Google Flu Trends in Canada: a comparison of digital disease surveillance data with physician consultations and respiratory virus surveillance data, 2010-2014.

The value of Google Flu Trends (GFT) remains unclear after it overestimated the proportion of physician visits related to influenza-like illness (ILI) in the United States in 2012-2013. However, GFT estimates (%GFT) have not been examined nationally in Canada nor compared with positivity for respiratory viruses other than influenza. For 2010-2014, we compared %GFT for Canada to Public Health Agency of Canada ILI consultation rates (%PHAC) and to positivity for influenza A and B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and rhinoviruses. %GFT correlated well with %PHAC (ρ = 0·77-0·90) and influenza A positivity (ρ = 0·64-0·96) and overestimated the 2012-2013 %PHAC peak by 0·99 percentage points. %GFT peaks corresponded temporally with peaks in positivity for influenza A and rhinoviruses (all seasons) and RSV and hMPV when their peaks preceded influenza peaks. In Canada, %GFT represented traditional surveillance data and corresponded temporally with patterns in circulating respiratory viruses.

Hepatitis B and C serologic profiles of Canadian organ donors and recipients: retrospective 10-year review at a single center.

BACKGROUND: Hepatitis C virus (HBV) and hepatitis C virus (HCV) are important causes of hepatitis and can be transmitted from organ donor to recipient. This study aimed to determine HBV and HCV serologic profiles of a population of Canadian solid organ transplant (SOT) donors and recipients, including prevalence of recipient HBV immunity. METHODS: Data on age, gender, organ transplanted, and pre-transplant HBV and HCV serology for SOT donors and recipients at a Canadian hospital from 2001 to 2011 were obtained from a transplant database. RESULTS: There were 2455 recipients (2205 adults, 250 children), and 1559 donors. Over 50% of adult and 44% of pediatric recipients were HBV non-immune pre-transplant. Pediatric recipients were more likely to have HBV vaccine immunity than were adult recipients (48.8% vs. 28.9%, P < 0.001). Prevalence of HBV vaccine immunity was highest in renal recipients (48.3% in adult, 63.2% in pediatric recipients). Recipient HBV vaccine immunity increased from 5.8% in 2001 to 44.5% in 2011 (P < 0.001). Of 134 adult recipients with prior HBV infection, 59 (44%) were co-infected with HCV. Only 0.6% of adult non-liver recipients had acute or chronic HBV infection and 3.2% were anti-HCV positive. Only 2 donors had acute or chronic HBV infection, 29 had prior HBV infection, 9 were isolated hepatitis B core antibody positive, and 15 were anti-HCV positive. CONCLUSIONS: The prevalence of HBV vaccine immunity in SOT candidates is low, but increased from 2001 to 2011. Opportunities for quality improvement in pre-transplant HBV immunization exist. HCV co-infection is common in recipients with prior HBV infection. Prevalence of HCV infection in non-liver transplant recipients is low.

Assessment of human virus removal during municipal wastewater treatment in Edmonton, Canada.

AIMS: To assess the removal of viruses through the multiple steps of wastewater treatment in a full-scale municipal wastewater treatment plant in Alberta, Canada. METHODS AND RESULTS: Samples were collected after each of the five treatment steps for a period of 16 months. The amount of viruses and their infectivity were analysed using real-time quantitative PCR (qPCR) and integrated viral cell culture (ICC), respectively. Bacterial indicator Escherichia coli was also tested using membrane filtration. Seven viruses including Norovirus (NoV), Rotavirus (RV), Sapovirus (SaV), Astrovirus (AsV), Adenovirus (AdV), Enterovirus (EV) and JC virus (JCV) were detected in 16 primary effluents in which infectious viruses were present. Different treatment steps showed various efficiencies in virus removal, with membrane ultrafiltration as the most effective at 4·6-7·0 log reduction. CONCLUSIONS: We observed high prevalence of viruses in raw wastewater and different viral reduction after various treatment steps. The discharge of treated wastewater with infectious viruses represents potential risks to human, animal and environmental health. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a comprehensive assessment of the removal of NoV, RV, SaV, AsV, AdV, EV, JCV and Reovirus from wastewater by current procedures of municipal wastewater treatment and discusses the applicability of various viruses as viral indicators for water quality.

