Vascular hippocampal plasticity after aerobic exercise in older adults.

Aerobic exercise in young adults can induce vascular plasticity in the hippocampus, a critical region for recall and recognition memory. In a mechanistic proof-of-concept intervention over 3 months, we investigated whether healthy older adults (60-77 years) also show such plasticity. Regional cerebral blood flow (rCBF) and volume (rCBV) were measured with gadolinium-based perfusion imaging (3 Tesla magnetic resonance image (MRI)). Hippocampal volumes were assessed by high-resolution 7 Tesla MRI. Fitness improvement correlated with changes in hippocampal perfusion and hippocampal head volume. Perfusion tended to increase in younger, but to decrease in older individuals. The changes in fitness, hippocampal perfusion and volume were positively related to changes in recognition memory and early recall for complex spatial objects. Path analyses indicated that fitness-related changes in complex object recognition were modulated by hippocampal perfusion. These findings indicate a preserved capacity of the aging human hippocampus for functionally relevant vascular plasticity, which decreases with progressing age.

Asymmetry in genitalia does not increase the rate of their evolution.

Left-right asymmetry is a frequently encountered phenomenon in the copulation organs of insects. While various causes have been proposed for genital asymmetry, we raise the question of whether asymmetry might facilitate, or even accelerate, morphological divergence of genitalia between species. We tested this hypothesis in the scarab chafer genus Schizonycha, which comprises species with symmetric as well as asymmetric male genitalia. Morphometric analyses were conducted in the context of their phylogeny, inferred from mitochondrial and nuclear ribosomal DNA sequence data (cox1, rrnL, and 28S) for a sample of 99 South African specimens, including 34 species and 5 outgroup taxa. Trees were reconstructed with maximum likelihood and Bayesian analysis. The extent of asymmetry and the variation of male copulation organs were analyzed with Generalized Procrustes analysis (GPA), by quantifying shape divergence of the parameres. We found a continuous transition in the degree of asymmetry among the investigated species. Ancestral state reconstruction revealed multiple origins and a high degree of evolutionary plasticity of paramere asymmetry in Schizonycha. However, no significant correlation between evolutionary rates of paramere shape divergence and the degree of paramere asymmetry was found, and so we conclude that asymmetric genitalia in Schizonycha do not increase the rate of genital shape divergence.

[Managed competition in the health-care services - the Dutch experience]. / Regulierter Wettbewerb im Gesundheitswesen - Erfahrungen aus den Niederlanden.

For some years in Switzerland, in Germany and in the Netherlands some experience has been gathered with managed competition in health care. Efficiency reserves in the health service should be opened up by stronger competition orientation. Since the fundamental reform of the health insurance system in the Netherlands in 2006 the longest experience with the new governance model exists in this country. Health system experts in Germany and Switzerland maybe interested to include the experiences from the Netherlands into their further reforms. The analysis of relevant statistics and publications shows that, after 6 years, the results of the health reform in the Netherlands are to be called rather "sobering up". The competition activities of the health insurances, the insured persons and the providers are rather weak. However the expenditures for health are rising continuously. The intended goals of managed competition (reduction of costs and efficiency increase) could not be achieved in the Netherlands so far. The role of the health insurance companies and the competition readiness of the insured persons were obviously overrated, at the same time as well as the market power of the provider was rather underestimated.

Why barcode? High-throughput multiplex sequencing of mitochondrial genomes for molecular systematics.

Mitochondrial genome sequences are important markers for phylogenetics but taxon sampling remains sporadic because of the great effort and cost required to acquire full-length sequences. Here, we demonstrate a simple, cost-effective way to sequence the full complement of protein coding mitochondrial genes from pooled samples using the 454/Roche platform. Multiplexing was achieved without the need for expensive indexing tags ('barcodes'). The method was trialled with a set of long-range polymerase chain reaction (PCR) fragments from 30 species of Coleoptera (beetles) sequenced in a 1/16th sector of a sequencing plate. Long contigs were produced from the pooled sequences with sequencing depths ranging from ∼10 to 100× per contig. Species identity of individual contigs was established via three 'bait' sequences matching disparate parts of the mitochondrial genome obtained by conventional PCR and Sanger sequencing. This proved that assembly of contigs from the sequencing pool was correct. Our study produced sequences for 21 nearly complete and seven partial sets of protein coding mitochondrial genes. Combined with existing sequences for 25 taxa, an improved estimate of basal relationships in Coleoptera was obtained. The procedure could be employed routinely for mitochondrial genome sequencing at the species level, to provide improved species 'barcodes' that currently use the cox1 gene only.

