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Motasim Jawi,1 Hadiah Bassam Al Mahdi,2,3 Hussam Daghistani,4,5 Yousef Almoghrabi,4,5 Rami Algahtani,6 Dalal Tawati,7 Mohammed R Algethami,8 Yasser Noorelahi,9 Zuhier Awan4 1Department of Physiology, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia; 2Al Borg Medical Laboratories, Al Borg Diagnostics, Research and Development Unit, Jeddah, Saudi Arabia; 3Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 5Regenerative Medicine Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 6Department of Medicine, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 7Department of Obstetrics and Gynecology, King Abdullah Medical Complex, Jeddah, Saudi Arabia; 8Department of Family and Community Medicine, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia; 9Department of Radiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Motasim Jawi, Department of Physiology, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia, Tel +966 569191939, Email mmjawi@uj.edu.saPurpose: Blood Lp(a) concentration is recognized as an independent risk factor for cardiovascular disease (CVD). Population-based lipoprotein(a) (Lp[a]) research in Saudi Arabia is rare. Thus, the primary goal of this pilot study was to identify age- and sex-specific reference ranges for Lp(a) levels, in addition to the associations between Lp(a) levels and other atherosclerotic markers in Saudi individuals.Patients and methods: A five-year retrospective study of Lp(a) and lipid markers in Saudi patients was conducted using the Al-Borg diagnostics database (2015– 2020). The population sample consisted of 361 Saudi individuals aged 18– 93 years (162 males, 199 females). An immunoturbidimetric technique was used to determine Lp(a) concentration.Results: The mean and median Lp(a) levels in the study population were 35 nmol/L and 50 nmol/L, respectively. Sex and age did not influence Lp(a) values. Lp(a) values showed a minor correlation with other atherosclerotic markers when the Pearson correlation coefficient was used. In Saudi Arabia, the distribution of Lp(a) concentrations is skewed to the left, favoring lower values.Conclusion: Lp(a) levels in individuals residing in Saudi Arabia were comparable to those observed in other ethnic groups. Additionally, standardizing Lp(a) measurements according to sex and age may enhance broader applicability and facilitate comparisons across different populations. However, larger studies are required to provide more comprehensive data for comparison.Keywords: lipoprotein(a), lipids, cardiovascular disease, reference range, reference interval, Saudi Arabia

Mohammad A Alfhili,1 Jawaher Alsughayyir,2 Ahmed M Basudan,1 Hazem K Ghneim,1 Mohammed Alfaifi,3 Hassan S Alamri,4 Zuhier A Awan,5,6 Mohammed R Algethami7 1Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; 4Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia; 5Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 6Department of Clinical Pathology, Al-Borg Medical Laboratories, Jeddah, Saudi Arabia; 7Ministry of Health, Jeddah, Saudi ArabiaCorrespondence: Mohammad A Alfhili, Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia, Tel +966-504-262-597, Email malfeehily@ksu.edu.saBackground: Risk factors of cardiovascular disease include dyslipidemia, hypertension (HTN), and anemia. Our objective is to assess the patterns of dyslipidemia in the anemic and non-anemic hypertensive Saudi population.Methods: A retrospective, cross-sectional study of the gender, blood pressure, lipid markers, and CBC parameters of 3111 subjects, which were retrieved from the database of Al-Borg Medical Laboratories over a six-year period (2014– 2019), was carried out. Means were compared among study groups and the prevalence, association, and diagnostic accuracy of lipid markers for HTN were evaluated.Results: TG, LDL/HDL, and TG/HDL were significantly higher (P < 0.0001) in hypertensives. Anemia reduces TC and LDL (P < 0.0001) in both genders, and reduces all markers and increases HDL (P < 0.01) in male hypertensives. HTN was more prevalent in anemics with high TC than normal TC (38.23% vs 11.17%, P < 0.001) and in non-anemics with high TG than normal TG (56.31% vs 21.22%, P < 0.001). Furthermore, non-anemics with high TG/HDL had the highest risk for HTN (RR = 1.20, 95% CI = 1.1551– 1.2473, P < 0.0001). Elevated TC (P = 0.0142), TG (P < 0.0001), TC/HDL (P < 0.0001), LDL/HDL (P < 0.0001), and TG/HDL (P < 0.0001), and low HDL (P < 0.0001) were risk factors for HTN as shown by ORs. In anemics, high TC/HDL, LDL/HDL, and TG/HDL were not. Importantly, only TG and TG/HDL had a discriminating capacity for HTN.Conclusion: The anemic state of hypertensive Saudi patients influences dyslipidemia which warrants further investigation.Keywords: hypertension, dyslipidemia, anemia, prevalence, Saudi Arabia

