Device-Embedded Cameras for Eye Tracking-Based Cognitive Assessment: Implications for Teleneuropsychology.

Introduction:Widespread screening for cognitive decline is an important challenge to address as the aging population grows, but there is currently a shortage of clinical infrastructure to meet the demand for in-person evaluation. Remotely delivered assessments that utilize eye-tracking data from webcams, such as visual paired comparison (VPC) tasks, could increase access to remote, asynchronous neuropsychological screening for cognitive decline but further validation against clinical-grade eye trackers is required.Methods:To demonstrate equivalence between a novel automated scoring system for eye-tracking metrics acquired through a laptop-embedded camera and a gold-standard eye tracker, we analyzed VPC data from 18 subjects aged 50+ with normal cognitive function across three visits. The eye tracker data were scored by the manufacturer's software, and the webcam data were scored by a novel algorithm.Results:Automated scoring of webcam-based VPC data revealed strong correlations with the clinical-grade eye-tracking camera. Correlation of mean VPC performance across all time points was robust: r = 0.95 (T1 r = 0.97; T2 r = 0.88; T3 r = 0.97; p's < 0.001). Correlation of per-trial performance across time points was also robust: r = 0.88 (T1 r = 0.85; T2 r = 0.89; T3 r = 0.92; p's < 0.001). Mean differences between performance data acquired by each device were 0.00.Conclusion:These results suggest that device-embedded cameras are a valid and scalable alternative to traditional laboratory-based equipment for gaze-based tasks measuring cognitive function. The validation of this technique represents an important technical advance for the field of teleneuropsychology.

Elevated brain lesion volumes in older adults who use calcium supplements: a cross-sectional clinical observational study.

Recent studies have implicated Ca supplements in vascular risk elevation, and therefore these supplements may also be associated with the occurrence of brain lesions (or hyperintensities) in older adults. These lesions represent damage to brain tissue that is caused by ischaemia. In the present cross-sectional clinical observational study, the association between Ca-containing dietary supplement use and lesion volumes was investigated in a sample of 227 older adults (60 years and above). Food and supplemental Ca intakes were assessed with the Block 1998 FFQ; participants with supplemental Ca intake above zero were categorised as supplement users. Lesion volumes were determined from cranial MRI (1.5 tesla) scans using a semi-automated technique; volumes were log-transformed because they were non-normal. ANCOVA models revealed that supplement users had greater lesion volumes than non-users, even after controlling for food Ca intake, age, sex, race, years of education, energy intake, depression and hypertension (Ca supplement use: ß = 0.34, SE 0.10, F(1,217)= 10.98, P= 0.0011). The influence of supplemental Ca use on lesion volume was of a magnitude similar to that of the influence of hypertension, a well-established risk factor for lesions. Among the supplement users, the amount of supplemental Ca was not associated with lesion volume (ß = - 0.000035, SE 0.00 015, F(1,139)= 0.06, P= 0.81). The present study demonstrates that the use of Ca-containing dietary supplements, even low-dose supplements, by older adults may be associated with greater lesion volumes. Evaluation of randomised controlled trials is warranted to determine whether this relationship is a causal one.

Ankle arthrodesis fusion rates for mesenchymal stem cell bone allograft versus proximal tibia autograft.

Ankle arthrodesis is commonly used in the treatment of ankle arthritis. The present study compared mesenchymal stem cell (MSC) bone allografts and proximal tibia autografts as adjuncts in performing ankle arthrodesis. A total of 109 consecutive ankle fusions performed from 2002 to 2008 were evaluated retrospectively. Of the 109 fusions, 24 were excluded from the present study, leaving 85 patients who had undergone ankle arthrodesis. Of the 85 patients, 41 had received a proximal tibia autograft and 44, an MSC bone allograft. These 2 groups were reviewed and compared retrospectively at least 2 years postoperatively for the overall fusion rate, interval to radiographic fusion, and interval to clinical fusion. A modified and adjusted American College of Foot and Ankle Surgeons ankle scale was used to measure patient satisfaction. The overall fusion rate was 84.1% in the MSC bone allograft group and 95.1% in the proximal tibia autograft group (p = .158). The corresponding mean intervals to radiographic fusion were 13.0 ± 2.5 weeks and 11.3 ± 2.8 weeks (p ≤ .001). The interval to clinical fusion was 13.1 ± 2.1 weeks and 11.0 ± 1.5 weeks (p ≤ .001) in the MSC bone allograft and proximal tibia autograft group, respectively. No statistically significant difference was found in the fusion rates between the MSC bone allograft and proximal tibia autograft groups. Also, no statistically significant difference was found between the preoperative and postoperative scores using a modified and adjusted American College of Foot and Ankle Surgeons ankle scale between the 2 groups (p = .41 and p = .44, respectively). A statistically significant delay to radiographic and clinical fusion was present in the MSC bone allograft group compared with the proximal tibia autograft group; however, no difference was found in patient satisfaction.

