METHODS: A school environment study was performed among randomly selected students in eight randomly selected secondary schools in Penang, Malaysia. Information on eye symptoms and demographic data was collected by a standardised questionnaire. BUT was measured by two methods, self-reported BUT (SBUT) and by the non-invasive Tearscope (NIBUT). Dust was collected by vacuuming in 32 classrooms and analysed for five fungal DNA sequences. Geometric mean (GM) for total fungal DNA was 7.31*104 target copies per gram dust and for Aspergillus/Penicillium DNA 3.34*104 target copies per gram dust. Linear mixed models and 3-level multiple logistic regression were applied adjusting for demographic factors.
RESULTS: A total of 368 students (58%) participated and 17.4% reported weekly eye symptoms the last 3 months. The median SBUT and TBUT were 15 and 12s, respectively. Students wearing glasses (OR 2.41, p=0.01) and with a history of atopy (OR=2.67; p=0.008) had more eye symptoms. Girls had less eye symptoms than boys (OR=0.34; p=0.006) Indoor carbon dioxide in the classrooms was low (range 380-720ppm), temperature was 25-30°C and relative air humidity 70-88%. Total fungal DNA in vacuumed dust was associated with shorter SBUT (4s shorter per 105 target copies per gram dust; p=0.04) and NIBUT (4s shorter per 105 target copies per gram dust; p<0.001). Aspergillus/Penicillium DNA was associated with shorter NIBUT (5s shorter per 105 target copies per gram dust; p=0.01).
CONCLUSION: Fungal contamination in schools in a tropical country can be a risk factor for impaired tear film stability among students.
PATIENTS AND METHODS: We report two siblings of a healthy but consanguineous Malaysian family presenting with severe short stature caused by CPHD with a variable phenotype. Importantly, at the beginning the girl presented with isolated GHD, whereas the boy was hypothyroid. As the most common gene alterations responsible for CPHD are within either the PROP-1- or the POU1F1- (PIT-1)-gene these two genes were further studied.
RESULTS: Subsequent sequencing of the six exons of the POU1F1-gene allowed the identification of a new N-terminal mutation (Q4ter) in these two children. A substitution of C to T induced a change from a glutamine (CAA) to a stop codon (TAA) in exon 1 of the PIT-1 protein. Both affected children were homozygous for the mutation, whereas the mother and father were heterozygous.
CONCLUSION: We describe two children with autosomal recessive inherited CPHD caused by a new N-terminal located mutation within the PUO1F1-gene. The clinical history of these two children underline the phenotypic variability and support the fact that children with any isolated and/or combined PHD need to be closely followed as at an any time other hormonal deficiencies may occur. In addition, molecular analysis of the possible genes involved might be most helpful for the future follow-up.
METHODS: To this end, we undertook a pilot genome-wide CNV analysis approach in 36 subjects (18 patients with high-grade PCa and 18 controls that were matched by age and ethnicity) in search of more accurate biomarkers that could potentially explain susceptibility toward high-grade PCa. We conducted this study using the array comparative genomic hybridization technique. Array results were validated in 92 independent samples (46 high-grade PCa, 23 benign prostatic hyperplasia, and 23 healthy controls) using polymerase chain reaction-based copy number counting method.
RESULTS: A total of 314 CNV regions were found to be unique to PCa subjects in this cohort (P<0.05). A log2 ratio-based copy number analysis revealed 5 putative rare or novel CNV loci or both associated with susceptibility to PCa. The CNV gain regions were 1q21.3, 15q15, 7p12.1, and a novel CNV in PCa 12q23.1, harboring ARNT, THBS1, SLC5A8, and DDC genes that are crucial in the p53 and cancer pathways. A CNV loss and deletion event was observed at 8p11.21, which contains the SFRP1 gene from the Wnt signaling pathway. Cross-comparison analysis with genes associated to PCa revealed significant CNVs involved in biological processes that elicit cancer pathogenesis via cytokine production and endothelial cell proliferation.
CONCLUSION: In conclusion, we postulated that the CNVs identified in this study could provide an insight into the development of advanced PCa.