In-fiber Mach-Zehnder interferometer based on hollow optic fiber for metal ion detection.

A new, to the best of our knowledge, in-fiber Mach-Zehnder interferometric sensor is proposed and experimentally demonstrated for detecting Cu2+ ions in an aqueous environment. The sensor is fabricated simply and cost-effectively by arc-fusing a short section of hollow optical fiber between two standard single-mode fibers and is functionalized by depositing chitosan and poly(acrylic acid) bilayers using electrostatic self-assembly. The proposed sensor shows a linear response with sensitivity of 42 nm/mM in the Cu2+ ion concentration from 0 to 40 µM. Moreover, the fiber sensor exhibits good reusability and repeatability and is a promising candidate for contamination detection in drinking water and industrial waste water.

Alcohol Selective Optical Sensor Based on Porous Cholesteric Liquid Crystal Polymer Networks.

A responsive hydrogen-bonded cholesteric liquid crystal polymer (CLCP) film with controlled porosity was fabricated as an optical sensor to distinguish between methanol and ethanol in alcohol solutions. To facilitate responding the alcohols, porosity was generated by removing the nonreactive liquid crystal agent, and the hydrogen bridges of CLCP were broken. The sensitivities of CLCPs to ethanol and methanol were obtained by monitoring the wavelength shifts of the transmission spectrum at different alcohol concentrations and ratios of methanol/ethanol. Changes in the central wavelength of the CLCP network transmission spectrum allowed the methanol-ethanol ratio to be discriminated. A linear relationship between wavelength shift of CLCP networks and alcohol concentration was obtained experimentally, and the sensor characteristics were explored. The sensitivities of the CLCPs were 1.35 and 0.18 nm/% to ethanol and methanol, respectively. The sensing sensitivity of cholesteric networks to alcohol molecules increased as the methanol-ethanol ratio declined. Therefore, CLCP could act as a stimuli-responsive material to distinguish the concentrations of acetone and ethanol in mixed solutions. Furthermore, the impact of UV intensity for curing a CLC mixture on the sensing sensitivity to the different alcohol concentrations was also studied. The higher UV intensity could enhance the sensitivity to alcohol molecules and distinguishing ability between methanol and ethanol.

Conditional knockout of the PDK-1 gene in osteoblasts affects osteoblast differentiation and bone formation.

Osteoblasts are the main functional cells of bone formation, and they are responsible for the synthesis, secretion, and mineralization of the bone matrix. Phosphatidylinositol-3-kinase/Akt is an important signaling pathway involved in the regulation of cell proliferation, death, and survival. Some studies have shown that 3-phosphoinositide-dependent protein kinase-1 (PDK-1) plays an important role in the phosphorylation of Akt. In the present study, an osteocalcin (OCN) promoter-driven Cre-LoxP system was established to specifically delete the PDK-1 gene in osteoblasts. It was found that the size and weight of PDK-1 conditional gene knockout (cKO) mice were significantly reduced. von Kossa staining and microcomputed tomography showed that the trabecular thickness, trabecular number, and bone volume were significantly decreased, whereas trabecular separation was increased, as compared with wide-type littermates, which were characterized by a decreased bone mass. A model of distal femoral defect was established, and it was found that cKO mice delayed bone defect repair. In osteoblasts derived from PDK-1 cKO mice, the alkaline phosphatase (ALP) secretion and ability of calcium mineralization were significantly decreased, and the expressions of osteoblast-related proteins, runt-related transcription factor 2, OCN, and ALP were also clearly decreased. Moreover, the phosphorylation level of Akt and downstream factor GSK3ß and their response to insulin-like growth factor-1 (IGF-1) decreased clearly. Therefore, we believe that PDK-1 plays a very important role in osteoblast differentiation and bone formation by regulating the PDK-1/Akt/GSK3ß signaling pathway.

Provincial Door-to-Needle Improvement Initiative Results in Improved Patient Outcomes Across an Entire Population.

