Can non-prosecutory enforcement of public health legislation reduce smoking amonq hiqh school students?

Background: Smoking by adolescents has been identified as a major public health issue. Raising the legal age of cigarette purchase from 16 to 18 years has attempted to address the issue by restricting adolescents? access. Methods/Strategy: A prospective study evaluating the impact of non-prosecutory enforcement of public health legislation involving ‘beat police’ was conducted in the Northern Sydney Health region. Secondary students, aged 12 to 17 years, from both intervention and control regions were surveyed about cigarette smoking habits by means of a self-completed questionnaire administered pre- and post-intervention. Results: 12,502 anonymous questionnaires were completed. At baseline, 19.3% of male students and 21.2% of female students indicated they were current smokers. Age and sex stratified chi-squared analysis revealed significantly lower post-intervention smoking prevalence for year 8 and 10 females and year 7 males among the intervention group. Higher post-intervention smoking prevalences were demonstrated for year 7 and 9 females and year 8 males among the intervention group and in year 10 males and year 11 females among the control group. The analysis of combined baseline and follow-up data from coeducational schools with logistic regression techniques demonstrated that the intervention had a significant effect in reducing smoking prevalence among year 7 students only (OR=0.54). Conclusion: Our study demonstrates the difficulties in restricting high school students? access to cigarettes. Isolated non-prosecutory strategies are likely to only have a limited impact on reducing smoking prevalence among high school students.     

Variable toxicity of dyes used in micropuncture studies

SUMMARY: This study evaluated the potential toxicity of Fast green and Lissamine green, the two dyes commonly used for visualizing tubular fluid flow in micropuncture studies. In both the in vitro perfused kidney and cultured tubular epithelial cells, Fast green exhibited a profound, dose-dependent toxicity. In contrast, Lissamine green was non-toxic. In conclusion, we recommend that Fast green not be used in micropuncture studies.     

HIV positive tests at Coronial Services in Victoria 1989–1996: lessons for HIV surveillance

Results of routine testing at other sites can supplement surveillance of the HIV epidemic in Australia which is largely basec upon voluntary testing. Since 1989, systematic onsite HIV testing has been undertaken on all bodies taken to the Victorian Institute of Forensic Medicine (VIFM). Information was collected on all cases of HIV infection detected at VIFM between 1989 and 1996, and matched to surveillance databases. In 8 years, 75 people were diagnosed with HIV; all except one were male. The age range was 14–70 years, mean 37.4 years. The major causes of death were suicide 35%, AIDS 21%, druc toxicity 16%, natural causes 12% and injury 7%. The major exposure categories were male homosexual 51%, male bisexual 11%, homosexual/bisexual IDU 16%, IDU other 8%, and haemophiliac 7%. For only two was exposure information unavailable. Seropositivity for anti-HCV and HBsAg was 37% and 11% respectively. The deceased was recorded as having HIV/AIDS on the police report in 73% of cases, and at least 90% of subjects had been diagnosed with HIV prior to their death. The study suggests there is relatively little undiagnosed HIV infection in Victoria, that HIV infection has not moved outside traditional risk groups, and that many tests for HIV are undertaken using false namecodes. Many patients could not be matched on the HIV/A|DS databases, identifying a problem with HIV surveillance systems in Victoria, and the need to capture all information on HIV positives detected at VIFM.     

Quality of life and later adverse health outcomes in patients with suspected heart attack

We tested the hypothesis that low quality of life (QOL) after discharge from hospital with ischaemic heart disease (IHD) is associated with higher rates of later adverse outcomes (death and subsequent hospital admission for acute myocardial infarction or congestive cardiac failure). Three hundred and seventy-five patients previously enrolled in an intervention study which assessed QOL six months after hospitalisation were followed up for an additional 18 months. The rates of adverse outcomes increased as QOL decreased (high QOL 9%; moderate 18%; low 28%). After adjustment for known prognostic factors, the risk of an adverse outcome was still higher in 'low' and 'moderate' compared to 'high' QOL subjects (low QOL adjusted OR=2.6, 95% Cl=1.2–5.8; moderate 1.9, 0.8-4.2). In conclusion, QOL after discharge from hospital appears to be an independent predictor of later morbidity and mortality.     

