Exploration of disease mechanism in acute kidney injury using a multiplex bead array assay: a nested case–control pilot study

Background: Acute kidney injury (AKI) following cardiac surgery with cardiopulmonary bypass (CPB) causes increased morbidity and mortality.

Objective: To evaluate the plasma profile of biomarkers potentially involved in AKI development following CPB.

Methods: In a nested case–control study, plasma levels of 27 biomarkers in 11 AKI cases were compared with 25 controls.

Results: Pre-CPB, plasma levels of epidermal growth factor and macrophage inflammatory protein-1β, 2?h following CPB, soluble vascular cell adhesion molecule-1 (sVCAM-1), fractalkine and macrophage inflammatory protein-1α, and at later time points, sVCAM-1 and interleukin-6 were associated with AKI.

Conclusion: Biomarkers associated with AKI following CPB may merit further study.     

Patients’ attitudes to the summary care record and HealthSpace: qualitative study

Objective To document the views of patients and the public towards the summary care record (SCR, a centrally stored medical record drawn from the general practice record) and HealthSpace (a personal health organiser accessible through the internet from which people can view their SCR), with a particular focus on those with low health literacy, potentially stigmatising conditions, or difficulties accessing health care.Design 103 semistructured individual interviews and seven focus groups.Setting Three early adopter primary care trusts in England where the SCR and HealthSpace are being piloted. All were in areas of relative socioeconomic deprivation.Participants Individual participants were recruited from general practice surgeries, walk-in centres, out of hours centres, and accident and emergency departments. Participants in focus groups were recruited through voluntary sector organisations; they comprised advocates of vulnerable groups and advocates of people who speak limited English; people with HIV; users of mental health services; young adults; elderly people; and participants of a drug rehabilitation programme.Methods Participants were asked if they had received information about the SCR and HealthSpace and about their views on shared electronic records in different circumstances.Results Most people were not aware of the SCR or HealthSpace and did not recall receiving information about it. They saw both benefits and drawbacks to having an SCR and described a process of weighing the former against the latter when making their personal choice. Key factors influencing this choice included the nature of any illness (especially whether it was likely to lead to emergency care needs); past and present experience of healthcare and government surveillance; the person’s level of engagement and health literacy; and their trust and confidence in the primary healthcare team and the wider NHS. Overall, people with stigmatising illness were more positive about the SCR than people who claimed to speak for “vulnerable groups.” Misconceptions about the SCR were common, especially confusion about what data it contained and who would have access to it. Most people were not interested in recording their medical data or accessing their SCR via HealthSpace, but some saw the potential for this new technology to support self management and lay care for those with chronic illness.Conclusion Despite an extensive information programme in early adopter sites, the public remains unclear about current policy on shared electronic records, though most people view these as a positive development. The “implied consent” model for creating and accessing a person’s SCR should be revisited, perhaps in favour of “consent to view” at the point of access.     

Mycophenolate sodium treatment in patients with primary Sjögren syndrome: a pilot trial

The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open-label pilot trial. At baseline, after 3 months, and after 6 months, we examined the clinical status, including glandular function tests, as well as different laboratory parameters associated with pSS. In addition, subjective parameters were determined on the basis of different questionnaires. Treatment with MPS was well tolerated in 8 of 11 patients. Due to vertigo or gastrointestinal discomfort, two patients did not complete the trial. One patient developed pneumonia 2 weeks after treatment and was withdrawn. In the remaining patients, MPS treatment resulted in subjective improvement of ocular dryness on a visual analogue scale and a reduced demand for artificial tear supplementations. However, no significant alterations of objective parameters for dryness of eyes and mouth were observed, although a substantial improvement of glandular functions occurred in two patients with short disease duration. In addition, treatment with MPS resulted in significant reduction of hypergammaglobulinemia and rheumatoid factors as well as an increase of complement levels and white blood cells. MPS promises to be an additional therapeutic option for patients with pSS, at least in those with shorter disease duration. Further investigations about the efficacy and safety of MPS in pSS have to be performed in larger numbers of patients.     

