• Lateral gene transfer between prokaryotes and eukaryotes

      Sieber, K.B.; Bromley, R.E.; Hotopp, Julie C.D. (Elsevier Inc., 2017)
      Lateral gene transfer (LGT) is an all-encompassing term for the movement of DNA between diverse organisms. LGT is synonymous with horizontal gene transfer, and the terms are used interchangeably throughout the scientific literature. While LGT has been recognized within the bacteria domain of life for decades, inter-domain LGTs are being increasingly described. LGTs between bacteria and complex multicellular organisms are of interest because they challenge the long-held dogma that such transfers could only occur in closely-related, single-celled organisms. Scientists will continue to challenge our understanding of LGT as we sequence more, diverse organisms, as we sequence more endosymbiont-colonized arthropods, and as we continue to appreciate LGT events, both young and old. Copyright 2017 The Authors
    • The effect of antibiotic exposure and specimen volume on the detection of bacterial pathogens in children with pneumonia

      Driscoll, A.J.; Knoll, M.D.; Hammitt, L.L. (Oxford University Press, 2017)
      Background: Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children. Methods: PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1–59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume. Results: Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%–7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%–0.54%), from 2% when volume was ≤1 mL to approximately 6% for ≥3 mL. Conclusions: Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management. Copyright The Author 2017.
    • Multicenter study of outcomes with ceftazidime-avibactam in patients with carbapenem-resistant Enterobacteriaceae infections

      King, M.; Heil, E.; Kuriakose, S. (American Society for Microbiology, 2017)
      Ceftazidime-avibactam is a novel cephalosporin-beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option. Copyright 2017 American Society for Microbiology. All Rights Reserved.
    • Antimicrobial activity of Lactobacillus salivarius and Lactobacillus fermentum against Staphylococcus aureus

      Kang, M.-S.; Lim, H.-S.; Oh, J.-S. (Oxford University Press, 2017)
      The increasing prevalence of methicillin-resistant Staphylococcus aureus has become a major public health threat. While lactobacilli were recently found useful in combating various pathogens, limited data exist on their therapeutic potential for S. aureus infections. The aim of this study was to determine whether Lactobacillus salivarius was able to produce bactericidal activities against S. aureus and to determine whether the inhibition was due to a generalized reduction in pH or due to secreted Lactobacillus product(s). We found an 8.6-log10 reduction of planktonic and a 6.3-log10 reduction of biofilm S. aureus. In contrast, the previously described anti-staphylococcal effects of L. fermentum only caused a 4.0-log10 reduction in planktonic S. aureus cells, with no effect on biofilm S. aureus cells. Killing of S. aureus was partially pH dependent, but independent of nutrient depletion. Cell-free supernatant that was pH neutralized and heat inactivated or proteinase K treated had significantly reduced killing of L. salivarius than with pH-neutralized supernatant alone. Proteomic analysis of the L. salivarius secretome identified a total of five secreted proteins including a LysM-containing peptidoglycan binding protein and a protein peptidase M23B. These proteins may represent potential novel anti-staphylococcal agents that could be effective against S. aureus biofilms. Copyright Crown 2017.
    • Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

      Bai, M.; Zhu, X.; Zhang, L. (John Wiley and Sons Ltd, 2017)
      Background: The mesocorticolimbic dopamine system, which originates from the ventral tegmental area (VTA) and projects primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy), plays a pivotal role in determining individual motivation and sensitivity to rewards, namely, anhedonia. Not all depressive individuals exhibited anhedonia, thus, it is natural to speculate that the heterogenous manifestations of depression might be related to the mesocorticolimbic dopamine system. Maternal deprivation (MD) and chronic unpredictable stress (CUPS) are two well-established depressogenic stressors, and they were proven to induce different depressive phenotypes. Methods: The depressive and anxiety-like behaviors of MD and CUPS-treated rats were measured by classical behavioral tests including open field, forced swimming, and sucrose preference test. The expression of D1-5 dopamine receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system of rats exposed to MD and CUPS were measured by real-time PCR and Western blot, respectively. Results: Severe anhedonia was observed in MD but not CUPS rats. Divergent expression of D1 and D2 receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system were found between MD and CUPS rats. Significant correlations between different depressive behaviors and D1-/D2-like receptors and DAT protein levels in the mesocorticolimbic dopamine system were observed. Conclusion: Different depressive behaviors of rats such as anhedonia, passive coping behavior, and declined exploratory interest might be related to divergent dopaminergic pathways. Anhedonia is associated with the dysfunction of VTA-NAc and VTA-OT dopaminergic pathways, the passive coping behavior is related to the dysregulation of VTA-PFC and VTA-AMy pathways, and individual exploratory interest is associated with abnormal activity of VTA-PFC and VTA-ST pathways. Copyright 2017 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
    • Departure from Hardy Weinberg Equilibrium and genotyping error

