Showing papers by "University of Tennessee Health Science Center published in 2005"
TL;DR: Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.
Abstract: Background— Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. Methods and Results— aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated wit...
1,196 citations
TL;DR: Clinical relevant cutpoints for usual gait speed are defined and their predictive value for health‐related events in older persons is investigated.
Abstract: OBJECTIVES: To define clinically relevant cutpoints for usual gait speed and to investigate their predictive value for health-related events in older persons. DESIGN: Prospective cohort study. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Three thousand forty-seven well-functioning older persons (mean age 74.2). MEASUREMENTS: Usual gait speed on a 6-m course was assessed at baseline. Participants were randomly divided into two groups to identify (Sample A; n = 2,031) and then validate (Sample B; n = 1,016) usual gait-speed cutpoints. Rates of persistent lower extremity limitation events (mean follow-up 4.9 years) were calculated according to gait speed in Sample A. A cutpoint (defining high- (<1 m/s) and low risk (≥1 m/s) groups) was identified based on persistent lower extremity limitation events. The predictive value of the identified cutpoints for major health-related events (persistent severe lower extremity limitation, death, and hospitalization) was evaluated in Sample B using Cox regression analyses. RESULTS: A graded response was seen between risk groups and health-related outcomes. Participants in the high-risk group had a higher risk of persistent lower extremity limitation (rate ratio (RR) = 2.20, 95% confidence interval (CI) = 1.76-2.74), persistent severe lower extremity limitation (RR = 2.29, 95% CI = 1.63-3.20), death (RR = 1.64, 95% CI = 1.14-2.37), and hospitalization (RR = 1.48, 95% CI = 1.02-2.13) than those in the low-risk group. CONCLUSION: Usual gait speed of less than 1 m/s identifies persons at high risk of health-related outcomes in well-functioning older people. Provision of a clinically meaningful cutpoint for usual gait speed may facilitate its use in clinical and research settings.
1,025 citations
TL;DR: These results reaffirm the close relationship of insomnia, depression, and anxiety, after rigorously controlling for other potential explanations for the relationship.
Abstract: Study objectives This study used empirically validated insomnia diagnostic criteria to compare depression and anxiety in people with insomnia and people not having insomnia. We also explored which specific sleep variables were significantly related to depression and anxiety. Finally, we compared depression and anxiety in (1) different insomnia types, (2) Caucasians and African Americans, and (3) genders. All analyses controlled for health variables, demographics, organic sleep disorders, and symptoms of organic sleep disorders. Design Cross-sectional and retrospective. Participants Community-based sample (N=772) of at least 50 men and 50 women in each 10-year age bracket from 20 to more than 89 years old. Measurements Self-report measures of health, sleep, depression, and anxiety. Results People with insomnia had greater depression and anxiety levels than people not having insomnia and were 9.82 and 17.35 times as likely to have clinically significant depression and anxiety, respectively. Increased insomnia frequency was related to increased depression and anxiety, and increased number of awakenings was also related to increased depression. These were the only 2 sleep variables significantly related to depression and anxiety. People with combined insomnia (ie, both onset and maintenance insomnia) had greater depression than did people with onset, maintenance, or mixed insomnia. There were no differences between other insomnia types. African Americans were 3.43 and 4.8 times more likely to have clinically significant depression and anxiety than Caucasians, respectively. Women had higher levels of depression than men. Conclusion These results reaffirm the close relationship of insomnia, depression, and anxiety, after rigorously controlling for other potential explanations for the relationship.
837 citations
TL;DR: A general approach to dissect genetic networks systematically across biological scale, from base pairs to behavior, using a reference population of recombinant inbred strains, found that a small number of major-effect quantitative trait loci jointly modulated large sets of transcripts and classical neural phenotypes in patterns specific to each tissue.
Abstract: Patterns of gene expression in the central nervous system are highly variable and heritable. This genetic variation among normal individuals leads to considerable structural, functional and behavioral differences. We devised a general approach to dissect genetic networks systematically across biological scale, from base pairs to behavior, using a reference population of recombinant inbred strains. We profiled gene expression using Affymetrix oligonucleotide arrays in the BXD recombinant inbred strains, for which we have extensive SNP and haplotype data. We integrated a complementary database comprising 25 years of legacy phenotypic data on these strains. Covariance among gene expression and pharmacological and behavioral traits is often highly significant, corroborates known functional relations and is often generated by common quantitative trait loci. We found that a small number of major-effect quantitative trait loci jointly modulated large sets of transcripts and classical neural phenotypes in patterns specific to each tissue. We developed new analytic and graph theoretical approaches to study shared genetic modulation of networks of traits using gene sets involved in neural synapse function as an example. We built these tools into an open web resource called WebQTL that can be used to test a broad array of hypotheses.