BACKGROUND AND PURPOSE: Improving door-to-needle times (DNTs) for thrombolysis of acute ischemic stroke patients improves outcomes, but participation in DNT improvement initiatives has been mostly limited to larger, academic medical centers with an existing interest in stroke quality improvement. It is not known whether quality improvement initiatives can improve DNT at a population level, including smaller community hospitals. This study aims to determine the effect of a provincial improvement collaborative intervention on improvement of DNT and patient outcomes. METHODS: A pre post cohort study was conducted over 10 years in the Canadian province of Alberta with 17 designated stroke centers. All ischemic stroke patients who received thrombolysis in the Canadian province of Alberta were included in the study. The quality improvement intervention was an improvement collaborative that involved creation of interdisciplinary teams from each stroke center, participation in 3 workshops and closing celebration, site visits, webinars, and data audit and feedback. RESULTS: Two thousand four hundred eighty-eight ischemic stroke patients received thrombolysis in the pre- and postintervention periods (630 in the post period). The mean age was 71 years (SD, 14.6 years), and 46% were women. DNTs were reduced from a median of 70.0 minutes (interquartile range, 51-93) to 39.0 minutes (interquartile range, 27-58) for patients treated per guideline (P<0.0001). The percentage of patients discharged home from acute care increased from 45.6% to 59.5% (P<0.0001); the median 90-day home time increased from 43.3 days (interquartile range, 27.3-55.8) to 53.6 days (interquartile range, 36.8-64.6) (P=0.0015); and the in-hospital mortality decreased from 14.5% to 10.5% (P=0.0990). CONCLUSIONS: The improvement collaborative was likely the key contributing factor in reducing DNTs and improving outcomes for ischemic stroke patients across Alberta.

Fob1 and Fob2 Proteins Are Virulence Determinants of Rhizopus oryzae via Facilitating Iron Uptake from Ferrioxamine.

Dialysis patients with chronic renal failure receiving deferoxamine for treating iron overload are uniquely predisposed for mucormycosis, which is most often caused by Rhizopus oryzae. Although the deferoxamine siderophore is not secreted by Mucorales, previous studies established that Rhizopus species utilize iron from ferrioxamine (iron-rich form of deferoxamine). Here we determined that the CBS domain proteins of Fob1 and Fob2 act as receptors on the cell surface of R. oryzae during iron uptake from ferrioxamine. Fob1 and Fob2 cell surface expression was induced in the presence of ferrioxamine and bound radiolabeled ferrioxamine. A R. oryzae strain with targeted reduced Fob1/Fob2 expression was impaired for iron uptake, germinating, and growing on medium with ferrioxamine as the sole source of iron. This strain also exhibited reduced virulence in a deferoxamine-treated, but not the diabetic ketoacidotic (DKA), mouse model of mucormycosis. The mechanism by which R. oryzae obtains iron from ferrioxamine involves the reductase/permease uptake system since the growth on ferrioxamine supplemented medium is associated with elevated reductase activity and the use of the ferrous chelator bathophenanthroline disulfonate abrogates iron uptake and growth on medium supplemented with ferrioxamine as a sole source of iron. Finally, R. oryzae mutants with reduced copies of the high affinity iron permease (FTR1) or with decreased FTR1 expression had an impaired iron uptake from ferrioxamine in vitro and reduced virulence in the deferoxamine-treated mouse model of mucormycosis. These two receptors appear to be conserved in Mucorales, and can be the subject of future novel therapy to maintain the use of deferoxamine for treating iron-overload.

Evaluation of a spirituality informed e-mental health tool as an intervention for major depressive disorder in adolescents and young adults - a randomized controlled pilot trial.

BACKGROUND: Depression in adolescents and young adults is a major mental health condition that requires attention. Research suggests that approaches that include spiritual concepts and are delivered through an online platform are a potentially beneficial approach to treating/managing depression in this population. The purpose of this study was to evaluate the effectiveness of an 8-week online spirituality informed e-mental health intervention (the LEAP Project) on depression severity, and secondary outcomes of spiritual well-being and self-concept, in adolescents and young adults with major depressive disorder of mild to moderate severity. METHODS: A parallel group, randomized, waitlist controlled, assessor-blinded clinical pilot trial was conducted in Calgary, Alberta, Canada. The sample of 62 participants with major depressive disorder (DSM-IV-TR) was defined by two age subgroups: adolescents (ages 13 to 18 years; n = 31) and young adults (ages 19 to 24 years; n = 31). Participants in each age subgroup were randomized into the study arm (intervention initiated upon enrolment) or the waitlist control arm (intervention initiated after an 8-week wait period). Comparisons were made between the study and waitlist control arms at week 8 (the point where study arm had completed the intervention and the waitlist control arm had not) and within each arm at four time points over 24-week follow-up period. RESULTS: At baseline, there was no statistical difference between study and waitlist participants for both age subgroups for all three outcomes of interest. After the intervention, depression severity was significantly reduced; comparison across arms at week 8 and over time within each arm and both age subgroups. Spiritual well-being changes were not significant, with the exception of an improvement over time for the younger participants in the study arm (p = 0.01 at week 16 and p = 0.0305 at week 24). Self-concept improved significantly for younger participants immediately after the intervention (p = 0.045 comparison across arms at week 8; p = 0.0175 in the waitlist control arm) and over time in the study arm (p = 0.0025 at week 16). In the older participants, change was minimal, with the exception of a significant improvement in one of six factors (vulnerability) in study arm over time (p = 0.025 at week 24). CONCLUSIONS: The results of the LEAP Project pilot trial suggest that it is an effective, online intervention for youth ages 13 to 24 with mild to moderate major depressive disorder with various life situations and in a limited way on spiritual well-being and self-concept. TRIAL REGISTRATION: ClinicalTrials.gov NCT00985686. Registered 24 September 2009.