      Chen, B.; Cole, J.W.; Grond-Ginsbach, C. (Frontiers Media S.A., 2017)
      Objective: Departure from Hardy Weinberg Equilibrium (HWE) may occur due to a variety of causes, including purifying selection, inbreeding, population substructure, copy number variation or genotyping error. We searched for specific characteristics of HWE-departure due to genotyping error. Methods: Genotypes of a random set of genetic variants were obtained from the Exome Aggregation Consortium (ExAC) database. Variants with <80% successful genotypes or with minor allele frequency (MAF) <1% were excluded. HWE-departure (d-HWE) was considered significant at p < 10E-05 and classified as d-HWE with loss of heterozygosity (LoH d-HWE) or d-HWE with excess heterozygosity (gain of heterozygosity: GoH d-HWE). Missing genotypes, variant type (single nucleotide polymorphism (SNP) vs. insertion/deletion); MAF, standard deviation (SD) of MAF across populations (MAF-SD) and copy number variation were evaluated for association with HWE-departure. Results: The study sample comprised 3,204 genotype distributions. HWE-departure was observed in 134 variants: LoH d-HWE in 41 (1.3%), GoH d-HWE in 93 (2.9%) variants. LoH d-HWE was more likely in variants located within deletion polymorphisms (p < 0.001) and in variants with higher MAF-SD (p = 0.0077). GoH d-HWE was associated with low genotyping rate, with variants of insertion/deletion type and with high MAF (all at p < 0.001). In a sub-sample of 2,196 variants with genotyping rate >98%, LoH d-HWE was found in 29 (1.3%) variants, but no GoH d-HWE was detected. The findings of the non-random distribution of HWE-violating SNPs along the chromosome, the association with common deletion polymorphisms and indel-variant type, and the finding of excess heterozygotes in genomic regions that are prone to cross-hybridization were confirmed in a large sample of short variants from the 1,000 Genomes Project. Conclusions: We differentiated between two types of HWE-departure. GoH d-HWE was suggestive for genotyping error. LoH d-HWE, on the contrary, pointed to natural variabilities such as population substructure or common deletion polymorphisms. Copyright 2017 Chen, Cole and Grond-Ginsbach.
    • Neurotrophic Factor‐α1: A Key Wnt‐β‐Catenin Dependent Anti‐Proliferation Factor and ERK‐Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment

      Selvaraj, P.; Xiao, L.; Lee, C. (Wiley-Blackwell, 2017)
      Embryonic neurodevelopment involves inhibition of proliferation of multipotent neural stem cells (NSCs) followed by differentiation into neurons, astrocytes and oligodendrocytes to form the brain. We have identified a new neurotrophic factor, NF‐α1, which inhibits proliferation and promotes differentiation of NSC/progenitors derived from E13.5 mouse cortex. Inhibition of proliferation of these cells was mediated through negatively regulating the Wnt pathway and decreasing β‐catenin. NF‐α1 induced differentiation of NSCs to astrocytes by enhancing Glial Fibrillary Acidic Protein (GFAP) expression through activating the ERK1/2‐Sox9 signaling pathway. Cultured E13.5 cortical stem cells from NF‐α1‐knockout mice showed decreased astrocyte numbers compared to wild‐type mice, which was rescued by treatment with NF‐α1. In vivo, immunocytochemistry of brain sections and Western blot analysis of neocortex of mice showed a gradual increase of NF‐α1 expression from E14.5 to P1 and a surge of GFAP expression at P1, the time of increase in astrogenesis. Importantly, NF‐α1‐Knockout mice showed ∼49% fewer GFAP positive astrocytes in the neocortex compared to WT mice at P1. Thus, NF‐α1 is critical for regulating antiproliferation and cell fate determination, through differentiating embryonic stem cells to GFAP‐positive astrocytes for normal neurodevelopment. Stem Cells 2017;35:557–571. Copyright 2016 AlphaMed Press
    • A novel method for extracting nucleic acids from dried blood spots for ultrasensitive detection of low-density Plasmodium falciparum and Plasmodium vivax infections

