A web-based review of global health programs in U.S. allopathic and osteopathic medical schools.

PURPOSE: There is no current centralized database of structured global health programs at U.S. medical schools and no published review in the past decade. This study aims to describe the prevalence, characteristics, and requirements of non-degree, longitudinal, structured global health programs in U.S. allopathic and osteopathic medical schools. MATERIALS AND METHODS: In July 2021, the authors performed a web-based review of existing structured global health programs for the 154 U.S. allopathic medical schools and 35 U.S. osteopathic medical schools established prior to 2019. RESULTS: Of 189 institutions examined, 74 (39%) had online information about a structured global health program. Forty-three (53%) programs reported coursework requirements, 44 (54%) required a global health experience, and one program required demonstration of language or cultural knowledge. More internally administered programs required experiential work, while more externally administered programs required didactic work. There were few differences in program requirements between allopathic and osteopathic medical schools. CONCLUSIONS: There has been a 75% increase over the past ten years in the number of U.S. allopathic medical schools with websites for structured global health programs. There appeared to be little standardization in their structure and requirements. The findings support the need for a web-based central repository for updated information regarding medical school global health curricula.

Epignatus con extensión intracraneana: autopsia, reporte de un caso, y revisión bibliográfica / Epignatus with intracranial extension: autopsy, case report, and literature review

Metodología y descripción: se reporta el caso de una paciente de 31 años de edad, primigesta, que consulta a las 20 semanas por hallazgo ecográfico de tumoración orofaríngea fetalAutopsia y resultados: se obtuvo un feto femenino de 950 grs con teratoma maduro de 10x6x5 cm que protruye a través de la boca. Discusión: en la actualidad, se aplica el término epignatus a cualquier teratoma de la cavidad orofaríngea sin especificar el sitio de origen. La pesquisa es por ecografía(3) pero es necesaria una resonancia obstétrica para descartar algunos diagnósticos diferenciales (meningo encefalocele, neuroblastoma, glioma nasal, teratoma cervical) y malformaciones en otras localizaciones que puedan asociarse(2). Pueden tener un crecimiento unidireccional o bidireccional. La mayoría de las publicaciones de epignatus con tumor intracraneano se limitan a reportes de casos. Conclusión: actualmente, el tratamiento quirúrgico agresivo del epignatus con extensión intracraneana no está recomendado. Creemos que correlacionando los estudios pre-natales con los hallazgos post-natales, se podría establecer una clasificación que determine la viabilidad fetal y los casos que serían candidatos a beneficiarse con un tratamiento quirúrgico.

Effectiveness of an Education Program on Donation and Transplant Aimed at Students of the Nursing Degree Course.

BACKGROUND: Health workers' awareness and knowledge of transplant medicine can improve people's sensitivity and reduce their degree of opposition to donations. The medical literature contains numerous examples of education programs aimed at university students. This work describes the experience of an education program for students of the second and third year of a nursing degree course. METHODS: From April to September 2013, an education program was set up for 80 university students. It was divided into 3 stages: group self-learning based on prearranged topics, sharing of the results, and participation in the final seminar. The effectiveness was assessed according to a pretest/posttest design. RESULTS: The first questionnaire contained 19 questions, and the second contained 27. The questions were subdivided into specific areas: subjective knowledge, objective knowledge, attitude, awareness, participation in the event, evaluation of the information material handed out, and appreciation of the tools used. There was a significant increase for items relating to knowledge, whereas awareness and attitude (already high at the start of the program) showed no changes. After the program, many students discussed the question of donation with their relatives and friends, and about 70% filled in a donor card. The students expressed a highly positive opinion of the initiative and the tools used. CONCLUSIONS: The initiative proved its validity, improving subjective and objective knowledge to a statistically significant extent and also increasing awareness and attitude. The students' evaluation was extremely positive.

The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL.