Husain Y Alkhaldy,1,2 Zuhier A Awan,3,4 Ahmed A Abouzaid,4,5 Hossameldin M Elbahaey,4,6 Saeed M Al Amoudi,5 Shehata F Shehata,7,8 Muhammad Saboor9,10 1Department of Internal Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia; 2Research Center for Advanced Materials Science, King Khalid University, Abha, Saudi Arabia; 3Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Clinical Pathology, Al-Borg Medical Laboratories, Jeddah, Saudi Arabia; 5Department of Medical Biochemistry, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 6Clinical Pathology Department, Suez Canal University, Ismailia Governorate, Egypt; 7Department of Community Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia; 8High Institute of Public Health, Alexandria University, Alexandria, Egypt; 9Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 10Medical Research Center, Jazan University, Jazan, Saudi ArabiaCorrespondence: Husain Y Alkhaldy, Department of internal medicine, College of Medicine, King Khalid University, P.O.BOX 641, Abha, 61421, Saudi Arabia, Tel +966 72417578 ; +966 5999-15-567, Fax +966 72418111, Email halkhaldy@kku.edu.sa Muhammad Saboor, Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan, Saudi Arabia, Tel +966 54 495 9029, Email msaboor@jazanu.edu.saPurpose: Complete blood count (CBC) is a commonly used blood test for health checks. This study was conducted to compare CBC from two different altitudes and from sea-level populations in order to suggest correction factor for altitude-related increment on the hemoglobin and red blood cell indices.Patients and Methods: In this retrospective lab records study, large datasets of CBCs over 5-year period were screened from three different regions of Saudi Arabia, Jeddah (a coastal city), Taif City located at 1879 m above sea level, and Abha City at located 2270 m above sea level. Descriptive analysis and significance testing of the CBC variables at different altitude were compared.Results: A total of 57,059 participants were included for final analysis. Mean hemoglobin (Hb) concentration (g/dL) was 14.81 for men and 13.77 for women at sea level, whereas Hb concentrations were 15.35 and 14.19 for men and women residing at Taif City, respectively, and 15.40 and 14.71 for men and women at Abha City, respectively. Hemoglobin and other red cell indices were significantly different among men and women across different altitude, except for mean corpuscular volume (MCV). The MCV 95th percentile range was lower at sea level and both altitudes as compared to current reference range (76– 91 fL vs 81– 98 fL).Conclusion: Although altitude-associated increment in Hb concentration was evident in both men and women, it was lower than as suggested by World Health Organization and Centers for Disease and Control. Results of this study can also be used to derive new CBC reference intervals for Saudi residents living at high altitude. A correction factor (ΔHb) of 0.30 g/dL per 1000 m altitude is suggested to be used in adult population living at high altitudes in Saudi Arabia which should help better define anemia and polycythemia at altitude.Keywords: high altitude, reference interval, CBC

Fahmy UA, Ahmed OAA, Badr-Eldin SM, et al. Int J Nanomedicine. 2020;15:5253-5264. The Editor and Publisher of International Journal of Nanomedicine are retracting the above published article. An investigation by the Publisher, found overlap in images from Figure 6 of the published article above and the images from Figure 6 of the following published article: Ahmed OAA, Fahmy UA, Badr-Eldin SM, et al. Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route. Nanomaterials. 2020; 10(7):1270 (https://doi.org/10.3390/nano10071270). Specifically, this included: From the published article above, Figure 6B, plain in situ gel group, and 6D, optimized FLB-NLC in situ gel group, are the same images as Figure 6D, rats treated with optimized FLB-TRF hydrogel (gp4) and 6C, rats treated with raw FLB loaded in hydrogel (gp3), respectively, from Ahmed et al, 2020. Furthermore, the images in Figure 6 of the published article above are derived from the same image but used to describe different results. Specifically, this included: From the published article above, Figure 6A, Control untreated group; 6B, plain in situ gel group; 6C, raw FLB loaded in situ gel group and 6D, optimized FLB-NLC in situ gel group, are all derived from the same image but used to describe different results. The authors cooperated with the investigation and provided data and associated documents concerning the histopathological experiments from the reported study. However, the Editor and Publisher determined that the evidence provided did not establish sufficient justification for the duplication. Therefore, the Editor and Publisher are retracting the article. The authors have agreed to retract the article and have informed the Publisher that the first author, Usama A Fahmy, takes responsibility for the error which occurred. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Zuhier A Awan,1,2 Saeed M Al Amoudi,2 Muhammad Saboor,3,4 Husain Y Alkhaldy5,6 1Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Clinical Pathology, Al-Borg Medical Laboratories, Jeddah, Saudi Arabia; 3Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Gazan, Saudi Arabia; 4Medical Research Centre (MRC), Jazan University, Jazan, Saudi Arabia; 5Department of Internal Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia; 6Research Center for Advanced Materials Science, King Khalid University, Abha, Saudi ArabiaCorrespondence: Husain Y AlkhaldyDepartment of Internal Medicine, College of Medicine, Research Center for Advanced Materials Science, King Khalid University, P.O.Box 9004, Abha, 61413, Saudi ArabiaTel +966599915567Email halkhaldy@kku.edu.saObjective: Isolated mild neutropenia is a common clinical problem in some ethnicities including Arabs and Middle Eastern population. The current study aims to authenticate the prevalence of isolated neutropenia in Southern and Southwestern Saudi Arabia, explore the effect of altitude or regional differences and to suggest a new reference range for neutrophil count.Methods: In this retrospective cross-sectional study, laboratory results of a commercial laboratory were screened over a period of 5 years (2016– 2020) in seven different cities of different altitudes in South and southwestern Saudi Arabia. Participants’ laboratory investigations were reviewed and excluded for any abnormal complete blood count, renal profile, liver profile, lipid profile, thyroid function test, fasting blood glucose, or HbA1c findings. Descriptive analysis and 95th percentile range were calculated using standard statistical methods.Results: A total of 91,880 complete blood count results were included in the final analysis. Isolated neutropenia was common laboratory finding, with a prevalence ranging from 11% to 23%. The 2.5th percentile of the neutrophil count was lower than currently utilized 1.5× 109/L in all studied seven cities.Conclusion: Mild to moderate neutropenia is common in Southern and Southwestern Saudi Arabia. Benign ethnic neutropenia (BEN) likely explains this high prevalence. Since BEN has no clinical significance, the reference range for normal neutrophil counts needs to be adjusted to reflect the effect of BEN.Keywords: isolated neutropenia, benign ethnic neutropenia, reference intervals, Saudi Arabia

