Retraction: Isolated Superior Mesenteric Artery Dissection After Methamphetamine Use: A Rare Adverse Effect.

[This retracts the article DOI: 10.7759/cureus.19551.].

Assessing the Awareness and Perception of Telemedicine Among the General Population in the Al-Baha Region, Saudi Arabia.

Telemedicine plays an important role in healthcare by improving the quality of the healthcare system. However, various challenges associated with the effective implementation of telemedicine have been reported. This study aimed to explore the awareness and utilization of telemedicine services among the general population in the Al-Baha region of Saudi Arabia and the factors affecting it. Using a cross-sectional design for the study, the quantitative approach was employed through a questionnaire-based survey. Data from 359 participants from the Al-Baha general population were collected, including both males and females over the age of 18. The analysis of the collected data shows a low level of familiarity within the general population; indeed, 54.9% (197) of participants have experienced using telemedicine services. Moreover, the study reveals that the major concerns influencing the use of telemedicine services are limited availability, privacy and security, and quality of care. Almost half of the participants have used telemedicine, and they expressed concerns related to quality of care, privacy and security, limited availability, and technical difficulties. However, telemedicine was positively perceived among the participants. There is a need to raise public awareness about the importance and effectiveness of telemedicine.

Evaluation of acute flaccid paralysis surveillance system in the River Nile State - Northern Sudan, 2021.

BACKGROUND: One of the four main elements of the worldwide polio eradication strategy is acute flaccid paralysis surveillance (AFP). This system is based on (acute flaccid paralysis (AFP) cases reported and tested at World Health Organization (WHO) accredited laboratories. To measure and monitor performance, indicators were created. The current study aims to evaluate the system components, performance, and efficiency in River Nile State, Northern Sudan, and their compliance with World Health Organization (WHO) requirements for it to be adopted as a good system; its results can be used to certify whether a country is polio-free or not. MATERIAL AND METHODS: A facility-based retrospective descriptive study was conducted in the River Nile State, Northern Sudan, from Jan 2017 to Dec 2020. This study included all reporting sites/units, workers who reported acute flaccid paralysis (AFP) cases, and officers at the locality level. A total of 50 health institutions were visited for surveillance, and interviews with 59 health workers who were part of the AFP surveillance system were undertaken. The data were collected from participants using a pre-tested questionnaire designed and constructed by the World Health Organization (WHO) framework, and the data were analyzed using the SPSS version (22). RESULTS: The River Nile State's AFP surveillance system was of high quality in terms of the infrastructure that had been put in place and the effectiveness of the system's operations, as evidenced by the following statistics: from 2017 to 2020, the reported non-polio acute flaccid paralysis (AFP) cases were at a mean rate of 4.02 per 100,000 children under the age of 15; the majority of AFP reported cases were under 10 years; and males made up 73.3% of reported cases; The completeness of reports and surveillance documents exceeded 80%, and active surveillance was applied in 80% of reporting sites. CONCLUSION: Despite the fact that the surveillance system is capable of detecting cases, Sudan continues to report cases of imported polio from other countries, highlighting the need to strengthen surveillance systems and eradication efforts in these countries.

Exome Sequencing Identifies the Extremely Rare ITGAV and FN1 Variants in Early Onset Inflammatory Bowel Disease Patients.

Background: Molecular diagnosis of early onset inflammatory bowel disease (IBD) is very important for adopting suitable treatment strategies. Owing to the sparse data available, this study aims to identify the molecular basis of early onset IBD in Arab patients. Methods: A consanguineous Arab family with monozygotic twins presenting early onset IBD was screened by whole exome sequencing (WES). The variants functional characterization was performed by a series of computational biology methods. The IBD variants were further screened in in-house whole exome data of 100 Saudi cohorts ensure their rare prevalence in the population. Results: Genetic screening has identified the digenic autosomal recessive mode of inheritance of ITGAV (G58V) and FN1 (G313V) variants in IBD twins with early onset IBD. Findings from pathogenicity predictions, stability and molecular dynamics have confirmed the deleterious nature of both variants on structural features of the corresponding proteins. Functional biology data suggested that both genes show abundant expression in gastrointestinal tract and immune organs, involved in immune cell restriction, regulation of different immune related pathways. Data from knockout mouse models for ITGAV gene has revealed that the dysregulated expression of this gene impacts intestinal immune homeostasis. The defective ITGAV and FN1 involved in integrin pathway, are likely to induce intestinal inflammation by disturbing immune homeostasis. Conclusions: Our findings provide novel insights into the molecular etiology of pediatric onset IBD and may likely pave way in developing genomic medicine.

