Biomarkers of Recent Cannabis Use in Blood, Oral Fluid and Breath.

Proving driving under the influence of cannabis (DUIC) is difficult. Establishing a biomarker of recent use to supplement behavioral observations may be a useful alternative strategy. We determined whether cannabinoid concentrations in blood, oral fluid (OF) or breath could identify use within the past 3 h-likely the period of the greatest impairment. In a randomized trial, 191 frequent (≥4/week) and occasional (<4/week) cannabis users smoked one cannabis (placebo [0.02%], or 5.9% or 13.4% Δ9-tetrahydrocannabinol [THC]) cigarette ad libitum. Blood, OF and breath samples were collected prior to and up to 6 h after smoking. Samples were analyzed for 10 cannabinoids in OF, 8 in blood and THC in breath. Frequent users had more residual THC in blood and were more likely to be categorized as 'recently used' prior to smoking; this did not occur in OF. Per se limits ranging from undetectable to 5 ng/mL THC in blood offered limited usefulness as biomarkers of recent use. Cannabinol (CBN, cutoff = 1 ng/mL) in blood offered 100% specificity but only 31.4% sensitivity, resulting in 100% positive predictive value (PPV) and 94.0% negative predictive value (NPV) at 4.3% prevalence; however, CBN may vary by cannabis chemovar. A 10 ng/mL THC cutoff in OF exhibited the overall highest performance to detect its use within 3 h (99.7% specificity, 82.4% sensitivity, 92.5% PPV and 99.2% NPV) but was still detectable in 23.2% of participants ∼4.4 h post-smoking, limiting specificity at later time points. OF THC may be a helpful indicator of recent cannabis intake, but this does not equate to impairment. Behavioral assessment of impairment is still required to determine DUIC. This study only involved cannabis inhalation, and additional research evaluating alternative routes of ingestion (i.e., oral) is needed.

The role of tacit knowledge in communication and decision-making during emerging public health incidents.

Strong communication systems for knowledge exchange are required to prevent, respond to and mitigate the effects of emerging public health incidents (EPHIs). The objective of this paper is to examine how "tacit knowledge" - implicit knowledge used to guide everyday practice - is employed in professional relationships and communication processes between public health and acute care settings. A qualitative study design was used to explore the experiences of key informants from public health and acute care settings in Ontario, Canada, to examine how specific dimensions of tacit knowledge are employed in communications about EPHIs. Twenty-six in-depth interviews were conducted from 2014 to 2015. The results describe the way in which participants employ discretion and knowledge of local context, and rely on relationships built on trust and credibility, to facilitate decision-making and communication during EPHIs. Given the uncertainty characterizing most EPHIs, communicators rely a great deal on their informal knowledge and networks which allow them to remain flexible and respond quickly to changing situations. The results reveal that communication about public health guidance during emergencies is a complex and active process that draws from past experiences of the individuals involved, and is shaped by the requirements of local circumstances. The broader implications of these findings for building resilient and responsive health systems are considered. In particular, for rethinking the authority of standardized forms of evidence in public health decision-making, and the importance of knowledge which is grounded in the uniqueness of specific local contexts.

