Fluorescence based detection of polychlorinated biphenyls (PCBs) in water using hydrophobic interactions.

Despite increasing controls in their production and disposal, persistent organic pollutants in water, even at concentrations below parts per million, represent an ongoing environmental health risk. Despite this concern, the detection of these compounds in water sources rely upon expensive, time consuming approaches that do not permit frequent monitoring and evaluation. In this work, a new fluorescence-based technique is presented for the detection of polychlorinated biphenyls (PCBs) in water. Benzopyrene (BaP) fluorescence was shown to increase with trace concentrations of aromatic organic pollutants. BaP forms a hydrophobic complex with PCBs, which has allowed for the successful detection of pollutants including PCB-126, PCB-153 and PCB-118. To determine the selectivity and robustness of this response, the impact of pH, ionic strength and humic acid to mimic surface water conditions is explored. While suppression of the signal was seen, these factors' impact on the detection of PCBs was minor, suggesting that a potential sensing strategy can be developed through this interaction. It is seen that the number and location of chlorine atoms are important along with the geometric orientation of molecule's structure.

Heart failure patients' future expectations and their association with disease severity, quality of life, depressive symptoms and clinical outcomes.

BACKGROUND: Although treatment of heart failure (HF) patients has improved, prognosis still remains poor. Current HF Guidelines recommend communication about prognosis with all patients. Little is known about HF patients' awareness of their shortened life expectancy. AIM: To explore HF patients' future expectations and to examine whether these expectations are associated with disease severity, quality of life, depressive symptoms and clinical outcomes. METHOD: Patients randomised to the intervention groups of the COACH study, who were at the end of HF hospitalisation, were asked about their future expectations. Patients were divided into three groups: patients expecting improvement/stabilisation, patients expecting deterioration and those not knowing what to expect. Depressive symptoms were measured by CES-D and quality of life with the Ladder of Life and RAND-36. RESULTS: Six hundred and seventy eight patients (age 70 ± 12; 41% female patients; LVEF 33% ± 15) participated in the study. Most patients (56%, N = 380) expected improvement or stabilisation, 8% (N = 55) expected deterioration and 21% (N = 144) did not know what to expect for the future. Patients who expected to deteriorate were significantly older, experienced a lower quality of life and more depressive symptoms compared with patients in the other two groups. They also had a higher mortality rate, both after 18 and 36 months, and had more HF admissions. No association with severity of the disease (NYHA-class, LVEF, BNP levels) was found. CONCLUSION: Many hospitalised HF patients are not aware of their poor prognosis. Depressive symptoms, poor quality of life, increased mortality and rehospitalisation were related to expected deterioration. Improvement of communication about prognosis with HF patients is needed in the future.

Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues.

Recent evidence has determined a phenotypic and functional heterogeneity for macrophage populations. This plasticity of macrophage function has been related to specific properties of subsets (M1 and M2) of these cells in inflammation, adaptive immune responses and resolution of tissue destructive processes. This investigation hypothesized that targeted alterations in the distribution of macrophage phenotypes in aged individuals, and with periodontitis would be skewed towards M1 inflammatory macrophages in gingival tissues. The study used a non-human primate model to evaluate gene expression profiles as footprints of macrophage variation in healthy and periodontitis gingival tissues from animals 3-23 years of age and in periodontitis tissues in adult and aged animals. Significant increases in multiple genes reflecting overall increases in macrophage activities were observed in healthy aged tissues, and were significantly increased in periodontitis tissues from both adults and aged animals. Generally, gene expression patterns for M2 macrophages were similar in healthy young, adolescent and adult tissues. However, modest increases were noted in healthy aged tissues, similar to those seen in periodontitis tissues from both age groups. M1 macrophage gene transcription patterns increased significantly over the age range in healthy tissues, with multiple genes (e.g. CCL13, CCL19, CCR7 and TLR4) significantly increased in aged animals. Additionally, gene expression patterns for M1 macrophages were significantly increased in adult health versus periodontitis and aged healthy versus periodontitis. The findings supported a significant increase in macrophages with aging and in periodontitis. The primary increases in both healthy aged tissues and, particularly periodontitis tissues appeared in the M1 phenotype.

Biofilm and cell adhesion strength on dental implant surfaces via the laser spallation technique.