Isolated Superior Mesenteric Artery Dissection After Methamphetamine Use: A Rare Adverse Effect.

Methamphetamine is the second most commonly abused drug worldwide. It is a sympathomimetic agent that works by inhibiting the reuptake of monoamine neurotransmitters, including dopamine, norepinephrine, and serotonin. Methamphetamine use is associated with early mortality, and cardiovascular complications are the leading cause of increased mortality. We discuss the case of a 41-year-old man who presented to the emergency department with a sudden abdominal pain of eight hours' duration. The pain was located in the epigastric area with radiation to the back. Upon examination, the patient appeared agitated and diaphoretic. His pupils were dilated bilaterally. His vital signs included tachycardia (120 bpm), tachypnea (24 bpm), hypertension (150/90 mmHg), and normal temperature (36.9 ℃). Abdominal examination revealed a soft and lax abdomen with no tenderness. His bowel sounds were normal. Given the physical signs, a toxicology screen was conducted and was positive for methamphetamine use. The patient reported that he used recreational drugs occasionally and admitted that the abdominal pain developed a few hours following methamphetamine use. The patient was treated with fluid resuscitation, analgesic, antihypertension medications, and anticoagulant therapy. The patient had significant improvement in his condition within 48 hours with complete resolution of the abdominal pain. Isolated superior mesenteric artery dissection is a very rare clinical condition. This case report highlights the importance of recognizing the cardiovascular adverse effects that may develop after methamphetamine use.

Saudi Familial Hypercholesterolemia Patients With Rare LDLR Stop Gain Variant Showed Variable Clinical Phenotype and Resistance to Multiple Drug Regimen.

Familial hypercholesterolemia (FH), a well-known lipid disease caused by inherited genetic defects in cholesterol uptake and metabolism is underdiagnosed in many countries including Saudi Arabia. The present study aims to identify the molecular basis of severe clinical manifestations of FH patients from unrelated Saudi consanguineous families. Two Saudi families with multiple FH patients fulfilling the combined FH diagnostic criteria of Simon Broome Register, and the Dutch Lipid Clinic Network (DLCN) were recruited. LipidSeq, a targeted resequencing panel for monogenic dyslipidemias, was used to identify causative pathogenic mutation in these two families and in 92 unrelated FH cases. Twelve FH patients from two unrelated families were sharing a very rare, pathogenic and founder LDLR stop gain mutation i.e., c.2027delG (p.Gly676Alafs*33) in both the homozygous or heterozygous states, but not in unrelated patients. Based on the variant zygosity, a marked phenotypic heterogeneity in terms of LDL-C levels, clinical presentations and resistance to anti-lipid treatment regimen (ACE inhibitors, ß-blockers, ezetimibe, statins) of the FH patients was observed. This loss-of-function mutation is predicted to alter the free energy dynamics of the transcribed RNA, leading to its instability. Protein structural mapping has predicted that this non-sense mutation eliminates key functional domains in LDLR, which are essential for the receptor recycling and LDL particle binding. In conclusion, by combining genetics and structural bioinformatics approaches, this study identified and characterized a very rare FH causative LDLR pathogenic variant determining both clinical presentation and resistance to anti-lipid drug treatment.

HCC-Mark: a simple non-invasive model based on routine parameters for predicting hepatitis C virus related hepatocellular carcinoma.