Non-invasive diagnosis of liver diseases by breath analysis using an optimized ion–molecule reaction-mass spectrometry approach: a pilot study

Breath composition is altered in liver diseases. We tested if ion–molecule-reaction mass spectrometry (IMR-MS) combined with a new statistical modality improves the diagnostic accuracy of breath analysis in liver diseases. We analysed 114 molecules in the breath of 126 individuals (healthy controls, and patients with non-alcoholic and alcoholic fatty liver disease and liver cirrhosis) by IMR-MS. Characteristic exhalation patterns were identified for each group. Combining two to seven molecules in the new stacked feature ranking model reached a diagnostic accuracy (area under the curve) for individual liver diseases between 0.88 and 0.97. IMR-MS followed by sophisticated statistical analysis is a promising tool for liver diagnostics by breath analysis.     

Predicting species’ tolerance to salinity and alkalinity using distribution data and geochemical modelling: a case study using Australian grasses

Background and Aims Salt tolerance has evolved many times independently in different plant groups. One possible explanation for this pattern is that it builds upon a general suite of stress-tolerance traits. If this is the case, then we might expect a correlation between salt tolerance and other tolerances to different environmental stresses. This association has been hypothesized for salt and alkalinity tolerance. However, a major limitation in investigating large-scale patterns of these tolerances is that lists of known tolerant species are incomplete. This study explores whether species’ salt and alkalinity tolerance can be predicted using geochemical modelling for Australian grasses. The correlation between taxa found in conditions of high predicted salinity and alkalinity is then assessed.Methods Extensive occurrence data for Australian grasses is used together with geochemical modelling to predict values of pH and electrical conductivity to which species are exposed in their natural distributions. Using parametric and phylogeny-corrected tests, the geochemical predictions are evaluated using a list of known halophytes as a control, and it is determined whether taxa that occur in conditions of high predicted salinity are also found in conditions of high predicted alkalinity.Key Results It is shown that genera containing known halophytes have higher predicted salinity conditions than those not containing known halophytes. Additionally, taxa occurring in high predicted salinity tend to also occur in high predicted alkalinity.Conclusions Geochemical modelling using species’ occurrence data is a potentially useful approach to predict species’ relative natural tolerance to challenging environmental conditions. The findings also demonstrate a correlation between salinity tolerance and alkalinity tolerance. Further investigations can consider the phylogenetic distribution of specific traits involved in these ecophysiological strategies, ideally by incorporating more complete, finer-scale geochemical information, as well as laboratory experiments.     

Can egg donor selection be improved? - a pilot study

Background

Accurate assessments of ovarian reserve (OR) in egg donor candidates are crucial for maximal donor selection. This study assesses whether recently reported new methods of OR assessment by age-specific (as-), rather than non-as (nas-) hormones, follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH), and triple nucleotide (CGG) repeats on the FMR1 (fragile X) gene have the potential of improving egg donor selection.

Methods

Seventy-three consecutive egg donor candidates (candidates), amongst those 21 who reached egg retrieval (donors), were prospectively investigated for as-FSH, as-AMH and number of CGG repeats. Abnormal findings were assessed in candidates and donors and oocyte yields in the latter were statistically associated with abnormal FSH and AMH (>/< 95% CI of as-levels) and with normal/abnormal numbers of CGG repeats (normal range 26-32).

Results

Amongst candidates mean as-AMH was 3.8 +/- 2.8 ng/mL (37.0% normal, 3.0 +/- 0.7 ng/mL; 26.6% low, 1.5 +/- 0.5 ng/mL; and 37.0% high, 5.8 +/- 2.2 ng/mL). AMH among donors was 4.2 +/- 1.7 ng/mL (33.3% normal, 14.3% low, and 52.4% high), yielding 17.8 +/- 7.2 oocytes, 42.9% in normal range (10-15), 9.5% in low (less than or equal to 9) and 47.6.% in high range (16-32). Candidates in 41.9% and donors in 38.1% demonstrated normal CGG counts; the remained were mostly heterozygous abnormal.

