Abstract Introduction: Existential suffering in patients with serious illness significantly impacts quality of life, yet it remains a challenge to define, assess, and manage adequately. Improving upon understanding and practice in the existential domain is a topic of interest for palliative care providers. Methods: As a quality improvement project, our palliative care team created an existential assessment tool utilizing a dialogue-oriented approach with four questions designed to identify sources of existential distress as well as strengths and challenges in coping with this distress. The tool utilized the mnemonic CASH, with each letter representing the core objective of the question. Providers who requested the palliative care consult were asked to evaluate the CASH assessment. On completion of the project, palliative care consultants evaluated the appropriateness of the CASH assessment tool. Results: Patient responses to the CASH questions were insightful and reflected their beliefs, priorities, and concerns. Eight of nine providers found that the assessment enabled understanding of their patient. Seven noted a positive impact on their practice, and five reported an improvement in patient care after the assessment. The palliative care consultants who used the tool enjoyed using it, and half of them suggested changes to patient care based on their assessment. The most common reasons for not using the CASH assessment were inappropriateness to the consult, lack of perceived patient/caregiver receptiveness, or consultation service too busy. Conclusion: Our quality improvement project demonstrated that the CASH assessment tool is useful in ascertaining existential concerns of patients with serious illness. It enhances patient care by the primary team as well as the palliative care team. As a brief set of questions with an easy-to-remember mnemonic, the CASH assessment tool is feasible for a busy palliative consult service. Furthermore, the positive results of this project merit more rigorous evaluation of the CASH assessment tool in the future.
In this study, attitudes and perceptions of U.S. dental students and faculty members were evaluated regarding four aspects of dental education: technology integration, instructional strategies, student diversity, and school duration. A survey instrument with eight statements using a five-point Likert scale and a free-text comment section was developed and distributed through Survey Monkey. A total of 426 students and 187 faculty members from ten U.S. dental schools participated, a response rate of 17 percent of those surveyed. Faculty and student responses were compared using the Mann-Whitney U test. The results of this analytic procedure revealed that the groups differed in their average responses for seven of the eight statements. Analysis of the faculty and student comments revealed similar themes between the two groups. Both dental students and dental faculty members stated that technology integration should be viewed as only a supplement to conventional instruction and showed mixed opinions about electronic textbooks. Further, both groups had positive views of the roles of problem-based learning, community service, and the integration of research practice into dental education. Both groups also valued diversity in the student body and supported the current four-year duration of dental school.
The Little Bighorn River flows through the Crow Indian Reservation in Montana. In 2008, Escherichia coli concentrations as high as 7179 MPN/100 ml were detected in the river at the Crow Agency Water Treatment Plant intake site. During 2008, 2009, and 2012, 10 different serotypes of E. coli, including O157:H7, harboring both intimin and Shiga toxin genes were isolated from a popular swim site of the Little Bighorn River in Crow Agency. As part of a microbial source tracking study, E. coli strains were isolated from river samples as well as from manure collected from a large cattle feeding operation in the upper Little Bighorn River watershed; 23% of 167 isolates of E. coli obtained from the manure tested positive for the intimin gene. Among these manure isolates, 19 were identified as O156:H8, matching the serotype of an isolate collected from a river sampling site close to the cattle feeding area.
The cardioinhibitory effects of cardiac vagal motoneurons (CVMs) are mediated by activation of postganglionic neurons in the epicardial ganglia which have been shown to exert functionally selective effects on heart rate and atrioventricular conduction in the rat. Here we investigate whether CVMs producing these responses may occupy different rostrocaudal positions within the nucleus ambiguus. Excitation of CVMs was attempted by microinjections of glutamate into the nucleus ambiguus of an arterially perfused preparation in a grid extending over 2mm in the rostrocaudal plane using the obex as a reference point. Microinjections were paired, one made during pacing to measure changes in atrioventricular conduction (P-R interval) independent of changes in heart rate and the other looking for changes in heart period (P-P interval) un-paced. Although evidence of a differential distribution was found in 7 cases, in the majority (13/20), sites producing maximal effects on both variables coincided. Maximal changes in atrioventricular conduction resulted from more rostral sites in 6 cases and from a more caudal site in only one. Overall, the ratio of the change in atrioventricular conduction to the change in heart rate for a given site was significantly greater 1mm rostral to the obex than at either end of the test grid. We conclude that while CVMs controlling atrioventricular conduction are distributed with a peak somewhat rostral to those controlling heart rate in a number of animals, there is a significant overlap and much greater variability in this distribution in the rat than in cats and dogs.
