Validity of prostate health index and percentage of [-2] pro-prostate-specific antigen as novel biomarkers in the diagnosis of prostate cancer: omani tertiary hospitals experience

Objectives: Prostate cancer is the leading cancer in older men. The Ministry of Health Oman Cancer Incidence Registry 2013 lists cancer of the prostate as the first most common cancer in males. Therefore, early detection is important and prostate-specific antigen [PSA] is widely used as an established laboratory test. However, despite its wide use, its value in screening, particularly in asymptomatic males, is controversial when considering the risks and benefits of early detection

Methods-. This prospective, observational study included 136 males [67.0+/-8.9 years; range 45-90] who were scheduled for a prostate biopsy in two different tertiary care teaching hospitals in Oman: the Royal Hospital and Sultan Qaboos University Hospital. Blood specimens from these patients were collected at the same setting before obtaining a prostatic biopsy

Three PSA markers [total PSA [tPSA], free PSA [fPSA], and [-2]proPSA [p2PSA]] were measured and the Prostate Health Index [phi] calculated. The histopathological report of the prostatic biopsy for each patient was obtained from the histopathology laboratory of the concerned hospital along with clinical and laboratory data through the hospital information system. Results: Phi has the highest validity markers compared with other prostate markers, with a sensitivity of 82.1%, specificity of 80.6%, and area under the curve [AUC] value of 0.81 at a cutoff of 41.9. The other prostatic markers showed sensitivities and specificities of 78.6% and 25.9% for tPSA; 35.7% and 92.6% for%fPSA; and 64.3% and 82.4% for%p2PSA, respectively. The AUCs at the best cutoff values were 0.67 at 10.1 pg/L for tPSA; 0.70 at 11.6% for%fPSA; and 0.55 at 1.4% for%p2PSA. An association between phi values and aggressiveness of prostate malignancy was noted. Of the 28 patients with prostate cancer, 22 patients had tPS A > 4 [ig/L. However, no patient had phi in the low-risk category, and five, six, and 17 patients had phi in the moderate-, high-, and very high-risk categories, respectively. Conclusions: Phi outperforms tPSA and f PSA when used alone or in combination, and appears to be more accurate than both markers in excluding prostate cancer before biopsy. Use of this biomarker helps clinicians to avoid unnecessary biopsies, particularly in patients with gray-zone tPSA level. Phi is the strongest marker that correlates proportionally with Gleason Score; therefore, it is also useful in predicting the aggressiveness of the disease. This is the first reported experience for the use of p2PSA and phi in Oman, the Middle East, and North Africa

[Frequencies of the Arg16Gly, Gln27Glu and Thr164Ile Adrenoceptor Beta 2 Polymorphisms among Omanis]

Objectives: This study aimed to assess the distribution of missense mutations in the adrenoceptor beta2 [ADRB2] gene in an Omani cohort. Methods: This study was carried out between May 2014 and March 2015 at the Sultan Qaboos University, Muscat, Oman. Blood samples were taken from 316 unrelated Omani subjects. Genotyping for rs1042713 [c.46A>G, p.Arg16Gly], rs1042714 [c.79C>G, p.Gln27Glu] and rs1800888 [c.491C>T, p.Thr164Ile] polymorphisms was performed by real-time polymerase chain reaction using single nucleotide polymorphism [SNP] genotyping assays. The allelic frequencies of these polymorphisms were estimated on the basis of the observed numbers of specific alleles from the genotype data for male and female subjects. The genotype frequencies for each polymorphism were tested for deviation from the Hardy-Weinberg equilibrium

Results: Gly16 and Glu27 were the most frequent variants found among the cohort [63% and 75%, respectively]. The Ile164 variant was not detected in the study population. There was a significant linkage disequilibrium between the rs1042713 and rs1042714 SNPs [r[2] = 0.209; P

Conclusion: The allelic distribution of variants in this Omani cohort was similar to distributions reported among Caucasian populations

Quality of diabetes care at outpatient clinic, Sultan Qaboos University Hospital

To assess the clinical care of type 2 diabetes mellitus [T2D] patients at Sultan Qaboos University Hospital [SQUH], a countrywide tertiary referral center in Muscat, Oman. We performed a retrospective, observational, cross-sectional study using a total of 673 Omani T2D patients from the Diabetes and Family Medicine Clinics at SQUH. We collected patient data from June 2010 to February 2012 from the Hospital Information System [HIS]. Patients had to be Omani, aged more than 18 years old, and have T2D with active follow-up and at least three visits within one year to be included in the study. Ninety-three percent of the patients [n=622] were on oral hypoglycemic drugs and/or insulin, and 70% were on statins. Patients' anthropometric data, biochemical investigations, blood pressure, and duration of diabetes were recorded from the HIS. Using the recommended standards and guidelines of medical care in diabetes [American Diabetes Association and the American National Cholesterol Education Program III NCDP NIII standards], we observed that 22% of the patients achieved a HbA1C goal of <7%, 47% achieved blood pressure goal of <140/80 mm Hg, 48% achieved serum low density lipoprotein cholesterol goal of <2.6 mmol/L, 67% achieved serum triglycerides goal of <1.7 mmol/L, 59% of males and 43% of females achieved high density lipoprotein cholesterol goals [males>1.0; females >1.3 mmol/L]. Almost 60% of the patients had urinary microalbumin/creatinine ratio within the normal range. The clinical outcomes of the care that T2D patients get at SQUH were lower than those reported in Europe and North America. However, it is similar to those reported in other countries in the Arabian Gulf

