Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs) using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides. These compounds may serve as potential drug leads. This review summarizes the insights gained from research on type III PKSs, from the discovery of chalcone synthase in plants to novel PKSs in bacteria and fungi. To date, at least 15 families of type III PKSs have been characterized, highlighting the utility of PKSs in the development of natural product libraries for therapeutic development.
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- Molecules, Vol. 21, Pages 806: Exploiting the Bios...
- Molecules, Vol. 21, Pages 809: Syk and IRAK1 Contr...
- Viruses, Vol. 8, Pages 176: Mouse Systems to Model...
- Entropy, Vol. 18, Pages 235: A PUT-Based Approach ...
- Viruses, Vol. 8, Pages 178: Marburg Virus Reverse ...
- Arts, Vol. 5, Pages 4: Cinematic Bodies
- Unit-based incident reporting and root cause analy...
- Cross-sectional study of coeliac autoimmunity in a...
- Tranexamic acid in hip fracture patients: a protoc...
- Systematic review of patients' participation in an...
- A pharmacoeconomic approach to assessing the costs...
- Predictors of seeking emergency medical help durin...
- The use of the reverse shock index to identify hig...
- Pulmonary embolism and mortality following total a...
- Hepatosplenic tuberculosis simulating secondary ma...
- Administrative Sciences, Vol. 6, Pages 6: The Stat...
- Peginterferon Lambda-1a/Ribavirin with Daclatasvir...
- Greenhouse Gas Molecule CO2 Detection Using a Capa...
- New Method for Sorting Endothelial and Neural Prog...
- High-Efficiency Capture of Individual and Cluster ...
- Role of Side Effects, Physician Involvement, and P...
- Spinal Cord Injury - Quality of Life Grief / Loss
- Methods for Acute and Subacute Murine Hindlimb Isc...
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Τρίτη 21 Ιουνίου 2016
Molecules, Vol. 21, Pages 806: Exploiting the Biosynthetic Potential of Type III Polyketide Synthases
Molecules, Vol. 21, Pages 809: Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid
Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA) was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays, kinase assays, immunoblot analyses, and overexpression strategies with lipopolysaccharide (LPS)-treated macrophages. AQCA was found to suppress the release of nitric oxide (NO) and prostaglandin (PG) E2 from LPS-treated peritoneal macrophages without displaying any toxic side effects. Molecular analysis revealed that AQCA was able to inhibit the activation of the nuclear factor (NF)-κB and activator protein (AP)-1 pathways by direct suppression of upstream signaling enzymes including interleukin-1 receptor-associated kinase 1 (IRAK1) and spleen tyrosine kinase (Syk). Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1.
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Viruses, Vol. 8, Pages 176: Mouse Systems to Model Hepatitis C Virus Treatment and Associated Resistance
While addition of the first-approved protease inhibitors (PIs), telaprevir and boceprevir, to pegylated interferon (PEG-IFN) and ribavirin (RBV) combination therapy significantly increased sustained virologic response (SVR) rates, PI-based triple therapy for the treatment of chronic hepatitis C virus (HCV) infection was prone to the emergence of resistant viral variants. Meanwhile, multiple direct acting antiviral agents (DAAs) targeting either the HCV NS3/4A protease, NS5A or NS5B polymerase have been approved and these have varying potencies and distinct propensities to provoke resistance. The pre-clinical in vivo assessment of drug efficacy and resistant variant emergence underwent a great evolution over the last decade. This field had long been hampered by the lack of suitable small animal models that robustly support the entire HCV life cycle. In particular, chimeric mice with humanized livers (humanized mice) and chimpanzees have been instrumental for studying HCV inhibitors and the evolution of drug resistance. In this review, we present the different in vivo HCV infection models and discuss their applicability to assess HCV therapy response and emergence of resistant variants.
