This episode: Microbes in tight spaces grow so much they can build up pressure and burst out!
(5.5 MB, 6 minutes)
Show notes:
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 11 Δεκεμβρίου 2016
BacterioFiles 280 - Saccharomyces Smash Small Spaces
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Thoracic Extramedullary Hematopoiesis Mimicking Metastatic Cancer
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Evaluation of the antibacterial activity of a conventional orthodontic composite containing silver/hydroxyapatite nanoparticles
One of the most important complications of fixed orthodontic treatment is the formation of white spots which are initial carious lesions. Addition of antimicrobial agents into orthodontic adhesives might be a ...
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Le Carbone, a charcoal supplement, modulates DSS-induced acute colitis in mice through activation of AMPKα and downregulation of STAT3 and caspase 3 dependent apoptotic pathways
Publication date: February 2017
Source:International Immunopharmacology, Volume 43
Author(s): Mst. Rejina Afrin, Somasundaram Arumugam, Md. Azizur Rahman, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Meilei Harima, Hiroshi Suzuki, Takashi Nakamura, Shizuka Miyashita, Kenji Suzuki, Kazuyuki Ueno, Kenichi Watanabe
Le Carbone (LC) is a charcoal supplement, which contains a large amount of dietary fibers. Several studies suggested that charcoal supplement may be beneficial for stomach disorders, diarrhea, gas and indigestion. But no studies address whether LC intake would suppress inflammation, cell proliferation or disease progression in colitis. In the present study, the effect of LC on experimental colitis induced by dextran sulfate sodium (DSS) in mice and its possible mechanism of action were examined. A study was designed for 8days, using C57BL/6 female mice that were administered with 3% DSS in drinking water for 7days followed by another 1day consumption of normal water with or without treatment. LC suspension was administered daily for 7days via oral gavage using 5mg/mouse in treatment group and normal group was supplied with drinking water. LC suspension significantly attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic changes were significantly reduced by LC treatment. The inflammatory mediators TNFα, IL-1β, p-STAT3 and p-NF-κB induced in the colon by DSS were markedly suppressed by LC. The increased activation of AMPKα in the colon was also detected in LC group. Furthermore, the apoptotic marker protein cleaved caspase 3 was down-regulated and anti-apoptotic proteins Bcl2 and Bcl-xL were significantly up-regulated by LC treatment. Taken together, our results demonstrate the ability of LC to inhibit inflammation, apoptosis and give some evidence for its potential use as adjuvant treatment of inflammatory bowel disease.
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The age dependent association between aortic pulse wave velocity and telomere length
Abstract
Introduction: Ageing is associated with marked large artery stiffening. Telomere shortening, a marker of cellular ageing, is linked with arterial stiffening. However, the results of existing studies are inconsistent, possibly because of the confounding influence of variable exposure to cardiovascular (CV) risk factors. Therefore, we investigated the relationship between telomere length (TL) and aortic stiffness in well-characterised, younger and older healthy adults, pre-selected on the basis of having either low or high aortic pulse wave velocity (aPWV), a robust measure of aortic stiffness. Methods: Demographic, haemodynamic and biochemical data were drawn from participants in the Anglo-Cardiff Collaborative Trial. Two age groups with an equal gender ratio were examined: those < 30 years (younger) or > 50 years (older). Separately for each age group and gender, DNA samples representing the highest (n = 125) and lowest (n = 125) extremes of aPWV (adjusted for blood pressure) were selected for analysis of leukocyte TL. Ultimately, this yielded complete phenotypic data on 904 individuals. Results: In younger subjects, TL was significantly shorter in those with high aPWV versus those low aPWV (P = 0.017). In contrast, in older subjects, TL was significantly longer in those with high aPWV (P = 0.001). Age significantly modified the relationship between aPWV and TL (P < 0.001). Discussion: Age modifies the relationship between aPWV and TL. Differential relationships are observed between aPWV and TL, with an inverse association in younger individuals and a positive association in older individuals. The links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life-course.
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Early prediction of thiopurine-induced hepatotoxicity in inflammatory bowel disease
Summary
Background
Hepatotoxicity, gastrointestinal complaints and general malaise are common limiting adverse reactions of azathioprine and mercaptopurine in IBD patients, often related to high steady-state 6-methylmercaptopurine ribonucleotide (6-MMPR) metabolite concentrations.
Aim
To determine the predictive value of 6-MMPR concentrations 1 week after treatment initiation (T1) for the development of these adverse reactions, especially hepatotoxicity, during the first 20 weeks of treatment.
Methods
The cohort study consisted of the first 270 IBD patients starting thiopurine treatment as part of the Dutch randomised-controlled trial evaluating pre-treatment thiopurine S-methyltransferase genotype testing (ClinicalTrials.gov NCT00521950). Blood samples for metabolite assessment were collected at T1. Hepatotoxicity was defined by alanine aminotransaminase elevations >2 times the upper normal limit or a ratio of alanine aminotransaminase/alkaline phosphatase ≥5.
Results
Forty-seven patients (17%) presented hepatotoxicity during the first 20 weeks of thiopurine treatment. A T1 6-MMPR threshold of 3615 pmol/8 × 108 erythrocytes was defined. Analysis of patients on stable thiopurine dose (n = 174) showed that those exceeding the 6-MMPR threshold were at increased risk of hepatotoxicity: OR = 3.8 (95% CI: 1.8–8.0). Age, male gender and BMI were significant determinants. A predictive algorithm was developed based on these determinants and the 6-MMPR threshold to assess hepatotoxicity risk [AUC = 0.83 (95% CI: 0.75–0.91)]. 6-MMPR concentrations above the threshold also correlated with gastrointestinal complaints: OR = 2.4 (95% CI: 1.4–4.3), and general malaise: OR = 2.0 (95% CI: 1.1–3.7).
Conclusions
In more than 80% of patients, thiopurine-induced hepatotoxicity could be explained by elevated T1 6-MMPR concentrations and the independent risk factors age, gender and BMI, allowing personalised thiopurine treatment in IBD to prevent early failure.
