Genetic diversity of Merozoite Surface Protein-1 gene block 2 allelic types in Plasmodium falciparum isolates from Malaysia and Thailand.

Malaria is the most common vector-borne parasitic disease in Malaysia and Thailand, especially in Malayan Borneo and along the Thailand border areas, but little is known about the genetic diversity of the parasite. Present study aims to investigate the genetic diversity of Plasmodium falciparum isolates in these two countries and eventually contributes to more effective malaria control strategies, particularly in vaccine and antimalarial treatment. One hundred and seventy three P. falciparum isolates were collected from Malaysia (n = 67) and Thailand (n = 106) and genotyped using nested PCR targeting the polymorphic region of MSP-1, block 2. Sequence analysis was conducted to investigate the allele diversity of the isolates. Three allelic families were identified in Malaysian and Thailand P. falciparum isolates, MAD20, K1 and RO33. Sequence analysis revealed that there were 5 different MAD20, 1 K1 and 2 different RO33 for Malaysian isolates. Thailand isolates exhibited greater polymorphism because there were 13 different MAD20, 6 different K1 and 2 different RO33 identified in this study. Multiclonal infections were observed for the isolates in both countries, however, low multiplicity of infection (MOI) was observed for Malaysian (1.1) and Thailand (1.2) isolates. Phylogenetic analysis showed that P. falciparum isolates of Malaysia and Thailand were clustered in the same group for all the allelic families. Population structure of P. falciparum isolates in Malaysia and Thailand exhibit extensive genetic polymorphism but showed high similarities as well as comparable MOI.

Ipsilateral nonrecurrent laryngeal nerve palsy and delayed palsy of the contralateral recurrent laryngeal nerve in a case of third-time reoperative thyroid surgery.

The occurrence of nonrecurrent laryngeal nerve and delayed nerve palsy of the contralateral nerve occurring simultaneously has never been described. A 67-year-old woman underwent reoperative completion thyroidectomy for enlarging thyroid nodules with recurrent hyperthyroidism and obstructive symptoms. Preoperative computed tomography of the neck showed a large compressive goitre with an aberrant right subclavian artery. At surgery, a type 1 nonrecurrent laryngeal nerve was found and inadvertently transected due to dense adhesions. It was repaired with ansa cervicalis graft. A fully preserved and functional recurrent laryngeal nerve was seen on the contralateral side at the end of surgery. However, the patient developed a delayed palsy on day 4 of the recurrent laryngeal nerve requiring a tracheostomy. Following successful speech and swallowing therapy, the patient was decannulated with good phonation and recovery of the left cord. Patients are at risk of bilateral nerve injury and late onset palsy in reoperative thyroid surgery. Management can be challenging and should be recognised to ensure appropriate therapy.

A systematic review of factors that influence treatment adherence in paediatric oncology patients.

WHAT IS KNOWN AND OBJECTIVE: Treatment adherence is an essential component in ensuring best outcomes in the management of paediatric cancers. Compared to the adult population, treatment adherence in the paediatric population is a more complex subject which involves unique dimensions. In this study, we aimed to systematically review the literature to identify factors associated with treatment adherence in the paediatric oncology population. METHODS: A literature search was carried out using related keywords on electronic databases. RESULTS AND DISCUSSION: A total of 1036 articles were reviewed, and 39 articles were found to be relevant. A comprehensive review of these articles identified 17 factors that influence adherence. These factors were classified into five major categories: patient-/caregiver-related factors; therapy-related factors; condition-related factors; health system-related factors; and social/economic factors. A baby bear model was proposed to better visualize these five categories that affect treatment adherence, and a framework of questions was designed to help clinicians identify those at risk of non-adherence for early intervention. WHAT IS NEW AND CONCLUSION: Seventeen factors reviewed were categorized into five main categories, namely patient-/caregiver-related factors, therapy-related factors, condition-related factors, health system factors and social/economic factors, as causes for poor medication adherence in the paediatric oncology population. Clinicians need to be aware that these factors can interact to influence treatment adherence and that some factors may be more relevant in specific contexts (e.g. third world countries, minority groups). The baby bear model is presented to help understand the issues affecting adherence in the paediatric oncology population, and a framework of questions is proposed to help clinicians identify patients at risk of non-adherence.

SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair.

