Detecting natural selection in RNA virus populations using sequence summary statistics

At present, most analyses that aim to detect the action of natural selection upon viral gene sequences use phylogenetic estimates of the ratio of silent to replacement mutations. Such methods, however, are impractical to compute on large data sets comprising hundreds of complete viral genomes, which are becoming increasingly common due to advances in genome sequencing technology. Here we investigate the statistical performance of computationally efficient tests that are based on sequence summary statistics, and explore their applicability to RNA virus data sets in two ways. Firstly, we perform extensive simulations in order to measure the type I error of two well-known summary statistic methods – Tajima's D and the McDonald–Kreitman test – under a range of virus-like mutational and demographic scenarios. Secondly, we apply these methods to a compilation of ～100 RNA virus alignments that represent natural RNA virus populations. In addition, we develop and introduce a new implementation of the McDonald–Kreitman test and show that it greatly improves the test's statistical reliability on typical viral data sets. Our results suggest that variants of the McDonald–Kreitman test could prove useful in the analysis of very large sets of highly diverse viral genetic data.     

Effects of Nigella sativa on outcome of hepatitis C in Egypt

AIM: To evaluate the safety, efficacy and tolerability of Nigella sativa (N. sativa ) in patients with hepatitis C not eligible for interferon (IFN)-α. METHODS: Thirty patients with hepatitis C virus (HCV) infection, who were not eligible for IFN/ribavirin therapy, were included in the present study. Inclusion criteria included: patients with HCV with or without cirrhosis, who had a contraindication to IFN-α therapy, or had refused or had a financial constraint to IFN-α therapy. Exclusion criteria included: patients on IFN-α therapy, infection with hepatitis B or hepatitis Ⅰ virus, hepatocellular carcinoma, other malignancies, major severe illness, or treatment non-compliance. Various parameters, including clinical parameters, complete blood count, liver function, renal function, plasma glucose, total antioxidant capacity (TAC), and polymerase chain reaction, were all assessed at baseline and at the end of the study. Clinical assessment included: hepato and/ or splenomegaly, jaundice, palmar erythema, flapping tremors, spider naevi, lower-limb edema, and ascites. N. sativa was administered for three successive months at a dose of (450 mg three times daily). Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. RESULTS: N. sativa administration significantly improved HCV viral load (380808.7 ± 610937 vs 147028.2 ± 475225.6, P = 0.001) and TAC (1.35 ± 0.5 vs 1.612 ± 0.56, P = 0.001). After N. sativa administration, the following laboratory parameters improved: total protein (7.1 ± 0.7 vs 7.5 ± 0.8, P = 0.001), albumin (3.5 ± 0.87 vs 3.69 ± 0.91, P = 0.008), red blood cell count (4.13 ± 0.9 vs 4.3 ± 0.9, P = 0.001), and platelet count (167.7 ± 91.2 vs 198.5 ± 103, P = 0.004). Fasting blood glucose (104.03 ± 43.42 vs 92.1 ± 31.34, P = 0.001) and postprandial blood glucose (143.67 ± 72.56 vs 112.1 ± 42.9, P = 0.001) were significantly decreased in both diabetic and non-diabetic HCV patients. Patients with lower-limb edema de     

Clinic-day surgery for children: a patient and staff perspective

Introduction

For the past 3 years, our institution has implemented a same clinic-day surgery (CDS) program, where common surgical procedures are performed the same day as the initial clinic evaluation. We sought to evaluate the patient and faculty/staff satisfaction following the implementation of this program.

Methods

After IRB approval, patients presenting for the CDS between 2014 and 2017 were retrospectively reviewed. Of these, patient families who received CDS were contacted to perform a telephone survey focusing on their overall satisfaction and to obtain feedback. In addition, feedback from faculty/staff members directly involved in the program was obtained to determine barriers and satisfaction with the program.

Results

Twenty-nine patients received CDS, with the most commonly performed procedures being inguinal hernia repair (34%) and umbilical hernia repair (24%). Twenty (69%) patients agreed to perform the telephone survey. Parents were overall satisfied with the CDS program, agreeing that the instructions were easy to understand. Overall, 79% of parents indicated that it decreased overall stress/anxiety, with 75% saying it allowed for less time away from work, and 95% agreeing to pursue CDS again if offered. The most common negative feedback was an unspecified operative start time (15%). While faculty/staff members agreed the program was patient-centered, there were concerns over low enrollment and surgeon continuity, because there were different evaluating and operating surgeons.