Husain Y Alkhaldy,1,2 Zuhier A. Awan,3,4 Ahmed A Abouzaid,4,5 Hossameldin M Elbahaie,4,6 Saeed M Al Amoudi,4 Mohamed Andarawi,7 Shehata F Shehata8,9 1Department of Internal Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia; 2Research Center for Advanced Materials Science, King Khalid University, Abha, Saudi Arabia; 3Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Clinical Pathology, Al-Borg Medical Laboratories, Jeddah, Saudi Arabia; 5Department of Medical Biochemistry, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 6Clinical Pathology Department, Suez Canal University, Ismailia, Egypt; 7Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia; 8Department of Community Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia; 9High Institute of Public Health, Alexandria University, Alexandria, EgyptCorrespondence: Husain Y AlkhaldyDepartment of Internal Medicine, College of Medicine, King Khalid University, Abha, P.O.Box 641, Aseer 61421, Saudi ArabiaTel +966 72417578Fax +966 72418111Email halkhaldy@kku.edu.saIntroduction: Isolated neutropenia is a common problem in hematology practice. Benign ethnic neutropenia (BEN) is the common form of neutropenia worldwide and it affects mainly African and Middle Eastern ethnicities. Most cases of isolated mild and moderate neutropenia are benign and associated with no clinical significance. The aim of this study was to estimate the prevalence of isolated neutropenia at high-altitude southern Saudi Arabia.Methods: A large dataset of complete blood counts (CBCs) was analyzed for walk-in patients of both genders, of age ranges from 12 to 60 years doing blood tests at a commercial lab for high altitude − 2,270 meters above sea level – (HA) group, and from sea level SL group. Abnormal biochemical or CBC results were excluded before analysis.Results: For HA group, 3123 CBCs were analyzed and for SL group 18,427 CBCs were analyzed. The prevalence of mild neutropenia, defined as absolute neutrophil count (ANC) in the range of 1.0− .5× 109/L, was 12.4% (n=399) versus 5.6% (n=1025), while moderate neutropenia, defined as ANC of 0.5– 1 × 109/L, was present 6% (n=191) versus 1.45% (n=269) in the high altitude and sea level groups, respectively. Severe neutropenia, defined as neutrophil count less than 0.5– 1 × 109/L, was rare in both groups.Conclusion: Isolated neutropenia is common in Saudis living at high altitude. While benign ethnic neutropenia (BEN) is thought to be the major contributing factor to this high prevalence, other factors including environmental factors and altitude are possible contributing factors along with underlying ethnic neutropenia.Keywords: ethnic neutropenia, high altitude, hematological, leukocyte count

The present study was performed to know the prevalence of coccidiosis and efficacy of anti-coccidial drugs in the capital city of Muzaffarabad, Azad Kashmir, Pakistan. A total of 573 broiler birds of different age groups were sampled from the study area farms and processed accordingly. Fecal flotation and McMaster egg counting techniques were used for Oocyst identification and counting, respectively. Postmortem of birds was performed to know the lesions and type of coccidiosis present in the birds. Drug trial was also carried out to evaluate the efficacy of anti-coccidial drugs available in the study area market. An overall 19.37% (111/573) prevalence of Coccidiosis was observed in study area. Among different age groups, broilers below three weeks of age were found more susceptible to infection. During summer season higher prevalence was recorded. Different risk factors were found associated with coccidial infection in the study area. Five anticoccidial drugs available in the market have been found effective with different efficacy level. Among the anticoccidial drugs used during the present investigation, Sulphadimerazine 86% had shown better effect. Besides these anticoccidial drugs, a herbal plant locally known as Sumbal was also used and found potent against Coccidiosis. This is a good alternate choice used in field conditions along with synthetic anti-coccidial for the treatment and control of coccidiosis. It was deduced that prevalence of coccidiosis recorded in study area was comparatively lower than prevalence recorded in other parts of the world. Furthermore, Sulphadimerazine 86% have shown comparatively better efficacy than other drugs. [ABSTRACT FROM AUTHOR]

Usama A Fahmy,1 Osama AA Ahmed,1 Shaimaa M Badr-Eldin,1,2 Hibah M Aldawsari,1 Solomon Z Okbazghi,3 Zuhier A Awan,4 Muhammed A Bakhrebah,5 Mohammad N Alomary,5 Wesam H Abdulaal,6 Carlos Medina,7 Nabil A Alhakamy1 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Global Analytical and Pharmaceutical Development, Alexion Pharmaceuticals, New Haven, Connecticut, NE 06510, USA; 4Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 5Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Kingdom of Saudi Arabia; 6Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 7School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin IrelandCorrespondence: Shaimaa M Badr-Eldin Email sbadr5@hotmail.comBackground and Aim: Flibanserin (FLB) is a multifunctional serotonergic agent used for treating hypoactive sexual desire disorder in premenopausal women via oral administration. FLB has a reported limited oral bioavailability of 33% that could be attributed to the drug’s first-pass metabolism. In addition, FLB has a pH-dependent solubility that could be a challenging factor for drug dissolution in the body neutral fluid, and consequently, absorption via mucosal barriers. Thus, this work aims at investigating the potential of utilizing nanostructured lipid carriers (NLCs) to overcome the aforementioned drawbacks and to enhance nose-to-brain drug delivery.Methods: Box-Behnken design was applied to explore the impact of solid lipid % (SL%, X1), liquid lipid % (LL%, X2), and sonication time (ST, X3) on particle size. The optimized NLC formulation was characterized and incorporated into gellan gum in situ gel. The prepared gel was subjected to in vitro drug release, in vivo pharmacokinetic performance, and histopathological assessment in rats.Results: Statistical analysis revealed a significant negative effect for both SL% and ST on NLCs size. In contrast, a significant positive effect was observed for the LL%. The optimized formulation showed spherical shape with vesicular size of 114.63 nm. The optimized FLB-NLC in situ gel exhibited adequate stability and enhanced in vitro release compared to raw FLB control gel. The plasma and brain concentrations of the drug after nasal administration in rats increased by more than 3– 6-fold, respectively, compared to raw FLB in situ gel. In addition, the histopathological studies revealed the absence of any pathological signs.Conclusion: The aforementioned results highlight the safety of FLB-NLC in situ nasal gel and its potential to improve the drug bioavailability and brain delivery.Keywords: flibanserin, nanostructured lipid carrier, Compritol® 888 ATO, almond oil, gellan gum, pharmacokinetics