Durability of radiofrequency ablation for treatment of esophageal squamous cell neoplasia: 5-year follow-up of a treated cohort in China.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is an accepted treatment for flat Barrett's neoplasia. Less is known about RFA for esophageal squamous cell neoplasia (ESCN). Our group has reported several prospective studies of RFA for ESCN in China with promising results through 12 months of follow-up. In this cohort study we aimed to evaluate longer term outcomes after RFA for ESCN. METHODS: Patients with flat unstained lesions (USLs) on Lugol's endoscopy containing moderate-/high-grade intraepithelial neoplasia (MGIN/HGIN) or mucosal cancer were treated with RFA every 3 months until complete remission (CR; no MGIN or a worse histologic grade). Patients with CR at 12 months (CR12) were included for follow-up and underwent annual Lugol's endoscopy with biopsy sampling and re-RFA for flat USLs. The clinical course of patients with persistent ESCN at 12 months (treatment failures) is also reported. RESULTS: Among the 78 patients in CR12, 67 (86%) had sustained CR during a median of 48 months (interquartile range, 48-48) of follow-up and 5 endoscopies (interquartile range, 4-6). Recurrence occurred in 7 of 78 patients (9%; MGIN, n = 6; HGIN, n = 1); all lesions were managed with RFA. Four other patients (5%) had progression (to HGIN, n = 1; submucosal esophageal squamous cell carcinoma, n = 3). During follow-up protocol violations occurred in 46 of 78 patients (59%). Of the 12 treatment failures, progression occurred in 6. Overall, 2 patients developed subepithelial disease that was not visible after Lugol's endoscopy. Based on post-hoc analysis, the pink-color sign at baseline (a pink color change after Lugol's endoscopy) significantly predicted failure after RFA. CONCLUSIONS: RFA is relatively easy to apply and can efficiently treat large areas with ESCN. Despite protocol violations that may have interfered with the efficacy of RFA in 59% of patients, most patients with CR12 had sustained CR during follow-up. However, some patients progressed to advanced disease and 2 developed subepithelial disease, not visible after Lugol's endoscopy. Based on currently available data, we advise the restriction of the use of RFA for flat MGIN and HGIN without the pink-color sign on Lugol's chromoendoscopy. (Clinical trial registration number: NCT02047305.).

Disseminated microsporidiosis due to Encephalitozoon hellem in an Egyptian fruit bat (Rousettus aegyptiacus).

Disseminated microsporidiosis was diagnosed in an adult female Egyptian fruit bat that died unexpectedly in a zoo. Gross findings, which were minimal, included poor body condition, bilateral renomegaly, and mottling of the liver. Histopathological lesions, which were particularly pronounced in the urogenital tract and liver, consisted primarily of inflammation associated with intracytoplasmic microsporidian spores. Polymerase chain reaction -based methods were used to establish the identity of the microsporidian as Encephalitozoon hellem. E. hellem is an emerging cause of human and avian disease, manifested mainly as opportunistic infection in immunosuppressed patients. This report describes the first documented case of E. hellem in a non-human mammalian species.

Carboplatin for treatment of a Sertoli cell tumor in a mallard (Anas platyrhynchos).

A 13-year-old male mallard was diagnosed with a non-resectable Sertoli cell tumor involving the left testis. The duck was treated with four doses of single-agent carboplatin given at 4- to 5-week intervals. Heteropenia, 2 weeks after each treatment, was the acute dose-limiting toxicity. The tumor reduced in size by 25%, and the duck's clinical condition improved for 12 months. Sertoli cell tumors are rare in birds, and this is the first report, to our knowledge, of attempted chemotherapy treatment in the veterinary literature.

Validation of electronic student encounter logs in an emergency medicine clerkship.

Handheld electronic patient encounter logs offer opportunities to understand and enhance medical students' clinical experiences. Before using the data, the reliability of log entries needs to be verified. We assessed the sensitivity and specificity of handheld patient encounter logs by comparing documented entries with reliable external data sources. During an Emergency Medicine clerkship, medical students voluntarily recorded their patients' diagnoses in an Electronic Student Encounter Log (E-SEL) on handheld computers. We used patient demographics to match anonymous log entries with medical charts. Most students recorded 60% or more of their patient encounters and on average 60% of their patients' medical problems in the log. The false positive rate was 26% for patient encounters and 19% for patient problems. In general, students recorded more diagnoses in more detail than was available in the patient's ED chart. Improvements in the log's interface and documentation incentives should enhance the log's accuracy and utility.

Loss of FBP function arrests cellular proliferation and extinguishes c-myc expression.

The c-myc regulatory region includes binding sites for a large set of transcription factors. The present studies demonstrate that in the absence of FBP [far upstream element (FUSE)-binding protein], which binds to the single-stranded FUSE, the remainder of the set fails to sustain endogenous c-myc expression. A dominant-negative FBP DNA-binding domain lacking effector activity or an antisense FBP RNA, expressed via replication-defective adenovirus vectors, arrested cellular proliferation and extinguished native c-myc transcription from the P1 and P2 promoters. The dominant-negative FBP initially augmented the single-stranded character of FUSE; however, once c-myc expression was abolished, melting at FUSE could no longer be supported. In contrast, with antisense FBP RNA, the single-stranded character of FUSE decreased monotonically as the transcription of endogenous c-myc declined. Because transcription is the major source of super-coiling in vivo, we propose that by binding torsionally strained DNA, FBP measures promoter activity directly. We also show that FUSE is predicted to behave as a torsion-regulated switch poised to regulate c-myc and to confer a higher order regulation on a large repertoire of factors.