Integration, stability and expression of the E. coli phytase transgene in the Cassie line of Yorkshire Enviropig™.

The genomic structure and generational stability of the transgene carried by the Cassie (CA) line of the transgenic Enviropig™, a prospective food animal, are reported here. This transgene is composed of the Escherichia coli phytase coding sequence regulated by the mouse parotid secretory protein promoter to direct secretion of phytase in the saliva. In the CA line the transgene integrated in chromosome 4 is present as a concatemer of three copies, two in a head to tail orientation and the third in a reverse orientation 3' to the other copies with a 6 kbp deletion in the 5' promoter region. The overall size of the integrated transgene complex is 46 kbp. During integration a 66 kbp segment of the chromosome was deleted, but a BLAST search of the segment from a GenBank clone did not reveal any essential genes. The transgene integration site was stable through 9 generations analyzed. Phytase activity in the saliva was similar among 11 day old hemizygous boars and gilts and remained relatively constant through nine generations of hemizygous pigs. However, as the pigs grew there generally was a gradual decrease in activity that stabilized when pigs reached the finisher phase of growth (4-6 months old). Homozygous pigs exhibited 1.5 fold higher phytase activity (P < 0.0001) than that of hemizygous littermates. Moreover, no differential salivary phytase activity was seen in hemizygotes arising from CA-Yorkshire and CA-Duroc breed outcrosses, suggesting that expression of the transgene is unaffected by genetic background. This data demonstrates that an exogenous phytase gene can be stably transmitted and expressed in the salivary glands of a domestic food animal.

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells. / çŸ­é“¾è„‚è‚ªé ¸é€šè¿‡è°ƒèŠ‚è°ƒèŠ‚æ€§T细胞和IL-17+ γδ T细胞的平衡来改善脊髓损伤的恢复.

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)|-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.

Conditional knockout of PDK1 in osteoclasts suppressed osteoclastogenesis and ameliorated prostate cancer-induced osteolysis in murine model.

BACKGROUND: The development and maintenance of normal bone tissue is maintained by balanced communication between osteoblasts and osteoclasts. The invasion of cancer cells disrupts this balance, leading to osteolysis. As the only bone resorbing cells in vivo, osteoclasts play important roles in cancer-induced osteolysis. However, the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in osteoclast resorption remains unclear. METHODS: In our study, we used a receptor activator of nuclear factor-kappa B (RANK) promoter-driven Cre-LoxP system to conditionally delete the PDK1 gene in osteoclasts in mice. We observed the effect of osteoclast-specific knockout of PDK1 on prostate cancer-induced osteolysis. Bone marrow-derived macrophage cells (BMMs) were extracted and induced to differentiate osteoclasts in vitro to explore the role of PDK1 in osteoclasts. RESULTS: In this study, we found that PDK1 conditional knockout (cKO) mice exhibited smaller body sizes when compared to the wild-type (WT) mice. Moreover, deletion of PDK1 in osteoclasts ameliorated osteolysis and rPDK1educed bone resorption markers in the murine model of prostate cancer-induced osteolysis. In vivo, we discovered that osteoclast-specific knockout of suppressed RANKL-induced osteoclastogenesis, bone resorption function, and osteoclast-specific gene expression (Ctsk, TRAP, MMP-9, NFATc1). Western blot analyses of RANKL-induced signaling pathways showed that conditional knockout of PDK1 in osteoclasts inhibited the early nuclear factor κB (NF-κB) activation, which consequently suppressed the downstream induction of NFATc1. CONCLUSION: These findings demonstrated that PDK1 performs an important role in osteoclastogenesis and prostate cancer-induced osteolysis by modulating the PDK1/AKT/NF-κB signaling pathway.

