Initial results from the New Horizons exploration of 2014 MU69, a small Kuiper Belt object.

The Kuiper Belt is a distant region of the outer Solar System. On 1 January 2019, the New Horizons spacecraft flew close to (486958) 2014 MU69, a cold classical Kuiper Belt object approximately 30 kilometers in diameter. Such objects have never been substantially heated by the Sun and are therefore well preserved since their formation. We describe initial results from these encounter observations. MU69 is a bilobed contact binary with a flattened shape, discrete geological units, and noticeable albedo heterogeneity. However, there is little surface color or compositional heterogeneity. No evidence for satellites, rings or other dust structures, a gas coma, or solar wind interactions was detected. MU69's origin appears consistent with pebble cloud collapse followed by a low-velocity merger of its two lobes.

A brief bedside visual art intervention decreases anxiety and improves pain and mood in patients with haematologic malignancies.

Treatment of cancer-related symptoms represents a major challenge for physicians. The purpose of this pilot study was to determine whether a brief bedside visual art intervention (BVAI) facilitated by art educators improves mood, reduces pain and anxiety in patients with haematological malignancies. Thirty-one patients (21 women and 10 men) were invited to participate in a BVAI where the goal of the session was to teach art technique for ~30 min. Primary outcome measures included the change in visual analog scale, the State-Trait Anxiety Inventory and the Positive and Negative Affect Schedule scale, from baseline prior to and immediately post-BVAI. Total of 21 patients (19 women and two men) participated. A significant improvement in positive mood and pain scores (p = .003 and p = .017 respectively) as well as a decrease in negative mood and anxiety (p = .016 and p = .001 respectively) was observed. Patients perceived BVAI as overall positive (95%) and wished to participate in future art-based interventions (85%). This accessible experience, provided by artists within the community, may be considered as an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain, and future studies with balanced gender participation may support the generalisability of these findings.

Oral application of a periodontal pathogen impacts SerpinE1 expression and pancreatic islet architecture in prediabetes.

BACKGROUND AND OBJECTIVES: Epidemiological studies suggest a close association between periodontitis and prediabetes/insulin resistance (IR) but whether periodontitis causes prediabetes in humans is not known. Using various animal models, we have recently established that periodontitis can be an initiator of prediabetes, which is characterized by glucose intolerance, hyperinsulinemia and IR. In addition, our in vitro studies indicated that Porphyromonas gingivalis (Pg) induced insulin secretion in MIN6 ß cells and this induction was in part SerpinE1 (plasminogen activator inhibitor 1, PAI1) dependent. However, the mechanism(s) by which periodontitis induces prediabetes is not known. As α and ß cells in pancreatic islets are the major modulators of glucose levels, we investigated whether experimental periodontitis by oral application of a periodontal pathogen caused molecular and/or cellular alterations in pancreatic islets and whether SerpinE1 was involved in this process. MATERIAL AND METHODS: We induced periodontitis in C57BL/6 mice by oral application of a periodontal pathogen, Pg, and determined changes that occurred in islets following 22 weeks of Pg application. Pancreatic islet architecture was determined by 2-D and 3-D immunofluorescence microscopy and SerpinE1 and its target, urokinase plasminogen activator (uPA), as well as insulin, glucagon and Pg/gingipain in islets were detected by immunofluorescence. The presence of apoptotic islet cells was determined by both histochemical and immunofluorescence TUNEL assays. To investigate further the direct effect of Pg on apoptosis and the involvement of SerpinE1 in this process, we used SerpinE1 knockdown and scrambled control clones of the MIN6 pancreatic ß-cell line. RESULTS: Pg/gingipain was detected in both the periodontium and pancreas in the experimental group. Islets from animals that were administered Pg orally (experimental group) developed significant changes in islet architecture, upregulation of SerpinE1, and increased ß-cell apoptosis compared with the control group. We also observed that exposure of MIN6 cells to Pg in vitro resulted in apoptosis. However, apoptosis was significantly reduced when SerpinE1 expression by MIN6 cells was knocked down. CONCLUSION: Oral application of the periodontal pathogen Pg to C57BL/6 mice induces periodontitis, translocation of Pg/gingipain to the pancreas and results in complex alterations in pancreatic islet morphology. SerpinE1 appears to be involved in this process.

Antemortem detection of mouse parvovirus and mice minute virus by polymerase chain reaction (PCR) of faecal samples.