OBJECTIVE: The aims of this study are to quantify the adhesion strength differential between an oral bacterial biofilm and an osteoblast-like cell monolayer to a dental implant-simulant surface and develop a metric that quantifies the biocompatible effect of implant surfaces on bacterial and cell adhesion. METHODS: High-amplitude short-duration stress waves generated by laser pulse absorption are used to spall bacteria and cells from titanium substrates. By carefully controlling laser fluence and calibration of laser fluence with applied stress, the adhesion difference between Streptococcus mutans biofilms and MG 63 osteoblast-like cell monolayers on smooth and rough titanium substrates is obtained. The ratio of cell adhesion strength to biofilm adhesion strength (i.e., Adhesion Index) is determined as a nondimensionalized parameter for biocompatibility assessment. RESULTS: Adhesion strength of 143 MPa, with a 95% C.I. (114, 176), is measured for MG 63 cells on smooth titanium and 292 MPa, with a 95% C.I. (267, 306), on roughened titanium. Adhesion strength for S. mutans on smooth titanium is 320 MPa, with a 95% C.I. (304, 333), and remained relatively constant at 332 MPa, with a 95% C.I. (324, 343), on roughened titanium. The calculated Adhesion Index for smooth titanium is 0.451, with a 95% C.I. (0.267, 0.622), which increased to 0.876, with a 95% C.I. (0.780, 0.932), on roughened titanium. SIGNIFICANCE: The laser spallation technique provides a platform to examine the tradeoffs of adhesion modulators on both biofilm and cell adhesion. This tradeoff is characterized by the Adhesion Index, which is proposed to aid biocompatibility screening and could help improve implantation outcomes. The Adhesion Index is implemented to determine surface factors that promote favorable adhesion of cells greater than biofilms. Here, an Adhesion Index ≫ 1 suggests favorable biocompatibility.

Self-care research: How to grow the evidence base? (reprint).

BACKGROUND AND OBJECTIVE: The number of studies in the area of self-care is growing and international researchers are increasingly developing self-care interventions to improve outcomes of individual patients and communities. However, growth of the evidence is still slow due to challenges with designing and testing self-care interventions. In this article we address major methodological challenges with regard to the definition of self-care, use of theory, and research design, intended to provide guidance to researchers in this field. METHOD: During the inaugural conference of the International Center for Self-Care Research held in Rome, Italy in June 2019 we identified important issues in existing self-care research. Discussion and literature review lead to eight recommendation for future self-care research. RESULTS: In preparation, begin with a theoretically sound definition of self-care. In planning the intervention, build on and extend previous studies. Use theory to develop self-care interventions and consider translational models to guide development, evaluation and implementation of complex self-care interventions. Employ a study design that fits the current phase and objectives of the research and measure self-care and related factors carefully. In reporting, describe the sample and setting sufficiently so that others can draw conclusions about generalizability and applicability to their practice and patient population. In interpretation, describe how the intervention is assumed to work (causal assumptions) and its key components. CONCLUSION: Our review of existing self-care research clearly illustrates that the recommendations we provide are needed if we are to substantially grow the evidence base supporting self-care. Embracing a core set of principles will allow us to build on each other's work. Tweetable abstract: A core set of methodological principles is needed to substantially grow the evidence base supporting self-care.

Self-care research: How to grow the evidence base?

BACKGROUND AND OBJECTIVE: The number of studies in the area of self-care is growing and international researchers are increasingly developing self-care interventions to improve outcomes of individual patients and communities. However, growth of the evidence is still slow due to challenges with designing and testing self-care interventions. In this article we address major methodological challenges with regard to the definition of self-care, use of theory, and research design, intended to provide guidance to researchers in this field. METHOD: During the inaugural conference of the International Center for Self-Care Research held in Rome, Italy in June 2019 we identified important issues in existing self-care research. Discussion and literature review lead to eight recommendation for future self-care research. RESULTS: In preparation, begin with a theoretically sound definition of self-care. In planning the intervention, build on and extend previous studies. Use theory to develop self-care interventions and consider translational models to guide development, evaluation and implementation of complex self-care interventions. Employ a study design that fits the current phase and objectives of the research and measure self-care and related factors carefully. In reporting, describe the sample and setting sufficiently so that others can draw conclusions about generalizability and applicability to their practice and patient population. In interpretation, describe how the intervention is assumed to work (causal assumptions) and its key components. CONCLUSION: Our review of existing self-care research clearly illustrates that the recommendations we provide are needed if we are to substantially grow the evidence base supporting self-care. Embracing a core set of principles will allow us to build on each other's work. Tweetable abstract: A core set of methodological principles is needed to substantially grow the evidence base supporting self-care.