A Study of Novel Exploratory Tools, Digital Technologies, and Central Nervous System Biomarkers to Characterize Unipolar Depression.

Background: Digital technologies have the potential to provide objective and precise tools to detect depression-related symptoms. Deployment of digital technologies in clinical research can enable collection of large volumes of clinically relevant data that may not be captured using conventional psychometric questionnaires and patient-reported outcomes. Rigorous methodology studies to develop novel digital endpoints in depression are warranted. Objective: We conducted an exploratory, cross-sectional study to evaluate several digital technologies in subjects with major depressive disorder (MDD) and persistent depressive disorder (PDD), and healthy controls. The study aimed at assessing utility and accuracy of the digital technologies as potential diagnostic tools for unipolar depression, as well as correlating digital biomarkers to clinically validated psychometric questionnaires in depression. Methods: A cross-sectional, non-interventional study of 20 participants with unipolar depression (MDD and PDD/dysthymia) and 20 healthy controls was conducted at the Centre for Human Drug Research (CHDR), the Netherlands. Eligible participants attended three in-clinic visits (days 1, 7, and 14), at which they underwent a series of assessments, including conventional clinical psychometric questionnaires and digital technologies. Between the visits, there was at-home collection of data through mobile applications. In all, seven digital technologies were evaluated in this study. Three technologies were administered via mobile applications: an interactive tool for the self-assessment of mood, and a cognitive test; a passive behavioral monitor to assess social interactions and global mobility; and a platform to perform voice recordings and obtain vocal biomarkers. Four technologies were evaluated in the clinic: a neuropsychological test battery; an eye motor tracking system; a standard high-density electroencephalogram (EEG)-based technology to analyze the brain network activity during cognitive testing; and a task quantifying bias in emotion perception. Results: Our data analysis was organized by technology - to better understand individual features of various technologies. In many cases, we obtained simple, parsimonious models that have reasonably high diagnostic accuracy and potential to predict standard clinical outcome in depression. Conclusion: This study generated many useful insights for future methodology studies of digital technologies and proof-of-concept clinical trials in depression and possibly other indications.

A new subtype-specific monoclonal antibody for IAP-survivin identifies high-risk patients with diffuse large B-cell lymphoma and improves the prognostic value of bcl-2.

Anti-apoptotic factors including IAP-survivin and bcl-2 are involved in carcinogenesis and predict for disease outcome for patients with cancer. We used RT-PCR and specific primers to generate two recombinant IAP-survivin proteins; one encoding for the full-length protein and the second comprising the survivin sequence incorporating amino acids 98 to 142. Both proteins were used to immunize mice and as capture antigens to screen NS1/immune splenocyte hybridoma supernatants for anti-survivin antibody in ELISA assays. The antibody designated F2-9C3 was most effective and reacted with both recombinant proteins and with the native protein present in lysates of A549 (lung carcinoma) and Jurkat cells in Western blots, immunoprecipitation and formalin-fixed tissue sections. Immunohistochemical staining of normal and neoplastic tissues showed association of the F2-9C3 antibody with the mitotic spindles. Expression of survivin was not detected elsewhere in sections of normal tissue while all neoplastic tissues examined, including those from patients with diffuse large B-cell lymphoma (DLBCL), showed significant expression of survivin. The intensity and localization of staining in these tumours varied and was observed in cytoplasm and/or nuclei. High nuclear expression of survivin predicted the disease outcome in patients with DLBCL. This association was evident when relating intensity to patient survival (p=0.0321) and strengthened when a score was calculated based on both staining intensity and the proportion of the reactive tumour cells (p=0.0128; reduction in the mean survival times: 35% and 46%, respectively). Elevated expression of bcl-2 protein also identified the high-risk patients (p=0.0095; reduction in mean survival time: 37%). Over-expression of both factors was a more powerful indicator of poor prognosis than either marker alone (p=0.0054, 70% reduction in mean survival time). In conclusion, our novel F2-9C3 monoclonal antibody is effective in determination of expression of IAP-survivin in neoplastic tissue. Nuclear overexpression of IAP-survivin using this antibody predicts the disease outcome in patients with DLBCL and significantly improves the predictive power of bcl-2 in these patients.

