Blue-Violet Laser Modification of Titania Treated Titanium: Antibacterial and Osteo-Inductive Effects

Background

Many studies on surface modifications of titanium have been performed in an attempt to accelerate osseointegration. Recently, anatase titanium dioxide has been found to act as a photocatalyst that expresses antibiotic properties and exhibits hydrophilicity after ultraviolet exposure. A blue-violet semiconductor laser (BV-LD) has been developed as near-ultraviolet light. The purpose of this study was to investigate the effects of exposure to this BV-LD on surface modifications of titanium with the goal of enhancing osteoconductive and antibacterial properties.

Methods

The surfaces of pure commercial titanium were polished with #800 waterproof polishing papers and were treated with anatase titania solution. Specimens were exposed using BV-LD (λ = 405 nm) or an ultraviolet light-emitting diode (UV-LED, λ = 365 nm) at 6 mW/cm² for 3 h. The surface modification was evaluated physically and biologically using the following parameters or tests: surface roughness, surface temperature during exposure, X-ray diffraction (XRD) analysis, contact angle, methylene blue degradation tests, adherence of Porphyromonas gingivalis, osteoblast and fibroblast proliferation, and histological examination after implantation in rats.

Results

No significant changes were found in the surface roughness or XRD profiles after exposure. BV-LD exposure did not raise the surface temperature of titanium. The contact angle was significantly decreased, and methylene blue was significantly degraded. The number of attached P. gingivalis organisms was significantly reduced after BV-LD exposure compared to that in the no exposure group. New bone was observed around exposed specimens in the histological evaluation, and both the bone-to-specimen contact ratio and the new bone area increased significantly in exposed groups.

Conclusions

This study suggested that exposure of titanium to BV-LD can enhance the osteoconductivity of the titanium surface and induce antibacterial properties, similar to the properties observed following exposure to UV-LED.     

In Vitro Analysis of Fibronectin-Modified Titanium Surfaces

Background

Glow discharge plasma (GDP) procedure is an effective method for grafting various proteins, including albumin, type I collagen, and fibronectin, onto a titanium surface. However, the behavior and impact of titanium (Ti) surface modification is yet to be unraveled.

Purpose

The purpose of this study is to evaluate and analyze the biological properties of fibronectin-grafted Ti surfaces treated by GDP.

Materials and Methods

Grade II Ti discs were initially cleaned and autoclaved to obtain original specimens. Subsequently, the specimens were GDP treated and grafted with fibronectin to form Ar-GDP (Argon GDP treatment only) and GDP-fib (fibronectin coating following GDP treatment) groups. Blood coagulation test and MG-63 cell culture were performed to evaluate the biological effects on the specimen.

Results

There was no significant difference between Ar-GDP and GDP-fib groups in blood compatibility analysis. While in the MTT test, cellular proliferation was benefited from the presence of fibronectin coating. The numbers of cells on Ar-GDP and GDP-fib specimens were greater than those in the original specimens after 24 h of culturing.

Conclusions

GDP treatment combined with fibronectin grafting favored MG-63 cell adhesion, migration, and proliferation on titanium surfaces, which could be attributed to the improved surface properties.     

A Strontium-Modified Titanium Surface Produced by a New Method and Its Biocompatibility In Vitro

Objective

To present a new and effective method of producing titanium surfaces modified with strontium and to investigate the surface characteristics and in vitro biocompatibility of titanium (Ti) surfaces modified with strontium (Sr) for bone implant applications.

Materials and Methods

Sr-modified Ti surfaces were produced by sequential treatments with NaOH, strontium acetate, heat and water. The surface characteristics and the concentration of the Sr ions released from the samples were examined. Cell adhesion, morphology and growth were investigated using osteoblasts isolated from the calvaria of neonatal Sprague-Dawley rats. Expression of osteogenesis-related genes and proteins was examined to assess the effect of the Sr-modified Ti surfaces on osteoblasts.

