Association between direct and indirect smoking and osteoarthritis prevalence in Koreans: a cross-sectional study

Objectives

To assess the association between smoking patterns and knee and hip joint osteoarthritis (OA) prevalence in Koreans aged 50 years or older with focus on knee OA.

Design

Cross-sectional study using nationally representative data.

Setting

Data were collected at portable Health Examination Centres in Korea.

Participants

Data of 9064 participants of the 5th Korean National Health and Nutrition Examination Survey (2010–2012) aged 50 years or older who received knee or hip joint X-rays out of 31 596 total surveyees were analysed.

Primary outcome measures

OA prevalence by smoking behaviour (current smoking, past smoking, indirect smoking and non-smoking).

Secondary outcome measures

Estimated risk of OA by smoking amount, period, pack-years and indirect smoking exposure time to assess the association between smoking-related factors and knee OA by calculating ORs and adjusting for covariates in a complex sampling design. A multinomial logistic regression analysis and backward elimination method was used.

Results

OA prevalence in Koreans aged 50 years or older was 13.9%, with prevalence about 3.5 times higher in women (men 5.7%, women 20.1%). ORs for knee and hip joint OA prevalence by smoking behaviour in male indirect-smokers were lower than those in non-smokers in age and sex (OR 0.271; 95% CI 0.088 to 0.828), and selective adjustments (OR 0.314; 95% CI 0.102 to 0.966). All other analyses for smoking behaviour and total OA prevalence, and knee OA prevalence were not significantly different. Associations between smoking amount, period, pack-years and knee OA prevalence were non-significant in ever-smokers. Associations between indirect smoking exposure time and knee OA prevalence were also non-significant.

Conclusions

This study found that though direct and previous smoking and OA prevalence were not associated, there was a weak relationship between indirect smoking and OA.

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Is herpes zoster an additional complication in old age alongside comorbidity and multiple medications? Results of the post hoc analysis of the 12-month longitudinal prospective observational ARIZONA cohort study

Objectives

To examine the burden of comorbidity, polypharmacy and herpes zoster (HZ), an infectious disease, and its main complication post-herpetic neuralgia (PHN) in young (50–70 years of age: 70–) and old (≥70 years of age: 70+) patients.

Design

Post hoc analysis of the results of the 12-month longitudinal prospective multicentre observational ARIZONA cohort study.

Settings and participants

The study took place in primary care in France from 20 November 2006 to 12 September 2008. Overall, 644 general practitioners (GPs) collected data from 1358 patients aged 50 years or more with acute eruptive HZ.

Outcome measures

Presence of HZ-related pain or PHN (pain persisting >3 months) was documented at day 0 and at months 3, 6, and 12. To investigate HZ and PHN burden, pain, quality of life (QoL) and mood were self-assessed using validated questionnaires (Zoster Brief Pain Inventory, 12-item Short-Form health survey and Hospital Anxiety and Depression Scale, respectively).

Results

As compared with younger patients, older patients more frequently presented with comorbidities, more frequently took analgesics and had poorer response on all questionnaires, indicating greater burden, at inclusion. Analgesics were more frequently prescribed to relieve acute pain or PHN in 70+ than 70– patients. Despite higher levels of medication prescription, poorer pain relief and poorer response to all questionnaires were reported in 70+ than 70– patients.

Conclusions

Occurrence of HZ and progression to PHN adds extra burden on top of pharmacological treatment and impaired quality of life, especially in older patients who already have health problems to cope with in everyday life.

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Hearing loss in workers exposed to epoxy adhesives and noise: a cross-sectional study

Objectives

Epoxy adhesives contain organic solvents and are widely used in industry. The hazardous effects of epoxy adhesives remain unclear. The objective of this study was to investigate the risk of hearing loss among workers exposed to epoxy adhesives and noise.

Design

Cross-sectional study.

Methods

For this cross-sectional study, we recruited 182 stone workers who were exposed to both epoxy adhesives and noise, 89 stone workers who were exposed to noise only, and 43 workers from the administrative staff who had not been exposed to adhesives or noise. We obtained demographic data, occupational history and medical history through face-to-face interviews and arranged physical examinations and pure-tone audiometric tests. We also conducted walk-through surveys in the stone industry. A total of 40 representative noise assessments were conducted in 15 workplaces. Air sampling was conducted at 40 workplaces, and volatile organic compounds were analysed using the Environmental Protection Agency (EPA) TO-15 method.

Results

The mean sound pressure level was 87.7 dBA (SD 9.9). The prevalence of noise-induced hearing loss was considerably increased in the stone workers exposed to epoxy adhesives (42%) compared with the stone workers who were not exposed to epoxy adhesives (21%) and the administrative staff group (9.3%). A multivariate logistic regression analysis revealed that exposure to epoxy adhesives significantly increased the risk of hearing loss between 2 and 6 kHz after adjusting for age. Significant interactions between epoxy adhesives and noise and hearing impairment were observed at 3, 4 and 6 kHz.

Conclusions

Epoxy adhesives exacerbate hearing impairment in noisy environments, with the main impacts occurring in the middle and high frequencies.

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How often are interventions in cluster-randomised controlled trials of complex interventions in general practices effective and reasons for potential shortcomings? Protocol and results of a feasibility project for a systematic review

Introduction

Most studies conducted at general practices investigate complex interventions and increasingly use cluster-randomised controlled trail (c-RCT) designs to do so. Our primary objective is to evaluate how frequently complex interventions are shown to be more, equally or less effective than routine care in c-RCTs with a superior design. The secondary aim is to discover whether the quality of a c-RCT determines the likelihood of the complex intervention being effective.

