The Effect of Cycloplegia on the Ocular Biometric and Anterior Segment Parameters: A Cross-Sectional Study.

INTRODUCTION: To evaluate the effects of cycloplegia on the biometric components and anterior segment parameters of the eye. METHODS: In this cross-sectional study, changes to axial length (AL), anterior chamber depth (ACD) lens thickness, anterior chamber angle (ACA) and volume, corneal thickness in the pupil center (PC), corneal curvature (CC) and white-to-white (WTW) following cycloplegia induced by tropicamide 1% in 42 eyes of patients aged 23-58 years were assessed. Biometric components and anterior segment parameters were measured using an IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany) and a Pentacam HR (Oculus Optikgeräte GmbH, Wetzlar, Germany), respectively. RESULTS: Significant statistical changes in ACD (increased by 0.06 ± 0.05 mm; p < 0.001), anterior chamber volume (increased by 15.19 ± 10.32 mm3; p < 0.001), ACA (decreased by 2.18 ± 10.20°; p = 0.029) and lens thickness (decreased by 0.02 ± 0.03 mm; p < 0.001) were observed post-cycloplegia, while the changes in CC, corneal thickness in the PC, WTW and AL were not statistically different (p > 0.05). Also, a significant inferior displacement of the PC along the vertical axes was seen (p = 0.020). CONCLUSION: Cycloplegia resulted in a deeper ACD and thinner lens thickness. These changes should be considered in determining intraocular lens (IOL) power to prevent refractive surprises in cataract surgery and also in the phakic IOL implantation.

Direct Lung Sampling Indicates That Established Pathogens Dominate Early Infections in Children with Cystic Fibrosis.

Culture and sequencing have produced divergent hypotheses about cystic fibrosis (CF) lung infections. Culturing suggests that CF lungs are uninfected before colonization by a limited group of CF pathogens. Sequencing suggests diverse communities of mostly oral bacteria inhabit lungs early on and diversity decreases as disease progresses. We studied the lung microbiota of CF children using bronchoscopy and sequencing, with measures to reduce contamination. We found no evidence for oral bacterial communities in lung lavages that lacked CF pathogens. Lavage microbial diversity varied widely, but decreases in diversity appeared to be driven by increased CF pathogen abundance, which reduced the signal from contaminants. Streptococcus, Prevotella, and Veillonella DNA was detected in some lavages containing CF pathogens, but DNA from these organisms was vastly exceeded by CF pathogen DNA and was not associated with inflammation. These findings support the hypothesis that established CF pathogens are primarily responsible for CF lung infections.

Evolved Aztreonam Resistance Is Multifactorial and Can Produce Hypervirulence in Pseudomonas aeruginosa.

While much attention has been focused on acquired antibiotic resistance genes, chromosomal mutations may be most important in chronic infections where isolated, persistently infecting lineages experience repeated antibiotic exposure. Here, we used experimental evolution and whole-genome sequencing to investigate chromosomally encoded mutations causing aztreonam resistance in Pseudomonas aeruginosa and characterized the secondary consequences of resistance development. We identified 19 recurrently mutated genes associated with aztreonam resistance. The most frequently observed mutations affected negative transcriptional regulators of the mexAB-oprM efflux system and the target of aztreonam, ftsI While individual mutations conferred modest resistance gains, high-level resistance (1,024 µg/ml) was achieved through the accumulation of multiple variants. Despite being largely stable when strains were passaged in the absence of antibiotics, aztreonam resistance was associated with decreased in vitro growth rates, indicating an associated fitness cost. In some instances, evolved aztreonam-resistant strains exhibited increased resistance to structurally unrelated antipseudomonal antibiotics. Surprisingly, strains carrying evolved mutations which affected negative regulators of mexAB-oprM (mexR and nalD) demonstrated enhanced virulence in a murine pneumonia infection model. Mutations in these genes, and other genes that we associated with aztreonam resistance, were common in P. aeruginosa isolates from chronically infected patients with cystic fibrosis. These findings illuminate mechanisms of P. aeruginosa aztreonam resistance and raise the possibility that antibiotic treatment could inadvertently select for hypervirulence phenotypes.IMPORTANCE Inhaled aztreonam is a relatively new antibiotic which is being increasingly used to treat cystic fibrosis patients with Pseudomonas aeruginosa airway infections. As for all antimicrobial agents, bacteria can evolve resistance that decreases the effectiveness of the drug; however, the mechanisms and consequences of aztreonam resistance are incompletely understood. Here, using experimental evolution, we have cataloged spontaneous mutations conferring aztreonam resistance and have explored their effects. We found that a diverse collection of genes contributes to aztreonam resistance, each with a small but cumulative effect. Surprisingly, we found that selection for aztreonam resistance mutations could confer increased resistance to other antibiotics and promote hypervirulence in a mouse infection model. Our study reveals inherent mechanisms of aztreonam resistance and indicates that aztreonam exposure can have unintended secondary effects.