Results

The modified titanium surface had a mesh structure with significantly greater porosity, and approximately5.37±0.35at.% of Sr was incorporated into the surface. The hydrophilicity was enhanced by the incorporation of Sr ions and water treatment. The average amounts of Sr released from the Sr-modified plates subjected to water treatment were slight higher than the plates without water treatment. Sr promoted cellular adhesion, spreading and growth compared with untreated Ti surfaces. The Sr-modified Ti plates also promoted expression of osteogenesis-related genes,and expression of OPN and COL-І by osteoblasts. Ti plates heat treated at 700°C showed increased bioactivity in comparison with those treated at 600°C. Water treatment upregulated the expression of osteogenesis-related genes.

Conclusions

These results show that Sr-modification of Ti surfaces may improve bioactivity in vitro. Water treatment has enhanced the response of osteoblasts. The Sr-modified Ti heat-treated at 700°C exhibited better bioactivity compared with that heated at 600°C.     

Bone Mesenchymal Stem Cells Contributed to the Neointimal Formation after Arterial Injury

Objectives

Recent findings suggest that in response to repair-to-injury bone marrow mesenchymal stem cells (BMSCs) participate in the process of angiogenesis. It is unclear what role BMSCs play in the structure of the vessel wall. In present study, we aimed to determine whether BMSCs had the capacity of endothelial cells (ECs).

Methods

BMSCs were separated and cultured. FACS and RT-PCR analysis confirmed the gene expression phenotype. The capacity of migration and adhesion and the ultrastructure of BMSCs were examined. The effect of BMSCs transplantation on the vascular repair was investigated in a murine carotid artery-injured model.

Results

BMSCs could express some markers and form the tube-like structure. The migration and adhesion capacity of BMSCs increased significantly after stimulated. In addition, BMSCs had the intact cell junction. In vivo the local transfer of BMSCs differentiated into neo-endothelial cells in the injury model for carotid artery and contributed to the vascular remodeling.

Conclusion

These results showed that BMSCs could contribute to neointimal formation for vascular lesion and might be associated with the differentiation into ECs, which indicated the important therapeutic implications for vascular diseases.     

The Association between Individual Income and Aggressive End-of-Life Treatment in Older Cancer Decedents in Taiwan

Objectives

To examine the association of individual income and end of life (EOL) care in older cancer decedents in Taiwan.

Design

Retrospective cohort study.

Setting

National Health Insurance Research Database (NHIRD) in Taiwan.

Participants

28,978 decedents >65 years were diagnosed with cancer and died during 2009-2011 in Taiwan. Of these decedents, 10941, 16535, and 1502 were categorized by individual income as having low, moderate, and high SES, respectively.

Main outcome measures

Indicators of aggressiveness of EOL care: chemotherapy use before EOL, more than one emergency department (ER) visit, more than one hospital admission, hospital length of stay >14 days, intensive care unit (ICU) admission, and dying in a hospital.

Results

Low individual income was associated with more aggressive EOL treatment (estimate -0.30 for moderate income, -0.27 for high income, both p<0.01). The major source of aggressiveness was the tendency for older decedents with low income to die in the acute care hospital. The indicators had an increasing trend from 2009 to 2011, except for hospital stay >14 days.

Conclusions

Low individual income is associated with more aggressive EOL treatment in older cancer decedents. Public health providers should make available appropriate education and hospice resources to these decedents and their families, to reduce the amount of aggressive terminal care such decedents receive.     

Effects of Textured Insoles on Balance in People with Parkinson’s Disease

Background

Degradation of the somatosensory system has been implicated in postural instability and increased falls risk for older people and Parkinson’s disease (PD) patients. Here we demonstrate that textured insoles provide a passive intervention that is an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet.

Methods

20 healthy older adults (controls) and 20 participants with PD were recruited for the study. We evaluated effects of manipulating somatosensory information from the plantar surface of the feet using textured insoles. Participants performed standing tests, on two different surfaces (firm and foam), under three footwear conditions: 1) barefoot; 2) smooth insoles; and 3) textured insoles. Standing balance was evaluated using a force plate yielding data on the range of anterior-posterior and medial-lateral sway, as well as standard deviations for anterior-posterior and medial-lateral sway.

Results

On the firm surface with eyes open both the smooth and textured insoles reduced medial-lateral sway in the PD group to a similar level as the controls. Only the textured insole decreased medial-lateral sway and medial-lateral sway standard deviation in the PD group on both surfaces, with and without visual input. Greatest benefits were observed in the PD group while wearing the textured insoles, and when standing on the foam surface with eyes closed.

