Three Groups in the 28 Joints for Rheumatoid Arthritis Synovitis – Analysis Using More than 17,000 Assessments in the KURAMA Database

Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease. Three composite indices evaluating the same 28 joints are commonly used for the evaluation of RA activity. However, the relationship between, and the frequency of, the joint involvements are still not fully understood. Here, we obtained and analyzed 17,311 assessments for 28 joints in 1,314 patients with RA from 2005 to 2011 from electronic clinical chart templates stored in the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Affected rates for swelling and tenderness were assessed for each of the 28 joints and compared between two different sets of RA patients. Correlations of joint symptoms were analyzed for swellings and tenderness using kappa coefficient and eigen vectors by principal component analysis. As a result, we found that joint affected rates greatly varied from joint to joint both for tenderness and swelling for the two sets. Right wrist joint is the most affected joint of the 28 joints. Tenderness and swellings are well correlated in the same joints except for the shoulder joints. Patients with RA tended to demonstrate right-dominant joint involvement and joint destruction. We also found that RA synovitis could be classified into three categories of joints in the correlation analyses: large joints with wrist joints, PIP joints, and MCP joints. Clustering analysis based on distribution of synovitis revealed that patients with RA could be classified into six subgroups. We confirmed the symmetric joint involvement in RA. Our results suggested that RA synovitis can be classified into subgroups and that several different mechanisms may underlie the pathophysiology in RA synovitis.     

The Impact of Health Behaviours on Incident Cardiovascular Disease in Europeans and South Asians – A Prospective Analysis in the UK SABRE Study

Background

There is consistent evidence on the impact of health behaviours on risk of cardiovascular disease (CVD) in European populations. As South Asians in the UK have an excess risk of CVD and coronary heart disease (CHD) compared to Europeans, we investigated whether a similar association between combined health behaviours and risk of CVD and CHD among this high-risk group exists, and estimated the population impact.

Methods and Findings

In a prospective cohort of 1090 Europeans and 1006 South Asians (40–69 y) without prevalent CVD at baseline (1988–1990), followed up for 21 years to 2011, there were 601 incident CVD events [Europeans n = 255; South Asians n = 346] of which 520 were CHD events [n = 207 and 313 respectively]. Participants scored between 0 to 4 points for a composite score including four baseline healthy behaviours (non-smoker, moderate alcohol intake, physically active, frequent fruit/vegetable intake). Adjusted hazard ratios (95% confidence intervals) for incident CHD in Europeans who had three, two, one, and zero compared to four health behaviours were 1.33 (0.78–2.29), 1.96 (1.15–3.33), 1.36 (0.74–2.48) and 2.45 (1.18–5.10), respectively, p-trend = 0.025. In South Asians, corresponding HRs were 2.88 (1.33–6.24), 2.28 (1.06–4.91), 3.36 (1.53–7.39) and 3.48 (1.38–8.81), p-trend = 0.022. The results were similar for incident CVD; Europeans HR 2.12 (1.14–3.94), p–trend = 0.014; South Asians HR 2.73 (1.20–6.21), p-trend = 0.018. The population attributable fraction in Europeans was 43% for CHD and 28% for CVD. In South Asians it was 63% and 51% respectively.

Conclusions

Lack of adherence to four combined health behaviours was associated with 2 to 3-fold increased risk of incident CVD in Europeans and South Asians. A substantial population impact in the South Asian group indicates important potential for disease prevention in this high-risk group by adherence to healthy behaviours.     

Use of Systems Biology Approaches to Analysis of Genome-Wide Association Studies of Myocardial Infarction and Blood Cholesterol in the Nurses' Health Study and Health Professionals’ Follow-Up Study

With the advance of genome-wide association studies and newly identified SNP (single-nucleotide polymorphism) associations with complex disease, important discoveries have emerged focusing not only on individual genes but on disease-associated pathways and gene sets. The authors used prospective myocardial infarction case-control studies nested in the Nurses’ Health and Health Professionals Follow-Up Studies to investigate genetic variants associated with myocardial infarction or LDL, HDL, triglycerides, adiponectin and apolipoprotein B (apoB). Using these case-control studies to illustrate an integrative systems biology approach, the authors applied SNP set enrichment analysis to identify gene sets where expression SNPs representing genes from these sets show enrichment in their association with endpoints of interest. The authors also explored an aggregate score approach. While power limited one’s ability to detect significance for association of individual loci with myocardial infarction, the authors found significance for loci associated with LDL, HDL, apoB and triglycerides, replicating previous observations. Applying SNP set enrichment analysis and risk score methods, the authors also found significance for three gene sets and for aggregate scores associated with myocardial infarction as well as for loci-related to cardiovascular risk factors, supporting the use of these methods in practice.     