Among all the electrocatalysts for Lithium-Air battery (Li-air), Platinum Pt is the best performing cathode material. However, the high cost of noble Pt metal and scarcity nature impedes the use of Pt-based catalysts from being extensivity used in commercial applications. Therefore, there is an urgent need to develop an efficient and cost-effective alternate electrocatalyst to replace Pt-based materials in lithium-oxygen (Li-O2) battaries. In the present work, δ-MnO2/N-rGO composite (MNGC) has been synthesized by a simple non-template hydrothermal approach. MNGC with a porous wall structure composed of ultrathin nanosheets exhibits excellent electrochemical properties for oxidation–reduction reaction (ORR). MNGC can provide numerous pathways for abundant oxygen and electrolyte access to facilitate the mass transfer of lithium-ion. Such a well-designed structure offers the right electrocatalyst for the air cathode in lithium-oxygen (Li-O2) battaries. The prepared samples principal characteristics are analyzed, which verified the successful synthesis of sheet-like δ-MnO2 grown over the surface of nitrogen-doped reduced graphene oxide (N-rGO). Linear sweep voltammetry (LSV) results of MNGC showed enhanced ORR performance compared to MnO2 and N-rGO in terms of the half-wave potential, limiting current, and onset potential. MNGC electrode displayed superior cyclic performances of Li-air with a stable specific capacity, decreased overpotential, reversibility, and rate capability. Li-O2 battery was also tested with MNGN electrode for limited discharge capacity of 500 mAh/g, long-term cycling was achieved without electrolyte degradation. A high specific capacity of 5250 mAh/g was obtained at a high current density of 0.2 mA/cm2. The interlinked effect of δ–MnO2 and N–rGO for supporting the electrochemical interaction between O2 and Li is explained for improved columbic and energy efficiency of Li–O2 battery

Abstract Background Nucleic acid amplification assays including PCR have revolutionized the detection of Mycobacterium tuberculosis (MTB). Tuberculosis spread to almost every organ of the body and is characterized on the basis of localization of infection. Therefore, different types of body fluids and tissues can be used for the detection of MTB. From 2004 to 2010 total 766 different types of smear negative samples from patients, clinically suspected for tuberculosis were received and investigated at Division of Molecular Diagnostics, University of the Punjab Lahore for the diagnosis of tuberculosis. Mycobacterial DNA was extracted followed by PCR amplification. Findings A total of 356 (46.5%) samples were found positive by PCR for MTB. These included; serum (4.8%), blood (36.3%), urine (46.6%), cerebro spinal fluid (CSF) (42.1%), ascetic fluid (67.6%), pleural fluid (52%), pericardial fluid (30%), pus (38.6%), bone marrow (60%), sputum (38.8%) and bronchoalveolar lavage (BAL) (70%). Over all there was no significant difference in males and females neither in different age groups for the identification of MTB. Conclusion We conclude that PCR is a useful and sensitive tool for the early diagnosis of MTB in variety of clinical samples.

Abstract Hepatitis C is a major health problem affecting more than 200 million individuals in the world. Current treatment regimen consisting of interferon alpha and ribavirin does not always succeed in eliminating the virus completely from patient's body. One of the mechanisms by which virus evades the antiviral effect of interferon alpha involves protein kinase (PKR) eukaryotic initiation factor 2 alpha (eIF2a) phosphorylation homology domain (PePHD). This domain in genotype 1 strains is reportedly homologous to PKR and its target eIF2a. By binding to PKR, PePHD inhibits its activity and therefore cause virus to evade antiviral activity of interferon (IFN). Many studies have correlated substitutions in this domain to the treatment response and lead to inconclusive results. Some studies suggested that substitutions favor response while others emphasized that no correlation exists. In the present study we therefore compared sequences of PePHD domain of thirty one variants of six hepatitis C virus patients of genotype 3. Three of our HCV 3a infected patients showed rapid virological response to interferon alpha and ribavirin combination therapy whereas the remaining three had breakthrough to the same combination therapy. It is found that PePHD domain is not entirely conserved and has substitutions in some isolates irrespective of the treatment response. However substitution of glutamine (Q) with Leucine (L) in one of the breakthrough responders made it more identical to HCV genotype 1a. These substitutions in the breakthrough responders also tended to increase average hydrophilic activity thus making binding of PePHD to PKR and inhibition of PKR more favorable.

Abstract Hepatitis C virus (HCV) is a member of Flaviviridae family and one of the major causes of liver disease. There are about 175 million HCV infected patients worldwide that constitute 3% of world's population. The main route of HCV transmission is parental however 90% intravenous drug users are at highest risk. Standard interferon and ribavirin remained a gold standard of chronic HCV treatment having 38-43% sustained virological response rates. Currently the standard therapy for HCV is pegylated interferon (PEG-INF) with ribavirin. This therapy achieves 50% sustained virological response (SVR) for genotype 1 and 80% for genotype 2 & 3. As pegylated interferon is expensive, standard interferon is still the main therapy for HCV treatment in under developed countries. On the other hand, studies showed that pegylated IFN and RBV therapy has severe side effects like hematological complications. Herbal medicines (laccase, proanthocyandin, Rhodiola kirilowii) are also being in use as a natural and alternative way for treatment of HCV but there is not a single significant report documented yet. Best SVR indicators are genotype 3 and 2, < 0.2 million IU/mL pretreatment viral load, rapid virological response (RVR) rate and age