Familial clustering of type 2 diabetes among Omanis

The aim of this study was to screen Omani individuals for the familial aggregation of type 2 diabetes mellitus. A random cohort of 1182 Omani individuals visiting the Family Medicine Clinic at Sultan Qaboos University Hospital [SQUH], Muscat, Oman, for regular medical checkup, aged >/= 40 years, were sampled. Patients were categorized into three groups: [1] individuals who claim not to have diabetes and had no family history of diabetes; [2] individuals who claim not to have diabetes but had family history of diabetes; [3] individuals with diabetes. Only 16% of these Omani individuals had no diabetes and no family history of diabetes. Another separate random cohort of 234 Omani type 2 diabetes mellitus patients, from the Diabetes Clinic at SQUH, were interviewed and questioned about their family history of type 2 diabetes mellitus. Ninety five percent of the patients had a family history of diabetes. Eighty percent had first degree relatives with diabetes and 46% had second degree relatives with diabetes. At least one parent with diabetes was reported among 55% of these diabetics, while maternal diabetes [55%] was found to be higher than paternal diabetes [47%]. However, only 15% had both parents with diabetes. Furthermore, almost half of the 234 diabetics were having at least one of the following relatives with diabetes: brother, sister, aunt or an uncle. The findings of this study confirm familial aggregation of diabetes among the Omani population. Compared to other populations, familial aggregation of type 2 diabetes mellitus among Omanis is relatively very high, and is perhaps due to the very high degree of consanguinity among Omanis. Since almost everyone seems to have a genetic predisposition to diabetes, the dramatic lifestyle changes over the past 25 years, could tip the population into an epidemic of type 2 diabetes mellitus

phenotype/genotype correlation of lactase persistence among Omani adults

To examine the correlation of lactase persistence phenotype with genotype in Omani adults. Lactase persistence phenotype was tested by hydrogen breath test in 52 Omani Adults using the Micro H2 analyzer. Results were checked against genotyping using direct DNA sequencing. Forty one individuals with C/C-13910 and T/T-13915 genotypes had positive breath tests [>/= 20 ppm]; while eight of nine individuals with T/C-13910 or T/G-13915 genotypes had negative breath tests [<20 ppm] and two subjects were non-hydrogen producers. The agreement between phenotype and genotype using Kappa value was very good [0.93]. Genotyping both T/C-13910 and T/G-13915 alleles can be used to assist diagnosis and predict lactose intolerance in the Omani population.

Detection of inborn errors of metabolism using tandem mass spectrometry among high-risk Omani patients

This is a report on the types and patterns of inborn errors of metabolism [IEMs] of amino acids, organic acids and fatty acids oxidation detected by Tandem Mass Spectrometry for a period of 10 years [1998-2008] at Sultan Qaboos University Hospital [SQUH], the major centre for diagnosis and management of IEM in Oman. Tandem mass spectrometry [MS/MS] was used in the initial screening and diagnosis of IEMs in high risk neonatal and pediatric populations. Out of 1100 patients investigated, 119 were detected positive for IEM by MS/MS spectrometry. Twenty six different metabolic diseases were detected. Patients were categorized into three major groups: a] 54 with amino acids and urea cycle disorders, b] 35 with organic acid disorders, and c] 30 with fatty acid oxidation disorders. The commonest conditions encountered were maple syrup urine disease [MSUD], phenylketonuria [PKU], propionic and isovaleric acidurias, as well as HMG-CoA lyase deficiency and glutaric aciduria type II [GA-II]. Most of these IEMs were over representedin babies born to consanguineous parents, which is consistent with the recessive autosomal inheritance. This study shows that various types of IEMs, reported elsewhere, were also prevalent in Oman, but the pattern of prevalence and distribution is different. The situation, therefore, warrants the development of a nationwide screening and prevention program

novel splice-site allelic variant is responsible for wilson disease in an Omani family