719 citations
TL;DR: This review will discuss the characterization of sputtered CaP coatings before and after post-deposition treatments and tissue responses to some of the characterized coating surfaces.
631 citations
TL;DR: Mice deficient in CuZn superoxide dismutase showed no overt abnormalities during development and early adulthood, but had a reduced lifespan and increased incidence of neoplastic changes in the liver, which likely contributes to hepatocarcinogenesis later in life.
Abstract: Mice deficient in CuZn superoxide dismutase (CuZnSOD) showed no overt abnormalities during development and early adulthood, but had a reduced lifespan and increased incidence of neoplastic changes in the liver. Greater than 70% of Sod1−/− mice developed liver nodules that were either nodular hyperplasia or hepatocellular carcinoma (HCC). Cross-sectional studies with livers collected from Sod1−/− and age-matched +/+ controls revealed extensive oxidative damage in the cytoplasm and, to a lesser extent, in the nucleus and mitochondria from as early as 3 months of age. A marked reduction in cytosolic aconitase, increased levels of 8-oxo dG and F2-isoprostanes, and a moderate reduction in glutathione peroxidase activities and porin levels were observed in all age groups of Sod1−/− mice examined. There were also age-related reductions in Mn superoxide dismutase activities and carbonic anhydrase III. Parallel to the biochemical changes, there were progressive increases in the DNA repair enzyme APEX1, the cell cycle control proteins cyclin D1 and D3, and the hepatocyte growth factor receptor Met. Increased cell proliferation in the presence of persistent oxidative damage to macromolecules likely contributes to hepatocarcinogenesis later in life.
625 citations
TL;DR: The authors psychometrically validated the TEMPS-A in affectively ill outpatients, leading to an instrument suitable for use in psychiatric, especially affective ill, populations, and conclude that the traits underlying affective disorders are very much part of human nature.
545 citations
TL;DR: Eight virus isolates that were nonpathogenic in ducks replicated and transmitted efficiently to naïve contacts, suggesting that highly pathogenic H5N1 viruses causing minimal signs of disease in ducks can propagate silently and efficiently among domestic and wild ducks in Asia and that they represent a serious threat to human and veterinary public health.
Abstract: Wild waterfowl are the natural reservoir of all influenza A viruses, and these viruses are usually nonpathogenic in these birds. However, since late 2002, H5N1 outbreaks in Asia have resulted in mortality among waterfowl in recreational parks, domestic flocks, and wild migratory birds. The evolutionary stasis between influenza virus and its natural host may have been disrupted, prompting us to ask whether waterfowl are resistant to H5N1 influenza virus disease and whether they can still act as a reservoir for these viruses. To better understand the biology of H5N1 viruses in ducks and attempt to answer this question, we inoculated juvenile mallards with 23 different H5N1 influenza viruses isolated in Asia between 2003 and 2004. All virus isolates replicated efficiently in inoculated ducks, and 22 were transmitted to susceptible contacts. Viruses replicated to higher levels in the trachea than in the cloaca of both inoculated and contact birds, suggesting that the digestive tract is not the main site of H5N1 influenza virus replication in ducks and that the fecal-oral route may no longer be the main transmission path. The virus isolates' pathogenicities varied from completely nonpathogenic to highly lethal and were positively correlated with tracheal virus titers. Nevertheless, the eight virus isolates that were nonpathogenic in ducks replicated and transmitted efficiently to naive contacts, suggesting that highly pathogenic H5N1 viruses causing minimal signs of disease in ducks can propagate silently and efficiently among domestic and wild ducks in Asia and that they represent a serious threat to human and veterinary public health.
465 citations
TL;DR: Follicular melanogenesis involves sequentially the melanogenic activity of follicular melanocytes, the transfer of melanin granules into cortical and medulla keratinocytes, and the formation of pigmented hair shafts, which is stringently coupled to the anagen stage of the hair cycle.