The Concept of Mainstream Medicine for All Californians—Part II Fifth Progress Report of the Committee on Role of Medicine in Society

This Fifth Progress Report is being printed in three parts in California Medicine. Following the appearance of Part III the report will be bound in a pamphlet which may be ordered at $1 a copy from 693 Sutter Publications, Inc., 693 Sutter Street, San Francisco, California 94102.     

Image guidance in clinical practice – Influence of positioning inaccuracy on the dose distribution for prostate cancer

BackgroundIn order to consider potential positioning errors there are different recipes for safety-margins for CTV-to-PTV expansion. The aim of this study is to simulate the effect of positioning inaccuracy with clinically realistic patient treatment plans.MethodsFor a collective of 40 prostate patients, the isocenter was shifted back appropriately to the applied table shifts after positioning verification, simulating that no positioning correction had been performed and the treatment plans were recalculated. All the treatment fractions with the appropriate isocenter-shifts were added to yield a new plan considering two scenarios:

• 1)Extreme scenario: summation of only shifted plans.
• 2)Realistic scenario: consideration of the original treatment plan for the fractions with verification imaging.

Afterwards all plans were analysed and compared with each other regarding target coverage, sparing of organs at risk (OAR) and normal tissue complication probability (NTCP).ResultsDose distributions and especially DVH show a deterioration of the target-coverage caused by the positioning inaccuracy. Deviations in dose at a single point can reach values of over 10 Gy. In single cases minimum plan agreement only achieved 66% pass within 3% local dose for the realistic case. Organs at risk and NTCP analysis result in a slightly better sparing of the rectum. Measures of quality like homogeneity and conformity differ just minimally regarding the different scenarios.ConclusionPTV-coverage suffers markedly by the positioning uncertainties, the shifted plans are in large parts clinically not acceptable. Surprisingly sparing of the OAR is not negatively affected by potential positioning errors for this prostate collective.     

The Concept of Mainstream Medicine for All Californians—Part I Fifth Progress Report of the Committee on Role of Medicine in Society

This Fifth Progress Report is to be printed in three parts in California Medicine. Following the appearance of Part III the report will be bound in a pamphlet which may be ordered at $1 a copy from 693 Sutter Publications, Inc., 693 Sutter Street, San Francisco, California 94102.     

Structural Analysis of Free N-Glycans in α-Glucosidase Mutants of Saccharomyces cerevisiae: Lack of the Evidence for the Occurrence of Catabolic α-Glucosidase Acting on the N-Glycans

Saccharomyces cerevisiae produces two different α-glucosidases, Glucosidase 1 (Gls1) and Glucosidase 2 (Gls2), which are responsible for the removal of the glucose molecules from N-glycans (Glc₃Man₉GlcNAc₂) of glycoproteins in the endoplasmic reticulum. Whether any additional α-glucosidases playing a role in catabolizing the glucosylated N-glycans are produced by this yeast, however, remains unknown. We report herein on a search for additional α-glucosidases in S. cerevisiae. To this end, the precise structures of cytosolic free N-glycans (FNGs), mainly derived from the peptide:N-glycanase (Png1) mediated deglycosylation of N-glycoproteins were analyzed in the endoplasmic reticulum α-glucosidase-deficient mutants. 12 new glucosylated FNG structures were successfully identified through 2-dimentional HPLC analysis. On the other hand, non-glucosylated FNGs were not detected at all under any culture conditions. It can therefore be safely concluded that no catabolic α-glucosidases acting on N-glycans are produced by this yeast.     

A preliminary study on the induction of dioestrous ovulation in the mare – a possible method for inducing prolonged luteal phase

Background  

Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares.     

The Concept of Mainstream Medicine for All Californians—Part III (Conclusion) Fifth Progress Report of the Committee on Role of Medicine in Society

This Fifth Progress Report is being printed in three parts in California Medicine. Following the appearance of Part III the report will be bound in a pamphlet which may be ordered at $1 a copy from 693 Sutter Publications, Inc., 693 Sutter Street, San Francisco, California 94102.     