Association between eNOS polymorphisms and risk of coronary artery disease in a Korean population: a meta-analysis.

Coronary artery disease (CAD), a multifactorial disease, is a common cause of mortality in humans. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (-786T>C, 4a4b, and 894G>T) have been previously associated with increased CAD risk. However, the sample size of this previous study was too small and limited to comprehensively define an association between eNOS polymorphisms and CAD; therefore, this analysis was duplicated with a larger population. The study was conducted on 559 patients with CAD and 574 healthy controls. Genetic DNA was extracted using the commercial G-DEX blood extraction kit and statistical analyses were performed on the GraphPad prism 4.0 and MedCalc 12.0 statistical software platforms. No single variant of the eNOS polymorphism was associated with CAD risk. The combination genotypes of eNOS -786TT/4a4b+4a4a [adjusted odds ratio (AOR) = 0.122; 95% confidence interval (CI): 0.042-0.358] and eNOS -786TC+CC/4b4b (AOR = 0.379; 95%CI: 0.147-0.979) were associated with decreased CAD incidence. Haplotype analysis revealed that the T-4a haplotype of eNOS -786T>C and 4a4b exerted a protective effect against CAD. The association between eNOS -786T>C and increased CAD risk was not replicated in this (larger) population. However, some combined genotypes showed a meaningful association with CAD risk.

Management of gastric epithelial neoplasia in patients requiring esophagectomy for esophageal cancer.

Esophageal squamous cell carcinoma is occasionally associated with malignancies located in other regions of the alimentary tract, as well as in the head, neck, and upper respiratory tract. The stomach is most commonly used for reconstruction of the alimentary tract after esophagectomy for esophageal cancer. When synchronous tumors are located in the stomach, it is often unsuitable for use in esophageal reconstruction. In such cases, an invasive procedure involving anastomosis between the esophagus and the colon must be performed. However, this procedure is associated with a high incidence of mortality and morbidity. Seven patients with synchronous esophageal cancer and gastric epithelial neoplasia were encountered. First, endoscopic submucosal dissection (ESD) was performed for the gastric epithelial neoplasia. Then, following successful ESD, Ivor-Lewis esophagectomy for esophageal cancer was planned 1 to 2 weeks later. A total of 11 gastric epithelial lesions were found in seven patients. En bloc resection by ESD was possible in all 11 lesions and histologically complete resection was achieved in all 11 lesions. Follow-up endoscopy was done 1-2 weeks after ESD; six patients with well-healing ulcers underwent esophagectomy the next day (8 or 15 days after ESD). In one patient with a poorly healed ulcer, a second follow-up endoscopy was done 1 week later and then esophagectomy was performed the next day (22 days after ESD). Post-surgical complications related to ESD, such as bleeding or mediastinal leak, were not seen in any of the seven patients. In patients with synchronous esophageal cancer and gastric epithelial neoplasia, ESD for gastric epithelial neoplasia followed by Ivor-Lewis esophagectomy 1 to 2 weeks later is an effective choice of treatment.

Utility of solar-powered oxygen delivery in a resource-constrained setting.

BACKGROUND: Pneumonia is a leading cause of childhood mortality globally. Children with severe pneumonia associated with hypoxaemia require oxygen (O2) therapy, which is scarce across resource-constrained countries. Solar-powered oxygen (SPO2) is a novel technology developed for delivering therapeutic O2 in resource-constrained environments. RESEARCH QUESTION: Is the introduction of SPO2 associated with a reduction in mortality, relative to the existing practice? STUDY DESIGN: This was a pragmatic, quasi-experimental study comparing mortality amongst children < 5 years of age with hypoxaemic respiratory illness before and after the installation of SPO2 in two resource-constrained hospitals. METHODS: Participants were children < 5 years old admitted with acute hypoxaemic respiratory illness. The intervention was SPO2, installed at two resource-constrained hospitals. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital mortality (time to death), length of hospital stay among survivors, duration of O2 therapy (time to wean O2), and O2 delivery system failure(s). RESULTS: Mortality amongst children admitted with acute hypoxaemic respiratory illness decreased from 30/50 (60%) pre-SPO2 to 15/50 (30%) post-SPO2 (relative risk reduction 50%, 95%CI 19 - 69, p = 0.0049). The post-SPO2 period was consistently associated with decreased mortality in statistical models adjusting for potential confounding factors. Likewise, survival curves pre- and post- SPO2 differed significantly (hazard ratio 0.39, 95% CI 0.20 - 0.74, p = 0.0043). A reduction in the frequency of O2 delivery interruptions due to fuel shortages and multiple patients needing the concentrator at once was observed, explaining the mortality reduction. INTERPRETATION: Solar-powered oxygen installation was associated with decreased mortality in resource-constrained settings.