Conclusions

Data suggested that textured insoles may provide a low-cost means of improving postural stability in high falls-risk groups, such as people with PD.     

Copper deficiency induced emphysema is associated with focal adhesion kinase inactivation

Background

Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1α) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein cross-linking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK).

Methodology

To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA).

Principal Findings

Copper depletion caused emphysematous changes, decreased HIF-1α activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim.

Conclusions

These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema, which may be associated with decreased HIF-1α and FAK activity in the lung.     

Association of Trichomonas vaginalis and Cytological Abnormalities of the Cervix in Low Risk Women

Objective

Is Trichomonas vaginalis (TV) an inducing factor for the development of (pre-)cancerous lesions of the cervix?

Design

Cross sectional study.

Setting

Screening healthy Belgian women with low infection risk.

Sample

63,251 consecutive liquid based cervical samples.

Methods

Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities.

Main Outcome Measures

Association of TV and HPV with cervix dysplasia

Results

The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6). In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05), mainly due to an increase in ASC-US and LSIL, but not HSIL.

Conclusions

We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.     

Stretch-Induced Stress Fiber Remodeling and the Activations of JNK and ERK Depend on Mechanical Strain Rate,but Not FAK

Background

Cells within tissues are subjected to mechanical forces caused by extracellular matrix deformation. Cells sense and dynamically respond to stretching of the matrix by reorienting their actin stress fibers and by activating intracellular signaling proteins, including focal adhesion kinase (FAK) and the mitogen-activated proteins kinases (MAPKs). Theoretical analyses predict that stress fibers can relax perturbations in tension depending on the rate of matrix strain. Thus, we hypothesized stress fiber organization and MAPK activities are altered to an extent dependent on stretch frequency.

Principal Findings

Bovine aortic endothelial cells and human osteosarcoma cells expressing GFP-actin were cultured on elastic membranes and subjected to various patterns of stretch. Cyclic stretching resulted in strain rate-dependent increases in stress fiber alignment, cell retraction, and the phosphorylation of the MAPKs JNK, ERK and p38. Transient step changes in strain rate caused proportional transient changes in the levels of JNK and ERK phosphorylations without affecting stress fiber organization. Disrupting stress fiber contractile function with cytochalasin D or Y27632 decreased the levels of JNK and ERK phosphorylation. Previous studies indicate that FAK is required for stretch-induced cell alignment and MAPK activations. However, cyclic uniaxial stretching induced stress fiber alignment and the phosphorylation of JNK, ERK and p38 to comparable levels in FAK-null and FAK-expressing mouse embryonic fibroblasts.

Conclusions

These results indicate that cyclic stretch-induced stress fiber alignment, cell retraction, and MAPK activations occur as a consequence of perturbations in fiber strain. These findings thus shed new light into the roles of stress fiber relaxation and reorganization in maintenance of tensional homeostasis in a dynamic mechanical environment.     

Mapping Cortical Thickness of the Patients with Unilateral End-Stage Open Angle Glaucoma on Planar Cerebral Cortex Maps

Purpose

To estimate and compare cerebral cortex thickness in patients with unilateral end-stage glaucoma with that of age-matched individuals with unaffected vision.

Methods

14 patients with unilateral end-stage primary open angle glaucoma (POAG) and 12 age-matched control individuals with no problems with vision were selected for the study based on detailed ophthalmic examination. For each participant 3D high-resolution structural brain T1-weighted magnetization prepared MR images were acquired on a 3.0 T scanner. Brain cortex thickness was estimated using the FreeSurfer image analysis environment. After warping of subjects'' cortical surfaces to FreeSurfer common space, differences between POAG and control groups were inferred at the group analysis level with the General Linear Model.

Results

The analysis performed revealed local thinning in the visual cortex areas in the POAG group. Statistically significant differences form 600 mm² clusters located in the Brodmann area BA19 in the left and right hemisphere.

Conclusion

Unilateral vision loss due to end-stage neuropathy from POAG is associated with significant thinning of cortical areas employed in vision.     

