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The article discusses a study which identified the predominance of T-lymphocyte in lesions of canine coccidiodomycosis. The researchers used immunohistochemistry for CD3 and CD79a to examine archived formalin-fixed, paraffin-embedded tissues from infected dogs to further characterize the lymphocytic infiltration. Results show the T-cell and B-cell scores with distribution of populations observed in sections from the sample tissues. Findings revealed the lesional density of T-lymphocytes.

Context: Recent reports suggest an increasing occurrence and severity of Clostridium difficile-associated disease. We assessed whether the use of gastric acid-suppressive agents is associated with an increased risk in the community.Objective: To determine whether the use of gastric acid-suppressive agents increases the risk of C difficile-associated disease in a community population.Design, Setting, and Patients: We conducted 2 population-based case-control studies using the United Kingdom General Practice Research Database (GPRD). In the first study, we identified all 1672 cases of C difficile recorded between 1994 and 2004 among all patients registered for at least 2 years in each practice. Each case was matched to 10 controls on calendar time and the general practice. In the second study, a subset of these cases defined as community-acquired, that is, not hospitalized in the prior year, were matched on practice and age with controls also not hospitalized in the prior year.Main Outcome Measures: The incidence of C difficile and risk associated with gastric acid-suppressive agent use.Results: The incidence of C difficile in patients diagnosed by their general practitioners in the General Practice Research Database increased from less than 1 case per 100,000 in 1994 to 22 per 100,000 in 2004. The adjusted rate ratio of C difficile-associated disease with current use of proton pump inhibitors was 2.9 (95% confidence interval [CI], 2.4-3.4) and with H2-receptor antagonists the rate ratio was 2.0 (95% CI, 1.6-2.7). An elevated rate was also found with the use of nonsteroidal anti-inflammatory drugs (rate ratio, 1.3; 95% CI, 1.2-1.5).Conclusions: The use of acid-suppressive therapy, particularly proton pump inhibitors, is associated with an increased risk of community-acquired C difficile. The unexpected increase in risk with nonsteroidal anti-inflammatory drug use should be investigated further. [ABSTRACT FROM AUTHOR]

Rationale: After the introduction of autotransfusion of shed mediastinal blood following cardiac surgery, the incidence of mediastinitis increased. The role of autotransfusion in the increased occurrence of this serious complication was examined.Methods: Using a case-control design, the preoperative, intraoperative, and postoperative characteristics of 11 patients with mediastinitis were compared to those of 33 randomly selected patients undergoing cardiac surgery between September 1, 2000, and April 15, 2001 (control subjects).Results: Patients with mediastinitis were significantly more likely to have a body mass index > 30 (unadjusted odds ratio [OR], 9.9; 95% confidence interval [CI], 2.3 to 42.5), to have received antibiotic therapy during the 2 weeks prior to cardiac surgery (OR, 12.0; 95% CI, 1.1 to 131), or to have required re-exploration within 24 h of the original operation (OR, 8.3; 95% CI, 1.8 to 39). Patients with mediastinitis had 3.4 known risk factors for mediastinitis, compared to only 1.4 risk factors per control subject (p = 0.0001), and longer duration of autotransfusion. After adjustment for other risk factors, autotransfusion for > 6 h was significantly associated with the development of mediastinitis (adjusted OR, 11.9; 95% CI, 1.4 to 97.2).Conclusion: Retransfusion of shed mediastinal blood for > 6 h after cardiac surgery was an independent risk factor for mediastinitis. [ABSTRACT FROM AUTHOR]

Objectives: (1) To establish risk factors for the development of delirium in an intensive care unit (ICU) and (2) to determine the effect of delirium on morbidity, mortality and length of stay.Design: Prospective study.Setting: Sixteen-bed medical/surgical ICU in a university hospital.Patients: Two hundred and sixteen consecutive patients admitted to the ICU for more than 24 h during 5 months were included in the study.Interventions: Medical history, selected laboratory values, drugs received and factors that may influence patient psychological and emotional well-being were noted. All patients were screened with a delirium scale. A psychiatrist confirmed the diagnosis of delirium. Major complications such as self-extubation and removal of catheters, as well as mortality and length of stay were recorded.Results: Forty patients (19%) developed delirium; of these, one-third were not agitated. In the multivariate analysis hypertension, smoking history, abnormal bilirubin level, epidural use and morphine were statistically significantly associated with delirium. Traditional factors associated with the development of delirium on general ward patients were not significant in our study. Morbidity (self-extubation and removal of catheters), but not mortality, was clearly increased.Conclusion: Predictive risk factors for the development of delirium in studies outside the ICU may not be applicable to critically ill patients. Delirium is associated with increased morbidity. Awareness of patients at risk may lead to better recognition and earlier intervention. [ABSTRACT FROM AUTHOR]