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Entropy, Vol. 18, Pages 235: A PUT-Based Approach to Automatically Extracting Quantities and Generating Final Answers for Numerical Attributes
Automatically extracting quantities and generating final answers for numerical attributes is very useful in many occasions, including question answering, image processing, human-computer interaction, etc. A common approach is to learn linguistics templates or wrappers and employ some algorithm or model to generate a final answer. However, building linguistics templates or wrappers is a tough task for builders. In addition, linguistics templates or wrappers are domain-dependent. To make the builder escape from building linguistics templates or wrappers, we propose a new approach to final answer generation based on Predicates-Units Table (PUT), a mini domain-independent knowledge base. It is deserved to point out that, in the following cases, quantities are not represented well. Quantities are absent of units. Quantities are perhaps wrong for a given question. Even if all of them are represented well, their units are perhaps inconsistent. These cases have a strong impact on final answer solving. One thousand nine hundred twenty-six real queries are employed to test the proposed method, and the experimental results show that the average correctness ratio of our approach is 87.1%.
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Viruses, Vol. 8, Pages 178: Marburg Virus Reverse Genetics Systems
The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.
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Arts, Vol. 5, Pages 4: Cinematic Bodies
It is difficult to imagine a cinema without bodies.[...]
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Unit-based incident reporting and root cause analysis: variation at three hospital unit types
Objectives
To minimise adverse events in healthcare, various large-scale incident reporting and learning systems have been developed worldwide. Nevertheless, learning from patient safety incidents is going slowly. Local, unit-based reporting systems can help to get faster and more detailed insight into unit-specific safety issues. The aim of our study was to gain insight into types and causes of patient safety incidents in hospital units and to explore differences between unit types.
DesignProspective observational study.
Setting10 emergency medicine units, 10 internal medicine units and 10 general surgery units in 20 hospitals in the Netherlands participated. Patient safety incidents were reported by healthcare providers. Reports were analysed with root cause analysis. The results were compared between the 3 unit types.
ResultsA total of 2028 incidents were reported in an average reporting period of 8 weeks per unit. More than half had some consequences for patients, such as a prolonged hospital stay or longer waiting time, and a small number resulted in patient harm. Significant differences in incident types and causes were found between unit types. Emergency units reported more incidents related to collaboration, whereas surgical and internal medicine units reported more incidents related to medication use. The distribution of root causes of surgical and emergency medicine units showed more mutual similarities than those of internal medicine units.
ConclusionsComparable incidents and causes have been found in all units, but there were also differences between units and unit types. Unit-based incident reporting gives specific information and therefore makes improvements easier. We conclude that unit-based incident reporting has an added value besides hospital-wide or national reporting systems that already exist in various countries.
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Cross-sectional study of coeliac autoimmunity in a population of Vietnamese children
Objective
The prevalence of coeliac disease (CD) in Vietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi.
SettingThe outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam.
ParticipantsChildren having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96%) were enrolled (838 females, 1123 males, median age 5.3 years).
OutcomesPrimary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG.
ResultsThe IgA anti-tTG test was positive in 21/1961 (1%; 95% CI 0.61% to 1.53%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33%; 95% CI 14.5% to 56.9%) of the anti-tTG-positive children and in 72/275 (26%; 95% CI 21% to 32%) of those who were negative.
ConclusionsCoeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings.
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Tranexamic acid in hip fracture patients: a protocol for a randomised, placebo controlled trial on the efficacy of tranexamic acid in reducing blood loss in hip fracture patients
Introduction
There is a high incidence of blood transfusion following hip fractures in elderly patients. Tranexamic acid (TXA) has proven efficacy in decreasing blood loss in general trauma patients as well as patients undergoing elective orthopaedic surgery. A randomised controlled trial will measure the effect of TXA in a population of patients undergoing hip fracture surgery.
MethodsThis is a double-blinded, randomised placebo-controlled trial. Patients admitted through the emergency room that are diagnosed with an intertrochanteric or femoral neck fracture will be eligible for enrolment and randomised to either treatment with 1 g of intravenous TXA or intravenous saline at the time of skin incision. Patients undergoing percutaneous intervention for non-displaced or minimally displaced femoral neck fractures will not be eligible for enrolment. Postoperative transfusion rates will be recorded and blood loss will be calculated from serial haematocrits.
Ethics and disseminationThis protocol was approved by the Institutional Review Board (IRB) and is registered with clinicaltrials.gov. The findings of the trial will be disseminated through peer-reviewed journals and conference presentations.
Trial registration numberNCT01940536.