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) is crucial in providing more effective therapies. As routine laboratory variables are readily accessible, this study aimed to develop a simple non-invasive model for predicting hepatocellular cancer. METHODS: Two groups of patients were recruited: an estimation group (n = 300) and a validation group (n = 625). Each comprised two categories: hepatocellular cancer and liver cirrhosis. Logistic regression analyses and receiver operating characteristic (ROC) curves were used to develop and validate the HCC-Mark model comprising AFP, high-sensitivity C-reactive protein, albumin and platelet count. This model was tested in cancer patients classified by the Barcelona Clinic Liver Cancer (BCLC), Cancer of Liver Italian Program (CLIP) and Okuda systems, and was compared with other non-invasive models for predicting hepatocellular cancer. RESULTS: HCC-Mark produced a ROC AUC of 0.89 (95% CI 0.85-0.90) for discriminating hepatocellular carcinoma from liver cirrhosis in the estimation group and 0.90 (0.86-0.90) in the validation group (both p < 0.0001). This AUC exceeded all other models, that had AUCs from 0.41 to 0.81. AUCs of HCC-Mark for discriminating patients with a single focal lesion, absent macrovascular invasion, tumour size <2 cm, BCLC (0-A), CLIP (0-1) and Okuda (stage Ι) from cirrhotic patients were 0.88 (0.85-0.90), 0.87 (0.85-0.89), 0.89 (0.85-0.93), 0.87 (0.84-0.89), 0.85 (0.82-0.87) and 0.86 (0.83-0.89), respectively (all p < 0.0001). CONCLUSION: HCC-Mark is an accurate and validated model for the detection of hepatocellular cancer and certain of its clinical features.

Toll-like receptor 7 mRNA is reduced in hepatitis C-based liver cirrhosis and hepatocellular carcinoma, out-performs alpha-fetoprotein levels, and with age and serum aspartate aminotransferase is a new diagnostic index.

BACKGROUND: Hepatitis B and C viruses are leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Toll-like receptor 7 (TLR-7) has been implicated in the pathogenesis of HCC linked to hepatitis B. We hypothesised a role of leukocyte TLR-7 mRNA in hepatitis C related liver cirrhosis and HCC, using alpha-fetoprotein (AFP) and liver function tests as comparators. METHODS: We recruited 102 patients with HCV-related HCC, 97 with HCV-related liver cirrhosis and 60 healthy controls. Quantification of TLR-7 mRNA was performed using real-time PCR, AFP and routine LFTs by standard techniques. RESULTS: TLR-7 mRNA levels were significantly lower in HCC patients compared to cirrhotic patients and lower again in healthy controls (p < 0.001 for trend). In multivariate analysis, age, aspartate transaminase (AST), AFP, and TLR-7 mRNA were significant predictors of HCC. The ROCC/AUC for age, AST and TLR-7 mRNA were all between 0.64 and 0.78 (all P < 0.01), but for AFP was 0.57 (95% CI 0.48-0.65, P = 0.09). We derived an index score using age, AST and TLR-7 mRNA for the diagnosis of HCC. The ROCC/AUC for the index was superior to all three root indices in the prediction of HCC. The index linked significantly with the Tokyo and Vienna liver cancer staging systems, but not with those of the CLIP and Okuda systems, in distinguishing HCC from liver cirrhosis. CONCLUSION: The combination of TLR-7 mRNA levels with age and AST improves the performance of TLR-7 in HCC diagnosis, out-performs alpha-fetoprotein and predicts early HCC.

Whole exome sequencing of a Saudi family and systems biology analysis identifies CPED1 as a putative causative gene to Celiac Disease.