Abstract Background Comfrey (Symphytum officinale) is a perennial plant and has been consumed by humans as a vegetable, a tea and an herbal medicine for more than 2000 years. It, however, is hepatotoxic and carcinogenic in experimental animals and hepatotoxic in humans. Pyrrolizidine alkaloids (PAs) exist in many plants and many of them cause liver toxicity and/or cancer in humans and experimental animals. In our previous study, we found that the mutagenicity of comfrey was associated with the PAs contained in the plant. Therefore, we suggest that carcinogenicity of comfrey result from those PAs. To confirm our hypothesis, we compared the expression of genes and processes of biological functions that were altered by comfrey (mixture of the plant with PAs) and riddelliine (a prototype of carcinogenic PA) in rat liver for carcinogenesis in this study. Results Groups of 6 Big Blue Fisher 344 rats were treated with riddelliine at 1 mg/kg body weight by gavage five times a week for 12 weeks or fed a diet containing 8% comfrey root for 12 weeks. Animals were sacrificed one day after the last treatment and the livers were isolated for gene expression analysis. The gene expressions were investigated using Applied Biosystems Rat Whole Genome Survey Microarrays and the biological functions were analyzed with Ingenuity Analysis Pathway software. Although there were large differences between the significant genes and between the biological processes that were altered by comfrey and riddelliine, there were a number of common genes and function processes that were related to carcinogenesis. There was a strong correlation between the two treatments for fold-change alterations in expression of drug metabolizing and cancer-related genes. Conclusion Our results suggest that the carcinogenesis-related gene expression patterns resulting from the treatments of comfrey and riddelliine are very similar, and PAs contained in comfrey are the main active components responsible for carcinogenicity of the plant.

Abstract Background Comfrey is consumed by humans as a vegetable and a tea, and has been used as an herbal medicine for more than 2000 years. Comfrey, however, is hepatotoxic in livestock and humans and carcinogenic in experimental animals. Our previous study suggested that comfrey induces liver tumors by a genotoxic mechanism and that the pyrrolizidine alkaloids in the plant are responsible for mutation induction and tumor initiation in rat liver. Results In this study, we identified comfrey-induced gene expression profile in the livers of rats. Groups of 6 male transgenic Big Blue rats were fed a basal diet and a diet containing 8% comfrey roots, a dose that resulted in liver tumors in a previous carcinogenicity bioassay. The animals were treated for 12 weeks and sacrificed one day after the final treatment. We used a rat microarray containing 26,857 genes to perform genome-wide gene expression studies. Dietary comfrey resulted in marked changes in liver gene expression, as well as in significant decreases in the body weight and increases in liver mutant frequency. When a two-fold cutoff value and a P-value less than 0.01 were selected, 2,726 genes were identified as differentially expressed in comfrey-fed rats compared to control animals. Among these genes, there were 1,617 genes associated by Ingenuity Pathway Analysis with particular functions, and the differentially expressed genes in comfrey-fed rat livers were involved in metabolism, injury of endothelial cells, and liver injury and abnormalities, including liver fibrosis and cancer development. Conclusion The gene expression profile provides us a better understanding of underlying mechanisms for comfrey-induced hepatic toxicity. Integration of gene expression changes with known pathological changes can be used to formulate a mechanistic scheme for comfrey-induced liver toxicity and tumorigenesis.

