Chronic minocycline treatment improves hippocampal neuronal structure, NMDA receptor function, and memory processing in Fmr1 knockout mice.

Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability, and is the leading known single-gene cause of autism spectrum disorder. FXS patients display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently there is no cure for this condition, however minocycline is becoming commonly prescribed as a treatment for FXS patients. Minocycline has been reported to alleviate social behavioural deficits, and improve verbal functioning in patients with FXS; however, its mode of action is not well understood. Previously we have shown that FXS results in learning impairments that involve deficits in N-methyl-d-aspartate (NMDA) receptor-dependent synaptic plasticity in the hippocampal dentate gyrus (DG). Here we tested whether chronic treatment with minocycline can improve these deficits by enhancing NMDA receptor-dependent functional and structural plasticity in the DG. Minocycline treatment resulted in a significant enhancement in NMDA receptor function in the dentate granule cells. This was accompanied by an increase in PSD-95 and GluN2A and GluN2B subunits in hippocampal synaptoneurosome fractions. Minocycline treatment also enhanced dentate granule cell dendritic length and branching. In addition, our results show that chronic minocycline treatment can rescue performance in novel object recognition in FXS mice. These findings indicate that minocycline treatment has both structural and functional benefits for hippocampal cells, which may partly contribute to the pro-cognitive effects minocycline appears to have for treating FXS.

Impaired bidirectional NMDA receptor dependent synaptic plasticity in the dentate gyrus of adult female Fmr1 heterozygous knockout mice.

Fragile-X syndrome (FXS) is caused by the transcriptional repression of the Fmr1 gene resulting in loss of the Fragile-X mental retardation protein (FMRP). This leads to cognitive impairment in both male and female patients, however few studies have focused on the impact of FXS in females. Significant cognitive impairment has been reported in approximately 35% of women who exhibit a heterozygous Fmr1 gene mutation, however to date there is a paucity of information regarding the mechanistic underpinnings of these deficits. We, and others, have recently reported that there is significant impairment in N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal dentate gyrus (DG) of male Fmr1 knock out mice. Here we examined if female mice displaying a heterozygous loss of the Fmr1 gene (Fmr1+/-) would exhibit similar impairments in DG-dependent spatial memory processing and NMDAR hypofunction. We found that Female Fmr1+/- mice did not show impaired metabotropic glutamate receptor (mGluR)-LTD in the CA1 region, and could perform well on a temporal ordering task that is thought to involve this brain region. In contrast, female Fmr1+/- mice showed impairments in a pattern separation task thought to involve the DG, and also displayed a significant impairment in both NMDAR-dependent LTD and LTP in this region. The LTP impairment could be rescued by administering the NMDAR co-agonist, glycine. Our data suggests that NMDAR hypofunction in the DG may partly contribute to learning and memory impairment in female Fmr1+/- mice. Targeting NMDAR-dependent mechanisms may offer hope as a new therapeutic approach for treating female FXS patients with learning and memory impairments.

IGFBP-2 inhibits adipogenesis and lipogenesis in human visceral, but not subcutaneous, adipocytes.

BACKGROUND/OBJECTIVE: IGF-binding protein (IGFBP)-2 is the principal IGFBP produced by white adipocytes during adipogenesis, and circulating levels are reduced in obesity. Overexpression of IGFBP-2 in transgenic mice prevents obesity, but depot-specific effects of IGFBP-2 on adipo/lipogenesis are unknown. The present study aimed to investigate whether IGFBP-2 affects adipo/lipogenesis in a depot-specific manner and explore potential mechanisms. METHODS: Following adipocyte characterisation, IGFBP-2 levels were measured from human subcutaneous and visceral preadipocytes, and IGFBP-2 dose-responses were then undertaken with exogenous IGFBP-2 in an in vitro IGF-I-free system to examine adipo/lipogenesis. Following this, both types of adipocytes were transfected with human siRNA IGFBP-2 to assess auto-/para-/intra-crine effects, with and without additional add-back IGFBP-2. To elucidate the potential mechanisms, visceral preadipocytes were treated with either wild-type or Heparin Binding Domain (HBD)-mutant IGFBP-2 (which is unable to bind to cell-surface components), and experiments were also undertaken using Echistatin (an integrin receptor blocker). Outcomes included gene expression profiles, protein levels and phosphorylation and lipid staining. RESULTS: Human visceral adipocytes produced significantly more IGFBP-2 than subcutaneous adipocytes. Subsequent dose-responses to IGFBP-2 demonstrated significant reductions in adipo/lipogenesis in visceral, but not subcutaneous, adipocytes in response to increasing IGFBP-2. Silencing IGFBP-2 resulted in exaggerated adipo/lipogenesis in visceral, but not subcutaneous, adipocytes, an effect completely inhibited by add-back IGFBP-2. These effects occurred in the absence of changes in IGF-I levels. HBD-mutant IGFBP-2 had reduced effects compared with wild-type IGFBP-2. Wild-type IGFBP-2 increased phosphorylation of focal adhesion kinase (FAK) and decreased phosphatase and tensin homolog (PTEN) levels, suggestive of integrin-mediated signalling. Blockade of this signalling, using Echistatin, completely negated the effects of IGFBP-2 on visceral adipo/lipogenesis. CONCLUSION: IGFBP-2 inhibits both adipogenesis and lipogenesis in visceral, but not subcutaneous, adipocytes. This depot-specific impairment appears to be independent of IGF-I and involves cell-surface association of IGFBP-2 and activation of integrin signalling pathways.