Appropriateness of proton pump inhibitor recommendations at hospital discharge and continuation in primary care.

Background: Inappropriate prescriptions of proton pump inhibitors (PPI) in hospital and primary care have been widely reported. Recommendations from hospital have been implicated as one reason for inappropriate prescriptions of PPI in primary care. Objective: To quantify the amount of appropriate PPI recommendations in hospital discharge letters and the influence of these recommendations on general practitioners' (GPs') PPI-prescriptions. Materials and Methods: This is an observational study in 31 primary care practices. We identified patients discharged from hospital with PPI recommendation between 2006 and 2007 and assessed practice records and PPI prescription six months prior and after hospital admission. Hospital recommendation for continuous PPI-treatment and continuation by GPs was classified as appropriate, inappropriate or uncertain. Logistic regression analysis was used to calculate factors associated with indicated and non-indicated PPI continuation. Results: In 263 (58%) out of 506 patients discharged from 35 hospitals with a PPI recommendation no indication could be found. Non-indicated PPIs were continued by GPs in 58% for at least 1 month. Indicated PPIs were discontinued in 33%. Two thirds of non-indicated PPIs were initiated in hospital. The strongest factor associated with non-indicated continuation was a PPI-prescription prior to hospital admission [OR: 3.0; 95% confidence interval (CI): 1.7-5.4]. This was also the strongest factor for continuation of an indicated PPI medication (OR: 3.2; 95% CI: 1.4-7.5). Conclusions: We found a strong influence of hospital recommendations and previous prescriptions on PPI prescriptions after discharge. Hospitals should critically review their practice of recommending PPI and document indications. GPs should carefully assess hospital recommendations and their medication prior to admission to avoid over- and under-prescribing.

Predictors of outcome after liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria.

The Milan criteria have been the cornerstone of selection policies for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT) globally for over two decades. Many groups have proposed the transplantation of patients with larger and more numerous tumors achieving comparable results. Many of these use radiologic morphometric criteria as surrogates for explant pathology to predict outcomes. Several other indices have been developed both within and beyond Milan incorporating biological indices as well as dynamic markers of response to pre-transplant locoregional treatments and waiting time. These have allowed for successful expansion of transplant selection criteria without compromising outcomes with limited organ supplies. In this review we will discuss the predictors of outcome in patients beyond Milan criteria.

[Polypharmacy: a dilemma in primary care? Results of group discussions with general practitioners]. / Polypharmazie: ein hausärztliches Dilemma? Ergebnisse aus Gruppendiskussionen mit Allgemeinärztinnen und Allgemeinärzten.

BACKGROUND: Due to the aging population and the associated increase in multi-morbidity, polypharmacy will become an important issue. Little is known about general practitioners' perception of polypharmacy. We have explored this issue within the framework of a research course organised by the German Society for General Practice and Family Medicine (Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin, DEGAM.) METHODS: A total of 21 participants were divided in three homogeneous groups and one heterogeneous group according to their professional concentration (full-time general practitioners, junior researchers, senior researchers). Each group was supervised by two non-directing moderators. A two-step analysis was performed. In a fist step, mind maps were generated and in a second step, mind maps were interpreted according to the grounded theory. RESULTS: We identified three core aspects of polypharmacy in general practice: overview of prescribed medication, communication between doctors, patients and other health care professionals as well as evidence for managing multi-morbidity. General practitioners are torn between providing individual medical care and guideline stipulations. Pharmacotherapy is influenced by interprofessional communication, prescriptions by multiple physicians, patient expectations, adherence, advertisements, guidelines and costs. One's view on polypharmacy is influenced by professional background and experience. CONCLUSIONS: From the general practitioner's perspective, interprofessional and doctor-patient communication are highly important for a good medication overview as well as dealing with uncertainties in daily medical care. Simply improving evidence for the care of patients with multi-morbidities in the form of meta-guidelines would not be sufficient to overcome the effects of the many other influencing factors.