Abstract Background Gender differences in gene expression were estimated in liver samples from 9 males and 9 females. The study tested 31,110 genes for a gender difference using a design that adjusted for sources of variation associated with cDNA arrays, normalization, hybridizations and processing conditions. Results The genes were split into 2,800 that were clearly expressed (expressed genes) and 28,310 that had expression levels in the background range (not expressed genes). The distribution of p-values from the 'not expressed' group was consistent with no gender differences. The distribution of p-values from the 'expressed' group suggested that 8 % of these genes differed by gender, but the estimated fold-changes (expression in males / expression in females) were small. The largest observed fold-change was 1.55. The 95 % confidence bounds on the estimated fold-changes were less than 1.4 fold for 79.3 %, and few (1.1%) exceed 2-fold. Conclusion Observed gender differences in gene expression were small. When selecting genes with gender differences based upon their p-values, false discovery rates exceed 80 % for any set of genes, essentially making it impossible to identify any specific genes with a gender difference.

Abstract Background Dysregulated expression of microRNAs (miRNAs) has been previously observed in human cancer tissues and shown promise in defining tumor status. However, there is little information as to if or when expression changes of miRNAs occur in normal tissues after carcinogen exposure. Results To explore the possible time-course changes of miRNA expression induced by a carcinogen, we treated mice with one dose of 120 mg/kg N-ethyl-N-nitrosourea (ENU), a model genotoxic carcinogen, and vehicle control. The miRNA expression profiles were assessed in the mouse livers in a time-course design. miRNAs were isolated from the livers at days 1, 3, 7, 15, 30 and 120 after the treatment and their expression was determined using a miRNA PCR Array. Principal component analysis of the miRNA expression profiles showed that miRNA expression at post-treatment days (PTDs) 7 and 15 were different from those at the other time points and the control. The number of differentially expressed miRNAs (DEMs) changed over time (3, 5, 14, 32, 5 and 5 at PTDs 1, 3, 7, 15, 30 and 120, respectively). The magnitude of the expression change varied with time with the highest changes at PTDs 7 or 15 for most of the DEMs. In silico functional analysis of the DEMs at PTDs 7 and 15 indicated that the major functions of these ENU-induced DEMs were associated with DNA damage, DNA repair, apoptosis and other processes related to carcinogenesis. Conclusion Our results showed that many miRNAs changed their expression to respond the exposure of the genotoxic carcinogen ENU and the number and magnitude of the changes were highest at PTDs 7 to 15. Thus, one to two weeks after the exposure is the best time for miRNA expression sampling.

Abstract Background The MicroArray Quality Control (MAQC) project evaluated the inter- and intra-platform reproducibility of seven microarray platforms and three quantitative gene expression assays in profiling the expression of two commercially available Reference RNA samples (Nat Biotechnol 24:1115-22, 2006). The tested microarrays were the platforms from Affymetrix, Agilent Technologies, Applied Biosystems, GE Healthcare, Illumina, Eppendorf and the National Cancer Institute, and quantitative gene expression assays included TaqMan® Gene Expression PCR Assay, Standardized (Sta) RT-PCR™ and QuantiGene®. The data showed great consistency in gene expression measurements across different microarray platforms, different technologies and test sites. However, SYBR® Green real-time PCR, another common technique utilized by half of all real-time PCR users for gene expression measurement, was not addressed in the MAQC study. In the present study, we compared the performance of SYBR Green PCR with TaqMan PCR, microarrays and other quantitative technologies using the same two Reference RNA samples as the MAQC project. We assessed SYBR Green real-time PCR using commercially available RT2 Profiler™ PCR Arrays from SuperArray, containing primer pairs that have been experimentally validated to ensure gene-specificity and high amplification efficiency. Results The SYBR Green PCR Arrays exhibit good reproducibility among different users, PCR instruments and test sites. In addition, the SYBR Green PCR Arrays have the highest concordance with TaqMan PCR, and a high level of concordance with other quantitative methods and microarrays that were evaluated in this study in terms of fold-change correlation and overlap of lists of differentially expressed genes. Conclusion These data demonstrate that SYBR Green real-time PCR delivers highly comparable results in gene expression measurement with TaqMan PCR and other high-density microarrays.

