[Memorandum on sustainable reinforcement of prevention and health promotion: challenges at the federal, state and local level]. / Memorandum--Prävention und Gesundheitsförderung nachhaltig stärken: Herausforderungen auf Bundes-, Landes- und kommunaler Ebene.

Research-based evidence and practice-based experience are core requirements for the effective implementation of preventive interventions. The knowledge gained in the Prevention Research Funding Initiative of the German Federal Ministry of Education and Research (2004-2013) was therefore amalgamated, reflected and consolidated in the Cooperation for Sustainable Prevention Research (KNP) meta-project. In annual strategy meetings, researchers and practitioners from the field and other experts developed 3 memoranda providing recommendations for the further development of research and practice in the field of prevention and health promotion. Memorandum III is primarily aimed at decision-makers in politics and administration at the federal, state and local level, in civil society and in the workplace. Its recommendations show that structuring efforts are urgently needed to achieve sustainable policy, particularly in the fields of health, education, employment and social affairs. Memorandum III brings together the knowledge extracted and problems identified in research projects. More so than its 2 predecessors, Memorandum III abstracts knowledge from the individual projects and attempts to derive guidance for action and decision-making, as shown by the 7 recommendations that appear to useful for consensus-building in practice and research. Value judgments are inevitable. Prevention and health promotion are an investment in the future: of social health, social capital and social peace. Improvement of the framework conditions is needed to achieve the harmonized awareness and the sustained effectiveness of these structure-building efforts in different policy areas, spheres of life, fields of action, and groups of actors. This includes the implementation of an overall national strategy as well as the expansion of sources of funding, extension of the legal framework, overarching coordination, and the establishment of a National Center of Excellence to develop and safeguard prevention and health promotion. The memorandum is intended to stimulate a discourse resulting in structure-building and stabilizing measures designed to ensure the sustainability of prevention and health promotion.

Cytotoxic effect of amphotericin B in a myofibroblast cell line.

In this study we investigate whether Amphotericin B (AmB), a widely used antifungal agent, could decrease the proliferation of a myofibroblast cell line - GRX, a model of activated hepatic stellate cells (HSC). Three different hepatic cell lines (GRX, Hep G2 and ARL-6) were treated with two concentrations of AmB (1.25 µg/mL or 2.50 µg/mL). Cytotoxicity was assessed by MTT assay. The effects of AmB on GRX migration was evaluated by Wound-healing Assay. Cell cycle arrest was investigated by flow cytometry. Apoptosis and autophagy were analyzed by Caspase 3 and LC3 immunostaining, respectively. Treatment with AmB 1.25 or 2.50 µg/mL showed a decrease in viability of GRX cells. This decrease was not observed for Hep G2 or ARL-6 in any of the two AmB concentrations tested. GRX cells treated with 1.25 µg/mL AmB were unable to close the wound after 96 h. Cell cycle analysis showed an increase in sub-G1 population and a decrease in G2/M population in AmB-treated cells. In addition, AmB-treated GRX cells showed increased expression of LC-3 and Caspase-3 by immunohistochemistry, suggesting an increase in both autophagy and apoptosis. Here we show that AmB is cytotoxic for GRX cells, a model of activated HSC, but not for hepatic lineages HepG2 and ARL6.

[Quality in prevention and health promotion. Developing a common framework for quality development for members of the Federal Association for Prevention and Health Promotion in Germany]. / Qualität in Prävention und Gesundheitsförderung. Entwicklung eines gemeinsamen Handlungsrahmens in der Qualitätsentwicklung für die Mitglieder der Bundesvereinigung Prävention und Gesundheitsförderung e.V.

Following the principles of participatory health research, a collaborative study was conducted by the German Federal Association for Prevention and Health Promotion (BVPG) and the Institute for Social Health at the Catholic University of Applied Sciences Berlin (KHSB). The purpose of the study was to create a framework for the members of the BVPG for taking joint action on developing the quality of health promotion and prevention measures. The 129 members of the BVPG are mainly nongovernmental organizations responsible for the implementation and coordination of prevention and health promotion interventions at the state and national levels. One of the explicit goals of the BVPG is to support the development of quality in prevention and health promotion. A theoretical sample was drawn of 14 member organizations to participate in individual interviews and a Delphi process to gather data on their current quality development practice, their need for further support, and their ideas for a common framework. Selected results from the interviews and the proposed framework are presented here.

