Mechanical Strain Stabilizes Reconstituted Collagen Fibrils against Enzymatic Degradation by Mammalian Collagenase Matrix Metalloproteinase 8 (MMP-8)

Background

Collagen, a triple-helical, self-organizing protein, is the predominant structural protein in mammals. It is found in bone, ligament, tendon, cartilage, intervertebral disc, skin, blood vessel, and cornea. We have recently postulated that fibrillar collagens (and their complementary enzymes) comprise the basis of a smart structural system which appears to support the retention of molecules in fibrils which are under tensile mechanical strain. The theory suggests that the mechanisms which drive the preferential accumulation of collagen in loaded tissue operate at the molecular level and are not solely cell-driven. The concept reduces control of matrix morphology to an interaction between molecules and the most relevant, physical, and persistent signal: mechanical strain.

Methodology/Principal Findings

The investigation was carried out in an environmentally-controlled microbioreactor in which reconstituted type I collagen micronetworks were gently strained between micropipettes. The strained micronetworks were exposed to active matrix metalloproteinase 8 (MMP-8) and relative degradation rates for loaded and unloaded fibrils were tracked simultaneously using label-free differential interference contrast (DIC) imaging. It was found that applied tensile mechanical strain significantly increased degradation time of loaded fibrils compared to unloaded, paired controls. In many cases, strained fibrils were detectable long after unstrained fibrils were degraded.

Conclusions/Significance

In this investigation we demonstrate for the first time that applied mechanical strain preferentially preserves collagen fibrils in the presence of a physiologically-important mammalian enzyme: MMP-8. These results have the potential to contribute to our understanding of many collagen matrix phenomena including development, adaptation, remodeling and disease. Additionally, tissue engineering could benefit from the ability to sculpt desired structures from physiologically compatible and mutable collagen.     

Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study

Background and Aims

Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD.

Methods

We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0–4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals.

Results

We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III.

Conclusions

This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading.     

Leptin Promotes Wound Healing in the Skin

Introduction

Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.

Methods

Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R) in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.

Results

Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.

Conclusion

Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin.     

Do Cells Contribute to Tendon and Ligament Biomechanics?

Introduction

Acellular scaffolds are increasingly used for the surgical repair of tendon injury and ligament tears. Despite this increased use, very little data exist directly comparing acellular scaffolds and their native counterparts. Such a comparison would help establish the effectiveness of the acellularization procedure of human tissues. Furthermore, such a comparison would help estimate the influence of cells in ligament and tendon stability and give insight into the effects of acellularization on collagen.

Material and Methods

Eighteen human iliotibial tract samples were obtained from nine body donors. Nine samples were acellularized with sodium dodecyl sulphate (SDS), while nine counterparts from the same donors remained in the native condition. The ends of all samples were plastinated to minimize material slippage. Their water content was adjusted to 69%, using the osmotic stress technique to exclude water content-related alterations of the mechanical properties. Uniaxial tensile testing was performed to obtain the elastic modulus, ultimate stress and maximum strain. The effectiveness of the acellularization procedure was histologically verified by means of a DNA assay.

Results

The histology samples showed a complete removal of the cells, an extensive, yet incomplete removal of the DNA content and alterations to the extracellular collagen. Tensile properties of the tract samples such as elastic modulus and ultimate stress were unaffected by acellularization with the exception of maximum strain.

Discussion

The data indicate that cells influence the mechanical properties of ligaments and tendons in vitro to a negligible extent. Moreover, acellularization with SDS alters material properties to a minor extent, indicating that this method provides a biomechanical match in ligament and tendon reconstruction. However, the given protocol insufficiently removes DNA. This may increase the potential for transplant rejection when acellular tract scaffolds are used in soft tissue repair. Further research will help optimize the SDS-protocol for clinical application.     

Complete Preoperative Evaluation of Pulmonary Atresia with Ventricular Septal Defect with Multi-Detector Computed Tomography

Objective

To compare multi-detector computed tomography (MDCT) with cardiac catheterization and transthoracic echocardiography (TTE) in comprehensive evaluation of the global cardiovascular anatomy in patients with pulmonary atresia with ventricular septal defect (PA-VSD).