Evolutionary origin of the feather epidermis.

The formation of scales and feathers in reptiles and birds has fascinated biologists for decades. How might the developmental processes involved in the evolution of the amniote ectoderm be interpreted to shed light on the evolution of integumental appendages? An Evo-Devo approach to this question is proving essential to understand the observation that there is homology between the transient embryonic layers covering the scale epidermis of alligators and birds and the epidermal cell populations of embryonic feather filaments. Whereas the embryonic layers of scutate scales are sloughed off at hatching, that their homologues persist in feathers demonstrates that the predecessors of birds took advantage of the ability of their ectoderm to generate embryonic layers by recruiting them to make the epidermis of the embryonic feather filament. Furthermore, observations on mutant chickens with altered scale and feather development (Abbott and Asmundson [1957] J. Hered. 18:63-70; Abbott [1965] Poult. Sci. 44:1347; Abbott [1967] Methods in developmental biology. New York: Thomas Y. Crowell) suggest that the ectodermal placodes of feathers, which direct the formation of unique dermal condensations and subsequently appendage outgrowth, provided the mechanism by which the developmental processes generating the embryonic layers diverged during evolution to support the morphogenesis of the epidermis of the primitive feather filament with its barb ridges.     

Validation of chromogenic in situ hybridization for detection of EGFR copy number amplification in nonsmall cell lung carcinoma.

Epidermal growth factor receptor (EGFR) gene copy number correlates with response to tyrosine kinase inhibitors in patients with nonsmall cell lung carcinoma. Fluorescence in situ hybridization (FISH), a standard methodology to detect EGFR copy number abnormalities in nonsmall cell lung carcinoma, is limited by instrumentation and cost. Chromogenic in situ hybridization (CISH) is an emerging alternative detection technique using light microscopy, but its utility in assessing EGFR copy number in lung cancer is not established. To address the utility of CISH, we studied paraffin-embedded nonsmall cell lung carcinoma specimens from 77 Taiwanese nonsmoking women treated by surgery alone. We recorded the number of signals per tumor cell nucleus, correlated EGFR copy number by CISH with FISH results, and used receiver operating characteristics to identify cut-off points for the CISH results. Tumors were classified as adenocarcinoma (n=28), mixed adenocarcinoma with bronchioloalveolar features (n=25), bronchioloalveolar carcinoma (n=2), squamous cell carcinoma (n=15), and adenosquamous carcinoma (n=7). By FISH, 29% of cases had no amplification, 18% had low polysomy, 35% had high polysomy, and 12% had gene amplification. EGFR copy number detected by CISH highly correlated with FISH (Spearman r=0.81, P<0.0001). We determined the optimal EGFR CISH cut-off points that discriminate between no amplification and low polysomy (2.8 signals, P=0.09); no amplification plus low polysomy and high polysomy plus gene amplification (4.5 signals, P<0.0001); and high polysomy and gene amplification (7.1 signals, P=0.0003). CISH is an alternative assay to FISH in determining EGFR copy number status that may contribute to stratification of patients with nonsmall cell lung carcinoma for clinical trials and identify a subset of patients that should be treated with tyrosine kinase inhibitors.     

Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-1alpha mutation carriers

OBJECTIVE: Patients with diabetes due to hepatocyte nuclear factor (HNF)-1alpha mutations have beta-cell deficiency, insulin sensitivity, altered proinsulin levels, and a low renal threshold for glucose. It is uncertain how many of these features precede the development of diabetes. The aim of our study was to test for these characteristics in young nondiabetic HNF-1alpha mutation carriers. RESEARCH DESIGN AND METHODS: A total of 47 offspring from 19 extended families underwent genetic testing, a standard oral glucose tolerance test, and urine testing. RESULTS: HNF-1alpha mutations were found in 20 offspring, 7 with diabetes and 13 without diabetes. The 13 nondiabetic mutation carriers were compared with 27 family control subjects, who were matched for age, sex, and BMI. There was marked beta-cell deficiency with reduced insulinogenic index (53.5 [31.5-90.9] vs. 226.0 [126.0-407.1], SD [range], P < 0.001) and area under the curve for insulin (P < 0.001). Insulin sensitivity was increased in mutation carriers (homeostatic model assessment of insulin sensitivity 144.6 [82.7-252.7] vs. 100 [66.9-149.4], P = 0.025). A total of 38% of mutation carriers had glycosuria at 2 h compared with 0% of control subjects (P = 0.0034). Those with glycosuria had peak glucose values that were higher than the mutations carriers without glycosuria (range 8.1-11.8 vs. 6.2-8.4 mmol/l, P = 0.002). The seven subjects with diabetes all showed glycosuria. CONCLUSIONS: We conclude that marked beta-cell deficiency, increased insulin sensitivity, and a low renal threshold are present in young nondiabetic HNF-1alpha mutation carriers. The presence of glycosuria post-glucose load could be used to screen children of mutation carriers as it occurs in all mutation carriers with a peak glucose in the oral glucose tolerance test >8.4 mmol/l.     

Interprofessional curriculum development achieves results: Initial evidence from a dementia-care protocol

This report describes the outcomes of a five-day, protocol-based interprofessional education (IPE) initiative to prepare undergraduate medical, nursing, and paramedic students for collaborative work with adults with dementia. Clinical placements provided a structured and supervised IPE experience for 127 students in two Residential Aged Care Facilities (RACFs) in Hobart, Australia, during 2013 and 2014. The IPE activity was based on a seven-step protocol formulated by an interprofessional team of educators and aged care practitioners that revolved around collaborative assessments of adults with complex health needs. This article describes the IPE protocol and presents the results of a pre- and post-placement attitude questionnaire and knowledge quiz administered to evaluate student attitudes towards IPE and knowledge of dementia. Data suggest that a five-day, supervised, and protocol-based IPE experience in a dementia-care setting can inculcate positive changes in student attitudes about collaborative practice and may encourage dementia-related learning outcomes.     

Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide

Inhibitors of the G(2) DNA damage checkpoint can selectively sensitize cancer cells with mutated p53 to killing by DNA-damaging agents. Isogranulatimide is a G(2) checkpoint inhibitor containing a unique indole/maleimide/imidazole skeleton identified in a phenotypic cell-based screen; however, the mechanism of action of isogranulatimide is unknown. Using natural and synthetic isogranulatimide analogues, we show that the imide nitrogen and a basic nitrogen at position 14 or 15 in the imidazole ring are important for checkpoint inhibition. Isogranulatimide shows structural resemblance to the aglycon of UCN-01, a potent bisindolemaleimide inhibitor of protein kinase C beta (IC(50), 0.001 micromol/L) and of the checkpoint kinase Chk1 (IC(50), 0.007 micromol/L). In vitro kinase assays show that isogranulatimide inhibits Chk1 (IC(50), 0.1 micromol/L) but not protein kinase C beta. Of 13 additional protein kinases tested, isogranulatimide significantly inhibits only glycogen synthase kinase-3beta (IC(50), 0.5 micromol/L). We determined the crystal structure of the Chk1 catalytic domain complexed with isogranulatimide. Like UCN-01, isogranulatimide binds in the ATP-binding pocket of Chk1 and hydrogen bonds with the backbone carbonyl oxygen of Glu(85) and the amide nitrogen of Cys(87). Unlike UCN-01, the basic N15 of isogranulatimide interacts with Glu(17), causing a conformation change in the kinase glycine-rich loop that may contribute importantly to inhibition. The mechanism by which isogranulatimide inhibits Chk1 and its favorable kinase selectivity profile make it a promising candidate for modulating checkpoint responses in tumors for therapeutic benefit.