Buffer capacity of 4% succinylated gelatin does not provide any advantages over acidic 6% hydroxyethyl starch 130/0.4 for acid-base balance during experimental mixed acidaemia in a porcine model.

BACKGROUND AND OBJECTIVE: Four percent gelatine is an alkaline compound due to NH2 groups, whereas 6% hydroxyethyl starch 130/0.4 (HES130) has acidic features. We investigated whether these solutions lead to differences in acid-base balance in pigs during acidaemia and correction of pH. METHODS: Anaesthetized pigs were randomized to HES130 or gelatine infusion (n = 5 per group). Animals received acid infusion (0.4 M solution of lactic acid and HCl diluted in normal saline) and low tidal volume ventilation (6-7 mL kg(-1), PaCO2 of 80-85 mmHg, pH 7.19-7.24). Measurements were made before and after induction of acidaemia, before and after correction of pH with haemofiltration (continuous venovenous haemofiltration) and tris-hydroxymethylaminomethane infusion. We measured parameters describing acid-base balance according to Stewart's approach, ketone body formation, oxygen delivery, haemodynamics, diuresis and urinary pH. RESULTS: Acid-base balance did not differ significantly between the groups. In HES130-treated pigs, the haemodilution-based drop of haemoglobin (1.4 +/- 1.0 g dL(-1), median +/- SD) was paralleled by an increase in the cardiac output (0.5 +/- 0.4 L min(-1). Lacking increases in cardiac output, gelatine-treated pigs demonstrated a reduction in oxygen delivery (149.4 +/- 106.0 mL min(-1)). Tris-hydroxymethylaminomethane volumes required for pH titration to desired values were significantly higher in the gelatine group (0.7 +/- 0.1 mL kg(-1) h(-1) vs. HES130: 0.5 +/- 0.2 mL kg(-1) h(-1)). CONCLUSION: The buffer capacity of gelatine did not lead to favourable differences in acid-base balance in comparison to HES130.

[Implementing knowledge. Tasks and activities of Working Group 3 on "Healthy Aging" of the German Platform for Prevention and Health Promotion]. / Wissen umsetzen. Aufgaben und Aktivitäten der Arbeitsgruppe 3 "Gesund altern" des Deutschen Forums Prävention und Gesundheitsförderung.

It is indisputable that preventive and health-promoting interventions are also effective for older people. In order to put this knowledge into practice, several important questions have to be answered first. Which preventive goals have priority? Which contents have to be conveyed in the context of "healthy aging"? Which strategies of intervention have proven effective so far? How can older people be addressed in their surroundings? Working Group 3 on "Healthy Aging" of the German Forum/Platform for Prevention and Health Promotion is currently discussing these questions. The following article presents the proceedings as well as the results of Working Group 3 up to now.

Segmental duplication associated with evolutionary instability of human chromosome 3p25.1.

Fluorescence in situ hybridization (FISH) of human bacterial artificial chromosome (BAC) clones to orangutan metaphase spreads localized a breakpoint between human chromosome 3p25.1 and orangutan chromosome 2 to a <30-kb interval. The inversion occurred in a relatively gene-rich region with seven genes within 500 kb. The underlying breakpoint is closely juxtaposed to validated genes, however no functional gene has been disrupted by the evolutionary rearrangement. An approximately 21-kb DNA segment at the 3p25.1 breakpoint region has been duplicated intrachromosomally and interchromosomally to multiple regions in the orangutan and human genomes, providing additional evidence for the role of segmental duplications in hominoid chromosome evolution.

Disruption of TCBA1 associated with a de novo t(1;6)(q32.2;q22.3) presenting in a child with developmental delay and recurrent infections.