The functional relevance of the B-cell receptor (BCR) and the evolution of protein kinases as therapeutic targets have recently shifted the paradigm for treatment of B-cell malignancies. Inhibition of p110δ with idelalisib has shown clinical activity in chronic lymphocytic leukemia (CLL). The dynamic interplay of isoforms p110δ and p110γ in leukocytes support the hypothesis that dual blockade may provide a therapeutic benefit. IPI-145, an oral inhibitor of p110δ and p110γ isoforms, sensitizes BCR-stimulated and/or stromal co-cultured primary CLL cells to apoptosis (median 20%, n=57; P<0.0001) including samples with poor prognostic markers, unmutated IgVH (n=28) and prior treatment (n=15; P<0.0001). IPI-145 potently inhibits the CD40L/IL-2/IL-10 induced proliferation of CLL cells with an IC50 in sub-nanomolar range. A corresponding dose-responsive inhibition of pAKT(Ser473) is observed with an IC50 of 0.36 nM. IPI-145 diminishes the BCR-induced chemokines CCL3 and CCL4 secretion to 17% and 37%, respectively. Pre-treatment with 1 µM IPI-145 inhibits the chemotaxis toward CXCL12; reduces pseudoemperipolesis to median 50%, inferring its ability to interfere with homing capabilities of CLL cells. BCR-activated signaling proteins AKT(Ser473), BAD(Ser112), ERK(Thr202/Tyr204) and S6(Ser235/236) are mitigated by IPI-145. Importantly, for clinical development in hematological malignancies, IPI-145 is selective to CLL B cells, sparing normal B- and T-lymphocytes.

Organ donation awareness project for Piedmont high school students.

FOREWORD: Law no. 91 of April 1, 1999 confirmed the principle of citizens' free choice and awareness with regards the donation of their own organs and tissue. Many studies have shown that information/communication programs aimed at secondary school students are able to significantly increase their propensity toward donation. Students who are made more aware of the topics of donation and transplantation are, in turn, a means of information for their families and acquaintances. METHODS: To be effective, communication must contain both cognitive and emotional elements. This is the principle underlying the development of an awareness-building project that involves the viewing of a play-"Two of Hearts"-telling the story of a transplant patient, followed by a brief scientific presentation aimed at clarifying the basic concepts of transplantation medicine, and then an open discussion between the students and experts. This initiative was promoted by the Piedmont Regional Tissue and Organ Procurement Coordination Agency, the Communication Office of the Piedmont Region, and the Regional Education Office for Piedmont. RESULTS: Seven meetings took place in the main town of each of the provinces that make up the Piedmont Region. These were attended by a total of 1373 students, who were each given an anonymous questionnaire. In all, 785 returned the questionnaire; of these, 95% affirmed that the contents of the meeting had been clearly presented, and 57% stated that they had spoken about it with their family and friends. The project proved be a good tool for communicating with young people and, via them, with their families; at least 2300 people were reached in this way.

Hospital health professionals' education about organ and tissue donation: a Turin hospital experience.

The culture of organ and tissue donation is not particularly well established among the general population, who often receive incorrect, incomplete information. Unfortunately, even among health workers not directly involved in the field of transplantation (laypersons), there is a poor level of knowledge concerning the underlying principles, mechanisms, and results. To increase lay health workers' knowledge and awareness of the importance of donation and transplantation, we organized an educational session for (nurses, doctors, healthcare workers, technicians, and other professionals) at a hospital coordinating service in Turin. The project was divided into 3 phases: first (February 2010), we performed an initial survey using an instrument containing 18 questions. We sought to assess the level of awareness of hospital personnel. Among 880 distributed questionnaires, 346 were compiled and returned to the authors (39.31%). During the second phase, covering the following 24 months, we held 15 educational courses on the subject of transplantation for 483 participants. In the third and last phase (February 2012), we performed a second survey, distributing, 785 questionnaires identical to the previous one, among which 404 were compiled and returned (51.46%).

Organ donation and transplantation in migrants: Piedmont reality from 2004 to 2011.

BACKGROUND: Over the last 20 years, an increasing number of people have immigrated into Italy. On January 1, 2011, there were 4,570,317 foreign residents in Italy, including 398,910 in the Piedmont region (Italian National Statistics Institute data). The Romanian community was the largest, followed by the Moroccan and Albanian ones. The numbers are even layer if we consider illegal immigrants. As a result, the number of foreign people with brain death has increased, as well as the number of foreign people needing organ transplantations. METHODS: The Piedmont Regional Coordination Agency of Tissue and Organ Procurement has analyzed our 1781 brain death situations between January 2004 and December 2011, including 126 (7%) in people not born in Italy (migrants). RESULTS: Non-refusal for donation occurred in 79 cases (62.7%). The agency also analyzed each community looking at number of brain deaths and non-refusals of donation. We utilized 61 donors, for 174 transplantations. Migrants in Italy are not only potential tissue and organ donors, but also potential tissue and organ recipients. Between 2004 and 2011, 222 patients who had not been born in Italy had been transplanted with: a liver (n = 66), a kidney (n = 130), a heart (n = 21) or a lung (n = 5).