Methods

The clinical and imaging data of 116 patients with PA-VSD confirmed by surgery were reviewed. Using findings at surgery as the reference standard, data from MDCT, TTE and catheterization were reviewed for assessment of native pulmonary vasculature and intracardiac defects.

Results

MDCT was more accurate than catheterization and TTE in identification of native pulmonary arteries. MDCT is also the most accurate test for delineation of the major aortopulmonary collateral arteries. The inter-modality agreement for evaluation of overriding aorta and VSD were both excellent. In the subgroup with surgical correlation, excellent agreement was found between TTE and surgery, and substantial agreement was also found at MDCT.

Conclusion

MDCT can correctly delineate the native pulmonary vasculatures and intracardiac defects and may be a reliable method for noninvasive assessment of global cardiovascular abnormalities in patients with PA-VSD.     

Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab

Background

Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix.

Objective

We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies.

Methods

Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days.

Results

Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects.

Conclusion and Clinical Relevance

Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.     

A Multicenter,Open-Label,Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

Background

Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.

Objective

This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.

Methods

Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.

Results

The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.

Limitations

The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.

Conclusion

MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.

Trial Registration

ClinicalTrials.gov NCT00316602     

Developing Repair Materials for Stress Urinary Incontinence to Withstand Dynamic Distension

Background

Polypropylene mesh used as a mid-urethral sling is associated with severe clinical complications in a significant minority of patients. Current in vitro mechanical testing shows that polypropylene responds inadequately to mechanical distension and is also poor at supporting cell proliferation.

Aims and Objectives

Our objective therefore is to produce materials with more appropriate mechanical properties for use as a sling material but which can also support cell integration.

Methods

Scaffolds of two polyurethanes (PU), poly-L-lactic acid (PLA) and co-polymers of the two were produced by electrospinning. Mechanical properties of materials were assessed and compared to polypropylene. The interaction of adipose derived stem cells (ADSC) with the scaffolds was also assessed. Uniaxial tensiometry of scaffolds was performed before and after seven days of cyclical distension. Cell penetration (using DAPI and a fluorescent red cell tracker dye), viability (AlamarBlue assay) and total collagen production (Sirius red assay) were measured for ADSC cultured on scaffolds.

Results

Polypropylene was stronger than polyurethanes and PLA. However, polypropylene mesh deformed plastically after 7 days of sustained cyclical distention, while polyurethanes maintained their elasticity. Scaffolds of PU containing PLA were weaker and stiffer than PU or polypropylene but were significantly better than PU scaffolds alone at supporting ADSC.

Conclusions

Therefore, prolonged mechanical distension in vitro causes polypropylene to fail. Materials with more appropriate mechanical properties for use as sling materials can be produced using PU. Combining PLA with PU greatly improves interaction of cells with this material.     

Pathway Implications of Aberrant Global Methylation in Adrenocortical Cancer

Context

Adrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options.

Objective

Understanding of the molecular pathogenesis of this disease has been aided by genomic analyses highlighting alterations in TP53, WNT, and IGF signaling pathways. Further elucidation is needed to reveal therapeutically actionable targets in ACC.

Design

In this study, global DNA methylation levels were assessed by the Infinium HumanMethylation450 BeadChip Array on 18 ACC tumors and 6 normal adrenal tissues. A new, non-linear correlation approach, the discretization method, assessed the relationship between DNA methylation/gene expression across ACC tumors.

Results

This correlation analysis revealed epigenetic regulation of genes known to modulate TP53, WNT, and IGF signaling, as well as silencing of the tumor suppressor MARCKS, previously unreported in ACC.

Conclusions

DNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors.     

The Characterization of Novel Tissue Microbiota Using an Optimized 16S Metagenomic Sequencing Pipeline

Background

Substantial progress in high-throughput metagenomic sequencing methodologies has enabled the characterisation of bacteria from various origins (for example gut and skin). However, the recently-discovered bacterial microbiota present within animal internal tissues has remained unexplored due to technical difficulties associated with these challenging samples.

