Recent Submissions

  • Laboratory diagnosis of biotinidase deficiency, 2017 update: A technical standard and guideline of the American College of Medical Genetics and Genomics

    Strovel, E.T.; Cowan, T.M.; Scott, A.I. (Nature Publishing Group, 2017)
    Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these Standards and Guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of others that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, clinical laboratory geneticists should apply their professional judgment to the specific circumstances presented by the patient or specimen. Clinical laboratory scientists and geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Biotinidase deficiency is an autosomal recessively inherited disorder of biotin recycling that is associated with neurologic and cutaneous consequences if untreated. Fortunately, the clinical features of the disorder can be ameliorated or prevented by administering pharmacological doses of the vitamin biotin. Newborn screening and confirmatory diagnosis of biotinidase deficiency encompasses both enzymatic and molecular testing approaches. These guidelines were developed to define and standardize laboratory procedures for enzymatic biotinidase testing, to delineate situations for which follow-up molecular testing is warranted, and to characterize variables that can influence test performance and interpretation of results.
  • An outpatient performance improvement project: A baseline assessment of adherence to pain reassessment standards

    Ross, A.; Feider, L.; Nahm, E.-S. (Association of Military Surgeons of the US, 2017)
    Background: This performance improvement (PI) project was conducted to recommend improvements for pain reassessment workflow and policies at a large military primary care clinic. The Joint Commission survey identified inconsistent pain reassessment practices at the facility in 2012. A review of the literature reveals that pain reassessment procedures can be affected by unclear organizational policies, poorly designed documentation procedures, and redundant or inefficient workflow practices. This PI project was designed to assess pain reassessment compliance rates, associated documentation, and clinic workflow, and to identify opportunities for improvement. Methods: Pain reassessment compliance was evaluated using an Electronic Medical Record (EMR) query for patients treated between February 1 and May 30, 2013, who received Toradol at a large military outpatient clinic (n = 151). In addition, observations of clinic workflow were conducted using tracer methodology as recommended by The Joint Commission to track a convenience sample of 12 patients moving through clinic care processes. Pain reassessment documentation and workflow procedures were then evaluated using the Situation Awareness (SA) framework, which is an approach used to evaluate operational implications of factors affecting staff decisions and performance (e.g., stress and workload, interface design, automation, complexity of workflow, staff abilities and training, goals and expectations). Results: The EMR review revealed compliance rates greater than 90% for all pain reassessment requirements with the exception of the maximum 30-minute interval between initial and follow-up pain assessment required by clinic policy, which had a compliance rate of 38%. Pain reassessments were documented to occur at a mean time of 48.25 minutes after initial assessment. During the tracer, none of the 12 patient encounters was fully compliant with clinic policies. An analysis of clinic workflow using the SA framework revealed that the SA of clinic staff was impacted by a lack of standardized procedures and heavy reliance on staff memory. Discussion: Recommendations for improvement included possible extension of the 30-minute time requirement, development of a template for pain reassessment documentation in the EMR, standardizing hand off and admission/discharge processes, and designing an electronic or manual dashboard to indicate pain reassessment times. Future PI projects in other military clinics would benefit from use of the SA perspective to review clinic policies, EMR documentation, and workflow analysis. Further analysis will be needed to evaluate the impact of these improvements.
  • Fatal pertussis in the neonatal mouse model is associated with pertussis toxin-mediated pathology beyond the airways

    Scanlon, K.M.; Snyder, Y.G.; Skerry, C. (American Society for Microbiology, 2017)
    In infants, Bordetella pertussis can cause severe disease, manifested as pronounced leukocytosis, pulmonary hypertension, and even death. The exact cause of death remains unknown, and no effective therapies for treating fulminant pertussis exist. In this study, a neonatal mouse model of critical pertussis is characterized, and a central role for pertussis toxin (PT) is described. PT promoted colonization, leukocytosis, T cell phenotypic changes, systemic pathology, and death in neonatal but not adult mice. Surprisingly, PT inhibited lung inflammatory pathology in neonates, a result which contrasts dramatically with observed PT-promoted pathology in adult mice. Infection with a PT-deficient strain induced severe pulmonary inflammation but not mortality in neonatal mice, suggesting that death in these mice was not associated with impaired lung function. Dissemination of infection beyond the lungs was also detected in neonatal mice, which may contribute to the observed systemic effects of PT. We propose that it is the systemic activity of pertussis toxin and not pulmonary pathology that promotes mortality in critical pertussis. In addition, we observed transmission of infection between neonatal mice, the first report of B. pertussis transmission in mice. This model will be a valuable tool to investigate causes of pertussis pathogenesis and identify potential therapies for critical pertussis.
  • Evaluation of the performance of national health systems in 2004-2011: An analysis of 173 countries