459 citations
TL;DR: CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors and efforts to interrupt this decline are warranted.
Abstract: Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment. Whether the longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score 5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores > or =80. Participants with CKD, defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2, were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [CI] 1.03 to 1.69) and OR 2.43 (95% CI, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m2 and <45 ml/min per 1.73 m2, respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted.
428 citations
TL;DR: The ability of Treg cells to efficiently enter the priming sites of pathogenic allo-reactive T cells appears to be a prerequisite for their protective function in aGVHD.
TL;DR: Large-scale mRNA expression analysis and gene mapping are combined to identify genes and loci that control hematopoietic stem cell (HSC) function and identify groups of coregulated transcripts that identify pathways that specify variation in stem cells.
Abstract: We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.
Ohio State University1, George Washington University2, National Institutes of Health3, University of Alabama at Birmingham4, University of Texas at Dallas5, University of Utah6, University of Chicago7, University of Pittsburgh8, Wake Forest University9, Thomas Jefferson University10, Wayne State University11, Columbia University12, University of Cincinnati13, Brown University14, Northwestern University15, University of Miami16, University of Tennessee Health Science Center17, University of Texas at San Antonio18, University of North Carolina at Chapel Hill19, University of Texas Health Science Center at Houston20, Case Western Reserve University21, Vanderbilt University22
TL;DR: Previous vaginal delivery including previous VBAC is the greatest predictor for successful TOL, and previous indication as dystocia, need for labor induction, or a maternal BMI > or = 30 significantly lowers success rates.
TL;DR: It is demonstrated that maintaining motion rather than fusion will prevent symptomatic adjacent-disc disease and will decrease adjacent-level radiological indicators of disease at a 24-month postoperative interval.
Abstract: Object. The authors compared the incidence of radiologically documented changes and symptomatic adjacent-level cervical disc disease after single-level discectomy and subsequent cervical fusion or arthroplasty in two independent prospective clinical studies. Methods. The patients were treated with the Affinity Anterior Cervical Cage System or the Bryan Artificial Cervical Disc. In each study the patients were required to undergo serial cervical radiography preoperatively and 24 months postoperatively, as well as serial clinical evaluations including documentation of adverse events, neurological status, and results of the 36-item Short Form Health Survey. All serial radiographs were reviewed prior to evaluating the clinical symptoms for development of increasing or new adjacent degenerative disc disease (DDD). Subsequently, the clinical data were analyzed. For various reasons of exclusion, the cases analyzed in the Bryan disc—treated cohort consisted of 74 patients and in the Affinity system—treated cohort...
TL;DR: The widespread expression of a cutaneous seorotoninergic/melatoninergic system indicates considerable selectivity of action to facilitate intra‐, auto‐, or paracrine mechanisms that define and influence skin function in a highly compartmentalized manner.
Abstract: It was recently discovered that mammalian skin can produce serotonin and transform it into melatonin. Pathways for the biosynthesis and biodegradation of serotonin and melatonin have been characterized in human and rodent skin and in their major cellular populations. Moreover, receptors for serotonin and melatonin receptors are expressed in keratinocytes, melanocytes, and fibroblasts and these mediate phenotypic actions on cellular proliferation and differentiation. Melatonin exerts receptor-independent effects, including activation of pathways protective of oxidative stress and the modification of cellular metabolism. While serotonin is known to have several roles in skin-e.g., pro-edema, vasodilatory, proinflammatory, and pruritogenic-melatonin has been experimentally implicated in hair growth cycling, pigmentation physiology, and melanoma control. Thus, the widespread expression of a cutaneous seorotoninergic/melatoninergic syste,m(s) indicates considerable selectivity of action to facilitate intra-, auto-, or paracrine mechanisms that define and influence skin function in a highly compartmentalized manner. Notably, the cutaneous melatoninergic system is organized to respond to continuous stimulation in contrast to the pineal gland, which (being insulated from the external environment) responds to discontinuous activation by the circadian clock. Overall, the cutaneous serotoninergic/melatoninergic system could counteract or buffer external (environmental) or internal stresses to preserve the biological integrity of the organ and to maintain its homeostasis.-Slominski, A. J., Wortsman, J., Tobin, D. J. The cutaneous serotoninergic/melatoninergic system: securing a place under the sun.