Abstract Background Hepatitis delta virus (HDV) and Hepatitis B virus (HBV) co-infection is well known to induce a spectrum of acute and chronic liver diseases which further advance to cirrhosis, fulminant hepatitis and hepatocellular carcinoma (HCC). Aim The aim of the present study was to determine the prevalence of hepatitis D virus super-infection among hepatitis B surface antigen (HBsAg) positive individuals in the highly populated province of Pakistan which is not well known. Methods Sera samples were subjected to HBsAg and anti-HDV screening and finally anti-HDV and HBsAg positive coinfected samples were used for HDV active RNA confirmation using nested polymerase chain reaction (PCR). Results Out of total 200 HBsAg positive samples by rapid device, 96 (48%) were also found reactive for HBsAg using enzyme linked immunosorbant assay (ELISA). Out of these HBsAg ELISA positive samples, 80 (88.8%) were anti-HDV ELISA positive which were then subjected to PCR. The amplification results further confirmed 24 (30%) samples to be HDV RNA positive. HDV super-infection was more common in male patients than female patients (81% VS 19%). Conclusion The current study shows a high prevalence rate of HDV-HBV co-infection in Pakistan that tends to increase over time.

Abstract Background The variability within the hepatitis C virus (HCV) genome has formed the basis for several genotyping methods and used widely for HCV genotyping worldwide. Aim The aim of the present study was to determine percent nucleotide identity and variability in HCV isolates prevalent in different geographical regions of Pakistan. Methods Sequencing analysis of the 5'noncoding region (5'-NCR) of 100 HCV RNA-positive patients representing all the four provinces of Pakistan were carried out using ABI PRISM 3100 Genetic Analyzer. Results The results showed that type 3 is the predominant genotypes circulating in Pakistan, with an overall prevalence of 50%. Types 1 and 4 viruses were 9% and 6% respectively. The overall nucleotide similarity among different Pakistani isolates was 92.50% ± 0.50%. Pakistani isolates from different areas showed 7.5% ± 0.50% nucleotide variability in 5'NCR region. The percent nucleotide identity (PNI) was 98.11% ± 0.50% within Pakistani type 1 sequences, 98.10% ± 0.60% for type 3 sequences, and 99.80% ± 0.20% for type 4 sequences. The PNI between different genotypes was 93.90% ± 0.20% for type 1 and type 3, 94.80% ± 0.12% for type 1 and type 4, and 94.40% ± 0.22% for type 3 and type 4. Conclusion Genotype 3 is the most prevalent HCV genotype in Pakistan. Minimum and maximum percent nucleotide divergences were noted between genotype 1 and 4 and 1 and 3 respectively.

Background: The purpose of this study was to quantify how much of the burden of visual impairment (VI) and unmet need in Talagang, identified by Rapid Assessment of Avoidable Blindness (RAAB) survey data, has been addressed by Community Eye Health (CEH) programme efforts., Methods: A RAAB survey was carried out in November 2018, with 2,824 participants in Talagang Tehsil, Punjab, Pakistan, aged 50 and over. Census data were used to extrapolate survey data to the population. Alongside this, a CEH programme was launched, consisting of community eye screening, and onward referral to rural health centres, secondary or tertiary ophthalmological services, as required. This health intervention aimed to address the eye care needs surfaced by the initial survey. From 2018 to 2022, 30,383 people aged 50 or over were screened; 14,054 needed referral to further steps of the treatment pathway and more detailed data collection. Programme data were compared to estimates of population unmet needs. Main outcome measures were prevalence of VI, and proportion of need met by CEH Programme, by cause and level of VI., Results: Among those aged 50 and over, 51.0% had VI in at least one eye. The leading causes were cataract (46.2%) and uncorrected refractive error (URE) (25.0%). In its first four years, the programme reached an estimated 18.3% of the unmet need from cataract, and 21.1% of URE, equally in both men and women., Conclusions: Robustly collected survey and programme data can improve eye health planning, monitoring and evaluation, address inequities, and quantify the resources required for improving eye health. This study quantifies the time required to reach eye health needs at the community level., (© 2024. The Author(s).)

Competing Interests: None.

Brain insulin resistance is linked to metabolic syndrome (MetS). A low-carbohydrate, high-fat (LCHF) diet has been proposed to have a protective effect. Therefore, this study aimed to investigate the brain insulin resistance markers in a rat animal model of MetS and the protective effects of the LCHF diet. Four groups of male rats (10/group) were created. Group I (Control) was fed a regular diet. Groups II-IV were injected with dexamethasone (DEX) to induce MetS. Group II received DEX with a regular diet. Group III (DEX + LCHF) rates were fed a low-carbohydrate, high-fat diet, while Group IV (DEX + HCLF) rats were fed a high-carbohydrate, low-fat (HCLF) diet. At the end of the four-week experiment, HOMA-IR was calculated. Moreover, cerebral gene expression analysis of S-100B, BDNF, TNF-α, IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, Bax, Bcl-2, and caspase-3 was carried out. In the DEX group, rats showed a significant increase in the HOMA-IR and a decrease in the gene expression of IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, BDNF, and Bcl2, with a concomitant rise in S100B, TNF-α, Bax, and caspase-3. The LCHF diet group showed a significantly opposite effect on all parameters. In conclusion, MetS is associated with dysregulated cerebral gene expression of BDNF, S100B, and TNF-α and disturbed IGF-1 signaling, with increased apoptosis and neuroinflammation. Moreover, the LCHF diet showed a protective effect, as evidenced by preservation of the investigated biochemical and molecular parameters.