Total flavonoids of hawthorn leaves protect spinal motor neurons via promotion of autophagy after spinal cord injury.

The death of spinal motor neurons (SMNs) after spinal cord injury (SCI) is a crucial cause, contributing to a permanent neurological deficit. Total flavonoids of hawthorn leaves (TFHL) have been confirmed to have potentially therapeutic for SCI. Nonetheless, the roles and mechanisms of TFHL in recovering neuromotor function and regenerating axons of SMNs have not been fully elucidated. In this study, TFHL was applied to treat rats with SCI and injured SMNs for 7 days. In vivo experiment, rats with SCI were evaluated by a BBB (Basso-Beattie-Bresnahan) score to assess their motor functional recovery. The morphology, microstructure, apoptosis, Nissl bodies, and autophagy of SMNs in spinal cord tissue were detected by Hematoxylin-eosin (HE) staining, transmission electron microscopy, TUNEL staining, Nissl staining, and immunohistochemistry respectively. In vitro experiment, the co-culture model of SMNs and astrocytes was constructed to simulate the internal environment around SMNs in the spinal cord tissue. The cell morphology, microstructure, axonal regeneration, and autophagy were observed via optical microscope, transmission electron microscopy, and immunofluorescence. The content of neurotrophic factors in the cell culture medium of the co-culture model was detected by ELISA. Moreover, the expression of axon-related and autophagy-related proteins in the spinal cord tissue and SMNs was measured by Western Blot. We demonstrated that TFHL improved the neuromotor function recovery in rats after SCI. We then found that TFHL significantly promoted injured spinal cord tissue repair, reduced apoptosis, and improved the functional status of neurons in spinal cord tissue in vivo. Meanwhile, the cell morphology, microstructure, and axonal regeneration of damaged SMNs also obviously were improved, and the secretion of neurotrophic factors was facilitated after treatment with TFHL in vitro. Further, we revealed that TFHL promoted autophagy and related protein expression in vivo and vitro. Taken together, our study suggested that TFHL might facilitate autophagy and have neuroprotective properties in SMNs to enhance the recovery of neuromotor function of rats with SCI.

Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle Arrest, and Apoptosis.

Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro. Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis. Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice. Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.

Development of an epilepsy-specific risk adjustment comorbidity index.

PURPOSE: To develop an epilepsy-specific comorbidity risk adjustment index for mortality outcomes research. METHODS: Data were extracted from five linked administrative databases in Calgary, Canada from April 1, 1996 to March 31, 2004. Epilepsy patients were defined using a validated ICD-9-CM- and ICD-10-CA-based case definition. An epilepsy-specific comorbidity index was developed using comorbidities from the Charlson and Elixhauser indexes and other relevant epilepsy comorbidities. In the final model, 14 comorbidities significantly associated with mortality remained and each was assigned a value of 1-6 based on the hazard ratio from the survival analysis. Total prognostic scores were calculated and compared for all subjects using the epilepsy-specific index and the Charlson index. Crude mortality and survival curves of both indices were compared. KEY FINDINGS: We identified 7,253 subjects who met our case definition for epilepsy. The mean age of participants was 38 years (range 0.03-96), and 52% were male. The mortality rate was 7.9%. High rates of chronic pulmonary disease (20.3%), hypertension (19.6%), cerebrovascular disease (13.7%), fracture (12.1%), depression (28.2%), and alcohol abuse (10.1%) were noted. Patients with lower total prognostic scores were more likely to survive than patients with higher scores, using both indices. However, increasing prognostic scores were more strongly associated with reduced survival using the epilepsy-specific index compared to the Charlson index. SIGNIFICANCE: A new comorbidity index for epilepsy, designed to include clinically relevant conditions, provided better discrimination of crude mortality in a population-based group of epilepsy patients compared with the Charlson index.

Effects of inhibiting PDK­1 expression in bone marrow mesenchymal stem cells on osteoblast differentiation in vitro.