Comparison of Conventional Versus Spiral Computed Tomography with Three Dimensional Reconstruction in Chronic Otitis Media with Ossicular Chain Destruction.

BACKGROUND: Chronic otitis media (COM) can be treated with tympanoplasty with or without mastoidectomy. In patients who have undergone middle ear surgery, three-dimensional spiral computed tomography (CT) scan plays an important role in optimizing surgical planning. OBJECTIVES: This study was performed to compare the findings of three-dimensional reconstructed spiral and conventional CT scan of ossicular chain study in patients with COM. PATIENTS AND METHODS: Fifty patients enrolled in the study underwent plane and three dimensional CT scan (PHILIPS-MX 8000). Ossicles changes, mastoid cavity, tympanic cavity, and presence of cholesteatoma were evaluated. Results of the two methods were then compared and interpreted by a radiologist, recorded in questionnaires, and analyzed. Logistic regression test and Kappa coefficient of agreement were used for statistical analyses. RESULTS: Sixty two ears with COM were found in physical examination. A significant difference was observed between the findings of the two methods in ossicle erosion (11.3% in conventional CT vs. 37.1% in spiral CT, P = 0.0001), decrease of mastoid air cells (82.3% in conventional CT vs. 93.5% in spiral CT, P = 0.001), and tympanic cavity opacity (12.9% in conventional CT vs. 40.3% in spiral CT, P=0.0001). No significant difference was observed between the findings of the two methods in ossicle destruction (6.5% conventional CT vs. 56.4% in spiral CT, P = 0.125), and presence of cholesteatoma (3.2% in conventional CT vs. 42% in spiral CT, P = 0.172). In this study, spiral CT scan demonstrated ossicle dislocation in 9.6%, decrease of mastoid air cells in 4.8%, and decrease of volume in the tympanic cavity in 1.6%; whereas, none of these findings were reported in the patients' conventional CT scans. CONCLUSION: Spiral-CT scan is superior to conventional CT in the diagnosis of lesions in COM before operation. It can be used for detailed evaluation of ossicular chain in such patients.

Empathy Score among Student Residence Assistants in Iran.

INTRODUCTION: Empathy, an essential component of the physician-patient relationship, may be linked to positive patient outcomes. This study aimed to determine the empathy score among student residence assistants (RAs). METHODS: In this descriptive design (cross-sectional study), 102 Iranian RAs participated in the study during 2015, completing the Jefferson Scale of Empathy (JSPE). Data collection was analyzed using SPSS version 17. MANOVA, independent-samples t-test, Spearman correlation and confirmatory factor analysis (CFA) were used for data analysis. RESULTS: Mean score of JSE in the sample was 87.06 (±15.14). The mean scores for perspective taking, compassionate care, and standing in the patients shoes were 38.90 (±13.11), 39.27 (±7.94), and 8.89 (±2.80) respectively. Among the three specialties, (psychiatric, internal medicine, surgery) results showed significant differences in total empathy score (p=0.001) and perspective taking score (p= 0.008). CONCLUSIONS: this study showed significant differences in total empathy score and perspective taking in three specialties. We suggest that the curriculum in Iranian RAs include more teaching on empathy and communicational skills.

Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs.

Bacterial lineages that chronically infect cystic fibrosis (CF) patients genetically diversify during infection. However, the mechanisms driving diversification are unknown. By dissecting ten CF lung pairs and studying ∼12,000 regional isolates, we were able to investigate whether clonally related Pseudomonas aeruginosa inhabiting different lung regions evolve independently and differ functionally. Phylogenetic analysis of genome sequences showed that regional isolation of P. aeruginosa drives divergent evolution. We investigated the consequences of regional evolution by studying isolates from mildly and severely diseased lung regions and found evolved differences in bacterial nutritional requirements, host defense and antibiotic resistance, and virulence due to hyperactivity of the type 3 secretion system. These findings suggest that bacterial intermixing is limited in CF lungs and that regional selective pressures may markedly differ. The findings also may explain how specialized bacterial variants arise during infection and raise the possibility that pathogen diversification occurs in other chronic infections characterized by spatially heterogeneous conditions.