MDM2 RNA binding is blocked by novel monoclonal antibody h-MDM2-F4-14.

Amplification of MDM2 has been described in a variety of human cancers. Prognostic studies have revealed that abnormal MDM2 expression correlates with poor prognosis. Many of the consequences of mdm2/p53 interactions have been investigated, and mdm2-p53 dependent events characterized. In contrast, understanding of mdm2-p53 independent activities is comparatively in it's infancy amongst these the ability of mdm2 to bind RNA. However, although the significance of this activity has been the subject of some speculation, the precise role and impact of this function upon cell replication or apoptosis has yet to be fully defined. These studies have been obstructed by a lack of specific reagents able to interfere with this reaction. As a prelude to further exploring the significance of mdm2 RNA binding we report the inhibition of mdm2 RNA binding activity by newly produced MDM2 monoclonal antibodies anti-h-mdm2 F4-14 and F2-2. A variety of MDM2 specific antibodies have been produced and applied in research without complete knowledge of their reactivity profiles, but in the face of the growing number of mdm2 RNA isoforms, the results of such studies can be difficult to interpret. Each of the RNA binding inhibitory antibodies produced in this study was found to be reactive with full length MDM2 protein expressed in tumor cell lysates, transfected NIH3T3 cell lysates and via eukaryotic cell free rabbit reticulocyte in vitro translation. Antibody F4-14, the most potently inhibitory antibody, reacts strongly with the full length MDM2 together with protein isoforms A, B, C and D. In contrast, antibody F2-2 reacts only with full-length MDM2 protein. The ability of h-mdm2-F4-14 and to a lesser extent F2-2 to inhibit RNA binding presents the possibility of modulating human mdm2s ability to bind RNA, compromise this function and present opportunities to investigate in more detail the biological significance of this activity.

Lack of Influence of Calcium/Phosphorus Ratio on Hip and Lumbar Bone Mineral Density in Older Americans: NHANES 2005-2006 Cross-Sectional Data.

OBJECTIVES: We sought to ascertain the effect of a low dietary calcium/phosphorus (Ca:P) ratio on the bone health of older adults in the United States. The present analysis assessed whether a high dietary consumption of P, which generally leads to a low dietary Ca:P ratio, has an unfavorable effect on the bone mineral density (BMD) of the hip and lumbar vertebrae in a representative sample of older US men and women. DESIGN: For the 1228 men and women aged 50 to 70 and ≥71 years included in the National Health and Nutrition Examination Survey (NHANES) 2005 to 2006 cycle, quintiles of the dietary Ca:P ratio were tested for their association with hip and lumbar BMD after adjusting for body mass index (BMI). All data in this observational study were cross-sectional. RESULTS: Women typically have higher dietary Ca:P ratios than men and lower BMDs. No trend emerged for any age or sex group when studying the relationship between the dietary Ca:P ratio and BMD with adjustment for BMI. CONCLUSIONS: A wide range of dietary Ca:P ratios in the diets of a cross-section of older adult men and women in the United States had little effect on the BMD of the hip (proximal femur) or the lumbar vertebrae (spine), even among those consuming large amounts of Ca supplements. Despite the lack of complete assessment of total P intake in the United States, these results suggest that high P consumption patterns and low dietary Ca:P ratios do not exert an adverse effect on BMD at major fracture sites in older adults.

Diet Quality-The Greeks Had It Right!