Negative surveillance endoscopy occurs frequently in patients with short-segment non-dysplastic Barrett's esophagus.

Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥ 2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barrett's esophagus segment length was < 1 cm, 32.14% (18/56) of all patients (with ≥ 2 surveillance endoscopies) had negative IM on consecutive surveillance endoscopies. Negative surveillance occurs frequently in short-segment NDBE. When an initial negative surveillance endoscopy occurs, it may be due to either a sampling error or lack of detectable IM on surveillance exam. When a <1 cm segment of NDBE is diagnosed, a significant proportion of patients may go on to have continuously undetected IM on consecutive surveillance endoscopic exams without intervention.

Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC): Asian subgroup analysis.

BACKGROUND: This preplanned subset analysis of the phase III MONET1 study aimed to determine whether motesanib combined with carboplatin/paclitaxel (C/P) would result in improved overall survival (OS) versus chemotherapy alone, in a subset of Asian patients with nonsquamous nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with nonsquamous NSCLC (stage IIIB/IV or recurrent) and no prior systemic therapy for advanced disease were randomized to IV carboplatin (AUC, 6 mg/ml min) and paclitaxel (200 mg/m2) for up to six 3-week cycles, plus either oral motesanib 125 mg q.d. or placebo. Primary end point was OS; secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: Two hundred twenty-seven Asian patients from MONET1 were included in this descriptive analysis. Median OS was 20.9 months in the motesanib plus C/P arm and 14.5 months in the placebo plus C/P arm (P=0.0223); median PFS was 7.0 and 5.3 months, respectively, (P=0.0004); and ORR was 62% and 27%, respectively, (P<0.0001). Grade≥3 adverse events were more common in the motesanib plus C/P arm versus placebo plus C/P (79% versus 61%). CONCLUSION: In this preplanned subset analysis of Asian patients with nonsquamous NSCLC, motesanib plus C/P significantly improved OS, PFS, and ORR versus placebo plus C/P. CLINICAL TRIAL NUMBER: NCT00460317.

Novel use of idebenone in Leber's hereditary optic neuropathy in Hong Kong.

We report a case of a young Chinese male presenting with sequential, painless, bilateral visual loss in Hong Kong. He was diagnosed to have Leber's hereditary optic neuropathy with genetic workup showing G11778A mutation with over 80% heteroplasmy. He was started on idebenone treatment 11 months after onset of the binocular disease. To our best knowledge, this is the first case of Leber's hereditary optic neuropathy treated with idebenone in Hong Kong. The recent evidence of the diagnosis and treatment of this devastating disease is reviewed.

Nutritional value, performance, carcass quality, visceral organ size, and blood clinical chemistry of broiler chicks fed 30% tannin-free fava bean diets.