Chemical transformations in individual ultrasmall biomimetic containers.

Individual phospholipid vesicles, 1 to 5 micrometers in diameter, containing a single reagent or a complete reaction system, were immobilized with an infrared laser optical trap or by adhesion to modified borosilicate glass surfaces. Chemical transformations were initiated either by electroporation or by electrofusion, in each case through application of a short (10-microsecond), intense (20 to 50 kilovolts per centimeter) electric pulse delivered across ultramicroelectrodes. Product formation was monitored by far-field laser fluorescence microscopy. The ultrasmall characteristic of this reaction volume led to rapid diffusional mixing that permits the study of fast chemical kinetics. This technique is also well suited for the study of reaction dynamics of biological molecules within lipid-enclosed nanoenvironments that mimic cell membranes.

Novel cryopreservation method for dissociated human embryonic stem cells in the presence of a ROCK inhibitor.

BACKGROUND: Human embryonic stem cells (hESCs) have potential use in clinical therapy and regenerative medicine. One of the major challenges regarding the application of these cells is the development of an efficient cryopreservation protocol, since current methods, which include slow-freezing-rapid thawing and vitrification of colonies in suspension, present poor viability and high differentiation rates. Dissociated hESC suspensions do not survive cryopreservation because they are susceptible to apoptosis upon cell detachment and dissociation. A selective Rho-associated kinase (ROCK) inhibitor has been reported to increase the survival of dissociated hESCs and their cloning efficiency. METHODS AND RESULTS: Here, we describe a novel method for dissociated hESCs cryopreservation in the presence of the ROCK inhibitor Y-27632. The addition of this inhibitor to the freezing and post-thawing medium significantly increased the survival rate and efficiency of colony formation. Moreover, the hESC colonies obtained after the cryopreservation in the presence of the ROCK inhibitor showed a very low rate of differentiation and a reduced time of recovery. After prolonged culture of frozen-thawed dissociated hESCs, the characteristic properties of pluripotent cells were observed, including normal karyotype, morphological features, marker expression (SSEA-4, TRA-1-60, TRA-1-81 and Oct-4) and the potential to differentiate into derivatives of all three germ layers after embryoid bodies formation. CONCLUSION: This novel method for the cryopreservation of dissociated hESCs may reduce the time required to amplify frozen stocks, and facilitate not only the storage of large numbers of hESCs but also the widespread use of these cells in regenerative medicine.

Impact of different green manures on the content of S-alk(en)yl-L-cysteine sulfoxides and L-ascorbic acid in leek (Allium porrum).

This field study investigated the impact of various fertilization strategies with red clover ( Trifolium pratense L.) green manure on the levels of S-alk(en)yl- l-cysteine sulfoxides (ACSO) and l-ascorbic acid in leek. Two of the 12 treatments were controls, one without fertilizers and the other with a commercial mineral fertilizer. The remaining 10 treatments were different forms and quantities of green manure prepared from red clover. One treatment consisted of direct incorporation into soil of the preceding red clover crop. The other 9 treatments comprised three types of red clover green manure [anaerobically digested red clover biomass (biodigestate), composted red clover, fresh red clover as mulch] applied at three different doses. Yield was increased only at the highest dose of compost and the highest dose of mulch. High doses of green manure decreased dry matter content in leek. The fertilizer treatments increased the nitrogen uptake and the nitrogen content of leek. Sulfur uptake and sulfur levels were increased only by the mineral fertilizer and by the compost. Nonfertilized leek contained 20.4 +/- 5.8 g/kg of dry weight (dw) ACSOs as determined by LC-MS/MS and 1.57 +/- 0.01 g/kg of dw ascorbic acid as determined by HPLC. The ACSOs were to 92-96% isoalliin, the rest being methiin. Alliin was identified in only 1 of 72 samples. The ACSO level was increased by 37% by the mineral fertilizer. Whereas direct incorporation of red clover, mulch, and red clover biodigestate had no influence on the ACSO level, the highest dose of compost increased the ACSO level by 55%. Ascorbic acid levels were not influenced by the mineral treatment. Green manures increased ascorbic acid levels only on a dry weight basis. A high correlation between the content of sulfur and ACSO indicated that delivering capacity of sulfur from the manure to the plant strongly affected the ASCO content of the leek. In conclusion, the composted green manure was the most useful organic fertilizer in this study and reached at least the efficiency of the mineral fertilizer.