Metastasis to the foot is rarely presented in the literature. We describe a 56-year-old woman with nonspecific pain in the left foot, ankle, and knee for 3 months. The patient was diagnosed as having urothelial carcinoma with metastasis to the left lower extremity, including the foot. This diagnosis was reached through the combined efforts of radiologic techniques and biopsies. This case discusses the importance of paying close attention to the details of the history and physical examination, performing appropriate tests, and obtaining suitable referrals.
Studies on marine mammals can inform our understanding of the environmental health of the ocean. To evaluate the potential for changes in antimicrobial resistance, we analyzed a database spanning 2004-2010 that consisted of bacterial isolate identity and antimicrobial sensitivity for stranded pinnipeds in the Northwest Atlantic. Samples (n = 170) from treated animals yielded 310 bacterial isolates representing 24 taxa. We evaluated changes in antimicrobial class resistance from 2004 to 2010 for eight taxa. Escherichia coli displayed a significant increase in resistance to several antimicrobial classes. Other taxa displayed significant increases in resistance to aminoglycosides, and/or fluoroquinolones. In addition, we observed a significant increase in multiple antimicrobial resistance in cultures from untreated animals. These results demonstrate an increase in resistance among common bacterial pathogens of marine mammals over a time span of 6 years.
Bile salts exhibit potent antibacterial properties, acting as detergents to disrupt cell membranes and as DNA-damaging agents. Although bacteria inhabiting the intestinal tract are able to resist biles antimicrobial effects, relatively little is known about how bile influences virulence of enteric pathogens. Escherichia coli O157:H7 is an important pathogen of humans, capable of causing severe diarrhea and more serious sequelae. In this study, the transcriptome response of E. coli O157:H7 to bile was determined. Bile exposure induced significant changes in mRNA levels of genes related to virulence potential, including a reduction of mRNA for the 41 genes making up the locus of enterocyte effacement (LEE) pathogenicity island. Bile treatment had an unusual effect on mRNA levels for the entire flagella-chemotaxis regulon, resulting in two- to four-fold increases in mRNA levels for genes associated with the flagella hook-basal body structure, but a two-fold decrease for "late" flagella genes associated with the flagella filament, stator motor, and chemotaxis. Bile salts also caused increased mRNA levels for seventeen genes associated with iron scavenging and metabolism, and counteracted the inhibitory effect of the iron chelating agent 2,2-dipyridyl on growth of E. coli O157:H7. These findings suggest that E. coli O157:H7 may use bile as an environmental signal to adapt to changing conditions associated with the small intestine, including adaptation to an iron-scarce environment.
Donation after cardiac death (DCD) or donation of organs after removal of life support is an accepted means of organ retrieval that usually occurs in the setting of sudden illness but has not been described in people with progressive neurologic illness. We report DCD in two people with progressive amyotrophic lateral sclerosis (ALS).
A probability risk assessment of anthracene, benzo(a)pyrene, chrysene, fluorene, phenanthrene and pyrene was carried out to examine the ecological risk of these six polycyclic aromatic hydrocarbons (PAHs) in aquatic ecosystems in China. The literature on PAH concentrations in surface water in China was collected to evaluate the environmental exposure concentrations (EEC). The 10th percentile of predicted no observed effect concentration (PNEC(10%)) of PAHs, calculated according to the data from the USEPA AQUIRE database and regulatory reviews, was applied as the toxicity assessment endpoint. The ratio of EEC and PNEC(10%), expressed as a risk quotient (RQ), was used to characterize the risk value. Bootstrapping method and Monte Carlo simulation were utilized to calculate the distribution of EEC, PNEC(10%), RQ and associated uncertainties. Risk assessment showed that reliable maximum RQs of anthracene, benzo(a)pyrene, chrysene, fluorene and phenanthrene were in the range of 0.064-0.755, lower than the acceptable value of 1. However, the reliable maximum RQ of pyrene was 1.39, indicating its potential ecological risk. Notwithstanding the uncertainty, these results suggest that the aquatic ecosystems with high PAH concentrations might pose potential ecological risks, and concerted efforts are required to ensure that surface water is protected.