Methods and analysis

All c-RCTs of any design that have a patient-relevant primary outcome and with a duration of at least 1 year will be included. The search will be performed in three electronic databases (MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews (CDSR)). The screening process, data collection, quality assessment and statistical data analyses (if suitably similar and of adequate quality) will be performed in accordance with requirements of the Cochrane Handbook for Systematic Reviews of Interventions. A feasibility project was carried out that was restricted to a search in MEDLINE and the CCTR for c-RCTs published in 1 of the 8 journals that are most relevant to general practice. The process from trial selection to data collection, assessment and results presentation was piloted. Of the 512 abstracts identified during the feasibility search, 21 studies examined complex interventions in a general practice setting. Extrapolating the preliminary search to include all relevant c-RCTs in three databases, about 5000 abstracts and 150 primary studies are expected to be identified in the main study. 14 studies included in the feasibility project (67%) did not show a positive effect on a primary patient-relevant end point.

Ethics and dissemination

Ethical approval is not being sought for this review. Findings will be disseminated via peer-reviewed journals that frequently publish articles on the results of c-RCTs and through presentations at international conferences.

Trial registration number

PROSPERO CRD201400923.

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Factors affecting uptake of influenza vaccination among family physicians

Publication date: Available online 18 February 2016
Source:Vaccine
Author(s): H. Akan, E. Yavuz, E. Yayla, H. Külbay, E. Altunok, O. Zahmacıoğlu, S. Badur
AimThe aim of this study was to determine the factors that influenced the decisions of family physicians working in primary care health services to receive influenza vaccines.MethodsThis cross-sectional study was performed between June 2014 and September 2014. Physicians were reached electronically via e-mail. A self-reported questionnaire consisting of 50 items covering potential factors that may have influenced their decision to receive vaccination, including perceived risk, severity of the perceived risk, perceived benefit, perceived barriers, cues to action, attitudes, social influences and personal efficacy, was administered to the study participants. Cronbach's alpha for the questionnaire was determined to be 0.92 in the pilot study.ResultsThe response rate was 27.5% (n=596). Regularly vaccinated physicians accounted for 27.3% of the responses. The median age was 41.84±7.80, and the median working duration of the group was 17.0±7.8years. The factors that led to increased vaccination compliance (p<0.05) included working duration, age, chronic disease history and living with a person over 65years. Nearly all major domains, i.e., perceived risk, severity of the perceived risk, perceived benefit, perceived barriers, attitudes, social influences and personal efficacy, there were differences between the compliant and noncompliant groups. Multi-regression analyses revealed that risk perception, organizational factors such as time and convenient vaccination increased vaccine compliance. However, the perceived necessity to be vaccinated annually had a negative effect on vaccination behaviour (p<0.05).ConclusionStrategies aimed to increase the flu vaccination ratio among physicians that do not take different factors into account are more likely to be unsuccessful. In the planning and implementation of strategies aiming to increase the vaccination ratio among physicians, it is both necessary and important to take into account behavioural and organizational factors.



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C, Vol. 2, Pages 6: The Kinetics of Single-Walled Carbon Nanotube Aggregation in Aqueous Media Is Sensitive to Surface Charge

Single-walled carbon nanotubes (SWCNTs) dispersed in aqueous media have many potential applications in chemistry, biology and medicine. To disperse SWCNTs into aqueous media, it is often necessary to modify the surface of SWCNTs by either covalent or noncovalent methods. As a result of this modification, the properties of SWCNTs may be profoundly influenced by the nature of the surface modification. Here, by using SWCNTs dispersed with single-stranded DNA of different lengths, we show that the kinetics of SWCNTs' aggregation in aqueous media is strongly dependent on the status of the overall surface charge. SWCNTs with a greater number of surface charges showed faster aggregation. The difference in the rate of aggregation can differ by more than ten-fold among different conditions tested. AFM imaging of the discrete time points along the aggregation process suggests that aggregation starts with the formation of microfilaments, which can further grow to form bigger aggregates. The formation of bigger aggregates also renders it more difficult to redisperse them back into the aqueous media. The concentration of counterions required to trigger SWCNT aggregation also shows a dependence on the concentration of KCl in the aqueous solution, which supports that electrostatic interactions instead of van der Waals interactions dominate the interactions among these individually-dispersed SWCNTs in aqueous media.

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Entropy, Vol. 18, Pages 59: An Optimization Approach of Deriving Bounds between Entropy and Error from Joint Distribution: Case Study for Binary Classifications

In this work, we propose a new approach of deriving the bounds between entropy and error from a joint distribution through an optimization means. The specific case study is given on binary classifications. Two basic types of classification errors are investigated, namely, the Bayesian and non-Bayesian errors. The consideration of non-Bayesian errors is due to the facts that most classifiers result in non-Bayesian solutions. For both types of errors, we derive the closed-form relations between each bound and error components. When Fano's lower bound in a diagram of "Error Probability vs. Conditional Entropy" is realized based on the approach, its interpretations are enlarged by including non-Bayesian errors and the two situations along with independent properties of the variables. A new upper bound for the Bayesian error is derived with respect to the minimum prior probability, which is generally tighter than Kovalevskij's upper bound.

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IJGI, Vol. 5, Pages 19: The Dual Half-Edge—A Topological Primal/Dual Data Structure and Construction Operators for Modelling and Manipulating Cell Complexes

There is an increasing need for building models that permit interior navigation, e.g., for escape route analysis. This paper presents a non-manifold Computer-Aided Design (CAD) data structure, the dual half-edge based on the Poincaré duality that expresses both the geometric representations of individual rooms and their topological relationships. Volumes and faces are expressed as vertices and edges respectively in the dual space, permitting a model just based on the storage of primal and dual vertices and edges. Attributes may be attached to all of these entities permitting, for example, shortest path queries between specified rooms, or to the exterior. Storage costs are shown to be comparable to other non-manifold models, and construction with local Euler-type operators is demonstrated with two large university buildings. This is intended to enhance current developments in 3D Geographic Information Systems for interior and exterior city modelling.

