingdom of Saudi Arabia; 2Emergency Medicine Department, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia; 3Family and Community Medicine Department, Jazan University, Jazan, Kingdom of Saudi Arabia; 4Department of Family and Community Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 5Emergency Medical Services Department, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia; 6King Abdullah International Medical Research Centre, Riyadh, Kingdom of Saudi Arabia; 7Department of Family and Community Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi ArabiaCorrespondence: Hani A Alghamdi, Department of Family and Community Medicine, College of Medicine, King Saud University, P.O Box 12372, Riyadh, 7065, Kingdom of Saudi Arabia, Tel +966507022266, Email [email protected]: E-referral systems, streamlining patient access to specialists, have gained global recognition yet lacked a comparative study between internal and external referrals in Saudi Arabia (KSA).Methods: This retrospective study utilized secondary data from the Saudi Medical Appointments and Referrals Centre system. The data covers 2020 and 2021, including socio-demographic data, referral characteristics, and specialties. Logistic regression analysis was used to assess factors associated with external referrals.Results: Out of 645,425 e-referrals from more than 300 hospitals, 19.87% were external. The northern region led with 48.65%. Males were 55%, and those aged 25– 64 were 56.68% of referrals. Outpatient clinic referrals comprised 47%, while 61% of referrals were due to a lack of specialty services. Several significant determinants are associated with higher rates of external referral with (p-value < 0.001) and a 95% Confidence interval. Younger individuals under 25 exhibit higher referral rates than those aged 25– 64. Geographically, compared to the central region, in descending order, there were increasing trends of external referral in the northern, western, and southern regions, respectively (OR = 19.26, OR = 4.48, OR 3.63). External referrals for outpatient departments (OPD) and dialysis services were higher than for routine admissions (OR = 1.38, OR = 1.26). The rate of external referrals due to the lack of available equipment was more predominant than other causes. Furthermore, in descending order, external referrals for organ transplantation and oncology are more frequent than for medical specialties, respectively (OR = 9.39, OR = 4.50).Conclusion: The study reveals trends in e-referrals within the KSA, noting regional differences, demographic factors, and types of specialties regarding external referrals, benefiting the New Model of Care for the 2030 Vision. Findings suggest expanding virtual consultations to reduce external referrals. Strengthening primary care and preventive medicine could also decrease future referrals. Future studies should assess resource distribution, including infrastructure and workforce, to further inform healthcare strategy.Keywords: e-referrals, health policy, epidemiology, public healt

Progress on Modified Calcium Oxide Derived Waste-Shell Catalysts for Biodiesel Production

The dwindling of global petroleum deposits and worsening environmental issues have triggered researchers to find an alternative energy such as biodiesel. Biodiesel can be produced via transesterification of vegetable oil or animal fat with alcohol in the presence of a catalyst. A heterogeneous catalyst at an economical price has been studied widely for biodiesel production. It was noted that various types of natural waste shell are a potential calcium resource for generation of bio-based CaO, with comparable chemical characteristics, that greatly enhance the transesterification activity. However, CaO catalyzed transesterification is limited in its stability and studies have shown deterioration of catalytic reactivity when the catalyst is reused for several cycles. For this reason, different approaches are reviewed in the present study, which focuses on modification of waste-shell derived CaO based catalyst with the aim of better transesterification reactivity and high reusability of the catalyst for biodiesel production. The catalyst stability and leaching profile of the modified waste shell derived CaO is discussed. In addition, a critical discussion of the structure, composition of the waste shell, mechanism of CaO catalyzed reaction, recent progress in biodiesel reactor systems and challenges in the industrial sector are also included in this review

Exploring the Impact of Iron Deficiency Anaemia on Glycated Haemoglobin A1c Levels in Pregnant and Non-Pregnant Women: A Systematic Review