Conclusion

This study successfully evaluated the satisfaction of patients and faculty/staff members after implementing a clinic-day surgery program. Our results demonstrated improved patient family satisfaction, with families reporting decreased anxiety and less time away from work. Despite this, faculty and staff members reported challenges with enrollment and surgeon continuity.

     

Distinguishing L from M photopigment coding sequences by hybridization to novel locked nucleic acid (LNA) oligonucleotide probes

Many attempts have been made over the years to distinguish human and primate L (long-wavelength sensitive) from M (middle-wavelength sensitive) cone photoreceptors using either immunohistochemistry or in situ hybridization. These attempts have been unsuccessful due to the very high degree of identity between the sequences of the L and M proteins and encoding mRNAs. The recent development of chemically modified oligonucleotide probes, referred to as locked nucleic acid (LNA) probes, has shown that they hybridize with much greater affinity and specificity to the target nucleic acid. This has greatly increased the potential for differentiating L from M cones by in situ hybridization. We have designed LNA oligonucleotide probes that are complementary to either the L or M coding sequences located in exon 5 of the Macaca nemestrina L and M pigment genes. We have shown that the LNA-M and LNA-L probes hybridize specifically to their respective target nucleic acid sequences in vitro. This result strongly suggests that these probes would be instrumental in rapidly distinguishing L from M cone in the entire retina, and in defining the cone mosaic during development and in adults.     

Identification of the sources of Escherichia coli in a watershed using carbon-utilization patterns and composite data sets

The field of bacterial source tracking (BST) has been rapidly evolving to meet the demands of water pollution analysis, specifically the contamination of waterways and drinking water reservoirs by point source and nonpoint source pollution. The goal of the current study was to create a BST library based on carbon-utilization patterns (CUP) for predicting sources of E. coli in a watershed, to compare this library to an antibiotic-resistance analysis (ARA) library previously published for the same isolates, and to determine the efficacy of using a composite dataset which combines data from both datasets into a single library for predicting the source of unknown isolates. This was accomplished by generating a CUP dataset and a composite ARA-CUP dataset for the E. coli isolates from known fecal sources within a watershed. These libraries were then used to predict the sources of E. coli isolates collected from 13 water sites in the same watershed and compared in regard to predictive accuracy. The dominant sources of E. coli in the South Bosque watershed were cattle as identified by all three methods. The 6-source composite library had higher average rates of correct classification (96.7%), specificity (99.2%), positive-predictive value (99.1%), and negative-predictive value (96.8%) than either the ARA or CUP 6 source libraries (ARCC 80.1% and 86.7% respectively). The current study is the first field study to compare two phenotypic methods, Antibiotic Resistance Analysis (ARA) and Carbon Utilization Profiling (CUP). This study is also the first to combine both of these methods to create a composite "toolbox" type approach.     

The appropriateness of use of coronary angiography in Lebanon: implications for health policy

BACKGROUND: Lebanon, characterized by a free-market health care system, has one of the highest reported per capita rates of cardiac catheterization facilities and coronary angiographies in the world. The aim of this study is to evaluate the appropriateness of performance of coronary angiography procedures in Lebanon. METHODS: Data derived from the 2004 Lebanese Interventional Coronary Registry (LICOR) included 5418 patients aged 30 years and older who had not undergone prior percutaneous coronary intervention or coronary artery bypass grafting. Appropriateness was evaluated based on the Class I indications of the ACC/AHA guidelines for coronary angiography. FINDINGS: The overall rate of appropriate procedures was 54.7% (95% CI 53.3-56.0%). Appropriateness varied significantly by gender and across administrative regions. Compared with females, males were more likely to be referred appropriately for coronary angiography (OR = 1.28, 95% CI = 1.15-1.44). Appropriateness was lowest (OR = 0.89, 95% CI = 0.71-1.12) in the region where the per capita density of cardiac catheterization labs increased by six-fold in the latter 2 years. The majority of the patients (84.3%) were not evaluated by any of the non-invasive tests prior to angiography, with only 10.8%, 4% and 1.5% of the patients referred for an exercise stress test, stress echocardiography and thallium stress tests, respectively. DISCUSSION: Findings indicate a high rate of procedures conducted without appropriate indications and a low utilization rate of pre-interventional non-invasive testing. This may be attributed to three factors: a surplus of catheterization facilities in certain regions, the insignificant cost gradient between non-invasive testing and coronary angiography, and the wide case-based reimbursement of coronary angiography, unlike non-invasive testing, by public insurance schemes.     

Sterile cerebrospinal fluid pleocytosis in young infants with urinary tract infections

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