The Mediterranean diet is upheld in the 2015-2020 Dietary Guidelines as an example of an eating pattern that promotes good health, a healthy body weight, and disease prevention throughout the lifespan. The Mediterranean eating pattern is based on a variety of unprocessed plant foods including fruits, vegetables, whole grains, legumes, nuts, and seeds that are high in polyphenols. The majority of polyphenols arrive in the colon where bacteria degrade them into smaller phenolics that can be translocated via the portal vein to the liver. In the liver, the phenolics undergo additional biotransformation prior to release into the circulation and transport to specific tissues where bioactive effects take place before removal in the urine. Recent epidemiologic studies using improved assessment techniques support that high versus low dietary polyphenol intake predicts reduced risk for neurodegenerative diseases, diabetes, cardiovascular disease, hypertension, obesity, and early death from all causes. Emerging science reveals that many of these health-related benefits can be traced to the biotransformed, gut-derived phenolics. In conclusion, the high consumption of unprocessed plant foods by inhabitants of countries bordering the Mediterranean Sea has been linked to multiple health and disease prevention benefits that are in large part due to a varied intake of polyphenols.

Calcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10-Year Follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, we assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC). METHODS AND RESULTS: We studied 5448 adults free of clinically diagnosed CVD (52% female; aged 45-84 years) from the Multi-Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles. Baseline CAC was measured by computed tomography, and CAC measurements were repeated in 2742 participants ≈10 years later. At baseline, mean calcium intakes across quintiles were 313.3, 540.3, 783.0, 1168.9, and 2157.4 mg/day. Women had higher calcium intakes than men. After adjustment for potential confounders, among 1567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake, were 1 (reference), 0.95 (0.79-1.14), 1.02 (0.85-1.23), 0.86 (0.69-1.05), and 0.73 (0.57-0.93). After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR=1.22 [1.07-1.39]). No relation was found between baseline calcium intake and 10-year changes in log-transformed CAC among those participants with baseline CAC >0. CONCLUSIONS: High total calcium intake was associated with a decreased risk of incident atherosclerosis over long-term follow-up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC.

Intakes of Calcium and Phosphorus and Calculated Calcium-to-Phosphorus Ratios of Older Adults: NHANES 2005-2006 Data.

BACKGROUND: High intakes of dietary phosphorus (P), relative to calcium (Ca) intake, are associated with a lower calcium:phosphorus ratio (Ca:P) ratio which potentially has adverse health effects, including arterial calcification, bone loss, and death. A substantial percentage of older adults (50 to 70 and 71 plus years) who have a higher risk of fracture rate than younger adults typically have low intakes of dietary Ca that are dominated by higher intakes of dietary P from natural and fortified foods, and lower Ca:P ratios than desirable. OBJECTIVE: This investigation was undertaken to examine Ca and P intakes and the resulting Ca:P ratios (by mass) across gender and older adult age groups, using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. DESIGN: NHANES data are based on a cross-sectional sample of the non-institutionalized United States (US) population within various regions. This sample is selected to be representative of the entire US population at all ages. National Cancer Institute (NCI) methods and SAS survey procedures were used for analyses. Ca:P ratios were calculated using total Ca from both foods and supplements, whereas P intakes were calculated from food composition values and supplements. The amounts of P additives in processed foods are not available. RESULTS: Mean Ca and P intakes demonstrated lower intakes of Ca and higher intakes of P compared to current Recommended Dietary Allowances (RDAs). The Ca:P ratios in older male and female adults were influenced by both low-Ca and high-P dietary consumption patterns. CONCLUSIONS: Both low total Ca intakes and high P amounts contribute to lower Ca:P ratios, i.e., ~0.7:1.0, in the consumption patterns of older adults than is recommended by the RDAs, i.e., ~1.5:1.0. Whether Ca:P ratios lower than recommended contribute to increased risk of bone loss, arterial calcification, and all-cause mortality cannot be inferred from these data. Additional amounts of chemical P additives in the food supply may actually reduce even further the Ca:P ratios of older adults of both genders, but, without P additive data from the food industry, calculation of more precise ratios from NHANES 2005-2006 data is not possible.