Comparative analysis of microbial sensing molecules in mucosal tissues with aging.

Host-bacterial interactions at mucosal surfaces require recognition of the bacteria by host cells enabling targeted responses to maintain tissue homeostasis. It is now well recognized that an array of host-derived pattern recognition receptors (PRRs), both cell-bound and soluble, are critical to innate immune engagement of microbes via microbial-associated molecular patterns (MAMP). This report describes the use of a nonhuman primate model to evaluate changes in the expression of these sensing molecules related to aging in healthy gingival tissues. Macaca mulatta aged 3-24 years were evaluated clinically and gingival tissues obtained, RNA isolated and microarray analysis conducted for gene expression of the sensing pattern recognition receptors (PRRs). The results demonstrated increased expression of various PRRs in healthy aging gingiva including extracellular (CD14, CD209, CLEC4E, TLR4), intracellular (NAIP, IFIH1, DAI) and soluble (PTX4, SAA1) PRRs. Selected PRRs were also correlated with both bleeding on probing (BOP) and pocket depth (PD) in the animals. These findings suggest that aged animals express altered levels of various PRRs that could affect the ability of the tissues to interact effectively with the juxtaposed microbial ecology, presumably contributing to an enhanced risk of periodontitis even in clinically healthy oral mucosal tissues with aging.

Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium.

Resident and recruited olfactory epithelial macrophages participate in the regulation of the survival, degeneration, and replacement of olfactory sensory neurons (OSNs). We have reported that liposome-encapsulated clodronate (Lip-C) induced selective and statistically significant depletion of macrophages in the OE of sham and 48 h OBX mice (38 and 35%, respectively) that resulted in increased OSN apoptosis and decreased numbers of mature OSNs and proliferating basal cells compared to controls (Lip-O). The aim of this study was to identify molecular mechanisms by which the selective depletion of macrophages in the OE resulted in these cellular changes by using a microarray expression pattern analysis. A 2x2 ANOVA identified 4,085 overall significantly (P < 0.01) regulated genes in the OE of Lip-O and Lip-C sham and 48 h OBX mice, and further statistical analysis using pairwise comparisons identified 4,024 genes that had either a significant (P < 0.01) treatment main effect (n = 2,680), group main effect (n = 778), or interaction effect (n = 980). The mean hybridization signals of immune response genes, e.g., Cxcr4, and genes encoding growth factors and neurogenesis regulators, e.g., Hdgf and Neurod1, respectively, were primarily lower in Lip-C mice compared with Lip-O mice. Apoptosis genes, e.g., Bak1, were also differentially regulated in Lip-C and/or OBX mice. Expression patterns of selected genes were validated with real-time RT-PCR; immunohistochemistry was used to localize selected gene products. These results identified the differential regulation of several novel genes through which alternatively activated macrophages regulate OSN progenitor cell proliferation, differentiation, and maturation, and the survival of OSNs.

Relationships between uterine culture, cytology and pregnancy rates in a Thoroughbred practice.