Discussion

Prospective assessment of even carefully prescreened candidates and donors still demonstrates shortcomings on both ends of the OR spectrum. Utilization of ovarian reserve testing methods, like as-hormones and CGG repeats on the FMR1 gene have potential of improving candidate selections.

     

Autologous bone marrow–derived cells for venous leg ulcers treatment: a pilot study

Background

Chronic venous leg ulcers (VLUs) are a common problem in clinical practice and available treatments are not satisfactory. The use of adjuvant therapies in combination with lower limb compression may lead to improved healing rates. Chronic wounds are candidates for new strategies in the emergent field of regenerative medicine. Bone marrow–derived cells (BMDCs) contain cells and secrete cytokines known to participate in wound healing. Thus, BMDC therapy seems a logical strategy for the treatment of chronic wounds. Our objective was to evaluate feasibility, safety and initial clinical outcome of autologous BMDC therapy associated with standard treatment in patients with VLUs.

An animal model for oroantral communications: a pilot study with Göttingen minipigs

A pilot study was performed to investigate whether the G?ttingen minipig is a suitable animal model for creating and closing oroantral communications (OACs) and to test whether these defects can be closed with a biodegradable polyurethane (PU) foam. In three adult minipigs, an OAC was created on both sides of the maxilla. The left side was closed by a standard surgical buccal flap procedure, the right side by applying a PU foam. The pigs were killed after two weeks, one month and three months, respectively. Postmortem and histological examination showed that an OAC was created in only one of six cases. In the remaining cases, the infraorbital canal was perforated instead of the floor of the maxillary sinus. It was concluded that the G?ttingen minipig is not a suitable animal model for OAC investigations. As a result, the closure of OACs with a biodegradable PU could not be evaluated.     

Are biodiversity ‘hotspots’ correlated with current ecoclimatic stability? A pilot study using the NOAA-AVHRR remote sensing data

The GAC (Global Area Coverage) by the NOAA-AVHRR satellites represents an excellent data set for studying global and regional patterns of variations in surface conditions driven in part by climatic variation. In this pilot study we examined whether biodiversity hotspots, defined from peak concentrations of neoendemics as well as geographically relict forms, differ in ecoclimatic stability from surrounding areas under present-day climatic conditions. Coefficients of variation of the ratio between brightness surface temperature (Ts) and the Normalized Difference Vegetation Index (NDVI) based upon 10 years' monthly composited scenes of tropical Africa revealed distinctive geographical patterns of interannual variability in surface conditions. Regions with a predominance of old species are characterized by spatial uniformity in the ecoclimatic variability, while regions where rapidly radiating groups dominate are spatially complex in this respect. However, the exact hotspots, with peak concentrations of endemic species, are characterized by a local reduction in ecoclimatic variability, or placement on the boundary to a stable region. This relationship was supported statistically by comparing ecoclimatic profiles across montane forests representing hotspots, and those of other montane forests. It is suggested that, because of interactions between prevailing atmospheric flows, topography and vegetation, the impact of extreme weather is moderated locally. The correlation between current stability and aggregates of neoendemics as well as old relics indicate that local moderation of climatic extremes persist through shifting climatic periods, permitting populations of unique species to survive in these places. The results are used to identify study sites for better ground truthing and for paleoclimatological studies which may be useful for more thorough studies of these relationships.     

Improving general flexibility with a mind-body approach: a randomized, controlled trial using neuro emotional Technique®

General flexibility is a key component of health, well-being, and general physical conditioning. Reduced flexibility has both physical and mental/emotional etiologies and can lead to musculoskeletal injuries and athletic underperformance. Few studies have tested the effectiveness of a mind-body therapy on general flexibility. The aim of this study was to investigate if Neuro Emotional Technique? (NET), a mind-body technique shown to be effective in reducing stress, can also improve general flexibility. The sit-and-reach test (SR) score was used as a measure of general flexibility. Forty-five healthy participants were recruited from the general population and assessed for their initial SR score before being randomly allocated to receive (a) two 20-minute sessions of NET (experimental group); (b) two 20-minute sessions of stretching instruction (active control group); or (c) no intervention or instruction (passive control group). After intervention, the participants were reassessed in a similar manner by the same blind assessor. The participants also answered questions about demographics, usual water and caffeine consumption, and activity level, and they completed an anxiety/mood psychometric preintervention and postintervention. The mean (SD) change in the SR score was +3.1 cm (2.5) in the NET group, +1.2 cm (2.3) in the active control group and +1.0 cm (2.6) in the passive control group. Although all the 3 groups showed some improvement, the improvement in the NET group was statistically significant when compared with that of either the passive controls (p = 0.015) or the active controls (p = 0.021). This study suggests that NET could provide an effective treatment in improving general flexibility. A larger study is required to confirm these findings and also to assess longer term effectiveness of this therapy on general flexibility.     