The aim of this experiment was to localize the mRNA and protein of ghrelin and its active receptor, growth hormone secretagogue 1A (GHS-R1A), within the reproductive tract of dairy cattle. Ghrelin is an orexigenic hormone that has been identified as a potent regulator of energy homeostasis. Recent evidence suggests that ghrelin may also serve as a metabolic signal to the reproductive tract. Ghrelin and GHS-R1A have been identified in the reproductive tract of several species, including humans, mice, and rats. However, ghrelin and GHS-R1A expression have not been described within bovine reproductive tissues. Therefore, the ampulla, isthmus, uterine body, corpus luteum, and follicles were harvested from 3 Holstein heifers (15.91 ± 0.07 mo of age) immediately following exsanguination. Duodenum and hypothalamus were collected as positive controls for ghrelin and GHS-R1A, respectively. Tissues were fixed in 10% formalin and embedded in paraffin for microscopy. Additional samples were stored at -80°C for detection of mRNA. Ghrelin and GHS-R1A mRNA and protein were observed in all tissue types within the reproductive tract of dairy heifers; however, expression appeared to be cell specific. Furthermore, ghrelin protein appeared to be localized to the cytoplasm, whereas GHS-R1A protein was found on the plasma membrane. Within the reproductive tissues, ghrelin mRNA and protein were most abundantly expressed in the ampulla of the oviduct. Concentrations of GHS-R1A were lower than those of ghrelin but differed between tissues. This is one of the first studies to provide molecular evidence for the presence of ghrelin and GHS-R1A within the entire reproductive tract. However, implications for fertility remain to be determined. [ABSTRACT FROM AUTHOR]

Accurate analysis of microplastic particles (MPs) in environmental samples requires removal of interferences during sample preparation. Wastewater samples are interference-rich and thus particularly challenging, with concentrated sulfuric acid currently deemed impractical as a reagent. Therefore, this study aimed to establish a straightforward, effective, and safe method employing concentrated sulfuric acid and potassium hydroxide to eliminate interferents from effluent samples obtained from wastewater treatment plants (WWTPs). We found that 80 % sulfuric acid at room temperature with a brief contact time of 5 min was viable through a qualitative spot test involving 37 plastics categorized into three types (I, II, and III) based on their polymer structure's oxygen position. A quantitative assessment revealed that treatments involving H 2 SO 4 and KOH (20 %, 24 h, 48 °C), either separately or in combination, had no discernible physical impact on the overall plastics, except for a subtle one for Type III plastics (e.g., nylon and PMMA) known to be labile under harsh pH conditions. This acid/alkaline digestion (AAD) method, incorporating such conditions for H 2 SO 4 and KOH treatments, yielded a high mass removal efficacy (97.8 ± 2.4 %, n = 13) for eliminating natural particle interferents for primary, secondary, and tertiary effluent samples. Furthermore, the AAD method allowed for the determination of MPs in effluents with high surrogate particle recoveries (e.g., 95.1 % for larger than 500 μm size fraction). This method is readily adaptable to create appropriate protocols for different types of environmental matrices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Purpose: With uncertain prognostic utility of existing predictive scoring systems for COVID-19-related illness, the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) 4C Mortality Score was developed by the International Severe Acute Respiratory and Emerging Infection Consortium as a COVID-19 mortality prediction tool. We sought to externally validate this score among critically ill patients admitted to an intensive care unit (ICU) with COVID-19 and compare its discrimination characteristics to that of the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores., Methods: We enrolled all consecutive patients admitted with COVID-19-associated respiratory failure between 5 March 2020 and 5 March 2022 to our university-affiliated and intensivist-staffed ICU (Jewish General Hospital, Montreal, QC, Canada). After data abstraction, our primary outcome of in-hospital mortality was evaluated with an objective of determining the discriminative properties of the ISARIC 4C Mortality Score, using the area under the curve of a logistic regression model., Results: A total of 429 patients were included, 102 (23.8%) of whom died in hospital. The receiver operator curve of the ISARIC 4C Mortality Score had an area under the curve of 0.762 (95% confidence interval [CI], 0.717 to 0.811), whereas those of the SOFA and APACHE II scores were 0.705 (95% CI, 0.648 to 0.761) and 0.722 (95% CI, 0.667 to 0.777), respectively., Conclusions: The ISARIC 4C Mortality Score is a tool that had a good predictive performance for in-hospital mortality in a cohort of patients with COVID-19 admitted to an ICU for respiratory failure. Our results suggest a good external validity of the 4C score when applied to a more severely ill population., (© 2023. Canadian Anesthesiologists' Society.)

