Attitude towards working in rural area and self-assessment of competencies in last year medical students: A survey of five countries in Asia.

BACKGROUND: Five countries in Asia including Bangladesh, China, India, Thailand and Vietnam formed a network called Asia-Pacific Network for Health Professional Education Reforms (ANHER). This network collectively conducted a survey at the national level and at the institutional level (for medical, nursing and public health education). We also undertook an assessment of final year graduates from these schools on their attitudes, competencies and willingness to work in rural areas. METHODS: Pretested anonymous questionnaire comprised of four sections including demographic data, attitudes towards working in rural area, where to work after graduation and perception about competency of respondents was used. Descriptive and analytical statistics were used for data analyses. RESULTS: About 60 % of students from Bangladesh and Thailand had positive attitude towards working in rural area, 50 % in both China and India and only 33 % in Vietnam. Students' positive attitudes towards their school in terms of preparing or inspiring them to work in rural areas were low across all five countries. Upon graduation and in the next five years, majority of students wanted to work in public sectors. Interestingly confidence about overall competency was quite low. DISCUSSION: Positive attitude towards working in rural areas varied significantly across five countries in Asia. Medical schools should improve the preparation and inspiration towards working in rural areas for their students. CONCLUSION: Medical schools should put more effort in improving students' attitude towards working in rural areas.

Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand.

Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P < 0.025), which is consistently significant across several linkage statistics. The most suggestive marker D3S1565 (Zlr > 2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.

A comparative study of visual evoked potentials in optic neuritis and optic neuritis with multiple sclerosis.

OBJECTIVE: To compare the visual evoked potentials (VEP) in patients with acute optic neuritis, recurrent optic neuritis, and optic neuritis with multiple sclerosis. MATERIAL AND METHOD: The authors retrospectively reviewed VEP latency records of the patients with optic neuritis in Siriraj Hospital from 1995 to 2005 and divided them into three groups, acute optic neuritis, recurrent optic neuritis, and optic neuritis with multiple sclerosis (ON/MS). The patients with non-recordable VEP in the analysis were excluded. Comparison of the mean latency of the VEP in affected eyes among the three groups was statistically analyzed by a nonparametric independent sample test. RESULTS: Twenty-two patients with acute optic neuritis, 8 patients with recurrent optic neuritis, and 22 patients with ON/MS participated in this study. The mean age among the three groups was not statistically significant. The median value of the latency of flash VEP (fVEP) and pattern reversal VEP (PRVEP) in the acute optic neuritis group was shorter than that of the recurrent optic neuritis group, and statistically significant (fVEP p = 0.012; PRVEP, p = 0.004). The median value of the latency of PRVEP in the acute optic neuritis group was shorter than that of the ON/MS group, and statistically significant (PRVEP p = 0.002). The median value of the latency of both fVEP and PRVEP in the recurrent optic neuritis group and ON/MS group were delayed with no statistical significance (fVEP p = 0.458; PRVEP, p = 0.403). CONCLUSION: The VEP can be used to demonstrate the demyelinating mechanism of optic neuritis and optic neuritis with multiple sclerosis, but cannot determine the susceptibility of the patients with acute ON to become MS. The significantly delayed latency of VEP in recurrent optic neuritis is possibly caused by severe damage of the optic nerve conduction from recurrent attacks.

Transmission of heteroplasmic G11778A in extensive pedigrees of Thai Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) is characterized by the acute or subacute bilateral painless loss of central vision, predominantly in young males. G11778A is the most common mitochondrial DNA mutation responsible for the disease. Thirty-seven percent of our LHON pedigrees (which is a much higher prevalence than that generally found) carried heteroplasmic G11778A. Analyses of four large Thai LHON pedigrees spanning four to six generations strongly suggested that the transmission of the heteroplasmic G11778A mutation is under selective pressure in favour of the mutated allele and that heteroplasmy influences the disease expression.

Mitochondrial DNA haplogroup distribution in pedigrees of Southeast Asian G11778A Leber hereditary optic neuropathy.

To investigate the association of mitochondrial DNA (mtDNA) haplogroups and Leber hereditary optic neuropathy (LHON) in the Southeast Asian population, mtDNA haplogroup determination was performed by high-resolution restriction fragment length polymorphism in 42 patients with LHON who were carrying the G11778A mutation and in control subjects drawn from a Thai urban population unaffected by LHON. The patients with LHON were of Thai, Thai-Chinese, and Indian origin. Three mtDNA haplogroups, M, B*, and B, were found in LHON patients in a frequency similar to that in control subjects. mtDNA haplogroup F was found in none of the patients with LHON but was the second most common haplogroup in control subjects. The G11778A mutation must have arisen in our population independently from the mutation in Caucasians. In contrast to Caucasians, no specific mtDNA haplotype was associated with the patients with LHON in the Southeast Asian population. The mitochondrial polymorphisms that modify the expression of LHON in Southeast Asians could not be identified in this study. The lack of haplogroup F in our patients with LHON may indicate the protective effect of this haplogroup in the expression of this disorder.

The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees.

Leber hereditary optic neuropathy (LHON) is characterized by acute or subacute bilateral visual loss, and affects mostly young males. The most common mitochondrial DNA mutation responsible for LHON worldwide is G11778A. Despite different genetic backgrounds, which are believed to influence the disease expression, most features of LHON are quite common in different populations. However, there seem to be a few ethnic-specific differences. Analyses of our 30 G11778A LHON pedigrees in Thailand showed some characteristics different from those of Caucasians and Japanese. In particular, our pedigrees showed a lower male to female ratio of affected persons (2.6:1) and much higher prevalence of G11778A blood heteroplasmy (37% of the pedigrees contained at least one heteroplasmic G11778A individual). Heteroplasmicity seemed to influence disease manifestation in our patients but did not appear to alter the onset of the disease. The estimated overall penetrance of our G11778A LHON population was 37% for males and 13% for females. When each of our large pedigrees were considered separately, disease penetration varied from 9 to 45% between the pedigrees, and also varied between different branches of the same large pedigree. Survival analysis showed that the secondary LHON mutations G3316A and C3497T had a synergistic deleterious effect with the G11778A mutation, accelerating the onset of the disease in our patients.

Proportion of 11778 mutant mitochondrial DNA and clinical expression in a thai population with leber hereditary optic neuropathy.

BACKGROUND: The proportion of mutant mtDNA in blood has been found to correlate with the frequency of visual loss in cases with mtDNA mutations associated with Leber hereditary optic neuropathy (LHON), especially in men. We sought to determine this correlation in a Thai population of LHON. METHODS: Densitometric quantification of blood mtDNA with the 11,778 LHON mutation in 137 symptomatic cases and their asymptomatic maternal relatives in 30 Asian pedigree families was performed. Asymptomatic maternal relatives under the age of 16 years were excluded. The visual outcome in symptomatic cases with homoplasmy and heteroplasmy was compared. RESULTS: Heteroplasmy was detected in eight (12.9%) symptomatic and 30 (40%) asymptomatic individuals. The quantification of blood mutant mtDNA in the eight symptomatic cases ranged from 44% to 93% (mean=75%). The visual outcome of the cases with heteroplasmy was not different from that of cases with homoplasmy. There was a correlation between the proportion of mutant mtDNA and the likelihood of visual loss. CONCLUSIONS: The prevalence of heteroplasmy among pedigrees of the 11,778 LHON mutation in Thailand was similar to that of other Asian populations and may be greater than in 11,778 LHON pedigrees from white backgrounds. The proportion of mutated mtDNA correlated with visual loss, but the effect of heteroplasmy on clinical expression seemed not to relate to gender.