Osteoblasts are the main functional cells in bone formation, which are responsible for the synthesis, secretion and mineralization of bone matrix. The PI3K/AKT signaling pathway is strongly associated with the differentiation and survival of osteoblasts. The 3­phosphoinositide­dependent protein kinase­1 (PDK­1) protein is considered the master upstream lipid kinase of the PI3K/AKT cascade. The present study aimed to investigate the role of PDK­1 in the process of mouse osteoblast differentiation in vitro. In the BX­912 group, BX­912, a specific inhibitor of PDK­1, was added to osteoblast induction medium (OBM) to treat bone marrow mesenchymal stem cells (BMSCs), whereas the control group was treated with OBM alone. Homozygote PDK1flox/flox mice were designed and generated, and were used to obtain BMSCsPDK1flox/flox. Subsequently, an adenovirus containing Cre recombinase enzyme (pHBAd­cre­EGFP) was used to disrupt the PDK­1 gene in BMSCsPDK1flox/flox; this served as the pHBAd­cre­EGFP group and the efficiency of the disruption was verified. Western blot analysis demonstrated that the protein expression levels of phosphorylated (p)­PDK1 and p­AKT were gradually increased during the osteoblast differentiation process. Notably, BX­912 treatment and disruption of the PDK­1 gene with pHBAd­cre­EGFP effectively reduced the number of alkaline phosphatase (ALP)­positive cells and the optical density value of ALP activity, as well as the formation of cell mineralization. The mRNA expression levels of PDK­1 in the pHBAd­cre­EGFP group were significantly downregulated compared with those in the empty vector virus group on days 3­7. The mRNA expression levels of the osteoblast­related genes RUNX2, osteocalcin and collagen I were significantly decreased in the BX­912 and pHBAd­cre­EGFP groups on days 7 and 21 compared with those in the control and empty vector virus groups. Overall, the results indicated that BX­912 and disruption of the PDK­1 gene in vitro significantly inhibited the differentiation and maturation of osteoblasts. These experimental results provided an experimental and theoretical basis for the role of PDK­1 in osteoblasts.

The incidence of injuries in persons with and without epilepsy--a population-based study.

PURPOSE: To compare the 1-year population-based incidence and types of injuries in persons with and without epilepsy. METHODS: Three administrative databases (inpatient visits, physician claims, and emergency room visits) were linked from fiscal years 1996-2003 using a provincial insurance plan registry, which captures 99% of a population of 1.4 million in a large Canadian health region. Epilepsy cases (all age groups) from fiscal year 1996-2002 were identified. Three people without epilepsy were matched to one person with epilepsy for age (±1 year) and sex. Injuries were defined as any of 16 types of injuries for which medical attention was sought that occurred within fiscal year 2003. RESULTS: Eight thousand eight hundred ninety subjects with epilepsy were identified and matched to 26,670 controls for age and sex. The mean age was 37.4 years (range 0.01-96.4 years), and 51.3% of subjects were male. The 1-year incidence of one or more injuries was 20.6% among persons with epilepsy and 16.1% among those without epilepsy (p < 0.001). Of the 16 types of injuries studied, 11 were higher in persons with epilepsy compared to those without epilepsy, and included fractures, crushing injuries, intracranial injuries, other types of head injuries, and multiple injuries. The difference was still significant after adjusting for age, gender, and comorbidities. DISCUSSION: The 1-year incidence of injuries in this study was greater in persons with epilepsy compared to those without epilepsy, for nearly all injury types. Injury prevention should be discussed during routine visits in persons with epilepsy.

The burden of hepatitis C virus infection is growing: a Canadian population-based study of hospitalizations from 1994 to 2004.

BACKGROUND: Nearly 1% of Canadians are infected with the hepatitis C virus (HCV). Simulation analyses have suggested that HCV will place an increasing burden on the health care system as the infected population ages, but supportive clinical data are limited. OBJECTIVES: To study temporal trends in HCV-related hospitalizations and predictors of increased health care utilization from a Canadian population-based perspective. METHODS: An administrative hospitalization database from the Calgary Health Region was used to identify patients who were admitted for HCV between 1994 and 2004. The primary outcomes were liver-related HCV hospitalizations, length of stay, hospital costs and in-hospital mortality. Average annual growth rates in outcomes were calculated and subgroup analyses were conducted according to age, sex and HIV/HCV coinfection status. RESULTS: Between 1994 and 2004, there were 4002 HCV-related hospitalizations; 22% were liver-related. Liver-related hospitalizations, lengths of stay and in-hospital mortality increased approximately fourfold or an average of 15% to 18% annually (P<0.0005). Patients aged 40 to 59 years and HIV/HCV coinfected patients experienced the largest average annual growth rates (19% to 27% and 30% to 40%, respectively; P<0.0005), reflecting the accelerated natural history of HCV in these subgroups. Hospital costs for liver-related HCV hospitalizations increased by an average of 41% annually (P=0.001) between 2000 and 2004. The average annual increase in liver-related hospitalizations remained significant in a sensitivity analysis, even when 75% of HCV cases were under-reported in 1994. CONCLUSIONS: The present studies' findings confirm the growing burden of HCV on the Canadian health care system. Strategies to prevent HCV infection and maximize the dissemination and most effective use of potentially curative antiviral therapies are necessary to reduce these trends.