Two experiments were conducted to evaluate the chemical and nutritional values of 5 tannin-free fava bean (FB) cultivars (FB9, FB10, FB13, FB17, and FB24) on growth, visceral organ size, and blood clinical chemistry of broiler chicks fed a corn-soybean meal 48 (SBM48) diet containing 30% tannin-free FB. In the first experiment, 49 Hy-line roosters, 55 wk of age, were individually precision-fed 30 g of each FB cultivar and soybean meal 44 (SBM44). Protein, methionine, and lysine contents of the FB seeds (0.005% tannin) were 27.7, 0.23, and 1.98% of DM, respectively. The AMEn of all FB cultivars was 2,839 kcal/kg and higher (P < 0.05) than SBM44. The true lysine digestibility of FB10 (94.1) was higher (P < 0.05) than FB9 (89.0%) and FB24 (89.2%), but comparable with the other fava beans. The FB cultivar's true methionine digestibilities were similar among each other and to SBM44. In a battery feeding trial, 6 corn-SBM48 diets containing 0 (control) or 30% of FB9, FB10, FB13, FB17, or FB24 seeds were each fed to Ross 308 1-wk-old male broiler chicks for 14 d. The determined FB nutrient values were used in formulating FB-containing diets. Birds fed FB-containing diets had better (P < 0.05) weight gain and feed conversion than those of the control. When compared with the control birds, relative weights of abdominal fat pad and liver were reduced (P < 0.05) by 30% inclusion of all dietary FB varieties, except for FB17 and FB13, respectively. Broiler chicks fed the FB13 diet had plasma thrombocyte and white blood cell (WBC) differential counts higher (P < 0.05) than those fed the FB10 diet and WBC count higher (P < 0.05) than the birds fed the FB17 diet. In conclusion, tannin-free FB was lower in protein, methionine, and lysine, but higher in AMEn, compared with SBM44. Moreover, FB seeds, especially FB10, can be included in a broiler chick diet with no adverse effects on performance, but FB13 increased WBC count.

Paperless medical physics QA in radiation therapy.

Physics quality assurance (QA) is an integral part of a medical physicist's role in the radiotherapy centre. Management of physics QA documents is an issue with a long-term accumulation. Storage space, archive administration and paper consumption are just some of the difficulties faced by physicists. Plotting trends and drawing meaningful conclusions from these results can be challenging using traditional QA methods. Remote checking of QA within a hospital network can also be problematic. The aim of this project is introduce a paperless QA system that will provide solutions to many of these issues.

Multi-disciplinary Psychiatric Case Management Model in Hong Kong: Service Coverage and Risk Stratification.

INTRODUCTION: Community mental health services in Hong Kong follow a multi-disciplinary case management model. We investigated whether at-risk patients received higher intensity care and whether risk stratification concorded between personalised care programmes and integrated community centres of mental wellness. METHODS: Records of all patients in North Lantau and Mongkok districts who received case management services (from personalised care programmes and/or integrated community centres of mental wellness) between 1 April 2014 and 30 June 2015 were reviewed. Patients' levels of risk, demographic data, and clinical characteristics were analysed. RESULTS: Identified at-risk patients received high-intensity care from personalised care programmes and integrated community centres of mental wellness. Case management was coordinated between the Hospital Authority and non-government organisations. However, risk stratification did not correlate with assessment rating scores of psychopathology or psychosocial functioning. Assessment rating scales appear unsuitable to provide any optimal cut-off scores for risk stratification. CONCLUSIONS: Risk stratification should be a structured clinical judgement based on comprehensive and accurate information of protective and risk factors, rather than relying on cut-off scores of assessment rating scales.

Chemiluminescence of anodized and etched silicon: evidence for a luminescent siloxene-like layer on porous silicon.

Treatment of anodized or chemically etched silicon ("porous silicon") with dilute nitric acid or persulfate solution results in weak chemiluminescence in the visible region. Concentrated nitric acid reacts violently with porous Si produced by anodization with a bright flash of light. The fact that similar reactions occur with siloxene (Si(6)H(6)O(3)) prepared from CaSi(2) suggests that the visible emission seen with porous Si can be attributed to this substance.

Atomic resolution imaging of adsorbates on metal surfaces in air: iodine adsorption on pt(111).