Results

We have optimized a specific 16S rDNA-targeted metagenomics sequencing (16S metabarcoding) pipeline based on the Illumina MiSeq technology for the analysis of bacterial DNA in human and animal tissues. This was successfully achieved in various mouse tissues despite the high abundance of eukaryotic DNA and PCR inhibitors in these samples. We extensively tested this pipeline on mock communities, negative controls, positive controls and tissues and demonstrated the presence of novel tissue specific bacterial DNA profiles in a variety of organs (including brain, muscle, adipose tissue, liver and heart).

Conclusion

The high throughput and excellent reproducibility of the method ensured exhaustive and precise coverage of the 16S rDNA bacterial variants present in mouse tissues. This optimized 16S metagenomic sequencing pipeline will allow the scientific community to catalogue the bacterial DNA profiles of different tissues and will provide a database to analyse host/bacterial interactions in relation to homeostasis and disease.     

Tolerance and Long-Term MRI Imaging of Gadolinium-Modified Meshes Used in Soft Organ Repair

Background

Synthetic meshes are frequently used to reinforce soft tissues. The aim of this translational study is to evaluate tolerance and long-term MRI visibility of two recently developed Gadolinium-modified meshes in a rat animal model.

Materials and Methods

Gadolinium-poly-ε-caprolactone (Gd-PCL) and Gadolinium-polymethylacrylate (Gd-PMA) modified meshes were implanted in Wistar rats and their tolerance was assessed daily. Inflammation and biocompatibility of the implants were assessed by histology and immunohistochemistry after 30 days post implantation. Implants were visualised by 7T and 3T MRI at day 30 and at day 90. Diffusion of Gadolinium in the tissues of the implanted animals was assessed by Inductively Coupled Plasma Mass Spectrometry.

Results

Overall Gd-PMA coated implants were better tolerated as compared to those coated with Gd-PCL. In fact, Gd-PMA implants were characterised by a high ratio collagen I/III and good vascularisation of the integration tissues. High resolution images of the coated mesh were obtained in vivo with experimental 7T as well as 3T clinical MRI. Mass spectrometry analyses showed that levels of Gadolinium in animals implanted with coated mesh were similar to those of the control group.

Conclusions

Meshes coated with Gd-PMA are better tolerated as compared to those coated with Gd-PCL as no signs of erosion or significant inflammation were detected at 30 days post implantation. Also, Gd-PMA coated meshes were clearly visualised with both 7T and 3T MRI devices. This new technique of mesh optimisation may represent a valuable tool in soft tissue repair and management.     

Chitosan Coated Textiles May Improve Atopic Dermatitis Severity by Modulating Skin Staphylococcal Profile: A Randomized Controlled Trial

Background

Atopic dermatitis (AD) patients may benefit from using textiles coated with skin microbiome–modulating compounds. Chitosan, a natural biopolymer with immunomodulatory and antimicrobial properties, has been considered potentially useful.

Objective

This randomized controlled trial assessed the clinical utility of chitosan-coated garment use in AD.

Methods

Of the 102 patients screened, 78 adult and adolescents were randomly allocated to overnight use of chitosan-coated or uncoated cotton long-sleeved pyjama tops and pants for 8 weeks. The primary outcome was change in disease severity assessed by Scoring Atopic dermatitis index (SCORAD). Other outcomes were changes in quality of life, pruritus and sleep loss, days with need for rescue medication, number of flares and controlled weeks, and adverse events. Changes in total staphylococci and Staphylococcus aureus skin counts were also assessed. Comparisons were made using analysis of variance supplemented by repeated measures analysis for the primary outcome. Interaction term between time and intervention was used to compare time trends between groups.

Results

Chitosan group improved SCORAD from baseline in 43.8%, (95%CI: 30.9 to 55.9), P = 0.01, placebo group in 16.5% (-21.6 to 54.6); P = 0.02 with no significant differences between groups; Dermatology Quality of life Index Score significantly improved in chitosan group (P = 0.02) and a significant increase of skin Coagulase negative Staphylococci (P = 0.02) was seen.

