A community action programme for reducing harmful drinking behaviour among adolescents: the Trelleborg Project

AIMS: To evaluate a 3-year community intervention programme by measuring changes in drinking patterns in a 15-16-year-old population. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: The action programme included five demand-reducing and one supply-reducing interventions. Cross-sectional, non-repeated data were collected from a questionnaire distributed in classrooms from 1999 to 2001 and 2003 (n = 1376, 724 boys and 652 girls; response rate = 92.3%). Stepwise logistic regression analyses were used to determine the relationship between different risk factors and excessive drinking, heavy episodic drinking, purchaser of alcohol and alcohol provided by parents. The results from the intervention community were also compared with similar Swedish cross-sectional data sets. FINDINGS: The results of our analyses indicated a decrease in harmful drinking behaviour in Trelleborg when comparing baseline with postintervention measurements. The comparison with other studies showed that the changes in these indicators were more rapid and consistent in Trelleborg. Finally, the multivariable logistic regression analyses showed that the outcomes were not likely to be attributed to changes in environmental factors. CONCLUSIONS: We concluded that a community action programme based on the systems approach reduced hazardous alcohol consumption effectively among adolescents in Trelleborg.     

A gene homologous to Saccharomyces cerevisiae SNF1 appears to be essential for the viability of Candida albicans.

The SNF1 gene of Saccharomyces cerevisiae (ScSNF1) is essential for the derepression of catabolic repression. We report here the isolation and characterization of an SNF1 homolog from Candida albicans (CaSNF1) which is apparently essential for the viability of this organism. The putative amino acid sequence of CaSNF1 has 68% identity with that of ScSNF1 and can restore the S. cerevisiae snf1 delta mutant's ability to utilize sucrose. Disruption of one of the CaSNF1 alleles resulted in morphological changes and decreased growth rates but did not modify the carbon source utilization pattern. Repetitive unsuccessful attempts to generate a snf1/snf1 homozygote by disruption of the second allele, using various vectors and approaches, suggest the lethal nature of this mutation. Integration into the second allele was possible only when a full-length functional SNF1 sequence was reassembled, further supporting this hypothesis and indicating that the indispensability of Snf1p prevented the isolation of snf1/snf1 mutants. The mutant bearing two disrupted SNF1 alleles and the SNF1 functional sequence maintained its ability to utilize sucrose and produced stellate colonies with extensive hyphal growth on agar media. It was demonstrated that in a mouse model, the virulences of this mutant and the wild-type strain are similar, suggesting that hyphal growth in vitro is not an indicator for higher virulence.     

Use of robotized DNA isolation and real-time PCR to quantify and identify close correlation between levels of Neisseria meningitidis DNA and lipopolysaccharides in plasma and cerebrospinal fluid from patients with systemic meningococcal disease

The present study, using robotized DNA isolation and quantitative PCR based on the Neisseria meningitidis-specific capsular transport A gene, demonstrates the ease, rapidity, specificity, and sensitivity of quantifying neisserial DNA in plasma (n = 65) and cerebrospinal fluid (CSF) (n = 12) from patients with systemic meningococcal disease. We found a close correlation between the levels of neisserial DNA and lipopolysaccharides in plasma (r = 0.905) and in CSF (r = 0.964). The median concentration of neisserial DNA in plasma in 23 patients with persistent shock was 2 x 10(7) copies/ml, versus <10(3) copies/ml in 42 nonshock patients. Furthermore, quantitative PCR made possible estimates of the total number of meningococci in plasma, as opposed to conventional blood cultures, suggesting about 1,000 dead meningococci for every viable bacterium. Finally, with logistic regression analyses, neisserial DNA may predict a patient's disease severity and outcome at hospital admission. The number of meningococci in plasma and CSF appears to be the main determinant of the lipopolysaccharide levels, clinical presentation, and outcome.     

The comparative effectiveness of tumor necrosis factor–blocking agents in patients with rheumatoid arthritis and patients with ankylosing spondylitis: A six‐month,longitudinal, observational,multicenter study

Objective

To compare the effectiveness of tumor necrosis factor (TNF)–blocking agents (etanercept and infliximab) in patients with rheumatoid arthritis (RA) and patients with ankylosing spondylitis (AS).

Methods

Data from an ongoing longitudinal, observational study in Norway were used to assess changes in health‐related quality of life (HRQOL) in patients with RA (n = 291) and AS (n = 62). Patients received anti‐TNF therapy, and changes in scores on the Short Form 36 (SF‐36), SF‐6D, modified Health Assessment Questionnaire, and visual analog scales for patients' assessments of pain, fatigue, and global status from baseline to followup examinations at 3 and 6 months were compared. Data were adjusted for age, sex, and baseline values and are presented as crude estimates as well as standardized response means.

Results

Both groups had improvements in all measures at 3 and 6 months. At 3 months, the changes were significantly better in the AS group compared with the RA group for all measures except the SF‐36 social functioning scores. At 6 months, all changes were numerically greater in the AS group. Differences were significant for the SF‐36 role emotional scores and were borderline significant for the SF‐36 physical functioning, role physical, and vitality scores and for the SF‐6D scores.

Conclusion

In this real‐life setting, patients with AS experienced improvement in HRQOL that was comparable to, and sometimes greater than, that observed in RA patients. These results support the idea that patients with AS should have the same access to TNF‐blocking agents as patients with RA.

     

Measurement of cardiac output with non-invasive Aesculon impedance versus thermodilution

Background: This study compared the non‐invasive thoracic electrical bioimpedance Aesculon^® technique (TEB_Aesculon) with thermodilution (TD) to evaluate whether TEB_Aesculon may offer a reliable means for estimating cardiac output (CO) in humans. Material and method: Cardiac output was measured with TD and TEB_Aesculon in 33 patients, with a mean age ± SEM of 59 ± 2·7 years, that underwent right heart catheterization for clinical investigation of pulmonary hypertension or severe heart failure. Four to five CO measurements were performed with each technique simultaneously in 33 patients at rest, 11 during exercise and seven during NO inhalation. Result: Cardiac output correlated poorly between TEB_Aesculon and TD at rest (r = 0·46, P<0·001), during exercise (r = 0·35, P<0·013) and NO inhalation (r = 0·41, P<0·017). CO was higher for TEB_Aesculon than TD with 0·86 ± 0·14 l min^?1 at rest (P<0·001) and 2·95 ± 0·69 l min^?1 during exercise (P<0·003), but similar during NO inhalation, with a tendency (P<0·079) to be 0·44 ± 0·19 l min^?1 higher for TEB_Aesculon than TD. CO increased from rest to exercise for TEB_Aesculon and TD with 6·11 ± 0·6 l min^?1 (P<0·001) and 3·91 ± 0·36 l min^?1 (P<0·001), respectively; an increase that was higher (P<0·002) for TEB_Aesculon than TD. During NO inhalation, compared to rest, CO decreased for TEB_Aesculon with 0·62 ± 0·11 l min^?1 (P<0·002), but not significantly for TD with 0·21 ± 0·12 l min^?1 (P<0·11). Bland–Altman analysis showed a poor agreement between TEB_Aesculon and TD. Conclusion: TEB_Aesculon overestimated CO compared to TD with ～17% at rest and ～34% during exercise, but the techniques showed similar results during NO inhalation. CO, furthermore, correlated poorly between TEB_Aesculon and TD. TEB_Aesculon may at present not replace TD for reliable CO measurements in humans.     

Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease

Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.