The adsorption of iodine on platinum single crystals was studied with the scanning tunneling microscope (STM) to define the limits of resolution that can be obtained while imaging in air and to set a target resolution for STM imaging of metal surfaces immersed in an electrochemical cell. Two iodine adlattice unit cells of slightly different iodine packing density were clearly imaged: ( radical7 x radical7) R19.1 degrees -I, surface coverage ø(I) = 3/7; and (3 x 3)-I, ø(I) = 4/9. The three iodine atoms in the ( radical7 x radical7) unit cell form a regular hexagonal lattice interatomic distance d(I) = 0.424 nanometer, with two atoms adsorbed in threefold hollow sites and one atom adsorbed at an atop site. The (3 x 3) unit cell showed two different packing arrangements of the four iodine atoms exit. In one of the (3 x 3) structures, the iodine atoms pack to form a hexagonal lattice, d(I) = 0.417 nanometer, with three of the iodine atoms at twofold adsorption sites and one atom at an atop site. Another packing arrangement of iodine into the (3 x 3) unit cell was imaged in which the iodine atoms are not arranged symmetrically.

Management decision of hospital surge: assessing seasonal upsurge in inpatient medical bed occupancy rate among public acute hospitals in Hong Kong.

BACKGROUND: There were recurrent upsurges in demand for public hospital services in Hong Kong. An understanding of the contribution of some possible factors for the rise in health care burden would help to inform hospital management strategies. AIM: To evaluate the utilization patterns of hospitalizations in medical wards among public acute hospitals in Hong Kong during surge periods. DESIGN: Retrospective study. METHODS: By extracting the information in press releases between 2014 and 2018, descriptive statistics about medical ward occupancy situation during six surge periods were generated. A time series model was constructed to estimate the occupancy rate at each hospital and assess its relationship with the intensity of seasonal influenza activity, extreme weather, day of week and long holidays. RESULTS: There was a significant increase in the number of admissions to medical wards in all six surge periods. A significant variation in occupancy rate between weekdays and geographic regions was observed. The occupancy rate in 10, out of 15, hospitals was significantly associated with the influenza activity, while there was limited effect of weather on the occupancy rate. A significant holiday effect was observed during Christmas and Chinese New Year, resulting in a lower bed occupancy rate. CONCLUSIONS: A differential burden in public hospitals during surge periods was reported. Contingency bed and staff management shall be tailored to individual hospitals, given their differences in the determinants for inpatient bed occupancy.

Serum IGFBP-2 levels are associated with reduced insulin sensitivity in obese children.

Insulin-like growth factor binding protein 2 (IGFBP-2) may represent a critical link between body composition and insulin sensitivity. We investigated the relationship between circulating IGFBP-2 levels, body composition, insulin sensitivity, energy intake and physical activity in children with obesity. Children were recruited via the Weight Management Service at the Royal Children's Hospital, Melbourne, as part of the Childhood Overweight BioRepository of Australia (COBRA). Comprehensive anthropometric, biochemical and environmental data were collected and compared to serum IGFBP-2 levels (measured by enzyme-linked immunosorbent assay). Multiple regression modelling was used to assess the influence of circulating IGFBP-2 levels on anthropometric and biochemical measures. One hundred and ninety-four children were included in this study (46% male). Circulating IGFBP-2 negatively correlated with age, anthropometric measures, blood pressure and insulin concentration. Positive associations were observed between insulin sensitivity index-homeostasis model assessment (ISI-HOMA) and serum IGFBP-2. In multiple regression modelling, IGFBP-2 significantly contributes to variance in systolic blood pressure (-19%, P < 0.05), circulating triglycerides (-16%, P < 0.05) and ISI-HOMA (18%, P < 0.05). No associations were observed between dietary energy intake or physical activity and IGFBP-2 levels. Circulating IGFBP-2 levels in children with obesity correlate inversely with body mass and markers of metabolic dysfunction, and positively with insulin sensitivity. These findings suggest that reduced levels of IGFBP-2 may play an important role in the pathogenesis of obesity complications in early life.

Intronic breakpoint definition and transcription analysis in DMD/BMD patients with deletion/duplication at the 5' mutation hot spot of the dystrophin gene.