TL;DR: Results show thatRNAi is activated during VSV infection and that RNAi is a genuine antiviral immune defence mechanism in the worm.
Abstract: The nematode Caenorhabditis elegans is an ideal model for the study of many aspects of cell biology, including the hot topic of RNA interference (RNAi). But there was a problem in using the worm to study antiviral RNAi responses: C. elegans seemed not to support viral replication. But now the insect pathogen Flock house virus and the mammalian pathogen vesicular stomatitis virus are both shown to infect the worm, and to provoke a strong RNAi-based antiviral defence. So this important genetic model is now available for the study of host–virus interactions, and the antiviral effect of RNAi. RNA interference (RNAi) is an evolutionarily conserved sequence-specific post-transcriptional gene silencing mechanism that is well defined genetically in Caenorhabditis elegans1,2,3,4. RNAi has been postulated to function as an adaptive antiviral immune mechanism in the worm, but there is no experimental evidence for this. Part of the limitation is that there are no known natural viral pathogens of C. elegans. Here we describe an infection model in C. elegans using the mammalian pathogen vesicular stomatitis virus (VSV) to study the role of RNAi in antiviral immunity. VSV infection is potentiated in cells derived from RNAi-defective worm mutants (rde-1; rde-4), leading to the production of infectious progeny virus, and is inhibited in mutants with an enhanced RNAi response (rrf-3; eri-1). Because the RNAi response occurs in the absence of exogenously added VSV small interfering RNAs, these results show that RNAi is activated during VSV infection and that RNAi is a genuine antiviral immune defence mechanism in the worm.
TL;DR: In this paper, the authors studied the pathogenicity of four human and nine avian H5N1/04 influenza viruses in ferrets (an excellent model for influenza studies).
Abstract: The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only to avian species but also to humans. We studied the pathogenicity of four human and nine avian H5N1/04 influenza viruses in ferrets (an excellent model for influenza studies). All four human isolates were fatal to intranasally inoculated ferrets. The human isolate A/Vietnam/1203/04 (H5N1) was the most pathogenic isolate; the severity of disease was associated with a broad tissue tropism and high virus titers in multiple organs, including the brain. High fever, weight loss, anorexia, extreme lethargy, and diarrhea were observed. Two avian H5N1/04 isolates were as pathogenic as the human viruses, causing lethal systemic infections in ferrets. Seven of nine H5N1/04 viruses isolated from avian species caused mild infections, with virus replication restricted to the upper respiratory tract. All chicken isolates were nonlethal to ferrets. A sequence analysis revealed polybasic amino acids in the hemagglutinin connecting peptides of all H5N1/04 viruses, indicating that multiple molecular differences in other genes are important for a high level of virulence. Interestingly, the human A/Vietnam/1203/04 isolate had a lysine substitution at position 627 of PB2 and had one to eight amino acid changes in all gene products except that of the M1 gene, unlike the A/chicken/Vietnam/C58/04 and A/quail/Vietnam/36/04 viruses. Our results indicate that viruses that are lethal to mammals are circulating among birds in Asia and suggest that pathogenicity in ferrets, and perhaps humans, reflects a complex combination of different residues rather than a single amino acid difference.
TL;DR: Although clinical signs of thyroid dysfunction are usually absent in affected males, the disturbances in blood levels of thyroid hormones suggest the possibility of systematic detection through screening of high-risk populations.
Abstract: Allan-Herndon-Dudley syndrome was among the first of the X-linked mental retardation syndromes to be described (in 1944) and among the first to be regionally mapped on the X chromosome (in 1990). Six large families with the syndrome have been identified, and linkage studies have placed the gene locus in Xq13.2. Mutations in the monocarboxylate transporter 8 gene (MCT8) have been found in each of the six families. One essential function of the protein encoded by this gene appears to be the transport of triiodothyronine into neurons. Abnormal transporter function is reflected in elevated free triiodothyronine and lowered free thyroxine levels in the blood. Infancy and childhood in the Allan-Herndon-Dudley syndrome are marked by hypotonia, weakness, reduced muscle mass, and delay of developmental milestones. Facial manifestations are not distinctive, but the face tends to be elongated with bifrontal narrowing, and the ears are often simply formed or cupped. Some patients have myopathic facies. Generalized weakness is manifested by excessive drooling, forward positioning of the head and neck, failure to ambulate independently, or ataxia in those who do ambulate. Speech is dysarthric or absent altogether. Hypotonia gives way in adult life to spasticity. The hands exhibit dystonic and athetoid posturing and fisting. Cognitive development is severely impaired. No major malformations occur, intrauterine growth is not impaired, and head circumference and genital development are usually normal. Behavior tends to be passive, with little evidence of aggressive or disruptive behavior. Although clinical signs of thyroid dysfunction are usually absent in affected males, the disturbances in blood levels of thyroid hormones suggest the possibility of systematic detection through screening of high-risk populations.
