Designing and developing an app to perform Hofstee cut-off calculations.

Determining a Hofstee cut-off point in medical education student assessment is problematic: traditional methods can be time-consuming, inaccurate, and inflexible.  To counter this, we developed a simple Android app that receives raw, unsorted student assessment data in .csv format, allows for multiple judges' inputs, mean or median inputs, calculates the Hofstee cut-off mathematically, and outputs the results with other guiding information. The app contains a detailed description of its functionality.

COVID-19 and the Clinical Phase of the Medical Doctorate Curriculum in Oman: Challenges and the way forward.

COVID-19 has gripped the world with lightning speed. Since the onset of the pandemic, activity throughout the world came to a grinding halt. However, business had to continue and people have to learn to live with the virus while the pandemic continues to rage. Medical education is no exception and may even deserve special mention, as it prepares frontline workers against the endemics of tomorrow. We discuss here the journey of medical education at the College of Medicine and Health Sciences at Sultan Qaboos University, Muscat, Oman, as the pandemic struck the world and Oman. This work suggests a roadmap for changes, discusses challenges and proposes measures to mitigate the effects of COVID-19 on medical schools.

Faculty Development Initiatives at the College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman.

Faculty development is necessary to improve and update teaching and learning methodologies. As such, a variety of learning activities have been designed to improve teaching competencies of individual teachers. The College of Medicine & Health Sciences at Sultan Qaboos University, Muscat, Oman, recognised the need for teacher training in order to bring faculty up-to-date in teaching and assessment methodologies. A programme of regular and one-time interventions consisting of short courses, workshops and a series of lectures was offered. Feedback from the participants and facilitators led to programme expansion and enhancement. This special contribution discusses the impact of the programme on faculty and the college.

Students' Perceived Benefits of Integrating a BSc in Health Sciences within a Medical Degree at Sultan Qaboos University.

OBJECTIVES: After completing the pre-clinical phase of a Doctor of Medicine (MD) curriculum, undergraduate medical students may choose to add a Bachelor of Science (BSc) degree in health sciences to their MD degree. Limited data exists on the motives behind students' decisions to undertake such intercalated degrees. Hence, this study aimed to identify the factors that influence students in making this choice. METHODS: Undergraduate students who chose the research-based academic track of the intercalated phase of the BSc programme at the College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman, between 2014-2018 were enrolled. A standardised and validated self-explanatory questionnaire examining motivations to join the intercalated phase was administered to all students in the first week of enrolment. RESULTS: Over a five-year period, out of 557 eligible students, 18 (3%) were enrolled in the intercalated phase and all completed the questionnaire. The mean age was 22 ± 1.5 years and the majority (83%) were female. Out of the 18 students, 10 (55%) had taken the university's foundation programme. A total of 45% of students chose to intercalate out of their own interest, regardless of career ambitions. The main reasons to intercalate were an opportunity to enhance research experience, alignment with long-term career goals and a chance to publish in indexed journals. CONCLUSION: Despite the benefits of obtaining an additional degree, a relatively small proportion of MD students were attracted to the intercalated phase. A better presentation of the BSc degree is needed to help students make a more informed decision.

Autozygosity-driven genetic diagnosis in consanguineous families from Italy and the Greater Middle East.

Autozygosity-driven exome analysis has been shown effective for identification of genes underlying recessive diseases especially in countries of the so-called Greater Middle East (GME), where high consanguinity unravels the phenotypic effects of recessive alleles and large family sizes facilitate homozygosity mapping. In Italy, as in most European countries, consanguinity is estimated low. Nonetheless, consanguineous Italian families are not uncommon in publications of genetic findings and are often key to new associations of genes with rare diseases. We collected 52 patients from 47 consanguineous families with suspected recessive diseases, 29 originated in GME countries and 18 of Italian descent. We performed autozygosity-driven exome analysis by detecting long runs of homozygosity (ROHs > 1.5 Mb) and by prioritizing candidate clinical variants within. We identified a pathogenic synonymous variant that had been previously missed in NARS2 and we increased an initial high diagnostic rate (47%) to 55% by matchmaking our candidate genes and including in the analysis shorter ROHs that may also happen to be autozygous. GME and Italian families contributed to diagnostic yield comparably. We found no significant difference either in the extension of the autozygous genome, or in the distribution of candidate clinical variants between GME and Italian families, while we showed that the average autozygous genome was larger and the mean number of candidate clinical variants was significantly higher (p = 0.003) in mutation-positive than in mutation-negative individuals, suggesting that these features influence the likelihood that the disease is autozygosity-related. We highlight the utility of autozygosity-driven genomic analysis also in countries and/or communities, where consanguinity is not widespread cultural tradition.