Lung cancer mortality report card: measuring progress in Wisconsin's counties, 1979-1998.

PURPOSE: To compare and contrast trends in lung cancer mortality in Wisconsin's 72 counties, as a measure of long-term progress in tobacco control. METHODS: Lung cancer mortality data were abstracted from the Centers for Disease Control and Prevention's WONDER database from 1979 to 1998. Percent change in lung cancer mortality rates were analyzed at the county and national levels from 1979-1983 to 1994-1998. RESULTS: In Wisconsin, lung cancer mortality rates increased 23%, compared to a 19% increase in the United States. There was more variation in lung cancer mortality trends between Wisconsin counties than between states, with increases in 67 of Wisconsin's 72 counties. Lung cancer mortality rates increased for men in 44 counties and for women in 68 counties. Only 4 counties in Wisconsin had fewer lung cancer deaths in 1994-1998 compared with 1979-1983. CONCLUSIONS: Progress in reducing lung cancer mortality in Wisconsin--a long-term measure of progress in tobacco control--has lagged behind the rest of the United States. Nevertheless, some Wisconsin counties have experienced more progress in reducing the health burden from lung cancer, suggesting that differences exist between communities in the effectiveness of their tobacco control efforts.

Trends in self-reported cigarette smoking, Wisconsin, 1984-1999.

The purpose of this study is to assess trends in self-reported cigarette smoking among adults in Wisconsin. Behavioral Risk Factor Survey data from 1984-1999 were analyzed to determine changes in smoking prevalence. Results of this analysis show almost no change in overall adult smoking prevalence over the past 15 years. Smoking prevalence rates did, however, decrease slightly for men from 29% in 1984 to 22% in 1999. Moreover, smoking prevalence for adults 18 to 24 years of age increased from 25% in 1994 to 36% in 1999. These results show that despite state and national efforts over the past 15 years to reduce cigarette smoking among adults, minimal progress has been made. Furthermore, the increase in smoking rates among 18 to 24 year olds highlights the need for additional prevention and cessation efforts targeted toward this group. Understanding past trends in cigarette smoking is critical for the Wisconsin Tobacco Control Board and other public health advocates to monitor progress toward the goal of reducing tobacco use.

[Health economy and health promotion -- self-responsibility for health?]. / Gesundheitsökonomie und Gesundheitsförderung - Eigenverantwortung für Gesundheit?

The social insurance systems in Germany are about to face radical changes, predominantly due to demographic developments. The solution might be an increasing self-responsibility of the population. The suitability of this health economical concept is to be verified for health insurance. The starting point of the health economic debate, discussing the issue of responsibility, is its description, and therefore the health of populations and the fundamental determinants for the maintenance of health and for illness. This is followed by a theoretical health economic discussion on the question whether insurants and patients are suitable market partners shoulder the responsibility transferred to them. The description of empiric evidence of the effects of co-payment questions the concept of self-responsibility and finally leads to discussing the individual versus social responsibility for health and illness.

[Comparative presentation of current economic evaluation studies for phenylketonuria screening]. / Vergleichende Darstellung bisheriger ökonomischer Evaluationsstudien zum Screening auf Phenylketonurie.

A systematic review was undertaken to assess the economic value of PKU screening in the framework of newborn screening for inborn errors of metabolism. Therefore, seven international studies on this topic were connected and examined with regard to differences and similarities. The relation between costs and benefits of PKU-screening programmes goes from 1:1,2 up to 1:9,25. The differences can be explained by varying incidence of PKU (in international comparison) and particularly by methodical differences in the respective study designs. This aspect is pointed out while taking up and emphasising the necessity of standardisation in economic evaluation studies. Furthermore, future developments (chances, trends, changes) in newborn screening are discussed, based on the potential use of new technologies.

An approach to rotational relapse.