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Spring and autumn phenology of hybrid aspen (Populus tremula L. × P. tremuloides Michx.) genotypes of different geographic origin in hemiboreal Estonia §
Background: Increasing demand for renewable energy resources and the need to mitigate climate change have raised interest in short-rotation forestry with fast-growing deciduous trees like hybrid aspen (Populus tremula L. × P. tremuloides Michx.) in northern Europe. Given that climate warming has already considerably extended the growing season in this region, northward transfer of genotypes could improve forest plantation productivity and enable more efficient mitigation of climate change. We studied the spring and autumn phenology of hybrid aspen genotypes of different geographic origin (European P. tremula parent from 51° to 60° N and North American P. tremuloides parent from 45° to 54° N) 3 and 6 years after planting in a progeny trial established in Estonia at 58° N.FindingsThe effect of geographic origin on spring and autumn phenology of hybrid aspen was evident at the age of 3 and 6 years. Geographic origin did not affect spring phenology. However, hybrids with P. tremula parents of northern origin, with bud-burst occurring some days later, were able to unfold and develop full-sized leaves faster than genotypes with early bud-burst. The main differences between different geographic origins appeared in the autumn of year 6, when genotypes of northern origin (60° N) started autumn defoliation significantly earlier than those of southern origin (51° to 57° N). The genotypes of southern origin (55° 53′ to 57° 31′ N) had a period from bud-burst to defoliation 27 days longer than that of genotypes of northern origin (60° 22′ N). The interval between spring and autumn phenological processes showed significant positive correlation with current annual height growth for both study years. Conclusions: Hybrid aspen genotypes from 55° to 57° N responded well to northward transfer, having a longer leafy period and greater height increment than southward transferred genotypes. Northward-transferred genotypes were apparently better adapted to climate-change-induced extension of the growing season at higher latitudes.
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Baseline susceptibility of different European lepidopteran and coleopteran pests to Bt proteins expressed in Bt maize: a systematic review
Background: Lepidopteran and coleopteran species are the most important pests in maize. They can be controlled using genetically modified (GM) crops expressing insecticidal Bacillus thuringiensis (Bt) proteins. The long-term success of this technology demands a pest resistance management. Important information for the successful management of resistance is the baseline susceptibility of the different target pests to the different Bt proteins. The data on baseline susceptibility should enable risk assessors and managers to assess whether a GM maize produces a Bt protein in a high-dose to specific target organisms and resistance has evolved during the commercial cultivation of this GM maize events. Methods: Our systematic search followed an a priori protocol including the database platforms Web of Science, Scopus, CAB abstracts, Science Direct and JSTOR. We additionally conducted a Google scholar search. We collated all search results and screened all retrieved articles using predetermined inclusion criteria. We identified 30 studies, which fulfilled the criteria of including a relevant Bt protein, a relevant species, an appropriate endpoint, and field-derived pest generations reared in the laboratory no longer than three generations. We then made a quality assessment to discover if the studies considered the dose response curves with confidence intervals, described the protein source, tested the protein concentration and the protein activity via positive controls, use more than ten larvae per concentration, more than two replications, and more than five protein concentrations. Since no quantitative synthesis was possible the synthesis of the results was done in a narrative form. Results: Seventy percent of the studies fulfilled five or more criteria and 17% fulfilled four of the seven criteria. Six Bt proteins were tested on one or more of the four species Ostrinia nubilalis, Helicoverpa armigera, Sesamia nonagrioides, and Diabrotica virgifera virgifera. We extracted the baseline susceptibility for the given protein-species-combinations and the test method with the Bt protein applied either on the surface of the diet or incorporated. Although, the data displays a high heterogeneity and are thus hard to compare, they give an overview of the baseline susceptibility of lepidopteran/coleopteran pests to Bt proteins. Conclusion: Our systematic review illustrates the heterogeneity of the data and indicates the necessity of standard protocols for testing susceptibility of insect pests, which provide comparable data. The cultivation of Bt crops, as with any other plant protection measure, is likely to result in resistance evolution in the target pests. Industry, policy makers, and research should combine knowledge to protect the benefits of this technology.
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It is worth 10 million working hours a year to have your toilet paper folded?
Background: From our experience the toilet paper is folded in the bathrooms in rooms in branded hotels. We aimed to study the total time yearly spent in the world on folding hotel toilet paper.MethodThree investigators clocked 60 folding toilet paper events and calculated the mean time. The mean folding time was 5.73 s (interquartile range 4.50–6.56). Using the calculated extra time it takes to fold the toilet paper and the number of hotel nights spent we estimated the total time spent in the world each year to fold the toilet paper. For sensitivity analyses we used different assumptions on number of hotel beds, occupancy rate and folding time. Results: Assuming an extra 10 s spent on folding toilet paper, approximately 10 million hours are globally spent on folding toilet paper every year. This corresponds to more than 5000 man-years of work. In a hotel with yearly full coverage of 200 beds skipping folding the toilet paper corresponds to around 200 h of time that could be spent elsewhere. Conclusion: To take away unnecessary duties from hotel room cleaners would increase their health and well-being and save time that could be better spent. Is it really defendable and appropriate that someone else has spent time on folding the toilet paper you are just about to use?
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The effect of obesity on treatment outcomes for low back pain
Background: The objective of this study was to estimate the effect of obesity, as measured by body mass index (BMI), on treatment outcomes for low back pain (LBP). Methods: Data from the University of California, Los Angeles, and Friendly Hills Healthcare Network low back pain study (collected from 1995 to 2000) were used to perform a secondary data analysis of this randomized clinical trial on adults who sought care for LBP. BMI was the primary predictor variable. Binary logistic regression modeling was performed to estimate odds ratios adjusted for the effects of confounders. Results: Using normal weight as the referent population, underweight and overweight populations did not display significant odds ratios for any of the outcome variables. The obese population demonstrated odds ratios of 0.615 (0.379, 0.998) for improvement of disability and 0.550 (0.341, 0.889) for improvement of most severe back pain. Conclusion: The results of this study support an association between obesity and less effective treatment outcomes whether measured by disability (Roland-Morris scale) or pain (most severe pain NRS). Overweight and underweight populations do not appear to have significantly different outcomes than normal weight populations.Trial registrationThis trial was designed and conducted prior to the advent of registries.