In silico analysis of a novel causative mutation in Cadherin23 gene identified in an Omani family with hearing loss.

BACKGROUND: Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every 500 newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. It is found to be expressed in the stereocilia of hair cells and in the retina photoreceptor cells. Defective CDH23 have been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12) deafness. The purpose of this study was to identify causative mutations in an Omani family diagnosed with severe-profound sensorineural hearing loss by whole exome sequencing technique and analyzing the detected variant in silico for pathogenicity using several in silico mutation prediction software. RESULTS: A novel homozygous missense variant, c.A7436C (p. D2479A), in exon 53 of CDH23 was detected in the family while the control samples were all negative for the detected variant. In silico mutation prediction analysis showed the novel substituted D2479A to be deleterious and protein destabilizing mutation at a conserved site on CDH23 protein. CONCLUSION: In silico mutation prediction analysis might be used as a useful molecular diagnostic tool benefiting both genetic counseling and mutation verification. The aspartic acid 2479 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

LHFPL5 mutation: A rare cause of non-syndromic autosomal recessive hearing loss.

Hearing loss is a debilitating disorder that impairs language acquisition, resulting in disability in children and potential isolation in adulthood. Its onset can have a genetic basis, though environmental factors, which are often preventable, can also cause the condition. The genetic forms are highly heterogeneous, and early detection is necessary to arrange appropriate patient support. Here we report the molecular basis of hereditary hearing loss in a consanguineous family with multiple affected members from Oman. Combining homozygosity mapping with whole exome sequencing identified a novel homozygous nucleotide substitution c.575T > C in the lipoma HMGIC fusion partner-like 5 gene (LHFPL5), that converted the 192nd amino acid residue in the protein from a leucine to a proline, p.(Leu192Pro). Sanger sequencing confirmed segregation with the disease phenotype as expected for a recessive condition and the variant was absent in 123,490 subjects from various disease-specific and population genetic studies as well as 150 unrelated individuals and 35 deaf patients of Omani ethnicity. This study, which describes a novel LHFPL5 mutation in a family of Omani origin with hereditary hearing loss, supports previous clinical descriptions of the condition and contributes to the genetic spectrum of mutations in this form of deafness.

A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman.

The increased risk for autosomal recessive disorders is one of the most well-known medical implications of consanguinity. In the Sultanate of Oman, a country characterized by one of the highest rates of consanguineous marriages worldwide, prevalence of genetic hearing loss (GHL) is estimated to be 6/10 000. Families of GHL patients have higher consanguinity rates than the general Omani population, indicating a major role for recessive forms. Mutations in GJB2, the most commonly mutated GHL gene, have been sporadically described. We collected 97 DNA samples of GHL probands, affected/unaffected siblings and parents from 26 Omani consanguineous families. Analyzing a first family by whole-exome sequencing, we identified a novel homozygous frameshift duplication (c.1171_1177dupGCCATCT) in MYO15A, the gene linked to the deafness locus DFNB3. This duplication was then found in a total of 8/26 (28%) families, within a 849 kb founder haplotype. Reconstruction of haplotype structure at MYO15A surrounding genomic regions indicated that the founder haplotype branched out in the past two to three centuries from a haplotype present worldwide. The MYO15A duplication emerges as the major cause of GHL in Oman. These findings have major implications for the design of GHL diagnosis and prevention policies in Oman.

A novel missense mutation in the C2C domain of otoferlin causes profound hearing impairment in an Omani family with auditory neuropathy.

OBJECTIVES: To identify genetic defects in an Omani family diagnosed with deafness.  METHODS: A cross-sectional association study was conducted at the Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khoud, Oman and the Centre of Medical Genetics, University of Antwerp, Antwerp, Belgium between August 2010 and September 2014. Microsatellites markers for nine non-syndromic genes were used to genotype the defective locus using the extracted DNA from family members. Sanger sequencing method was used to identify the disease causative mutation. Eazy linkage 5.05 was used to calculate the logarithm of odds score. Lasergene suite was used to detect the mutation position, and Phyre2, SMART, Rasmol, and GOR IV were used to predict the effects of the defect on protein structure and function.  RESULTS: The disease was linked to markers located on chromosome-2 and covering the OTOF (DFNB9) gene. A novel missense mutation that changed nucleotide C to G at position c.1469 and consequently the amino acid Proline to Arginine (P490R) on exon 15 was detected. Protein modeling analysis revealed the impact of the mutation on protein structure and the relevant C2C domain. The mutation seems to create a new protein isoform homologous to the complement component C1q.  CONCLUSION: These findings suggest that the mutation found in C2C domain of the OTOF gene is likely to cause deafness in the studied family reflecting the importance of C2 domains of otoferlin in hearing loss.