Parvoviruses remain one of the most common viral infections seen in laboratory mouse colonies. The purpose of this study was to develop an antemortem polymerase chain reaction (PCR) assay to detect mice infected with mouse parvovirus-1 (MPV) and mice minute virus (MMV) using faecal samples. The MMV PCR assay consistently detected as few as 100 plasmid copies of MMV in faecal samples, while the MPV PCR assay detected as few as 10 plasmid copies of MPV. Faecal pellets from infected mice held at room temperature from 1 to 7 days tested positive by MMV and MPV PCR, respectively. This demonstrates that parvovirus DNA is stable in faecal samples kept at room temperature. PCR assays were also used to follow the length of MMV and MPV shedding in faeces from SENCAR mice, which were endemically infected with multiple agents. MMV faecal shedding was detected in 60-70% of the mice 5-7 weeks old, and by 13 weeks of age, faecal samples from all mice were negative for MMV. MPV faecal shedding was detected in 90-100% of the mice 5-11 weeks old; however, by 19 weeks of age, faecal samples from all mice were negative for MPV. These findings confirm that faecal shedding occurs for a limited time and suggest that 5-9-week-old mice are the most appropriate age group in endemically infected mice for faecal testing by MMV and MPV PCR.

Detection of rat parvovirus type 1 and rat minute virus type 1 by polymerase chain reaction.

Two newly recognized parvovirus species, rat parvovirus 1 (RPV-1) and rat minute virus 1 (RMV-1), were recently identified in naturally infected rats. In this study, two polymerase chain reaction (PCR) assays were developed to specifically detect RPV-1 and RMV-1. The RPV-1 PCR assay amplified the expected 487-bp deoxyribonucleic acid (DNA) fragment only in the presence of RPV-1 DNA; the RMV-1 PCR assay amplified the expected 843-bp product only from RMV-1 DNA, not from other rodent parvoviruses. The RPV-1 and the RMV-1 PCR assays detected approximately 18 and 70 copies of DNA template, respectively. These two PCR assays were shown to be sensitive, specific and rapid methods for detecting RPV-1 and RMV-1 infections in rats. These assays may also be valuable for evaluation of biological specimens for parvovirus contamination.

The traditional Chinese medicine Cordyceps sinensis and its effects on apoptotic homeostasis.

Cordyceps sinensis is a medicinal fungus of Traditional Chinese Medicine. While there are a wide range of reported uses of Cordyceps sinensis in the literature, the reports that extracts of this fungus may alter apoptotic homeostasis are most intriguing. However, there are significant challenges regarding research surrounding Cordyceps sinensis, such as the difficulty identifying the various species of Cordyceps and the many conflicting reports of pharmacological function in the literature. In this review we outline what is known about the ability of Cordyceps sinensis to alter apoptotic homeostasis, attempt to reconcile the differences in reported function, identify the challenges surrounding future Cordyceps sinensis research, and delineate options for overcoming these critical hurdles.

Bioprospecting Rumphius's Ambonese Herbal: Volume I.

Collaborating with traditional healers remains a valid method for the identification of potential lead compounds for novel pharmaceuticals. However, the knowledge of these traditional healers is rapidly being lost. Historic herbal texts provide a unique window to identify plants whose specific uses are no longer known. We have identified nine plants in the 17th century Ambonese Herbal: Volume I which were documented as having medicinal properties but which have not been examined in the current literature. We demonstrate that by evaluating plant and herb efficacy reports from historic texts, in the context of comprehensive modern databases such as NAPRALERT, we can ultimately identify candidate specimens deserving further pharmacological study.

Cordyceps sinensis extracts do not prevent Fas-receptor and hydrogen peroxide-induced T-cell apoptosis.

Aqueous and alcohol extracts of Cordyceps sinensis (Berk) Succ. are used as a traditional medicine in China for the treatment of a wide range of diseases and are reported to have antioxidant and antiapoptotic properties. We therefore examined the ability of aqueous, organic, and alcohol extracts of Cordyceps sinensis to inhibit apoptosis induced either by hydrogen peroxide or Fas-receptor ligation; both stimuli induce apoptosis dependent on reactive oxygen species. Cells pre-incubated with Cordyceps sinensis extracts were equally sensitive to hydrogen peroxide and Fas-mediated apoptosis. Thus, the putative antioxidant and antiapoptotic properties of Cordyceps sinensis are insufficient to rescue cells from apoptosis induced by these stimuli in vitro.