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Complexity and medical education
As a major quality management issue, in health care we have to deal with limitless complexity, be it at the level of the individual patient or at the level of the health system. Today complexity is characterized by four aspects: (1) unprecedented diversity, (2) interconnectedness, (3) speed, and (4) limited influenceability. In constrast, one has to admit that all our medical interventions are single measures (or a couple of single measures) with effects difficult to predict. Therefore formal medical education has to reduce complexity in order to make it understandable and manageable to our students. Though we will not be able to grasp complexity as a whole, we should at least aim at a multi-perspective view, as it is, for example, offered with the bio-psycho-social model. At the same time, one has to remain aware of the limitations of our cognitive approaches and to avoid relapsing in mechanistic world views. In due balance, we will enable our students to acquire a sense of coherence according to Antonovsky, comprising understandability, manageability and meaningfulness. This will help our students and our physicians to act with modesty and a sufficient and realistic degree of self-confidence. This will turn out as a paramount prerequisite for reducing risks, promoting patient safety and maintaining and fostering quality in health care.
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Mapping the decision pathways of acute infection management in secondary care among UK medical physicians: a qualitative study
Background: The inappropriate use of antimicrobials drives antimicrobial resistance. We conducted a study to map physician decision-making processes for acute infection management in secondary care to identify potential targets for quality improvement interventions. Methods: Physicians newly qualified to consultant level participated in semi-structured interviews. Interviews were audio recorded and transcribed verbatim for analysis using NVIVO11.0 software. Grounded theory methodology was applied. Analytical categories were created using constant comparison approach to the data and participants were recruited to the study until thematic saturation was reached. Results: Twenty physicians were interviewed. The decision pathway for the management of acute infections follows a Bayesian-like step-wise approach, with information processed and systematically added to prior assumptions to guide management. The main emerging themes identified as determinants of the decision-making of individual physicians were (1) perceptions of providing 'optimal' care for the patient with infection by providing rapid and often intravenous therapy; (2) perceptions that stopping/de-escalating therapy was a senior doctor decision with junior trainees not expected to contribute; and (3) expectation of interactions with local guidelines and microbiology service advice. Feedback on review of junior doctor prescribing decisions was often lacking, causing frustration and confusion on appropriate practice within this cohort. Conclusion: Interventions to improve infection management must incorporate mechanisms to promote distribution of responsibility for decisions made. The disparity between expectations of prescribers to start but not review/stop therapy must be urgently addressed with mechanisms to improve communication and feedback to junior prescribers to facilitate their continued development as prudent antimicrobial prescribers.
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A qualitative analysis of participants’ reflections on body image during participation in a randomized controlled trial of acceptance and commitment therapy
Background: Negative body image is a risk factor for development and relapse in eating disorders (ED). Many patients continue to be dissatisfied with their body shape or weight after treatment. This study presents a qualitative analysis of written reflections on body image from patients with an ED and a negative body image before and after an Acceptance and Commitment Therapy group treatment at a specialized ED-unit.MethodBefore and after the treatment participants (n = 47) answered a questionnaire with open ended questions on their thoughts on body image. Data were analyzed through conventional content analysis. Results: Body image meant different things for different participants. For some it had to do with how you evaluate your body, whereas others focused on whether their body image was realistic or not. Some emphasized their relationship with their body, while some described body image as strongly related to global self-esteem. These different views on the concept of body image affected the participants' descriptions of their own body image, and how they wanted it to change. Body image was considered a state that fluctuated from day to day. After treatment the participants described changes in their body image, for instance perceiving oneself as less judgmental towards one's body, and a shift in focus to the important things in life. Conclusions: The participants had different views on body image and how they wished it to change. Thus treatment interventions targeting negative body image needs to address various aspects of this complex construct.Trial registrationThis study is part of an RCT registered 02/06/2014 in Clinical Trials, registration number: NCT02058121.
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Achieving development goals for HIV, tuberculosis and malaria in sub-Saharan Africa through integrated antenatal care: barriers and challenges
Background: The global health community is currently transitioning from the Millennium Development Goals (MDGs) to the Sustainable Development Goals (SDGs). Unfortunately, progress towards maternal, newborn and infant health MDGs has lagged significantly behind other key health goals, demanding a renewed global effort in this key health area. The World Health Organization and other institutions heralded integrated antenatal care (ANC) as the best way to address the inter-related health issues of HIV, tuberculosis (TB) and malaria in the high risk groups of pregnant women and infants; integrated ANC services also offer a mechanism to address slow progress towards improved maternal health.DiscussionThere is remarkably limited evidence on best practice approaches of program implementation, acceptability and effectiveness for integrated ANC models targeting multiple diseases. Here, we discuss current integrated ANC global guidelines and the limited literature describing integrated ANC implementation and evidence for their role in addressing HIV, malaria and TB during pregnancy in sub-Saharan Africa. We highlight the paucity of data on the effectiveness of integrated ANC models and identify significant structural barriers in the health system (funding, infrastructure, distribution, human resources), the adoption system (limited buy-in from implementers, leadership, governance) and, in the broader context, patient-centred barriers (fear, stigma, personal burdens) and barriers in funding structures. We highlight recommendations for action and discuss avenues for the global health community to develop systems to integrate multiple disease programs into ANC models of care that better address these three priority infectious diseases.SummaryWith the current transition to the SDGs and concerns regarding the failure to meet maternal health MDGs, the global health community, researchers, implementers and funding bodies must work together to ensure the establishment of quality operational and implementation research to inform integrated ANC models. It is imperative that the global health community engages in a timely discussion about such implementation innovations and instigates appropriate actions to ensure advances in maternal health are sufficient to meet applicable SDGs.
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Surprising Outcomes of Classic Ring Expansion Conditions Applied to Octaethyloxochlorin. 1. Baeyer-Villiger Oxidation Conditions
The conversion of synthetic porphyrins to derivatives that contain a non-pyrrolic building block is an enticing modality to generate porphyrinoids with functional groups at their periphery for sensing applications or chromophores with fine-tuned electronic properties for a number of technical and biomedical applications. Baeyer-Villiger oxidations are potentially suited to generate such pyrrole-expanded porphyrinoids from known octaethyloxochlorin. However, the application of a number of Baeyer-Villiger oxidation conditions to this ketone merely led to the formation of novel or known porphyrinic meso-OH or N-oxide derivatives. The work demonstrates how the extraordinary structural stability of the porphyrin macrocycle redirects the reactivity of classic ring expansion reactions, delineating some limits of the methodology to convert a pyrrole into a non-pyrrolic building block.