Endometrial cytology and culture specimens (n=2123) were collected concurrently with a guarded uterine culture instrument from 970 mares (738 barren, 1230 foaling and 155 maiden mares) during three breeding seasons (2001-2004). Results were compared to the 28-d pregnancy rate for the cycle from which the samples were taken. Cytological smears were evaluated for inflammation at x100 and graded as: not inflammatory (0-2 neutrophils/field), moderate inflammation (2-5 neutrophils/field), severe inflammation (>5 neutrophils/field), or hypocellular (scant epithelial cells and no neutrophils). Uterine culture swabs were plated within 6h, incubated for 72 h and results determined at 24, 48, and 72 h. Approximately, 20% (n=423) cytology samples were positive for inflammation (>2 neutrophils), whereas approximately 11% (n=231) of cultures had microorganisms recovered. A majority (64%) of the positive cultures (147/231) had inflammation on cytology smears. Streptococcus equi subsp. zooepidemicus was associated with more positive cytology results than coliforms (P<0.01). Mares with positive cytology or culture had lower pregnancy rates than mares with normal findings (P<0.01). Lowest pregnancy rates were recorded for mares with severe endometrial inflammation (21%, versus moderate inflammation 48%). Isolation of a microorganism from mares with endometrial inflammation was not associated with a further reduction in pregnancy rates. In barren, foaling and maiden mares, cytology was positive in 28, 17, and 5%, respectively, and culture was positive in 12.2, 11.1, and 3.2%. Foaling and maiden mares had higher pregnancy rates than barren mares (62, 69, and 44%, respectively, P<0.001). In conclusion, a positive cytology was twice as common as a positive culture, and isolation of microorganisms was associated with reduced pregnancy rates, even in the apparent absence of inflammation.

Attitudes of nurses towards family involvement in the care for patients with cardiovascular diseases.

INTRODUCTION: There is increasing evidence supporting the relationship between family support and patient outcomes. Therefore, involving families in the care of cardiovascular patients is expected to be beneficial for patients. The quality of the encounter with families highly depends on the attitudes of nurses towards the importance of families in patient care. AIM: The aim of this study was to describe the attitudes of nurses towards family involvement in patient care and to investigate the individual contributions of demographic, professional and regional background characteristics. METHOD: A survey was distributed among cardiovascular nurses attending an international conference in Norway and a national conference in Belgium. Nurses were asked to complete a questionnaire, including the Families' Importance in Nursing Care - Nurses' Attitudes scale. The study population consisted of respondents from Belgium ( n = 348) and from Scandinavian countries (Norway, Sweden and Denmark; n = 77). RESULTS: In general, nurses viewed the family as important in care. However, attitudes towards actively inviting families to take part in patient care were less positive. Higher educational level and a main practice role in research, education or management were significantly associated with more positive attitudes. Furthermore, the attitudes of respondents living in Scandinavia were more positive as compared to the attitudes of respondents living in Belgium. CONCLUSION: Education on the importance of families and active family involvement in patient care seems to be necessary in basic, undergraduate education, but also in clinical practice. More research is necessary in order to explore the cultural and regional differences in the attitudes of nurses towards the involvement of families in patient care.

Development of an international comorbidity education framework.

CONTEXT: The increasing number of people living with multiple chronic conditions in addition to an index condition has become an international healthcare priority. Health education curricula have been developed alongside single condition frameworks in health service policy and practice and need redesigning to incorporate optimal management of multiple conditions. AIM: Our aims were to evaluate current teaching and learning about comorbidity care amongst the global population of healthcare students from different disciplines and to develop an International Comorbidity Education Framework (ICEF) for incorporating comorbidity concepts into health education. METHODS: We surveyed nursing, medical and pharmacy students from England, India, Italy and Sweden to evaluate their understanding of comorbidity care. A list of core comorbidity content was constructed by an international group of higher education academics and clinicians from the same disciplines, by searching current curricula and analysing clinical frameworks and the student survey data. This list was used to develop the International Comorbidity Education Framework. RESULTS: The survey sample consisted of 917 students from England (42%), India (48%), Italy (8%) and Sweden (2%). The majority of students across all disciplines said that they lacked knowledge, training and confidence in comorbidity care and were unable to identify specific teaching on comorbidities. All student groups wanted further comorbidity training. The health education institution representatives found no specific references to comorbidity in current health education curricula. Current clinical frameworks were used to develop an agreed list of core comorbidity content and hence an International Comorbidity Education Framework. CONCLUSIONS: Based on consultation with academics and clinicians and on student feedback we developed an International Comorbidity Education Framework to promote the integration of comorbidity concepts into current healthcare curricula.

Increased birth weight is associated with altered gene expression in neonatal foreskin.

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v. the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. CONTROLS: Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.

Temporal gene expression profiles of target-ablated olfactory epithelium in mice with disrupted expression of scavenger receptor A: impact on macrophages.