      Zainabadi, K.; Han, Z.Y.; Adams, Matthew (BioMed Central Ltd., 2017)
      Background: Greater Mekong Subregion countries are committed to eliminating Plasmodium falciparum malaria by 2025. Current elimination interventions target infections at parasite densities that can be detected by standard microscopy or rapid diagnostic tests (RDTs). More sensitive detection methods have been developed to detect lower density “asymptomatic” infections that may represent an important transmission reservoir. These ultrasensitive polymerase chain reaction (usPCR) tests have been used to identify target populations for mass drug administration (MDA). To date, malaria usPCR tests have used either venous or capillary blood sampling, which entails complex sample collection, processing and shipping requirements. An ultrasensitive method performed on standard dried blood spots (DBS) would greatly facilitate the molecular surveillance studies needed for targeting elimination interventions. Methods: A highly sensitive method for detecting Plasmodium falciparum and P. vivax 18S ribosomal RNA from DBS was developed by empirically optimizing nucleic acid extraction conditions. The limit of detection (LoD) was determined using spiked DBS samples that were dried and stored under simulated field conditions. Further, to assess its utility for routine molecular surveillance, two cross-sectional surveys were performed in Myanmar during the wet and dry seasons. Results: The lower LoD of the DBS-based ultrasensitive assay was 20 parasites/mL for DBS collected on Whatman 3MM filter paper and 23 parasites/mL for Whatman 903 Protein Saver cards—equivalent to 1 parasite per 50 µL DBS. This is about 5000-fold more sensitive than standard RDTs and similar to the LoD of ≤16–22 parasites/mL reported for other ultrasensitive methods based on whole blood. In two cross-sectional surveys in Myanmar, nearly identical prevalence estimates were obtained from contemporaneous DBS samples and capillary blood samples collected during the wet and dry season. Conclusions: The DBS-based ultrasensitive method described in this study shows equal sensitivity as previously described methods based on whole blood, both in its limit of detection and prevalence estimates in two field surveys. The reduced cost and complexity of this method will allow for the scale-up of surveillance studies to target MDA and other malaria elimination interventions, and help lead to a better understanding of the epidemiology of low-density malaria infections. Copyright 2017 The Author(s).
    • Femoral artery plaque characteristics, lower extremity collaterals, and mobility loss in peripheral artery disease

      McDermott, M.M.; Carroll, T.; Carr, J. (SAGE Publications Ltd, 2017)
      Little is known about the prognostic significance of specific characteristics of magnetic resonance imaging (MRI) measured plaque in the superficial femoral artery (SFA). Associations of MRI-measured plaque quantity, lumen area, and plaque composition in the SFA with subsequent mobility loss were studied in people with lower extremity peripheral artery disease (PAD). Participants with an ankle–brachial index (ABI) < 1.00 were identified from Chicago medical centers and underwent direct visualization of atherosclerotic plaque in the SFA using MRI. Participants were followed annually for up to 4 years. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or walk one-quarter of a mile without assistance among participants without mobility impairment at baseline. Analyses adjusted for age, sex, race, comorbidities, ABI, physical activity, and other confounders. Of 308 PAD participants without baseline mobility impairment, 100 (32.5%) developed mobility loss during follow-up. Compared to the lowest mean plaque area tertile at baseline, participants in the highest (worst) plaque area tertile had a higher rate of mobility loss (hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.14–3.79, p = 0.018). Compared to the highest mean lumen area tertile, the smallest (worst) mean lumen area tertile was associated with greater mobility loss (HR = 2.18, 95% CI = 1.20–3.96, p = 0.011). Neither lipid rich necrotic core nor calcium in the SFA were associated with mobility loss. In conclusion, greater plaque quantity and smaller lumen area in the proximal SFA, but not lipid rich necrotic core or calcium, were associated with higher mobility loss in people with PAD. Copyright The Author(s) 2017.
    • Pathology of human coronary and carotid artery atherosclerosis and vascular calcification in diabetes mellitus

      Yahagi, K.; Kolodgie, F.D.; Lutter, C. (Lippincott Williams and Wilkins, 2017)
      The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. Copyright 2016 American Heart Association, Inc.
    • Electrophysiological evidence for hyperfocusing of spatial attention in schizophrenia