Can investigator certification improve the quality of clinical research?

With costs and competitive pressures increasing, pharmaceutical sponsors and contract research organizations are examining the drug development process. Investigators who conduct clinical studies significantly impact research quality and, thereby, costs. This article reviews current investigator selection methods and their shortcomings. Using one organization's experience certifying clinical research coordinators and clinical research associates, the authors highlight certification as a means of assessing competency and discuss investigator certification as a potentially accurate indicator of competence for conducting research and as a predictor of inherent quality at the research site.

Modelling cortical cataractogenesis 21: in diabetic rat lenses taurine supplementation partially reduces damage resulting from osmotic compensation leading to osmolyte loss and antioxidant depletion.

The concentration of taurine and the amino acids, glutathione, cysteine, ascorbate and ATP were determined in the lenses of rats made diabetic with streptozotocin. In the clear lenses, prior to vacuole formation after 1 or 2 weeks of diabetes, the increase in concentration of sorbitol and the total decrease of all these osmolytes were not significantly different. The major components of the osmolytes lost were taurine and amino acids, which together accounted for over 75% of the total osmolyte loss. Since glutathione, ascorbate, taurine and cysteine have been reported to have antioxidant activity, it appears that their loss may potentiate damage occurring as a result of free radicals generated by nonenzymic glycation by the Maillard reaction. Amino acids also lost as a result of the osmotic compensation, are estimated to be responsible for almost half of the antioxidant activity lost. To test this hypothesis, normal and streptozotocin diabetic female Wistar rats were given taurine at 0.05% or 0.10% (w/w) in the diet. This treatment resulted in small only marginally significant increases in serum taurine levels. At the end of 6 weeks the rats were examined for weight gain or loss and at the time of killing, blood was collected for measurement of serum glucose. gamma-Crystallin levels were determined in vitreous and aqueous humours using a radioimmunoassay. A lens from each rat was homogenized in 8 m guanidinium chloride for adenosine triphosphate (ATP) analysis. In normal rats, a small amount of gamma-crystallin was found in the vitreous humour, and an even smaller amount in the aqueous humour. Diabetes caused a 4- to 5-fold increase in the vitreous humour and a 4-fold increase in gamma-crystallin in the aqueous humour. Diabetes also led to a significant worsening in general body condition, loss of body weight, formation of cataracts, and decrease in lens ATP levels. Addition of taurine to the diet of diabetic animals resulted in a significant decrease of gamma-crystallin leakage into the vitreous but not the aqueous humour. Taurine had no effect on the lens ATP levels. Neither streptozotocin diabetes nor taurine in the diet appeared to affect the weight of the lenses.

An analysis of frequent users of emergency care at an urban university hospital.

STUDY OBJECTIVE: This study was designed to identify patients who frequently use the emergency department, compare them with the general ED population, and determine why they choose the ED over other sources of medical care. METHODS: This study used a patient survey administered to a convenience sample of ED patients at an urban university teaching hospital and Level I trauma center. "Frequent" ED patients were identified as having 2 ED visits within the previous month or 4 visits in the previous year. Patients with scheduled revisits or suture removals were excluded. No medical interventions were used in the study. RESULTS: One hundred thirty-four of 6,523 ED patients were identified as frequent ED users and completed the survey. Seventy-three percent of the study group had a usual source of medical care other than the ED, and only 27% said they had difficulty in seeing a primary care physician. Sixty percent of visits by the study group were for existing or recurrent medical problems. Seventy-two percent of responders believed their chief complaint was moderately or very serious, and 59% thought they needed immediate attention. Participants had a 28% admission rate to the hospital compared with 16% for the general ED population during the study period. The study group was more likely to be black patients who have Medicare or Medicaid as their primary insurance and less likely to have workers' compensation. CONCLUSION: Frequent users of emergency care have access to other sources of primary care, but use the ED for complaints they believe are serious and need immediate attention. These patients often have chronic complaints and are more likely to be admitted to the hospital. Efforts to cut medical costs should not limit access to the ED, which often becomes an important source of medical care for such patients.

