METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records.
RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood.
CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.
METHODS: Using as little as 20 ng of DNA from formalin-fixed paraffin-embedded tissues, we analysed 25 previously characterised gliomas for multi-locus copy number losses (CNLs) on 1p and 19q, including 11 oligodendrogliomas (ODG) and 14 non-oligodendroglial (non-ODG) controls. Fluorescence in-situ hybridisation (FISH) was used as a reference standard.
RESULTS: The software confidently detected combined contiguous 1p/19q CNLs in 11/11 ODGs (100% sensitivity), using a copy number cut-off of ≤1.5 and a minimum of 10 amplicons covering the regions. Only partial non-specific losses were identified in non-ODGs (100% specificity). Copy number averages of ODG and non-ODG groups were significantly different (p<0.001). NGS was concordant with FISH and was superior to it in distinguishing partial from contiguous losses indicative of whole-arm chromosomal deletion.
CONCLUSIONS: This commercial NGS panel, along with the standard Ion Torrent algorithm, accurately detected 1p/19q losses in ODG samples, obviating the need for specialised custom-made informatic analyses. This can easily be incorporated into routine glioma workflow as an alternative to FISH.
Aim: This work investigated the occurrence of chromosome aberrations in Rusa timorensis, Rusa unicolor and Axis axis raised in a nucleus deer farm in Malaysia with a history of declining fertility of unknown origin.
Materials & methods: Blood samples were collected from 60 animals through venipuncture, cultured for 72 h and arrested at metaphase. SmartType® and Ideokar® software were used to karyotype the chromosomes.
Results: We found 15 out of the 60 animals screened from both sexes harbor some form of chromosome aberration. Chromosomal aberrations exist at the rate of 25% and may not be unconnected with the observed reduced fertility on the farm. Further investigations should be carried out, especially on the offspring of the studied animals to transmission of these aberrations. The animals that are confirmed to transmit the chromosomal aberrations should be culled to arrest the propagation of their abnormalities.
Design: This study was a retrospective cohort study. The national hospital admissions database was reviewed and children who had died who had life-limiting illnesses were identified.
Setting: This study was conducted at Ministry of Health hospitals, Malaysia.
Patients: Children aged 18 years and below who had died between January 1, 2012 and December 31, 2014.
Main Outcome Measures: Life-limiting diagnoses based on Hain et al.'s directory of LLI or the ACT/RCPCH categories of life-limiting disease trajectories.
Results: There were 8907 deaths and 3958 (44.4%) were that of children with LLI. The majority, 2531 (63.9%) of children with LLI were neonates, and the most common diagnosis was extreme prematurity <28 weeks with 676 children (26.7%). For the nonneonatal age group, the median age at admission was 42 months (1-216 months). A majority, 456 (32.0%) had diagnoses from the ICD-10 chapter "Neoplasms" followed by 360 (25.3%) who had a diagnoses from "Congenital malformations, deformations, and chromosomal abnormalities" and 139 (9.7%) with diagnoses from "Disease of the nervous system." While a majority of the terminal admissions were to the general ward, there were children from the nonneonatal age group, 202 (14.2%) who died in nonpediatric wards.
Conclusion: Understanding the characteristics of children with LLI who die in hospitals could contribute toward a more efficient pediatric palliative care (PPC) service development. PPC service should include perinatal and neonatal palliative care. Palliative care education needs to extend to nonpediatric healthcare providers who also have to manage children with LLI.
MATERIALS AND METHODS: Silymarin was isolated from seeds of milk thistle. Various genotoxicity bioassays of silymarin were performed using mice. First, the bone marrow cell proliferation was estimated by calculating mitotic index. Second, the chromosomal abnormalities in mice bone marrow cells were studied. Third, micronucleated polychromatic erythrocytes (MPE) test and in vivo activation of sister chromatid exchanges (SCEs) were carried out in mice bone marrow cells. Finally, primary spermatocytes were analyzed to estimate genotoxic effect of silymarin on germ cells.
RESULTS: We found that silymarin is capable of inducing a significant increase (P ≤ 0.05) in cell proliferation of bone marrow cells. There is no increase in chromosomal aberrations following silymarin treatments. Results clearly showed that it significantly (P ≤ 0.05) decreased the MPE. Likewise, it was found to be a negative inducer of SCEs. It decreased in total abnormal metaphase, SCEs, MPE, and aberrant diakinesis.
CONCLUSION: The results demonstrated that silymarin has a strong anticlastogenic activity upon mice genome in somatic and germ cells, indicating its safe use as a medicinal substance. Furthermore, it is not only safe but also has protective effect from clastogens.
METHODS: 50 asymptomatic (subjects have remained leukemia-free since treatment cessation) CLS and 50 healthy controls were recruited in this cross-sectional study. Of 50 CLS, 44 had acute lymphoblastic leukemia and 6 had acute myeloid leukemia. G-banded karyotyping was performed on unstimulated peripheral blood leukocytes of all subjects.