A randomized controlled trial of the accuracy of clinical record retrieval using SNOMED-RT as compared with ICD9-CM.

BACKGROUND: Concept-based Indexing is purported to provide more granular data representation for clinical records.1,2 This implies that a detailed clinical terminology should be able to provide improved access to clinical records. To date there is no data to show that a clinical reference terminology is superior to a precoordinated terminology in its ability to provide access to the clinical record. Today, ICD9-CM is the most commonly used method of retrieving clinical records. OBJECTIVE: In this study, we compare the sensitivity, specificity, positive likelihood ratio, positive predictive value and accuracy of SNOMED-RT vs. ICD9-CM in retrieving ten diagnoses from a random sample of 2,022 episodes of care. METHOD: We randomly selected 1,014 episodes of care from the inpatient setting and 1,008 episodes of care from the outpatient setting. Each record had associated with it, the free text final diagnoses from the Master Sheet Index at the Mayo Clinic and the ICD9-CM codes used to bill for the encounters within the episode of care. The free text diagnoses were coded by two expert indexers (disagreements were addressed by a Staff Clinician) as to whether queries regarding one of 5 common or 5 uncommon diagnoses should return this encounter. The free text entries were automatically coded using the Mayo Vocabulary Processor. Each of the ten diagnoses was exploded in both SNOMED-RT and ICD9-CM and using these entry points, a retrieval set was generated from the underlying corpus of records. Each retrieval set was compared with the Gold Standard created by the expert indexers. RESULTS: SNOMED-RT produced significantly greater specificity in its retrieval sets (99.8% vs. 98.3%, p<0.001 McNemar Test). The positive likelihood ratios were significantly better for SNOMED-RT retrieval sets (264.9 vs. 33.8, p<0.001 McNemar Test). The positive predictive value of a SNOMED-RT retrieval was also significantly better than ICD9-CM (92.9% vs. 62.4%, p<0.001 McNemar Test). The accuracy defined as 1 (the total error rate (FP+FN) / Total # episodes queried (20,220)) was significantly greater for SNOMED-RT (98.2% vs. 96.8%, p=0.002 McNemar Test). Interestingly, the sensitivity of the SNOMED-RT generated retrieval set was not significantly different from ICD9-CM, but there was a trend toward significance (60.4% vs. 57.6%, p=0.067 McNemar Test). However, if we examine only the outpatient practice SNOMED-RT produced a more sensitive retrieval set than ICD9-CM (54.8% vs. 46.4%, p=0.002 McNemar Test). CONCLUSIONS: Our data clearly shows that information regarding both common and rare disorders is more accurately identified with automated SNOMED-RT indexing using the Mayo Vocabulary Processor than it is with traditional hand picked constellations of codes using ICD9-CM. SNOMED-RT provided more sensitive retrievals of outpatient episodes of care than ICD9-CM.

A randomized controlled trial of concept based indexing of Web page content.

OBJECTIVE: Medical information is increasingly being presented in a web-enabled format. Medical journals, guidelines, and textbooks are all accessible in a web-based format. It would be desirable to link these reference sources to the electronic medical record to provide education, to facilitate guideline implementation and usage and for decision support. In order for these rich information sources to be accessed via the medical record they will need to be indexed by a single comparable underlying reference terminology. METHODS: We took a random sample of 100 web pages out of the 6,000 web pages on the Mayo Clinic's Health Oasis web site. The web pages were divided into four datasets each containing 25 pages. These were humanly reviewed by four clinicians to identify all of the health concepts present (R1DA, R2DB, R3DC, R4DD). The web pages were simultaneously indexed using the SNOMED-RT beta release. The indexing engine has been previously described and validated. A new clinician reviewed the indexed web pages to determine the accuracy of the automated mappings as compared with the human identified concepts (R4DA, R3DB, R2DC, R1DD). RESULTS: This review found 13,220 health concepts. Of these 10,383 concepts were identified by the initial human review (78.5% +/- 3.6%). The automated process identified 10,083 concepts correctly (76.3% +/- 4.0%) from within this corpus. The computer identified 2,420 concepts, which were not identified by the clinician's review but were upon further consideration important to include as health concepts. There was on average a 17.1% +/- 3.5% variability in the human reviewers ability to identify the important health concepts within web page content. Concept Based Indexing provided a positive predictive value (PPV) of finding a health concept of 79.3% as compared with keyword indexing which only has a PPV of 33.7% (p < 0.001). CONCLUSION: SNOMED-RT is a reasonable ontology for web page indexing. Concept based indexing provides a significantly greater accuracy in identifying health concepts when compared with keyword indexing.