Celiac disease (CD) is a gastrointestinal disorder whose genetic basis is not fully understood. Therefore, we studied a Saudi family with two CD affected siblings to discover the causal genetic defect. Through whole exome sequencing (WES), we identified that both siblings have inherited an extremely rare and deleterious CPED1 genetic variant (c.241 A > G; p.Thr81Ala) segregating as autosomal recessive mutation, suggesting its putative causal role in the CD. Saudi population specific minor allele frequency (MAF) analysis has confirmed its extremely rare prevalence in homozygous condition (MAF is 0.0004). The Sanger sequencing analysis confirmed the absence of this homozygous variant in 100 sporadic Saudi CD cases. Genotype-Tissue Expression (GTEx) data has revealed that CPED1 is abundantly expressed in gastrointestinal mucosa. By using a combination of systems biology approaches like protein 3D modeling, stability analysis and nucleotide sequence conservation analysis, we have further established that this variant is deleterious to the structural and functional aspects of CPED1 protein. To the best of our knowledge, this variant has not been previously reported in CD or any other gastrointestinal disease. The cell culture and animal model studies could provide further insight into the exact role of CPED1 p.Thr81Ala variant in the pathophysiology of CD. In conclusion, by using WES and systems biology analysis, present study for the first-time reports CPED1 as a potential causative gene for CD in a Saudi family with potential implications to both disease diagnosis and genetic counseling.

A novel serum metabolome score for breast cancer diagnosis.

INTRODUCTION: Early detection of breast cancer is important in diagnosis and treatment, and so in enhancing patient survival and reducing death rates. Because of the low diagnostic sensitivity and specificity of widely used breast cancer biomarkers such as CA15-3, we hypothesised that a panel of new metabolic markers would provide superior sensitivity and specificity for this disease. MATERIAL & METHODS: We recruited 120 women with malignant breast cancer, 47 with benign breast disease and 55 females as a healthy control group. Metabolites 8-hydroxy-2'-deoxyguanosine, 1-methylguanosine, and 1-methyl adenosine were detected and quantified by gas chromatography-mass spectrometry, CA15.3 by ELISA. Cut-off values of individual and combined metabolome with CA15-3 were analysed using the receiver operating characteristics curve (ROCC) to test the efficiency of the candidate metabolome in identifying breast cancer. RESULTS: The overall linear trend of biomarkers across the groups was significant with highest levels in breast cancer (all p < 0.05). Using cut-off values of CA15-3, 8-hydroxy-2'-deoxyguanosine, 1-methylguanosine and 1-methyl adenosine of 30.5 U/l, 15.0 µg/l, 18.5 µg/l and 22.0 µg/l, respectively, diagnostic performance analyses of combined metabolome with CA15-3 gave a ROCC area under the curve of 0.94 (95% CI: 0.91-0.98)(p < 0.01) with good sensitivity (88.8%), specificity (86.8%) and efficiency (90.6%). Unlike CA15.3, the highest levels of each of the metabolite were in the early stage of breast cancer. CONCLUSION: The diagnostic combination test of candidate metabolome with CA15.3 may be a useful tool for the early detection of breast cancer and used as a metabolomics signature in this disease.

Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients.

Alström syndrome (AS, OMIM ID 203800) is a rare childhood multiorgan disorder, which is widely studied in non-Arab ethnic patients. The clinical and molecular basis of AS and the mode of disease inheritance in consanguineous Arab populations is not well investigated. Therefore, to identify the molecular basis of AS in familial forms, the present study performed whole exome sequencing of 5 AS patients belonging to 2 different Bedouin families from Saudi Arabia. The present study identified the AS causative rare biallelic mutations in ALMS gene:T376S in exon 5 and S909* in exon 8 for family A and an R2721* in exon 10 (R2721*) for family B. ALMS1 targeted genetic sequencing of healthy population controls and family members has confirmed its extremely rare frequency and autosomal recessive mode of inheritance. The truncating mutations S909* and R2721* could cause the loss of CC domains and ALMS motif on C-terminal end of the protein and creates unstable protein, which eventually undergoes intracellular degradation. The premature protein truncating mutations described in our study may eventually provide further insight into the functional domains of the ALMS1 protein and contribute to the understanding of the phenotypic spectrum of AS. Whole exome sequencing based molecular diagnosis is expected to rule out ambiguity surrounding clinical diagnosis of suspected AS cases.

Exome sequencing and metabolomic analysis of a chronic kidney disease and hearing loss patient family revealed RMND1 mutation induced sphingolipid metabolism defects.

