Examining the relationship between nutrition and cerebral structural integrity in older adults without dementia.

The proportion of adults aged 60 years and over is expected to increase over the coming decades. This ageing of the population represents an important health issue, given that marked reductions to cerebral macro- and microstructural integrity are apparent with increasing age. Reduced cerebral structural integrity in older adults appears to predict poorer cognitive performance, even in the absence of clinical disorders such as dementia. As such, it is becoming increasingly important to identify those factors predicting cerebral structural integrity, especially factors that are modifiable. One such factor is nutritional intake. While the literature is limited, data from available cross-sectional studies indicate that increased intake of nutrients such as B vitamins (for example, B6, B12 and folate), choline, n-3 fatty acids and vitamin D, or increased adherence to prudent whole diets (for example, the Mediterranean diet) predicts greater cerebral structural integrity in older adults. There is even greater scarcity of randomised clinical trials investigating the effects of nutritional supplementation on cerebral structure, though it appears that supplementation with B vitamins (B6, B12 and folic acid) or n-3 fatty acids (DHA or EPA) may be beneficial. The current review presents an overview of available research examining the relationship between key nutrients or adherence to select diets and cerebral structural integrity in dementia-free older adults.

Stannous Fluoride Effects on Gene Expression of Streptococcus mutans and Actinomyces viscosus.

A genome-wide transcriptional analysis was performed to elucidate the bacterial cellular response of Streptococcus mutans and Actinomyces viscosus to NaF and SnF2. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of SnF2 were predetermined before microarray study. Gene expression profiling microarray experiments were carried out in the absence (control) and presence (experimental) of 10 ppm and 100 ppm Sn2+ (in the form of SnF2) and fluoride controls for 10-min exposures (4 biological replicates/treatment). These Sn2+ levels and treatment time were chosen because they have been shown to slow bacterial growth of S. mutans (10 ppm) and A. viscosus (100 ppm) without affecting cell viability. All data generated by microarray experiments were analyzed with bioinformatics tools by applying the following criteria: 1) a q value should be ≤0.05, and 2) an absolute fold change in transcript level should be ≥1.5. Microarray results showed SnF2 significantly inhibited several genes encoding enzymes of the galactose pathway upon a 10-min exposure versus a negative control: lacA and lacB (A and B subunits of the galactose-6-P isomerase), lacC (tagatose-6-P kinase), lacD (tagatose-1,6-bP adolase), galK (galactokinase), galT (galactose-1-phosphate uridylyltransferase), and galE (UDP-glucose 4-epimerase). A gene fruK encoding fructose-1-phosphate kinase in the fructose pathway was also significantly inhibited. Several genes encoding fructose/mannose-specific enzyme IIABC components in the phosphotransferase system (PTS) were also downregulated, as was ldh encoding lactate dehydrogenase, a key enzyme involved in lactic acid synthesis. SnF2 downregulated the transcription of most key enzyme genes involved in the galactose pathway and also suppressed several key genes involved in the PTS, which transports sugars into the cell in the first step of glycolysis.

Exudative cloacitis in the kakapo (Strigops habroptilus) potentially linked to Escherichia coli infection.

AIM: To investigate the initiating causes of cloacitis (inflammation of the cloaca) in kakapo (Strigops habroptilus). METHODS: Metagenomics using unbiased RNA or DNA sequencing was applied to faecal material from an 11-year-old female kakapo with exudative cloacitis, and a pool of eight birds (male and female aged 1-20 years) with no current signs or history of the disease. Faecal material from the diseased bird was collected pre- and post-treatment. For RNA sequencing, extracted RNA/DNA was subject to DNase, and the remaining RNA reverse transcribed to cDNA and subject to multiple displacement amplification prior to sequencing. RESULTS: No significant alignment to any known avian virus sequence was obtained from any faecal samples. However significant BLAST alignments to five bacteriophages known to infect enterobacteria were obtained. Strong evidence was obtained for the presence of the bacteriophage Escherichia phage TL-2011b, a bacteriophage known to occur in Escherichia coli causing outbreaks of foodborne disease in humans, in the sample from the diseased bird, but not the non-diseased pool. Differences in E. coli community structure between the diseased bird and the non-diseased pool were also apparent. CONCLUSIONS: Escherichia coli infection of human origin is suggested as a possible cause of exudative cloacitis, although confirmatory work is required to test this hypothesis.

The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment.