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3D TOCSY-HSQC NMR for Metabolic Flux Analysis Using Non-Uniform Sampling

Analytical Chemistry

DOI: 10.1021/acs.analchem.5b04535

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Effects of Safflower Yellow on the Treatment of Severe Sepsis and Septic Shock: A Randomized Controlled Clinical Trial

Objective. To evaluate the clinical effect of safflower yellow on the treatment of severe sepsis and septic shock. Methods. 85 patients with severe sepsis and septic shock were randomly selected to receive either therapy according to the international guidelines for management of severe sepsis and septic shock (Surviving Sepsis Campaign 2012) (control group, n = 45) or conventional therapy plus safflower yellow (study group, n = 40). The 28-day mortality and 28-day Kaplan-Meier survival curves were compared as primary outcomes. Results. The 28-day mortality from all causes and in-hospital mortality were significantly lower in the study group (50%, 17.5%) as compared to the control group (78.58%, 54.76%) (P = 0.007, all causes, P

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Black Raspberry Extract Increased Circulating Endothelial Progenitor Cells and Improved Arterial Stiffness in Patients with Metabolic Syndrome: A Randomized Controlled Trial

Journal of Medicinal Food , Vol. 0, No. 0.


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Embryo-fetal erythroid cell selection from celomic fluid allows earlier antenatal diagnosis of hemoglobinopathies

Abstract

Objective

Celocentesis, which involves aspiration of celomic fluid at 7-9 weeks' gestation, can potentially provide early prenatal diagnosis of single genes disorders. The main barrier to wide acceptability of this technique is contamination of the sample by maternal cells. This problem can be overcome through selection of embryo-fetal erythroid precursors which are found in celomatic fluid.

Method

Embryo-fetal erythroid precursors were selected by an anti-CD71 MicroBeads method or by direct micromanipulator pick up of the cells selected on the basis of their morphology.

Results

In our series of 302 singleton pregnancies at high-risk for hemoglobinopathies, celocentesis provided a sample of celomic fluid in all cases. In 100 (33.1%) samples maternal contamination was absent or very low (<5%) and unambiguous results were obtained without the need for any preliminary procedures. In 160 (53%) cases the contamination was between 5% and 60% and selection of embryo-fetal erythroid precursors was successfully achieved by anti-CD71 MicroBeads. In 42 (13.9%) cases the contamination was >60% and selection of embryo-fetal cells was achieved by micromanipulation. In all 302 cases there was concordance between DNA obtained from celomatic fluid samples and fetal or newborn DNA.

Conclusions

Celocentesis can be a reliable procedure for earlier prenatal diagnosis of fetal monogenic diseases. This article is protected by copyright. All rights reserved.

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Down syndrome: perinatal mortality risks with each additional week of expectant management

Abstract

Objective

To evaluate the gestational age (GA) at which perinatal mortality risk is minimized for fetuses with Down syndrome (DS).

Methods

Retrospective cohort of singleton pregnancies delivered between 24 and 41 weeks, using 2005-2006 United States linked birth and death certificate data. Among fetal DS cases, prospective risk of intrauterine fetal demise (IUFD) and risk of infant death were calculated for each week, and composite risk of fetal/infant mortality with expectant management was compared to delivery.

Results

Of 3,113,098 pregnancies, 1,766 had fetal DS (0.06%). IUFD occurred in 7.4% with DS, and infant death in 6.5%. Prospective risk of IUFD increased from 37 weeks onward to reach 50.7 per 1,000 pregnancies (95% CI 33.2-68.3) at 42 weeks. Comparing mortality with expectant management to delivery, expectant management carried increasing risk from 38 (RR 1.18; 95% CI 1.05-1.33) to 41 weeks (RR 1.84; 95% CI 1.66-2.05). Further, number needed to deliver to avoid one excess death decreased from 38 (109.17; 95% CI 64.52-344.83) to 41 weeks (24.08; 95% CI 20.59-29.04).

Conclusions

Although further research is needed to clarify risk factors for fetal and neonatal death in cases of DS, risk of perinatal mortality appears to be minimized with delivery at 38 weeks. This article is protected by copyright. All rights reserved.

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Molecular identification of emergent GII.P17-GII.17 norovirus genotype, Romania, 2015

The novel GII.P17-GII.17 norovirus genotype has been reported as cause of gastroenteritis outbreaks in China and Japan since the winter season 2014/15, replacing the pandemic strain GII.4 Sydney 2012. These emergent strains have also been sporadically reported on other continents than Asia. GII.P17-GII.17 isolates, similar to Kawasaki308 2015, were identified in three patients during a large outbreak of acute gastroenteritis affecting 328 people in Romania, in neighbouring localities, in 2015.

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Hepatitis B vaccination coverage and risk factors associated with incomplete vaccination of children born to hepatitis B surface antigen-positive mothers, Denmark, 2006 to 2010

In Denmark, universal screening of pregnant women for hepatitis B has been in place since November 2005, with the first two years as a trial period with enhanced surveillance. It is unknown what the change to universal screening without enhanced surveillance has meant for vaccination coverage among children born to hepatitis B surface antigen (HBsAg)-positive mothers and what risk factors exist for incomplete vaccination. This retrospective cohort study included 699 children of mothers positive for HBsAg. Information on vaccination and risk factors was collected from central registers. In total, 93% (651/699) of the children were vaccinated within 48 hours of birth, with considerable variation between birthplaces. Only 64% (306/475) of the children had received all three vaccinations through their general practitioner (GP) at the age of two years, and 10% (47/475) of the children had received no hepatitis B vaccinations at all. Enhanced surveillance was correlated positively with coverage of birth vaccination but not with coverage at the GP. No or few prenatal examinations were a risk factor for incomplete vaccination at the GP. Maternity wards and GPs are encouraged to revise their vaccination procedures and routines for pregnant women, mothers with chronic HBV infection and their children.

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ECDC public consultation on the use of neuraminidase inhibitors

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Vaccine effectiveness in preventing laboratory-confirmed influenza in primary care patients in a season of co-circulation of influenza A(H1N1)pdm09, B and drifted A(H3N2), I-MOVE Multicentre Case-Control Study, Europe 2014/15

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Author's reply: Is there a need for special treatment of refugees at hospital admission?