A boy with developmental delay, particularly of speech, a distinct face, antineutrophil cytoplasmic antibodies, and recurrent infections was found to have an apparently balanced de novo t(1;6)(q32.3;q22.3) translocation. Fluorescent in situ hybridisation with BAC/PAC clones and long range polymerase chain reaction products assessed in the human genome sequence localised the chromosome 1 breakpoint to a 9.8 kb segment within a hypothetical gene, LOC388735, and the chromosome 6 breakpoint to a 12.8 kb segment in intron 4 of the T-cell lymphoma breakpoint-associated target 1 (TCBA1) gene. Disruption and/or formation of TCBA1 fusion genes in T cell lymphoma and leukaemia cell lines suggests a role for this gene in tumorigenesis. The isolated mouse Tcba1 gene shows 91% amino acid sequence similarity with human TCBA1. It is expressed in fetal and adult brain and with lower levels in liver and testis. The human gene has been reported to be expressed exclusively in brain and thymus. Reduced TCBA1 expression in brain and thymus may explain at least some of the symptoms in this patient. It is concluded that germline alterations of the TCBA1 gene are associated with developmental delay and typical physical features.

Genomic structure and paralogous regions of the inversion breakpoint occurring between human chromosome 3p12.3 and orangutan chromosome 2.

Intrachromosomal duplications play a significant role in human genome pathology and evolution. To better understand the molecular basis of evolutionary chromosome rearrangements, we performed molecular cytogenetic and sequence analyses of the breakpoint region that distinguishes human chromosome 3p12.3 and orangutan chromosome 2. FISH with region-specific BAC clones demonstrated that the breakpoint-flanking sequences are duplicated intrachromosomally on orangutan 2 and human 3q21 as well as at many pericentromeric and subtelomeric sites throughout the genomes. Breakage and rearrangement of the human 3p12.3-homologous region in the orangutan lineage were associated with a partial loss of duplicated sequences in the breakpoint region. Consistent with our FISH mapping results, computational analysis of the human chromosome 3 genomic sequence revealed three 3p12.3-paralogous sequence blocks on human chromosome 3q21 and smaller blocks on the short arm end 3p26-->p25. This is consistent with the view that sequences from an ancestral site at 3q21 were duplicated at 3p12.3 in a common ancestor of orangutan and humans. Our results show that evolutionary chromosome rearrangements are associated with microduplications and microdeletions, contributing to the DNA differences between closely related species.

Digestion of DNA with restriction endonucleases.

Restriction endonucleases recognize short DNA sequences and cleave double-stranded DNA at specific sites within or adjacent to the recognition sequences. Restriction endonuclease cleavage of DNA into discrete fragments is one of the most basic procedures in molecular biology. The first method presented in this unit is the cleavage of a single DNA sample with a single restriction endonuclease. A number of common applications of this technique are also described. These include digesting a given DNA sample with more than one endonuclease, digesting multiple DNA samples with the same endonuclease, and partially digesting DNA such that cleavage only occurs at a subset of the restriction sites. A protocol for methylating specific DNA sequences and protecting them from restriction endonuclease cleavage is also presented. A collection of tables describing restriction endonucleases and their properties (including information about recognition sequences, types of termini produced, buffer conditions, and conditions for thermal inactivation) is given at the end of the unit.

Conservation of the deleted-in-azoospermia-like-1 (DAZL1) gene structure in old world monkeys points to a homologous function of DAZL1 in this primate class.

We isolated the complete deleted-in-azoospermia-like-1 (DAZL1) gene of the old world monkey Macaca fascicularis (tentatively designated as MafaDAZL1) and compared its sequence structure to that of the other DAZL1 genes isolated so far. In addition to the homologous RNA recognition motif (RRM domain), we only identified a high conservation of the Mafa-DAZL1 coding region to the mammalian DAZL1 genes (i.e. mouse: Dazl1; and human: DAZL1) and to that of Xenopus (xdazl). Only in the primates, Macaca fascicularis and human, sequences and lengths of the 5' and 3' untranslated DAZL1 gene structures (UTRs) displayed a similar conservation as their coding regions (i.e. 91-94%). Both belong to the primate class of old world monkeys evolutionarily separated 36-55 million years ago (1). The strong conservation of the complete DAZL1 gene structure in both primate species suggests a similar control and maturation pathway of DAZL1 transcripts in the germ line of old world monkeys and also indicates a homologous function of the DAZL1 RNA-binding protein in this primate class.

[Tubero-pustular demodicosis]. / Tuberös-pustulöse Demodikose.