TL;DR: Changes in the gene expression profile of Candida albicans following exposure to representatives of the four currently available classes of antifungal agents used in the treatment of systemic fungal infections are examined.
Abstract: Antifungal agents exert their activity through a variety of mechanisms, some of which are poorly understood. We examined changes in the gene expression profile of Candida albicans following exposure to representatives of the four currently available classes of antifungal agents used in the treatment of systemic fungal infections. Ketoconazole exposure increased expression of genes involved in lipid, fatty acid, and sterol metabolism, including NCP1, MCR1, CYB5, ERG2, ERG3, ERG10, ERG25, ERG251, and that encoding the azole target, ERG11. Ketoconazole also increased expression of several genes associated with azole resistance, including CDR1, CDR2, IFD4, DDR48, and RTA3. Amphotericin B produced changes in the expression of genes involved in small-molecule transport (ENA21), and in cell stress (YHB1, CTA1, AOX1, and SOD2). Also observed was decreased expression of genes involved in ergosterol biosynthesis, including ERG3 and ERG11. Caspofungin produced changes in expression of genes encoding cell wall maintenance proteins, including the beta-1,3-glucan synthase subunit GSL22, as well as PHR1, ECM21, ECM33, and FEN12. Flucytosine increased the expression of proteins involved in purine and pyrimidine biosynthesis, including YNK1, FUR1, and that encoding its target, CDC21. Real-time reverse transcription-PCR was used to confirm microarray results. Genes responding similarly to two or more drugs were also identified. These data shed new light on the effects of these classes of antifungal agents on C. albicans.
TL;DR: A framework of reach, efficacy/effectiveness, adoption, implementation, and maintenance known as RE-AIM is described and how it can be used to plan and design studies with features that can strengthen the potential translation of interventions.
Abstract: Failing to retain an adequate number of study participants in behavioral intervention trials poses a threat to interpretation of study results and its external validity. This qualitative investigation describes the retention strategies promoted by the recruitment and retention committee of the Behavior Change Consortium, a group of 15 university-based sites funded by the National Institutes of Health to implement studies targeted toward disease prevention through behavior change. During biannual meetings, focus groups were conducted with all sites to determine barriers encountered in retaining study participants and strategies employed to address these barriers. All of the retention strategies reported were combined into 8 thematic retention categories. Those categories perceived to be most effective for retaining study participants were summarized and consistencies noted among site populations across the life course (e.g., older adults, adults, children, and adolescents). Further, possible discrepancies between site populations of varying health statuses are discussed, and an ecological framework is proposed for use in future investigations on retention.
Vanderbilt University1, University of Utah2, Johns Hopkins University3, Fox Chase Cancer Center4, Memorial Sloan Kettering Cancer Center5, Duke University6, Northwestern University7, University of Nebraska Medical Center8, Washington University in St. Louis9, University of Tennessee Health Science Center10, Ohio State University11, University of Washington12, Dana Corporation13, University of South Florida14, Harvard University15, University of California, San Francisco16, Roswell Park Cancer Institute17
TL;DR: Experts believe that the treatment of urothelial tumors will evolve rapidly over the next few years, with improved outcomes for patients at all stages of disease.
Abstract: Urothelial tumors represent a spectrum of diseases with a range of prognosis. After a diagnosis is established at any point within the urothelial tract, the patient remains at risk for developing a new lesion at a different or the same location and at a similar or more advanced stage. Continued monitoring for recurrence is an essential part of management, because most recurrences are superficial and can be managed endoscopically. Within each category of disease, more refined methods to determine prognosis and guide management, based on molecular staging, are under development with the goal of optimizing the individual patient's likelihood of cure and chance for organ preservation. For patients with more extensive disease, newer treatments typically involve combined-modality approaches, using recently developed surgical procedures, or three-dimensional treatment planning for more precise delivery of radiation therapy. Although these are not appropriate in all cases, they do offer the promise of an improved quality of life and prolonged survival. Finally, within the category of metastatic disease, a number of new agents have been identified that appear to be superior to those currently considered to be standard therapies. Experts believe, therefore, that the treatment of urothelial tumors will evolve rapidly over the next few years, with improved outcomes for patients at all stages of disease.