Effects of genistein on expression of bone markers during MC3T3-E1 osteoblastic cell differentiation.

In this in vitro study, the hypothesis that the beneficial effects of dietary genistein on bone are through the modulation of the bone marker synthesis by osteoblastic MC3T3-E1 cells was tested, and the possible roles of estrogen receptors in the actions of genistein on osteoblastic cells were also examined. Interleukin-6 production was decreased 40% to 60% in osteoblastic cells treated with genistein from either day 8-16 or day 12-16, at dietarily achievable concentrations (10(-10) to 10(-8) M) (P<0.05). The mRNA expression of osteoprotegerin increased about 140% in cells treated from with genistein day 4-8 at a concentration of 10(-8) M (P<0.05). The ratio of estrogen receptor-alpha to beta expression increased 10-fold from day 0 to 12 of culture (P<0.05). Correlating with this time-dependent variation in estrogen receptor expression, treatments of 17beta-estradiol and genistein had opposite dose patterns on the ratio of estrogen receptor-alpha to beta expression following treatment from day 4 to 6 compared to from day 0 to 2. The addition of ICI-182,780, an estrogen receptor blocker, reduced the inhibitory effect of genistein on IL-6 production by 30-50%. In summary, these findings suggest that the beneficial skeletal effects of genistein, at dietarily achievable levels, appear to be mediated, at least in part, by interleukin-6 and osteoprotegerin, and estrogen receptors play important roles in the inhibition of interleukin-6 synthesis by genistein in osteoblastic MC3T3-E1 cells.

Complication rates in diabetics with first metatarsophalangeal joint arthrodesis.

BACKGROUND: First metatarsophalangeal joint (MTPJ) arthrodesis has been an effective surgical entity when indicated, but a range of severe to mild complications can occur from this procedure. Patients with diabetes mellitus have an increased risk in surgical complications, most commonly associated with soft tissue and bone healing, when compared to non-diabetic patients. The purpose of this study was to evaluate the complication rates of first MTPJ arthrodesis in diabetic patients and compare them to the existing complication rates for the procedure. METHODS: A retrospective chart review was done on 76 diabetic patients, from June 2002 to August 2012. Thirty-two males and 44 females were included in the study. The authors evaluated many variables that could impact postoperative complications, including age, gender, bone graft incorporation, hemoglobin A1c, tobacco use, body mass index, peripheral neuropathy, hallux extensus, hallux interphalangeal arthritis, and rheumatoid arthritis, and compared them with the complication findings. Patient follow-up was no less than 24 months. RESULTS: Overall, approximately two-thirds of the patients had no complications and 35.5% of patients had at least one mild or moderate complication. Of the non-union and mal-union complications, 80 and 70% had peripheral neuropathy, respectively. One hundred percent of the patients that had mal-positions or hardware failure also had peripheral neuropathy. No severe complications were seen during follow-up. Only two of the moderate complications needed revisions, and the rest of those with moderate complications were asymptomatic. CONCLUSION: In conclusion, first MTPJ arthrodesis is overall an effective and beneficial procedure in patients with diabetes mellitus. Diabetic patients with peripheral neuropathy have an increased risk for mild and moderate complications.

Healthy Eating Index 2005 and selected macronutrients are correlated with improved lung function in humans.

A number of dietary components have been associated with lung function. However, a comprehensive measure of a healthy diet has not been compared with lung function. Herein, we test the hypothesis that a healthy overall diet, as assessed by the Healthy Eating Index 2005 (HEI-2005), will be associated with increased lung function. This is an investigation using the Atherosclerosis Risk in Communities Research Materials obtained from the National Heart Lung Blood Institute. The study surveyed dietary habits of 15 567 American subjects from 4 communities in 1987 to 1990. Spirometric measures of lung function were also taken at entry to the study and a second time 3 years later. Based on food and nutritional data collected by food frequency questionnaire, an HEI-2005 score was calculated for each subject. This total score, together with its 12 components scores and associated macronutrient, was compared with lung function results by linear regression. Models were controlled for smoking behavior, demographics, and other important covariates. The HEI-2005 total scores were positively associated with forced expiratory volume in 1 second per forced vital capacity (FEV(1)/FVC) at visit 1 (ß = .101 per increase in 1 quintile of HEI-2005) and visit 2 (ß = .140), and FEV(1) as percentage of the predicted FEV(1) at visit 2 (ß = .215) (P < .05). In addition, HEI-2005 component scores that represented high intakes of whole grains (ß = .127 and .096); saturated fats (ß = -.091); and solid fats, alcohol, and added sugar (ß = -.109 and -.131) were significantly associated with FEV(1)/FVC at either visit 1 or visit 2. Intakes of total calories (ß =-.082 at visit 1) and saturated fatty acids (ß = -.085 at visit 2) were negatively associated with FEV(1)/FVC. Dietary polyunsaturated fatty acids (ß = .085 and .116) and long-chain omega-3 fatty acids (ß = .109 and .103), animal protein (ß = .132 and .093), and dietary fiber (ß = .129) were positively associated with lung health. An overall healthy diet is associated with higher lung function.