Endoscopic submucosal resection of esophageal subepithelial lesions using band ligation.

Subepithelial lesions (SELs) are occasionally found in the esophagus during upper endoscopy. Sometimes endoscopic resection is needed for accurate diagnosis or in the rare cases of malignant transformation of SELs. In this case series, we evaluated the usefulness of endoscopic submucosal resection with a ligation device (ESMR-L) in esophageal SELs. Twenty-three patients with 25 esophageal SELs that were no larger than 13 mm and were localized within the muscularis mucosae or submucosa were enrolled. ESMR-L was successfully performed in all 25 SELs. The en bloc resection rate was 100% (25/25), and histologically complete resection was achieved in 24 lesions (24/25, 96%). After resection of the lesion by snare, minor immediate bleeding occurred in four cases, but there was no delayed bleeding or perforation.

Electrophoretic deposition of polymethylmethacrylate and composites for biomedical applications.

For the first time, an electrophoretic deposition (EPD) method has been developed for the deposition of polymethylmethacrylate (PMMA) and PMMA-alumina films for biomedical implant applications. The proposed biomimetic approach was based on the use of a bile salt, sodium cholate (NaCh), which served as a multifunctional solubilizing, charging, dispersing and film-forming agent. Investigations revealed PMMA-Ch- and PMMA-alumina interactions, which facilitated the deposition of PMMA and PMMA-alumina films. This approach allows for the use of a non-toxic water-ethanol solvent for PMMA. The proposed deposition strategy can also be used for co-deposition of PMMA with other functional materials. The PMMA and composite films were tested for biomedical implant applications. The PMMA-alumina films showed statistically improved metabolic results compared to both the bare stainless steel substrate and pure PMMA films. Alkaline phosphatase (ALP) activity affirmed the bioactivity and osteoconductive potential of PMMA and composite films. PMMA-alumina films showed greater ALP activity than both the PMMA-coated and uncoated stainless steel.

Biomimetic modification of poly-l-lysine and electrodeposition of nanocomposite coatings for orthopaedic applications.

For the first time, a biomimetic method has been developed for the chemical modification of poly-l-lysine (PLL) with catechol in order to improve polymer adhesion to inorganic particles and surfaces. The method is based on the Schiff base reaction of amino groups of PLL monomers and aldehyde groups of 3,4-dihydroxybenzylaldehyde (DHBA) molecules. It was found that adherent PLL-DHBA films can be prepared by cathodic electrophoretic deposition (EPD). Nanocomposite coating with dual micro-nano topography has been developed for orthopaedic and dental coating applications. The catechol groups of PLL-DHBA facilitated its adsorption on hydroxyapatite (HA) and rutile (TiO2) and allowed the fabrication of stable suspensions for EPD. PLL-DHBA was used as both a charging and film-forming agent for EPD of HA and TiO2. Moreover, the methods allowed co-deposition of HA and TiO2 and fabrication of composite films, which allows the benefits of both bioceramics to be combined. In addition to having dual scale topography, the films exhibited both sub-micron surface roughness and hydrophilic behaviour, which both have been found to promote osteoblast adhesion and proliferation. in vitro studies revealed that the fabricated coatings showed increased cell metabolism and alkaline phosphatase activity over the period studied, with PLL-DHBA-TiO2 showing the greatest increase. This work paves the way for both the development of the next generation of biomedical implant coatings, with improved osseointegration and lifespan, as well as one-step low-temperature processing.