Previous research has suggested that multivitamin (MV) supplementation may be associated with beneficial effects for mood and general well-being, although treatment durations have typically been less than 90 days, samples have often been restricted to males only and acute effects have not been adequately differentiated from chronic effects. In the current study a MV supplement containing high levels of B-vitamins was administered daily to 138 healthy young adult participants between the ages of 20 and 50 years over a 16-week period. Chronic mood measures (GHQ-28, POMS, Chalder fatigue, PILL, Bond-Lader and custom visual analogue scales) were administered pre-dose at baseline, 8- and 16-weeks. Changes in Bond-Lader and VAS in response to a multi-tasking framework (MTF) were also assessed at 8- and 16-weeks. For a subset of participants, at-home mobile-phone assessments of mood were assessed on a weekly basis using Bond-Lader and VAS. No significant treatment effects were found for any chronic laboratory mood measures. In response to the MTF, a significant treatment x time interaction was found for STAI-S, with a trend towards a greater increase in stress ratings for male participants in the MV group at 16 weeks. However, this finding may have been attributable to a larger proportion of students in the male MV group. In contrast, at-home mobile-phone assessments, where assessments were conducted post-dose, revealed significantly reduced stress, physical fatigue and anxiety in the MV group in comparison to placebo across a number of time points. Further research using both acute and chronic dosing regimens are required in order to properly differentiate these effects.

Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets.

Pancreas transplantation is an option to achieve better metabolic control and decrease chronic complications in patients with diabetes. Xenotransplantation becomes an important alternative. In this study, we show the clinical outcome of patients with type 1 diabetes transplanted with neonatal pig islets without immunosuppression. In a longitudinal study of 23 patients with type 1 diabetes, who received porcine islets between 2000 and 2004, we registered demographic and clinical characteristics every 3 months and chronic complications evaluation yearly. Porcine C-peptide was measured in urine samples under basal conditions and after stimulation with l-arginine. More than 50% were female, median current age was 20·8 years, median diabetes duration at transplantation 5·5 years, median current diabetes duration 11 years and median time post-transplantation 5·7 years. Their media of glycosylated haemoglobin reduced significantly after the first transplantation. Insulin doses remain with a reduction greater than 33% in more than 50% of the patients. Before transplantation, 14 of the 21 patients presented mild chronic complications and currently only two patients presented these complications. Porcine C-peptide was present in all urine samples under basal conditions and increased post-stimulation with l-arginine. These patients achieved an excellent metabolic control after the first transplantation. This could explain, as well as the remaining function of transplanted cells, the low frequency of chronic complications compared to patients with similar diabetes duration and age.

Vascularization of artificial beds for pancreatic islet transplantation in a rat model.

An alternative prevascularized bed with a subcutaneously located entrance would substantially improve islet engraftment, requiring much less invasive surgery. Studies have described times necessary for the creation of an artificial pouch suitable for subsequent islet transplantation. Polymeric mesh shaped in rounded scaffolds were implanted both subcutaneously and into the major omentum of Brown Norway female rats (n = 7). The connective tissue together with vessels were embedded into scaffolds at 1 week without regard to site. In contrast to the major omentum, vessels within the subcutaneous connective tissue surrounding the devices started to decline in 2 weeks and almost disappeared 1 week later. Magnetic resonance imaging (MRI) detected changes in fibrous tissue surrounding the wall, but only large veins located beside the devices were visible using basic MRI. The blood supply to the internal surface of the created beds was important for islet engraftment, but information could be obtained only by using dynamic contrast-enhanced MRI.

Nanostructured optical fibre arrays for high-density biochemical sensing and remote imaging.

Optical fibre bundles usually comprise a few thousand to tens of thousands of individually clad glass optical fibres. The ordered arrangement of the fibres enables coherent transmission of an image through the bundle and therefore enables analysis and viewing in remote locations. In fused bundles, this architecture has also been used to fabricate arrays of various micro to nano-scale surface structures (micro/nanowells, nanotips, triangles, etc.) over relatively large areas. These surface structures have been used to obtain new optical and analytical capabilities. Indeed, the imaging bundle can be thought of as a "starting material" that can be sculpted by a combination of fibre drawing and selective wet-chemical etching processes. A large variety of bioanalytical applications have thus been developed, ranging from nano-optics to DNA nanoarrays. For instance, nanostructured optical surfaces with intrinsic light-guiding properties have been exploited as surface-enhanced Raman scattering (SERS) platforms and as near-field probe arrays. They have also been productively associated with electrochemistry to fabricate arrays of transparent nanoelectrodes with electrochemiluminescent imaging properties. The confined geometry of the wells has been loaded with biosensing materials and used as femtolitre-sized vessels to detect single molecules. This review describes the fabrication of high-density nanostructured optical fibre arrays and summarizes the large range of optical and bioanalytical applications that have been developed, reflecting the versatility of this ordered light-guiding platform.