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Letter to the editor: Is there a need for special treatment of refugees at hospital admission?

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First European Union Laboratory Capability Monitoring System report published

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Simple and Sensitive Molecularly Imprinted Polymer – Mn-Doped ZnS Quantum Dots Based Fluorescence Probe for Cocaine and Metabolites Determination in Urine

Analytical Chemistry

DOI: 10.1021/acs.analchem.5b04250

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A Colloidal Stability Assay Suitable for High-Throughput Screening

Analytical Chemistry

DOI: 10.1021/acs.analchem.5b04915

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3D HPLC-MS with Reversed-Phase Separation Functionality in All Three Dimensions for Large-Scale Bottom-Up Proteomics and Peptide Retention Data Collection

Analytical Chemistry

DOI: 10.1021/acs.analchem.5b04567

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Patient Reported Mobility: A Systematic Review

Publication date: Available online 18 February 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Arrate Pinto-Carral, Tania Fernández Villa, Antonio José Molina de la Torre
ObjectiveTo identify the self-administered instruments to assess mobility in adults with disability, to link the mobility assessed by these instruments to the International Classification of Functioning, Disability and Health (ICF) and to evaluate their methodological quality.Data SourcesScopus, Science Direct and Web of Science were systematically searched up to July 2015.Study SelectionStudies on the development and validation of self-administered questionnaires in which at least half of the items were related to movement or mobility were included.Data ExtractionThe mobility assessed by the instruments was classified according to the ICF categories. The methodological quality was assessed according to the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist.Data Synthesis34 studies out of 5791 papers were eligible for inclusion. Only 10 of the instruments contained items that exclusively assessed mobility. The most frequently linked ICF categories were "changing basic body position" (19.4%), "walking" (14.8%) and "moving around" (13.5%). Measurement properties evaluated included internal consistency (5 studies), reliability (5 studies), measurement error (1 study), content validity (9 studies), structural validity (4 studies), hypotheses testing (6 studies) and responsiveness (1 study). Only content validity obtained the highest quality, probably because the studies included in the review reported the development and initial validation of the instruments.ConclusionsSelf-administered mobility questionnaires published in the scientific literature assess mobility activities rather than functions related to movement, and do so from the perspective of disability, frequently including self-care and domestic life as domains for assessment. The instruments that presented the highest methodological quality were OPTIMAL, MAM and Mobam-in.



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The effect of age alone, and age combined with pinprick, on recovery of walking function in motor complete, sensory incomplete spinal cord injury

Publication date: Available online 18 February 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Christina V. Oleson, Ralph J. Marino, Benjamin E. Leiby, John F. Ditunno
ObjectiveTo determine if age, pinprick scores in the lower extremities, and neurological severity of injury influence recovery of ambulation in persons with motor complete, sensory incomplete (AIS B), spinal cord injury (SCI) one year after initial injury.DesignThis retrospective analysis examined AIS B subjects from the Spinal Cord Injury Model System Database (SCIMSDB) from 2006 to 2015. The baseline neurological examination upon rehabilitation admission (2-4 weeks post-injury) was used for comparison with one-year outcome measures of locomotion.SettingFifteen acute inpatient rehabilitation centers (participants in the SCIMSDB).ParticipantsParticipants with AIS B SCI (249) were enrolled in SCIMSDB in 2 cycles (2006-2010 and 2011-2015).InterventionsNot applicable.Main Outcome MeasuresHousehold ambulation at one year by Fone-FIM and by direct interview, as part of the annual neurological exam; change in ASIA score one-year post-injury.ResultsFindings demonstrate a statistically non-significant increase in likelihood of walking for those age <50 compared with >50 years (RR=1.99 with 95% CI: [0.80, 3.04]). Presence of pinprick in at least one-half of the lower extremity dermatomes L2-S1 was associated with higher likelihood of walking (RR=5.57; p=0.0023). Pinprick was significant for patients <age 50 (RR 4.58, p=0.0090) but not for those >50 (p=0.15).ConclusionCompared with younger individuals, participants >age 50 with AIS B SCI are less likely to achieve walking function one-year post-injury. Likewise, preservation of pinprick sensation post-injury in the majority of lower extremity dermatomes L2-S1 increases the chances of walking in individuals <age 50.



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Central airway obstruction: benign strictures, tracheobronchomalacia and malignancy-related

The purpose of this article is to provide an update on methods for palliating symptoms in patients suffering from histologically benign and malignant central airway obstruction. We review the published literature within the last decade on post intubation, post tracheostomy, tuberculosis-and transplant-related airway strictures, tracheobronchomalacia and malignant airway obstruction. We review terminology, classification systems and parameters that impact treatment decisions. The focus is on how airway stent insertion fits into the best algorithm of care. Several case series and cohort studies demonstrate that airway stents improve dyspnea, lung function, and quality of life in patients with airway obstruction. Airway stenting is, however, associated with high rates of adverse events and should only be used when curative open surgical interventions are not feasible or are contraindicated.

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Physical Activity and Symptoms in Pulmonary Arterial Hypertension

Background

Fatigue is a common symptom in patients with pulmonary arterial hypertension (PAH); however, the impact of fatigue on daily physical activity in PAH is unknown. Accelerometry is a validated measure for assessing physical activity. We hypothesized that patients with PAH reporting higher levels of fatigue would have lower daily physical activity measured by accelerometry.

Methods

We performed a prospective cohort study of 15 women with PAH. On Day 1, subjects completed the Multidimensional Fatigue Inventory (MFI), the United States Cambridge Pulmonary Hypertension Outcome Review (US CAMPHOR), and a 6 minute walk test. Subjects wore the accelerometer on their dominant hip and completed an activity diary for 7 days. On Day 15, subjects repeated the MFI, the US CAMPHOR, and then wore the accelerometer and completed an activity diary for an additional 7 days. All multivariate analyses were adjusted for age, body mass index and PAH type.