A randomized,controlled trial of interferon-β-1a (Avonex<Superscript>®</Superscript>) in patients with rheumatoid arthritis: a pilot study [ISRCTN03626626]

The objective of this study was to evaluate the safety and possible efficacy of IFN-β-1a for the treatment of patients with rheumatoid arthritis (RA). Twenty-two patients with active RA were enrolled in a phase II randomized, double-blind, placebo-controlled trial of 30 μg IFN-β-1a by weekly self-injection for 24 weeks. The primary outcome of the study was safety. Secondary outcomes included the proportion of patients achieving an American College of Rheumatology (ACR) 20 response at 24 weeks. There were no significant differences in adverse events reported in the two groups. Fewer than 20% of patients in each arm of the study achieved an ACR 20 response at 24 weeks (P = 0.71). Sixty-nine percent of patients receiving IFN-β and 67% receiving placebo terminated the study early, most of them secondary to a perceived lack of efficacy. Overall, IFN-β-1a had a safety profile similar to that of placebo. There were no significant differences in the proportion of patients achieving an ACR 20 response between the two groups.     

Plasma lipoproteome in Alzheimer’s disease: a proof-of-concept study

Background

Although total plasma lipoproteome consists of proteins that have shown promises as biomarkers that can identify Alzheimer’s disease (AD), effect sizes are modest. The objective of this study is to provide initial proof-of-concept that the plasma lipoproteome more likely differ between AD cases and controls when measured in individual plasma lipoprotein fractions than when measured as total in immunodepleted plasma.

Methods

We first developed a targeted proteomics method based on selected reaction monitoring (SRM) and liquid chromatography and tandem mass spectrometry for measurement of 120 tryptic peptides from 79 proteins that are commonly present in plasma lipoproteins. Then in a proof-of concept case–control study of 5 AD cases and 5 sex- and age-matched controls, we applied the targeted proteomic method and performed relatively quantification of 120 tryptic peptides in plasma lipoprotein fractions (fractionated by sequential gradient ultracentrifugation) and in immunodepleted plasma (of albumin and IgG). Unadjusted p values from two-sample t-tests and overall fold change was used to evaluate a peptide relative difference between AD cases and controls, with lower p values (<?0.05) or greater fold differences (>?1.05 or?<?0.95) suggestive of greater peptide/protein differences.

Results

Within-day and between-days technical precisions (mean %CV [SD] of all SRM transitions) of the targeted proteomic method were 3.95% (2.65) and 9.31% (5.59), respectively. Between-days technical precisions (mean % CV [SD]) of the entire plasma lipoproteomic workflow including plasma lipoprotein fractionation was 27.90% (14.61). Ten tryptic peptides that belonged to 5 proteins in plasma lipoproteins had unadjusted p values?<?0.05, compared to no peptides in immunodepleted plasma. Furthermore, 27, 32, 17, and 20 tryptic peptides in VLDL, IDL, LDL and HDL, demonstrated overall peptide fold differences?>?1.05 or?<?0.95, compared to only 6 tryptic peptides in immunodepleted plasma. The overall comparisons, therefore, suggested greater peptide/protein differences in plasma lipoproteome when measured in individual plasma lipoproteins than as total in immunodepleted plasma. Specifically, protein complement C3’s peptide IHWESASLLR, had unadjusted p values of 0.00007, 0.00012, and 0.0006 and overall 1.25, 1.17, 1.14-fold changes in VLDL, IDL, and LDL, respectively. After positive False Discovery Rate (pFDR) adjustment, the complement C3 peptide IHWESASLLR in VLDL remained statistically different (adjusted p value?<?0.05).