A 38-year-old female patient suddenly developed an unusual tuberous, pustular tumor on her chin. On the basis of clinical pattern, histological and microbiological investigations the diagnosis of demodicosis was established. Histological investigation revealed follicular cysts and a chronic granulomatous perifolliculitis with many of Demodex folliculorum. A large number of mites could be also identified by microscopy of smears from pustules. No cellular or humoral immunological defects, tumours nor systemic disorders were found. After oral therapy with steroids and metronidazole, the lesions improved rapidly.

Spectral control of an alexandrite laser for an airborne water-vapor differential absorption lidar system.

A narrow-linewidth pulsed alexandrite laser has been greatly modified for improved spectral stability in an aircraft environment, and its operation has been evaluated in the laboratory for making water-vapor differential absorption lidar measurements. An alignment technique is described to achieve the optimum free spectral range ratio for the two étalons inserted in the alexandrite laser cavity, and the sensitivity of this ratio is analyzed. This technique drastically decreases the occurrence of mode hopping, which is commonly observed in a tunable, two-intracavity-étalon laser system. High spectral purity (> 99.85%) at 730 nm is demonstrated by the use of a water-vapor absorption line as a notch filter. The effective cross sections of 760-nm oxygen and 730-nm water-vapor absorption lines are measured at different pressures by usingthis laser, which has a finite linewidth of 0.02 cm(-1) (FWHM). It is found that for water-vapor absorption linewidths greater than 0.04 cm(-1) (HWHM), or for altitudes below 10 km, the laser line can be considered monochromatic because the measured effective absorption cross section is within 1% of the calculated monochromatic cross section. An analysis of the environmental sensitivity of the two intracavity étalons is presented, and a closed-loop computer control for active stabilization of the two intracavity étalons in the alexandrite laser is described. Using a water-vapor absorption line as a wavelength reference, we measure a long-term frequency drift (≈ 1.5 h) of less than 0.7 pm in the laboratory.

Airborne differential absorption lidar system for measurements of atmospheric water vapor and aerosols.

An airborne differential absorption lidar (DIAL) system has been developed at the NASA Langley Research Center for remote measurements of atmospheric water vapor (H(2)O) and aerosols. A solid-state alexandrite laser with a 1-pm linewidth and > 99.85% spectral purity was used as the on-line transmitter. Solid-state avalanche photodiode detector technology has replaced photomultiplier tubes in the receiver system, providing an average increase by a factor of 1.5-2.5 in the signal-to-noise ratio of the H(2)O measurement. By incorporating advanced diagnostic and data-acquisition instrumentation into other subsystems, we achieved additional improvements in system operational reliability and measurement accuracy. Laboratory spectroscopic measurements of H(2)O absorption-line parameters were perfo med to reduce the uncertainties in our knowledge of the absorption cross sections. Line-center H(2)O absorption cross sections were determined, with errors of 3-6%, for more than 120 lines in the 720-nm region. Flight tests of the system were conducted during 1989-1991 on the NASA Wallops Flight Facility Electra aircraft, and extensive intercomparison measurements were performed with dew-point hygrometers and H(2)O radiosondes. The H(2)O distributions measured with the DIAL system differed by ≤ 10% from the profiles determined with the in situ probes in a variety of atmospheric conditions.

Hawaii's near-universal health insurance--lessons learned.

To date, Hawaii is the only state to have implemented near-universal health insurance. The cornerstone of this program is the country's only requirement that employers provide health insurance for all employees who work at least 20 hours per week. Combined with low unemployment, voluntary modified community rating by health insurers, and expanded Medicaid and Medicare, this employer mandate has been part of a patchwork mechanism that insures upwards to 95 percent of the state's population. Indeed, by adding a state-sponsored gap group-insurance program, Hawaii may now insure in excess of 95 percent of its population. The program has generated good health outcomes, good consumer satisfaction, and relatively modest overall health care expenditures. But for all that near-universal insurance provides, there is still a great need for community-based preventive and primary care programs with outreach and family support services. In addition, traditionally underserved populations continue to be at increased risk. Both funding reform and continued infrastructure development must occur to achieve universal access to care.