Amani M AlQarni,1 Amal A Alghamdi,1 Hussain J Aljubran,2 Omar A Bamalan,2 Abdullah H Abuzaid,2 Mohammed A AlYahya,2 Ahmed M AlAwami,2 Mohammed D Al Shubbar,2 Ghada F Al Yousif1 1Department of Family and Community Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Amani M AlQarni, Family and community medicine department, King Fahd Hospital of the University, Imam Abdulrahman bin Faisal University, Dammam, 34212, Saudi Arabia, Tel +966133333766 ; +966591775751, Email [email protected]: Haemoglobin A1C (HbA1c) is fundamental in monitoring glycaemic control during pregnancy. However, several conditions could affect this test’s accuracy, including iron deficiency anaemia (IDA). Hence, this systematic review delves into the underexplored connection between IDA, iron replacement therapy (IRT), and haemoglobin A1C (HbA1c) during pregnancy. An electronic search of the Cochrane, MEDLINE, and Embase databases was conducted by six authors. From a comprehensive search strategy, 968 records were obtained. After applying the inclusion and exclusion criteria, seven studies were included, comprising 365 women selected for analysis. Six studies indicated a positive correlation between IDA and HbA1c levels, while one found no correlation. The average HbA1c level of the included studies in pregnant women was 5.64%. In comparison, it was found that non-pregnant women had lower HbA1c levels. Among the included studies, the mean HbA1c levels decreased from 5.1% to 4.89% after treating pregnant women with IRT. The review emphasises the complexity of interpreting HbA1c levels in pregnant women with IDA, highlighting the influence of pregnancy-induced physiological changes. In addition, this suggests that HbA1c should not be the sole criterion for diabetes management in pregnant women with IDA. Future research should focus on alternative glycaemic monitoring methods unaffected by IDA.Keywords: iron deficiency anaemia, iron replacement therapy, pregnancy, gestational diabetes, glycated haemoglobin, HbA1

Intravenous magnesium prevents atrial fibrillation after coronary artery bypass grafting: a meta-analysis of 7 double-blind, placebo-controlled, randomized clinical trials

<p>Abstract</p> <p>Background</p> <p>Postoperative atrial fibrillation (POAF) is the most common complication after coronary artery bypass grafting (CABG). The preventive effect of magnesium on POAF is not well known. This meta-analysis was undertaken to assess the efficacy of intravenous magnesium on the prevention of POAF after CABG.</p> <p>Methods</p> <p>Eligible studies were identified from electronic databases (Medline, Embase, and the Cochrane Library). The primary outcome measure was the incidence of POAF. The meta-analysis was performed with the fixed-effect model or random-effect model according to heterogeneity.</p> <p>Results</p> <p>Seven double-blind, placebo-controlled, randomized clinical trials met the inclusion criteria including 1,028 participants. The pooled results showed that intravenous magnesium reduced the incidence of POAF by 36% (RR 0.64; 95% confidence interval (CI) 0.50-0.83; <it>P </it>= 0.001; with no heterogeneity between trials (heterogeneity <it>P </it>= 0.8, <it>I</it>²= 0%)).</p> <p>Conclusions</p> <p>This meta-analysis indicates that intravenous magnesium significantly reduces the incidence of POAF after CABG. This finding encourages the use of intravenous magnesium as an alternative to prevent POAF after CABG. But more high quality randomized clinical trials are still need to confirm the safety.</p

Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei

Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. We demonstrate that TbAQP2’s unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug permeation. Introduction of key TbAQP2 amino acids into TbAQP3 renders the latter permeable to pentamidine. Molecular dynamics demonstrates that permeation by dicationic pentamidine is energetically favourable in TbAQP2, driven by the membrane potential, although aquaporins are normally strictly impermeable for ionic species. We also identify the structural determinants that make pentamidine a permeant although most other diamidine drugs are excluded. Our results have wide-ranging implications for optimising antitrypanosomal drugs and averting cross-resistance. Moreover, these new insights in aquaporin permeation may allow the pharmacological exploitation of other members of this ubiquitous gene family