Mitochondrial disorders (MIDs) shows overlapping clinical presentations owing to the genetic and metabolic defects of mitochondria. However, specific relationship between inherited mutations in nuclear encoded mitochondrial proteins and their functional impacts in terms of metabolic defects in patients is not yet well explored. Therefore, using high throughput whole exome sequencing (WES), we screened a chronic kidney disease (CKD) and sensorineural hearing loss (SNHL) patient, and her family members to ascertain the mode of inheritance of the mutation, and healthy population controls to establish its rare frequency. The impact of mutation on biophysical characteristics of the protein was further studied by mapping it in 3D structure. Furthermore, LC-MS tandem mass spectrophotometry based untargeted metabolomic profiling was done to study the fluctuations in plasma metabolites relevant to disease causative mutations and kidney damage. We identified a very rare homozygous c.631G > A (p.Val211Met) pathogenic mutation in RMND1 gene in the proband, which is inherited in an autosomal recessive fashion. This gene is involved in the mitochondrial translational pathways and contribute in mitochondrial energy metabolism. The p.Val211Met mutation is found to disturb the structural orientation (RMSD is -2.95 Å) and stability (ΔΔG is -0.552 Kcal/mol) of the RMND1 protein. Plasma metabolomics analysis revealed the aberrant accumulation of metabolites connected to lipid and amino acid metabolism pathways. Of these metabolites, pathway networking has discovered ceramide, a metabolite of sphingolipids, which plays a role in different signaling cascades including mitochondrial membrane biosynthesis, is highly elevated in this patient. This study suggests that genetic defects in RMND1 gene alters the mitochondrial energy metabolism leading to the accumulation of ceramide, and subsequently promote dysregulated apoptosis and tissue necrosis in kidneys.

End-of-life care following leg amputation in patients with peripheral artery disease or diabetes.

BACKGROUND: The aim was to characterize end-of-life care in patients who have had a leg amputated for peripheral artery disease (PAD) or diabetes. METHODS: This was a population-based retrospective cohort study of patients with PAD or diabetes who died in Ontario, Canada, between 2011 and 2017. Those who had a leg amputation within 3 years of death were compared with a control cohort of deceased patients with PAD or diabetes, but without leg amputation. The patients were identified from linked health records within the single-payer healthcare system. Place and cause of death, as well as health services and costs within 90 days of death, were compared between the amputee and control cohorts. Among amputees, multivariable regression models were used to characterize the association between receipt of home palliative care and in-hospital death, as well as time spent in hospital at the end of life. RESULTS: Compared with 213 300 controls, 3113 amputees were less likely to die at home (15·5 versus 24·9 per cent; P < 0·001) and spent a greater number of their last 90 days of life in hospital (median 19 versus 8 days; P < 0·001). Amputees also had higher end-of-life healthcare costs across all sectors. However, receipt of palliative care was less frequent among amputees than controls (inpatient: 13·4 versus 16·8 per cent, P < 0·001; home: 14·5 versus 23·8 per cent, P < 0·001). Among amputees, receipt of home palliative care was associated with a lower likelihood of in-hospital death (odds ratio 0·49, 95 per cent c.i. 0·40 to 0·60) and fewer days in hospital (rate ratio 0·84, 0·76 to 0·93). CONCLUSION: Palliative care is underused after amputation in patients with PAD or diabetes, and could contribute to reducing in-hospital death and time spent in hospital at the end of life.