RESULTS: CLS had significantly higher occurrence of karyotypic abnormalities compared to controls. Five CLS harbored six nonclonal abnormalities (mostly aneuploidy) while none were found in controls.
CONCLUSION: Subpopulations with nonclonal chromosomal aberrations were present in peripheral blood leukocytes of our cohort of childhood leukemia long-term survivors.
RESULTS: In the present study, in silico prediction of MAR/SAR was performed in the ABL gene. More than 80% of the predicted MAR/SAR sites are closely associated with previously reported patient breakpoint cluster regions (BCR). By using inverse polymerase chain reaction (IPCR), we demonstrated that hydrogen peroxide (H2O2)-induced apoptosis in normal nasopharyngeal epithelial and NPC cells led to chromosomal breakages within the ABL BCR that contains a MAR/SAR. Intriguingly, we detected two translocations in H2O2-treated cells. Region of microhomology was found at the translocation junctions. This observation is consistent with the operation of microhomology-mediated NHEJ.
CONCLUSIONS: Our findings suggested that oxidative stress-induced apoptosis may participate in chromosome rearrangements of NPC. A revised model for oxidative stress-induced apoptosis mediating chromosome rearrangement in NPC is proposed.
METHODS: We tested the ability of BA at neutral and acidic pH in inducing phosphatidylserine (PS) externalisation, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) disruption, and caspase 3/7 activity in normal nasopharyngeal epithelial (NP69) and NPC (TWO4) cells. Inverse-PCR (IPCR) was employed to detect AF9 gene cleavages. To investigate the role of CAD in mediating these cleavages, caspase inhibition was performed. IPCR bands representing AF9 cleaved fragments were sequenced.
RESULTS: BA-treated cells showed higher levels of PS externalisation, ROS production, MMP loss and caspase 3/7 activity than untreated control cells. The effect of BA in the induction of these intracellular events was enhanced by acid. BA at neutral and acidic pH also induced significant cleavage of the AF9 gene. These BA-induced gene cleavages were inhibited by Z-DEVD-FMK, a caspase-3 inhibitor. Intriguingly, a few chromosome breaks were identified within the AF9 region that was previously reported to participate in reciprocal translocation between the mixed lineage leukaemia (MLL) and AF9 genes in an acute lymphoblastic leukaemia (ALL) patient.
CONCLUSIONS: These findings suggest a role for BA-induced apoptosis in mediating chromosome rearrangements in NPC. In addition, CAD may be a key player in chromosome cleavages mediated by BA-induced apoptosis. Persistent exposure of sinonasal tract to gastric duodenal refluxate may increase genomic instability in surviving cells.
METHODS: An observational study of children aged between 0-18 years receiving palliative care at 13 hospitals between 1st January and 31st December 2014 was carried out.
RESULTS: There were 315 patients analysed, 90 (28.6%) and 46 (14.6%) were neonates and adolescents respectively. The main ICD-10 diagnostic categories for all patients were identified to be 'Congenital malformations, deformations and chromosomal abnormalities' 117 (37.1%), 'Diseases of nervous system' 76 (24.1%) and 'Neoplasms' 60 (19.0%). At referral 156 (50%) patients had holistic needs assessments. Patients with 'Diseases of nervous system' were assessed to have significantly more physical needs than the other two diagnostic categories. Majority of patients who knew of their diagnosis and prognosis were those with malignancy. Over a fifth of referrals were at their terminal admission. Of 144 who died, 111 (77.1%) had advanced care plans. There was bereavement follow-up in 98 (68.1%) patients.
CONCLUSION: Patients referred for palliative care have varied diagnoses and needs. To ensure all paediatricians are competent to deliver quality care to all children, further education and training initiatives is imperative.
CASE PRESENTATION: A 25-year-old super morbidly obese female (body mass index = 55 kg/meter2) presented with worsening shortness of breath. For MV, pairing of a 6 mm (mm) diameter ETT to accommodate the patient's vocal cord edema, with a CSS not designed to maintain a clean catheter tip, precipitated ETT blockage and respiratory acidosis. Replacement of these devices with a 6.5 mm ETT and a CSS designed to keep the catheter tip clean resolved the complications. After use of the different ETT and CSS for approximately one week, the patient was discharged to home.
DISCUSSION: The clean-tip catheter CSS enabled a more patent airway than its counterpart device that did not have this feature. Use of a clean-tip catheter CSS was an important care development for this patient, because this individual's super morbidly obese condition minimized tolerance for MV complications that would exacerbate her pre-existing tenuous respiratory health status.
CONCLUSION: Special attention should be given to the choices of ETT size and CSS to manage super morbidly obese patients who have a history of difficult airway access.