Conclusions

Chitosan coated textiles may impact on disease severity by modulating skin staphylococcal profile. Moreover, a potential effect in quality of life may be considered.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01597817","term_id":"NCT01597817"}}NCT01597817     

Impact of Somatic Mutations in the D-Loop of Mitochondrial DNA on the Survival of Oral Squamous Cell Carcinoma Patients

Objectives

The aim of this study was to investigate somatic mutations in the D-loop of mitochondrial DNA (mtDNA) and their impact on survival in oral squamous cell carcinoma patients.

Materials and Methods

Surgical specimen confirmed by pathological examination and corresponding non-cancerous tissues were collected from 120 oral squamous cell carcinoma patients. The sequence in the D-loop of mtDNA from non-cancerous tissues was compared with that from paired cancer samples and any sequence differences were recognized as somatic mutations.

Results

Somatic mutations in the D-loop of mtDNA were identified in 75 (62.5%) oral squamous cell carcinoma patients and most of them occurred in the poly-C tract. Although there were no significant differences in demographic and tumor-related features between participants with and without somatic mutation, the mutation group had a better survival rate (5 year disease-specific survival rate: 64.0% vs. 43.0%, P = 0.0266).

Conclusion

Somatic mutation in D-loop of mtDNA was associated with a better survival in oral squamous cell carcinoma patients.     

A Comparison of Technique Modifications in Laparoscopic Donor Nephrectomy: A Systematic Review and Meta-Analysis

Objective

To compare the effectiveness of different technique modifications in laparoscopic donor nephrectomy.

Design

Systematic review and meta-analyses.

Data Sources

Searches of PubMed, EMBASE, Web of Science and Central from January 1st 1997 until April 1st 2014.

Study Design

All cohort studies and randomized clinical trials comparing fully laparoscopic donor nephrectomy with modifications of the standard technique including hand-assisted, retroperitoneoscopic and single port techniques, were included.

Data-Extraction and Analysis

The primary outcome measure was the number of complications. Secondary outcome measures included: conversion to open surgery, first warm ischemia time, estimated blood loss, graft function, operation time and length of hospital stay. Each technique modification was compared with standard laparoscopic donor nephrectomy. Data was pooled with a random effects meta-analysis using odds ratios, weighted mean differences and their corresponding 95% confidence intervals. To assess heterogeneity, the I2 statistic was used. First, randomized clinical trials and cohort studies were analyzed separately, when data was comparable, pooled analysis were performed.

Results

31 studies comparing laparoscopic donor nephrectomy with other technique modifications were identified, including 5 randomized clinical trials and 26 cohort studies. Since data of randomized clinical trials and cohort studies were comparable, these data were pooled. There were significantly less complications in the retroperitoneoscopic group as compared to transperitoneal group (OR 0.52, 95%CI 0.33–0.83, I2 = 0%). Hand-assisted techniques showed shorter first warm ischemia and operation times.

Conclusions

Hand-assistance reduces the operation and first warm ischemia times and may improve safety for surgeons with less experience in laparoscopic donor nephrectomy. The retroperitoneoscopic approach was significantly associated with less complications. However, given the, in general, poor to intermediate quality and considerable heterogeneity in the included studies, further high-quality studies are required.

Trial Registration

The review protocol was registered in the PROSPERO database before the start of the review process (CRD number 42013006565).     

Dynamic Change of CD34 Level during the Survival Process of Narrow Pedicle Flap

Objective

To evaluate the dynamic change of CD34 level during the survival process of narrow pedicle flaps.

Methods

Twenty-five white pigs were randomly and equally divided into 5 experimental groups. Five different type of narrow pedicle with different length-to-width ratio were employed, and each type of narrow pedicle was covered with 5 different size random flaps and which was classified into A, B, C, D and E for 5 groups. Group A was control group. Each type narrow pedicle with 5 different skin flaps were implanted onto the back of the pigs along the midline of back with a reverse direction. A 0.3 cm×0.3 cm full thickness skin flap in the middle of distal segment was collected and on 3rd, 5th, 7th and 14th days of post-operation. The expression of CD34 was measured by immunohistochemistry and enzyme-linked immunosorbent (ELISA).