Effect of dual-acupoint and single-acupoint electric stimulation on postoperative outcomes in elderly patients subjected to gastrointestinal surgery: study protocol for a randomized controlled trial.

BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) has shown benefits when used peri-operatively. However, the role of numbers of areas with acupoint stimulation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using TEAS in elderly patients subjected to gastrointestinal surgery, and comparing dual-acupoint and single-acupoint stimulation. METHODS/DESIGN: A multicenter, randomized, controlled, three-arm design, large-scale trial is currently undergoing in four hospitals in China. Three hundred and forty-five participants are randomly assigned to three groups in a 1:1:1 ratio, receiving dual-acupoint TEAS, single-acupoint TEAS, and no stimulation, respectively. The primary outcome is incidence of pulmonary complications at 30 days after surgery. The secondary outcomes include the incidence of pulmonary complications at 3 days after surgery; the all-cause mortality within 30 days and 1 year after surgery; admission to the intensive care unit (ICU) and length of ICU stay within 30 days after surgery; the length of postoperative hospital stay; and medical costs during hospitalization after surgery. DISCUSSION: The result of this trial (which will be available in September 2019) will confirm whether TEAS before and during anesthesia could alleviate the postoperative pulmonary complications after gastrointestinal surgery in elderly patients, and whether dual-acupoint stimulation is more effective than single-acupoint stimulation. TRIALS REGISTRATIONS: ClinicalTrials.gov, ID: NCT03230045 . Registered on 10 July 2017.

A home study-based spirituality education program decreases emotional distress and increases quality of life--a randomized, controlled trial.

CONTEXT: Although epidemiological studies have reported protective effects of religion and spirituality on mental health, it is unknown whether spirituality can be used as an intervention to improve psychological well-being. OBJECTIVE: To evaluate the efficacy of a home study-based spirituality program on mood disturbance in emotionally distressed patients. DESIGN, SETTING, AND PARTICIPANTS: A non-blinded, randomized, wait list-controlled trial of 165 individuals with mood disturbance [score of >40 on the Profile of Mood States (POMS)] were recruited from primary care clinics in a Canadian city between August 2000 and March 2001. INTERVENTIONS: Participants were randomized to a spirituality group (an 8-week audiotaped spirituality home-study program), a mindfulness meditation-based stress reduction group (attendance at facilitated classes for 8 weeks), or a wait-list control group (no intervention for 12 weeks). MAIN OUTCOME MEASURES: Primary outcomes were mood disturbance, measured using POMS, and quality of life, measured using the SF-36, a short-form health survey with 36 questions. The POMS and the SF-36 were completed at baseline, at 8 weeks, and at 12 weeks. RESULTS: At the end of the 8-week intervention period, the mean POMS score improvement was -43.1 (-45.7%) for the spirituality group, -22.6 (-26.3%) for the meditation group, and -10.3 (11.3%) for the control group (P<.001 for spirituality vs control group; P=.034 for spirituality vs meditation group). Mean improvement in the SF-36 mental component summary score was 14.4 (48.6%) for the spirituality group, 7.1 (22.3%) for the meditation group, and 4.7 (16.1%) for the control group (P<.001 for spirituality vs control group; P=.029 for spirituality vs meditation group). At 12 weeks, POMS and SF-36 scores remained significantly different from baseline for the spirituality group.

A validated case definition for chronic rhinosinusitis in administrative data: a Canadian perspective.