Defining mechanisms that generate intratumour heterogeneity and branched evolution may inspire novel therapeutic approaches to limit tumour diversity and adaptation. SETD2 (Su(var), Enhancer of zeste, Trithorax-domain containing 2) trimethylates histone-3 lysine-36 (H3K36me3) at sites of active transcription and is mutated in diverse tumour types, including clear cell renal carcinomas (ccRCCs). Distinct SETD2 mutations have been identified in spatially separated regions in ccRCC, indicative of intratumour heterogeneity. In this study, we have addressed the consequences of SETD2 loss-of-function through an integrated bioinformatics and functional genomics approach. We find that bi-allelic SETD2 aberrations are not associated with microsatellite instability in ccRCC. SETD2 depletion in ccRCC cells revealed aberrant and reduced nucleosome compaction and chromatin association of the key replication proteins minichromosome maintenance complex component (MCM7) and DNA polymerase δ hindering replication fork progression, and failure to load lens epithelium-derived growth factor and the Rad51 homologous recombination repair factor at DNA breaks. Consistent with these data, we observe chromosomal breakpoint locations are biased away from H3K36me3 sites in SETD2 wild-type ccRCCs relative to tumours with bi-allelic SETD2 aberrations and that H3K36me3-negative ccRCCs display elevated DNA damage in vivo. These data suggest a role for SETD2 in maintaining genome integrity through nucleosome stabilization, suppression of replication stress and the coordination of DNA repair.

Integrative analysis of array-comparative genomic hybridisation and matched gene expression profiling data reveals novel genes with prognostic significance in oesophageal adenocarcinoma.

BACKGROUND AND AIMS: The incidence of oesophageal adenocarcinoma (OAC) has been increasing rapidly with a dismal survival rate of less than 20%. Understanding the genomic aberrations and biology of this cancer may enhance disease interventions. This study aimed to use genome-wide genomic and expression data to enhance the understanding of OAC pathogenesis and identify groups with differential outcomes. METHODS: Array-comparative genomic hybridisation (aCGH) analysis was carried out on 56 fresh frozen OAC resection samples with long-term clinical follow-up data. Samples with aberrations were further analysed with whole-genome single-nucleotide polymorphism arrays to confirm aCGH findings. Matched gene expression microarray data were used to identify genes with high copy number-expression correlations. Nested-multiplex PCR on DNA from microdissected specimens and fluorescence in situ hybridisation assays were used for target validation. Immunohistochemistry on the same cohort and independent samples (n=371) was used for subsequent validation. Kaplan-Meier survival analyses were performed based on aCGH data after unsupervised K-means clustering (K=5, 50 iterations) and immunohistochemistry data. RESULTS: aCGH identified 17 common regions (>5% samples) of gains and 11 common regions of losses, including novel regions in OAC (loci 11p13 and 21q21.2). Integration of aCGH data with matched gene expression microarray data highlighted genes with high copy number-expression correlations: two deletions (p16/CDKN2A, MBNL1) and four gains (EGFR, WT1, NEIL2, MTMR9). Immunohistochemistry demonstrated protein over-expression of targets with gains: EGFR (10%), WT1 (20%), NEIL2 (14%) and MTMR9 (25%). These targets individually (p<0.060) and in combination had prognostic significance (p=0.008). On the genomic level, K-means clustering identified a cluster (32% of cohort) with differential log(2) ratios of 16 CGH probes (p<4×10(-7)) and a worse prognosis (median survival=1.37 years; p=0.015). CONCLUSIONS: Integration of aCGH and gene expression data identified copy number aberrations and novel genes with prognostic potential in OAC.

Planar focusing elements using spatially varying near-resonant aperture arrays.

Resonances in subwavelength apertures are accompanied by wavelength-dependent phase shifts in the transmitted fields offering a potential for manipulation of wavefields. Here, we present Finite Element Method simulations and experiments investigating light passing through arrays of nanometric spatially varying near-resonant slits perforated in a silver film. We demonstrate that a one-dimensional focusing element can be obtained by tailoring the phase across the device through varying slit sizes around the resonant dimensions for a particular design wavelength.

Three-dimensional refractive index reconstruction with quantitative phase tomography.

Optical tomography based on quantitative phase microscopy is used to determine nondestructively and with high spatial resolution the three-dimensional (3D) refractive index distributions within optical fiber devices. After obtaining a series of phase images of the fiber as it is rotated around its longitudinal axis at regularly-spaced angular positions, filtered backprojection is used to reconstruct a 3D map of the refractive index. The 3D refractive index distribution of the join region between two fusion spliced optical fibers is reconstructed with accuracy better than 10(-3).