Purpose: The optimal noninvasive modality for oxygenation support in COVID-19-associated hypoxemic respiratory failure and its association with healthcare worker infection remain uncertain. We report here our experience using high-flow nasal oxygen (HFNO) as the primary support mode for patients with COVID-19 in our institution., Methods: We conducted a single-centre historical cohort study of all COVID-19 patients treated with HFNO for at least two hours in our university-affiliated and intensivist-staffed intensive care unit (Jewish General Hospital, Montreal, QC, Canada) between 27 August 2020 and 30 April 2021. We report their clinical characteristics and outcomes. Healthcare workers in our unit cared for these patients in single negative pressure rooms wearing KN95 or fit-tested N95 masks; they underwent mandatory symptomatic screening for COVID-19 infection, as well as a period of asymptomatic screening., Results: One hundred and forty-two patients were analysed, with a median [interquartile range (IQR)] age of 66 [59-73] yr; 71% were male. Patients had a median [IQR] Sequential Organ Failure Assessment Score of 3 [2-3], median [IQR] oxygen saturation by pulse oximetry/fraction of inspired oxygen ratio of 120 [94-164], and a median [IQR] 4C score (a COVID-19-specific mortality score) of 12 [10-14]. Endotracheal intubation occurred in 48/142 (34%) patients, and overall hospital mortality was 16%. Barotrauma occurred in 21/142 (15%) patients. Among 27 symptomatic and 139 asymptomatic screening tests, there were no cases of HFNO-related COVID-19 transmission to healthcare workers., Conclusion: Our experience indicates that HFNO is an effective first-line therapy for hypoxemic respiratory failure in COVID-19 patients, and can be safely used without significant discernable infection risk to healthcare workers., (© 2022. Canadian Anesthesiologists' Society.)

A domestic cat was presented for lethargy and coughing. Thoracic radiographs identified a mass within the right cranial lung lobe and a nodule in the left cranial lung lobe. Cryptococcus spp. was diagnosed via ultrasound-guided fine needle aspirate cytology. Despite fluconazole and prednisolone treatment, clinical signs progressed and suggested airway obstruction. Computed tomography revealed mass invasion into the trachea and other areas of the lower airway resulting in obstruction. Bronchoscopy was performed to debulk the tracheal mass and obtain biopsies. Histopathology confirmed Cryptococcus spp. At the time of this report, the patient remained clinically stable with daily itraconazole (5 mg/kg) treatment., (© 2019 American College of Veterinary Radiology.)

BACKGROUND Internal hernias involve protrusion of the small bowel through a peritoneal or mesenteric space in the abdominal or pelvic cavity. Congenital internal small bowel hernias are rare and patients with them usually present with small bowel obstruction (SBO) at a young age, whereas in older patients, internal small bowel hernias usually are acquired secondary to previous surgery. The present report is of a rare case of SBO due to dual congenital internal small bowel hernias in a 51-year-old man with no history of abdominal surgery. CASE REPORT We report a case of dual congenital internal hernias of the small bowel in a patient who presented with symptoms and signs of SBO. He had no history of abdominal trauma, surgery, or comorbid conditions. His abdomen was mildly distended with minimal tenderness in the upper left quadrant but there was no guarding or rebound tenderness. Abdominal X-rays confirmed the SBO. A contrast-enhanced computed tomography scan of the patient's abdomen revealed SBO with transition at 2 points, suggestive of a closed-loop obstruction. However, the exact cause of the SBO was confirmed at laparotomy, which revealed dual internal hernias (intramesosigmoid and paraduodenal). The hernias were managed individually and the patient had a successful outcome after surgery. CONCLUSIONS Although the present report is of a rare presentation of internal small bowel hernia, the case underscores that patients with this condition may present with SBO. Successful surgical management requires knowledge of the intra-abdominal peritoneal spaces and management of the hernia sac.