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Surprising Outcomes of Classic Ring Expansion Conditions Applied to Octaethyloxochlorin. 3. Schmidt Reaction Conditions
The Schmidt reaction (treatment of a ketone with sodium azide and a mineral acid) is an alternative to the Beckmann rearrangement to expand a cyclic ketone to a lactam. However, this approach toward the conversion of a synthetic porphyrin to a derivative containing a non-pyrrolic building block failed to generate the expected lactam. Instead, using sulfuric acid as a catalyst, a novel heptaethyl-2-hydroxy-chlorin-3-one was formed, structurally characterized, and its mechanism of formation deduced. The work demonstrates how the extraordinary structural stability of the porphyrin macrocycle redirects the reactivity of classic ring expansion reactions. Using hydrochloric acid as a catalyst, a somewhat regioselective chlorination of the meso-positions of the oxochlorin was observed. The halogenation sites were determined spectroscopically and by X-ray crystallography of select derivatives. The regioselectivity of the halogenation was computationally rationalized. This method to generate regioselectively 5-chloro-, 10-chloro-, and 5,10-dichloro-oxochlorins is superior over alternative halogenation methods.
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Surprising Outcomes of Classic Ring Expansion Conditions Applied to Octaethyloxochlorin. 2. Beckmann Rearrangement Conditions
The step-wise conversion of synthetic porphyrins to derivatives that contain a non-pyrrolic building block is an enticing modality to generate functionalized porphyrinoids. Applied to octaethyloxochlorin oxime, a Beckmann rearrangement is potentially suited to generate a nitrogen-expanded porphyrinoid. Unexpectedly, this reaction led to a ring-expansion by an oxygen atom. The mechanism—an abnormal Beckmann reaction, followed by an intra¬molecular ring-closing reaction and hydrolysis—was conclusively derived by the trapping and structural characterization of the key secochlorin intermediate. The UV-vis spectral and structural changes observed upon ring-expansion of the oxochlorin are discussed. Other Beckmann reaction conditions failed to produce ring-expanded products altogether. The work demonstrates in many ways how the extraordinary structural stability of the porphyrin macrocycle redirects the reactivity of classic ring expansion reactions, delineating the limits of the "breaking and mending of porphyrins" approach toward pyrrole-modified porphyrins.
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Management of Unruptured Saccular Aneurysms of the M1 Segment with Flow Diversion
Abstract
Purpose
The optimal strategy for the treatment of M1 segment aneurysms has not yet been determined as both standard microneurosurgical and endovascular techniques can pose challenges. We sought to determine the efficacy of flow diverting stents to treat small, unruptured aneurysms of the M1 segment.
Methods
We retrospectively reviewed our database of prospectively collected information for all patients treated with flow diversion for an unruptured saccular aneurysm of the middle cerebral artery (MCA) between February 2009 and February 2016. The relationship to early cortical branches, aneurysm fundus size, number and type of flow diverting stent (FDS), complications and follow-up data were recorded.
Results
In total 15 patients were identified that matched our inclusion criteria (11 female and 4 male). The average age of the patients was 58.3 years (range 14–76 years). All patients had a single aneurysm affecting the M1 segment of the MCA, 10 (66.6%) of which were related to early cortical branches and 10 aneurysms were located on the left (66.6%). The average aneurysm fundus size was 3 mm (range 2–9 mm) and 13 patients had follow-up angiographic studies. In total, 8 aneurysms were completely excluded, and 6 remained incompletely occluded (3 modified Raymond-Roy classification [mRRC] II and 3 mRRC IIIa). One patient suffered a stroke and another patient had an iatrogenic vessel dissection that was not flow limiting.
Conclusion
Flow diversion can be used to treat small, unruptured aneurysms of the M1 segment of the MCA and even though side vessel occlusion can occur clinically relevant infarction occurs infrequently.
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Evaluation of Cerebral Hyperperfusion After Carotid Artery Stenting Using C‑Arm CT Measurements of Cerebral Blood Volume
Abstract
Purpose
Hyperperfusion syndrome (HPS) after carotid artery stenting (CAS) causes serious symptoms; therefore, early evaluation after CAS is considered to be important. Measurement of cerebral blood volume using C‑arm computed tomography (C-arm CBV) has recently become possible. Here, the usefulness of C‑arm CBV for the evaluation of hyperperfusion was investigated.
Methods
C-arm CBV was measured before and immediately after CAS in 30 patients. The regions of interest (ROI) were set in the bilateral middle cerebral artery perfused regions, and the affected/healthy side ratio of measured C‑arm CBV (CBV ratios) was determined to evaluate cerebral perfusion. For comparing values before and after CAS, the CBV ratio increase rate (postoperative CBV ratios/preoperative CBV ratios) was also determined.
Results
C-arm CBV was successfully measured in 30 patients. Intracerebral hemorrhage (ICH) was detected in 3 patients, and no other patient had hyperperfusion syndrome. In the patients who developed ICH, postoperative C‑arm CBV on the affected side was high, and a marked increase was confirmed in the postoperative CBV ratios. Postoperative CBV ratios were 1.03 ± 0.40 and 1.45 ± 0.68 in the non-ICH and ICH groups, and CBV ratio increase rates were 2.7 ± 24.0% and 28.5 ± 26.7% in the non-ICH and ICH groups, respectively; these differences were statistically significant (P < 0.01).
Conclusion
C-arm CT allows CBV measurements immediately after CAS without requiring transport of the patient out of the angiography room, and it may enable the evaluation of hyperperfusion before and after CAS.