No evidence of porcine endogenous retrovirus in patients with type 1 diabetes after long-term porcine islet xenotransplantation.

Xenotransplantation is a promising alternative for donor shortage to ameliorate physiologic and metabolic disorders. The major concern for xenotransplant is the risk of zoonosis mainly by the porcine endogenous retrovirus (PERV), presentation in the piglet genome. Twenty-three patients with type 1 diabetes were transplanted with porcine islets using collagen-generating devices which were implanted subcutaneously in the anterior wall of the abdomen. Clinical characteristics and metabolic tests were recorded in each visit. They were tested for PERV using PCR and RT-PCR from blood pretransplantation and every 3 months during a 4.6- to 8-year follow-up after their first xenotransplant. Tests by PCR of every DNA sample (780 samples) revealed that there was no PERV infection in the DNA of white cells. No evidence of PERV activation was found in this group of patients with type 1 diabetes during clinical long-term follow-up.

Optical fibre SERS sensors.

Surface-enhanced Raman scattering (SERS) has established itself as an important analytical technique. However, efforts to transfer the technology from the laboratory to the production line, clinic or field have been frustrated by the lack of robust affordable substrates and the complexity of interfacing between sample and spectrometer. Prompted by the success of optical fibre systems for implementing normal Raman scattering spectroscopy in remote locations and biomedical applications, attention has now shifted to the development of SERS-active optical fibres. Other workers have attempted to develop SERS probes with extended interaction lengths and both far-field and near-field SERS imaging techniques for high-resolution chemical mapping of surfaces. This review discusses the development of these technologies and presents the current state of the art. Although recent developments show great promise, some outstanding challenges and opportunities remain to be addressed.

Nanoimprinted optical fibres: Biotemplated nanostructures for SERS sensing.

Optical fibre surface-enhanced Raman scattering (SERS) sensors offer a potential solution for monitoring low chemical concentrations in remote or in situ sensing scenarios. The SERS effect relies on the interaction of analyte molecules with nanostructured metal surfaces. We demonstrate a nanoscale biotemplating approach to fabricating these sensors, using nanoimprint lithography to replicate cicada wing antireflective nanostructures onto the end faces of standard silica optical fibres. These SERS-compatible nanoarrays are coated with silver to make them SERS active, and thiophenol and rhodamine 6G are used as test analytes, from which strong SERS spectra are collected using both direct endface illumination and through-fibre interrogation. This combination of biological templates with nanoscale replication and optical fibres demonstrates a high-resolution, low-cost approach to fabricating high-performance optical fibre SERS sensors.

Comparison of a stabilized stannous fluoride/sodium hexametaphosphate dentifrice and a zinc citrate dentifrice on plaque formation measured by digital plaque imaging (DPIA) with white light illumination.

OBJECTIVES: The objectives of this study were to verify use of a white light-illuminated adaptation of an established digital plaque image analysis (DPIA) technique to measure changes in plaque levels, and to compare the antiplaque efficacy of a 0.454% stannous fluoride/sodium hexametaphosphate dentifrice (SnF2/SHMP) and a 0.76% sodium monofluorophosphate/zinc citrate (ZnCit/SMFP) dentifrice using the white light DPIA system. METHODS: White Light DPIA Qualification--17 subjects were enrolled in the study. The following four images were captured on different days: a) non-disclosed morning plaque; b) disclosed morning plaque; c)just-brushed plaque; and d) post-prophylaxis plaque levels. Comparative Dentifrice Assessment-Following the qualification study, 21 subjects were enrolled in the dentifrice assessment. During Phase I (two weeks acclimatization phase), subjects used a standardized oral hygiene regimen twice per day, consisting of a sodium fluoride dentifrice and a standard flat-profile manual toothbrush. In Phase II (two-week treatment phase), subjects were randomized to one of two treatment groups: SnF2/SHMP dentifrice (Crest Pro-Health) or the ZnCit/SMFP formulation (Viadent). During each phase, plaque levels were assessed in the morning prior to the morning tooth brushing (a.m.), post-brushing in the morning (p.b.), and in the afternoon (p.m.). RESULTS: White Light DPIA Qualification--All 17 subjects completed the trial. The white light modification of DPIA successfully distinguished known variations in plaque coverage. Mean plaque coverage of the 12 anterior facial surfaces, as determined by the system for the four images, was: a) 0.07%; b) 11.44%; c) 4.99%; and d) 2.16%. Comparative Dentifrice Assessment-All 21 subjects completed the study. The SnF2/SHMP dentifrice provided a statistically significant 25% lower a.m. pre-brushing plaque level (p = 0.0385) versus ZnCit/SMFP. SnF2/SHMP also showed a directional 23% lower p.m. plaque (p = 0.09) level, and 15% less (p = 0.10) post-brushing plaque compared to ZnCit/SMFP. CONCLUSION: The white light DPIA system was shown to be a sensitive method to measure changes in plaque levels. Using this system, a SnF2/SHMP dentifrice was found to be significantly more effective than a ZnCit/SMFP dentifrice in the prevention of overnight plaque growth.