Background: The coronavirus disease 2019 (COVID-19) pandemic is responsible for millions of infections worldwide, and a substantial number of these patients will be admitted to the intensive care unit (ICU). Our objective was to describe the characteristics, outcomes and management of critically ill patients with COVID-19 pneumonia at a single designated pandemic centre in Montréal, Canada., Methods: A descriptive analysis was performed on consecutive critically ill patients with COVID-19 pneumonia admitted to the ICU at the Jewish General Hospital, a designated pandemic centre in Montréal, between Mar. 5 and May 21, 2020. Complete follow-up data corresponding to death or discharge from hospital health records were included to Aug. 4, 2020. We summarized baseline characteristics, management and outcomes, including mortality., Results: A total of 106 patients were included in this study. Twenty-one patients (19.8%) died during their hospital stay, and the ICU mortality was 17.0% (18/106); all patients were discharged home or died, except for 4 patients (2 awaiting a rehabilitation bed and 2 awaiting long-term care). Twelve of 65 patients (18.5%) requiring mechanical ventilation died. Prone positioning was used in 29 patients (27.4%), including in 10 patients who were spontaneously breathing; no patient was placed on extracorporeal membrane oxygenation. High-flow nasal cannula was used in 51 patients (48.1%). Acute kidney injury was the most common complication, seen in 20 patients (18.9%), and 12 patients (11.3%) required renal replacement therapy. A total of 53 patients (50.0%) received corticosteroids., Interpretation: Our cohort of critically ill patients with COVID-19 had lower mortality than that previously described in other jurisdictions. These findings may help guide critical care decision-making in similar health care systems in further COVID-19 surges., Competing Interests: Competing interests: Paul Warshawsky reports personal fees from Gilead Sciences Canada, outside the submitted work. No other competing interests were declared., (Copyright 2020, Joule Inc. or its licensors.)

Objective: To compare nurse preparedness and quality of patient handoff during interfacility transfers from a pretransfer emergency department to a PICU when conducted over telemedicine versus telephone., Design: Cross-sectional nurse survey linked with patient electronic medical record data using multivariable, multilevel analysis., Setting: Tertiary PICU within an academic children's hospital., Participants: PICU nurses who received a patient handoff between October 2017 and July 2018., Interventions: None., Main Results and Measurements: Among 239 eligible transfers, 106 surveys were completed by 55 nurses (44% survey response rate). Telemedicine was used for 30 handoffs (28%), and telephone was used for 76 handoffs (72%). Patients were comparable with respect to age, sex, race, primary spoken language, and insurance, but handoffs conducted over telemedicine involved patients with higher illness severity as measured by the Pediatric Risk of Mortality III score (4.4 vs 1.9; p = 0.05). After adjusting for Pediatric Risk of Mortality III score, survey recall time, and residual clustering by nurse, receiving nurses reported higher preparedness (measured on a five-point adjectival scale) following telemedicine handoffs compared with telephone handoffs (3.4 vs 3.1; p = 0.02). There were no statistically significant differences in both bivariable and multivariable analyses of handoff quality as measured by the Handoff Clinical Evaluation Exercise. Handoffs using telemedicine were associated with increased number of Illness severity, Patient summary, Action list, Situation awareness and contingency planning, Synthesis by receiver components (3.3 vs 2.8; p = 0.04), but this difference was not significant in the adjusted analysis (3.1 vs 2.9; p = 0.55)., Conclusions: Telemedicine is feasible for nurse-to-nurse handoffs of critically ill patients between pretransfer and receiving facilities and may be associated with increased perceived and objective nurse preparedness upon patient arrival. Additional research is needed to demonstrate that telemedicine during nurse handoffs improves communication, decreases preventable adverse events, and impacts family and provider satisfaction.

Primary hypoplasia of the portal vein with secondary portal hypertension and acquired portosystemic collateral circulation is infrequently reported in the veterinary literature. Diagnosis of this condition requires documentation of abnormal hepatocellular function, the lack of intrahepatic or extrahepatic macroscopic congenital portosystemic shunts, and liver histopathology demonstrating portal hypoperfusion in the absence of hepatic inflammation or nodular regeneration. Due to a perceived poor prognosis, many patients with this condition are euthanized; however, those that are spared can be medically managed, in some cases for years. This case report describes the diagnosis and management of a patient with primary hypoplasia of the portal vein and secondary portal hypertension that presented with the severe but typical clinical manifestations of ascites and hepatic encephalopathy, normal liver enzyme concentrations, and normal serum bile acid concentrations.