      Kreither, J.; Lopez-Calderon, J.; Leonard, C.J. (Society for Neuroscience, 2017)
      A recently proposed hyperfocusing hypothesis of cognitive dysfunction in schizophrenia proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more narrowly but more intensely than healthy control subjects (HCS). The present study tests a key prediction of this hypothesis, namely, that PSZ will hyperfocus on information presented at the center of gaze. This should lead to greater filtering of peripheral stimuli when the task requires focusing centrally but reduced filtering of central stimuli when the task requires attending broadly in the periphery. These predictions were tested in a double oddball paradigm, in which frequent standard stimuli and rare oddball stimuli were presented at central and peripheral locations while event-related potentials were recorded. Participants were instructed to discriminate between the standard and oddball stimuli at either the central location or at the peripheral locations. PSZ and HCS showed opposite patterns of spatial bias at the level of early sensory processing, as assessed with the P1 component: PSZ exhibited stronger sensory suppression of peripheral stimuli when the task required attending narrowly to the central location, whereas HCS exhibited stronger sensory suppression of central stimuli when the task required attending broadly to the peripheral locations. Moreover, PSZ exhibited a stronger stimulus categorization response than HCS, as assessed with the P3b component, for central stimuli when the task required attending to the peripheral region. These results provide strong evidence of hyperfocusing in PSZ, which may provide a unified mechanistic account of multiple aspects of cognitive dysfunction in schizophrenia. Copyright 2017 the authors.
    • The contributing risk of tobacco use for ARDS development in burn-injured adults with inhalation injury

      Afshar, M.; Netzer, G.; Mosier, M.J. (American Association for Respiratory Care, 2017)
      BACKGROUND: This study aims to determine the relationship between tobacco use, inhalation injury, and ARDS in burn-injured adults. METHODS: This study was an observational cohort of 2,485 primary burn admissions to a referral burn center between January 1, 2008 and March 15, 2015. Subjects were evaluated by methods used to account for mediation and traditional approaches (multivariable logistic regression and propensity score analysis). Mediation analysis examined both the (1) indirect effect of tobacco use via inhalation injury as the mediator on ARDS development and (2) the direct effect of tobacco use alone on ARDS development. RESULTS: ARDS development occurred in 6.8% (n = 170) of the cohort. Inhalation injury occurred in 5.0% (n = 125) of the cohort, and ARDS developed in 48.8% (n = 83) of the subjects with inhalation injury. Tobacco use was 2-fold more common in subjects with ARDS. In the mediated model, the direct effect of tobacco use on ARDS, including interaction between tobacco use and inhalation injury, was not significant (odds ratio [OR] 1.63, 95% CI 0.91-2.92, P =.10). However, the indirect effect of tobacco use via inhalation injury as the mediator was significant (OR 1.61, 95% CI 1.25-2.07, P <.001), and the proportion of the total effect of tobacco use operating through the mediator was 55.6%. In the non-mediation models (multivariable logistic regression and propensity score analysis), which controlled for inhalation injury and other covariables, the OR for the association between tobacco use and ARDS was 1.84 (95% CI 1.22-2.81, P <.001) and 1.69 (95% CI 1.04-2.75, P =.03), respectively. CONCLUSIONS: In mediation analysis, inhalation injury was the overwhelming predictor for ARDS development, whereas tobacco use has its strongest effect indirectly through inhalation injury. Patients with at least moderate inhalation injury are at greatest risk for ARDS development despite baseline risk factors like tobacco use. Copyright 2017 by Daedalus Enterprises.
    • Chaperone-usher pili loci of colonization factor-negative human enterotoxigenic Escherichia coli

      Del Canto, Felipe; O'Ryan, Miguel; Pardo, Mirka (Frontiers Media S.A., 2017)
      Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea worldwide. Among the 25 different ETEC adhesins, 22 are known as "colonization factors" (CFs), of which 17 are assembled by the chaperone-usher (CU) mechanism. Currently, there is no preventive therapy against ETEC, and CFs have been proposed as components for vaccine development. However, studies of diarrhea-causing ETEC strains worldwide indicate that between 15 and 50% of these are negative for known CFs, hindering the selection of the most widespread structures and suggesting that unknown adhesins remain to be identified. Here, we report the result of a comprehensive analysis of 35 draft genomes of ETEC strains which do not carry known adhesin genes; our goal was to find new CU pili loci. The phylogenetic profiles and serogroups of these strains were highly diverse, a majority of which produced only the heat-labile toxin. We identified 10 pili loci belonging to CU families ? (1 locus), ? 2 (7 loci), ? (1 locus), and p (1 locus), all of which contained the required number of open reading frames (ORFs) to encode functional structures. Three loci were variants of previously-known clusters, three had been only-partially described, and four are novel loci. Intra-loci genetic variability identified would allow the synthesis of up to 14 different structures. Clusters of putative ? 2 -CU pili were most common (23 strains), followed by putative ?-CU pili (12 strains), which have not yet been fully characterized. Overall, our findings significantly increase the number of ETEC adhesion genes associated with human infections. Copyright 2017 The Authors
    • A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Type and Timing of Anticoagulant Thromboprophylaxis