Padrão de utilização clínica dos digitálicos: necessidade de reavaliação / Clinical Use of Digitalis. Need for Reassessment

Objetivo - Avaliar o padrão de utilização dos digitálicos, indicações de seu emprego e a freqüência de suspensão do fármaco em pacientes hospitalizados. Métodos - Foram estudados os prontuários de todos os pacientes internados nas enfermarias de medicina interna e especialidades médicas do Hospital de Clínicas de Porto Alegre. A coleta de dados foi realizada em 5 dias, sendo 3 no inverno e 2 no verão, mantendo um intervalo de pelo menos 2 semanas entre cada coleta. A presença de insuficiência cardíaca foi avaliada objetivamente através do escore proposto por Carlson e col. Resultados - De um total de 881 pacientes, 114 (13%) faziam uso de digoxina. A idade média ± DP desses pacientes foi de 66 ± 13 anos, sendo que 47% eram do sexo masculino. Dos pacientes que recebiam digoxina, 32% apresentavam escores compatíveis com insuficiência cardíaca definida ou possível; 26% apresentavam fibrilação ou flutter" atrial; 18% tinham insuficiência cardíaca e taquiarritmia supraventricular; e 24% não tinham indicação precisa segundo os critérios deste estudo. Oitenta e cinco por cento dos pacientes faziam uso prévio de digoxina e em 32% desses, a droga foi suspensa durante a internação. Considerando aqueles pacientes sem indicação para usar digitálicos, apenas 44% tiveram o tratamento com digoxina suspenso. Conclusão - De acordo com critérios contemporâneos, um percentual elevado de pacientes internados recebe digoxina sem indicação precisa. Estes dados sugerem que a reavaliação do uso de digitálicos deve ser incorporada à prática médica

Purpose - To evaluate the pattern of utilization of digitalis in an academic hospital. Methods - Clinical files of all patients admitted in medical wards at the Hospital de Clínicas de Porto Alegre were studied. Data were collected during five different days, three in the winter and two in the summer, keeping an interval of at least two weeks between each data collection. Heart failare diagnosis was evaluated objectively by means of a score proposed by Carlson et al. Results - From a total number of 881 patients, 114 (13%) were receiving digoxin. Mean age was 66 ± 13 years and 47% were males. Considering the patients who were taking digoxin, 32% presented scores compatible with definite or possible heart fuilare; 26% had atrial flutter or fibrillation; 18% had heart failare and supraventricular tachyarrhytmias; and in 24% no clear indications were found according to our criteria. Previous use of digoxin was found in 85% of the patients and 32% were withdrawn during the hospitalization. Considering just the patients who had no reason for using digoxin, only 44% had the drug withdrawn. Conclusion - According to current criteria, many hospitalized patients receive digoxin without a definite indication. These data suggest that reassessment of the use of digitalis should be incorporated into clinical practice

A stochastic branching model with formation of subunits applied to the growth of intestinal crypts.

The intestinal epithelium is one of the most rapidly regenerating tissues in mammals. Cell production takes place in the intestinal crypts which contain about 250 cells. Only a minority of 1-60 proliferating cells are able to maintain a crypt over a long period of time. However, so far attempts to identify these stem cells were unsuccessful. Therefore, little is known about their cellular growth and selfmaintenance properties. On the other hand, the crypts appear to exhibit a life cycle which starts by fission of existing crypts and ends by fission or extinction. Data on these processes have recently become available. Here, we demonstrate how these data on the life cycle of the macroscopic crypt structure can be used to derive a quantitative model of the microscopic process of stem cell growth. The model assumptions are: (1) stem cells undergo a time independent supracritical Markovian branching process (Galton-Watson process); (2) a crypt divides if the number of stem cells exceeds a given threshold and the stem cells are distributed to both daughter crypts according to binomial statistics; (3) the size of the crypt is proportional to the stem cell number. This model combining two different stochastic branching processes describes a new class of processes whose stationary stability and asymptotic behavior are examined. This model should be applicable to various growth processes with formation of subunits (e.g. population growth with formation of colonies in biology, ecology and sociology). Comparison with crypt data shows that intestinal stem cells have a probability of over 0.8 of dividing asymmetrically and that the threshold number should be 8 or larger.