    Sun, D.; Ahn, H.; Lievens, T. (Public Library of Science, 2017)
    In an effort to improve health service delivery and achieve better health outcomes, the World Health Organization (WHO) has called for improved efficiency of health care systems to better use the available funding. This study aims to examine the efficiency of national health systems using longitudinal country-level data. Data on health spending per capita, infant mortality rate (IMR), under 5 mortality rate (U5MR), and life expectancy (LE) were collected from or imputed for 173 countries from 2004 through 2011. Data envelopment analyses were used to evaluate the efficiency and regression models were constructed to examine the determinants of efficiency. The average efficiency of the national health system, when examined yearly, was 78.9%, indicating a potential saving of 21.1% of health spending per capita to achieve the same level of health status for children and the entire population, if all countries performed as well as their peers. Additionally, the efficiency of the national health system varied widely among countries. On average, Africa had the lowest efficiency of 67%, while West Pacific countries had the highest efficiency of 86%. National economic status, HIV/AIDS prevalence, health financing mechanisms and governance were found to be statistically associated with the efficiency of national health systems. Taking health financing as an example, a 1% point increase of social security expenses as a percentage of total health expenditure correlated to a 1.9% increase in national health system efficiency. The study underscores the need to enhance efficiency of national health systems to meet population health needs, and highlights the importance of health financing and governance in improving the efficiency of health systems, to ultimately improve health outcomes. Copyright 2017 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  • Association of electroconvulsive therapy with psychiatric readmissions in US hospitals

    Slade, E.P.; Jahn, D.R.; Regenold, W.T. (American Medical Association, 2017)
    IMPORTANCE: Although electroconvulsive therapy (ECT) is considered the most efficacious treatment available for individuals with severe affective disorders, ECT's availability is limited and declining, suggesting that information about the population-level effects of ECT is needed. OBJECTIVE: To examine whether inpatient treatment with ECT is associated with a reduction in 30-day psychiatric readmission risk in a large, multistate sample of inpatients with severe affective disorders. DESIGN, SETTING, AND PARTICIPANTS: A quasi-experimental instrumental variables probit model of the association correlation of ECT administration with patient risk of 30-day readmission was estimated using observational, longitudinal data on hospital inpatient discharges from US general hospitals in 9 states. From a population-based sample of 490 252 psychiatric inpatients, a sample was drawn that consisted of 162 691 individuals with a principal diagnosis of major depressive disorder (MDD), bipolar disorder, or schizoaffective disorder. The key instrumental variable used in the analysis was ECT prevalence in the prior calendar year at the treating hospital. To examine whether ECT's association with readmissions was heterogeneous across population subgroups, analyses included interactions of ECT with age group, sex, race/ethnicity, and diagnosis group. The study was conducted from August 27, 2015, to March 7, 2017. MAIN OUTCOME AND MEASURES: Readmission within 30 days of being discharged. RESULTS Overall, 2486 of the 162 691 inpatients (1.5%) underwent ECT during their index admission. Compared with other inpatients, those who received ECT were older (mean [SD], 56.8 [16.5] vs 45.9 [16.5] years; P < .001) and more likely to be female (65.0% vs 54.2%; P < .001) and white non-Hispanic (85.3% vs 62.1%; P < .001), have MDD diagnoses (63.8% vs 32.0%; P < .001) rather than bipolar disorder (29.0% vs 40.0%; P < .001) or schizoaffective disorder (7.1% vs 28.0%; P < .001), have a comorbid medical condition (31.3% vs 26.6%; P < .001), have private (39.4% vs 21.7%; P < .001) or Medicare (49.2% vs 39.4%; P < .001) insurance coverage, and be located in urban small hospitals (31.2% vs 22.3%; P < .001) or nonurban hospitals (9.0% vs 7.6%; P = .02). Administration of ECT was associated with a reduced 30-day readmission risk among psychiatric inpatients with severe affective disorders from an estimated 12.3% among individuals not administered ECT to 6.6% among individuals administered ECT (risk ratio [RR], 0.54; 95% CI, 0.28-0.81). Significantly larger associations with ECT on readmission risk were found for men compared with women (RR, 0.44; 95% CI, 0.20-0.69 vs 0.58; 95% CI, 0.30-0.88) and for individuals with bipolar disorder (RR, 0.42; 95% CI, 0.17-0.69) and schizoaffective disorder (RR, 0.44; 95% CI, 0.11-0.79) compared with those who had MDD (RR, 0.53; 95% CI, 0.26-0.81). CONCLUSIONS AND RELEVANCE: Electroconvulsive therapy may be associated with reduced short-term psychiatric inpatient readmissions among psychiatric inpatients with severe affective disorders. This potential population health effect may be overlooked in US hospitals' current decision making regarding the availability of ECT.
  • The Potential of Clinical Phenotyping of Heart�Failure With Imaging Biomarkers for�Guiding�Therapies: A Focused Update

