Whole Exome Sequencing in a Korean Child with Joubert Syndrome-related Disorders

Joubert syndrome and Joubert syndrome-related disorders (JSRDs) are rare autosomal recessive or X-linked disorders characterized by cerebellar vermis hypoplasia and a brain stem malformation, which presents as the “molar tooth sign” in magnetic resonance imaging (MRI). JSRDs are a group of clinically heterogeneous conditions that exhibit neurological manifestations and multiple organ involvement. JSRDs are also genetically heterogeneous, and approximately 20 causative genes that account for 45% of JSRDs have been identified. A 7-yr-old boy visited Wonkwang University Sanbon Hospital with the following presentations: no ocular fixation, ataxia, growth retardation, and hypotonia. Physical examination revealed facial dysmorphism, spindle shaped fingers, and height (99 cm) and weight (13 kg) below the third percentile. Ophthalmic examination revealed retinal dystrophy. A diagnosis of JSRDs was made based on clinical and brain MRI findings. We found two heterozygous variants c.2945 G>T; p.Arg982Met (G>T) and c.2216dupA; p.Phe740Valfs*2 (dupA) in AHI1, and a heterozygous c.3973C>T; p.Arg1325Trp (C>T) variant in KIF7 by whole exome sequencing (WES). Genetic analysis on the proband's father revealed that he had both AHI1 variants, but did not have the KIF7 variant, which was inconsistent with autosomal recessive inheritance. Therefore, the G>T variant and C>T variant were presumed to be of “uncertain significance.” Furthermore, one novel dupA variant was interpreted as “pathogenic,” while the second allele was not detected. Caution should be exercised while interpreting the significance of variants detected by WES. In addition, the involvement of genes other than the 20 known ones will require further investigation to elucidate the pathogenesis of JSRDs.

The Effects of a Horticultural Program based on Cox's Interaction Model on Ability for Daily Life and Depression in Older Patients with Mild Dementia / 재활간호학회지

PURPOSE: This study attempts to examine the effects of a horticultural program on activities of daily living (ADL) and depression among older patients with mild dementia. METHODS: This study adopted a quasi-experimental design-based nonequivalent control group pretest and posttest design, enrolling 30 older patients with mild dementia. The Korean Form of Geriatric Depression Scale was utilized, while the data was collected from the experimental group for 60 minutes, twice weekly for 6 weeks in 12 sessions. ADL and depression were assessed for both the experimental and the control group. Overall functions were assessed only for the experimental group. RESULTS: The experimental group showed improvement in physical function, cognitive function, as well as psychological, emotional function and social function following each session (p<.001). The horticulture program was effective in both ADL (Z²=5.65, p<.001) and depression (t=-5.24, p<.001). CONCLUSION: In this study, the horticultural therapy based on the Cox's interaction model had positive effects for older patients with mild dementia. Therefore, horticultural therapy may be commendably applied to older patients with mild dementia as a nursing intervention.

Effect of a Low Iodine Diet vs. Restricted Iodine Diet on Postsurgical Preparation for Radioiodine Ablation Therapy in Thyroid Carcinoma Patients

PURPOSE: The radioiodine ablation therapy is required for patients who underwent a total thyroidectomy. Through a comparative review of a low iodine diet (LID) and a restricted iodine diet (RID), the study aims to suggest guidelines that are suitable for the conditions of Korea. MATERIALS AND METHODS: The study was conducted with 101 patients. With 24-hour urine samples from the patients after a 2-week restricted diet and after a 4-week restricted diet, the amount of iodine in the urine was estimated. The consumed radioiodine amounts for 2 hours and 24 hours were calculated. RESULTS: This study was conducted with 47 LID patients and 54 RID patients. The amounts of iodine in urine, the 2-week case and 4-week case for each group showed no significant differences. The amounts of iodine in urine between the two groups were both included in the range of the criteria for radioiodine ablation therapy. Also, 2 hours and 24 hours radioiodine consumption measured after 4-week restrictive diet did not show statistical differences between two groups. CONCLUSION: A 2-week RID can be considered as a type of radioiodine ablation therapy after patients undergo a total thyroidectomy.

Paxilline enhances TRAIL-mediated apoptosis of glioma cells via modulation of c-FLIP, survivin and DR5

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. However, many cancer cells are resistant to TRAIL-induced cell death. Here, we report that paxilline, an indole alkaloid from Penicillium paxilli, can sensitize various glioma cells to TRAIL-mediated apoptosis. While treatment with TRAIL alone caused partial processing of caspase-3 to its p20 intermediate in TRAIL-resistant glioma cell lines, co-treatment with TRAIL and subtoxic doses of paxilline caused complete processing of caspase-3 into its active subunits. Paxilline treatment markedly upregulated DR5, a receptor of TRAIL, through a CHOP/GADD153-mediated process. In addition, paxilline treatment markedly downregulated the protein levels of the short form of the cellular FLICE-inhibitory protein (c-FLIPS) and the caspase inhibitor, survivin, through proteasome-mediated degradation. Taken together, these results show that paxilline effectively sensitizes glioma cells to TRAIL-mediated apoptosis by modulating multiple components of the death receptor-mediated apoptotic pathway. Interestingly, paxilline/TRAIL co-treatment did not induce apoptosis in normal astrocytes, nor did it affect the protein levels of CHOP, DR5 or survivin in these cells. Thus, combined treatment regimens involving paxilline and TRAIL may offer an attractive strategy for safely treating resistant gliomas.

Radiologic findings of anthracofibrosis

PURPOSE: To evaluate the CT findings of bronchial anthracofibrosis. MATERIAL AND METHOD: Fourteen patientswith bronchoscopically confirmed anthracofibrosis were involved in this study. CT findings (n=12) wereretrospectively analysed ; the pattern, distribution and extent of bronchial and parenchymal abnormalities andadditional findings such as mediastinal lymphadenopathy and pleural effusion were assessed. Age, sex, andoccupational and disease history were also reviewed. RESULT: Patients were aged between 63 and 95 (mean,71.3)years, and ten were female. Only one patient had an occupational history, but four had a history of pulmonarytuberculosis. Frequent radiologic findings were bronchial wall thickening(n=6), atelectasis(n=8), mediastinallymphadenopathy(n=7) and mass(n=4). Other accompanying findings were bronchial wall calcification(n=3),consolidation(n=2) and pleural effusion(n=2). Right upper (n=7) and right middle lobe(n=7) were the most commonlyinvolved sites, and multifocal involvement(n=7) was frequent. CONCLUSION: Bronchial wall thickening, atelectasisand mediastinal lymphadenopathy were characteristic CT findings of anthracofibrosis. When such findings are notedin older or aged female patients, anthracofibrosis should be included in the differential diagnosis.

Size of Pancreas in Non-insulin-dependent Diabetes Mellitus: A Study Based on CT

PURPOSE: To evaluate changes of pancreatic size with aging in control subjects and in non-insulin-dependent diabetic patients. MATERIALS AND METHODS: Two groups of non-insulin-dependent diabetic patients were examined; one had been treated with an oral hypoglycemic agent(n=59), and the other with insulin(n=56). The CT findings of 175 patients without clinical evidence of pancreatic disease were included as a normal control. RESULTS: In control subjects, pancreatic size and age correlated. The pancreas was smaller in non-insulin-dependent diabetics than incontrol subjects and smaller in insulin- treated non-insulin-dependent diabetics than in non-insulin treated patients. CONCLUSION: The pancreas was smaller in non-insulin-dependent diabetic patients than in control subjects within the same age range.