Beattyfranco1892

A Virtual Lesion Clinic (VLC) using teledermatoscopy was established to improve efficiency of the melanoma referral pathway.

To assess diagnostic accuracy and to compare wait-times and costs of VLC and conventional clinics.

Patients with suspected melanoma referred from primary care into a publicly funded health system attended local skin imaging centres, rather than hospital outpatient clinics. A teledermatologist assessed each lesion choosing specialist assessment/excision, General Practitioner (GP) follow-up, to re-image in 3 months, or self-monitoring/no concern.

613 skin lesions in 310 patients were evaluated over 12 months. Median time between receipt of referral and attendance at the VLC was 9 days compared to 26.5 days for standard outpatient assessment. Sixty-six percent (404/613) of lesions were considered benign, and 12% (73/613) were suspicious for melanoma. Of 129 lesions excised, 98 were skin cancers including 48 histologically confirmed melanomas with one spitzoid tumour of unknown malignant potential (STUMP), i.e. one melanoma per 1.59 suspected lesions biopsied and one melanoma in every 12.8 referred to the service. There were 49 non-melanoma skin cancers (NMSC). Teledermatoscopic diagnosis of melanomas was found to have a positive predictive value (PPV) of 63%. Compared to the conventional clinic, cost reductions from running the VLC for 1 year were in excess of NZ$364,000 (or NZ$1174/patient seen).

The VLC offered an efficient, accurate and cost effective way of processing suspected melanoma referrals to the public health system.

The VLC offered an efficient, accurate and cost effective way of processing suspected melanoma referrals to the public health system.

To determine the nature of primary vesicoureteral reflux (VUR) and the association of VUR with hydronephrosis and renal damage.

The medical records of children ≤ 15 years diagnosed with VUR, attending the Department of Pediatrics, Prince of Songkla University, Thailand between 1987 and 2013 were reviewed. Bcl-2 inhibitor review Renal ultrasound and technetium-99m dimercaptosuccinic acid renal scan (DMSA) results were examined to determine the severity of hydronephrosis and renal damage, respectively.

There were 177 boys and 211 girls. 350 (90.2%) were diagnosed following urinary tract infection (UTI). The median (IQR) age at diagnosis of first VUR was 7.6 (4.3-12.2) months in boys and 18.6 (9.0-46.6) months in girls (P < 0.001). Renal ultrasound was performed in 340 patients. Hydronephrosis was found in 105 patients and 135 kidneys and 22.5% VUR kidneys and 11.0% non-VUR kidneys (P = 0.01). The severity of hydronephrosis was associated with VUR grade (44.2% of grades IV and V VUR had hydronephrosis vs 11.9% of grades I-III VUR, P < 0.001). DMSA was performed in 332 patients. Abnormalities were found in 30.1% VUR kidneys and 4.1% non-VUR kidneys (P < 0.001). Abnormal DMSA results were strongly associated with VUR grade (17.8% for VUR grades I-III vs 60.5% for VUR grades IV and V, P < 0.001).

Primary VUR in this group was most commonly diagnosed following investigation of UTI and detected during infancy, earlier in boys. Hydronephrosis and renal damage were associated with severity of VUR.