The tendency of rotated teeth to relapse after treatment following retention is partially because of the supra-alveolar fibers which are stretched during rotational correction. Early treatment, overrotation, a long retention period, and proper contouring of contact points have been used to reduce relapse. With several surgical methods, it has been shown that releasing the tension in the periodontal fibers by severing the supracrestal and transseptal fibers significantly reduced relapse tendencies following rotation. This study was designed to test a simple surgical method (Vanarsdall) and to examine the effect of transsecting supra-alveolar fibers in orthodontically rotated teeth. Twelve cases in which a tooth and its antimere were rotated in excess of 10 degrees prior to orthodontic treatment were chosen for this study. One of the two rotated teeth was chosen for the gingival fibrotomy, while its antimere was retained by conventional orthodontic means and served as a control. The incision was made at a 45-degree angle to the long axis of the tooth, on the labial and lingual aspects of each tooth, 2 months prior to debanding. A significant decrease in the amount of relapse up to 30 days following removal of appliances in the fibrotomy group as compared to the control group (0.42 degrees and 5.75 degrees, respectively) suggests that the procedure be considered for overcoming rotational relapse.

Identification and partial purification of the cardiac sodium-calcium exchange protein.

Cardiac sarcolemmal vesicles were solubilized in 2% sodium cholate/0.5 M NaCl/soybean phospholipids (25 mg/ml), and reconstituted following the procedure of Miyamoto and Racker [Miyamoto, H. & Racker, E. (1980) J. Biol. Chem. 255, 2656-2658]. Initial rates of Na-Ca exchange in the reconstituted proteoliposomes were 17-fold higher than in the native vesicles. Total recovery of exchange activity often exceeded 100%, indicating that the exchange system had been activated by the reconstitution procedure. Examination of native and reconstituted vesicles by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed two protein bands that were substantially enriched in the reconstituted system: one at 48 kDa and a diffuse band centered at 82 kDa. A cholate extract of the vesicles was applied to a Sephacryl S-300 column and the various eluted fractions were reconstituted, assayed for Na-Ca exchange and examined by polyacrylamide gel electrophoresis. The activity profile, after correcting for loss of activity on the column, showed a good correlation with the presence of the diffuse 82-kDa band. A cholate extract of the vesicles was treated with Pronase (1 mg/ml) for 10 min at 37 degrees C and reconstituted using a procedure similar to that described by Wakabayashi and Goshima [Wakabayashi, S. & Goshima, K. (1982) Biochim. Biophys. Acta 693, 125-133]. The resulting proteoliposomes catalyzed Na-Ca exchange with a specific activity 30- to 100-fold greater than that of native vesicles. Upon examination by polyacrylamide gel electrophoresis, these proteoliposomes exhibited a single major band at 82 kDa, with several minor bands at lower molecular weights that migrated identically to the components of Pronase. The results suggest that the 82-kDa band represents the cardiac Na-Ca exchange protein.

Purification and amino-terminal sequence of the bovine cardiac sodium-calcium exchanger: evidence for the presence of a signal sequence.

The Na(+)-Ca2+ exchange carrier was purified from bovine cardiac tissue by a new procedure which relies principally upon anion-exchange chromatography. The purified protein exhibited two major bands on sodium dodecyl sulfate gels, at 120 and 160 kDa. The relative intensities of the two bands could be altered by variations in the procedures used for preparing the samples for electrophoresis, suggesting that they represent two different conformational states of the same protein. The NH2-terminal amino acid sequences of the 120- and 160-kDa bands were identical and agreed closely with a region of the deduced amino acid sequence of the recently cloned canine cardiac exchanger. The NH2-terminal sequence was preceded in the deduced sequence by a 32-residue segment that exhibited the characteristics of a signal sequence; the initial amino acid in the NH2-terminal sequence followed immediately after the predicted cleavage site for the signal sequence. The Na(+)-Ca2+ exchanger appears to be unique among membrane transport carriers in encoding a cleaved signal sequence. The characteristics of the sequences flanking the first putative transmembrane segment of the mature exchanger suggest that the signal sequence is necessary to ensure the correct topological orientation of the exchanger in the membrane.