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Screening of molecular cell targets for carcinogenic heterocyclic aromatic amines by using CALUX® reporter gene assays
Abstract
Heterocyclic aromatic amines (HCAs) are compounds formed when meat or fish are cooked at high temperatures for a long time or over an open fire. To determine which pathways of toxicity are activated by HCAs, nine out of the ten HCAs known to be carcinogenic in rodents (2-amino-9H-pyrido[2,3-b]indole (AαC), 2-aminodipyrido[1,2-a:3′,2-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2)) were tested in the estrogen receptor α (ERα), androgen receptor (AR), glucocorticoid receptor (GR), peroxisome proliferator-activated receptor γ2 (PPARγ2), polycyclic aromatic hydrocarbons (PAH), Nrf2, and p53 CALUX® reporter gene assays. Trp-P-1 was the only HCA that led to a positive response in the ERα, PPARγ2, and Nrf2 CALUX® assays. In the PAH CALUX® assay, Trp-P-2, MeAαC, and AαC induced luciferase activity to a greater extent than MeIQ and PhIP. In the p53 CALUX® assay without a coupled metabolic activation, only Trp-P-1 and Trp-P-2 enhanced luciferase expression; when a metabolic activation step was coupled to the p53 CALUX® assay, Trp-P-1, Glu-P-2, MeIQ, MeIQx, and PhIP induced a positive response. No HCA was positive in the AR and GR CALUX® assays. Taken together, the results obtained show that the battery of CALUX® assays performed in the present study can successfully be used to screen for molecular cell targets of carcinogenic compounds such as HCAs.
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Phylogenetic profiling and gene expression studies implicate a primary role of PSORS1C2 in terminal differentiation of keratinocytes
Abstract
PSORS1C2 is a gene located between Coiled-Coil Alpha-Helical Rod protein 1 (CCHCR1) and Corneodesmosin (CDSN) within the psoriasis susceptibility locus 1 (PSORS1). Here, we performed a comparative genomics analysis of the as yet incompletely characterized PSORS1C2 gene and determined its expression pattern in human tissues. In contrast to CCHCR1, which is common to all vertebrates investigated, PSORS1C2 and CDSN are present exclusively in mammals, indicating that the latter genes have originated after the evolutionary divergence of mammals and reptiles. CDSN is conserved in aquatic mammals whereas PSORS1C2 orthologs contain gene-inactivating frame-shift mutations in whales and dolphins, in which the epidermal differentiation program has degenerated. Reverse transcription-PCR screening demonstrated that, in human tissues, PSORS1C2 is expressed principally in the epidermis and weakly in the thymus. PSORS1C2 mRNA was strongly upregulated during terminal differentiation of human keratinocytes in vitro. Immunohistochemistry revealed exclusive expression of PSORS1C2 in the granular layer of the epidermis and in cornifying epithelial cells of Hassall′s corpuscles of the thymus. In summary, our results identify PSORS1C2 as a keratinocyte cornification-associated protein that has originated in evolutionarily basal mammals and has undergone gene inactivation in association with the loss of the skin barrier function in aquatic mammals.
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Aberrant connective tissue differentiation towards cartilage and bone underlies human keloids in African Americans
Abstract
Keloids are benign fibroproliferative tumors more frequently found among African Americans. Until now, keloid etiopathogenesis is not fully understood. To characterize keloids in African Americans, we performed transcriptional profiling of biopsies from large chronic keloids, adjacent nonlesional (NL) skin (n=3) and a newly formed keloid lesion using Affymetrix HGU133 2.0 plus arrays. Quantitative RT-PCR (qRT-PCR) and immunohistochemistry staining were done to confirm increased expression of relevant genes. We identified 1,202 up-regulated and 961 down-regulated differentially expressed genes (DEGs) between keloid and NL skin; 1,819 up- and 1,867 down-regulated DEGs between newly formed keloid and NL skin; and 492 up- and 775 down-regulated DEGs between chronic and newly formed keloid (Fold change >2, False discovery rate <0.05). Many of the top up-regulated DEGs between chronic keloid and NL skin, and between newly formed keloid and NL skin are involved in bone/cartilage formation including Fibrillin 2(FBN2), Collagen type X alpha1(COL10A1), Asporin(ASPN), Cadherin 11(CDH11), Bone morphogenic protein 1(BMP1), Secreted phosphoprotein 1(SPP1), and Runt-related transcription factor2(RUNX2). qRT-PCR confirmed significant (p<0.05) up-regulation of BMP1, RUNX2, CDH11 and FBN2 in chronic keloid compared to NL skin. Immunohistochemistry staining showed increased protein expression of ASPN, CDH11, BMP1 and RUNX2 on chronic and newly formed keloid compared to NL skin. Our study shows that large keloids in African Americans represent a dysplasia of cutaneous connective tissue towards immature cartilage or bone differentiation. The phenotype is potentially regulated by overexpression of RUNX2. This knowledge may give insights to guide the development of better treatment for the disease in the future.
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IL-22 induced miR-122-5p promotes keratinocyte proliferation by targeting Sprouty2
Abstract
Psoriasis is a common inflammatory skin disease but the exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated its vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. Here, we showed the differentially expressed miRNAs and their potential targets in HaCaT cells stimulated by IL-22 using miRNA and mRNA microarrays. We revealed a total of 20 significantly changed (more than 2-fold) miRNAs in HaCaT cells and validated the results with quantitative reverse transcriptase PCR (qRT-PCR). We demonstrated that miR-122-5p was up regulated both in HaCaT cells stimulated by IL-22 and in psoriatic lesions. Then we aimed to investigate the biological roles and potential mechanism of miR-122-5p in keratinocytes. As a result, CCK-8 assay indicated that overexpression of miR-122-5p in keratinocytes promoted proliferation and conversely inhibition of endogenous miR-122-5p suppressed proliferation. According to the microarray analysis, we assumed that Sprouty2 (Spry2), a negative regulator of extracellular signal regulated kinase/mitogen-activated protein kinase (Erk/MAPK) signaling pathway, was a direct target gene of miR-122-5p. We found that the staining of Spry2 in cytoplasm was mainly localized in both basal and suprabasal layers of epidermis and showed a markedly decreased expression in psoriasis than in normal control by immunohistochemistry. Luciferase reporter and western blot assays in HaCaT cells demonstrated that Spry2 was a direct target gene of miR-122-5p. In conclusion, IL-22 induced miR-122-5p promotes keratinocyte proliferation possibly by down-regulating the expression of Spry2 thus playing important roles in the pathogenesis of psoriasis.