    Sengupta, P.P.; Kramer, C.M.; Narula, J. (Elsevier Inc., 2017)
    The need for noninvasive assessment of cardiac volumes and ejection fraction (EF) ushered in the use of cardiac imaging techniques in heart failure (HF) trials that investigated the roles of pharmacological and device-based therapies. However, in contrast to HF with reduced EF (HFrEF), modern HF pharmacotherapy has not improved outcomes in HF with preserved EF (HFpEF), largely attributed to patient heterogeneity and incomplete understanding of pathophysiological insights underlying the clinical presentations of HFpEF. Modern cardiac imaging methods offer insights into many sets of changes in cardiac tissue structure and function that can precisely link cause with cardiac remodeling at organ and tissue levels to clinical presentations in HF. This has inspired investigators to seek a more comprehensive understanding of HF presentations using imaging techniques. This article summarizes the available evidence regarding the role of cardiac imaging in HF. Furthermore, we discuss the value of cardiac imaging techniques in identifying HF patient subtypes who share similar causes and mechanistic pathways that can be targeted using specific HF therapies.
  • Association between endothelial cell density and transplant suitability of corneal tissue with type 1 and type 2 diabetes

    Margo, J.A.; Munir, W.M.; Brown, C.H. (American Medical Association, 2017)
    IMPORTANCE The rate of types 1 and 2 diabetes in the United States is increasing. The effect of diabetes on corneal donor tissue is unknown. OBJECTIVES To determine the association between endothelial cell density and suitability for transplantation in cornea donors with type 1 or 2 diabetes and determine the effect of diabetes on technician-induced endothelial damage during cornea donor tissue processing. DESIGN, SETTING, AND PARTICIPANTS Donor informationwas obtained from the SightLife Eye Bank for donors from June 1, 2012, to June 30, 2015. The presence of diabetes was determined based on donor medical history. Severe diabetes was classified based on the presence of comorbidities of diabetes. The donor data set contained information on 34 497 donated eyes during the 3-year period, including donor demographics, time from death to refrigeration and preservation of the cornea, endothelial cell count, lens status, medical and surgical history, and suitability for transplantation. MAIN OUTCOMES AND MEASURES Endothelial cell density, suitability for transplantation based on tissue analysis, and technician-induced endothelial damage. RESULTS Among 14 532 donors (mean [SD] age, 58.6 [13.4] years; 8516 men and 6016 women), the mean (SD) endothelial cell count was 2732 (437) cells/mm2. Type 1 or 2 diabetes was listed in the medical history for 8552 of 27 948 donor eyes (30.6%); 5242 eyes (18.8%) were from patients with severe diabetes. After adjusting for age, race/ethnicity, sex, lens status, time from death to refrigeration, and time from death to preservation, the presence of diabetes (adjusted odds ratio, 0.79; 95%CI, 0.51-1.22; P = .28) and severe diabetes (adjusted odds ratio, 95%CI, 0.86; 95%CI, 0.54-1.39; P = .54) were not associated with poor transplant suitability based on results of tissue examination. Donors with diabetes (mean [SD] cell count difference, 9.0 [6.7] cells/mm2; 95%CI,-4.1 to 22.2; P = .18) and severe diabetes (mean [SD] cell count difference, 7.7 [8.1] cells/mm2; 95%CI,-8.1 to 23.6; P = .34) did not exhibit lower cell counts. Technician-induced endothelial damage occurred in 59 corneas (0.2%) but was not associated with the presence of diabetes (adjusted odds ratio, 1.23; 95%CI, 0.66-2.32; P = .52). CONCLUSIONS AND RELEVANCE These data suggest that cornea donors have a high frequency of diabetes. However, this analysis was not able to show that the presence of diabetes was associated with technician-induced endothelial damage, reduced transplant suitability, or reductions in endothelial cell counts. Eye banks may need to collect medical history in a more robust manner. Additional studiesmay be valuable to determine the effect on long-term transplant outcomes of diabetes in cornea donors.
  • Devices for preventing percutaneous exposure injuries caused by needles in healthcare personnel