Potential health concerns of dietary phosphorus: cancer, obesity, and hypertension.

Adult Americans typically consume on average 1400 mg, or more, of phosphorus (P) daily in meals, which almost doubles the recommended dietary allowance. After a meal phosphorus is rapidly absorbed at a high efficiency and hormonal mechanisms act swiftly to maintain the serum inorganic phosphate (Pi) concentration within fairly narrow limits. Both parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) reduce serum phosphate during postprandial periods through homeostatic actions on the kidney. However, it is speculated that exposure of cells to a brief high-serum Pi concentration may signal alterations in cell functions that lead to deleterious effects. Elevation of serum FGF-23 or PTH may also be harmful to specific cell types. Examples of possible adverse health effects include cancer, obesity, and hypertension. Here I review potential mechanisms through which high-P intake may contribute to cell metabolic abnormalities and the development of chronic disease; high-dietary phosphorus, especially from foods processed with phosphate salts, may be associated with these chronic diseases. Further investigation is needed to establish the significance of high-phosphate diets within a large segment of the U.S. population with normal renal function.

Risk of high dietary calcium for arterial calcification in older adults.

Concern has recently arisen about the potential adverse effects of excessive calcium intakes, i.e., calcium loading from supplements, on arterial calcification and risks of cardiovascular diseases (CVD) in older adults. Published reports that high calcium intakes in free-living adults have relatively little or no beneficial impact on bone mineral density (BMD) and fracture rates suggest that current recommendations of calcium for adults may be set too high. Because even healthy kidneys have limited capability of eliminating excessive calcium in the diet, the likelihood of soft-tissue calcification may increase in older adults who take calcium supplements, particularly in those with age or disease-related reduction in renal function. The maintenance of BMD and bone health continues to be an important goal of adequate dietary calcium consumption, but eliminating potential risks of CVDs from excessive calcium intakes needs to be factored into policy recommendations for calcium by adults.

Serum ionized calcium may be related to white matter lesion volumes in older adults: a pilot study.

White matter lesions have detrimental effects upon older adults, while serum calcium levels have been associated with elevated vascular risk and may be associated with these lesions. Depression, a serious mental disorder characterized by disturbances in calcium metabolism, may be an important contributor to any calcium-lesion relationship. This cross-sectional pilot study examined the association between serum ionized calcium (the physiologically active form of calcium) and white matter lesion volumes in a sample of depressed and non-depressed older adults (N = 42; 60 years and older). Serum ionized calcium was determined using an ion-selective electrode technique, while lesion volumes were estimated from magnetic resonance imaging using an automated expectation-maximization segmentation. A linear regression model, controlling for age and group (depression vs. comparison), showed a trend for a positive relationship between serum ionized calcium and white matter lesion volume (ß = 4.34, SE = 2.27, t = 1.91, p = 0.063). Subsample analyses with depressed participants showed a significant positive relationship between higher ionic calcium and greater lesion volume (ß = 6.41, SE = 2.53, t = 2.53, p = 0.018), but no association was found for non-depressed participants. Sex-specific subsample analyses showed a significant positive relationship between higher calcium and greater lesion volume in men only (ß = 7.49, SE = 3.42, t = 2.19, p = 0.041). These preliminary results indicate that serum ionized calcium may be associated with white matter lesions in older adults, particularly among men and individuals with depression. Larger studies are needed to confirm these findings.