Helicobacter pylori is a gram-negative bacterium that colonizes the human stomach and is responsible for causing gastric ulcers. H. pylori is known to become stressed and nonculturable after exposure to unfavorable conditions. In this study, we enhanced previously published resuscitation procedures, characterized conditions under which stressed H. pylori can be recovered, and formulated a selective and differential resuscitation medium. Results showed that a specialized broth supplemented with trace minerals and lysed human erythrocytes and serum is required for the recovery of nonculturable H. pylori. The type of stress was an important factor in the efficacy of resuscitation, with cells exposed to atmospheric oxygen more readily resuscitated than nutrient deprived cells. After resuscitation, culturable cells were recovered from previously nonculturable oxygen stressed cells (24 and 72 h of exposure) and nonculturable nutrient deprived cells (24 h of exposure). The length of time the cells were exposed to the stress was also an important factor in the recovery of stressed H. pylori. RNA levels were quantified and transcription of the cell division related gene, cdrA (HP0066), was assessed by qRT-PCR. The low levels of RNA detected in stressed cells, after resuscitation, support the idea that a small population of viable cells may be responsible for the colonies recovered on solid agar. The modification of the resuscitation broth into a selective and differential slant culture medium also allowed the recovery of stressed H. pylori. The methods presented here highlight the benefits and limitations of using human blood products for recovering nonculturable H. pylori.
Heart failure constitutes a significant source of morbidity and mortality in the United States, and its incidence and prevalence continue to grow, increasing its burden on the healthcare system. Renal dysfunction in patients with heart failure is common and has been associated with adverse clinical outcomes. This interaction, termed the cardiorenal syndrome, is a complex phenomenon characterized by a pathophysiologic disequilibrium between the heart and the kidney, in which malfunction of 1 organ consequently promotes the impairment of the other. Multiple neurohumoral mechanisms are involved in this cardiorenal interaction, including the deficiency of and/or resistance to compensatory natriuretic peptides, leading to sodium retention, volume overload and organ remodeling. Management of patients with the cardiorenal syndrome can be challenging and should be individualized. Emerging therapies must address the function of both organs to secure better clinical outcomes. To this end, a multidisciplinary approach is recommended to achieve optimal results.
Homology modeling and molecular docking were used to in silico analyze the interactions between six endocrine disrupting chemicals (EDCs) and 11 androgen receptors (ARs) of different vertebrate species. The MODELLER 9V7 program was employed to construct the homology models of AR ligand binding domains (LBDs) from birds, amphibians, bony fishes and cartilaginous fishes. The Surflex-Dock program was applied to calculate and analyze the binding affinities between the six EDCs and AR LBDs. The docking experiment showed that AR LBDs had high affinities with nonyl phenol (NP) and butyl benzyl phthalate (BBP), but low affinities with the 2,2,4,4,5,5-hexabromodiphenyl ether (BDE153). The results of cluster analysis suggested that predicted binding affinities were species-specific, which was consistent with the phylogenetic analysis of AR LBDs. The difference of binding affinities could be mainly due to the different hydrogen bonds and the orientation of ligands in the binding pockets. Our results suggest that integrated methods of phylogenetic analysis, homology modeling and molecular docking might be a potential tool to predict the different interactions between contaminants and associated receptors in different trophic levels.
HiLo microscopy is a widefield fluorescence imaging technique that provides depth discrimination by combining two images, one with non-uniform illumination and one with uniform illumination. We discuss the theory of this technique and a variety of practical implementations in brain-tissue imaging and fluorescence endomicroscopy.