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TRIM21 is important in the early phase of inflammation in the imiquimod-induced psoriasis-like skin inflammation mouse model
Abstract
Tripartite motif-containing protein 21 (TRIM21) regulates pro-inflammatory cytokines and type I interferons and acts as an autoantigen in certain autoimmune diseases, but TRIM21 has not been investigated in psoriasis.
It has been suggested that TRIM21 may have a dual function; In the early phase of inflammation, it may function as a stimulator; but upon immune stimulation, its ubiquitinating mode of action may shift from stabilization to degradation of IRF3 causing inhibition of the immune responses.
The imiquimod (IMQ)-induced psoriasis-like mouse model displays features similar to those of human psoriasis. However, chronicity is lacking in this model.
We investigated whether the role of TRIM21 in psoriasis was pro-inflammatory or anti-inflammatory. We hypothesized that a shift of the TRIM21-ubiquitinating mode of action may explain the lack of chronicity in the IMQ-induced psoriasis-like mouse model.
We showed that TRIM21 expression is increased in lesional psoriatic skin and in the early phase of IMQ-induced inflammation both in vitro and in vivo.
Surprisingly, inflammation was significantly less pronounced in TRIM21 knockout (KO) mice than in WT mice as shown by ear thickness measured at day 8, 9 and 10 after treatment start, by spleen weight as a marker of systemic effect of IMQ at 10 days after treatment start and by expression of IL-12p40 at day 3 and 10 after treatment start and IL-17A at day 3 after treatment start.
Therefore, induction of TRIM21 expression cannot explain the lack of chronicity in the IMQ-induced psoriasis-like skin inflammation mouse model.
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Immune-related alopecia (areata and universalis-type) in cancer patients receiving immune checkpoint inhibitors
Abstract
CTLA-4, PD-1, and PD-L1 monoclonal antibodies, commonly known as immune checkpoint inhibitors, are used for the treatment of various malignancies. The mechanism of action involves the inhibition of negative regulators of immune activation, which results in many patients developing immune-related adverse events (irAEs) including endocrinopathies, pneumonitis, colitis, hepatitis and dermatologic events. Dermatologic irAEs include maculopapular rash, pruritus, vitiligo, blistering disorders, mucocutaneous lichenoid eruptions, rosacea, and exacerbation of psoriasis. Alopecia secondary to immune checkpoint inhibitors has been reported in 1.0-1.6% of patients. We characterize four cases of alopecia areata (AA) secondary to immune checkpoint inhibitors with images, histology, and concomitant nail findings, including the first report of anti-PD-L1 therapy induced AA, and a review of the literature. Patients treated with immune checkpoint inhibitors, singly or in combination, who developed partial or complete alopecia (areata and universalis-type) during treatment for their underlying cancer were analyzed (N=4). Three (75%) patients had AA, while one (25%) had universalis-type. Two patients had resolution after topical, oral, or intralesional therapies and one patient had resolution after discontinuation of immunotherapy; all regrown hair exhibited poliosis. One (25%) patient had coincident onychodystrophy. This report describes a series of four patients who developed partial or complete alopecia (i.e. areata and universalis-type) during treatment with immune-checkpoint inhibitor therapies for cancer. Recognition and management of hair-related irAEs are important for pretherapy counseling and interventions that would contribute to maintaining optimal health-related quality of life.
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miR-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma
Abstract
Cutaneous squamous cell carcinoma is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as poor-prognosis diseases, and therefore it is important to identify new markers to better predict its clinical evolution. Here, we identified the expression pattern of miRNAs at different stages of skin cancer progression in a panel of murine skin cancer cell lines. We determined that miR-203 and miR-205 are differentially expressed in this panel, and evaluated their potential use as biomarkers of prognosis in human tumours. MiR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. MiR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. MiR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. This work highlights the utility of miRNA-205 and miRNA-203 as prognostic markers in cutaneous squamous cell carcinoma.
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Treatment of moderate-to-severe atopic eczema in adults within the UK: results of a national survey of dermatologists
Abstract
Background
Little is known about UK dermatologists' treatment approaches towards adult patients with recalcitrant moderate-to-severe atopic eczema.
Objectives
We wanted to learn about the i) treatment approaches used for this disease in the UK; ii) factors that influence treatment decisions; and iii) perceived gaps in evidence on treatment safety and efficacy and priorities for future trials.
Methods
We conducted an online survey of consultant-level dermatologists in the UK.
Results
61 respondents from at least 35 centres reported on management of moderate-to-severe atopic eczema in adults, outwith the context of an acute flare. Phototherapy/PUVA was the most common therapeutic modality chosen as first-line (46%), and this was usually narrowband UVB. Systemic therapy was chosen as a first-line approach by 36% of dermatologists, with most using azathioprine (46%), followed by oral corticosteroids (43%), ciclosporin (37%) and methotrexate (25%). Methotrexate was the most common second-line treatment, chosen by 49% of respondents. The key factors that influenced decision-making on the use of phototherapy and systemic agents were: respondent's clinical experience, results of baseline tests (systemic agents), and knowledge of both efficacy and acute and chronic side-effect profiles. The most important evidence gaps identified were: the relative effectiveness of treatments, the alternatives to current approaches and the safety of long-term maintenance treatment. With regard to future trials, respondents suggested that priority should be given to studies involving methotrexate.
Conclusions
While survey study designs have limitations, including the possibility of selection and recall bias, we found that phototherapy, in particular narrow-band UVB, was respondents' preferred first-line treatment for adults with recalcitrant moderate-to-severe atopic eczema, perhaps reflecting access to, and clinical experience of, this approach. Azathioprine is widely used as a longer-term maintenance treatment.
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The treatment of hidradenitis suppurativa with the glucagon-like peptide -1 agonist liraglutide
Abstract
Hidradenitis suppurativa (HS) is a cutaneous disease associated with systemic inflammation, obesity and metabolic syndrome. Effective treatment options are limited. The anti-diabetic agents, incretins, have been used successfully to treat psoriasis – a disease also associated with metabolic syndrome. We report the use of liraglutide, a glucagon-like peptide -1 agonist, in a patient with HS, leading to subsequent weight loss and improvement in disease control. To our knowledge, this is the first report of liraglutide used in the treatment of HS.