ANTECEDENTES: Caracterizar la atención al final de la vida en pacientes con amputación de la extremidad inferior por enfermedad arterial periférica (peripheral arterial disease, PAD) o diabetes. MÉTODOS: Se trata de un estudio de cohortes retrospectivo de base poblacional en sujetos fallecidos con PAD o diabetes en Ontario, Canadá (2011-2017). A partir de los registros sanitarios incluidos en un sistema de salud de una sola entidad pagadora, se identificaron los individuos con amputación de la extremidad inferior en los 3 años previos al fallecimiento y una cohorte control de fallecidos con PAD o diabetes sin amputación. Entre las cohortes de amputados y controles se comparó el lugar del fallecimiento y la causa, así como el uso de servicios sanitarios y costes en los últimos 90 días de vida. En el grupo de los amputados, se utilizaron modelos de regresión para caracterizar la asociación entre recibir cuidados paliativos domiciliarios y el fallecimiento en el hospital, así como los días de estancia hospitalaria al final de la vida. RESULTADOS: En comparación con los controles (n = 213.300), los sujetos con amputación (n = 3.113) era menos probable que fallecieran en el domicilio (16% versus 25%, P < 0,001) y pasaron un mayor número de sus últimos 90 días de vida en el hospital (mediana 19 versus 8 días, P < 0,001). Los costes de atención sanitaria al final de la vida en todos los sectores también fueron mayores para los amputados. Sin embargo, recibir cuidados paliativos fue menos frecuente en los amputados que en los controles (en el hospital 13% versus 17%, P < 0,001; domiciliarios 14% versus 24%, P < 0,001). En el grupo de los amputados, recibir cuidados paliativos domiciliarios se asociaba con una menor probabilidad de fallecimiento en el hospital (razón de oportunidades, odds ratio 0,49, i.c. del 95% 0,40-0,60) y menos días de hospitalización (tasa de riesgo 0,84, i.c. del 95% 0,76-0,93). CONCLUSIÓN: Los cuidados paliativos están infrautilizados en pacientes con PAD o diabetes y pueden contribuir a disminuir los fallecimientos en el hospital y los días de hospitalización al final de la vida.

A panel of a mitogenic (PDGF), biochemical (albumin) and demographic (age) parameters for the non-invasive assessment of hepatic fibrosis.

Background: Several studies have investigated certain fibrosis markers that incorporate liver function tests, fragments of liver-matrix components and/or degraded products generated by hepatic stellate cells for determining the degree of hepatic fibrosis. However, the role of these molecules in the development of hepatic fibrosis is unclear. This work aimed (a) to determine whether platelet-derived growth factor (PDGF) is linked to different stages of hepatic fibrosis and (b) investigate its diagnostic performance alongside other laboratory and demographic factors in assessing liver fibrosis in chronic hepatitis C infection. Methods: Liver-fibrosis was staged according to Fibroscan, PDGF quantified using ELISA, and liver function tests and other analytes determined by standard techniques in 239 patients with chronic hepatitis C virus infection. Results: Patients with significant (F2-F4), advanced fibrosis (F3-F4) and cirrhotic liver disease (F4) showed significantly (P<0.0001) higher PDGF levels increase respectively compared to stage F0/1. We used this to construct the PARA-Index (PDGF/albumin ratio, age), which performed well in assessing hepatic-fibrosis stages with AUCs of 0.91, 0.87 and 0.86 for identifying F2-F4, F3-F4 and F4, respectively. Additionally, the PARA-Index correlated strongly (r=0.65, P<0.0001) with the severity of the fibrosis. An elevated PARA-index provided odds ratios of 21.0, 20.7 and 10.3 for developing F2-F4, F3-F4 and F4, respectively. Conclusion: A panel of mitogenic (PDGF), biochemical (albumin) and demographical (age) parameters may improve liver-fibrosis staging with a high degree of accuracy in those with a hepatitis C virus infection.

Clinical value of a diagnostic score for colon cancer based on serum CEA, CA19-9, cytokeratin-1 and mucin-1.

BACKGROUND: Although established markers such as CEA and CA19-9 are important for diagnosing early stages of colon cancer, they are not ideal. Developing promising markers include cytokeratin 1 (CK1) and mucin-1 (MUC1), but the combined value of each of these markers is unclear. We therefore evaluated the value of a combined laboratory-based score of these four markers in the diagnosis of colon cancer. METHODS: Two hundred patients who had undergone colonoscopic examination (150 colon cancer, 50 benign growths) were recruited. The study was controlled by 35 healthy subjects. CEA, CA19-9, CK1 and MUC1 were measured by ELISA and evaluated for cancer diagnosis using area under the receiver operating characteristic curve (AUC). RESULTS: Serum levels of all four markers were increased in the order colon cancer > benign disease > healthy controls (p < 0.001). In multivariate analysis, CA19.9 (p = 0.025), CK1 (p < 0.001) and MUC1 (p = 0.009) were significant independent predictors of colon cancer. A score that gave the greatest power of discrimination for colon cancer was defined as 1.06 + [0.001 × CA19.9 result] + [0.003 × CEA result] + [0.03 × CK1 result] + [0.05 × MUC1 result]. The colon score provided superior discrimination, AUC, and sensitivity and specificity for colon cancer versus benign growth than each of the individual markers. Similarly, the colon score provided superior AUC, and sensitivity and specificity that each individual marker for tumour stage, lymph node invasion and distant organ metastases than each individual marker. CONCLUSION: A colon score derived from serum CEA, CA19-9, CK1 and MUC1 is a potential valuable non-invasive index that could be used for detection and screening early stage colon cancer patients.