Lifetime Victimization and Physical Health Outcomes among Lesbian and Heterosexual Women

Background

Lifetime victimization experiences, including child sexual abuse (CSA), child physical abuse (CPA), adult sexual assault (ASA), and adult physical assault (APA), are associated with health problems.

Purpose

To examine relationships between cumulative victimization and physical health among heterosexual and lesbian women and determine whether these relationships differ by sexual identity.

Methods

Large samples of heterosexual (n = 482) and lesbian women (n = 394) were interviewed. Questions included lifetime victimization experiences and physical health problems.

Results

Compared to women who reported no childhood victimization, those who reported experiencing both CSA and CPA were 44% more likely to report health problems and women who experienced all four types of victimization (CSA, CPA, APA, ASA) were nearly 240% as likely to report physical health problems. Interaction analyses revealed the association between victimization and physical health did not differ by sexual identity.

Conclusions

Although lesbians were more likely to report all types of victimization, results suggest that victimization conferred increased physical health risks regardless of sexual identity.     

Using Information from the Electronic Health Record to Improve Measurement of Unemployment in Service Members and Veterans with mTBI and Post-Deployment Stress

Objective

The purpose of this pilot study is 1) to develop an annotation schema and a training set of annotated notes to support the future development of a natural language processing (NLP) system to automatically extract employment information, and 2) to determine if information about employment status, goals and work-related challenges reported by service members and Veterans with mild traumatic brain injury (mTBI) and post-deployment stress can be identified in the Electronic Health Record (EHR).

Design

Retrospective cohort study using data from selected progress notes stored in the EHR.

Setting

Post-deployment Rehabilitation and Evaluation Program (PREP), an in-patient rehabilitation program for Veterans with TBI at the James A. Haley Veterans'' Hospital in Tampa, Florida.

Participants

Service members and Veterans with TBI who participated in the PREP program (N = 60).

Main Outcome Measures

Documentation of employment status, goals, and work-related challenges reported by service members and recorded in the EHR.

Results

Two hundred notes were examined and unique vocational information was found indicating a variety of self-reported employment challenges. Current employment status and future vocational goals along with information about cognitive, physical, and behavioral symptoms that may affect return-to-work were extracted from the EHR. The annotation schema developed for this study provides an excellent tool upon which NLP studies can be developed.

Conclusions

Information related to employment status and vocational history is stored in text notes in the EHR system. Information stored in text does not lend itself to easy extraction or summarization for research and rehabilitation planning purposes. Development of NLP systems to automatically extract text-based employment information provides data that may improve the understanding and measurement of employment in this important cohort.     

Galectin-8 Promotes Cytoskeletal Rearrangement in Trabecular Meshwork Cells through Activation of Rho Signaling

Purpose

The trabecular meshwork (TM) cell-matrix interactions and factors that influence Rho signaling in TM cells are thought to play a pivotal role in the regulation of aqueous outflow. The current study was designed to evaluate the role of a carbohydrate-binding protein, galectin-8 (Gal8), in TM cell adhesion and Rho signaling.

Methods

Normal human TM cells were assayed for Gal8 expression by immunohistochemistry and Western blot analysis. To assess the role of Gal8 in TM cell adhesion and Rho signaling, the cell adhesion and spreading assays were performed on Gal8-coated culture plates in the presence and the absence of anti-β₁ integrin antibody and Rho and Rho-kinase inhibitors. In addition, the effect of Gal8-mediated cell-matrix interactions on TM cell cytoskeleton arrangement and myosin light chain 2 (MLC2) phosphorylation was examined.

Principal Findings

We demonstrate here that Gal8 is expressed in the TM and a function-blocking anti-β₁ integrin antibody inhibits the adhesion and spreading of TM cells to Gal8-coated wells. Cell spreading on Gal8 substratum was associated with the accumulation of phosphorylated myosin light chain and the formation of stress fibers that was inhibited by the Rho inhibitor, C3 transferase, as well as by the Rho-kinase inhibitor, Y27632.

Conclusions/Significance

The above findings present a novel function for Gal8 in activating Rho signaling in TM cells. This function may allow Gal8 to participate in the regulation of aqueous outflow.     