Primary VUR in this group was most commonly diagnosed following investigation of UTI and detected during infancy, earlier in boys. Hydronephrosis and renal damage were associated with severity of VUR.Mitochondrial RNA processing is an essential step for the synthesis of the components of the electron transport chain in all eukaryotic organisms, yet several aspects of mitochondrial RNA biogenesis and regulation are not sufficiently understood. RNA interactome capture identified several disease-relevant RNA-binding proteins (RBPs) with noncanonical RNA-binding architectures, including all six members of the FASTK (FAS-activated serine/threonine kinase) family of proteins. A mutation within one of these newly assigned FASTK RBPs, FASTKD2, causes a rare form of Mendelian mitochondrial encephalomyopathy. To investigate whether RNA binding of FASTKD2 contributes to the disease phenotype, we identified the RNA targets of FASTKD2 by iCLIP. FASTKD2 interacts with a defined set of mitochondrial transcripts including 16S ribosomal RNA (RNR2) and NADH dehydrogenase subunit 6 (ND6) messenger RNA. CRISPR-mediated deletion of FASTKD2 leads to aberrant processing and expression of RNR2 and ND6 mRNA that encodes a subunit of the respiratory complex I. Metabolic phenotyping of FASTKD2-deficient cells reveals impaired cellular respiration with reduced activities of all respiratory complexes. This work identifies key aspects of the molecular network of a previously uncharacterized, disease-relevant RNA-binding protein, FASTKD2, by a combination of genomic, molecular, and metabolic analyses.The human hnRNP C is a ubiquitous cellular protein involved in mRNA maturation. Recently, we have shown that this protein specifically recognizes uridine (U) pentamers through its single RNA recognition motif (RRM). However, a large fraction of natural RNA targets of hnRNP C consists of much longer contiguous uridine stretches. To understand how these extended sites are recognized, we studied the binding of the RRM to U-tracts of 8-11 bases. In vivo investigation of internal translation activation of unr (upstream of N-ras) mRNA indicates that the conservation of the entire hnRNP C binding site, UC(U)8, is required for hnRNP C-dependent IRES activation. The assays further suggest a synergistic interplay between hnRNP C monomers, dependent on the protein's ability to oligomerize. In vitro spectroscopic and thermodynamic analyses show that isolated RRMs bind to (U)11 oligomers as dimers. Structural modeling of a ternary double-RRM/RNA complex indicates additionally that two RRM copies can be accommodated on the canonical sequence UC(U)8. The proposed tandem RRM binding is in very good agreement with the transcriptome-wide recognition of extended U-tracts by full-length hnRNP C, which displays a cross-linking pattern consistent with a positively cooperative RRM dimer binding model.Riboswitches are RNA molecules that regulate gene expression using conformational change, affected by binding of small molecule ligands. A crystal structure of a ligand-bound class II preQ1 riboswitch has been determined in a previous structural study. To gain insight into the dynamics of this riboswitch in solution, eight total molecular dynamic simulations, four with and four without ligand, were performed using the Amber force field. In the presence of ligand, all four of the simulations demonstrated rearranged base pairs at the 3' end, consistent with expected base-pairing from comparative sequence analysis in a prior bioinformatic analysis; this suggests the pairing in this region was altered by crystallization. Additionally, in the absence of ligand, three of the simulations demonstrated similar changes in base-pairing at the ligand binding site. Significantly, although most of the riboswitch architecture remained intact in the respective trajectories, the P3 stem was destabilized in the ligand-free simulations in a way that exposed the Shine-Dalgarno sequence. This work illustrates how destabilization of two major groove base triples can influence a nearby H-type pseudoknot and provides a mechanism for control of gene expression by a fold that is frequently found in bacterial riboswitches.Sandflies vary in their distributions and role in pathogen transmission. Attempts to record distributions of sandflies in Thailand have faced difficulties due to their high abundance and diversity. We aim to provide an insight into the diversity of sandflies in Thailand by (i) conducting a literature review, and (ii) DNA barcoding sandflies collected from Wihan Cave where eight morphologically characterized species were recorded. DNA barcodes generated for 193 sandflies fell into 13 distinct species clusters under four genera (Chinius, Idiophlebotomus, Phlebotomus and Sergentomyia). Five of these species could be assigned Linnaean species names unambiguously and two others corresponded to characterized morphospecies. Two species represented a complex under the name Sergentomyia barraudi while the remaining four had not been recognized before in any form. The resulting species checklist and DNA barcode library contribute to a growing set of records for sandflies which is useful for monitoring and vector control.Streptococcus mutans utilizes maltooligosaccharides, including maltose derived from human dietary starch. We recently reported that the glucose-phosphotransferase system (Glc-PTS) was also involved in the metabolism of glucose derived from intracellular maltooligosaccharides in S. mutans. The activity of the Glc-PTS was mediated by the mannose-(manLMN) and cellobiose-PTSs (celABRCD) in this organism. The purpose of this study was to identify which kind of glucose transporter was involved in this process. A celD, manLM, and glk triple mutant, cm6vU1, was constructed and its growth in maltose or glucose broth measured. When cm6vU1 cells were inoculated into a fresh glucose broth following prolonged incubation with glucose, their growth rate was greater than that in the initial inoculum. This suggested that an additional Glc-PTS was induced in these cells. To investigate this possibility, permeabilized S. mutans cells were constructed and Glc-PTS activity examined by photometrical assay method. Activity in the cells was higher in the secondary inocula than in the initial inocula. These results suggest that S. mutans possesses an additional as yet uncharacterized PTS transporter for glucose in addition to the mannose- and cellobiose-PTSs.Supernumerary teeth in the molar area are classified as paramolars or distomolars based on location. They occur frequently in the maxilla, but only rarely in the mandible. These teeth are frequently fused with adjacent teeth. When this occurs, the pulp cavities may also be connected. This makes diagnosis and planning of endodontic treatment extremely difficult. Here we report a case of a mandibular second molar fused with a paramolar, necessitating dental pulp treatment. Intraoral and panoramic radiographs were obtained for an evaluation and diagnosis. Although the images revealed a supernumerary tooth-like structure between the posterior area of the mandibular second molar and mandibular third molar, it was difficult to confirm the morphology of the tooth root apical area. Subsequent cone-beam computed tomography (CBCT) revealed that the supernumerary tooth-like structure was concrescent with the root apical area of the mandibular second molar. Based on these findings, the diagnosis was a fused mandibular second molar and paramolar with a concrescent supernumerary tooth. A 3-dimensional (3-D) printer was used to produce models based on the CBCT data to aid in treatment planning and explanation of the proposed procedures to the patient. These models allowed the complicated morphology involved to be clearly viewed, which facilitated a more precise diagnosis and better treatment planning than would otherwise have been possible. These technologies were useful in obtaining informed consent from the patient, promoting 3-D morphological understanding, and facilitating simulation of endodontic treatment.