Anatomical and Visual Effects of the MyoRing Implantation Measured by the ABCD Keratoconus Grading System.

OBJECTIVE: To assess the anatomical changes produced by implantation of the complete intracorneal ring (MyoRing; DIOPTEX, GmbH, Linz, Austria) on the different corneal anatomical layers as measured by the ABCD keratoconus staging system 6 months after operation. METHODS: Seventeen eyes of 17 keratoconic patients implanted with MyoRing using the femtosecond laser were assessed preoperatively and postoperatively. Distance uncorrected visual acuity and distance corrected visual acuity (DCVA), refraction, and Scheimpflug tomography with Pentacam HR were determined for each patient. The 4 ABCD parameters were recorded, which include the anterior and posterior radius of curvature from a 3.0-mm optical zone centered on the thinnest point (TP) (A & B, respectively), the thinnest corneal thickness (C), and DCVA (D). RESULTS: Statistically significant improvement (preoperatively vs. postoperatively) in the DCVA (0.40±0.21 vs. 0.67±0.20 in decimal notation, P=0.001) associated with significant flattening effect was observed in both anterior (6.02±0.40 vs. 7.18±0.54 mm, P<0.001) and posterior (4.49±0.41 vs. 4.66±0.40 mm, P=0.001) radius of curvature. There was no significant change in the corneal thickness at the TP (P=0.981). The largest magnitude of change occurred on the anterior surface as measured by the "A" parameter. The average ABCD keratoconus staging before MyoRing implantation was A4B4C2D2 and changed to A1B4C2D1 6 months after ring implantation. CONCLUSION: Despite the placement of MyoRings in the posterior one-third of the cornea, the greatest changes in curvature occurred on the anterior corneal surface. The ABCD classification and staging system allows for a differential assessment of the different anatomical layers and may prove useful in better understanding of the geometric (structural) and functional changes after MyoRing implantation, as well as with other corneal procedures.

Double-blind, randomized, clinical trial of metformin as add-on treatment with clozapine in treatment of schizophrenia disorder.

BACKGROUND: One of the major causes of death in schizophrenia is a metabolic syndrome. The clozapine has the highest rate of weight gain among antipsychotics. It has been shown that metformin can promote weight loss. We aimed to investigate the effect of metformin as an adjunctive therapy with clozapine to prevent metabolic syndrome in patients with schizophrenia. MATERIALS AND METHODS: A total of 37 patients consisting metformin group (19 cases) and a group of placebo consisting of 18 cases were evaluated. A brief psychiatric rating scale score (BPRS) and metabolic profiles was determined for all patients. All of the variables were also determined at 2, 8, 16, and 20 weeks after the onset of the study. RESULTS: The mean age of the group of metformin was 47.2 ± 10.4 compared with 45.8 ± 10.2 for the group of placebo. The difference in mean waist circumference and serum level of triglyceride at baseline compared with the end of study showed a statistically significant difference between two groups (P = 0. 000). A statistically significant difference was also observed in a comparison of mean difference of weight and body mass index at baseline compared with end of study (P = 0. 000). There was a statistically significant difference of fasting blood sugar (P = 0.011) and serum high-density lipoprotein (P = 0.000) between two groups but this difference was not significant for mean BPRS scores, mean systolic and diastolic blood pressure, serum level of triiodothyronine, thyroxin and thyroid stimulating hormone, serum low-density lipoprotein and serum cholesterol. CONCLUSION: Metformin could be considered an adjunctive therapy with clozapine to prevent metabolic syndrome in schizophrenic patients.

Comparison the effectiveness of aripiprazole and risperidone for the treatment of acute bipolar mania.

BACKGROUND: Second-generation antipsychotics, approved for the treatment of mania, are associated with adverse effects such as weight gain and metabolic disorders. Aripiprazole, a recently introduced second-generation antipsychotic, are thought to account for its low propensity for weight gain, metabolic disturbances and sedation. The purpose of this study was to investigate the effect of risperidone versus aripiprazole in the treatment of acute mania. MATERIALS AND METHODS: Fifty patients with acute episodes of mania were enrolled in this study, and they were randomly assigned into a risperidone group of 24 cases and an aripiprazole group of 26 cases. In group A, aripiprazole with a dose of 5-30 mg/day and in group B, risperidone with a dose of 2-8 mg/day was given to patients. The average dose of aripiprazole was 27 mg/day, and the average dose of risperidone was 6 mg/day. The effects of each drug for the treatment of acute mania were assessed on the 1(st) day of admission and on days 2, 4, 6, 8 and at weeks 2, 4 and 6 after therapy using the young mania rating scale (YMRS) and at the baseline and on weeks 3 and 6 after admission using the clinical global impression (CGI) scale. RESULTS: The mean age of the group of risperidone was 34 ± 8.6 years and in a group of aripiprazole it was 34 ± 9.1 years (P = 0.83). Comparison of YMRS scores over the period of 6 weeks revealed a statistically significant difference in both groups (P < 0.0001). There was also a statistically significant difference in YMRS scores between risperidone and aripiprazole at day 8 (P = 0.026) and weeks 2 (P = 0.035) and 4 (P = 0.042). There was also a statistically significant difference in CGI-Severity scale score at weeks 3 (P = 0.003) and 6 (P = 0.000) and in CGI-Improvement scale score at weeks 3 (P = 0.005) and 6 (P = 0.002). The most common side-effect observed in both groups was headache (0%15/4 in aripiprazole vs. %16/7 in risperidone). CONCLUSION: Aripiprazole that is readily available in our market, could be considered more effective than risperidone in the treatment of acute mania.

Down syndrome and consanguinity.