Recent events clearly illustrate a continued vulnerability of large populations to infectious diseases, which is related to our changing human-constructed and natural environments. A single person with multidrug-resistant tuberculosis in 2007 provided a wake-up call to the United States and global public health infrastructure, as the health professionals and the public realized that todays ease of airline travel can potentially expose hundreds of persons to an untreatable disease associated with an infectious agent. Ease of travel, population increase, population displacement, pollution, agricultural activity, changing socioeconomic structures, and international conflicts worldwide have each contributed to infectious disease events. Today, however, nothing is larger in scale, has more potential for long-term effects, and is more uncertain than the effects of climate change on infectious disease outbreaks, epidemics, and pandemics. We discuss advances in our ability to predict these events and, in particular, the critical role that satellite imaging could play in mounting an effective response.
The temporal activity, abundance and diversity of microbial communities were evaluated across a metal-contamination gradient around a Superfund site in Montana. In order to analyze short-term variability, samples were collected from six sites on four occasions over 12 months. Measurements of community activity, diversity and richness, quantified by dehydrogenase activity and through denaturant gradient gel electrophoresis (DGGE), respectively, were higher at contaminated sites adjacent to the smelter, relative to reference sites. 16S rRNA gene copy numbers, measured by quantitative PCR, showed seasonal variability, yet were generally higher within polluted sediments. Jaccard similarity coefficients of DGGE profiles, found sites to cluster based primarily on geographical proximity rather than geochemical similarities. Intra-site clustering of the most polluted sites also suggests a stable metal-tolerant community. Sequences from DGGE-extracted bands were predominantly Beta and Gammaproteobacteria, although the communities at all sites generally maintained a diverse phylogeny changing in composition throughout the sampling period. Spearmans rank correlations analysis found statistically significant relationships between community composition and organic carbon (r-value = 0.786) and metals (r-values As = 0.65; Cu = 0.63; Zn = 0.62). A diverse and abundant community at the most polluted site indicates that historical contamination selects for a metal-resistant microbial community, a finding that must be accounted for when using the microbial community within ecosystem monitoring studies. This study highlights the importance of using multiple time-points to draw conclusions on the affect of metal contamination.
To control the antibiotic resistance epidemic, it is necessary to understand the distribution of genetic material encoding antibiotic resistance in the environment and how anthropogenic inputs, such as wastewater, affect this distribution. Approximately two-thirds of antibiotics administered to humans are beta-lactams, for which the predominant bacterial resistance mechanism is hydrolysis by beta-lactamases. Of the beta-lactamases, the TEM family is of overriding significance with regard to diversity, prevalence, and distribution. This paper describes the design of DNA probes universal for all known TEM beta-lactamase genes and the application of a quantitative PCR assay (also known as Taqman) to quantify these genes in environmental samples. The primer set was used to study whether sewage, both treated and untreated, contributes to the spread of these genes in receiving waters. It was found that while modern sewage treatment technologies reduce the concentrations of these antibiotic resistance genes, the ratio of bla(TEM) genes to 16S rRNA genes increases with treatment, suggesting that bacteria harboring bla(TEM) are more likely to survive the treatment process. Thus, beta-lactamase genes are being introduced into the environment in significantly higher concentrations than occur naturally, creating reservoirs of increased resistance potential.
Heart failure constitutes a significant source of morbidity and mortality in the United States and its incidence and prevalence continue to grow, increasing its burden on the health care system. Renal dysfunction in patients with heart failure is common and has been associated with adverse clinical outcomes. This complex interaction is characterized by a pathophysiological disequilibrium between the heart and the kidney, in which cardiac malfunction promotes renal impairment, which in turn feeds back for further deterioration of cardiovascular function. Multiple neurohumoral and hemodynamic mechanisms are involved in this cardiorenal dyshomeostasis, including the deficiency of and/or resistance to compensatory natriuretic peptides, leading to sodium retention, volume overload and organ remodeling. Management of patients with cardiorenal dysfunction can be challenging and should be individualized. Emerging therapies must address the impairment of both organs to secure better clinical outcomes. To this end, a multidisciplinary approach is warranted to achieve optimal results.
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