      Fehlings, M.G.; Tetreault, L.A.; Aarabi, B. (SAGE Publications Ltd, 2017)
      Introduction: The objective of this study is to develop evidence-based guidelines that recommend effective, safe and cost-effective thromboprophylaxis strategies in patients with spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions relating to thromboprophylaxis in SCI. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.” Results: Based on conclusions from the systematic review and expert panel opinion, the following recommendations were developed: (1) “We suggest that anticoagulant thromboprophylaxis be offered routinely to reduce the risk of thromboembolic events in the acute period after SCI;” (2) “We suggest that anticoagulant thromboprophylaxis, consisting of either subcutaneous low-molecular-weight heparin or fixed, low-dose unfractionated heparin (UFH) be offered to reduce the risk of thromboembolic events in the acute period after SCI. Given the potential for increased bleeding events with the use of adjusted-dose UFH, we suggest against this option;” (3) “We suggest commencing anticoagulant thromboprophylaxis within the first 72 hours after injury, if possible, in order to minimize the risk of venous thromboembolic complications during the period of acute hospitalization.” Conclusions: These guidelines should be implemented into clinical practice in patients with SCI to promote standardization of care, decrease heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions. Copyright The Author(s) 2017.
    • Feasibility of CBCT-based dose with a patient-specific stepwise HU-to-density curve to determine time of replanning

      Chen, S.; Le, Q.; Mutaf, Y. (John Wiley and Sons Ltd, 2017)
      Purpose: (a) To investigate the accuracy of cone‐beam computed tomography (CBCT)–derived dose distributions relative to fanbeam–based simulation CT‐derived dose distributions; and (b) to study the feasibility of CBCT dosimetry for guiding the appropriateness of replanning. Methods and materials: Image data corresponding to 40 patients (10 head and neck [HN], 10 lung, 10 pancreas, 10 pelvis) who underwent radiation therapy were randomly selected. Each patient had both intensity‐modulated radiation therapy and volumetric‐modulated arc therapy plans; these 80 plans were subsequently recomputed on the CBCT images using a patient‐specific stepwise curve (Hounsfield units‐to‐density). Planning target volumes (PTVs; D98%, D95%, D2%), mean dose, and V95% were compared between simulation‐CT–derived treatment plans and CBCT‐based plans. Gamma analyses were performed using criterion of 3%/3 mm for three dose zones (>90%, 70%~90%, and 30%~70% of maximum dose). CBCT‐derived doses were then used to evaluate the appropriateness of replanning decisions in 12 additional HN patients whose plans were previously revised during radiation therapy because of anatomic changes; replanning in these cases was guided by the conventional observed source‐to‐skin‐distance change‐derived approach. Results: For all disease sites, the difference in PTV mean dose was 0.1% ± 1.1%, D2% was 0.7% ± 0.1%, D95% was 0.2% ± 1.1%, D98% was 0.2% ± 1.0%, and V95% was 0.3% ± 0.8%; For 3D dose comparison, 99.0% ± 1.9%, 97.6% ± 4.4%, and 95.3% ± 6.0% of points passed the 3%/3 mm criterion of gamma analysis in high‐, medium‐, and low‐dose zones, respectively. The CBCT images achieved comparable dose distributions. In the 12 previously replanned 12 HN patients, CBCT‐based dose predicted well changes in PTV D2% (Pearson linear correlation coefficient = 0.93; P < 0.001). If 3% of change is used as the replanning criteria, 7/12 patients could avoid replanning. Conclusions: CBCT‐based dose calculations produced accuracy comparable to that of simulation CT. CBCT‐based dosimetry can guide the decision to replan during the course of treatment. Copyright 2017 American Association of Physicists in Medicine.
    • A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Use of Methylprednisolone Sodium Succinate