Nm23/PuF does not directly stimulate transcription through the CT element in vivo.

Decreased levels of the nm23 gene product have been correlated with increased tumor metastatic potential in a variety of malignancies. At least a subset of the regulatory properties of Nm23 has been proposed to be due to transactivation of the human c-myc oncogene through binding to a homopyrimidine tract 140 base pairs upstream of the transcription start site (termed the CT element or the PuF site). Conventional transcription factors possess DNA binding and transactivation domains; Nm23 fusion proteins were used to address two questions. First, if provided with a well characterized DNA binding domain, does Nm23 possess a transactivation domain capable of stimulating transcription of an appropriate reporter? Second, if provided with a potent transactivation domain, is the DNA binding of Nm23 of sufficient specificity and affinity to direct the fusion protein to a CT-dependent reporter? Since reporter gene expression was not stimulated in either case, we conclude that Nm23 does not directly stimulate transcription through binding to the CT element and that its antimetastatic and other reported functions are likely due to other biochemical activities.

Marking of active genes on mitotic chromosomes.

During development and differentiation, cellular phenotypes are stably propagated through numerous cell divisions. This epigenetic 'cell memory' helps to maintain stable patterns of gene expression. DNA methylation and the propagation of specific chromatin structures may both contribute to cell memory. There are two impediments during the cell cycle that can hinder the inheritance of specific chromatin configurations: first, the pertinent structures must endure the passage of DNA-replication forks in S phase; second, the chromatin state must survive mitosis, when chromatin condenses, transcription is turned off, and almost all double-stranded DNA-binding proteins are displaced. After mitosis, the previous pattern of expressed and silent genes must be restored. This restoration might be governed by mass action, determined by the binding affinities and concentrations of individual components. Alternatively, a subset of factors might remain bound to mitotic chromosomes, providing a molecular bookmark to direct proper chromatin reassembly. Here we analyse DNA at transcription start sites during mitosis in vivo and find that it is conformationally distorted in genes scheduled for reactivation but is undistorted in repressed genes. These protein-dependent conformational perturbations could help to re-establish transcription after mitosis by 'marking' genes for re-expression.

Cysteine and ascorbate loss in the diabetic rat lens prior to hydration changes.

PURPOSE: Glutathione (GSH) loss precedes vacuole formation in the diabetic rat lens, but the cause of this loss is not known. Cysteine availability is a rate limiting factor to glutathione biosynthesis in rat and human lenses but its concentration is not known; therefore free cysteine was measured prior to lens hydration in the diabetic rat lens. GSH can regenerate ascorbate from dehydroascorbate within the lens and potentially modulate the ascorbate pool; therefore ascorbate loss is also a possibility that has not been examined previously. METHODS: Diabetes was induced in Wistar rats to provide a slowly progressing model of cortical cataract. Age-matched control rats were injected with buffer vehicle only. Lens condition was monitored by binocular slit-lamp microscope after pupil dilation. Lens cysteine and glutathione were measured in the same lens, while ascorbate and total ascorbate (ascorbate + dehydroascorbate) of the contralateral lens were quantified by high performance liquid chromatography electrochemical detection. The 1- and 2-week periods of diabetes were chosen as they both preceded lens hydration changes and Na+/K+ changes, to avoid leakage due to ruptured cell membranes. RESULTS: Lens weights were not significantly different compared to controls at either the 1- or 2-week periods, and lenses were completely free of initial vacuole formation. Lens GSH concentration was diminished by 72% compared with controls after 1 week of diabetes and 74% after 2 weeks of diabetes. Lens free cysteine was decreased by 62% and 78% compared with controls after 1 and 2 weeks of diabetes, respectively. Total lens ascorbate concentration was decreased by 34% after 1 week of diabetes and 48% after 2 weeks of diabetes. Dehydroascorbate levels represented less than 10% of the total lens ascorbate pool in all experimental groups. GSH and ascorbate concentration were correlated after 1 week of diabetes (p < 0.005) and after 2 weeks of diabetes (p < 0.001). GSH and cysteine concentration were also correlated after 1 week of diabetes (p < 0.001) and after 2 weeks of diabetes (p < 0.001). CONCLUSIONS: Decreased free cysteine, in the diabetic rat lens, precedes hydration changes and vacuole formation, contributing to decreased glutathione content. While cysteine was not abundant in the lens, its concentration is greater than previously supposed. The lens ascorbate pool was also diminished prior to lens hydration.