Chromatography and Atomic Absorption Spectrometry for the Assessment of Heavy Metal Distribution among Amino Acids Used in Parenteral Nutrition Formulations—Studies with Cadmium and Lead

The distribution of Cd (II) and Pb (II) among amino acids in parenteral nutrition formulations was investigated by coupling ion-chromatography (HPLC/IC) and electrothermal atomic absorption spectrometry. The methodology was based on ion-exchange separation and fluorimetric amino acid detection after post-column derivatization. Cd (II) and Pb (II) were assayed in 500-µL fractions of the column effluent. The distribution of Cd (II) and Pb (II) in alanine (Ala), aspartic acid (Asp), glutamic acid (Glu), glycine (Gly), histidine (His), methionine (Met), phenylalanine (Phe), serine (Ser), and threonine (Thr) were analyzed by monitoring changes in the concentration of free amino acids by HPLC/IC. The results indicated that Cd (II) and Pb (II) were distributed according to the following trend: Gly–Cd?>?Gly–Pb?>?Ala–Cd?>?Ala–Pb?>?His–Cd?～?His–Pb?>?Thr–Cd?>?Thr–Pb?>?Phe–Cd?～?Phe–Pb?～?Asp–Cd?～?Asp–Pb?～?Met–Cd?～?Met–Pb?～?Glu–Cd?～?Glu–Pb?>?Ser–Cd?～?Ser–Pb. The effects of amino acid concentration and stability constants of amino acid–metal complexes are discussed.     

Investigating the Effectiveness of an Inquiry-Based Intervention on Human Reproduction in Relation to Students’ Gender,Prior Knowledge and Motivation for Learning in Biology

Despite the importance of understanding how the human reproductive system works, adolescents worldwide exhibit weak conceptual understanding, which leads to serious risks, such as unwanted pregnancies and sexually transmitted diseases. Studies focusing on the development and evaluation of inquiry-based learning interventions, promoting the knowledge of human reproduction, are very few. The purpose of this study was to evaluate the effectiveness of an inquiry-based intervention on human reproduction in relation to students’ gender, prior knowledge and motivation for learning in biology. Data collection methods included students’ pre- and post-tests, evaluating students’ conceptual understanding regarding human reproduction, and measurements of students’ motivation employing the Motivational Learning Environment survey. The sample for the pre- and post-test conceptual understanding data included the whole population of the 7th graders in Cyprus (n = 6465). Students’ motivation data were collected from a representative sample of the entire 7th graders population (n = 946 students). Statistical analyses indicated a statistically significant increase in students’ conceptual understanding as well as in their motivation for learning in biology. However, students’ gender, prior knowledge and initial motivation for learning in biology seemed to mediate the effectiveness of the inquiry-based intervention. All of these variables are deemed, therefore, as of great importance for the design, implementation and evaluation of biology teaching interventions.     

Determination of erythema-effective solar radiation in Japan and Germany with a spore monolayer film optimized for the detection of UVB and UVA – results of a field campaign

The available physical and biological broadband radiometers designed to determine erythema-effective radiation do not show any response or over/underestimate the biologically effective radiation to a high extent in the ultraviolet (UV)A spectral region. The data presented in this paper demonstrate that the biological system used in this study is the first one to make possible measurements of erythema-effective radiation in the sun in the UVA and UVB spectral region. These measurements were performed with a spore-film filter system as well as with spectroradiometers. It was demonstrated that this biotechnological method could be used to determine exact values expressed as minimal erythemal dose (MED). The spore-film system was tested in various field campaigns performed in Germany and in Japan. The seasonal daily variation of UV radiation in Germany determined in the period November 1995 to December 1996 using the spore-film filter system in sunny conditions tallied well with model calculations. The daily dose in Germany measured with the spore-film system close to the summer solstice, in sunny conditions (20.45 MED), was approximately 20 times higher than the lowest value measured close to the winter solstice (0.82 MED), a result which was in accordance with model calculations. The data determined with the spore-film filter system in Sapporo and Naha, Japan, fitted to the erythema-weighted data calculated from spectroradiometric measurements (Brewer), even at low solar radiation angles in a solar spectrum with less UVB but significant UVA. The spore-film dosimeter values were about 103 ± 8% of the integrated dose of the Brewer instrument. The standard deviation of the spore-film measurements obtained in Japan was 12.8%. The responsivity of the spore-film system towards longer wavelengths within the UVA spectrum was tested with the Okasaki Large Spectrograph with monochromatic radiation. At a wavelength of 365 nm – in a spectral region which is dominant in many tanning lamps and with minor importance for solar radiation in summer conditions – the tested spore-film system gave results that were close (112% compared to the calibration dose) to the calibration dose which was used for irradiation. Received: 27 January 1998 / Received last revision: 21 July 1998 / Accepted: 29 July 1998     

Model-Based Analysis of Costs and Outcomes of Non-Invasive Prenatal Testing for Down’s Syndrome Using Cell Free Fetal DNA in the UK National Health Service

Background

Non-invasive prenatal testing (NIPT) for Down’s syndrome (DS) using cell free fetal DNA in maternal blood has the potential to dramatically alter the way prenatal screening and diagnosis is delivered. Before NIPT can be implemented into routine practice, information is required on its costs and benefits. We investigated the costs and outcomes of NIPT for DS as contingent testing and as first-line testing compared with the current DS screening programme in the UK National Health Service.