Results

The mean age was 50.5 years and 53% had idiopathic or heritable PAH. Over the two weeks, subjects were mostly sedentary (85% of the time) while 10% of their time was spent performing low level activity. Lower average daily counts were associated with worse self-reported energy levels, whereas less day-to-day physical activity variability was associated with more self-reported mental fatigue, physical fatigue and total activity. Higher percentage of activity bouts was also associated with worse energy.

Conclusions

Women with PAH may spend most time being sedentary and lower self-reported energy levels are associated with less daily activity. Interventions to improve symptoms such as fatigue may also increase physical activity levels in PAH.

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Pressure-flow during exercise catheterization predicts survival in pulmonary hypertension

Background

Pulmonary hypertension manifests with impaired exercise capacity. Our aim was to investigate whether mean pulmonary arterial pressure to cardiac output relationship (mPAP/CO) predict transplant-free survival in pulmonary arterial and inoperable chronic thromboembolic pulmonary hypertension (PAH and CTEPH).

Methods

Hemodynamic data by right heart catheter in PAH and CTEPH patients at rest and during supine incremental cycle exercise were analyzed. Transplant-free-survival and predictive value of hemodynamics were assessed by Kaplan-Meier and Cox-regression-analysis.

Results

70 patients (43 female, 54 PAH, 16 CTEPH; median (quartiles) age 65(50;73) years, mPAP 34(29;44) mmHg, cardiac index (CI) 2.8(2.3;3.5) (l/min)/m2 were followed 610(251;1256) days. 1, 3, 5, 7-year survival was 89, 80, 71, 59 %. Age, WHO-functional class, 6-minute-walk distance and mixed-venous SO2 but not resting hemodynamics predicted transplant-free-survival. Maximal workload (hazard ratio, 95%-CI; p-value: 0.94(0.89-0.99); 0.027), peak and change in CI (0.51(0.27-0.95);0.034 and 0.25(0.06-0.94); 0.040) and mPAP/CO (1.02(1.01-1.03); 0.003) during exercise predicted survival. mPAP/CO predicted 3-year transplant-free-survival with an area under the curve of 0.802 (95%-CI: 0.66-0.95, p=0.004).

Conclusions

In this collective of patients with PAH or CTEPH, pressure-flow-relationship during exercise predicted transplant-free-survival and correlated with established markers of disease severity and prognosis. Exercise right heart catheterization may provide important complementary prognostic information in the management of PH.

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Biomechanical design considerations for transradial prosthetic interface: A review

Traditional function and comfort assessment of transradial prostheses pay scant attention to prosthetic interface. With better understanding of the biomechanics of prosthetic interface comes better efficiency and safety for interface design; in this way, amputees are more likely to accept prosthetic usage. This review attempts to provide design and selection criteria of transradial interface for prosthetists and clinicians. Various transradial socket types in the literature were chronologically reviewed. Biomechanical discussion of transradial prosthetic interface design from an engineering point of view was also done. Suspension control, range of motion, stability, as well as comfort and safety of socket designs have been considered in varying degrees in the literature. The human–machine interface design should change from traditional "socket design" to new "interface design." From anatomy and physiology to biomechanics of the transradial residual limb, the force and motion transfer, together with comfort and safety, are the two main aspects in prosthetic interface design. Load distribution and transmission should mainly rely on achieving additional skeletal control through targeted soft tissue relief. Biomechanics of the residual limb soft tissues should be studied to find the relationship between mechanical properties and the comfort and safety of soft tissues.

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Molecules, Vol. 21, Pages 230: New 3-Cyano-2-Substituted Pyridines Induce Apoptosis in MCF 7 Breast Cancer Cells

The synthesis of new 3-cyano-2-substituted pyridines bearing various pharmacophores and functionalities at position 2 is described. The synthesized compounds were evaluated for their in vitro anti-cancer activities on five cancer cell lines using 5-FU as reference compound. The results revealed that the benzohydrazide derivative 9a induced growth inhibition in human breast cancer cell line MCF-7 with an IC50 value of 2 μM and it showed lower cytotoxicity on MCF-12a normal breast epithelial cells. Additionally, 9a induced apoptotic morphological changes and induced apoptosis in MCF-7 in a dose and time-dependent manner according to an enzyme linked immunosorbent apoptosis assay which is further confirmed by a TUNEL assay. Flow cytometric analysis indicated that 9a arrested MCF-7 cells in the G1 phase, which was further confirmed by increased expression of p21 and p27 and reduced expression of CDK2 and CDK4. Western blot data revealed significant upregulation of the expression of p53, Bax, caspase-3 and down-regulation of Bcl-2, Mdm-2 and Akt. Additionally, 9a increased the release of cytochrome c from mitochondria to cytoplasm which provokes the mitochondrial apoptotic pathway while it showed no significant change on the expression of the death receptor proteins procaspase-8, caspase-8 and FAS. Furthermore, 9a reduced the expression of phospho AKT and β-catenin in dose dependent manner while inhibiting the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). Our findings suggest that compound 9a could be considered as a lead structure for further development of more potent apoptosis inducing agents with anti-metastatic activities.

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Marine Drugs, Vol. 14, Pages 38: Biosurfactants Produced by Marine Microorganisms with Therapeutic Applications

Marine microorganisms possess unique metabolic and physiological features and are an important source of new biomolecules, such as biosurfactants. Some of these surface-active compounds synthesized by marine microorganisms exhibit antimicrobial, anti-adhesive and anti-biofilm activity against a broad spectrum of human pathogens (including multi-drug resistant pathogens), and could be used instead of existing drugs to treat infections caused by them. In other cases, these biosurfactants show anti-cancer activity, which could be envisaged as an alternative to conventional therapies. However, marine biosurfactants have not been widely explored, mainly due to the difficulties associated with the isolation and growth of their producing microorganisms. Culture-independent techniques (metagenomics) constitute a promising approach to study the genetic resources of otherwise inaccessible marine microorganisms without the requirement of culturing them, and can contribute to the discovery of novel biosurfactants with significant biological activities. This paper reviews the most relevant biosurfactants produced by marine microorganisms with potential therapeutic applications and discusses future perspectives and opportunities to discover novel molecules from marine environments.