Familial hypercholesterolemia (FH) is a globally underdiagnosed genetic condition associated with premature cardiovascular death. The genetic etiology data on Arab FH patients is scarce. Therefore, this study aimed to identify the genetic basis of FH in a Saudi family using whole exome sequencing (WES) and multidimensional bioinformatic analysis. Our WES findings revealed a rare heterozygous gain-of-function variant (R496W) in the exon 9 of the PCSK9 gene as a causal factor for FH in this family. This variant was absent in healthy relatives of the proband and 200 healthy normolipidemic controls from Saudi Arabia. Furthermore, this variant has not been previously reported in various regional and global population genomic variant databases. Interestingly, this variant is classified as "likely pathogenic" (PP5) based on the variant interpretation guidelines of the American College of Medical Genetics (ACMG). Computational functional characterization suggested that this variant could destabilize the native PCSK9 protein and alter its secondary and tertiary structural features. In addition, this variant was predicted to negatively influence its ligand-binding ability with LDLR and Alirocumab antibody molecules. This rare PCSK9 (R496W) variant is likely to expand our understanding of the genetic basis of FH in Saudi Arabia. This study also provides computational structural insights into the genotype-protein phenotype relationship of PCSK9 pathogenic variants and contributes to the development of personalized medicine for FH patients in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shaik, Al-Shehri, Athar, Awan, Khalili, Al Mahadi, Hejazy, Saadah, Al-Harthi, Elango, Banaganapalli, Alefishat and Awan.)

Aims: Lipids are central in the development of cardiovascular disease, and the present study aimed to characterize variation in lipid profiles across different countries to improve understanding of cardiovascular risk and opportunities for risk-reducing interventions., Methods and Results: This first collaborative report of the Global Diagnostics Network (GDN) evaluated lipid distributions from nine laboratory organizations providing clinical laboratory testing in 17 countries on five continents. This cross-sectional study assessed aggregated lipid results from patients aged 20-89 years, tested at GDN laboratories, from 2018 through 2020. In addition to mean levels, the World Health Organization total cholesterol risk target (<5.00 mmol/L, <193 mg/dL) and proportions in guideline-based low-density lipoprotein cholesterol (LDL-C) categories were assessed. This study of 461 888 753 lipid results found wide variation by country/region, sex, and age. In most countries, total cholesterol and LDL-C peaked at 50-59 years in females and 40-49 years in males. Sex- and age-group adjusted mean total cholesterol levels ranged from 4.58 mmol/L (177.1 mg/dL) in the Republic of Korea to 5.40 mmol/L (208.8 mg/dL) in Austria. Mean total cholesterol levels exceeded the World Health Organization target in Japan, Australia, North Macedonia, Switzerland, Germany, Slovakia, and Austria. Considering LDL-C categories, North Macedonia had the highest proportions of LDL-C results >4.91 mmol/L (>190 mg/dL) for both females (9.9%) and males (8.7%). LDL-C levels <1.55 mmol/L (<60 mg/dL) were most common among females in Canada (10.7%) and males in the UK (17.3%)., Conclusion: With nearly a half billion lipid results, this study sheds light on the worldwide variability in lipid levels, which may reflect inter-country differences in genetics, lipid testing, lifestyle habits, and pharmacologic treatment. Despite variability, elevated atherogenic lipid levels are a common global problem, and these results can help inform national policies and health system approaches to mitigate lipid-mediated risk of cardiovascular disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Inflammatory bowel disease (IBD) is a chronic autoimmune disorder characterized by severe inflammation and mucosal destruction of the intestine. The specific, complex molecular processes underlying IBD pathogenesis are not well understood. Therefore, this study is aimed at identifying and uncovering the role of key genetic factors in IBD., Method: The whole exome sequences (WESs) of three consanguineous Saudi families having many siblings with IBD were analyzed to discover the causal genetic defect. Then, we used a combination of artificial intelligence approaches, such as functional enrichment analysis using immune pathways and a set of computational functional validation tools for gene expression, immune cell expression analyses, phenotype aggregation, and the system biology of innate immunity, to highlight potential IBD genes that play an important role in its pathobiology., Results: Our findings have shown a causal group of extremely rare variants in the LILRB1 (Q53L, Y99N, W351G, D365A, and Q376H) and PRSS3 (F4L and V25I) genes in IBD-affected siblings. Findings from amino acids in conserved domains, tertiary-level structural deviations, and stability analysis have confirmed that these variants have a negative impact on structural features in the corresponding proteins. Intensive computational structural analysis shows that both genes have very high expression in the gastrointestinal tract and immune organs and are involved in a variety of innate immune system pathways. Since the innate immune system detects microbial infections, any defect in this system could lead to immune functional impairment contributing to IBD., Conclusion: The present study proposes a novel strategy for unraveling the complex genetic architecture of IBD by integrating WES data of familial cases, with computational analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jan, Al-Numan, Al-Twaty, Alrayes, Alsufyani, Alaifan, Alhussaini, Shaik, Awan, Qari, Saadah, Banaganapalli, Mosli and Elango.)