Unna's boot dressings facilitate outpatient skin grafting of hands.

Present day economics have challenged health care providers to minimize the length of hospitalization without sacrificing quality of care. Within this context, the purpose of this study was to determine whether supporting the hand and wrist with an Unna's boot dressing (Medicopaste bandage; Graham-Field, Inc., Hauppauge, N.Y.) and splint, and covering the skin graft donor site with calcium alginate (Kaltostat; Calgon Vestal, St. Louis, Mo.), would allow successful outpatient skin grafting of burns to the upper extremity. Twelve patients with burns underwent debridement and split-thickness skin grafting on a total of 16 upper extremities with this method. Only patients who were otherwise healthy, had adequate home environments, and had burns limited to distal to the elbow were included for this initial trial. All skin graft donor sites were obtained from either the upper thigh or buttocks. Patients were discharged to home after 4 to 6 hours of observation and given amoxicillin for 5 days after surgery. Patients returned to the burn unit on the fifth postgrafting day for removal of the Unna's boot dressing, initiation of occupational therapy to the hands, and reapplication of a new calcium alginate dressing if needed. This and subsequent follow-up visits revealed a 95% or more take on all skin grafts, without any infectious complications. These results demonstrate the efficacy of Unna's boot support and calcium alginate dressings of donor sites in limited skin graft procedures. Furthermore, these results suggest that more extensive surgical debridements and skin graftings may be successfully shifted to outpatient procedures with use of these adjuvants.

Simplification of emergency department discharge instructions improves patient comprehension.

STUDY OBJECTIVE: Emergency department patients have been shown to have difficulty understanding written discharge instructions. We attempted to determine whether improvements in comprehension can be achieved by simplification of available materials. DESIGN: We have previously tested patient understanding of standard discharge instructions. For this study, we simplified the standard instructions. Patients were given one of two simplified instruction sets. After reading the instructions, each patient was asked to answer five specific written questions about them. Results were compared with those from the original study. SETTING: ED of a large inner-city university hospital. PARTICIPANTS: Four hundred twenty-three adult ED patients who presented on randomly selected days. RESULTS: The current and original groups were well matched for demographic variables. Each subject's responses were analyzed for overall success and for success with individual questions. The mean score for the current group was significantly improved over that of the original group. A trend toward improvement was demonstrated in all demographic groups with use of the simplified instructions. CONCLUSION: Simplified written materials may help patients who do not understand current standard materials. Health care providers should simplify written materials to make them understandable to the greatest number of patients.

Outbreaks of yersiniosis caused by Yersinia pseudotuberculosis in farmed cervids.

Yersiniosis, caused by Yersinia pseudotuberculosis, was diagnosed in 25 deer submitted to the Veterinary Diagnostic Laboratories of the Ontario Ministry of Agriculture and Food from 8 farms in Ontario, Canada, over the 4-year period of January 1990 to December 1993. The organism was cultured, usually in large numbers, from the intestines and, less frequently, mesenteric lymph nodes and/or the spleen of 13 red deer (Cervus elaphus), 6 elk (C. e. canadiensis), 4 fallow deer (Dama dama), and 2 red deer-elk hybrids. Outbreaks occurred almost exclusively in the fall (September-November) and affected recently weaned calves, 4-6 months old. Sudden death usually signalled the start of an outbreak. Outbreaks often occurred during inclement weather; usually a sudden cold snap, with or without rain, after a period of relatively mild fall weather. At necropsy, the animals were usually emaciated and dehydrated, and the perineum and tail were sometimes fecally stained. The small and large intestines were congested and filled with serofibrinous and/or seroanguineous fluid. Mesenteric lymph nodes were edematous and congested. Microabscesses surrounding large bacterial colonies in the lamina propria in the jejunum and ileum were typical lesions seen histologically. Peyer's patches were depleted and sometimes contained microabscesses. Purulent lymphadenitis associated with bacterial colonies was the prominent histologic lesion in mesenteric lymph nodes.