This article is protected by copyright. All rights reserved.
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A clinical and serological study of linear IgA bullous dermatosis without linear immunoglobulin deposition other than IgA at the basement membrane zone in direct immunofluorescence
Summary
Background
Linear IgA bullous dermatosis (LABD) is a heterogeneous disease. Different diagnostic criteria have been used in different reports.
Objectives
We aimed to reappraise the characteristic features of LABD with only IgA deposition at the basement membrane zone (BMZ) in direct immunofluorescence (DIF).
Methods
We retrospectively collected 101 patients who had a) blisters on the skin and/or mucous membrane, b) subepidermal blisters in a biopsy specimen, and c) linear IgA deposition along BMZ with/without linear C3 deposition at the BMZ in DIF from our archival records from January 1, 1996, through December 31, 2014. Most patients were referred for serological evaluation. Patients who showed concurrent linear IgG and/or IgM deposition at the BMZ in DIF were excluded. Clinical manifestations and serological findings were analyzed.
Results
Heterogeneity of autoantigens in LABD was confirmed in this study. Fifty-four (53.5%) of 101 patients had IgG antibodies detected by either indirect immunofluorescence, immunoblotting (IB), or enzyme-linked immunosorbent assays (ELISA). No statistical difference in clinical manifestations was found between the IgG antibody-possessing group and remaining group.
Conclusion
An association of IgG anti-BMZ antibodies with LABD may increase if new IgG IB or ELISA becomes available. Consensus for diagnostic criteria for LABD is desired for prospective data storage although it may be arbitrary.
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Specimens processed with extraction solution of Dermatophyte Test Strip can be used for direct microscopy
Abstract
Dermatophyte Test Strip is a recently developed product that permits the detection of dermatophyte antigens in samples such as scales and nails by immunochromatography using monoclonal antibodies that react with dermatophytes.1 This test strip is useful clinically because it does not require special devices or skills and can detect dermatophyte antigens from clinical samples within a short period of time.
This article is protected by copyright. All rights reserved.
http://ift.tt/2gyGD0o
Frequency of Squamous Cell Carcinoma In Situ and Squamous Cell Carcinoma in Re-Excisions of Biopsy-Proven Cutaneous Squamous Cell Carcinoma In Situ
Abstract
Multiple surgical and nonsurgical treatments for cutaneous squamous cell carcinoma in situ (SCCIS), sometimes called Bowen's disease, have been described. The best treatment option has not yet been determined. Efficacy comparison studies are rare and difficult to execute due to the variety of treatment protocols used and follow-up periods1.
This article is protected by copyright. All rights reserved.
http://ift.tt/2hhLRft
Combination therapy of infliximab and cyclosporin in the treatment of recalcitrant psoriasis. A case series
Abstract
In the systemic treatment of moderate-to-severe psoriasis, monotherapy is usually effective. However, some patients require combination therapy to adequately control their disease1,2. In fact, data from recent european reports indicate that biological therapy is given concomitantly with traditional systemic drugs in up to 30% of psoriasis patients1,3. Combination therapy of cyclosporin (CyA) with biologic drugs, particularly etanercept and adalimumab, has been rarely reported in the literature, including non-randomized trials and case reports1,4-8.
This article is protected by copyright. All rights reserved.
http://ift.tt/2gyMN0B
Evidence from the development and testing of compassion, a theory-based complex intervention for a model of integrated care for people with advanced dementia toward the end of life
Moore, K; Candy, B; Davis, S; Gola, A; Harrington, C; Kupeli, N; Vickerstaff, V; Moore, K; Candy, B; Davis, S; Gola, A; Harrington, C; Kupeli, N; Vickerstaff, V; King, M; Leavey, G; Morris, S; Nazareth, I; Omar, R; Jones, C; Sampson, E; - view fewer (2016) Evidence from the development and testing of compassion, a theory-based complex intervention for a model of integrated care for people with advanced dementia toward the end of life. In:
http://ift.tt/2god6U5
Use of an 'adapted Zelen' design in a randomised controlled trial of a physiotherapist-led exercise intervention in patients with myeloma.
McCourt, O; Heinrich, M; Fisher, A; Paton, B; Beeken, R; Hackshaw, A; Rismani, A; McCourt, O; Heinrich, M; Fisher, A; Paton, B; Beeken, R; Hackshaw, A; Rismani, A; D'Sa, S; Yong, K; - view fewer (2016) Use of an 'adapted Zelen' design in a randomised controlled trial of a physiotherapist-led exercise intervention in patients with myeloma. In: Physiotherapy
http://ift.tt/2hccvsw
Experience of Primary Care Services Among Early Adolescents in England and Association With Health Outcomes.
Yassaee, AA; Hargreaves, DS; Chester, K; Lamb, S; Hagell, A; Brooks, FM; (2016) Experience of Primary Care Services Among Early Adolescents in England and Association With Health Outcomes. J Adolesc Health 10.1016/j.jadohealth.2016.09.022 .
http://ift.tt/2go4o88
L'RRK de Triomphe: a solution for LRRK2 GTPase activity?
Nixon-Abell, J; Berwick, DC; Harvey, K; (2016) L'RRK de Triomphe: a solution for LRRK2 GTPase activity? Biochem Soc Trans , 44 (6) pp. 1625-1634. 10.1042/BST20160240 .
http://ift.tt/2hcdSY9
Refuse disposal in the Early Epipalaeolithic? Preliminary zooarchaeological evidence from Kharaneh IV, Eastern Jordan
Allentuck, A; Martin, L; Roe, J; Refuse disposal in the Early Epipalaeolithic? Preliminary zooarchaeological evidence from Kharaneh IV, Eastern Jordan. Bulletin of the Council for British Research in the Levant , 10 10.1179/1752726015Z.00000000034 . (In press).
http://ift.tt/2gocspo
Hubris and Humility Effect and the Domain-Masculine Intelligence Type in Two Countries: Colombia and the UK.