Herbal therapy: what a clinician needs to know to counsel patients effectively.

The use of herbal medicine in the United States has been increasing at a steady pace over the past decade. Most recent estimates suggest that the US population spends $5 billion per year for herbal supplements alone. Herbal supplements are receiving increasing exposure through national media, in lay journals, and more recently in the scientific press. Interest in herbal medicine has been facilitated by multiple factors, including the perception that pharmaceutical medications are expensive, overprescribed, and often dangerous. Alternatively, herbal medicine is often perceived as being "natural" and is therefore considered safe. While the growth of the herbal medicine industry in the United States can probably not continue at this accelerated pace indefinitely, there is little indication of any major slowing. Therefore, patients will continue to use herbal medications. Knowledge of these preparations (including their potential benefits and risks as well as their ability to interact with pharmaceutical medications) will enable physicians to provide a balanced and objective view to patients seeking information on herbal therapy.

A randomized double-blind controlled trial of automated term dissection.

OBJECTIVE: To compare the accuracy of an automated mechanism for term dissection to represent the semantic dependencies within a compositional expression, with the accuracy of a practicing Internist to perform this same task. We also compare the results of four evaluators to determine the inter-observer variability and the variance between term sets, with respect to the accuracy of the mappings and the consistency of the failure analysis. METHODS: 500 terms, which required a compositional expression to effect an exact match, were randomly distributed into two sets of 250 terms (Set A and Set B). Set A was dissected using the Automated Term Dissection (ATD) Algorithm. A physician specializing in Internal Medicine dissected set B. He had no prior knowledge of the dissection algorithm or how it functioned. In this manuscript, the authors use Human Term Dissection (HTD) to refer to this method. Set A was randomized to two sets of 125 terms (Set A1 and Set A2). Set B was randomized to two sets of 125 terms (Set B1 and Set B2). A new set of 250 terms Set C was created from Set A1 and Set B2. A second new set of 250 terms Set D was created from Set A2 and Set B1. Two expert Indexers reviewed Set C and another two expert Indexers reviewed Set D. They were blinded to which terms were dissected by the clinician and which terms were dissected by the automated term dissection algorithm. The person providing the files for review to the Indexers was also unaware of which terms were dissected by ATD vs. the HTD method. The Indexers recorded whether or not the dissection was the best possible representation of the input concept. If not, a failure analysis was conducted. They recorded whether or not the dissection was in error and if so was a modifier not subsumed or was a Kernel concept subsumed when it should not have been. If a concept was missing, the Indexers recorded whether it was a Kernel concept, a modifier, a qualifier or a negative qualifier. RESULTS: The ATD method was judged to be accurate and readable in 265 out of the 424 terms with adequate content (62.7%). The HTD method was judged to be accurate in 272 out of 414 terms with adequate content (65.7%). There was no statistically significant difference between the rates of acceptability of the ATD and HTD methods (p = 0.33). There was a non-significant trend toward greater acceptability of the ATD method in the subgroup of terms with three or more compositional elements. ATD was acceptable in 53.6% of the terms where the HTD was only acceptable in 43.6% (p = 0.11). The failure analysis showed that both methods misrepresented kernel concepts and modifiers much more commonly than qualifiers (p < 0.001). CONCLUSIONS: There is no statistically significant difference in the accuracy and readability of terms dissected using the automated term dissection method when compared with human term dissection, as judged by four expert medical indexers. There is a non-significant trend toward improved performance of the ATD method in the subset of more complex terms. The authors submit that this may be due to a tendency for users to be less compulsive when the time to complete the task is long. Automated term dissection is a useful and perhaps preferable method for representing readable and accurate compound terminological expressions.

Characterization of a WaaF (RfaF) homolog expressed by Haemophilus ducreyi.