Relationship between enteric pathogens and acute gastroenteritis disease severity: a prospective cohort study.

OBJECTIVES: To evaluate the relationship between individual bacterial and viral pathogens and disease severity. METHODS: Children <18 years with three or more episodes of vomiting and/or diarrhoea were enrolled in two Canadian paediatric emergency departments between December 2014 and August 2016. Specimens were analysed employing molecular panels, and outcome data were collected 14 days after enrolment. The primary outcome was severe disease over the entire illness (symptom onset until 14-day follow-up), quantified employing the Modified Vesikari Scale (MVS) score. The score was additionally analysed in two other time periods: index (symptom onset until enrolment) and follow-up (enrolment until 14-day follow-up). RESULTS: Median participant age was 20.7 (IQR: 11.3, 44.2) months; 47.4% (518/1093) and 73.4% (802/1093) of participants had index and total MVS scores ≥11, respectively. The most commonly identified pathogens were rotavirus (289/1093; 26.4%) and norovirus (258/1093; 23.6%). In multivariable analysis, severe disease over the entire illness was associated with rotavirus (OR = 9.60; 95%CI: 5.69, 16.19), Salmonella (OR = 6.61; 95%CI: 1.50, 29.17), adenovirus (OR = 2.53; 95%CI: 1.62, 3.97), and norovirus (OR = 1.43; 95%CI: 1.01, 2.01). Pathogens associated with severe disease at the index visit were: rotavirus only (OR = 6.13; 95%CI: 4.29, 8.75), Salmonella (OR = 4.59; 95%CI: 1.71, 12.29), adenovirus only (OR = 2.06; 95%CI: 1.41, 3.00), rotavirus plus adenovirus (OR = 3.15; 95%CI: 1.35, 7.37), and norovirus (OR = 0.68; 95%CI: 0.49, 0.94). During the follow-up period, rotavirus (OR = 2.21; 95%CI: 1.50, 3.25) and adenovirus (OR = 2.10; 95%CI: 1.39, 3.18) were associated with severe disease. CONCLUSIONS: In children presenting for emergency department care with acute gastroenteritis, pathogens identified were predominantly viruses, and several of which were associated with severe disease. Salmonella was the sole bacterium independently associated with severe disease.

Respiratory failure associated with human metapneumovirus infection in an infant posthepatic transplant.

This is the first reported case of respiratory failure associated with human metapneumovirus (hMPV) infection in a liver transplant recipient or in a pediatric solid transplant recipient. A 9-month-old female developed respiratory distress 8 days following a liver transplant. hMPV was detected and she required intubation followed by extracorporeal membrane oxygenation for 26 days. Immunosuppressive medications were stopped during the acute infection except for methylprednisolone as treatment for acute respiratory distress. Serial Doppler ultrasounds were used to monitor for hepatic vessel thromboses and serum liver function tests to assess for hepatic dysfunction and there was no evidence of allograft rejection. The patient recovered from the nosocomial hMPV infection with satisfactory pulmonary function and possible mild developmental delay.

A PHEX gene mutation is responsible for adult-onset vitamin D-resistant hypophosphatemic osteomalacia: evidence that the disorder is not a distinct entity from X-linked hypophosphatemic rickets.

Previous investigators described a kindred with an X-linked dominant form of phosphate wasting in which affected children did not have radiographic evidence of rickets, whereas older individuals were progressively disabled by severe bowing. They proposed that this kindred suffered from a distinct disorder that they referred to as adult-onset vitamin D-resistant hypophosphatemic osteomalacia (AVDRR). We recently identified a gene, PHEX, that is responsible for the disorder X-linked hypophosphatemic rickets. To determine whether AVDRR is a distinct form of phosphate wasting, we searched for PHEX mutations in affected members of the original AVDRR kindred. We found that affected individuals have a missense mutation in PHEX exon 16 that results in an amino acid change from leucine to proline in residue 555. Clinical evaluation of individuals from this family indicates that some of these individuals display classic features of X-linked hypophosphatemic rickets, and we were unable to verify progressive bowing in adults. In light of the variability in the clinical spectrum of X-linked hypophosphatemic rickets and the presence of a PHEX mutation in affected members of this kindred, we conclude that there is only one form of X-linked dominant phosphate wasting.