Split thickness skin grafts for the treatment of non-healing foot and leg ulcers in patients with diabetes: a retrospective review.

We retrospectively reviewed 107 diabetic patients who received a split thickness skin graft (STSG) for treatment of a non-healing diabetic foot or leg ulcer to describe healing times based on patient characteristics, comorbidities or complications. The minimum follow-up was 6 months from the time of STSG application. The mean time to healing among all patients was 5.1 weeks (3 to 16 weeks). The mean healing time for patients with complications was 12.0 weeks (10 to 16 weeks) while the mean healing time for those without complications was 4.9 weeks (3 to 10 weeks). Overall complication rate was 2.8%. Patients with a STSG take of less than 95% had a mean healing time of 7.9 weeks compared to 4.8 weeks for those with a STSG take of 100% (p<0.001). The use of autologous STSG for treatment of non-healing diabetic foot and leg wounds is a viable method for soft tissue closure and may present a low complication rate and a satisfactory rate of healing.

Recombinant human MDM2 oncoprotein shows sequence composition selectivity for binding to both RNA and DNA.

MDM2 is a 90 kDa nucleo-phosphoprotein that binds p53 and other proteins contributing to its oncogenic properties. Its structure includes an amino proximal p53 binding site, a central acidic domain and a carboxy region which incorporates Zinc and Ring Finger domains suggestive of nucleic acid binding or transcription factor function. It has previously been reported that a bacculovirus expressed MDM2 protein binds RNA in a sequence-specific manner through the Ring Finger domain, however, its ability to bind DNA has yet to be examined. We report here that a bacterially expressed human MDM2 protein binds both DNA as well as the previously defined RNA consensus sequence. DNA binding appears selective and involves the carboxy-terminal domain of the molecule. RNA binding is inhibited by an MDM2 specific antibody, which recognises an epitope within the carboxy region of the protein. Selection cloning and sequence analysis of MDM2 DNA binding sequences, unlike RNA binding sequences, revealed no obvious DNA binding consensus sequence, but preferential binding to oligopurine:pyrimidine-rich stretches. Our results suggest that the observed preferential DNA binding may occur through the Zinc Finger or in a charge-charge interaction through the Ring Finger, thereby implying potentially different mechanisms for DNA and RNA MDM2 binding.

A 9 series microRNA signature differentiates between germinal centre and activated B-cell-like diffuse large B-cell lymphoma cell lines.

The microRNAs are endogenous, non-coding RNAs that play key roles in a range of pathophysiological processes by up- or down-regulating gene expression. Recent studies have shown that some microRNAs have oncogenic or tumour suppressor activity. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin's lymphoma with a heterogeneous biology, which has impeded the clinical assessment of patients. The currently-used clinically-based IPI provides useful information for treatment decision making, but has limited predictive power. Recent immunohistochemical approaches have identified two different prognostic groups: the more indolent germinal centre (GC)- and the higher risk activated B-cell (ABC)-like phenotypes. Although useful, prediction based on immunophenotype has limitations. The present study uses microRNA profiling and a number of well-characterised B-cell lymphoma cell lines to identify microRNA signatures that are correctly assigned to the DLBCL prognostic subgroups and distinguish DLBCL from other more indolent lymphoma, including follicular lymphoma (FL). MicroRNA microarray analysis was based on miRBase version 12.0 and analysis was performed using an unsupervised hierarchical clustering model. Discriminatory microRNAs were validated by qRT-PCR. We identified a 9 microRNA signature that discriminated between ABC- and GC-like DLBCL. This included 3 newly identified microRNAs, not previously associated with DLBCL and predicted to target genes that are de-regulated in lymphoma. DLBCL was distinguished from FL by 4 microRNAs and a total of 18 microRNAs were identified that differentiated between all lymphoma and control populations. Most of the discriminatory microRNAs have been reported previously to be known oncomiRs or act as tumour suppressors. In conclusion, the present study identified a microRNA signature that correctly classified GC and ABC phenotypes in DLBCL cell lines. This signature has yet to be assessed for prediction in clinical samples.