Target ablation [removal of the olfactory bulb (OBX)] induces apoptotic death of olfactory sensory neurons (OSNs) and an immune response in which activation and recruitment of macrophages (ms) into the olfactory epithelium (OE) occupy a central role. Ms phagocytose apoptotic neurons and secrete cytokines/growth factors that regulate subsequent progenitor cell proliferation and neurogenesis. Scavenger receptor A (SR-A) is a pattern recognition receptor that mediates binding of ms to apoptotic cells and other relevant immune response functions. The aim of this study was to determine the impact of the absence of SR-A on the immune response to OBX. The immune response to OBX was evaluated in mice in which functional expression of the m scavenger receptor (MSR) was eliminated by gene disruption (MSR-/-) and wild-type (wt) mice of the same genetic background. OBX induced significant apoptotic death of mature OSNs in the two strains. However, subsequent m infiltration and activation and progenitor cell proliferation were significantly reduced in MSR-/- vs. wt mice. Gene expression profiling at short intervals after OBX demonstrated significant differences in temporal patterns of expression of several gene categories, including immune response genes. Many immune response genes that showed different temporal patterns of expression are related to m function, including cytokine and chemokine secretion, phagocytosis, and m maturation and activation. These studies suggest that impairment of the immune response to OBX in the OE of MSR-/- mice most likely resulted from decreased m adhesion and subsequent reduced infiltration and activation, with a resultant decrease in neurogenesis.

Oral hyaluronan gel reduces post operative tarsocrural effusion in the yearling Thoroughbred.

REASONS FOR PERFORMING STUDY: Hyaluronan (HA) has been used to treat joint disease via intra-articular, i.v. and oral administration. The efficacy of intra-articular and i.v. use has been evaluated but the oral route has yet to be examined. OBJECTIVES: To determine the effect of oral hyaluronan gel on joint effusion following arthroscopic surgery for osteochondritis dissecans (OCD) of the tarsocrural joint of yearling Thoroughbreds. METHODS: Forty-eight yearlings diagnosed with unilateral or bilateral osteochondritis dessicans (OCD) of the tarsus were arbitrarily chosen prior to arthroscopic surgery. The yearlings were included only if they had mild or no synovial effusion pre-surgery. Twenty-four of the yearlings (27 joints) were treated with 100 mg of HA orally for 30 days post operatively and 24 (30 joints) with a placebo orally for 30 days. At 30 days post operation, a blinded examiner scored the effusion of the dorsomedial tarsocrural joint individually using a scale of 0 to 5 (0 = no effusion, 1 = barely palpable effusion, 2 = palpable effusion [without plantar effusion], 3 = golf ball sized effusion with plantar effusion, 4 = tennis ball sized effusion with plantar effusion, 5 = > tennis ball sized effusion with plantar effusion). Half grades were allowed and OCD lesion sizes and locations were compared. RESULTS: A total of 57 joints were examined, of which 33 had OCD of the distal intermediate ridge of the tibia, 19 OCD of the distal lateral trochlear ridge of the talus and 5 OCD of the medial malleolus. The mean 30 day effusion score of the HA treated group (27 joints) was 0.67 while the mean of the 30 day placebo group (30 joints) was 2.05 (P < or = 0.0001). Similar results were noted when comparing treated vs. placebo for each lesion location as well as for lesion sizes. CONCLUSIONS AND POTENTIAL RELEVANCE: Oral preparations of hyaluronan are being used to treat joint disease in horse. Anecdotal reports supporting the efficacy of these preparations already exist. This study provides objective evidence that oral HA reduces joint effusion post operatively following the arthroscopic removal of an OCD lesion in the tarsocrural joint.

Effects of aging in the expression of NOD-like receptors and inflammasome-related genes in oral mucosa.