The objective of this study was to characterise Wilson's Disease [WD] [OMIM 277900] genetically and test for allelic variants in the copper transport gene [ATPase, Cu[++] transporting, beta polypeptide, ATP7B] responsible for the disease in an Omani family. Three index patients from an Omani family had been previously diagnosed with WD. All three patients suffered neurological symptoms and signs. Forty-six relatives in the family were screened for WD. Eleven more individuals were positive, but asymptomatic. Thirteen non-disease-causing allelic gene variants, described previously, were identified in the ATP7B gene from 46 family members. A putative novel disease-causing splice-site variant [c.2866-2A>G], which has not been reported previously, was detected in this family. It is located upstream of exon 13 which encodes part of transmembrane copper channel [Ch/Tm6]. Reverse transcription polymerase chain reaction was used to amplify a complementary DNA [cDNA] fragment containing exons 12, 13 and 14. Exon 13 was entirely skipped from the transcript which probably would result in a defective ATP7B protein. A new ATP7B splice-site allelic variant, found among the 14 WD patients segregated with the disease in a recessive manner, suggests it is a disease-causing variant

In silico design of novel anticoagulant peptides targeting blood coagulation factor VIIa

The coagulation cascade initiated during vascular injury prevents bleeding. Unwanted clot formation is however detrimental and requires the use of anticoagulants for prophylaxis and treatment. Anticoagulants targeting a specific step or an enzyme in the clotting process are most preferred as they minimise disadvantageous side-effects. A principal step in the discovery of novel anticoagulants encompasses the in silico design of potential leads. This study depicts the in silico design of peptide anticoagulants targeting coagulation factor VIIa. Applying the proline bracket rule and using various bioinformatics tools: the basic alignment search tool [BLAST] of National Center for Biotechnology Information; the T-coffee module provided by European Molecular Biology Laboratory-European Bioinformatics Institute, and several modules available on the ExPASy server, we designed five bivalent chimeric anticoagulants targeting factor VIIa, using factor VIIa inhibitors - hemextin A from Hemachatus haemachatus [African Ringhals cobra] venom and factor VIIa exosite-inhibitor peptide as templates. Six peptides were derived from hemextin A, which were concomitantly fused with factor VIIa exosite-inhibitor peptide intermediated by a polyalanine spacer, and analysed for structural stability using the SWISS-MODEL software developed at the Swiss Institute of Bioinformatics and WebLab ViewerPro [Version 4.2]. Twelve chimeric peptides were obtained; only five exhibited stable structures in silico. The five peptides obtained are probable anticoagulant leads that should be further evaluated using suitable in vitro and in vivo assays. Further, this study shows how simple web-based modules can be used for the rational design of probable leads targeting specific physiological molecular targets

Lipids-risk categories in Omani type 2 diabetics. Impact of the national cholesterol educational program

To evaluate the impact of the National Cholesterol Educational Program Adult Treatment Panel III [ATP III] and the Framingham Offspring Study on Omani diabetic subjects. 221 subjects with type 2 diabetes [86 females and 135 males] and 156 non-diabetic subjects [70 females and 86 males] aged 30-70 years attending Sultan Qaboos University Hospital between 1999-2002 were recruited. Lipid profile, glucose,%HbA[1c], apoproteinA-1 and apoproteinB were measured. Low density lipoprotein was calculated using the Friedwald formula. ATP-III and Framingham Offspring Study guidelines were used to classify lipid parameters into coronary heart disease-risk categories. Diabetic compared to non-diabetic subjects had significantly higher triglycerides of >1.7 mmol/L [p=0.01] and lower low density lipoprotein cholesterol of >4.2 mmol/L [p=0.012] and, in female subjects only, lower high density lipoprotein cholesterol of <1.15 mmol/L for [p<0.0001]. In addition, 57% of diabetic subjects had abnormal aplipoproteinB of >1.2 g/L compared to 49% of non-diabetic subjects. Combined raised levels of triglycerides, apolipoproteinB and low levels of high density lipoprotein were found in 42% of diabetic compared to 26% of the non-diabetic subjects [p=0.05]. Diabetic subjects had significantly higher [p=0.008] NCEP risk-score for coronary artery disease, however, only 34% conformed to a NCEP 10-year-risk score of >10%. A substantial proportion of the Omani diabetic subjects were dyslipidaemic according to the ATP III guidelines. This study recommends the implementation of a lower cut-off threshold for starting lipid-modifying agents for Omani diabetics when using the 10-year Framingham Risk Scoring equation

Genotypes and allele frequencies of angiotensin converting enzyme [ACE] insertion/deletion polymorphism among Omanis

To describe the angiotensin converting enzyme [ACE] genotype frequencies among Omani Arabs. A polymerase chain reaction [PCR] test, based on separation of different size DNA fragments, was developed to test the presence or absence [polymorphism] of a small DNA deletion in the ACE gene. The subjects were 124 Omani Arab students of Sultan Qaboos University, Muscat. The frequency of the I allele was 0.29, while that of the D allele was 0.71. The gene frequency distribution did not deviate from Hardy-Weinberg equilibrium. The frequency of D allele among Omanis is similar to that among other Arabs and Africans, but differs significantly from that among the Japanese and Chinese