The European General Practice Research Network Presents the Translations of Its Comprehensive Definition of Multimorbidity in Family Medicine in Ten European Languages

Background

Multimorbidity, according to the World Health Organization, exists when there are two or more chronic conditions in one patient. This definition seems inaccurate for the holistic approach to Family Medicine (FM) and long-term care. To avoid this pitfall the European General Practitioners Research Network (EGPRN) designed a comprehensive definition of multimorbidity using a systematic literature review.

Objective

To translate that English definition into European languages and to validate the semantic, conceptual and cultural homogeneity of the translations for further research.

Method

Forward translation of the EGPRN’s definition of multimorbidity followed by a Delphi consensus procedure assessment, a backward translation and a cultural check with all teams to ensure the homogeneity of the translations in their national context. Consensus was defined as 70% of the scores being higher than 6. Delphi rounds were repeated in each country until a consensus was reached

Results

229 European medical expert FPs participated in the study. Ten consensual translations of the EGPRN comprehensive definition of multimorbidity were achieved.

Conclusion

A comprehensive definition of multimorbidity is now available in English and ten European languages for further collaborative research in FM and long-term care.     

Testosterone,Sex Hormone-Binding Globulin and the Metabolic Syndrome in Men: An Individual Participant Data Meta-Analysis of Observational Studies

Background

Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably.

Objectives

We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components.

Data sources

Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE.

Study Eligibility Criteria

Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men.

Methods

We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied.

Results

Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension.

Conclusions

Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.     

Inhibiting AKT Phosphorylation Employing Non-Cytotoxic Anthraquinones Ameliorates TH2 Mediated Allergic Airways Disease and Rhinovirus Exacerbation

Background

Severe asthma is associated with T helper (T_H) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro.

Objective

To determine the anti-inflammatory potential of anthraquinones in-vivo.

Methods

BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation.

Results

Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of T_H2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung.

Conclusion

Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT.     

An Open Source Based High Content Screening Method for Cell Biology Laboratories Investigating Cell Spreading and Adhesion

Background

Adhesion dependent mechanisms are increasingly recognized to be important for a wide range of biological processes, diseases and therapeutics. This has led to a rising demand of pharmaceutical modulators. However, most currently available adhesion assays are time consuming and/or lack sensitivity and reproducibility or depend on specialized and expensive equipment often only available at screening facilities. Thus, rapid and economical high-content screening approaches are urgently needed.

Results

We established a fully open source high-content screening method for identifying modulators of adhesion. We successfully used this method to detect small molecules that are able to influence cell adhesion and cell spreading of Swiss-3T3 fibroblasts in general and/or specifically counteract Nogo-A-Δ20-induced inhibition of adhesion and cell spreading. The tricyclic anti-depressant clomipramine hydrochloride was shown to not only inhibit Nogo-A-Δ20-induced cell spreading inhibition in 3T3 fibroblasts but also to promote growth and counteract neurite outgrowth inhibition in highly purified primary neurons isolated from rat cerebellum.

Conclusions

We have developed and validated a high content screening approach that can be used in any ordinarily equipped cell biology laboratory employing exclusively freely available open-source software in order to find novel modulators of adhesion and cell spreading. The versatility and adjustability of the whole screening method will enable not only centers specialized in high-throughput screens but most importantly also labs not routinely employing screens in their daily work routine to investigate the effects of a wide range of different compounds or siRNAs on adhesion and adhesion-modulating molecules.     

A Cross-Sectional Randomised Study of Fracture Risk in People with HIV Infection in the Probono 1 Study

Objective

To determine comparative fracture risk in HIV patients compared with uninfected controls.

Design

A randomised cross-sectional study assessing bone mineral density (BMD), fracture history and risk factors in the 2 groups.

Setting

Hospital Outpatients.

Subbbjects

222 HIV infected patients and an equal number of age-matched controls. Assessments: Fracture risk factors were assessed and biochemical, endocrine and bone markers measured. BMD was assessed at hip and spine. 10-year fracture probability (FRAX) and remaining lifetime fracture probability (RFLP) were calculated.

Main Outcome Measures

BMD, and history of fractures.