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Viruses, Vol. 8, Pages 24: The Pathogenesis of Saffold Virus in AG129 Mice and the Effects of Its Truncated L Protein in the Central Nervous System

Saffold Virus (SAFV) is a human cardiovirus that has been suggested to cause severe infection of the central nervous system (CNS). Compared to a similar virus, Theiler's murine encephalomyelitis virus (TMEV), SAFV has a truncated Leader (L) protein, a protein essential in the establishment of persistent CNS infections. In this study, we generated a chimeric SAFV by replacing the L protein of SAFV with that of TMEV. We then compared the replication in cell cultures and pathogenesis in a mouse model. We showed that both SAFV and chimeric SAFV are able to infect Vero and Neuro2a cells well, but only chimeric SAFV was able to infect RAW264.7. We then showed that mice lacking IFN-α/β and IFN-γ receptors provide a good animal model for SAFV infection, and further identified the locality of the infection to the ventral horn of the spine and several locations in the brain. Lastly, we showed that neither SAFV nor chimeric SAFV causes persistence in this model. Overall, our results provide a strong basis on which the mechanisms underlying Saffold virus induced neuropathogenesis can be further studied and, hence, facilitating new information about its pathogenesis.

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JCM, Vol. 5, Pages 26: Homeostatic Signaling by Cell–Cell Junctions and Its Dysregulation during Cancer Progression

The transition of sessile epithelial cells to a migratory, mesenchymal phenotype is essential for metazoan development and tissue repair, but this program is exploited by tumor cells in order to escape the confines of the primary organ site, evade immunosurveillance, and resist chemo-radiation. In addition, epithelial-to-mesenchymal transition (EMT) confers stem-like properties that increase efficiency of colonization of distant organs. This review evaluates the role of cell–cell junctions in suppressing EMT and maintaining a quiescent epithelium. We discuss the conflicting data on junctional signaling in cancer and recent developments that resolve some of these conflicts. We focus on evidence from breast cancer, but include other organ sites where appropriate. Current and potential strategies for inhibition of EMT are discussed.

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Sustainability, Vol. 8, Pages 178: Does Land Tenure Security Promote Manure Use by Farm Households in Vietnam?

Facing widespread poverty and land degradation, Vietnam started a land reform in 1993 as part of its renovation policy package known as "Doi Moi". This paper examines the impacts of improved land tenure security, via this land reform, on manure use by farm households. As manure potentially improves soil fertility by adding organic matter and nutrients to the soil surface, it might contribute to improving soil productive capacity and reversing land degradation. Random effect regression models are applied to a panel dataset of 133 farm households in the Northern Uplands of Vietnam collected in 1993, 1998, and 2006. The results confirm that land tenure security has positive effects on manure use, but the levels of influence differ depending on whether the land has been privatized or whether the land title has already been issued. In addition, manure use is also influenced by the number of cattle and pigs, the education level and ethnicity of household heads, farm land size and non-farm income. The findings suggest that speeding up land privatization and titling, encouraging cattle and pig rearing, and improving education would promote manure use in farm production. However, careful interpretation of our research findings is required as land privatization, together with economic growth and population pressure, might lead to overuse of farm inputs.

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IJMS, Vol. 17, Pages 248: Hinokitiol Inhibits Melanogenesis via AKT/mTOR Signaling in B16F10 Mouse Melanoma Cells

H inokitiol purified from the heartwood of cupressaceous plants has had various biological functions of cell differentiation and growth. Hinokitiol has been demonstrated as having an important role in anti-inflammation and anti-bacteria effect, suggesting that it is potentially useful in therapies for hyperpigmentation. Previously, hinokitiol inhibited the production of melanin by inhibiting tyrosinase activity. The autophagic signaling pathway can induce hypopigmentation. This study is warranted to investigate the mechanism of hinokitiol-induced hypopigmentation through autophagy in B16F10 melanoma cells. The melanin contents and expression of microthphalmia associated transcription factor (MITF) and tyrosinase were inhibited by treatment with hinokitiol. Moreover, the phosphorylation of the protein express levels of phospho-protein kinase B (P-AKT) and phospho-mammalian targets of rapamycin (P-mTOR) were reduced after hinokitiol treatment. In addition, the microtubule associated protein 1 light chain 3 (LC3) -II and beclin 1 (autophagic markers) were increased after the B16F10 cell was treated with hinokitiol. Meanwhile, hinokitiol decreased cellular melanin contents in a dose-dependent manner. These findings establish that hinokitiol inhibited melanogenesis through the AKT/mTOR signaling pathway.

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IJMS, Vol. 17, Pages 249: Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis

The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E2 (PGE2) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment.

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IJMS, Vol. 17, Pages 246: Systems Pharmacology in Small Molecular Drug Discovery

Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

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IJMS, Vol. 17, Pages 160: The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract.

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Energies, Vol. 9, Pages 114: A New Fluctuation Index: Characteristics and Application to Hydro-Wind Systems

Hydro-wind system output fluctuations are the primary factors used to assess the effects of hydropower on power companies compensating for wind power intermittency. Considering that most fluctuation indices can only characterize one aspect of fluctuations, namely, the quantitative or contour variations, we present a new index that uses the standard deviation (SD) and rotation angle to detect the quantitative variations and contour changes, respectively. Herein, the new index is compared with commonly used indices, specifically, the first-order difference, SD, and Richards-Baker flashiness indices. The results of tests performed using various processes and disposals show that: (1) when dealing with the process by moving average, repeating or overlay disposal, the new index performs comparably to the other indices, while when dealing with the process by zooming disposal, it more fully describes the fluctuation characteristics by taking both quantitative and contour variations into consideration; (2) when the new index is used to characterize the hydro-wind output fluctuations with different resources and capacities, the outcomes coincide with the mechanisms of hydro-wind systems. This study presents a new way to characterize the fluctuation of hydro-wind output.