Fibro-Mark: a panel of laboratory parameters for predicting significant fibrosis in chronic hepatitis C patients.

BACKGROUND: Fibrosis markers are useful for the prediction of cirrhosis but clinical scores such as King's score, AST-Platelet ratio index (APRI), Biotechnology research center (BRC), Fibrosis routine test (FRT), Fibro-α score and Fibro-quotient (FibroQ) have limited accuracy for diagnosing significant fibrosis. We hypothesised that new markers (reflecting the balance between hepatic fibrogenesis and fibrolysis) together with other indirect fibrosis markers would together construct a more sensitive and specific score capable of identifying fibrosis than existing scores. METHODS: Collagen IV, hyaluronic acid, platelet-derived growth factor (PDGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by ELISA, and AST, ALT, platelet count, albumin, total bilirubin, INR and AFP by routine methods in 148 patients with hepatitis C induced liver disease. Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were used to create a predictive score and compare it to others. RESULTS: Patients with significant fibrosis (n = 100, F2-F4) showed 2.08, 2.14, 1.80 and 1.90-fold increase in collagen IV, hyaluronic acid, PDGF and TIMP-1, respectively, over patients with no or mild fibrosis (n = 48, F0/F1)(all p < 0.01). Significant independent predictors of F2-F4 were AFP (AUC 0.79), age (0.76), PDGF (0.74), collagen IV (0.78) and TIMP (0.75), which together formed a five-marker score 'Fibro-Mark' for predicting F2-F4. In comparison with other scores, AUC for Fibro-Mark was 0.89, BRC was 0.83, followed by FRT and King's score (both 0.82), APRI (0.80), Fibro-α (0.70) and finally Fibro Q (0.63). CONCLUSIONS: The Fibro-Mark score provides better discrimination in hepatic-fibrosis staging in chronic hepatitis C patients than existing scores.

In Silico Approach to Investigate the Structural and Functional Attributes of Familial Hypercholesterolemia Variants Reported in the Saudi Population.

Familial hypercholesterolemia (FH) is a metabolic disorder that leads primarily to premature cardiovascular diseases, the main cause of mortality in Saudi Arabia (SA). FH is underreported and underdiagnosed in SA with statistical evidence of high expected prevalence in such a consanguineous community. Lacking knowledge of which and how these alterations are actually impacting lipid metabolism is one of the main reasons why FH is insufficiently diagnosed in the region. The aim of this study was to develop a fast prediction approach using an integrated bioinformatics method for future screening of the potential causative variants from national registries. A total of 21 variants were detected with majority rate in LDLR (81%). Variants were classified based on the type of mutation. Missense variants resulting in amino acid changes, c.1429G>A (p.D477N), c.1474G>A (p.D492N), c.1731G>T (p.W577C), and c.1783C>T (p.R595W) in LDLR gene, in addition to c.9835A>G (p.S3279G) in APOB, were shown to be deleterious by concordant analysis. Furthermore, functional interaction deformities showed a significant loss and gain of energies in the mutated proteins. These findings will help in distinguishing the most harmful mutations needed to be screened for clinically diagnosed FH patients in SA. Such computational research is necessary to avoid time consumption and the usage of expensive biological experiments. This can be a fast track to facilitate the future filtering and screening of causative mutations from national registries.