    Reddy, V.K.; Lavoie, M.-C.; Verbeek, J.H. (John Wiley and Sons Ltd, 2017)
    Background: Percutaneous exposure injuries from devices used for blood collection or for injections expose healthcare workers to the risk of blood borne infections such as hepatitis B and C, and human immunodeficiency virus (HIV). Safety features such as shields or retractable needles can possibly contribute to the prevention of these injuries and it is important to evaluate their effectiveness. Objectives: To determine the benefits and harms of safety medical devices aiming to prevent percutaneous exposure injuries caused by needles in healthcare personnel versus no intervention or alternative interventions. Search methods: We searched CENTRAL, MEDLINE, EMBASE, NHSEED, Science Citation Index Expanded, CINAHL, Nioshtic, CISdoc and PsycINFO (until 11 November 2016). Selection criteria: We included randomised controlled trials (RCT), controlled before and after studies (CBA) and interrupted time-series (ITS) designs of the effect of safety engineered medical devices on percutaneous exposure injuries in healthcare staff. Data collection and analysis: Two of the authors independently assessed study eligibility and risk of bias and extracted data. We synthesized study results with a fixed-effect or random-effects model meta-analysis where appropriate. Main results: We included six RCTs with 1838 participants, two cluster-RCTs with 795 participants and 73,454 patient days, five CBAs with approximately 22,000 participants and eleven ITS with an average of 13.8 data points. These studies evaluated safe modifications of blood collection systems, intravenous (IV) systems, injection systems, multiple devices, sharps containers and legislation on the implementation of safe devices. We estimated the needlestick injury (NSI) rate in the control groups to be about one to five NSIs per 1000 person-years. There were only two studies from low- or middle-income countries. The risk of bias was high in 20 of 24 studies. Safe blood collection systems: We found one RCT that found a safety engineered blood gas syringe having no considerable effect on NSIs (Relative Risk (RR) 0.2, 95% Confidence Interval (95% CI) 0.01 to 4.14, 550 patients, very low quality evidence). In one ITS study, safe blood collection systems decreased NSIs immediately after the introduction (effect size (ES) -6.9, 95% CI -9.5 to -4.2) but there was no further decrease over time (ES -1.2, 95% CI -2.5 to 0.1, very low quality evidence). Another ITS study evaluated an outdated recapping shield, which we did not consider further. Safe Intravenous systems There was very low quality evidence in two ITS studies that NSIs were reduced with the introduction of safe IV devices, whereas one RCT and one CBA study provided very low quality evidence of no effect. However, there was moderate quality evidence produced by four other RCT studies that these devices increased the number of blood splashes when the safety system had to be engaged actively (relative risk (RR) 1.6, 95% CI 1.08 to 2.36). In contrast there was low quality evidence produced by two RCTs of passive systems that showed no effect on blood splashes. Yet another RCT produced low quality evidence that a different safe active IV system also decreased the incidence of blood leakages. Safe injection devices There was very low quality evidence provided by one RCT and one CBA study showing that introduction of safe injection devices did not considerably change the NSI rate. One ITS study produced low quality evidence showing that the introduction of safe passive injection systems had no effect on NSI rate when compared to safe active injection systems. Multiple safe devices There was very low quality evidence from one CBA study and two ITS studies. According to the CBA study, the introduction of multiple safe devices resulted in a decrease in NSI,whereas the two ITS studies found no change. Safety containers One CBA study produced very low quality evidence showing that the introduction of safety containers decreased NSI. However, two ITS studies evaluating the same intervention found inconsistent results. Legislation There was low to moderate quality evidence in two ITS studies that introduction of legislation on the use of safety-engineered devices reduced the rate of NSIs among healthcare workers. There was also low quality evidence which showed a decrease in the trend over time for NSI rates. Twenty out of 24 studies had a high risk of bias and the lack of evidence of a beneficial effect could be due to both confounding and bias. This does not mean that these devices are not effective. Authors' conclusions: For safe blood collection systems, we found very low quality evidence of inconsistent effects on NSIs. For safe passive intravenous systems, we found very low quality evidence of a decrease in NSI and a reduction in the incidence of blood leakage events but moderate quality evidence that active systems may increase exposure to blood. For safe injection needles, the introduction of multiple safety devices or the introduction of sharps containers the evidence was inconsistent or there was no clear evidence of a benefit. There was low to moderate quality evidence that introduction of legislation probably reduces NSI rates. More high-quality cluster-randomised controlled studies that include cost-effectiveness measures are needed, especially in countries where both NSIs and blood-borne infections are highly prevalent.
  • Acute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs Contextual Memory in Adult Rats