Dystrophin mutations occurring at the 5' end of the gene frequently behave as exceptions to the "frame rule," their clinical severity being variable and often not related to the perturbation of the translation reading frame. The molecular mechanisms underlying the phenotypic variability of 5' dystrophin mutations have not been fully clarified. We have characterized the genomic breakpoints within introns 2, 6 and 7 and identified the splicing profiles in a cohort of DMD/BMD patients with deletion of dystrophin exons 3-7, 3-6 and duplication of exons 2-4. Our findings indicate that the occurrence of intronic cryptic promoter as well as corrective splicing events are unlikely to play a role in exons 3-7 deleted patients phenotypic variability. Our data suggest that re-initiation of translation could represent a major mechanism responsible for the production of a residual dystrophin in some patients with exons 3-7 deletion. Furthermore, we observed that the out-of-frame exon 2a is almost constantly spliced into a proportion of the dystrophin transcripts in the analysed patients. In the exons 2-4 duplicated DMD patient, producing both in-frame and out-of-frame transcripts, this splicing behaviour might represent a critical factor contributing to the severe phenotype. In conclusion, we suggest that multiple mechanisms may have a role in modulating the outcome of 5' dystrophin mutations, including recoding mechanisms and unusual splicing choices.

Cryptosporidium parvum infection attenuates the ex vivo propagation of murine intestinal enteroids.

Cryptosporidium, a ubiquitous coccidian protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces, is an important opportunistic pathogen for immunocompromised individuals and a common cause of diarrhea in young children in the developing countries. One of the pathological hallmarks of intestinal cryptosporidiosis is villous atrophy, which results in a shorter height of intestinal villi. Here, we investigated the effects of Cryptosporidium infection on intestinal epithelial growth, using an ex vivo model of intestinal cryptosporidiosis employing enteroids from mice. We detected infection of enteroids isolated from immunocompetent adult and neonatal mice after ex vivo exposure to Cryptosporidium sporozoites. We observed a significant inhibition of enteroid propagation following infection. Intriguingly, we identified a decreased expression level of intestinal stem cell markers in enteroids following C. parvum infection. We further measured the expression levels of several Wnt antagonists or agonists in infected enteroids, as induction of the Wnt/ß-catenin activation is a key factor for intestinal stem cell function. We detected a markedly increased level of the Dickkopf-related protein 1 and decreased level of the Wnt family member 5a in enteroids after infection. The low density lipoprotein receptor-related protein 5, one of the Wnt co-receptors, is downregulated in the infected enteroids. In addition, increased apoptotic cell death and cell senescence were observed in the infected enteroids. Our results demonstrate a significant inhibitory effect of Cryptosporidium infection on the ex vivo propagation of enteroids from mice, providing additional insights into the impact of Cryptosporidium infection on intestinal epithelial growth.

Molecular-level thermodynamic and kinetic parameters for the self-assembly of apoferritin molecules into crystals.

The self-assembly of apoferritin molecules into crystals is a suitable model for protein crystallization and aggregation; these processes underlie several biological and biomedical phenomena, as well as for protein and virus self-assembly. We use the atomic force microscope in situ, during the crystallization of apoferritin to visualize and quantify at the molecular level the processes responsible for crystal growth. To evaluate the governing thermodynamic parameters, we image the configuration of the incorporation sites, "kinks", on the surface of a growing crystal. We show that the kinks are due to thermal fluctuations of the molecules at the crystal-solution interface. This allows evaluation of the free energy of the intermolecular bond phi=3.0 k(B)T=7.3 kJ/mol. The crystallization free energy, extracted from the protein solubility, is -42 kJ/mol. Published determinations of the second virial coefficient and the protein solubility between 0 and 40 degrees C revealed that the enthalpy of crystallization is close to zero. Analyses based on these three values suggest that the main component in the crystallization driving force is the entropy gain of the water molecules bound to the protein molecules in solution and released upon crystallization. Furthermore, monitoring the incorporation of individual molecules in to the kinks, we determine the characteristic frequency of attachment of individual molecules at one set of conditions. This allows a correlation between the mesoscopic kinetic coefficient for growth and the molecular-level thermodynamic and kinetic parameters determined here. We found that step growth velocity, scaled by the molecular size, equals the product of the kink density and attachment frequency, i.e. the latter pair are the molecular-level parameters for self-assembly of the molecules into crystals.

IGFBP-2: The dark horse in metabolism and cancer.