Apolipoprotein E-epsilon 4 and recurrent genital herpes in individuals co-infected with herpes simplex virus type 2 and HIV.

Apolipoprotein E (APOE) alleles have been associated with the severity of, or susceptibility to, infection by various microbes. We investigated the potential association between the APOE-epsilon 4 allele and the rate of recurrence of genital herpes in patients who were HIV positive and herpes simplex virus type 2 (HSV-2) seropositive. The APOE-epsilon 4 allele was significantly associated with recurrent genital ulceration independent of ethnicity, antiretroviral therapy and CD4 count (OR 8.3; 95% CI 2.4 to 28.5). To our knowledge, this is the first published study to demonstrate this association and suggests that APOE-epsilon 4 may represent a future prognostic marker for symptomatic recurrence of genital herpes in individuals with HIV.

Trends in sexually transmitted infections (other than HIV) in older people: analysis of data from an enhanced surveillance system.

OBJECTIVE: This study examines the distribution of selected sexually transmitted infections (STIs) in older people (aged >/=45 years) attending genitourinary medicine (GUM) clinics in the West Midlands, UK. METHODS: Analysis of data from the regional enhanced STI surveillance system for the period 1996-2003. Selected STIs were chlamydia, genital herpes, genital warts, gonorrhoea and syphilis. RESULTS: Altogether, 4445 STI episodes were reported among older people during the study period. Between 1996 and 2003 older people accounted for 3.7% and 4.3%, respectively, of all GUM clinic attendances. The rate of STIs in older people more than doubled in 2003 compared with 1996 (p<0.0001). Rates for all five selected diagnoses were significantly higher in 2003 compared to 1996. A significantly increasing trend over time was seen overall (p<0.0001) and for each of the selected diagnoses. Overall, males and those aged 55-59 years of age were significantly more likely to be affected. CONCLUSIONS: This study provides evidence of significant increases in attendance at GUM clinics by older people. Although it is recognised that young people should remain the focus of sexual health programmes, the results indicate that sexual risk-taking behaviour is not confined to young people but also occurs among older people. There is therefore a need to develop and implement evidence-based multifaceted sexual health programmes that while aiming to reduce STI transmission among all age groups should include interventions aimed specifically at older people and address societal and healthcare attitudes, myths and assumptions about sexual activity among older people.

Addition of lenalidomide to melphalan in the treatment of newly diagnosed multiple myeloma: the National Cancer Institute of Canada Clinical Trials Group MY.11 trial.

Oral melphalan and prednisone remain an effective and tolerable treatment for patients with multiple myeloma. For approximately 40 years, this combination has been the standard of care for patients not proceeding to stem cell transplant. Within the last 10 years, new agents have been found to be efficacious in the relapsed/refractory setting. Within the last year, two trials of added thalidomide in the newly diagnosed setting have demonstrated outcomes superior to those achieved with melphalan and prednisone alone. This improved outcome comes at the cost of increased toxicity.The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has recently developed a randomized phase ii trial (MY.11) that uses a combination of lenalidomide with melphalan for patients with newly diagnosed multiple myeloma. Lenalidomide is a thalidomide analogue and, like thalidomide, is thought to work through immunomodulatory effects. It was shown to have activity in patients with relapsed or refractory disease and, in combination with dexamethasone, is superior to dexamethasone alone. Lenalidomide holds promise as a more effective and potentially less toxic derivative of thalidomide. Experience with lenalidomide in combination with chemotherapy is very limited, and the purpose of MY.11 is to establish tolerability and to gain knowledge about efficacy. The information gained from MY.11 is expected to help inform dosing levels and schedules for a large phase iii trial being developed by the Eastern Cooperative Oncology Group that will include participation by the NCIC CTG.