      Fehlings, M.G.; Wilson, J.R.; Tetreault, L.A. (SAGE Publications Ltd, 2017)
      Introduction: The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.” Results: The main conclusions from the systematic review included the following: (1) there were no differences in motor score change at any time point in patients treated with MPSS compared to those not receiving steroids; (2) when MPSS was administered within 8 hours of injury, pooled results at 6- and 12-months indicated modest improvements in mean motor scores in the MPSS group compared with the control group; and (3) there was no statistical difference between treatment groups in the risk of complications. Our recommendations were: (1) “We suggest not offering a 24-hour infusion of high-dose MPSS to adult patients who present after 8 hours with acute SCI”; (2) “We suggest a 24-hour infusion of high-dose MPSS be offered to adult patients within 8 hours of acute SCI as a treatment option”; and (3) “We suggest not offering a 48-hour infusion of high-dose MPSS to adult patients with acute SCI.” Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in SCI patients. Copyright The Author(s) 2017.
    • A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Type and Timing of Rehabilitation

      Fehlings, M.G.; Tetreault, L.A.; Aarabi, B. (SAGE Publications Ltd, 2017)
      Introduction: The objective of this study is to develop guidelines that outline the appropriate type and timing of rehabilitation in patients with acute spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to rehabilitation in patients with acute SCI. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the type and timing of rehabilitation. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest. Results: Based on the findings from the systematic review, our recommendations were: (1) We suggest rehabilitation be offered to patients with acute spinal cord injury when they are medically stable and can tolerate required rehabilitation intensity (no included studies; expert opinion); (2) We suggest body weight–supported treadmill training as an option for ambulation training in addition to conventional overground walking, dependent on resource availability, context, and local expertise (low evidence); (3) We suggest that individuals with acute and subacute cervical SCI be offered functional electrical stimulation as an option to improve hand and upper extremity function (low evidence); and (4) Based on the absence of any clear benefit, we suggest not offering additional training in unsupported sitting beyond what is currently incorporated in standard rehabilitation (low evidence). Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care, decreasing the heterogeneity of management strategies and encouraging clinicians to make evidence-informed decisions. Copyright The Author(s) 2017.
    • Role of attitudes and intentions in predicting adherence to oral diabetes medications

      Fai, E.K.; Anderson, C.; Ferreros, V. (BioScientifica Ltd., 2017)
      The purpose of this quantitative study was to investigate the extent to which patient attitudes and intentions predict adherence to the use of oral antihyperglycemic regimens in African Americans. This cross-sectional study of 115 participants used correlation analysis to establish relationships among patient attitudes, intentions and adherence. Data analyses showed significant correlations between the variables. Multiple regression analysis was used to establish predictions between the variables. A prediction model containing attitudes, subjective norms and perceived behavioral control (PBC) explained 37% of the variance to behavioral intention. Intentions accounted for 8.5% of the variance to adherence. Attitudes predicted behavioral intentions. The findings support the theory of planned behavior model and identify important correlations between attitudes, intentions and behaviors. In addition, the results underscore the need for promoting positive attitudes and positive intentions in effective adherence to the use of oral antihyperglycemic regimens. Achieving adequate adherence through behavioral counseling can effect positive social change by reducing the mortality and morbidity that are associated with inadequate adherence to the use of oral diabetic agents. Copyright 2017 The authors Published by Bioscientifica Ltd.
    • Dissection of additive, dominance, and imprinting effects for production and reproduction traits in Holstein cattle

      Jiang, J.; Shen, B.; O'Connell, J.R. (BioMed Central Ltd., 2017)
      Background: Although genome-wide association and genomic selection studies have primarily focused on additive effects, dominance and imprinting effects play an important role in mammalian biology and development. The degree to which these non-additive genetic effects contribute to phenotypic variation and whether QTL acting in a non-additive manner can be detected in genetic association studies remain controversial. Results: To empirically answer these questions, we analyzed a large cattle dataset that consisted of 42,701 genotyped Holstein cows with genotyped parents and phenotypic records for eight production and reproduction traits. SNP genotypes were phased in pedigree to determine the parent-of-origin of alleles, and a three-component GREML was applied to obtain variance decomposition for additive, dominance, and imprinting effects. The results showed a significant non-zero contribution from dominance to production traits but not to reproduction traits. Imprinting effects significantly contributed to both production and reproduction traits. Interestingly, imprinting effects contributed more to reproduction traits than to production traits. Using GWAS and imputation-based fine-mapping analyses, we identified and validated a dominance association signal with milk yield near RUNX2, a candidate gene that has been associated with milk production in mice. When adding non-additive effects into the prediction models, however, we observed little or no increase in prediction accuracy for the eight traits analyzed. Conclusions: Collectively, our results suggested that non-additive effects contributed a non-negligible amount (more for reproduction traits) to the total genetic variance of complex traits in cattle, and detection of QTLs with non-additive effect is possible in GWAS using a large dataset. Copyright 2017 The Author(s).