Saturable binding of the echinoderm microtubule-associated protein (EMAP) on microtubules, but not filamentous actin or vimentin filaments.

The echinoderm microtubule-associated protein (EMAP) is a 75-kDa, WD-repeat protein associated with the mitotic spindle apparatus. To understand EMAP's biological role, it is important to determine its affinity for microtubules (MTs) and other cytoskeletal components. To accomplish this goal, we utilized a low-cost, bubble-column bioreactor to express EMAP as a hexahistidine fusion (6his) protein in baculovirus-infected insect cells. After optimizing cell growth conditions, up to 30 mg of EMAP was obtained in the soluble cell lysate from a 1-liter culture. EMAP was purified to homogeneity in a two-step process that included immobilized metal-affinity chromatography (IMAC) and anion-exchange chromatography. In vitro binding studies on cytoskeletal components were performed with the 6his-EMAP. EMAP bound to MTs, but not actin or vimentin filaments, with an intrinsic dissociation constant of 0.18 microM and binding stoichiometry of 0.7 mol EMAP per mol tubulin heterodimer. In addition, we show that a strong MT binding domain resides in the 137 amino acid, NH(2)-terminus of EMAP and a weaker binding site in the WD-domain. Previous work has shown that the EMAP concentration in the sea urchin egg is over 4 microM. Together, these results show that there is sufficient EMAP in the egg to regulate the assembly of a large pool of maternally stored tubulin.

Expression of matrix metalloproteinase 9 (96-kd gelatinase B) in human rheumatoid arthritis.

OBJECTIVE: To determine the expression of matrix metalloproteinase 9/gelatinase B (MMP-9) in synovial fluid (SF), plasma, and synovial tissue from individuals with rheumatoid arthritis (RA), inflammatory arthritis (IA), and osteoarthritis (OA), using specific monoclonal antibody reagents. METHODS: Gelatinolytic activity in the SF and plasma of patients with RA, IA, and OA was assessed by gelatin zymography. A mouse monoclonal antiserum, 277.13, which selectively recognizes soluble latent forms of human MMP-9, was used to quantitate MMP-9 levels in patient synovial effusions, plasma, and synovial tissue with a capture sandwich enzyme-linked immunosorbent assay (ELISA). Fifty-one SF samples (31 RA, 9 OA, 11 IA) were analyzed. Immunolocalization of MMP-9 in RA, OA, and normal synovium was investigated using MMP-9-specific antisera. RESULTS: MMP-9 antigen levels in synovial effusions were elevated 67-fold in RA samples compared with OA samples. In addition, although MMP-9 antigen levels in IA synovial effusions were 2.7-fold less than the values in RA samples, they were elevated 34-fold over the values in OA samples. These data indicate an association between increased MMP-9 levels and inflammatory arthritis. A predominant 92-kd gelatinolytic activity (specifically inhibited by EDTA) was evident in RA and IA samples, but no activity was observed in OA samples. Among 86 plasma samples (17 RA, 9 IA, 60 normal controls) analyzed for MMP-9 antigen levels by immunocapture ELISA, MMP-9 antigen levels were elevated 7-fold in RA plasma compared with normal plasma. RA synovial tissue extracts demonstrated elevated levels of MMP-9 antigen compared with OA synovial tissue. MMP-9 immunolocalization studies demonstrated expression in infiltrating leukocytes (neutrophils and macrophages), endothelial cells, and synovial fibroblasts in RA synovium. CONCLUSION: Latent MMP-9 and/or MMP-9-tissue inhibitor of metalloproteinases 1 (TIMP-1) complexes are elevated in RA and IA SF compared with OA SF. In addition, MMP-9 is increased in RA plasma versus normal control plasma. Synovial tissue levels of MMP-9 antigen are also elevated in RA versus OA. The tissue distribution of MMP-9 within RA synovium is localized to sites of inflammation comprising surface synovial lining cells, endothelium, and leukocytes. Taken together, these observations suggest that connective tissue turnover occurs as a result of excessive MMP activity over TIMP action in the invading pannus, periarticular tissue, or SF. Further studies such as those used in the present investigation will help elucidate the role of a number of different enzymes and inhibitors in the destructive arthropathies.