    Pocivavsek, A.; Baratta, A.M.; Mong, J.A. (2017)
    Study Objectives: Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction. Modest increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts as an antagonist at N-methyl-d-aspartate and ?7 nicotinic acetylcholine receptors in the brain, result in cognitive impairments. As glutamatergic and cholinergic neurotransmissions are critically involved in modulation of sleep, our current experiments tested the hypothesis that elevated KYNA adversely impacts sleep quality.Methods: Adult male Wistar rats were treated with vehicle (saline) and kynurenine (25, 50, 100, and 250 mg/kg), the direct bioprecursor of KYNA, intraperitoneally at zeitgeber time (ZT) 0 to rapidly increase brain KYNA. Levels of KYNA in the brainstem, cortex, and hippocampus were determined at ZT 0, ZT 2, and ZT 4, respectively. Analyses of vigilance state-related parameters categorized as wake, rapid eye movement (REM), and non-REM (NREM) as well as spectra power analysis during NREM and REM were assessed during the light phase. Separate animals were tested in the passive avoidance paradigm, testing contextual memory.Results: When KYNA levels were elevated in the brain, total REM duration was reduced and total wake duration was increased. REM and wake architecture, assessed as number of vigilance state bouts and average duration of each bout, and theta power during REM were significantly impacted. Kynurenine challenge impaired performance in the hippocampal-dependent contextual memory task.Conclusions: Our results introduce kynurenine pathway metabolism and formation of KYNA as a novel molecular target contributing to sleep disruptions and cognitive impairments.
  • The double-stranded RNA binding protein RDE-4 can act cell autonomously during feeding RNAi in C. elegans

    Raman, P.; Zaghab, S.M.; Traver, E.C. (Oxford University Press, 2017)
    Long double-stranded RNA (dsRNA) can silence genes ofmatching sequence upon ingestion inmany invertebrates and is therefore being developed as a pesticide. Such feeding RNA interference (RNAi) is best understood in the worm Caenorhabditis elegans, where the dsRNA-binding protein RDE-4 initiates silencing by recruiting an endonuclease to process long dsRNA into short dsRNA. These short dsRNAs are thought to move between cells because muscle-specific rescue of rde-4 using repetitive transgenes enables silencing in other tissues. Here, we extend this observation using additional promoters, report an inhibitory effect of repetitive transgenes, and discover conditions for cell-autonomous silencing in animals with tissue-specific rescue of rde-4. While expression of rde-4(+) in intestine, hypodermis, or neurons using a repetitive transgene can enable silencing also in unrescued tissues, silencing can be inhibited wihin tissues that express a repetitive transgene. Single-copy transgenes that express rde-4(+) in body-wall muscles or hypodermis, however, enable silencing selectively in the rescued tissue but not in other tissues. These results suggest that silencing by the movement of short dsRNA between cells is not an obligatory feature of feeding RNAi in C. elegans. We speculate that similar control of dsRNA movement could modulate tissue-specific silencing by feeding RNAi in other invertebrates. Copyright The Author(s) 2017.
  • Clostridium difficile colonization of nursing home residents

    Roghmann, M.-C.; Andronescu, L.R.; Stucke, E.M. (Cambridge University Press, 2017)
  • Single session of functional electrical stimulation-assisted walking produces corticomotor symmetry changes related to changes in poststroke walking mechanics