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Sustainability, Vol. 8, Pages 176: Sustaining Competitiveness: Moving Towards Upstream Manufacturing in Specialized-Market-Based Clusters in the Chinese Toy Industry

Western industrial cluster literature pays little attention to specialized markets (SMs) and the geographical agglomeration of distributors or sale agencies (SAs). This paper takes Linyin, Shandong, a famous commodity city in Northeastern China, as an example, to discuss the determinants that make SAs in SMs of the toy industry move towards upstream manufacturing. A structured questionnaire survey and subsequent interviews were carried out during 2011 and 2012 to collect data, and a Binary Logistic Regression Model was used to process the data. This paper looks from the perspective of global production networks theory, establishes an analytical framework that combines individual motivations of intra-firm coordination, local inter-firm relationships and dynamic cross-regional level relationships. The findings indicate that the expansion of SAs towards manufacturing allows them to sustain competitiveness under changing circumstances. The local inter-firm relationships within SM-based clusters not only makes it easy to obtain material and human resources with lower manufacturing costs, but also facilitates the access to production knowledge and technologies for an expansion of production scale. Cross-regional relationships with suppliers provide an informal channel for SAs to obtain skills, which is fundamental for an expansion into manufacturing. In addition, it is a preference for strengthening competitiveness rather than the simple pursuit of economic profit that encourages SAs to invest in manufacturing.

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Remote Sensing, Vol. 8, Pages 155: Representation of Block-Based Image Features in a Multi-Scale Framework for Built-Up Area Detection

The accurate extraction and mapping of built-up areas play an important role in many social, economic, and environmental studies. In this paper, we propose a novel approach for built-up area detection from high spatial resolution remote sensing images, using a block-based multi-scale feature representation framework. First, an image is divided into small blocks, in which the spectral, textural, and structural features are extracted and represented using a multi-scale framework; a set of refined Harris corner points is then used to select blocks as training samples; finally, a built-up index image is obtained by minimizing the normalized spectral, textural, and structural distances to the training samples, and a built-up area map is obtained by thresholding the index image. Experiments confirm that the proposed approach is effective for high-resolution optical and synthetic aperture radar images, with different scenes and different spatial resolutions.

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IJMS, Vol. 17, Pages 160: The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract.

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Materials, Vol. 9, Pages 115: Structure and Compressive Properties of Invar-Cenosphere Syntactic Foams

The present study investigates the mechanical performance of syntactic foams produced by means of the metal powder injection molding process having an Invar (FeNi36) matrix and including cenospheres as hollow particles at weight fractions (wt.%) of 5 and 10, respectively, corresponding to approximately 41.6 and 60.0 vol.% in relation to the metal content and at 0.6 g/cm3 hollow particle density. The synthesis process results in survival of cenospheres and provides low density syntactic foams. The microstructure of the materials is investigated as well as the mechanical performance under quasi-static and high strain rate compressive loads. The compressive stress-strain curves of syntactic foams reveal a continuous strain hardening behavior in the plastic region, followed by a densification region. The results reveal a strain rate sensitivity in cenosphere-based Invar matrix syntactic foams. Differences in properties between cenosphere- and glass microsphere-based materials are discussed in relation to the findings of microstructural investigations. Cenospheres present a viable choice as filler material in iron-based syntactic foams due to their higher thermal stability compared to glass microspheres.

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Hydrology, Vol. 3, Pages 6: Soil Erosion Processes in European Vineyards: A Qualitative Comparison of Rainfall Simulation Measurements in Germany, Spain and France

Small portable rainfall simulators are considered a useful tool to analyze soil erosion processes in cultivated lands. European research groups in Spain (Valencia, Málaga, Lleida, Madrid and La Rioja), France (Reims) and Germany (Trier) have used different rainfall simulators (varying in drop size distribution and fall velocities, kinetic energy, plot forms and sizes, and field of application) to study soil loss, surface flow, runoff and infiltration coefficients in different experimental plots (Valencia, Montes de Málaga, Penedès, Campo Real and La Rioja in Spain, Champagne in France and Mosel-Ruwer valley in Germany). The measurements and experiments developed by these research teams give an overview of the variety of methodologies used in rainfall simulations to study the problem of soil erosion and describe the erosion features in different climatic environments, management practices and soil types. The aims of this study are: (i) to investigate where, how and why researchers from different wine-growing regions applied rainfall simulations with successful results as a tool to measure soil erosion processes; (ii) to make a qualitative comparison about the general soil erosion processes in European terroirs; (iii) to demonstrate the importance of the development of standard method for measurement of soil erosion processes in vineyards, using rainfall simulators; and (iv) and to analyze the key factors that should be taken into account to carry out rainfall simulations. The rainfall simulations in all cases allowed infiltration capacity, susceptibility of the soil to detachment and generation of sediment loads to runoff to be determined. Despite using small plots, the experiments were useful to analyze the influence of soil cover to reduce soil erosion, to make comparisons between different locations, and to evaluate the influence of different soil characteristics. The comparative analysis of the studies performed in different study areas points out the need to define an operational methodology to carry out rainfall simulations, which allows us to obtain representative and comparable results and to avoid errors in the interpretation in order to achieve comparable information about runoff and soil loss.

