To adequately identify patients at risk for surgical site infection in dermatological surgery and effectively prescribe antibiotic prophylaxis, a prediction model may be helpful. Such a model was ...developed using data from 1,407 patients who underwent dermatological surgery without antibiotic prophylaxis. The multivariable logistic regression model included type of closure, tumour location and defect size as risk factors. Bootstrapping was used for internal validation. The overall performance of the model was good, with an area under the curve of 84.1%. The decision curve analysis showed that the model is potentially useful if one is willing to treat more than 8 patients with antibiotic prophylaxis to avoid 1 infection. For those who prefer more restrictive use of antibiotic prophylaxis, a default strategy of treating no patients at all with prophylaxis would be the best choice. External validation of the model is required before it can be widely applied.
Colistin is a last-resort treatment option for infections with multidrug-resistant Gram-negative bacteria. However, colistin resistance is increasing.
A six-month prospective matched case-control ...study was performed in which 22 Dutch laboratories with 32 associated hospitals participated. Laboratories were invited to send a maximum of five colistin-resistant
or
(COLR-EK) isolates and five colistin-susceptible isolates (COLS-EK) to the reference laboratory, matched for patient location, material of origin and bacterial species. Epidemiological/clinical data were collected and included in the analysis. Characteristics of COLR-EK/COLS-EK isolates were compared using logistic regression with correction for variables used for matching. Forty-six ColR-EK/ColS-EK pairs were analysed by next-generation sequencing (NGS) for whole-genome multi-locus sequence typing and identification of resistance genes, including
genes. To identify chromosomal mutations potentially leading to colistin resistance, NGS reads were mapped against gene sequences of
and
.
In total, 72 COLR-EK/COLS-EK pairs (75%
and 25%
) were included. Twenty-one percent of COLR-EK patients had received colistin, in contrast to 3% of COLS-EK patients (OR > 2.9). Of COLR-EK isolates, five contained
and two
. One isolate lost
after repeated sub-culturing, but retained colistin resistance. Among 46 sequenced COLR-EK isolates, genetic diversity was large and 19 (41.3%) isolates had chromosomal mutations potentially associated with colistin resistance.
Colistin resistance is present but uncommon in the Netherlands and caused by the
gene in a minority of COLR-EK isolates. There is a need for surveillance of colistin resistance using appropriate susceptibility testing methods.
This study aimed to determine clinical characteristics of coagulase-negative staphylococcal (CoNS) sepsis in neonates, to assess the molecular epidemiology and biofilm forming properties of isolated ...strains, and to assess antibiotic susceptibility of clonal compared with incidentally occurring strains.
We performed a retrospective study on late-onset CoNS sepsis in infants in the neonatal intensive care unit of a Dutch university hospital in 2003. CoNS isolates were genotyped by restriction fragment end labeling and pulsed-field gel electrophoresis. Resistance profiles, biofilm production, and the presence of mecA and icaA were determined.
Twenty-six percent of all 339 infants developed late-onset sepsis, 66% of these with CoNS sepsis. Eighty-six percent of all CoNS sepsis occurred in very low birth weight infants. Sixty-six CoNS strains were isolated. In multivariate analysis, small for gestational age and prolonged hospitalization were associated with CoNS sepsis. Among 3 restriction fragment end labeling clusters, we found 1 large cluster comprising 32% of the isolates. Biofilm producing Staphylococcus epidermidis were more frequently icaA positive than nonbiofilm formers (74% vs. 12%; P < 0.001). In other species, this association was not found. Nearly all isolates were resistant to antibiotics. MecA was present in 87% of the isolates. Multiresistance occurred in 77% of all strains and in 73% of clustered strains. There was significantly less multiresistance among the largest cluster.
Small for gestational age and prolonged hospitalization were associated with CoNS sepsis. The icaA gene is a predictor for biofilm formation in S. epidermidis, but not in other species. Multiresistance is not associated with clonality.
About 40 years ago Abs against the fungus Madurella mycetomatis were first demonstrated to be present in eumycetoma patients, a disease characterized by tumorous swellings. To date nothing is known ...about the individual immunoreactive Ags present in this fungus. In the present study, we identify its first immunogenic Ag, a protein homologous to the translationally controlled tumor protein (TCTP), a well-conserved histamine release factor in a range of eukaryotes. The gene for this Ag was demonstrated to be present in two variants in M. mycetomatis, with 13% aa difference between the two proteins encoded. In vitro, TCTP was secreted into the culture medium. In vivo, it was found to be expressed on hyphae present in developing stages of the eumycetoma-characteristic black grain. Significant IgG and IgM immune responses, against the whole protein and selected M. mycetomatis-specific peptides, were determined. The Ab levels correlated with lesion size and disease duration. Overall, the patients with the largest lesions had the highest Ab level, which lowered with decreasing size of the lesion. After 6-15 years of disease duration the Ab levels were the highest. TCTP is the first well-characterized immunogenic Ag, simultaneously the first monomolecular vaccine candidate, identified for the fungus M. mycetomatis.
We have developed a new method based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) for analysis of zidovudine-triphosphate and ...(deoxy)nucleotide-triphosphates, which ultimately can be used for nucleoside reverse transcriptase inhibitor (NRTI) treatment monitoring in HIV-1 infected children and adults. Four different matrices were compared for sensitivity and reproducibility of zidovudine-triphosphate detection and anthranilic acid mixed with nicotinic acid (AA/NA) was selected as most suitable matrix. Solutions of zidovudine-triphosphate, ATP, and dGTP were detected up to 0.5fmol per sample. Furthermore, intracellular zidovudine-triphosphate, ATP, and dGTP were detected in peripheral blood mononuclear cells (PBMCs). Zidovudine-triphosphate, ATP, and dGTP yield identical mass spectra, however MALDI-TOF post-source decay analysis can be used for discrimination between these compounds. We conclude that this method based on MALDI-TOF MS can be used for analysis of intracellular zidovudine-triphosphate and (deoxy)nucleotide-triphosphates in PBMCs.