    Palmer, J.A.; Hsiao, H.Y.; Wright, T. (American Physical Therapy Association, 2017)
    Background. Recent research demonstrated that the symmetry of corticomotor drive with the paretic and nonparetic plantarflexor muscles was related to the biomechanical ankle moment strategy that people with chronic stroke used to achieve their greatest walking speeds. Rehabilitation strategies that promote corticomotor balance might improve poststroke walking mechanics and enhance functional ambulation. Objective. The study objectives were to test the effectiveness of a single session of gait training using functional electrical stimulation (FES) to improve plantarflexor corticomotor symmetry and plantarflexion ankle moment symmetry and to determine whether changes in corticomotor symmetry were related to changes in ankle moment symmetry within the session. Design. This was a repeated-measures crossover study. Methods. On separate days, 20 people with chronic stroke completed a session of treadmill walking either with or without the use of FES of their ankle dorsi- and plantarflexor muscles. We calculated plantarflexor corticomotor symmetry using transcranial magnetic stimulation and plantarflexion ankle moment symmetry during walking between the paretic and the nonparetic limbs before and after each session. We compared changes and tested relationships between corticomotor symmetry and ankle moment symmetry following each session. Results. Following the session with FES, there was an increase in plantarflexor corticomotor symmetry that was related to the observed increase in ankle moment symmetry. In contrast, following the session without FES, there were no changes in corticomotor symmetry or ankle moment symmetry. Limitations. No stratification was made on the basis of lesion size, location, or clinical severity. Conclusions. These findings demonstrate, for the first time (to our knowledge), the ability of a single session of gait training with FES to induce positive corticomotor plasticity in people in the chronic stage of stroke recovery. They also provide insight into the neurophysiologic mechanisms underlying improvements in biomechanical walking function.
  • Loop-Mediated isothermal amplification for detection of the 5.8s ribosomal ribonucleic acid internal transcribed spacer 2 gene found in trypanosoma brucei gambiense

    Nikolskaia, O.V.; Thekisoe, O.M.; Stephen, Dumler, J. (American Society of Tropical Medicine and Hygiene, 2017)
    The loop-mediated isothermal amplification (LAMP) assay with its advantages of cost effectiveness, rapidity, and simplicity, has evolved as a sensitive and specific method for the detection of African trypanosomes. Highly sensitive LAMP reactions specific for Trypanosoma brucei rhodesiense or that recognize but do not discriminate between Trypanosoma brucei brucei, T. b. rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma evansi have been developed. A sensitive LAMP assay targeting the T. b. gambiense 5.8S ribosomal RNA internal transcribed spacer 2 (5.8SITS2) gene is also available but this assay does not target binding sites that span the CCCA (C3A) (557-560 bps) insertion site that further differentiates T. b. gambiense from T. b. brucei. Here we describe 5.8S-ITS2-targeted LAMP assay that fit these criteria. The LAMP primer sets containing the T. b. gambiense-specific C3A tetranucleotide at the start of the outer forward primer sequences showed high specificity and sensitivity down to at least 0.1 fg T. b. gambiense genomic DNA.
  • A practical framework for understanding and reducing medical overuse: Conceptualizing overuse through the patient-clinician interaction

    Morgan, D.J.; Leppin, A.L.; Smith, C.D. (Society of hospital medicine, 2017)
    Overuse of medical services is an increasingly recognized driver of poor-quality care and high cost. A practical framework is needed to guide clinical decisions and facilitate concrete actions that can reduce overuse and improve care. We used an iterative, expert-informed, evidence- based process to develop a framework for conceptualizing interventions to reduce medical overuse. Given the complexity of defining and identifying overused care in nuanced clinical situations and the need to define care appropriateness in the context of an individual patient, this framework conceptualizes the patient�clinician interaction as the nexus of decisions regarding inappropriate care. This interaction is influenced by other utilization drivers, including healthcare system factors, the practice environment, the culture of professional medicine, the culture of healthcare consumption, and individual patient and clinician factors. The variable strength of the evidence supporting these domains highlights important areas for further investigation.
  • Review of breast screening: Toward clinical realization of microwave imaging: Toward