BACKGROUND: Pharmacoepidemiological research using administrative databases has become increasingly popular for chronic rhinosinusitis (CRS); however, without a validated case definition the cohort evaluated may be inaccurate resulting in biased and incorrect outcomes. The objective of this study was to develop and validate a generalizable administrative database case definition for CRS using International Classification of Diseases, 9th edition (ICD-9)-coded claims. METHODS: A random sample of 100 patients with a guideline-based diagnosis of CRS and 100 control patients were selected and then linked to a Canadian physician claims database from March 31, 2010, to March 31, 2015. The proportion of CRS ICD-9-coded claims (473.x and 471.x) for each of these 200 patients were reviewed and the validity of 7 different ICD-9-based coding algorithms was evaluated. RESULTS: The CRS case definition of ≥2 claims with a CRS ICD-9 code (471.x or 473.x) within 2 years of the reference case provides a balanced validity with a sensitivity of 77% and specificity of 79%. Applying this CRS case definition to the claims database produced a CRS cohort of 51,000 patients with characteristics that were consistent with published demographics and rates of comorbid asthma, allergic rhinitis, and depression. CONCLUSION: This study has validated several coding algorithms; based on the results a case definition of ≥2 physician claims of CRS (ICD-9 of 471.x or 473.x) within 2 years provides an optimal level of validity. Future studies will need to validate this administrative case definition from different health system perspectives and using larger retrospective chart reviews from multiple providers.

Utilization Patterns of Topical Intranasal Steroid Therapy for Chronic Rhinosinusitis: A Canadian Population-Based Analysis.

Importance: Practice guidelines have provided a strong recommendation for the daily use of topical intranasal steroid therapy for patients with chronic rhinosinusitis (CRS). Deficiencies in utilization of intranasal steroid therapy may represent a gap in quality of care. Objective: To evaluate the utilization patterns of topical intranasal steroid therapy for CRS in the Canadian population. Design, Setting, and Participants: Retrospective review of a Canadian population-based health care administrative database. A validated case definition for CRS was applied, and the utilization of topical intranasal steroid therapy within this cohort was quantified during the 2014-2015 fiscal year. Interventions: Intranasal steroid spray for CRS. Main Outcomes and Measures: Primary outcome was the rate (per 100 patients) and quantity (per patient) of intranasal steroid spray utilization in patients with CRS. Secondary outcome was the geographic variation in the rate and quantity of intranasal steroid spray utilization for CRS. Results: A total of 19 057 adult patients with CRS were evaluated. The overall rate of intranasal steroid spray utilization was 20.1 per 100 patients with CRS (3821 of 19 057). In the 3821 patients with CRS who used an intranasal steroid spray during 2014 to 2015, the mean quantity of utilization was 2.4 U (1 U = 1 bottle per month) per patient (9314 U divided by 3821 patients with CRS). There was large geographic variation in both the rate and quantity of intranasal steroid spray utilization (P < .001 for both comparisons). Conclusions and Relevance: Topical intranasal steroid therapy continues to be underutilized for patients with CRS. Given the negative impact of low-quality medical care, outcomes from this study indicate a need to further evaluate factors leading to the underutilization of a recommended treatment in patients with CRS to improve overall health system performance.

Bicarbonate correction of ketoacidosis alters host-pathogen interactions and alleviates mucormycosis.

Patients with diabetic ketoacidosis (DKA) are uniquely predisposed to mucormycosis, an angioinvasive fungal infection with high mortality. Previously, we demonstrated that Rhizopus invades the endothelium via binding of fungal CotH proteins to the host receptor GRP78. Here, we report that surface expression of GRP78 is increased in endothelial cells exposed to physiological concentrations of ß-hydroxy butyrate (BHB), glucose, and iron that are similar to those found in DKA patients. Additionally, expression of R. oryzae CotH was increased within hours of incubation with DKA-associated concentrations of BHB, glucose, and iron, augmenting the ability of R. oryzae to invade and subsequently damage endothelial cells in vitro. BHB exposure also increased fungal growth and attenuated R. oryzae neutrophil-mediated damage. Further, mice given BHB developed clinical acidosis and became extremely susceptible to mucormycosis, but not aspergillosis, while sodium bicarbonate reversed this susceptibility. BHB-related acidosis exerted a direct effect on both GRP78 and CotH expression, an effect not seen with lactic acidosis. However, BHB also indirectly compromised the ability of transferrin to chelate iron, as iron chelation combined with sodium bicarbonate completely protected endothelial cells from Rhizopus-mediated invasion and damage. Our results dissect the pathogenesis of mucormycosis during ketoacidosis and reinforce the importance of careful metabolic control of the acidosis to prevent and manage this infection.