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Systematic review of patients' participation in and experiences of technology-based monitoring of mental health symptoms in the community
Objectives
To review systematically the literature on patients' experiences of, and participation in, technology-based monitoring of mental health symptoms. This practice was defined as patients monitoring their mental health symptoms, emotions or behaviours outside of routine clinical appointments by submitting symptom data using technology, with feedback arising from the data (for example, supportive messages or symptom summaries, being sent to the patient, clinician or carer).
DesignSystematic review following PRISMA guidelines of studies evaluating technology-based symptom monitoring. Tools from narrative synthesis were used to analyse quantitative findings on participation rates and qualitative findings on patient views.
Data sourcesPubMed, EMBASE, PsycINFO, BNI, CINAHL, Cochrane Registers and Web of Science electronic databases were searched using a combination of 'psychiatry', 'symptom monitoring' and 'technology' descriptors. A secondary hand search was performed in grey literature and references.
Results57 papers representing 42 studies met the inclusion criteria for the review. Technology-based symptom monitoring was used for a range of mental health conditions, either independently of a specific therapeutic intervention or as an integrated component of therapeutic interventions. The majority of studies reported moderate-to-strong rates of participation, though a third reported lower rates. Qualitative feedback suggests that acceptability of monitoring is related to perceived validity, ease of practice, convenient technology, appropriate frequency and helpfulness of feedback, as well as the impact of monitoring on participants' ability to manage health and personal relationships.
ConclusionsSuch symptom monitoring practices appear to be well accepted and may be a feasible complement to clinical practice. However, there is limited availability of data and heterogeneity of studies. Future research should examine robustly patients' role in the development and evaluation of technology-based symptom monitoring in order to maximise its clinical utility.
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A pharmacoeconomic approach to assessing the costs and benefits of air quality interventions that improve health: a case study
Objective
This paper explores the use of pharmacoeconomic methods of valuation to health impacts resulting from exposure to poor air quality. In using such methods, interventions that reduce exposure to poor air quality can be directly compared, in terms of value for money (or cost-effectiveness), with competing demands for finite resources, including other public health interventions.
DesignUsing results estimated as part of a health impact assessment regarding a West Yorkshire Low Emission Zone strategy, this paper quantifies cost-saving and health-improving implications of transport policy through its impact on air quality.
Data sourceEstimates of health-related quality of life and the National Health Service (NHS)/Personal Social Services (PSS) costs for identified health events were based on data from Leeds and Bradford using peer-reviewed publications or Office for National Statistics releases.
PopulationInhabitants of the area within the outer ring roads of Leeds and Bradford.
Main outcomes measuresNHS and PSS costs and quality-adjusted life years (QALYs).
ResultsAverting an all-cause mortality death generates 8.4 QALYs. Each coronary event avoided saves £28 000 in NHS/PSS costs and generates 1.1 QALYs. For every fewer case of childhood asthma, there will be NHS/PSS cost saving of £3000 and a health benefit of 0.9 QALYs. A single term, low birthweight birth avoided saves £2000 in NHS/PSS costs. Preventing a preterm birth saves £24 000 in NHS/PSS costs and generates 1.3 QALYs. A scenario modelled in the West Yorkshire Low Emission Zone Feasibility Study, where pre-EURO 4 buses and HGVs are upgraded to EURO 6 by 2016 generates an annual benefit of £2.08 million and a one-off benefit of £3.3 million compared with a net present value cost of implementation of £6.3 million.
ConclusionsInterventions to improve air quality and health should be evaluated and where improvement of population health is the primary objective, cost-effectiveness analysis using a NHS/PSS costs and QALYs framework is an appropriate methodology.
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Predictors of seeking emergency medical help during overdose events in a provincial naloxone distribution programme: a retrospective analysis
Objectives
This study sought to identify factors that may be associated with help-seeking by witnesses during overdoses where naloxone is administered.
SettingOverdose events occurred in and were reported from the five regional health authorities across British Columbia, Canada. Naloxone administration forms completed following overdose events were submitted to the British Columbia Take Home Naloxone programme.
ParticipantsAll 182 reported naloxone administration events, reported by adult men and women and occurring between 31 August 2012 and 31 March 2015, were considered for inclusion in the analysis. Of these, 18 were excluded: 10 events which were reported by the person who overdosed, and 8 events for which completed forms did not indicate whether or not emergency medical help was sought.