Functional studies on the interaction between human replication protein A and Xeroderma pigmentosum group A complementing protein (XPA).

The human replication protein A (RPA; also known as human single-stranded DNA binding protein, HSSB) is a multisubunit complex (70, 34 and 11 kDa subunits) involved in the three processes of DNA metabolism; replication, repair, recombination. We found that both 34 and 70 kDa subunits (p34 and p70, respectively), of RPA interacts with the Xeroderma pigmentosum group A complementing protein (XPA), a protein that specifically recognizes UV-damaged DNA. Our mutational analysis indicated that no particular domains of RPA p70 were essential for its interaction with XPA. We also examined the effect of this XPA-RPA interaction on in vitro simian virus 40 (SV40) DNA replication catalyzed by the crude extract and monopolymerase system. XPA inhibited SV40 DNA replication in vitro through its interaction with RPA. Taken together, these results suggest that there is a role for RPA in the regulation of DNA metabolism through its ability to modulate the interactions of proteins involved in the processes of DNA metabolism.

Influence of maternal serum levels of vitamins C and E during the second trimester on birth weight and length.

OBJECTIVE: It has been known that maternal oxidative stress during pregnancy plays an important role in fetal growth. However, the association between antioxidant vitamin levels and birth outcomes is not conclusive. We investigated the relationship between maternal serum levels of vitamins C and E during the second trimester and birth weight and length. DESIGN: Prospective cohort study. SETTING: Outpatient-clinic of obstetrics, Ewha Womans University Hospital, South Korea. SUBJECTS AND METHODS: The study subjects were 239 healthy, pregnant women who visited an obstetric clinic for antenatal care, and their singleton live births, in Seoul, Korea, between August 2001 and March 2003. We measured the levels of vitamins C and E in maternal serum during the period 24-28 gestational weeks. Each woman was interviewed for dietary intake by trained interviewers during the second trimester. RESULTS: The serum concentration of maternal vitamin C during the second trimester was significantly associated with birth weight and length in the group of full-term deliveries. An increase of 1 microg/ml in the serum vitamin C level increased the birth weight by 27.2 g and the birth length by 0.17 cm. When we considered the levels of vitamins C and E together in the relationship with birth weight and length, we found that the heaviest birth weight and the longest birth length belonged to the group of upper vitamin C/upper vitamin E. However, dietary intake estimated by 24-h recall method was not a predictor of the levels of serum vitamins C and E. CONCLUSION: We found that maternal serum vitamin C levels during the second trimester were positively correlated with birth weight and length in full-term babies. We also found that birth weight and length were highest when the levels of both vitamins C and E were high. Our results indicate the importance of antioxidant nutrient balance for pregnant women who are exposed to various oxidants through food, drinking water, or inhaled air.

Development of screening systems for evaluation of materials used in mammalian embryo transfer.

Embryo transfer units use a wide variety of materials that come in contact with embryos. Studies were conducted to evaluate procedures that could be utilized to determine the toxicity of some commonly used materials in embryo collection, culture and transfer. Forty-five female mice were sacrificed on Day 3 or 4 of gestation (Day 1 = vaginal plug), and the uterus and oviducts were removed and minced. A total of 522 embryos was collected (4-cell to blastocyst stages). Four to 16 cell embryos were cultured in Phosphate Buffered Saline (PBS) plus 20% fetal bovine serum. Morula to blastocyst stage embryos were cultured in Nutrient Mixture F10 (HAM) plus 20% fetal bovine serum gassed with 5% CO(2), 5% O(2) and 90% N(2). In Experiment I, embryos and culture media were placed in a covered embryological watch glass (EWG, control) or sealed in the lumen of a siliconized Foley catheter or a section of 1) latex tubing, 2) tygon tubing or 3) silastic tubing. In Experiment II, embryos were placed in EWG and cultured alone (control) or cocultured with sections of 1) tygon tubing, 2) silastic tubing or 3) latex tubing. In Experiment III, embryos were cultured in covered plastic petri dishes containing 15 ml of media, alone (control) or co-cultured with two new plunger tips from sterile Monoject syringes. All embryos were cultured at 32 to 34 degrees C for 24 h. The Criterion used for development was two or more cellular divisions within the 24-h period. Embryo development in Experiment I was lower (P<0.05) in latex (0%) and tygon (24%) tubing and in the siliconized Foley catheter (2%) than in silastic tubing (51%) and the EWG (46%), which did not differ. Experiment II embryos that were co-cultured with latex tubing (5%) showed very little development as compared with those co-cultured with tygon tubing (76%), silastic tubing (76%) and EWG (93%), the last of which were not significantly different. Embryos co-cultured with Monoject syringe plunger tips had a reduced embryo development rate compared to embryos in the control group (0% vs 52%). Although the embryos did not remain in contact with these seemingly toxic materials for prolonged periods, our results indicate that a significant reduction in embryo viability may occur due to this exposure.