Paget's disease of bone (PDB) is the second most prevalent metabolic bone disorder worldwide, with a prevalence rate of 1.5%-8.3%. It is characterized by localized areas of accelerated, disorganized, and excessive bone production and turnover. Typically, PDB develops in the later stages of life, particularly in the late 50s, and affects men more frequently than women. PDB is a complex disease influenced by both genetic and environmental factors. PDB has a complex genetic basis involving multiple genes, with SQSTM1 being the gene most frequently associated with its development. Mutations affecting the UBA domain of SQSTM1 have been detected in both familial and sporadic PDB cases, and these mutations are often associated with severe clinical expression. Germline mutations in other genes such as TNFRSF11A, ZNF687 and PFN1, have also been associated with the development of the disease. Genetic association studies have also uncovered several PDB predisposing risk genes contributing to the disease pathology and severity. Epigenetic modifications of genes involved in bone remodelling and regulation, including RANKL, OPG, HDAC2, DNMT1, and SQSTM1, have been implicated in the development and progression of Paget's disease of bone, providing insight into the molecular basis of the disease and potential targets for therapeutic intervention. Although PDB has a tendency to cluster within families, the variable severity of the disease across family members, coupled with decreasing incidence rates, indicates that environmental factors may also play a role in the pathophysiology of PDB. The precise nature of these environmental triggers and how they interact with genetic determinants remain poorly understood. Fortunately, majority of PDB patients can achieve long-term remission with an intravenous infusion of aminobisphosphonates, such as zoledronic acid. In this review, we discuss aspects like clinical characteristics, genetic foundation, and latest updates in PDB research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Banaganapalli, Fallatah, Alsubhi, Shetty, Awan, Elango and Shaik.)

Competing Interests: There are no conflicts of interest.

Objectives: Dyslipidemia is a prevalent condition with significant morbidity and mortality across the world, including in the Arabian Gulf. The present study aimed to describe the characteristics of patients receiving evolocumab in clinical practice., Methods: ZERBINI was a multi-country, observational, retrospective/prospective study of subjects receiving evolocumab as part of routine clinical management of their hyperlipidemia. This regional publication reports on adult participants from Saudi Arabia and Kuwait who have had ≥1 dose of evolocumab before enrollment and ≤6 months' prior exposure to evolocumab. Patient characteristics and treatment persistence data were collected in addition to baseline and follow-up data up to 12 months post-evolocumab initiation., Results: Overall, 225 patients were included from two sites, Saudi Arabia (N = 155) and Kuwait (N = 70). Mean age was comparable across sites and most patients had baseline coronary artery disease and/or hypertension. Baseline LDL-C levels (mean ± SD 3.6 ± 1.4 mmol/L in Saudi Arabia, 3.1 ± 1.4 mmol/L in Kuwait) were reduced by approximately 57%-62% in the first 6 months after evolocumab initiation (1.5 ± 1.2 mmol/L in Saudi Arabia [n = 63], 1.2 ± 0.8 mmol/L in Kuwait [n = 28]). This decrease was maintained over the 12-month follow-up period. Most patients achieved ACC 2018 LDL-C goals (<1.8 mmol/L; 74.6% in Saudi Arabia, 93.1% in Kuwait) and ESC 2019 LDL-C goals (<1.4 mmol/L; 66.7% in Saudi Arabia, 75.9% in Kuwait) in the first 6 months after evolocumab initiation. Medication persistence with evolocumab was high (up to 90.7%). Evolocumab had a favorable safety profile and no treatment-emergent adverse events were observed at either site., Conclusion: Evolocumab is an effective lipid-lowering treatment in local populations. LDL-C goal achievement is increased when evolocumab is added to background lipid-lowering therapy with high tolerability and persistence. Long-term follow-up and large-scale data are needed to further support these observations., Competing Interests: The authors MS, MAJ and RD have declared that no competing interests exist KF: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Consultancies from: Saudi Heart Association; Saudi Council for Health Specialties Commission; Gulf Intervention Society; Amgen; Novartis; Sanofi; Medtronic; Boehringer Ingelheim; Lectures from: Amgen; Novartis; Sanofi; Medtronic; Boehringer Ingelheim; Clinical studies from: Amgen MA: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Lectures from: Amgen, Sanofi, AstraZeneca, Bayer,Boehringer Ingelheim, MSD, Novartis, Pfizer, Novonordisk, Servier, Abbott, Algorithm GAH: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Lectures from Amgen; Boehringer Ingelhein; Novartis. Clinical studies from: Amgen. AAQ: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Lectures from Amgen; Novartis. Clinical studies and research grants from Amgen; Other: GHA FAN: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Consultancies, lectures and Clinical studies from Amgen ZA: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Consultancies from: AlBorg Diagnostic; Lectures from: Amgen; Sanofi; Pfizer. Clinical studies from: Amgen. Research grants from: King Abdulaziz University A. Essam: I have read the journal’s policy and the authors of this manuscript have the following competing interests: employed by the funder of the study, Amgen. A. Emara: I have read the journal’s policy and the authors of this manuscript have the following competing interests: employed by the funder of the study, Amgen. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Al Faraidy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A medication's approximate release profile should be sustained in order to generate the desired therapeutic effect. The drug's release site, duration, and rate must all be adjusted to the drug's therapeutic aim. However, when designing drug delivery systems, this may be a considerable hurdle. Electrospinning is a promising method of creating a nanofibrous membrane since it enables drugs to be placed in the nanofiber composite and released over time. Nanofiber composites designed through electrospinning for drug release purposes are commonly constructed of simple structures. This nanofiber composite produces matrices with nanoscale fiber structure, large surface area to volume ratio, and a high porosity with small pore size. The nanofiber composite's large surface area to volume ratio can aid with cell binding and multiplication, drug loading, and mass transfer processes. The nanofiber composite acts as a container for drugs that can be customized to a wide range of drug release kinetics. Drugs may be electrospun after being dissolved or dispersed in the polymer solution, or they can be physically or chemically bound to the nanofiber surface. The composition and internal structure of the nanofibers are crucial for medicine release patterns.