Results

Histological examination showed that with the increasing of length-to-width ratio of the narrow pedicle skin flaps, the expression of CD34 increased in the skin flaps. Increased level of CD34 was found on 3rd day post-operation, and the peak expression was found on 7th day. Persistent high level of CD34 was found until 14th day.

Conclusion

Increased CD34 level in the distal skin flap, there is the association between CD34 level and ischemia injury. Moreover, CD34 expression plays an important role during the repair processes of pedicle flaps.     

Stem Cell Therapy for Erectile Dysfunction of Cavernous Nerve Injury Rats: A Systematic Review and Meta-Analysis

Introduction

Stem cell treatment is a novel therapeutic strategy for erectile dysfunction (ED) patients with bilateral cavernous nerve injury (CNI). The relative animal studies provide important clues to design pre-clinical studies and clinical studies further in the future.

Purpose

This study aims to evaluate the effects and influential factors of stem cell transplantation on ED rats with CNI.

Materials and Methods

We searched PubMed and EBSCO databases published before April 30, 2014 for pre-clinical studies to evaluate the efficacy of stem cell transplantation in the treatment of ED rats with CNI. A systematic review and a planned subgroup analysis were performed to identify whether or not some certain influential factors could bring significant effects on stem cell treatment.

Results

12 studies with 319 rats were enrolled in this meta-analysis. Pooled analysis results confirmed the efficacy of stem cell transplantation. Subgroup analysis results showed that treatment effects were not related to CNI models, follow-up time, stem cell species, stem cell sources, markers and delivery approaches in the transplantation. Uncultured stem cells were poorly effective compared with cultured stem cells. Periprostatic implantation (PPI) with acellular scaffolds could promote cavernous nerve regeneration, but was less effective for smooth muscle cell recovery. Stem cells modified by NGF or BDNF combined with udenafil/bFGF seemed to be more effective than those modified by BDNF alone.

Conclusion

This meta-analysis shows that stem cell therapy can be performed to recover erectile function. Future studies should focus on nerve restoration and vascular cell recovery. The synergistic actions of multiple growth factors following stem cell transplantation should also be considered as beneficial strategies to obtain preferable effects.     

Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis

Background

Elevated levels of advanced glycation end products (AGEs) within tissues may contribute to endothelial dysfunction, an early indicator of atherosclerosis. We aimed to investigate whether levels of skin AGEs could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis.

Methods and Results

One hundred and nineteen uremic patients on hemodialysis and 57 control subjects with moderate-to-high cardiovascular risk factors and without chronic kidney disease (CKD) were enrolled. We used ultrasound to measure flow-mediated vasodilation (FMD). An AGE reader measured skin autoflurorescence (AF). We then compared differences in FMD and skin AF values between the two groups. The uremic subjects had significantly higher levels of skin AF (3.47±0.76 AU vs. 2.21±0.45 arbitrary units; P<0.01) and significantly lower levels of FMD (4.79%±1.88% vs. 7.19%±2.17%; P<0.01) than the non-CKD subjects. After adjusting for all potential covariates, we found that skin AF level independently predicted FMD in both the hemodialysis and the non-CKD groups. In the hemodialysis group, skin AF ≥ 3.05 arbitrary units predicted abnormal FMD at a sensitivity of 87.9% and a specificity of 78.6% (P<0.01).

Conclusions

Skin AF could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis.     

Buttonhole Cannulation Is Not Associated with More AVF Infections in a Low-Care Satellite Dialysis Unit: A Long-Term Longitudinal Study

Background

Buttonhole cannulation (BHC) has been associated with a greater risk of arteriovenous fistula (AVF)-related infections and septicemia than the rope ladder cannulation (RLC) in in-center hemodialysis (HD). Such infections have never been studied in satellite HD units.

Study Design

Retrospective single center study.

Setting and Participant

All patients in our satellite HD unit using a native AVF from 1 January, 1990, to 31 December, 2012.

Study Period

Two different kinds of cannulation have been used during the study period: From 1 January, 1990 to 1, January, 1998 RLC was used in the unit (period 1). After 1 January, 1998 onwards, all the patients were switched within 3 months to BHC (period 2).