Hantavirus pulmonary syndrome: Report of the first Canadian paediatric case.

Hantavirus pulmonary syndrome (HPS) was first recognized as a severe respiratory illness transmitted through rodent excreta in the southwestern United States in 1993. As of November 1997, 175 cases have been reported in the United States. The mortality rate of this disease has been reported to be as high as 52% in the United States, and the majority of the cases (94%) involved adults. Twenty-one cases have been recognized in Canada. This paper describes the first Canadian paediatric case and discusses some of the clinical features of this disease.

Sequential contrast-enhanced MR imaging of the penis.

PURPOSE: To determine the enhancement patterns of the penis at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Sequential contrast material-enhanced MR images of the penis in a flaccid state were obtained in 16 volunteers (12 with normal penile function and four with erectile dysfunction). RESULTS: Subjects with normal erectile function showed gradual and centrifugal enhancement of the corpora cavernosa, while those with erectile dysfunction showed poor enhancement with abnormal progression. CONCLUSION: Sequential contrast-enhanced MR imaging provides additional morphologic information for the evaluation of erectile dysfunction.

Comparative study of mortality and morbidity in premature infants (birth weight, < 1,250 g) with candidemia or candidal meningitis.

Little information is available on long-term neurodevelopment of premature neonates with invasive candidal infections. We retrospectively studied the outcomes for 25 premature neonates (birth weight, < 1,250 g) with candidemia or candidal meningitis (cases) and compared them with 25 neonates matched for birth weight (+/- 100 g) and gestational age (+/- 1 week) (controls). Durations of antibiotic therapy, artificial ventilation, invasive catheterizations, and hyperalimentation were longer for cases than for controls. Cases had a higher final grade of intraventricular hemorrhage than did controls (median: 3.0 vs. 2.5, respectively; P < .05). Forty-four percent (11 of 25) of cases and 16% (4 of 25) of controls died (P > .05), and 29% (4 of 14) of surviving cases and 14% (3 of 21) of controls were disabled (P > .05). More cases had combined mortality and neurodevelopmental disabilities than did controls (60% vs. 28%, respectively; P < .05). Use of invasive therapies should be minimized for premature neonates at risk for invasive candidal infection that is associated with adverse outcomes.

Peritonitis caused by Mycobacterium kansasii in a patient undergoing continuous ambulatory peritoneal dialysis.

Mycobacterium kansasii was isolated from the peritoneal fluid, peritoneal biopsy, and the Tenckhoff catheter of a 62-year-old woman undergoing continuous ambulatory peritoneal dialysis (CAPD) who presented with the clinical picture of peritonitis. To the best of our knowledge, this is the first case of CAPD-associated peritonitis caused by M kansasii. Routine susceptibility tests using standard concentrations of isoniazid indicated isoniazid resistance; however, the organism was inhibited in vitro by a higher concentration of this drug. The patient responded to combination therapy with isoniazid and rifampin, as well as removal of the catheter. This report emphasizes the importance of mycobacterial cultures, in certain circumstances, in patients with CAPD-associated peritonitis and the utility of quantitative in vitro susceptibility testing.