Tgf-beta downregulation of distinct chloride channels in cystic fibrosis-affected epithelia.

RATIONALE: The cystic fibrosis transmembrane conductance regulator (CFTR) and Calcium-activated Chloride Conductance (CaCC) each play critical roles in maintaining normal hydration of epithelial surfaces including the airways and colon. TGF-beta is a genetic modifier of cystic fibrosis (CF), but how it influences the CF phenotype is not understood. OBJECTIVES: We tested the hypothesis that TGF-beta potently downregulates chloride-channel function and expression in two CF-affected epithelia (T84 colonocytes and primary human airway epithelia) compared with proteins known to be regulated by TGF-beta. MEASUREMENTS AND MAIN RESULTS: TGF-beta reduced CaCC and CFTR-dependent chloride currents in both epithelia accompanied by reduced levels of TMEM16A and CFTR protein and transcripts. TGF-beta treatment disrupted normal regulation of airway-surface liquid volume in polarized primary human airway epithelia, and reversed F508del CFTR correction produced by VX-809. TGF-beta effects on the expression and activity of TMEM16A, wtCFTR and corrected F508del CFTR were seen at 10-fold lower concentrations relative to TGF-beta effects on e-cadherin (epithelial marker) and vimentin (mesenchymal marker) expression. TGF-beta downregulation of TMEM16A and CFTR expression were partially reversed by Smad3 and p38 MAPK inhibition, respectively. CONCLUSIONS: TGF-beta is sufficient to downregulate two critical chloride transporters in two CF-affected tissues that precedes expression changes of two distinct TGF-beta regulated proteins. Our results provide a plausible mechanism for CF-disease modification by TGF-beta through effects on CaCC.

Multicenter intestinal current measurements in rectal biopsies from CF and non-CF subjects to monitor CFTR function.

Intestinal current measurements (ICM) from rectal biopsies are a sensitive means to detect cystic fibrosis transmembrane conductance regulator (CFTR) function, but have not been optimized for multicenter use. We piloted multicenter standard operating procedures (SOPs) to detect CFTR activity by ICM and examined key questions for use in clinical trials. SOPs for ICM using human rectal biopsies were developed across three centers and used to characterize ion transport from non-CF and CF subjects (two severe CFTR mutations). All data were centrally evaluated by a blinded interpreter. SOPs were then used across four centers to examine the effect of cold storage on CFTR currents and compare CFTR currents in biopsies from one subject studied simultaneously either at two sites (24 hours post-biopsy) or when biopsies were obtained by either forceps or suction. Rectal biopsies from 44 non-CF and 17 CF subjects were analyzed. Mean differences (µA/cm(2); 95% confidence intervals) between CF and non-CF were forskolin/IBMX=102.6(128.0 to 81.1), carbachol=96.3(118.7 to 73.9), forskolin/IBMX+carbachol=200.9(243.1 to 158.6), and bumetanide=-44.6 (-33.7 to -55.6) (P<0.005, CF vs non-CF for all parameters). Receiver Operating Characteristic curves indicated that each parameter discriminated CF from non-CF subjects (area under the curve of 0.94-0.98). CFTR dependent currents following 18-24 hours of cold storage for forskolin/IBMX, carbachol, and forskolin/IBMX+carbachol stimulation (n=17 non-CF subjects) were 44%, 47.5%, and 47.3%, respectively of those in fresh biopsies. CFTR-dependent currents from biopsies studied after cold storage at two sites simultaneously demonstrated moderate correlation (n=14 non-CF subjects, Pearson correlation coefficients 0.389, 0.484, and 0.533). Similar CFTR dependent currents were detected from fresh biopsies obtained by either forceps or suction (within-subject comparisons, n=22 biopsies from three non-CF subjects). Multicenter ICM is a feasible CFTR outcome measure that discriminates CF from non-CF ion transport, offers unique advantages over other CFTR bioassays, and warrants further development as a potential CFTR biomarker.