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IJGI, Vol. 5, Pages 18: Laser Scanning and Data Integration for Three-Dimensional Digital Recording of Complex Historical Structures: The Case of Mevlana Museum

Terrestrial laser scanning method is widely used in three-dimensional (3-D) modeling projects. Nevertheless it usually requires measurement data from other sources for full measurement of the shapes. In this study a 3-D model of the historical Mevlana Museum (Mevlana Mausoleum) in Konya, Turkey was created using state-of-the art measurement techniques. The building was measured by terrestrial laser scanner (TLS). In addition, some shapes of the indoor area were measured by a time-of-flight camera. Thus, a 3-D model of the building was created by combining datasets of all measurements. The point cloud model was created with 2.3 cm and 2.4 cm accuracy for outdoor and indoor measurements, and then it was registered to a georeferenced system. In addition a 3-D virtual model was created by mapping the texture on a mesh derived from the point cloud.

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IJMS, Vol. 17, Pages 248: Hinokitiol Inhibits Melanogenesis via AKT/mTOR Signaling in B16F10 Mouse Melanoma Cells

H inokitiol purified from the heartwood of cupressaceous plants has had various biological functions of cell differentiation and growth. Hinokitiol has been demonstrated as having an important role in anti-inflammation and anti-bacteria effect, suggesting that it is potentially useful in therapies for hyperpigmentation. Previously, hinokitiol inhibited the production of melanin by inhibiting tyrosinase activity. The autophagic signaling pathway can induce hypopigmentation. This study is warranted to investigate the mechanism of hinokitiol-induced hypopigmentation through autophagy in B16F10 melanoma cells. The melanin contents and expression of microthphalmia associated transcription factor (MITF) and tyrosinase were inhibited by treatment with hinokitiol. Moreover, the phosphorylation of the protein express levels of phospho-protein kinase B (P-AKT) and phospho-mammalian targets of rapamycin (P-mTOR) were reduced after hinokitiol treatment. In addition, the microtubule associated protein 1 light chain 3 (LC3) -II and beclin 1 (autophagic markers) were increased after the B16F10 cell was treated with hinokitiol. Meanwhile, hinokitiol decreased cellular melanin contents in a dose-dependent manner. These findings establish that hinokitiol inhibited melanogenesis through the AKT/mTOR signaling pathway.

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Energies, Vol. 9, Pages 113: Ice Storage Air-Conditioning System Simulation with Dynamic Electricity Pricing: A Demand Response Study

This paper presents an optimal dispatch model of an ice storage air-conditioning system for participants to quickly and accurately perform energy saving and demand response, and to avoid the over contact with electricity price peak. The schedule planning for an ice storage air-conditioning system of demand response is mainly to transfer energy consumption from the peak load to the partial-peak or off-peak load. Least Squares Regression (LSR) is used to obtain the polynomial function for the cooling capacity and the cost of power consumption with a real ice storage air-conditioning system. Based on the dynamic electricity pricing, the requirements of cooling loads, and all technical constraints, the dispatch model of the ice-storage air-conditioning system is formulated to minimize the operation cost. The Improved Ripple Bee Swarm Optimization (IRBSO) algorithm is proposed to solve the dispatch model of the ice storage air-conditioning system in a daily schedule on summer. Simulation results indicate that reasonable solutions provide a practical and flexible framework allowing the demand response of ice storage air-conditioning systems to demonstrate the optimization of its energy savings and operational efficiency and offering greater energy efficiency.

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IJMS, Vol. 17, Pages 249: Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis

The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E2 (PGE2) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment.

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JFMK, Vol. 1, Pages 69-89: Effects of Synthetic Anti-Inflammatory Sterol in CB3V-Induced Myocarditis: A Morphological Study on Heart Muscle Tissue

Cell-mediated immune events play a role in the pathogenesis of myocarditis provoked by Group B coxsackievirus (CVB). Studies indicated the synthetic derivative of androstene-3β,7β,17β-triol, HE3286 (17α-ethynyl-5-androstene-3β,7β,17β-triol), may ameliorate the course of immunoinflammatory and autoimmune diseases in rodents. The aim of this study was to evaluate effects of HE3286 on histological signs of CVB-induced myocarditis. BALB/c mice were infected with coxsackie B3 virus (CB3V) and treated by intraperitoneal administration of dexamethasone (Dex) or by oral gavage with HE3286 or with its vehicle, HERF405, for 18 days. Mice were sacrificed and hearts were explanted for histological and immunohistochemical analysis (TNF-α, IL-6, MMP9, ADAM10 and HSP-70). Heart tissues of Dex-treated mice showed a better histological structure compared with mice treated with HERF405. An almost complete resolution of myocarditis was observed in HE3286-treated mice as evidenced by lack of inflammatory infiltration. Immunohistochemical findings confirmed HE3286 had a more pronounced effect than Dex in reducing inflammatory response associated with in situ modulation of cytokine expression and tissue remodeling. Our data demonstrate HE3286 has better results in inhibiting establishment and progression of murine CVB-induced myocarditis than Dex, suggesting this drug may also have a therapeutic role in treatment of CVB-induced myocarditis.

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IJERPH, Vol. 13, Pages 225: Screening for Structural Hemoglobin Variants in Bahia, Brazil

Brazil was the country that received the largest number of Africans during the time of colonization, and Bahia was the Brazilian state that received the largest number of slaves from Africa. The purpose of this study was to evaluate the coverage of the newborn screening program for sickle cell disease in the Recôncavo Baiano region of the state of Bahia, and to show the frequency of the subjects with hemoglobin variants in the 2006–2009 period. Blood samples from neonates in twelve cities in the Recôncavo Baiano region were analyzed by High Performance Liquid Chromatography. A total of 16,402 children were born in this period, 14,773 of which underwent newborn screening. In this period 1416 children were born carrying hemoglobin variants HbS and HbC. Forty-seven patients—20 HbSS genotype and 27 HbSC genotype—were diagnosed in eleven of the twelve cities surveyed. The proportion of children born with sickle cell disease in the Recôncavo Baiano region was 1/314, which was higher than the 1/650 rate for the state of Bahia. The data presented in this study confirm the high frequency of sickle cell disease in Recôncavo Baiano, demonstrating the need to create a referral center for the care of patients with sickle cell diseases in the region.

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