BACKGROUND: Among the genetics disorders, Down syndrome (DS) is the major cause of mental retardation, congenital heart and intestinal disease. So far, no certain therapeutic method has been suggested for the treatment of this syndrome. The aim of the current survey was to investigate the frequency of parental consanguinity, maternal age in the patients with DS. MATERIALS AND METHODS: This study was conducted on 38 consecutive patients with clinically and laboratory confirmed DS who referred to the genetic lab of a referral University Hospital. The G-banding method for karyotyping was employed. RESULTS: The patients were 21 males and 17 females within the age of 16 days to 28 years old. Free trisomy (92.1%, n = 35) was the most common chromosomal abnormality. The frequency of DS was higher among the non-consanguine marriages (71.1%) in comparison with the consanguine marriages (28.9%). Mean age of the mothers in the consanguine marriages (mean = 27.1 ± 6.3) was lower than in the non-consanguine marriages (mean = 31.1 ± 7.7). CONCLUSION: Higher frequency of DS among the non-consanguine marriages in comparison with the consanguine marriages, may suggest that DS diagnostic tests might be done on all embryos regardless of the parents' familial relationship.

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.

Empathy score among medical students in Mashhad, Iran: study of the Jefferson Scale of Physician Empathy.

BACKGROUND: Empathy is one of the essential components of physician-patient relationship that has a significant effect on treatment outcomes. OBJECTIVE: The aim of this study was to assess the empathy score among medical students in Mashhad, Iran. METHODS: In this cross-sectional study in 2015, 624 medical students at Mashhad University of Medical Science (Iran) completed the Jefferson Scale of Physician Empathy (JSPE). Data were analyzed by SPSS ver. 16, using independent-samples t-test, Chi-square, MANOVA, Spearman correlation, and Confirmatory factor analysis. RESULTS: Of the 38.4% males and 65% females who participated in this study, the mean score of JSPE in the sample was 103.67 (±15.34) which was higher in women than in men. Also, the mean scores for each of the three factors of the scale were calculated. The total empathy score, compassionate care, and taking perspectives among different age groups were significant (p=0.000). Furthermore, students having high interest in their field were more empathic (p=0.008). Empathy of interns in relation to three areas of basic sciences (the first year, the second year and the first half of the third year), physiopathology (the second half of the third year, and the fourth year), and clinical trainings (the fifth year, and the first half of the sixth year), experienced significant reduction (p≤0.001). CONCLUSIONS: This study showed that empathy was higher in women in their first medical year and who were of younger age. The overall rate of empathy in the basic sciences period was more than that in the clinical period. Therefore, the initial exposure to clinical education, especially patient education and empathy, has a very prominent effect on the ability of medical students.

Impact of Propranolol on Preventing Renal Dysfunction in Patients with Cirrhosis.

BACKGROUND One of the earliest diagnostic signs of hepatorenal syndrome in patients suffering from liver cirrhosis is an increase in the renal vascular resistive index (RI). In this study, the impact of propranolol on decreasing this index and to postpone the probability of hepatorenal syndrome has been investigated. METHODS In the current research, 30 patients with liver cirrhosis with different age and sexes have been enrolled. Demographic data and complete medical history have been collected using a specific questionnaire. At first, renal artery Doppler ultrasonography was performed to determine the RI. The patients were then treated with propranolol, and under supervision, the dose of the drug was increased gradually every 3 to 5 days to reach the target of 25% decrease in resting heart rate. One month after reaching the target dose of the medicine, Doppler ultrasonography was repeated for the patients and the second RI was compared with the pretreatment ones. RESULTS According to our results after treatment with propranolol, a significant decrease of RI was observed (p < 0.01). However, there was no significant difference in the glomerular filtration rate (GFR) before and after treatment with propranolol (p = 0.290). In our study, we found that administering propranolol was associated with significant changes in RI and GFR between the patients with compensated and decompensated cirrhosis (mean change: -0.005 ± 0.017 vs. -0.058 ± 0.045; p < 0.01 for RI and -4.226 ± 17.440 vs. 13.486 ± 12.047; p < 0.01 for GFR in patients with compensated and decompensated cirrhosis, respectively). CONCLUSION Propranolol reduces renal vascular RI in patients with cirrhosis. The response rates in the patients with decompensating cirrhosis were significantly higher than the patients with compensating cirrhosis.

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.

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.

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.

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.

Investigation of serum oxidized low-density lipoprotein IgG levels in patients with angiographically defined coronary artery disease.

It has been suggested that antioxidized low-density lipoprotein (anti-oxLDL) antibodies play a role in the pathogenesis of atherosclerosis. The aim of this study was to measure serum ox-LDL IgG levels in 31 patients with angiographically defined coronary artery disease (CAD) (≥50% stenosis in at least one major coronary artery; CAD(+) group) and compare these levels with those of 32 subjects with <50% coronary stenosis (CAD(-) group) and 24 healthy age- and sex-matched controls using ELISA. We did not find any significant difference between CAD(+), CAD(-), and control groups in regard to oxLDL IgG levels (P = 0.83). Serum oxLDL IgG levels did not differ between 1VD (one vessel disease), 2VD (2 vessels disease), and 3VD (3 vessels disease) subgroups of CAD(+) patients (P = 0.20). Serum anti-oxLDL titers were only significantly correlated with LDL-C in the CAD(+) group (P < 0.05) and waist and hip circumference (P < 0.05 and P < 0.01, resp.) in the CAD(-) group. In stepwise regression analysis, none of the conventional cardiovascular risk factors was associated with serum ox-LDL IgG levels. The present results suggest that serum levels of ox-LDL IgG are neither associated with the presence and severity of CAD nor with the conventional cardiovascular risk factors.

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.