    Modiri, A.; Goudreau, S.; Rahimi, A. (John Wiley and Sons Ltd., 2017)
    Microwave imaging (MI) technology has come a long way to introduce a noninvasive, inexpensive, fast, convenient, and safe screening tool for clinical breast monitoring. However, there is a niche between the existing understanding of MI by engineers versus clinicians. Our manuscript targets that niche and highlights the state of the art in MI technology compared to the existing breast cancer detection modalities (mammography, ultrasound, molecular imaging, and magnetic resonance). The significance of our review article is in consolidation of up-to-date breast clinician views with the practical needs and engineering challenges of a novel breast screening modality. We summarize breast tissue abnormalities and highlight the benefits as well as potential drawbacks of the MI as a cancer detection methodology. Our goal is to present an article that MI researchers as well as practitioners in the field can use to assess the viability of the MI technology as a competing or complementary modality to the existing means of breast cancer screening.
  • Is Mycobacterium avium paratuberculosis the trigger in the Crohn's disease spectrum?

    Oken, H.A.; Saleeb, P.G.; Redfield, R.R. (Oxford University Press, 2017)
    We present and discuss a 30-month investigation of a patientthat presented with abdominal pain, postprandial diarrhea,bloating, and night sweats and was treated for Crohn's diseasewithout significant improvement. The patient underwent an ileocecetomywith removal of an atonic segment with resolutionof functional gastrointestinal symptoms, but profound nightsweats continued postoperatively. The patient was presumptivelytreated for a mixed mycobacterial infection, blood cultureslater grew Mycobacterium avium paratuberculosis (MAP),and she improved over time. We discuss MAP and its possiblerelationship to Crohn's disease. Copyright The Author 2017.
  • An in Vitro Model for the Ocular Surface and Tear Film System

    Lu, Q.; Yin, H.; Grant, M.P. (Nature Publishing Group, 2017)
    Dry eye is a complicated ocular surface disease whose exact pathogenesis is not yet fully understood. For the therapeutic evaluation and pathogenesis study of dry eye, we established an in vitro three-dimensional (3D) coculture model for the ocular surface. It is composed of rabbit conjunctival epithelium and lacrimal gland cell spheroids, and recapitulates the aqueous and mucin layers of the tear film. We first investigated the culture conditions for both cell types to optimize their secretory functions, by employing goblet cell enrichment, air-lifting culture, and 3D spheroid formation techniques. The coculture of the two cell components leads to elevated secretion and higher expression of tear secretory markers. We also compared several coculture systems, and found that direct cell contact between the two cell types significantly increased tear secretion. Inflammation was induced to mimic dry eye disease in the coculture model system. Our results showed that the coculture system provides a more physiologically relevant therapeutic response compared to monocultures. Our work provides a complex 3D model as a recapitulation of the ocular surface and tear film system, which can be further developed as a model for dry eye disease and therapeutic evaluation. Copyright 2017 The Author(s).
  • Is there a doctor on board? In-flight medical emergencies

    Nablel, J.V.; Tupe, C.L.; Gehle, B.D. (Cleveland Clinic Educational Foundation, 2017)
    Although not legally required to render assistance in the event of a medical emergency aboard an airplane, physicians have an ethical obligation to do so and should be prepared.
  • The changing landscape of Trauma care, Part 1

    Menne, A.; Haase, D.; Menaker, J. (Quadrant Healthcom Inc., 2017)
  • Human immune responses against Shigella and enterotoxigenic E. coli: Current advances and the path forward

    McArthur, M.A.; Maciel, M.; Jr. (Elsevier Ltd, 2017)
    Robust and well-established immunological assays and firm immune correlates of protection that can predict disease outcome and/or vaccine efficacy are essential to adequately assess human immune responses to infection and vaccination. The availability of reagents and calibrated controls is also critically important to standardize assays and generate comparable results among different laboratories. The workshop �Human Immune Responses against Shigella and ETEC: Current Advances and the Path Forward� held during the VASE meeting provided an opportunity to disseminate and discuss recent advances in the field of Shigella and ETEC immunology, identify research needs, and propose collaborative activities to advance the field. Four presentations featured current knowledge on humoral and cellular immune responses to Shigella and ETEC during infection and vaccination. A discussion followed on immunological methods relevant for clinical studies, immune parameters associated with protection, harmonization of assays among laboratories, and availability of reagents and standards. Specific recommendations proposed to facilitate �the path forward� included supporting communication among scientists, harmonization of assays and sharing of protocols, the creation of a repository of reagents and calibrated controls and distribution of such material to the research community, and expansion of exploratory studies to better understand the interactions between these pathogens and the human immune system and the ensuing responses.

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