Three-yr follow-up of a type 1 diabetes mellitus patient with an islet xenotransplant.

In order to alleviate the shortage of human donors, the use of porcine islets of Langerhans for xenotransplantation in diabetic patients has been proposed as a solution. To overcome rejection, we have developed a procedure for protecting the islets by combining them with Sertoli cells and placing them in a novel subcutaneous device, that generates an autologous collagen covering. A type 1 diabetic woman was closely monitored for 10 months, and then transplanted in two devices with two months of difference and a third time after 22 months. Here we present a three-yr follow-up. The close monitoring induced a rapid decrease in exogenous insulin requirements, which stabilized between 19 and 28 IU/d for nine months. After transplantation, the requirements reduced further to below 6 IU/d and for some weeks she was insulin free. Glycosylated hemoglobin levels decreased concomitantly. Porcine insulin could be detected in the serum after a glucose challenge and insulin positive cells inside a removed device after two yr. No complications have arisen and no porcine endogenous retrovirus infection has been detected through PCR and RT-PCR. This case demonstrates the feasibility of using the xenotransplantation of porcine cells to alleviate metabolic complications and insulin requirements in type 1 diabetic patients.

A method to study sustained antimicrobial activity of rinse and dentifrice components on biofilm viability in vivo.

AIM: To develop an improved method for quantitative assessment of antimicrobial efficacy and substantivity of mouth rinses and dentifrices on in vivo treated plaque. MATERIAL AND METHODS: Nine- and 72-h-old plaques were formed in volunteers carrying out standardized hygiene using NaF-containing dentifrice. Plaques were collected before (baseline) in vivo treatment with dentifrices or chlorhexidine mouth rinse, immediately post-treatment and after 1 or 6 h, dispersed in demineralized water and stained with live/dead stain after which bacteria were enumerated. Dispersed baseline plaques were treated with dentifrices or chlorhexidine to determine antimicrobial efficacy against planktonic bacteria. RESULTS: Baseline plaques revealed 56-41% viable organisms in 9- and 72-h-old plaques, respectively. Treatment of planktonic (dispersed baseline plaque) bacteria resulted in 1-4% viable organisms. Chlorhexidine mouth rinse and dentifrices produced strong immediate antimicrobial effects, but after 1 or 6 h, the proportion of viable organisms in 9-h-old plaques rebounded significantly with only chlorhexidine mouth rinse retaining significant efficacy. Seventy-two-hour-old plaques were less susceptible to antimicrobials, although dentifrices appeared more effective after 6 h than initially, whereas efficacy of chlorhexidine rinse continued to drop with time post-treatment. CONCLUSIONS: The proposed method holds promise for assessment of both immediate and retained antimicrobial actions of oral treatments against dental plaque in vivo.

Psychosocial aspects of xenotransplantation: survey in adolescent recipients of porcine islet cells.

INTRODUCTION: Transplantation is a process with several psychosocial challenges. Regarding the case of xenotransplantation, the perceived similarity between humans and pigs may be stressful. Adjustment disorders have been reported among transplantation recipients. We sought to assess the psychosocial aspects of xenotransplantation among porcine islet-cell recipients and their efforts to adapt themselves to this condition. MATERIAL AND METHODS: Ten insulin-dependent diabetes mellitus patients aged 14.58 +/- 7.93 who received porcine islet-cells were included. The bioartificial steel/fibrous tissue chamber method was used. All patients and their relatives were interviewed about their expectations, overall functioning, and experiences. The quality of life, enjoyment, and satisfaction scale and the hospital anxiety and depression scales were used. A 1-year follow-up was done. RESULTS: Their motivation was centered on autonomy; there were no troubles regarding the graft origin. Xenotransplantation was perceived with pragmatism, seeing pigs as an unlimited resource. The patients with best outcomes also had the greatest improvements in several quality of life areas (QOL) while the medium responders had fewer QOL improvements. The nonresponders experienced mainly frustration. Parents' concerns were not related to their children's health but to their recently gained autonomy. CONCLUSIONS: In addition to enthusiasm, the perception of animals as an unlimited source of organs may affect patient compliance; in this group, xenotransplantation was seen as using as a long-lasting drug, with chamber walls considered as a physical, immunologic, and, in certain manner, a psychological barrier.