Methods

We used a pre-existing model to evaluate the costs and outcomes associated with NIPT compared with the current DS screening programme. The analysis was based on a hypothetical screening population of 10,000 pregnant women. Model inputs were taken from published sources. The main outcome measures were number of DS cases detected, number of procedure-related miscarriages and total cost.

Results

At a screening risk cut-off of 1∶150 NIPT as contingent testing detects slightly fewer DS cases, has fewer procedure-related miscarriages, and costs the same as current DS screening (around UK£280,000) at a cost of £500 per NIPT. As first-line testing NIPT detects more DS cases, has fewer procedure-related miscarriages, and is more expensive than current screening at a cost of £50 per NIPT. When NIPT uptake increases, NIPT detects more DS cases with a small increase in procedure-related miscarriages and costs.

Conclusions

NIPT is currently available in the private sector in the UK at a price of £400-£900. If the NHS cost was at the lower end of this range then at a screening risk cut-off of 1∶150 NIPT as contingent testing would be cost neutral or cost saving compared with current DS screening. As first-line testing NIPT is likely to produce more favourable outcomes but at greater cost. Further research is needed to evaluate NIPT under real world conditions.     

Impact of land use on plant biodiversity and measures for biodiversity conservation in the Loess Plateau in China – a case study in a hilly-gully region of the Northern Loess Plateau

The Loess Plateau is a special natural–cultural unit in northern China. Intensive land use in the past has had, and forestation and grass planting at present will have inevitable impacts on plant biodiversity in the Loess Plateau. Based on the analysis of floristic features within three sampling sites with different land use practices and analysis of species richness among different land use types, we discuss impacts of land use on species richness and floristic features in the Northern Loess Plateau. The results drawn from this case study are as follows: (1) It appears that forestation and grass planting have had a positive influence on the local species diversity, but they have contributed little to the native vegetation in terms of conserving its floristic features. (2) Caragana intermedia shrubland, Pinus tabulaeformis forestland, and natural grassland have made important contributions to supporting indigenous species and maintaining local plant biodiversity. (3) There is a significant positive correlation between land use diversity and species richness. These results imply that practicing biodiversity conservation in situ is feasible and the suitable choice for the Loess Plateau. Concrete measures for biodiversity conservation in the area can include setting up small nature reserves and diversifying land use patterns to maintain as much habitat as possible for native vegetation. The artificial Hippophae rhamnoides shrubland should not be further promoted, considering its negative influence on biodiversity conservation.     

Polymer coated liposomes for use in the oral cavity – a study of the in vitro toxicity,effect on cell permeability and interaction with mucin

In this study we investigated the in vitro toxicity, impact on cell permeability and mucoadhesive potential of polymer-coated liposomes intended for use in the oral cavity. A TR146 cell line was used as a model. The overall aim was to end up with a selection of safe polymer coated liposomes with promising mucoadhesive properties for drug delivery to the oral cavity. The following polymers were tested: chitosan, low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), amidated pectin (AM-pectin), Eudragit, poly(N-isopropylacrylamide-co-methacrylic acid) (p(NIPAAM-co-MAA)), hydrophobically modified hydroxyethyl cellulose (HM-HEC), and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). With chitosan as an exception, all the systems exhibited no significant effect on cell viability and permeability at the considered concentrations. Additionally, all the formulations showed to a varying degree an interaction with mucin (BSM type I-S); the positively charged formulations exhibited the strongest interaction, while the negatively and neutrally charged formulations displayed a moderate or low interaction. The ability to interact with mucin makes all the liposomal formulations promising for oromucosal administration. Although the chitosan-coated liposomes affected the cell viability, this formulation also influenced the cell permeability, which makes it an interesting candidate for systemic drug delivery from the oral cavity.     

Abolishing Fees at Health Centers in the Context of Community Case Management of Malaria: What Effects on Treatment-Seeking Practices for Febrile Children in Rural Burkina Faso?