Assessment methods in undergraduate medical education.

Various assessment methods are available to assess clinical competence according to the model proposed by Miller. The choice of assessment method will depend on the purpose of its use: whether it is for summative purposes (promotion and certification), formative purposes (diagnosis, feedback and improvement) or both. Different characteristics of assessment tools are identified: validity, reliability, educational impact, feasibility and cost. Whatever the purpose, one assessment method will not assess all domains of competency, as each has its advantages and disadvantages; therefore a variety of assessment methods is required so that the shortcomings of one can be overcome by the advantages of another.

Is performance in pre-clinical assessment a good predictor of the final Doctor of Medicine grade?

OBJECTIVE: To investigate if any correlation exists between students' grades on their final doctor of Medicine (MD) assessment and their overall preclinical grade point average (GPA) and its component parts. METHODS: Student data available from the Deanship of Admissions and Registration were analyzed. Pearson correlation coefficient was obtained to assess the degree of linear relationship between performance in the preclinical and the MD assessment of 529 students who graduated from the College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khoud, Oman from June 1998 to June 2005. Simple and multiple regression analyses were performed to evaluate individual and combined impact of the preclinical courses' grades on MD grades. RESULTS: Preclinical GPA correlated highly with MD GPA (r=0.641). The science component taught early in the preclinical phase correlated more strongly (r=0.457) than student electives (r=0.246). This correlation was better in the good English group. Students' performance, however, was best in electives, but worst in English. Most students who had low MD GPA (<2.0) had also preclinical and science GPA of <2.5. The students with low GPA were found to spend longer in the medical program. CONCLUSION: Restricting progression to the clinical phase to those students whose preclinical GPA is >2.5, and limiting the credit hour requirement of electives by the College seems to be justified.

Medical education units: history, functions, and organisation.

Most medical schools have established a medical education unit (MEU) or similar bodies in response to various reforms in medical education. Such units have a variety of titles and operate either independently or under the office of the dean. Their activities include conducting educational research, teaching and providing service and career development of academic staff. The scope of their activities ranges from serving medical faculty only to all other health professionals at either the undergraduate or postgraduate levels. Several factors contribute to the success of MEUs and their establishment is seen to have a positive effect on their medical school.

A PCR-RFLP test for simultaneous detection of two single-nucleotide insertions in the Connexin-26 gene promoter.

Comparisons of Connexin-26 (GJB2) gene sequences available in the GenBank data base indicate the presence of a polymorphism in the promoter, but no easy method is available for the detection of this polymorphism. We have developed a PCR-RFLP test for simultaneous detection of two single nucleotide insertions (G and A) in the GJB2 promoter. The test is based on amplification of a 146-bp DNA fragment, which was digested with Mae I to detect the G insertion in the promoter. A similar digestion with Hinf I detects the A insertion. The test was validated using direct DNA sequencing of amplified DNA from 33 samples. After validation, we have used it to investigate DNA samples from 160 control subjects and 51 unrelated patients with nonsyndromic autosomal recessive deafness. All of the samples analyzed using the PCR test and DNA sequencing were found to contain both the G and A insertions in the GJB2 gene promoter. This PCR test will be useful in studying the prevalence of these two insertions in other populations.

A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) test to detect the common mutation (35delG) in the connexin-26 gene.

OBJECTIVE: To develop a polymerase chain reaction (PCR) based test for the detection of a common frame-shift mutation (35delG) in the connexin-26 (GJB2) gene, and to investigate the status of this mutation in Oman. METHOD: A PCR test, based on site-directed mutagenesis, was developed for the 35delG mutation. A mutagenesis primer generated an EcoN I site in a short (87 bp) DNA fragment amplified from the connexin-26 gene. The EcoN I site is generated only if the 35delG mutation is present. Thus, a restriction fragment length polymorphism (RFLP) analysis of the amplified DNA fragment with EcoN I allowed us to detect the 35delG mutation in the connexin 26 gene. RESULT: After validating the test using quality control DNA samples, which contained the 35delG mutation in either homozygous or heterozygous form, 120 healthy subjects and 35 unrelated Omani patients with nosyndromic autosomal recessive deafness (NARD), were screened for 35delG mutation. The mutation was not present in any individual tested. CONCLUSION: We have been able to develop a new PCR-RFLP test for detecting the 35delG common mutation in the connexin 26 gene. Our preliminary results from application of this test on a limited number of Omani patients indicate that the 35delG mutation may not be associated with NARD in Oman.