Discussion

The findings may warrant future studies to investigate plasma lipoproteome when measured in individual plasma lipoprotein fractions for AD diagnosis.

     

Productivity of a Polish child’s inflectional noun morphology: a naturalistic study

In the current paper, we examine the degree to which a 2-year-old Polishspeaking child exhibits productivity in her use of noun morphology. Using densely collected naturalistic data (five recording sessions per week) we assess the range of noun inflections she produces, the degree of productivity in her use of individual nouns, and the contextual productivity in her use of individual inflections. We adopt careful controls to allow comparison between the child’s noun use and that of her caregiver. Our data show that although the child uses the same range of noun inflections as her mother, she shows a much more limited productivity in her use of both individual nouns and individual inflections with respect to their contexts of use. We discuss the results in the light of two different theoretical approaches to inflectional morphology: the usage-based, schema approach and the rule-based approach.     

A coupled mathematical model between bone remodeling and tumors: a study of different scenarios using Komarova’s model

This paper aims to construct a general framework of coupling tumor–bone remodeling processes in order to produce plausible outcomes of the effects of tumors on the number of osteoclasts, osteoblasts, and the frequency of the bone turnover cycle. In this document, Komarova’s model has been extended to include the effect of tumors on the bone remodeling processes. Thus, we explored three alternatives for coupling tumor presence into Komarova’s model: first, using a “damage” parameter that depends on the tumor cell concentration. A second model follows the original structure of Komarova, including the tumor presence in those equations powered up to a new parameter, called the paracrine effect of the tumor on osteoclasts and osteoblasts; the last model is replicated from Ayati and collaborators in which the impact of the tumor is included into the paracrine parameters. Through the models, we studied their stability and considered some examples that can reproduce the tumor effects seen in clinic and experimentally. Therefore, this paper has three parts: the exposition of the three models, the results and discussion (where we explore some aspects and examples of the solution of the models), and the conclusion.

     

Human serum elements’ levels and leukemia: A first pilot study from an adult Greek cohort

BackgroundThe present study focuses on the evaluation of potential relationships between trace elements and acute and chronic types of leukemia, via the determination of their levels in human blood serum.MethodsA total of 199 serum samples from a Greek cohort were examined, including both leukemia cases and controls. Elements’ analysis was carried out using inductively coupled plasma mass spectrometry (ICP-MS) and demographic features such as age, gender, smoking habits and area of residence were recorded and statistically treated applying Shapiro-Wilk, Kolmogorov-Smirnov, Mann Whitney and Kruskal Wallis tests (p < 0.05). Spearman correlation and principal component analysis (PCA) were also performed to investigate possible associations.ResultsThe results demonstrated significantly higher (p < 0.05) trace elements concentrations in cases’ serum compared to that of controls excluding Ba, with Cu (median concentration 1295 μg L⁻¹) being the most abundant in cases. Additionally, concentration of toxic Pb and Cd were found at seven and four fold higher concentrations in cases, respectively. Among the trace elements examined, only Rb (164 μg L⁻¹) was detected in higher concentrations in controls. Ba, Cd and Co presented the lowest concentrations (lower than 1 μg L⁻¹). PCA was performed for overall and classified data, indicating a stronger relation among the toxic As, Cd, Ni and Pb in cases than controls, particularly referring to smokers and industrial sites’ residents. Hematological parameters and factors such as age and gender did not present any significant outcome or correlation.ConclusionsThe findings from this pilot study suggest a potential relationship between metals and leukemia, especially concerning the toxic ones. Results from the employed source apportionment tools imply that smoking and atmospheric degradation may be positively related with higher metal serum levels in leukemia patients.     

The King–Devick test as a predictor of cognitive effects after chronic partial sleep restriction: a pilot study

Sleep and Biological Rhythms - The King–Devick test (K–D) is sensitive to the effects of acute sleep deprivation. It remains unclear whether the K–D is sensitive to the effects of...