Producer attitudes regarding antimicrobial use and resistance in Canadian cow-calf herds.

Objective: To describe producer attitudes toward antimicrobial use (AMU) and antimicrobial resistance (AMR), identify factors associated with attitudes, and inform stewardship initiatives. Animal: Beef cattle, cow-calf. Procedure: Cow-calf producers from the Canadian Cow-Calf Surveillance Network (C3SN) completed a survey (n = 146) on producers' attitudes toward AMU, AMR, and impacts of recent regulatory changes requiring a prescription for the purchase of medically important antimicrobials (MIA). Results: Most producers (78%, 114/146) reported being aware of initiatives to improve antimicrobial stewardship within the beef industry and 67% (97/146) indicated that AMR was a highly important issue to the industry and producers personally. Almost half of producers reported concerns that AMR development has impacted AMU decisions on their operations. Overall, veterinarians were producers' primary source of information regarding AMU, including treatment protocols, stewardship programs, and regulatory changes. Following introduction of the 2018 prescription-only regulations, 95% (138/146) of producers reported no change in AMU on their operations. Similarly, 77% (112/146) of producers reported no change in antimicrobial product access, whereas 63% (91/146) reported no change in cost. Conclusion: Most producers reported little change in access to antimicrobials and in AMU following the introduction of regulations requiring a prescription for MIA. Clinical relevance: Producers rely on veterinarians as their primary source of information regarding antimicrobial regulations and AMU. It is therefore important for veterinarians to understand their role as educators for beef cow-calf producers. Ultimately, veterinarians and producers need to work together to ensure that the health and welfare of animals are protected while using antimicrobials in a responsible manner.

Attitudes des producteurs à l'égard de l'utilisation des antimicrobiens et de la résistance dans les troupeaux vache-veau canadiens. Objectif: Décrire les attitudes des producteurs à l'égard de l'utilisation des antimicrobiens (AMU) et de la résistance aux antimicrobiens (RAM), identifier les facteurs associés à ces attitudes et les informations sur les initiatives de gouvernance. Animal: Bovins de boucherie, vache-veau. Procédure: Les producteurs naisseurs du Réseau canadien de surveillance vache-veau (C3SN) ont répondu à une enquête (n = 146) sur les attitudes des producteurs à l'égard de l'AMU, de la RAM et des impacts des récents changements réglementaires exigeant une ordonnance pour l'achat d'antimicrobiens médicalement importants (MIA). Résultats: La plupart des producteurs (78 %, 114/146) ont déclaré être au courant des initiatives visant à améliorer la gouvernance des antimicrobiens au sein de l'industrie du bœuf et 67 % (97/146) ont indiqué que la RAM était un problème très important pour l'industrie et les producteurs personnellement. Près de la moitié des producteurs ont fait part de leurs inquiétudes quant au fait que le développement de la RAM ait un impact sur les décisions d'AMU sur leurs opérations. Dans l'ensemble, les médecins vétérinaires étaient la principale source d'information des producteurs concernant l'AMU, y compris les protocoles de traitement, les programmes de gouvernance et les changements réglementaires. À la suite de l'introduction de la réglementation sur prescription uniquement en 2018, 95 % (138/146) des producteurs n'ont signalé aucun changement dans l'AMU de leurs opérations. De même, 77 % (112/146) des producteurs n'ont signalé aucun changement dans l'accès aux produits antimicrobiens, tandis que 63 % (91/146) n'ont signalé aucun changement dans le coût. Conclusion: La plupart des producteurs ont signalé peu de changements dans l'accès aux antimicrobiens et dans l'AMU par suite de l'introduction de réglementations exigeant une prescription pour le MIA. Pertinence clinique: Les producteurs comptent sur les médecins vétérinaires comme principale source d'information concernant la réglementation antimicrobienne et l'AMU. Il est donc important que les médecins vétérinaires comprennent leur rôle d'éducateurs auprès des producteurs de vaches-veaux de boucherie. En fin de compte, les médecins vétérinaires et les producteurs doivent travailler ensemble pour garantir la protection de la santé et du bien-être des animaux tout en utilisant les antimicrobiens de manière responsable.(Traduit par Dr Serge Messier).

The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment.

BACKGROUND: Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome. AIM: To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD. METHODS: Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing. RESULTS: Alpha diversity decreased linearly during treatment across the entire cohort (P = 0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella. CONCLUSION: The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.

Aquaculture Reuse Water, Genetic Line, and Vaccination Affect Rainbow Trout (Oncorhynchus mykiss) Disease Susceptibility and Infection Dynamics.