Introduction

Burkina Faso started nationwide community case management of malaria (CCMm) in 2010. In 2011, health center user fees for children under five were abolished in some districts.

Objective

To assess the effects of concurrent implementation of CCMm and user fees abolition on treatment-seeking practices for febrile children.

Methods

This is a natural experiment conducted in the districts of Kaya (CCMm plus user fees abolition) and Zorgho (CCMm only). Registry data from 2005 to 2014 on visits for malaria were collected from all eight rural health centers in the study area. Annual household surveys were administered during malaria transmission season in 2011 and 2012 in 1,035 randomly selected rural households. Interrupted time series models were fitted for registry data and Fine and Gray’s competing risks models for survey data.

Results

User fees abolition in Kaya significantly increased health center use by eligible children with malaria (incidence rate ratio for intercept change = 2.1, p <0.001). In 2011, in Kaya, likelihood of health center use for febrile children was three times higher and CHW use three times lower when caregivers knew services were free. Among the 421 children with fever in 2012, the delay before visiting a health center was significantly shorter in Kaya than in Zorgho (1.46 versus 1.79 days, p <0.05). Likelihood of visiting a health center on the first day of fever among households <2.5km or <5 km from a health center was two and three times higher in Kaya than in Zorgho, respectively (p <0.001).

Conclusions

User fees abolition reduced visit delay for febrile children living close to health centers. It also increased demand for and use of health center for children with malaria. Concurrently, demand for CHWs’ services diminished. User fees abolition and CCMm should be coordinated to maximize prompt access to treatment in rural areas.     

The efficacy of dexamethasone on reduction in the reoperation rate of chronic subdural hematoma – the DRESH study: straightforward study protocol for a randomized controlled trial

Background

Clinical studies are a necessity for new medications and therapies. Many studies, however, struggle to meet their recruitment numbers in time or have problems in meeting them at all. With increasing numbers of electronic health records (EHRs) in hospitals, huge databanks emerge that could be utilized to support research. The Innovative Medicine Initiative (IMI) funded project ‘Electronic Health Records for Clinical Research’ (EHR4CR) created a standardized and homogenous inventory of data elements to support research by utilizing EHRs. Our aim was to develop a Data Inventory that contains elements required for site feasibility analysis.

Methods

The Data Inventory was created in an iterative, consensus driven approach, by a group of up to 30 people consisting of pharmaceutical experts and informatics specialists. An initial list was subsequently expanded by data elements of simplified eligibility criteria from clinical trial protocols. Each element was manually reviewed by pharmaceutical experts and standard definitions were identified and added. To verify their availability, data exports of the source systems at eleven university hospitals throughout Europe were conducted and evaluated.

Results

The Data Inventory consists of 75 data elements that, on the one hand are frequently used in clinical studies, and on the other hand are available in European EHR systems. Rankings of data elements were created from the results of the data exports. In addition a sub-list was created with 21 data elements that were separated from the Data Inventory because of their low usage in routine documentation.

Conclusion

The data elements in the Data Inventory were identified with the knowledge of domain experts from pharmaceutical companies. Currently, not all information that is frequently used in site feasibility is documented in routine patient care.     

Meeting report of the OECD conference on “Genome Editing: Applications in Agriculture—Implications for Health,Environment and Regulation”

Transgenic Research - The “OECD Conference on Genome Editing: Applications in Agriculture—Implications for Health, Environment and Regulation” was held on the 28–29 June...     

EVALUATION OF GRIP LOSS—A Factor of Permanent Partial Disability in California: Summation and Conclusions of the Subcommittee for Study of Grasping Power of the Committee on Industrial Health and Rehabilitation of the California Medical Association

Loss of grasping power is a ratable factor of permanent partial disability by the Industrial Accident Commission of the State of California. The ratings that issue therefrom are based upon the proportion of grasping power actually lost as a result of the injury sustained. The conditions which most frequently impair grasping power are, (1) amputation; (2) limited motion of digits, wrists, forearm, elbow or shoulder; (3) pain; (4) muscular weakness. The examining physician can greatly facilitate proper rating if he carefully and fully reports data needed by the I.A.C. Grip readings should be measured by the most precise instrument which can be obtained. Makeshift devices such as using a blood pressure cuff are not acceptable. A committee of the California Medical Association appointed to study the subject of loss of grip for purposes of establishing compensation rating, concluded that a dynamometer that registers pounds force is preferable to one registering pressure.