Primary and secondary outcome measuresSeeking emergency medical help (calling 911), as reported by participants, was the sole outcome measure of this analysis.
ResultsMedical help was sought (emergency services—911 called) in 89 (54.3%) of 164 overdoses where naloxone was administered. The majority of administration events occurred in private residences (50.6%) and on the street (23.4%), where reported rates of calling 911 were 27.5% and 81.1%, respectively. Overdoses occurring on the street (compared to private residence) were significantly associated with higher odds of calling 911 in multivariate analysis (OR=10.68; 95% CI 2.83 to 51.87; p<0.01), after adjusting for other variables.
ConclusionsOverdoses occurring on the street were associated with higher odds of seeking emergency medical help by responders. Further research is needed to determine if sex and stimulant use by the person who overdosed are associated with seeking emergency medical help. The results of this study will inform interventions within the British Columbia Take Home Naloxone programme and other jurisdictions to encourage seeking emergency medical help.
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The use of the reverse shock index to identify high-risk trauma patients in addition to the criteria for trauma team activation: a cross-sectional study based on a trauma registry system
Objectives
The presentation of decrease blood pressure with tachycardia is usually an indicator of significant blood loss. In this study, we used the reverse shock index (RSI), a ratio of systolic blood pressure (SBP) to heart rate (HR), to evaluate the haemodynamic status of trauma patients. As an SBP lower than the HR (RSI<1) may indicate haemodynamic instability, the objective of this study was to assess whether RSI<1 can help to identify high-risk patients with potential shock and poor outcome, even though these patients do not yet meet the criteria for multidisciplinary trauma team activation (TTA).
DesignCross-sectional study.
SettingTaiwan.
ParticipantsWe retrospectively reviewed the data of 20 106 patients obtained from the trauma registry system of a level I trauma centre for trauma admissions from January 2009 through December 2014. Patients for whom a trauma team was not activated (regular patients) and who had RSI<1 were compared with regular patients with RSI≥1. The ORs of the associated conditions and injuries were calculated with 95% CIs.
Main outcome measuresIn-hospital mortality.
ResultsAmong regular patients with RSI<1, significantly more patients had an Injury Severity Score (ISS) ≥25 (OR 2.4, 95% CI 1.58 to 3.62; p<0.001) and the mortality rate was also higher (2.1% vs 0.5%; OR 3.9, 95% CI 2.10 to 7.08; p<0.001) than in regular patients with RSI≥1. The intensive care unit length of stay was longer in regular patients with RSI<1 than in regular patients with RSI≥1.
ConclusionsAmong patients who did not reach the criteria for TTA, RSI<1 indicates a potentially worse outcome and a requirement for more attention and aggressive care in the emergency department.
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Pulmonary embolism and mortality following total ankle replacement: a data linkage study using the NJR data set
Objective
To determine the mortality rate following total ankle replacement (TAR) and incidence of 90 day pulmonary embolism (PE) along with the associated risk factors.
DesignData-linkage study of the UK National Joint Registry (NJR) data and Hospital Episodes Statistics (HES) database. Linkage was performed in a deterministic fashion. HES episodes 90 days after the index procedure were analysed for PE. Mortality data were obtained pertaining to all the index procedures from the NJR for analysis.
ParticipantsAll primary and revision ankle replacement patients captured on the NJR between February 2008 and February 2013.
ResultsThe 90-day mortality following TAR was 0.13% (95% CI 0.03 to 0.52) and 1-year mortality was 0.72% (95% CI 0.40 to 1.30); no deaths were as a result of PE. The incidence of PE within 90 days following primary TAR was 0.51% (95% CI 0.23 to 1.13). There was only one PE following revision surgery. Patients with an Royal College of Surgeons Charlson score greater than zero were at 13 times greater risk of PE (p=0.003).
ConclusionsThere is low incidence of PE following TAR, but multiple comorbidities are a leading risk factor for its occurrence.
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Hepatosplenic tuberculosis simulating secondary malignant lesions with cholangitis
Hepatic and/or splenic tuberculosis may simulate much pathology including malignancies, which can roam the diagnosis. Biopsy is necessary for diagnosis. The treatment allows healing and a cleaning of radiologi...
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Administrative Sciences, Vol. 6, Pages 6: The State of Innovation and Entrepreneurship Research
Innovation is informed by the ability to see connections, spot opportunities, and take advantage of them.