Infectious hematopoietic necrosis virus (IHNV) and Flavobacterium psychrophilum are major pathogens of farmed rainbow trout. Improved control strategies are desired but the influence of on-farm environmental factors that lead to disease outbreaks remain poorly understood. Water reuse is an important environmental factor affecting disease. Prior studies have established a replicated outdoor-tank system capable of varying the exposure to reuse water by controlling water flow from commercial trout production raceways. The goal of this research was to evaluate the effect of constant or pulsed reuse water exposure on survival, pathogen prevalence, and pathogen load. Herein, we compared two commercial lines of rainbow trout, Clear Springs Food (CSF) and Troutex (Tx) that were either vaccinated against IHNV with a DNA vaccine or sham vaccinated. Over a 27-day experimental period in constant reuse water, all fish from both lines and treatments, died while mortality in control fish in spring water was <1%. Water reuse exposure, genetic line, vaccination, and the interaction between genetic line and water exposure affected survival (P<0.05). Compared to all other water sources, fish exposed to constant reuse water had 46- to 710-fold greater risk of death (P<0.0001). Tx fish had a 2.7-fold greater risk of death compared to CSF fish in constant reuse water (P ≤ 0.001), while risk of death did not differ in spring water (P=0.98). Sham-vaccinated fish had 2.1-fold greater risk of death compared to vaccinated fish (P=0.02). Both IHNV prevalence and load were lower in vaccinated fish compared to sham-vaccinated fish, and unexpectedly, F. psychrophilum load associated with fin/gill tissues from live-sampled fish was lower in vaccinated fish compared to sham-vaccinated fish. As a result, up to forty-five percent of unvaccinated fish were naturally co-infected with F. psychrophilum and IHNV and the coinfected fish exhibited the highest IHNV loads. Under laboratory challenge conditions, co-infection with F. psychrophilum and IHNV overwhelmed IHNV vaccine-induced protection. In summary, we demonstrate that exposure to reuse water or multi-pathogen challenge can initiate complex disease dynamics that can overwhelm both vaccination and host genetic resistance.

The oral microbiome of patients undergoing treatment for severe aplastic anemia: a pilot study.

The microbiome, an intriguing component of the human body, composed of trillions of microorganisms, has prompted scientific exploration to identify and understand its function and role in health and disease. As associations between microbiome composition, disease, and symptoms accumulate, the future of medicine hinges upon a comprehensive knowledge of these microorganisms for patient care. The oral microbiome may provide valuable and efficient insight for predicting future changes in disease status, infection, or treatment course. The main aim of this pilot study was to characterize the oral microbiome in patients with severe aplastic anemia (SAA) during their therapeutic course. SAA is a hematologic disease characterized by bone marrow failure which if untreated is fatal. Treatment includes either hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). In this study, we examined the oral microbiome composition of 24 patients admitted to the National Institutes of Health (NIH) Clinical Center for experimental SAA treatment. Tongue brushings were collected to assess the effects of treatment on the oral microbiome. Twenty patients received standard IST (equine antithymocyte globulin and cyclosporine) plus eltrombopag. Four patients underwent HSCT. Oral specimens were obtained at three time points during treatment and clinical follow-up. Using a novel approach to 16S rRNA gene sequence analysis encompassing seven hypervariable regions, results demonstrated a predictable decrease in microbial diversity over time among the transplant patients. Linear discriminant analysis or LefSe reported a total of 14 statistically significant taxa (p < 0.05) across time points in the HSCT patients. One-way plots of relative abundance for two bacterial species (Haemophilus parainfluenzae and Rothia mucilaginosa) in the HSCT group, show the differences in abundance between time points. Only one bacterial species (Prevotella histicola) was noted in the IST group with a p value of 0.065. The patients receiving immunosuppressive therapy did not exhibit a clear change in diversity over time; however, patient-specific changes were noted. In addition, we compared our findings to tongue dorsum samples from healthy participants in the Human Microbiome Project (HMP) database and found among HSCT patients, approximately 35% of bacterial identifiers (N = 229) were unique to this study population and were not present in tongue dorsum specimens obtained from the HMP. Among IST-treated patients, 45% (N = 351) were unique to these patients and not identified by the HMP. Although antibiotic use may have likely influenced bacterial composition and diversity, some literature suggests a decreased impact of antimicrobials on the oral microbiome as compared to their effect on the gut microbiome. Future studies with larger sample sizes that focus on the oral microbiome and the effects of antibiotics in an immunosuppressed patient population may help establish these potential associations.

RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder.

RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.

Evaluation of the internal consistency, factor structure, and validity of the Depression Change Expectancy Scale.

The psychometric properties and predictive validity of the Depression Change Expectancy Scale (DCES), a modification of an expectancy scale originally developed for patients with anxiety disorders, were examined in two studies. In Study 1, the 20-item scale was administered along with a battery of questionnaires to a sample of 416 dysphoric undergraduate students and demonstrated good internal consistency. A two-factor solution most parsimoniously accounted for the variance, with one factor containing all pessimistically worded items (DCES-P) and the second containing all optimistically worded items (DCES-O). The DCES-P showed patterns of correlations with other measures of related constructs consistent with hypothesized relationships; the DCES-O showed similar, but weaker, relationships with the other measures. Multilevel modeling was used to examine the predictive utility of the DCES in a clinical sample of 63 adults (Study 2). Improved depressive symptoms (over 6 weeks) were strongly associated with optimistic expectancies but were unrelated to pessimistic expectancies for change. The DCES appears to be a promising measure of expectancies for improvement among individuals with depressive symptoms.

Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways.

PURPOSE: Neuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson's. The symptoms in Parkinson's including fatigue are thought to be related to α-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT). PATIENTS AND METHODS: Sixteen men with non-metastatic prostate cancer who were scheduled to receive EBRT were enrolled. Fatigue scores and blood were obtained at baseline (prior to EBRT, D0); one hour following initiation of EBRT (D1), day 7 (D7), day 14 (D14), midpoint (days 19-21, D21), completion (days 38-42, D42), and four weeks post-EBRT (days 68-72, D72). Gene expression profiling using microarray analysis was performed from peripheral blood and confirmatory qPCR and protein (ELISA) analyses verified the microarray results. Correlations between fatigue and gene/protein expressions were determined using a mixed model approach. RESULTS: Microarray data showed significant, differential expression of 463 probesets following EBRT. SNCA had a 2.95-fold change at D21 from baseline. SNCA expression was confirmed by qPCR (p<0.001) and ELISA (p<0.001) over time during EBRT. Fatigue scores were significantly correlated with SNCA gene expression on D14 (r=0.55, p<0.05) and plasma α-synuclein concentrations on D42 of EBRT (r=0.54, p=0.04). CONCLUSION: Fatigue experienced during EBRT may be mediated by α-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population.

Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes.

BACKGROUND: Leukotriene B(4) (LTB(4)) and cysteinyl leukotrienes (cysLTs) are important immune mediators, often found concomitantly at sites of inflammation. Although some of the leukotriene-mediated actions are distinctive (e.g., bronchial constriction for cysLTs), many activities such as leukocyte recruitment to tissues and amplification of inflammatory responses are shared by both classes of leukotrienes. OBJECTIVE: We used human monocytes to characterize leukotriene-specific signaling, gene expression signatures, and functions and to identify interactions between LTB(4)- and cysLTs-induced pathways. METHODS: Responsiveness to leukotrienes was assessed using oligonucleotide microarrays, real-time PCR, calcium mobilization, kinase activation, and chemotaxis assays. RESULTS: Human monocytes were found to express mRNA for high- and low-affinity LTB(4) receptors, BLT(1) and BLT(2), but signal predominantly through BLT(1) in response to LTB(4) stimulation as shown using selective agonists, inhibitors, and gene knock down experiments. LTB(4) acting through BLT(1) coupled to G-protein α inhibitory subunit activated calcium signaling, p44/42 mitogen-activated protein kinase, gene expression, and chemotaxis. Twenty-seven genes, including immediate early genes (IEG), transcription factors, cytokines, and membrane receptors were significantly up-regulated by LTB(4). LTB(4) and LTD(4) had similar effects on signaling, gene expression, and chemotaxis indicating redundant cell activation pathways but costimulation with both lipid mediators was additive for many monocyte functions. CONCLUSION: Leukotriene B(4) and LTD(4) display both redundant and cooperative effects on intracellular signaling, gene expression, and chemotaxis in human monocytes. These findings suggest that therapies targeting either leukotriene alone may be less effective than approaches directed at both.

Transcriptome analysis and molecular signature of human retinal pigment epithelium.