The molecular changes underlying the higher risk of chronic inflammatory disorders during aging remain incompletely understood. Molecular variations in the innate immune response related to recognition and interaction with microbes at mucosal surfaces could be involved in aging-related inflammation. We developed an ontology analysis of 20 nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and seven inflammasome-related genes (IRGs) in healthy and inflamed/periodontitis oral mucosal tissues from young, adolescent, adult, and aged non-human primates (Macaca mulatta) using the GeneChip(®) Rhesus Macaque Genome array. Validation of some of the significant changes was done by quantitative reverse transcription-polymerase chain reaction. The expression of NLRB/NAIP, NLRP12, and AIM2 increased with aging in healthy mucosa whereas NLRC2/NOD2 expression decreased. Although higher expression levels of some NLRs were generally observed with periodontitis in adult mucosal tissues (e.g. NLRB/NAIP, NLRP5, and NLRX1), various receptors (e.g. NLRC2/NOD2 and NLRP2) and the inflammasome adaptor protein ASC, exhibited a significant reduction in expression in aged periodontitis tissues. Accordingly, the expression of NLR-activated innate immune genes, such as HBD3 and IFNB1, was impaired in aged but not adult periodontitis tissues. Both adult and aged tissues showed significant increase in interleukin-1ß expression. These findings suggest that the expression of a subset of NLRs appears to change with aging in healthy oral mucosa, and that aging-related oral mucosal inflammation could involve an impaired regulation of the inflammatory and antimicrobial response associated with downregulation of specific NLRs and IRGs.

Harnessing the power of gene microarrays for the study of brain aging and Alzheimer's disease: statistical reliability and functional correlation.

During normal brain aging, numerous alterations develop in the physiology, biochemistry and structure of neurons and glia. Aging changes occur in most brain regions and, in the hippocampus, have been linked to declining cognitive performance in both humans and animals. Age-related changes in hippocampal regions also may be harbingers of more severe decrements to come from neurodegenerative disorders such as Alzheimer's disease (AD). However, unraveling the mechanisms underlying brain aging, AD and impaired function has been difficult because of the complexity of the networks that drive these aging-related changes. Gene microarray technology allows massively parallel analysis of most genes expressed in a tissue, and therefore is an important new research tool that potentially can provide the investigative power needed to address the complexity of brain aging/neurodegenerative processes. However, along with this new analytic power, microarrays bring several major bioinformatics and resource problems that frequently hinder the optimal application of this technology. In particular, microarray analyses generate extremely large and unwieldy data sets and are subject to high false positive and false negative rates. Concerns also have been raised regarding their accuracy and uniformity. Furthermore, microarray analyses can result in long lists of altered genes, most of which may be difficult to evaluate for functional relevance. These and other problems have led to some skepticism regarding the reliability and functional usefulness of microarray data and to a general view that microarray data should be validated by an independent method. Given recent progress, however, we suggest that the major problem for current microarray research is no longer validity of expression measurements, but rather, the reliability of inferences from the data, an issue more appropriately redressed by statistical approaches than by validation with a separate method. If tested using statistically defined criteria for reliability/significance, microarray data do not appear a priori to require more independent validation than data obtained by any other method. In fact, because of added confidence from co-regulation, they may require less. In this article we also discuss our strategy of statistically correlating individual gene expression with biologically important endpoints designed to address the problem of evaluating functional relevance. We also review how work by ourselves and others with this powerful technology is leading to new insights into the complex processes of brain aging and AD, and to novel, more comprehensive models of aging-related brain change.

Patients with heart failure in primary health care: effects of a nurse-led intervention on health-related quality of life and depression.

AIMS: To determine the effects of a nurse-led intervention designed to improve self-management of patients with heart failure in a primary health care setting regarding health-related quality of life and depression. METHODS: Patients at eight primary health care centres were screened by the Diagnosis Related Groups registry for the diagnosis of heart failure and eligibility for a cluster randomised study. A total of 153 patients were included (n=78 in the intervention group, 54% males, mean age 79 years, 59% in New York Heart Association class III-IV). The intervention involved patient and family education about heart failure and self-management and monthly telephone follow-up during 12 months by a primary health care nurse. RESULTS: The effects of the nurse-led intervention were limited. Significant differences were found in the physical dimension measured by the SF-36 health survey, and in depression measured by the Zung Self-rating Depression Scale. In comparison within groups at the 3 and 12-month follow-up, the intervention group significantly maintained their health-related quality of life measured by the SF-36 health survey, and their experience of depression measured by the Zung Self-rating Depression Scale to a greater extent than in the control group, especially among women. CONCLUSION: A nurse-led intervention directed toward patients with heart failure in a primary health care setting resulted in limited effects between the groups, although the physical and mental status were retained during 12 months of follow-up to a greater extent than in the control group.