TL;DR: On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptitiscal disease.
Abstract: Background Group A streptococcus (GAS) causes illness ranging from uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic shock, and rheumatic fever. Attempts to develop an M protein-based vaccine have been hindered by the fact that some M proteins elicit both protective antibodies and antibodies that cross-react with human tissues. New molecular techniques have allowed the previous obstacles to be largely overcome. Methods The vaccine is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that contain N-terminal peptides from streptococcal protective antigen and M proteins of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty healthy adult subjects received intramuscular 26-valent GAS vaccine (400 microg) at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and immunogenicity using assays for tissue cross-reactive antibodies, type-specific M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M protein antibodies. Results The incidence of local reactogenicity was similar to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject developed evidence of rheumatogenicity or nephritogenicity, and no induction of human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic peptides evoked a >4-fold increase in the geometric mean antibody titer over baseline. The mean log2 fold-increase in serum antibody titer (+/- standard error of the mean) for all 27 antigens was 3.67 +/- 0.21. A significant mean log2 reduction in streptococcal bacterial counts in serum samples obtained after immunization was seen in opsonization assays for all M serotypes. Conclusions On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptococcal disease.
TL;DR: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity, and in participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL- 6.
Abstract: Background: Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance.
Methods: The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70–79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD).
Results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H2O v 74.2 cm H2O, p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p<0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL-6 (adjusted regression coefficients (β) = −5.3 (95% CI −9.1 to−1.5) and −3.1 (95% CI −4.3 to −1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (β = −6.4 (95% CI −12.8 to −0.03) and −3.4 (95% CI −5.4 to −1.3), respectively, for IL-6 and β = −10.1 (95% CI −18.7 to −1.5) and −3.8 (95% CI −7 to −0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups.
Conclusions: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity.
TL;DR: Peginterferon alfa‐2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post‐OLT setting and Randomized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT.
TL;DR: In this paper, the authors discuss various forms of bullying in schools, prevalence rates, and the consequences of bullying for the bully, the victim and the school community, and best practices guidelines for implementing bullying prevention programs in schools are discussed.
Abstract: Reducing violence in schools is a major concern of educators, parents, and legislators. Violence manifests itself in numerous ways, and there is growing evidence that low-level or underlying forms of violence have a profound effect on the learning environment ofthe school. Bullying is the most prevalent form of low-level violence in schools today and, if left unchecked, can lead to more serious forms of violence. Consequently, an essential aspect of school violence prevention is the identification and implementation of interventions and strategies designed to prevent or reduce bullying in schools. The authors discuss various forms of bullying in schools, prevalence rates, and the consequences of bullying for the bully, the victim, and the school community. Practical bullying prevention strategies that target multiple levels (that is, individual, classroom, and school) are provided, and best practices guidelines for implementing bullying prevention programs in schools are discussed.
TL;DR: The prevalence of and risk factors for hearing loss in a sample of older adults enrolled in the Health, Aging and Body Composition (Health ABC) Study are determined.
Abstract: Objectives: To determine the prevalence of and risk factors for hearing loss in a sample of 2,052 older adults (aged 73–84; 46.9% male, 37.3% black) enrolled in the Health, Aging and Body Composition (Health ABC) Study.
Design: Cross-sectional analysis of a longitudinal cohort study.
Setting: Pittsburgh, Pennsylvania, and Memphis, Tennessee, areas.
Participants: Random sample of Medicare beneficiary subjects enrolled in the Health ABC program from 1997 to 1998. They included 2,052 individuals: 660 white men (32.2%), 631 white women (30.8%), 310 black men (15.1%), and 451 black women (22.0%). Participants ranged in age from 73 to 84, with a mean age of 77.5.