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Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b
Journal of Interferon & Cytokine Research , Vol. 0, No. 0.
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Greenhouse Gas Molecule CO2 Detection Using a Capacitive Micromachined Ultrasound Transducer
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New Method for Sorting Endothelial and Neural Progenitors from Human Induced Pluripotent Stem Cells by Sedimentation Field Flow Fractionation
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High-Efficiency Capture of Individual and Cluster of Circulating Tumor Cells by a Microchip Embedded with Three-Dimensional Poly(dimethylsiloxane) Scaffold
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Role of Side Effects, Physician Involvement, and Patient Perception in Non-Adherence with Oral Bisphosphonates
Abstract
Introduction
The benefits of osteoporosis therapy are compromised by low adherence, thus requiring a better understanding of its barriers and unmet needs. The objective of this study was to assess reasons for non-adherence with oral bisphosphonates among osteoporotic women.
Methods
A cross-sectional patient survey of women who initiated therapy with risedronate or alendronate between the years 2010 and 2012 were non-adherent [Medication Possession Ratio (MPR) <70%] or switched therapy within the first year. Survey participants were identified using Maccabi Health Services computerized database. Patients who gave informed consent completed a 20-min telephonic survey, assessing reasons for discontinuation or switching, including physician involvement, side effects, administration regimen, perceptions of bone health, and medications' efficacy.
Results
The study population included 493 females (mean age = 66 ± 7) of whom 40% discontinued all anti-osteoporotic therapy (mean MPR = 19%), 9% remained on initial therapy (mean MPR = 47%), and 51% switched therapy (mean MPR = 62%). Family history, fracture history, socioeconomic status, and index drug class and frequency were similar in all groups. The most common reasons for switching or discontinuation of the first-line therapy were gastrointestinal side effects, such as heartburn, acid reflux or other (40.0%), and physician recommendation (26.7%). The major reasons for complete discontinuation of therapy were side effects (26.9%) and physician recommendation (20.0%). Perceived low importance was more commonly mentioned than high cost of medication (14% vs. 3%).
Conclusion
Our findings highlight the importance of low tolerability to non-adherence with osteoporosis therapy and underlines poor patients' awareness and sub-optimal physicians' involvement in conveying the importance of this therapy.
Funding
Merck & Co Inc.
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Spinal Cord Injury - Quality of Life Grief / Loss
The SCI-QOL Grief / Loss instrument assesses the emotional reactions of grief and feelings of loss in response to sustaining a spinal cord injury (SCI).
The SCI-QOL Grief / Loss instrument is an item response theory (IRT)-calibrated item bank with 17 items that is available for administration as a computer adaptive test (CAT; range 4-12 items) or 9 item short form (SF).
- Full Item Bank: Mean SEM= 2.18 (Range= 0.16-0.48)
- 9-Item Short Form: Mean SEM= 0.27 (Range= 0.20 - 0.51)
- 9-Item Fixed CAT: Mean SEM= 0.25 (Range= 0.19-0.49)
- Variable-length CAT (Min 8): Mean SEM= 0.56 (Range= 0.20 - 0.49)
- Variable Length CAT (Min 4): Mean SEM= 0.30 (0.26-0.49)
- Full Item Bank: MDC= 6.04
- 9-Item Fixed CAT: MDC= 0.69
- Variable Length CAT (Min 4): MDC= 0.83
- Excellent: (Pearson's r= 0.84)
- Excellent: (ICC= 0.83)
- Full Item Bank - Excellent: (Cronbach's alpha= 0.95)
- Floor Effect: Adequate to Excellent (4.8%)
- Ceiling Effect: Excellent (0.3%)
- Floor Effect: Adequate to Excellent (6.2%)
- Ceiling Effect: Adequate to Excellent (1.4%)
- Floor Effect: Adequate to Excellent (5.4)
- Ceiling Effect: Excellent (0.3%)
- Floor Effect: Adequate to Excellent (4.9%)
- Ceiling Effect: Excellent (0.3%)
- Floor Effect: Adequate to Excellent (4.9%)
- Ceiling Effect: Excellent (0.3%)
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Methods for Acute and Subacute Murine Hindlimb Ischemia
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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