Outcomes

Three different infectious events were observed during the two periods: local AVF infection, bacteremia, and combined infection. The aim of this study was to evaluate the incidence of AVF-related infections in our low-care HD unit and to determine whether BHC is associated with an increased risk of infection in this population.

Results

162 patients were analyzed; 68 patients participated to period 1 and 115 to period 2. Sixteen infectious events occurred. Incidences of AVF-related infectious events were 0.05 [95% CI, 0.02–0.16] and 0.13/1000 AVF-days [95% CI, 0.0.8–0.23], for period 1 and 2 (p = 0.44) respectively. Recurrence of AVF-related infection was observed only during period 2. Unadjusted incidence rate ratio (IRR) of all infections was 0.39 (95%CI 0.12–1.37). Two complicated infections occurred during the study period: one in period 1 and one in period 2.

Limitations

Observational retrospective single centre study

Conclusions

BHC is not associated with an increased infectious incidence in our HD population from a satellite dialysis unit. In the rare patients with AVF-related infection it seems necessary to change cannulation sites as recurrence of infection might be an event more frequent with BHC.     

Japanese Lifestyle during Childhood Prevents the Future Development of Obesity among Japanese-Americans

Objective

To evaluate whether a Japanese lifestyle during childhood could protect against the future development of obesity-associated metabolic diseases by comparing native Japanese with Japanese-Americans in whom genetic factors are the same.

Methods

Study subjects were 516 native Japanese and 781 Japanese-Americans who underwent medical examinations between 2007 and 2010. Japanese-Americans were divided into 444 first-generation immigrants (JA-1), who were born in Japan, and 337 second- or later-generation descendants (JA-2), who were born in the United States. The JA-2 group was then divided into the kibei subgroup (N = 79), who had moved to Japan before the age of 18 years and later returned to the United States, and the non-kibei subgroup (N = 258), who had never lived in Japan.

Results

The JA-2 group had the highest percentages of obesity, metabolic syndrome, and type 2 diabetes compared with native Japanese and JA-1. Furthermore, among JA-2, the prevalence of obesity and metabolic syndrome in the kibei subgroup was significantly lower than that in the non-kibei subgroup. The prevalence of diabetes in the kibei subgroup also tended to be lower than in the non-kibei subgroup.

Conclusions

The prevalence of obesity and metabolic diseases differed with residence in Japan during childhood among Japanese-Americans. These findings indicate the possibility that Japanese lifestyle during childhood could reduce the future risks for obesity-associated metabolic diseases.     

Identification of Novel Adipokines in the Joint. Differential Expression in Healthy and Osteoarthritis Tissues

Objectives

Emerging data suggest that several metabolic factors, released mainly by white adipose tissue (WAT) and joint tissues, and collectively named adipokines, might have a role in the pathophysiology of OA. Recently, novel adipokines such as SERPINE2, WISP2, GPNMB and ITIH5 have been identified in WAT. The main goal of this study was to analyse the expression of these novel adipokines in synovium, infrapatellar fat pad and chondrocytes and to compare the expression of these molecules in healthy and OA tissues.

Methods

Synovial tissues, infrapatellar fat pad and chondrocytes were obtained from 36 OA patients (age 52–85; mean BMI 28.9) who underwent total knee replacement surgery. Healthy synovial tissues and infrapatellar fat pad were obtained from 15 traumatic knee patients (age 23–53; mean BMI 23.5). mRNA and protein expression were determined by qRT-PCR and western blot analysis respectively.

Results

All the novel adipokines, matter of our study, are expressed in OA synovium, infrapatellar fat pad and chondrocytes. Moreover, we detected a differential expression of SERPINE2 and ITIH5 in OA synovial tissues as compared to healthy samples. Finally, we also observed an increased expression of WISP2 in OA infrapatellar fat pad in comparison to healthy controls.

Conclusions

In this study we demonstrated for the first time the expression of four novel adipokines in different joint tissues and how these molecules are differentially expressed in healthy and OA joint tissues.