Measurements: Hearing sensitivity was measured using pure-tone threshold testing. Hearing loss was defined based on two averages of hearing thresholds: 500, 1,000, and 2,000 Hz greater than 25-decibel (dB) hearing level (HL) (hearing loss); and 2,000, 4,000, and 8,000 Hz greater than 40-dB HL (high-frequency hearing loss). Potential hearing loss correlates, including demographics, medical history, ototoxic medication use, occupational noise exposure, and lifestyle factors, were collected via questionnaire.
Results: The prevalence of hearing loss was 59.9%; the prevalence of high-frequency hearing loss was 76.9%. Hearing loss was most common in white men, followed by white women, black men, and black women. Older age, white race, diabetes mellitus, cerebrovascular disease, smoking, poorer cognitive status, occupational noise exposure, and ear surgery were associated with hearing loss after multivariable adjustment. Race- and sex-specific risk factors included higher blood pressure and occupational noise exposure (white men), poorer cognitive status and smoking (black women), and low total hip bone mineral density (black men). Possible protective factors included salicylate use (overall sample, black men) and moderate alcohol intake (black women).
Conclusion: Hearing loss was extremely common in this population. Because many of the identified hearing loss risk factors are modifiable, some of the burden associated with hearing loss in older people should be preventable.
TL;DR: At present, the clinician must base their clinical practice on the few high-quality observational studies and intervention trials available rather than on meta-analyses, as there is a scarcity of good clinical trials.
TL;DR: A distinction can be made preoperatively between NEC and IP based on abdominal radiographic findings and the patient's age at operation, and future randomized trials that compare laparotomy versus drainage would likely benefit from stratification of treatment assignment based on preoperative diagnosis.
Abstract: Objective:
Purposes of this study were: 1) to compare mortality and postoperative morbidities (intra-abdominal abscess, wound dehiscence, and intestinal stricture) in extremely low birth weight (ELBW) infants who underwent initial laparotomy or drainage for necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP); 2) to determine the ability to distinguish NEC from IP preoperatively and the importance of this distinction on outcome measures; and 3) to evaluate the association between extent of intestinal disease determined at operation and outcome measures.
TL;DR: This review paper critically examines the empirical evidence, applying the efficacy guidelines jointly established by the Association for Applied Psychophysiology and Biofeedback (AAPB) and the International Society for Neuronal Regulation (ISNR), and determined EEG biofeedback to be “probably efficacious” for the treatment of ADHD.
Abstract: Historically, pharmacological treatments for attention-deficit/hyperactivity disorder (ADHD) have been considered to be the only type of interventions effective for reducing the core symptoms of this condition. However, during the past three decades, a series of case and controlled group studies examining the effects of EEG biofeedback have reported improved attention and behavioral control, increased cortical activation on quantitative electroencephalographic examination, and gains on tests of intelligence and academic achievement in response to this type of treatment. This review paper critically examines the empirical evidence, applying the efficacy guidelines jointly established by the Association for Applied Psychophysiology and Biofeedback (AAPB) and the International Society for Neuronal Regulation (ISNR). On the basis of these scientific principles, EEG biofeedback was determined to be “probably efficacious” for the treatment of ADHD. Although significant clinical improvement was reported in approximately 75% of the patients in each of the published research studies, additional randomized, controlled group studies are needed in order to provide a better estimate of the percentage of patients with ADHD who will demonstrate such gains in clinical practice.
TL;DR: The association of motor performance was consistently greater for the DSST than the 3MS and, among the motor tests, gait speed retained a significant association with both cognitive measures independent of demographic, weight, physical activity and comorbid health conditions.
Abstract: Performance measures of physical function (gait speed, chair stands, standing balance) and cognitive function [Teng-modified Mini-Mental Status Exam (3MS) and digit symbol substitution test (DSST)] were assessed at baseline in 3,075 participants in the Health, Aging and Body Composition Study. Each physical function measure was examined for the strength and magnitude of association with cognitive function. All physical function measures were associated with both the 3MS and DSST scores (p < 0.001), and in multivariate analysis each relationship was independent of demographic characteristics, weight, physical activity and comorbid health conditions of participants. The association of motor performance was consistently greater for the DSST than the 3MS and, among the motor tests, gait speed retained a significant association with both cognitive measures independent of demographic, weight, physical activity and comorbid health conditions. In this large cohort of high-functioning older adults, the correlation between physical and cognitive function was not entirely explained by demographics. Longitudinal studies are needed to determine the direction of causality in this relationship.