Abstract
Introduction
Mirabegron is the first selective β3-adrenoceptor agonist (AR) approved for treatment of overactive bladder (OAB). We report a case of worsening of obstructive sleep apnea (OSA) ...in a patient who was started on Mirabegron.
Report of Case
70-year-old female with diagnosis of OSA on CPAP at 16 cmH2O was noted to have an elevated residual Apnea-hypopnea-Index (AHI). Her CPAP pressure was increased gradually to 20 cmH2O by her previous pulmonologist. When seen at our sleep center, her AHI was 16.3/hour despite use of CPAP pressure at 20 cmH2O. She was sent for a titration study, which showed an inability of BIPAP to control events despite a maximal possible pressure of 30/25 cm H2O. A repeat titration study with a positional belt showed a pressure of 28/22 cm H2O to be moderately effective. CT neck ruled out anatomic obstruction. Upon further questioning, the timeline of her worsening OSA correlated with the initiation of Mirabegron. This concern was discussed with her urologist and the patient was transitioned to desmopressin for OAB. After discontinuation of Mirabegron, her BIPAP pressures were slowly lowered to 22/18 and AHI improved to 4/hour.
Discussion
Mirabegron, in addition to β3-ARs, also partly acts through blockade of α1A-adrenoceptors and α1D-adrenoceptors.1 Data have suggested another potentially important aspect of adrenergic receptors in endocrine and other disorders - the role of genetic variants of these receptors. Several classes of adrenergic receptors are polymorphic, with coding sequence variants that can influence receptor expression. Of particular importance are data related to the possible contribution of α2- and β3-adrenergic receptor variants in obesity.2 Sympathetic nervous system activity and β -adrenoceptor may contribute to the onset and maintenance of obesity3 and may be a contributing factor to our patient’s worsening OSA. Previously, no adverse reaction of worsening sleep apnea has been reported for Mirabegron.
•Synthesis of rhodamine based chemosensor extended with Bis-1,2,3-triazole.•Discriminative detection of Fe3+ ions through conversion from non-fluorescent to fluorescent.•pH and reversibility studies ...were carried out with cysteine.•Bio-imaging studies of chemosensor and its complex with Fe3+ were performed with DL-tumor cell.•Molecular docking was done with Bcl-XL.
The discriminatory identification of Fe3+ ions among the series of metal ions in an aqueous medium is a significant importance of chemosensors, a bis-1,2,3-triazole associated with rhodamine (R1) was developed with a perfect hetero-atomic cavity. The chemosensor R1 was synthesized using a simple and well-known click reaction to generate a nitrogen enrich triazoles unit in the R1. Through the naked eyes, Fe3+ ion was detected on the spot at tremendously low concentrations with the alterations of fluorescent from non-fluorescent and colored from colorless R1. After formation of complex R1:Fe3+, it is highly pH sustained range from pH 2.0–10.0 and reversible with cysteine in solution and on a paper strip. The formed complex R1:Fe3+, it exhibits excellent pH stability within the range of pH 2.0–10.0. Moreover, its reversibility can be achieved through interaction with cysteine, both in solution and on a paper strip. R1 was also feasible to detect Fe3+ ions in real water samples. In DL-tumor cells, cytocompatibility was investigated using MTT assay, and found that cell viability was greater than 80 %. The binding interaction of R1 with the crystal structure of the anti-apoptotic protein Bcl-XL (PDB ID: 2YXJ) showed that R1 fits well at the active site of Bcl-XL with binding energy (ΔG) − 10.42 kcal/mol (Ki = 22.97 nM). The result shows that R1 is cytocompatible and may be exploited as a fluorescent probe for selectively detecting Fe3+ in living cells.
To estimate the magnitude, determinants, and causes of visual impairment (VI) and blindness among people >40 years.
In this cross-sectional survey, 2,968 people >40 years from 34 clusters were ...examined. A cluster random sampling method with a compact segment sampling technique was used to select the study participants. Prevalence of any VI (presenting visual acuity (PVA) <6/12 in better eye), severe VI (PVA <6/60 - 3/60), and blindness (PVA <3/60 in better eye) were expressed as percentage with 95% confidence interval. Logistic regression was performed to determine the risk factors associated with blindness. A P value of less than 0.05 was considered statistically significant.
The mean age of the participants was 54.6 years (Standard deviation ± 11.2 years). The prevalence of mild, moderate, and severe visual impairment was 14.2% (12.95-15.49), 13.7% (12.46-14.97), and 0.7% (0.47-1.12), respectively. The prevalence of blindness was 1.3% (0.94-1.79, n = 39). The overall prevalence of VI (presenting Visual Acuity <6/12) was 12.0% (95% CI: 10.8-13.2%). The major causes of VI were cataract (78.08%), refractive error (12.07%), and optic atrophy (2.22%), and corneal opacity (2.22%) and the major cause of blindness was cataract (77.27%). Blindness was strongly associated with increasing age- OR 17.1 (95% CI: 4.9-59.8) for people >70 years, and OR 7.6 (95% CI: 2.2-26.5) for people aged between 60 and 69 years compared to those aged 41-50 years and people living near coastal regions (Within 50 km of coast) (OR: 3.9, 95% CI: 1.6-7.3).
Blindness and vision impairment are of public health concern in this geographic region. Eye care services need to be augmented to address this challenge.