Background: Over one billion people worldwide live with avoidable blindness or vision impairment. Eye Health Programmes tackle this by providing screening, primary eye care, refractive correction, and referral to hospital eye services. One point where patients can be lost in the treatment journey is adherence to hospital referral., Context: Peek Vision's software solutions have been used in Pakistan with the goal of increasing eye health programme coverage and effectiveness. This involved collaboration between health system stakeholders, international partners, local community leaders, social organizers and "Lady Health Workers"., Results: From the beginning of the programmes in November 2018, to the end of December 2021, 393,759 people have been screened, 26% of whom ( n = 101,236) needed refractive services or secondary eye care, and so were referred onwards to the triage centers or hospital services. Except for a short period affected heavily by COVID-19 pandemic, the programmes reached an increasing number of people over time: screening coverage improved from 774 people per month to over 28,300 people per month. Gathering and discussing data regularly with stakeholders and implementers has enabled continuous improvement to service delivery. The quality of screening and adherence to hospital visits, gender balance differences and waiting time to hospital visits were also improved. Overall attendance to hospital appointments improved in 2020 compared to 2019 from 45% (95% CI: 42-48%) to 78% (95% CI: 76-80%) in women, and from 48% (95% CI: 45-52%) to 70% (95% CI: 68-73%) in men. These patients also accessed treatment more quickly: 30-day hospital referral adherence improved from 12% in 2019 to 66% in 2020. This approach helped to utilize refractive services more efficiently, reducing false positive referrals to triage from 10.6 to 5.9%. Hospital-based services were also utilized more efficiently, as primary eye care services and refractive services were mainly delivered at the primary healthcare level., Discussion: Despite various challenges, we demonstrate how data-driven decisions can lead to health programme systems changes, including patient counseling and appointment reminders, which can effectively improve adherence to referral, allowing programmes to better meet their community's needs., (Copyright © 2022 Khan, Talpur, Awan, Arteaga, Bolster, Katibeh, Watts and Bastawrous.)

Familial hypercholesterolemia (FH) is a monogenic lipid disorder which promotes atherosclerosis and cardiovascular diseases. Owing to the lack of sufficient published information, this study aims to identify the potential genetic biomarkers for FH by studying the global gene expression profile of blood cells. The microarray expression data of FH patients and controls was analyzed by different computational biology methods like differential expression analysis, protein network mapping, hub gene identification, functional enrichment of biological pathways, and immune cell restriction analysis. Our results showed the dysregulated expression of 115 genes connected to lipid homeostasis, immune responses, cell adhesion molecules, canonical Wnt signaling, mucin type O-glycan biosynthesis pathways in FH patients. The findings from expanded protein interaction network construction with known FH genes and subsequent Gene Ontology (GO) annotations have also supported the above findings, in addition to identifying the involvement of dysregulated thyroid hormone and ErbB signaling pathways in FH patients. The genes like CSNK1A1, JAK3, PLCG2, RALA, and ZEB2 were found to be enriched under all GO annotation categories. The subsequent phenotype ontology results have revealed JAK3I , PLCG2, and ZEB2 as key hub genes contributing to the inflammation underlying cardiovascular and immune response related phenotypes. Immune cell restriction findings show that above three genes are highly expressed by T-follicular helper CD4 + T cells, naïve B cells, and monocytes, respectively. These findings not only provide a theoretical basis to understand the role of immune dysregulations underlying the atherosclerosis among FH patients but may also pave the way to develop genomic medicine for cardiovascular diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Vertigo is a sensation of movement that results from disorders of the inner ear balance organs and their central connections, with aetiologies that are often benign and sometimes serious. An individual who develops vertigo can be effectively treated only after a correct diagnosis of the underlying vestibular disorder is reached. Recent advances in artificial intelligence promise novel strategies for the diagnosis and treatment of patients with this common symptom. Human analysts may experience difficulties manually extracting patterns from large clinical datasets. Machine learning techniques can be used to visualize, understand, and classify clinical data to create a computerized, faster, and more accurate evaluation of vertiginous disorders. Practitioners can also use them as a teaching tool to gain knowledge and valuable insights from medical data. This paper provides a review of the literatures from 1999 to 2021 using various feature extraction and machine learning techniques to diagnose vertigo disorders. This paper aims to provide a better understanding of the work done thus far and to provide future directions for research into the use of machine learning in vertigo diagnosis.

Background and Aims: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf countries (Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain)., Methods: The multicentre, multinational Gulf FH registry included adults (≥18 years old) recruited from outpatient clinics in 14 tertiary-care centres across five Arabian Gulf countries over the last five years. The Gulf FH registry had four phases: 1- screening, 2- classification based on the Dutch Lipid Clinic Network, 3- genetic testing, and 4- follow-up., Results: Among 34,366 screened patient records, 3713 patients had suspected FH (mean age: 49±15 years; 52% women) and 306 patients had definite or probable FH. Thus, the estimated FH prevalence was 0.9% (1:112). Treatments included high-intensity statin therapy (34%), ezetimibe (10%), and proprotein convertase subtilisin/kexin type 9 inhibitors (0.4%). Targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol were achieved by 12% and 30%, respectively, of patients at high ASCVD risk, and by 3% and 6%, respectively, of patients at very high ASCVD risk (p <0.001; for both comparisons)., Conclusions: This snap-shot study was the first to show the high estimated prevalence of FH in the Arabian Gulf region (about 3-fold the estimated prevalence worldwide), and is a "call-to-action" for further confirmation in future population studies. The small proportions of patients that achieved target LDL-C values implied that health care policies need to implement nation-wide screening, raise FH awareness, and improve management strategies for FH., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: KA reports grants from Sanofi during the conduct of the study and other funs from Sanofi, Abbott, and MSD outside the submitted work; NA reports personal fees from Sanofi, Aegerion, Merck Sharp, Abbott, AstraZeneca, Pfizer, and Amgen outside the submitted work; HS reports personal fees from Sanofi and Amgen outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.