The ubiquitous nature of the IGF system, expressed early in embryonic development throughout postnatal and adult life, indicates a key role for this system in human biology. Studies of transgenic mice over-expressing components of the IGF system or mice with disruptions of the same genes have clearly shown that the IGF system plays an important role in vivo. The activity of the IGF ligands, elicited via their receptors and transduced by various intracellular signal pathways, is modulated by the IGFBPs. Among all the IGFBPs, IGFBP-2 has been implicated in the regulation of IGF activity in the nervous system, peripheral tissue and organs. Besides binding to IGFs in the circulation, these IGF-regulatory activities of IGFBP-2 involve interactions with components of the extracellular matrix and cell surface proteoglycans and integrin receptors. In addition to these "local" peri-cellular activities of IGFBP-2, it became evident that IGFBP-2 exerts other key functions within the cell. In the cytoplasm IGFBP-2, most likely in the absence of the IGFs, interacts with regulatory proteins including transcription factors and cytoplasm-nuclear transporters. Within the nucleus IGFBP-2, directly or indirectly, promotes transcriptional activation of specific genes. These intrinsic activities of IGFBP-2 are mediated via specific functional domains. All of these IGFBP-2 activities, intrinsic or dependent on IGFs, contribute to its functional roles in growth/development, metabolism and malignancy as evidenced by studies in IGFBP-2 animal models and also by many in vitro studies. Finally, preclinical studies have demonstrated that IGFBP-2 administration can be beneficial in improving metabolic responses (inhibition of adipogenesis and enhanced insulin sensitivity), while blockade of IGFBP-2 appears to be an effective approach to inhibiting tumor growth and metastasis.

Interlaboratory studies to determine optimal analytical methods for measuring the oxidation index of UHMWPE.

Fourier transform infrared spectroscopy has emerged as the technique of choice for the quantification of oxidation in ultra-high molecular weight polyethylene used in orthopedic implants. We initiated interlaboratory studies to determine the method of normalization, hence quantification, that provided the highest level of reproducibility across multiple institutions. The goal of this research was to identify optimal normalization methods that minimize the experimental uncertainties associated with interlaboratory reproducibility and intralaboratory repeatability of oxidation index measurements. Test samples were prepared from GUR 4150 HP, gamma irradiated in air, and had a shelf age of two years. Samples were analyzed according to ten oxidation index test methods during two interlaboratory studies, which were conducted in accordance with ASTM E691. Variations in reproducibility and repeatability were evaluated using analysis of variance (ANOVA). The basis of the test methods (peak area-based vs. peak height-based), as well as the normalization method, were both found to be associated with significant differences in reproducibility (p = 0.0006 andp < 0.0001, respectively). Normalization techniques based on the 1370 and 2022cm(-1) peaks areas were found to be the most reproducible methods, and were associated with mean interlaboratory uncertainties of 16.5% and 24.2%, respectively. Repeatability of the test methods was not sensitive to the normalization technique; the mean intralaboratory repeatability for all of oxidation index measurements was found to be 10.2%. The results of this interlaboratory research will be a useful basis for the development of a new oxidation index standard for the orthopedics community.

Interlaboratory reproducibility of standard accelerated aging methods for oxidation of UHMWPE.

During accelerating aging, experimental uncertainty may arise due to variability in the oxidation process, or due to limitations in the technique that is ultimately used to measure oxidation. The purpose of the present interlaboratory study was to quantify the repeatability and reproducibility of standard accelerated aging methods for ultra-high molecular weight polyethylene (UHMWPE). Sections (200 microm thick) were microtomed from the center of an extruded rod of GUR 4150 HP, gamma irradiated in air or nitrogen, and circulated to 12 institutions in the United States and Europe for characterization of oxidation before and after accelerated aging. Specimens were aged for 3 weeks at 80 degrees C in an air circulating oven or for 2 weeks at 70 degrees C in an oxygen bomb (maintained at 503 kPa (5 atm.) of O2) in accordance with the two standard protocols described in ASTM F 2003-00. FTIR spectra were collected from each specimen within 24 h of the start and finish of accelerated aging, and oxidation indices were calculated by normalizing the peak area of the carbonyl region by the reference peak areas at 1370 or 2022 cm(-1). The mean relative interlaboratory uncertainty of the oxidation data was 78.5% after oven aging and 129.1% after bomb aging. The oxidation index measurement technique was not found to be a significant factor in the reproducibility. Comparable relative intrainstitutional uncertainty was observed after oven aging and bomb aging. For both aging methods, institutions successfully discriminated between air-irradiated and control specimens. However, the large interinstitutional variation suggests that absolute performance standards for the oxidation index of UHMWPE after accelerated aging may not be practical at the present time.