The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the ...functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34(+) cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.
Thyroid surgery is moderately painful, but is increasingly being considered as a day-case procedure. Bilateral superficial cervical plexus block (BSCPB) provides an adjuvant technique to facilitate ...this approach, but there is great evidential heterogeneity in randomised controlled trials (RCTs) about its use.
A systematic search, critical appraisal, and analysis of RCTs was performed. Trials investigating preoperative or postoperative BSCPB compared with control in patients undergoing thyroid surgery via neck incision were included. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for dichotomous data, whilst continuous data were analysed using standard mean difference. Primary outcome was rescue analgesic requirement in the first 24 postoperative hours. Secondary outcomes were visual analogue scale (VAS) scores at 0, 4, and 24 h, time until first analgesic request, intraoperative analgesic requirements, length of hospital stay, and incidence of postoperative nausea and vomiting (PONV).
Fourteen RCTs published between 2001 and 2016 including 1154 patients were included. The overall effect of BSCPB compared with control showed a reduction in analgesic requirement (OR 0.30; 95% CI 0.18, 0.51; P<0.00001). There was improvement in VAS scores (P<0.002) and time to first analgesic requirement in the BSCPB group (P<0.00001). Length of hospital stay was reduced by 6 h by use of BSCPB. There was no significant change in the incidence of PONV with its use (OR 0.82; 95% CI 0.49–1.37; P=0.44).
BSCPB offers analgesic efficacy in the early postoperative period for up to 24 h after thyroid surgery, with reduced length of hospital stay, but without any beneficial effect on PONV.
Oxaliplatin-based chemotherapy is used to treat patients with esophageal adenocarcinoma (EAC), but no biomarkers are currently available for patient selection. We performed a prospective, clinical ...trial to identify potential biomarkers associated with clinical outcomes. Tumor tissue was obtained from 38 patients with resectable EAC before and after 2 cycles of oxaliplatin-fluorouracil chemotherapy. Pre-treatment mRNA expression of 280 DNA repair (DNAR) genes was tested for association with histopathological regression at surgery, disease-free survival (DFS) and overall survival (OS). High expression of 13 DNA damage repair genes was associated with DFS less than one year (P < 0.05); expression of 11 DNAR genes were associated with worse OS (P < 0.05). From clinical associations with outcomes, two genes, ERCC1 and EME1, were identified as candidate biomarkers. In cell lines in vitro, we showed the mechanism of action related to repair of oxaliplatin-induced DNA damage by depletion and knockout of protein binding partners of the candidate biomarkers, XPF and MUS81 respectively. In clinical samples from the clinical trial, pre-treatment XPF protein levels were associated with pathological response, and MUS81 protein was associated with 1-year DFS. XPF and MUS81 merit further validation in prospective clinical trials as biomarkers that may predict clinical response of EAC to oxaliplatin-based chemotherapy.
Gloving reduces acquisition of vancomycin-resistant Enterococcus species (VRE) on the hands, and it should be considered for routine inpatient care, even for contact with the intact skin of patients ...who may be colonized with VRE. However, gloving does not completely prevent contamination of the hands, and hand washing is necessary after glove removal.
Summary
Background Fungal infection of the skin is a common clinical problem, and laboratory confirmation of the diagnosis is important to ensure appropriate treatment. The identification of the ...species of fungus is also important, because different fungal species have different modes of transmission, and this may be of importance both in preventing re‐infection and in avoidance of infection of others.
Objectives This study examined the potential of using volatile production patterns for the detection and discrimination between four Trichophyton species (T. mentagrophytes, T. rubrum, T. verrucosum and T. violaceum) in vitro on solid media and in broth culture.
Methods Two different sensor array systems (conducting polymer and metal oxide sensors) were examined for comparing the qualitative volatile fingerprints produced in the headspace by these species over periods of 24–120 h. The relative sensitivity of detection of two of the species (T. mentagrophytes, T. rubrum) was determined for log 1 to log 7 inoculum levels over the same time period.
Results The conducting polymer‐based system was unable to differentiate between species based on volatile fingerprints over the experimental period. However, metal oxide‐based sensor arrays were found to be able to differentiate between the four species within 96 h of growth using principal component analysis which accounted for approximately 94% of the data in principal components 1 and 2 based on the qualitative volatile production patterns. This differentiation was confirmed by cluster analysis of the data using Euclidean distance and Ward's linkage. Studies of the sensitivity of detection showed that for T. mentagrophytes and T. rubrum it was possible to differentiate between log 3, log 5 and log 7 inoculum levels within 96 h.
Conclusions This is the first detailed study of the use of qualitative volatile fingerprints for identification and discrimination of dermatophytes. This approach could have potential for rapid identification of patient samples, reducing significantly the time to treatment.
There has been interest in the development of techniques for the rapid early detection of mycotoxigenic moulds in the food production chain. The development of sensor arrays that respond to the ...presence of different volatiles produced by such moulds has been examined as a potential method for the development of such detection systems. Commercial devices based on such sensor arrays, so-called 'electronic noses', have been examined extensively for the potential application of determining the presence of mycotoxigenic moulds in food raw materials. There is also interest in using the qualitative volatile production patterns to discriminate between non-mycotoxigenic and mycotoxigenic strains of specific mycotoxigenic species, e.g. Fusarium section Liseola, Penicillium verrucosum and Aspergillus section Nigri. This paper reviews the technology and available evidence that the non-destructive analysis of the headspace of samples of food raw materials or the discrimination between strains (mycotoxigenic and non-mycotoxigenic) can be determined using volatile fingerprints.
Visual and auditory analysis of respiratory sound signals promises improved detection of certain types of lung diseases. LabVIEW software was used to design a system that monitors the respiratory ...activity of the patient. The program developed calculates the respiratory rate, displays the time expanded waveform of the lung sound, and computes the fast Fourier transform and short-time Fourier transform to present the power spectrum and spectrogram respectively. These parameters are transmitted synchronously to the remote station using the Internet for online monitoring of the patient.
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