Retinal pigment epithelium (RPE) is a polarized cell layer critical for photoreceptor function and survival. The unique physiology and relationship to the photoreceptors make the RPE a critical determinant of human vision. Therefore, we performed a global expression profiling of native and cultured human fetal and adult RPE and determined a set of highly expressed 'signature' genes by comparing the observed RPE gene profiles to the Novartis expression database (SymAtlas: http://wombat.gnf.org/index.html) of 78 tissues. Using stringent selection criteria of at least 10-fold higher expression in three distinct preparations, we identified 154 RPE signature genes, which were validated by qRT-PCR analysis in RPE and in an independent set of 11 tissues. Several of the highly expressed signature genes encode proteins involved in visual cycle, melanogenesis and cell adhesion and Gene ontology analysis enabled the assignment of RPE signature genes to epithelial channels and transporters (ClCN4, BEST1, SLCA20) or matrix remodeling (TIMP3, COL8A2). Fifteen RPE signature genes were associated with known ophthalmic diseases, and 25 others were mapped to regions of disease loci. An evaluation of the RPE signature genes in a recently completed AMD genomewide association (GWA) data set revealed that TIMP3, GRAMD3, PITPNA and CHRNA3 signature genes may have potential roles in AMD pathogenesis and deserve further examination. We propose that RPE signature genes are excellent candidates for retinal diseases and for physiological investigations (e.g. dopachrome tautomerase in melanogenesis). The RPE signature gene set should allow the validation of RPE-like cells derived from human embryonic or induced pluripotent stem cells for cell-based therapies of degenerative retinal diseases.

Expression of aquaporin 8 is diversely regulated by osmotic stress in amnion epithelial cells.

AIM: Water absorption across fetal chorioamniotic membranes is a critical regulatory pathway for amniotic fluid volume homeostasis. Aquaporin 8 (AQP8) is a water channel regulating osmotic water travel across membranes. This study was to investigate the distribution and expression of AQP8 in amnion epithelial cells (AEC) in response to different osmotic stresses. METHODS: Cells derived from the amnion were subjected to different osmotic culture media. Reverse transcriptase-polymerase chain reaction, Western blotting and immunofluorescence analysis were used to determine expression and localization of AQP8. RESULTS: Immunofluorescent staining confirmed the expression of AQP8 on cytomembrane and in cytoplasm. Hypotonic media increased AQP8 on cytomembrane of AEC. Compared to isosmolar media, hypotonic media significantly enhanced AQP8 mRNA and protein expression (P < 0.05), while hypertonic media significantly decreased expression (P < 0.05). CONCLUSION: The expression and distribution of AQP8 in AEC are diversely regulated by osmotic loads suggesting a role for AQP8 in intramembranous water transport and the balance of amniotic fluid.

Bending gender, ending gender: theoretical foundations for social work practice with the transgender community.

Gender is a ubiquitous social construct that wields power over every individual in our society. The traditional dichotomous gender paradigm is oppressive, especially for transgendered people whose sense of themselves as gendered people is incongruent with the gender they were assigned at birth. Transgendered individuals are targeted for mistreatment when others attempt to enforce conventional gender boundaries. This article discusses gender-based oppression and the resulting psychosocial difficulties experienced by many transgendered individuals. The discussion advances a critical analysis of the dominant gender paradigm using two alternative theoretical perspectives on gender--queer theory and social constructionism. The article argues that the transgender community is an at-risk population and that empowering practice with this population calls on social workers to target society's traditional gender dichotomy for change. An overview of practice implications and research needs is provided.

Colposcopically obtained images of vulvar, vaginal, and cervical epithelium for assessment of safety of intravaginal agents among normal adolescent females: comparison with in vivo exam and interobserver agreement.

OBJECTIVES: This study was designed to assess identification of epithelial abnormalities of both in vivo examination as compared with colposcopically obtained images and interobserver assessment of the same images of the lower genital tract in healthy women. MATERIALS AND METHODS: Ninety women between the ages of 14 and 21 years were recruited for a phase II trial of a vaginal Lactobacillus crispatus capsule. All women underwent a baseline and 1-week colposcopic examination. Multiple genital tract areas were evaluated for abnormalities and photographed. The original examiner and two experienced colposcopists reevaluated all images masked to previous interpretations. Agreement was evaluated using kappa statistics. RESULTS: The representative kappa statistics for direct observation vs photographic interpretation for the vulva, vagina, and cervix are: 37%, -2%, and -4%, respectively. The kappa statistics comparing the three observers ranged from 1% to 39%. CONCLUSIONS.: There is poor agreement between in vivo exams and photographic interpretation, and interobserver assessments of lower genital tract photographs.