Haemophilus ducreyi lipooligosaccharide (LOS) is capable of inducing an inflammatory response in skin (A. A. Campagnari, L. M. Wild, G. Griffiths, R. J. Karalus, M. A. Wirth, and S. M. Spinola, Infect. Immun. 59:2601-2608, 1991) and likely contributes to the virulence of this sexually transmitted pathogen (B. A. Bauer, M. K. Stevens, and E. J. Hansen, Infect. Immun. 68:4290-4298, 1998). An open reading frame in H. ducreyi 35000 was found to encode a predicted protein that was 59% identical to the protein product of the rfaF (waaF) gene of Salmonella typhimurium. The H. ducreyi waaF gene was able to complement an S. typhimurium rfaF (waaF) mutant, a result which confirmed the identity of this gene. In contrast to the rfaF (waaF) gene of enteric bacteria, the H. ducreyi waaF gene was not located adjacent to other genes involved in lipopolysaccharide expression. Inactivation of the H. ducreyi waaF gene by insertion mutagenesis resulted in expression of a LOS that migrated much faster than wild-type LOS in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The LOS of this mutant also did not bind a monoclonal antibody directed against a cell surface-exposed epitope of wild-type H. ducreyi LOS. Testing of the wild-type H. ducreyi strain and its isogenic waaF mutant in the temperature-dependent rabbit model for dermal lesion production by H. ducreyi revealed that this waaF mutant was less virulent than the wild-type parent strain. Complementation of the H. ducreyi waaF mutant with the wild-type H. ducreyi waaF gene resulted in expression of both wild-type LOS and wild-type virulence by this mutant.

Involvement of the Haemophilus ducreyi gmhA gene product in lipooligosaccharide expression and virulence.

The lipooligosaccharide (LOS) present in the outer membrane of Haemophilus ducreyi is likely a virulence factor for this sexually transmitted pathogen. An open reading frame in H. ducreyi 35000 was found to encode a predicted protein that had 87% identity with the protein product of the gmhA (isn) gene of Haemophilus influenzae. In H. influenzae type b, inactivation of the gmhA gene caused the synthesis of a significantly truncated LOS which possessed only lipid A and a single 2-keto-3-deoxyoctulosonic acid molecule (A. Preston, D. J. Maskell, A. Johnson, and E. R. Moxon, J. Bacteriol. 178:396-402, 1996). The H. ducreyi gmhA gene was able to complement a gmhA-deficient Escherichia coli strain, a result which confirmed the identity of this gene. When the gmhA gene of H. ducreyi was inactivated by insertion of a cat cartridge, the resultant H. ducreyi gmhA mutant, 35000.252, expressed a LOS that migrated much faster than wild-type LOS in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When the wild-type H. ducreyi strain and its isogenic gmhA mutant were used in the temperature-dependent rabbit model for dermal lesion production by H. ducreyi, the gmhA mutant was found to be substantially less virulent than the wild-type parent strain. The H. ducreyi gmhA gene was amplified by PCR from the H. ducreyi chromosome and cloned into the pLS88 vector. When the H. ducreyi gmhA gene was present in trans in gmhA mutant 35000.252, expression of the gmhA gene product restored the virulence of this mutant to wild-type levels. These results indicate that the gmhA gene product of H. ducreyi is essential for the expression of wild-type LOS by this pathogen.

Incidence and outcomes of asthma in the elderly. A population-based study in Rochester, Minnesota.

STUDY OBJECTIVE: To estimate the incidence of asthma in an elderly population and to describe the clinical characteristics, use of health services, and long-term survival of persons with onset of asthma after age 65 years. DESIGN: Retrospective cohort study. SETTING: Rochester, Minn. PATIENTS: All Rochester, Minn, residents age 65 years or older who met criteria for onset of definite or probable asthma from 1964 through 1983. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Ninety-eight Rochester residents (52 female, 46 male) with onset of asthma at or after age 65 years were identified. The age- and sex-adjusted incidence was 95/100,000 (95% confidence interval, 76 to 115/100,000). The age-specific incidence of asthma was 103/100,000 in residents aged 65 to 74 years, 81/100,000 in those aged 75 to 84 years, and 58/100,000 in residents older than 85 years. Only 11% had allergy skin tests, 24% had at least one office peak flow measurement, and 43% had at least one spirometry measurement. After the diagnosis of asthma, 40% had unscheduled ambulatory visits, 22% had emergency department visits, and 42% had at least one hospitalization for asthma. Observed survival was not significantly different from expected survival. CONCLUSIONS: Asthma is common in the elderly. Diagnostic evaluation was less intensive than present guidelines recommend. Following the diagnosis of asthma, a substantial proportion of these individuals required unscheduled ambulatory visits, emergency department visits, or hospitalizations. Asthma with onset after age 65 years was not associated with reduced survival.