Results

Reported fractures occurred more frequently in HIV than controls, (45 vs. 16; 20.3 vs. 7%; OR=3.27; p=0.0001), and unsurprisingly in this age range, non-fragility fractures in men substantially contributed to this increase. Osteoporosis was more prevalent in patients with HIV (17.6% vs. 3.6%, p<0.0001). BMD was most reduced, and predicted fracture rates most increased, at the spine. Low BMD was associated with antiretroviral therapy (ART), low body mass index and PTH. 10-year FRAX risk was <5% for all groups. RLFP was greater in patients with HIV (OR=1.22; p=0.003) and increased with ART (2.4 vs. 1.50; OR= 1.50; p=0.03).

Conclusions

The increased fracture rate in HIV patients in our relatively youthful population is partly driven by fractures, including non-fragility fractures, in men. Nonetheless, these findings may herald a rise in osteoporotic fractures in HIV patients. An appropriate screening and management response is required to assess these risks and identify associated lifestyle factors that are also associated with other conditions such as cardiovascular disease and diabetes.     

Differential Adipose Tissue Gene Expression Profiles in Abacavir Treated Patients That May Contribute to the Understanding of Cardiovascular Risk: A Microarray Study

Objective

To compare changes in gene expression by microarray from subcutaneous adipose tissue from HIV treatment naïve patients treated with efavirenz based regimens containing abacavir (ABC), tenofovir (TDF) or zidovidine (AZT).

Design

Subcutaneous fat biopsies were obtained before, at 6- and 18–24-months after treatment, and from HIV negative controls. Groups were age, ethnicity, weight, biochemical profile, and pre-treatment CD4 count matched. Microarray data was generated using the Agilent Whole Human Genome Microarray. Identification of differentially expressed genes and genomic response pathways was performed using limma and gene set enrichment analysis.

Results

There were significant divergences between ABC and the other two groups 6 months after treatment in genes controlling cell adhesion and environmental information processing, with some convergence at 18–24 months. Compared to controls the ABC group, but not AZT or TDF showed enrichment of genes controlling adherence junction, at 6 months and 18–24 months (adjusted p<0.05) and focal adhesions and tight junction at 6 months (p<0.5). Genes controlling leukocyte transendothelial migration (p<0.05) and ECM-receptor interactions (p = 0.04) were over-expressed in ABC compared to TDF and AZT at 6 months but not at 18–24 months. Enrichment of pathways and individual genes controlling cell adhesion and environmental information processing were specifically dysregulated in the ABC group in comparison with other treatments. There was little difference between AZT and TDF.

Conclusion

After initiating treatment, there is divergence in the expression of genes controlling cell adhesion and environmental information processing between ABC and both TDF and AZT in subcutaneous adipose tissue. If similar changes are also taking place in other tissues including the coronary vasculature they may contribute to the increased risk of cardiovascular events reported in patients recently started on abacavir-containing regimens.     

Association of Proteinuria Threshold in Pre-Eclampsia with Maternal and Perinatal Outcomes: A Nested Case Control Cohort of High Risk Women

Objectives

To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499mg and ≥500mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension.

Design

Secondary analysis of the Vitamins in Pre-Eclampsia Trial.

Setting

25 UK hospitals in ten geographical areas.

Population

946 women with pre-existing risk factors for pre-eclampsia.

Methods

Women with pre-eclampsia and proteinuria 300-499mg/24h (PE300, referent group, n=60) or proteinuria ≥500 mg/24h (PE500, n=161) were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615) or gestational hypertension (GH, n=110).

Main Outcome Measures

Maternal: progression to severe hypertension. Perinatal: small for gestational age (SGA) <5^th centile, gestation at delivery.

Results

Severe hypertension occurred more frequently in PE500 (35%) and PE300 (27%) than CHT (5.9%; P≤0.01) and GH (10%; p≤0.001). Gestation at delivery was earlier in PE500 (33.2w) than PE300 (37.3w; P≤0.001), and later in CHT (38.3w; P≤0.05) and GH (39.1w; P≤0.001). SGA infants were more frequent in PE300 (32%) than in CHT (13.3%; P≤0.001) and GH (16.5%; P≤0.05). Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P≤0.001), and to receive magnesium sulphate (17% vs. 1.7%, P≤0.05).

Conclusion

Women with PE300 have complication rates above those of women managed as out-patients (GH and CHT), meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500.