Storek, J; Furnham, A; (2016) Hubris and Humility Effect and the Domain-Masculine Intelligence Type in Two Countries: Colombia and the UK. Span J Psychol , 19 E82-. 10.1017/sjp.2016.90 .
http://ift.tt/2hc6lJ5
The price of a loaf of bread: some conceptions of family support
Penn, H; Gough, D; (2002) The price of a loaf of bread: some conceptions of family support. Children and Society , 16 pp. 17-32.
http://ift.tt/2gog2Qh
ECHOES II: the creation of a technology enhanced learning environment for typically developing children and children on the autism spectrum
Guldberg, K; Porayska-Pomsta, K; Keay-Bright, W; (2010) ECHOES II: the creation of a technology enhanced learning environment for typically developing children and children on the autism spectrum. Journal of Assistive Technologies , 4 (1) pp. 49-53.
http://ift.tt/2hc518V
Felt tip pens and school councils : children's participation rights in four English schools
Wyse, D; (2001) Felt tip pens and school councils : children's participation rights in four English schools. Children and Society , 15 (4) pp. 209-218.
http://ift.tt/2go9Tny
An exploratory randomized control study of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with ischaemic cardiomyopathy: the REGENERATE-IHD clinical trial.
Choudhury, T; Mozid, A; Hamshere, S; Yeo, C; Pellaton, C; Arnous, S; Saunders, N; Choudhury, T; Mozid, A; Hamshere, S; Yeo, C; Pellaton, C; Arnous, S; Saunders, N; Brookman, P; Jain, A; Locca, D; Archbold, A; Knight, C; Wragg, A; Davies, C; Mills, P; Parmar, M; Rothman, M; Choudry, F; Jones, DA; Agrawal, S; Martin, J; Mathur, A; - view fewer (2016) An exploratory randomized control study of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with ischaemic cardiomyopathy: the REGENERATE-IHD clinical trial. Eur J Heart Fail 10.1002/ejhf.676 .
http://ift.tt/2hc504P
Competence in the face of adversity: the influence of early family environment and long-term consequences
Schoon, I; Parsons, S; (2002) Competence in the face of adversity: the influence of early family environment and long-term consequences. Children and Society , 16 pp. 260-272.
http://ift.tt/2goh2E5
Beyond the resolution limit: Diffusion parameter estimation in partial volume
Eaton-Rosen, Z; Melbourne, A; Jorge Cardoso, M; Marlow, N; Ourselin, S; (2016) Beyond the resolution limit: Diffusion parameter estimation in partial volume. In: (pp. pp. 605-612).
http://ift.tt/2hcgpS2
Assessing Essential Qualities of Urban Space with Emotional and Visual Data Based on GIS Technique
Li, X; Hijazi, I; Koenig, R; Lv, Z; Zhong, C; Schmitt, G; (2016) Assessing Essential Qualities of Urban Space with Emotional and Visual Data Based on GIS Technique. ISPRS International Journal of Geo-Information , 5 (11) p. 218. 10.3390/ijgi5110218 .
http://ift.tt/2hccTHw
Quality Index for Stereoscopic Images by Jointly Evaluating Cyclopean Amplitude and Cyclopean Phase
Lin, Y; Yang, J; Wen, L; Meng, Q; Lv, Z; Song, H; (2016) Quality Index for Stereoscopic Images by Jointly Evaluating Cyclopean Amplitude and Cyclopean Phase. IEEE Journal of Selected Topics in Signal Processing p. 1. 10.1109/JSTSP.2016.2632422 .
http://ift.tt/2goh273
Two-Stage Linearization Filter for Direct-Detection Subcarrier Modulation
Li, Z; Sezer Erkilinc, M; Maher, R; Galdino, L; Shi, K; Thomsen, BC; Bayvel, P; Li, Z; Sezer Erkilinc, M; Maher, R; Galdino, L; Shi, K; Thomsen, BC; Bayvel, P; Killey, RI; - view fewer (2016) Two-Stage Linearization Filter for Direct-Detection Subcarrier Modulation. IEEE Photonics Technology Letters , 28 (24) pp. 2838-2841. 10.1109/LPT.2016.2623491 . (In press).
http://ift.tt/2hceqxn
Sexual and reproductive health in the European refugee crisis.
Finnerty, F; Shahmanesh, M; (2016) Sexual and reproductive health in the European refugee crisis. Sex Transm Infect 10.1136/sextrans-2016-052538 .
http://ift.tt/2god3rn
Design and Demonstration of a 400 Gb/s Indoor Optical Wireless Communications Link
Gomez, A; Shi, K; Quintana, C; Maher, R; Faulkner, G; Bayvel, P; Thomsen, BC; Gomez, A; Shi, K; Quintana, C; Maher, R; Faulkner, G; Bayvel, P; Thomsen, BC; OBrien, D; - view fewer (2016) Design and Demonstration of a 400 Gb/s Indoor Optical Wireless Communications Link. Journal of Lightwave Technology , 34 (22) pp. 5332-5339. 10.1109/JLT.2016.2616844 .
http://ift.tt/2hc3dN8
Investigate and Estimate Attendant's Propelling Work Against Wheelchair's Load
UCHIYAMA, H; SUZUKI, T; KURATA, J; MURAKAMI, Y; (2006) Investigate and Estimate Attendant's Propelling Work Against Wheelchair's Load. TRANSACTIONS OF THE JAPAN SOCIETY OF MECHANICAL ENGINEERS Series A , 72 (715) pp. 842-849. 10.1299/kikaic.72.842 .
http://ift.tt/2goh6Us
Estimation of autonomous steady attendant's propelling a wheelchair
SUZUKI, T; UCHIYAMA, H; KURATA, J; MURAKAMI, Y; (2006) Estimation of autonomous steady attendant's propelling a wheelchair. JES Ergonomics , 42 (6) pp. 357-363. 10.5100/jje.42.357 .
http://ift.tt/2hcdNnj
Investigation of the Light Load in Propelling a Handcart on Various Road Resistances
SUZUKI, T; UCHIYAMA, H; (2009) Investigation of the Light Load in Propelling a Handcart on Various Road Resistances. JBSE , 4 (3) pp. 423-433. 10.1299/jbse.4.423 .
http://ift.tt/2goa2Hi
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