Prevention of silica health effects in Italy: current challenges for the Occupational Health and Safety Unit of the Italian National Health Service.

BACKGROUND: Since its foundation in 2002, the Italian Silica Network (NIS), a collaborative network of professionals and public authorities, has been engaged in several aspects of research, control, and prevention of silica exposure and effects, and also in support for compensation claims for silica-related occupational health effects in Italy. METHODS: We start with a report on the NIS point of view concerning the recent scientific results (from epidemiology and laboratory studies), including those carried out by NIS in cooperation with Italian universities and other public agencies. This is followed by a description of the data on silica exposure in different Italian workplaces and guidelines for the management of occupational exposure to silica, as developed by two model regional programmes for the ceramics industry, metal foundries and tunnel excavation. RESULTS: The NIS initiatives highlighted the persistence of workplace conditions posing a significant risk for silica-related health effects, particularly in small industries and workshops. Experimental work has also shown that a number of physical and chemical factors affect the bioreactivity of silica particles. CONCLUSION: Based on NIS experience, it appears clear that currently conditions exist in Italy so as to positively contribute to the WHO Programme for the eradication of silicosis and the other diseases related to silica exposure. In order to achieve this goal, a coordinated and wide-ranging effort is required to reduce the wide gap in specific prevention activities, particularly in small industries and workshops, where high levels of silica exposure sometimes occur.

Effect of dominant negative SNAP-23 expression on platelet function.

BACKGROUND: The protein SNAP-23 is part of the secretory pathway in platelets. It is, however, not entirely clear to what extent this protein contributes to the secretory function of platelets. Therefore, we overexpressed a dominant negative mutant with a novel technology that allows the creation of intact transgene-expressing platetets. RESULTS: Overexpression of a dominant negative SNAP-23 mutant that inhibited the binding of the native protein to the docking site within the secretory machinery resulted in significant suppression of the agonist-dependent surface recruitment of P-selectin and CD40L. Simultaneously, release from dense granules was clearly suppressed in the presence of this construct. Also agonist-dependent surface expression of fibrinogen receptor markers CD41 and CD61 was reduced, and agonist-triggered aggregation was inhibited. CONCLUSION: The dominant negative inhibition of SNAP-23 resulted in clear effects on platelet functions. The novel method using recombinant culture-derived platelets allowed the rapid clarification of the functional importance of this protein in intact platelets.

Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?

BACKGROUND: The suspect carcinogens, heterocyclic amines (HAAs), found in well-done meat require host-mediated metabolic activation before inducing DNA mutations. The role of SULT1A1 and of NAT2 on the activation of HAAs suggests that NAT2 rapid acetylator genotype and SULT1A1 allele variants can have an effect on HAA carcinogenicity. METHODS: Data were collected as part of a case-control study nested within the EPIC cohort, the Gen Air investigation. EPIC is a prospective study designed to investigate the relationship between nutrition and cancer. Information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire. The subjects were restricted to non-smokers. We calculated the matched odds ratio for bladder cancer risk using logistic regression, controlling for potential confounders. RESULTS: There were 227 bladder cases and 612 controls matched 1:3. Meat intake and NAT2 genotype were not independently associated with bladder cancer risk. A significant relationship was observed between bladder cancer risk and consumption of meat only among subjects with the rapid NAT2 genotype (odds ratios [OR] 2.9, 95% CI 1.0-7.9 for the 2nd quartile of meat intake; 3.6, 95% CI 1.3-9.7 for the 3rd quartile; and 3.5, 95% CI 1.2-9.7 for the 4th quartile), and was not present among subjects with the slow genotype. An interaction between NAT2 and meat intake was found in logistic regression (P = 0.034). No association was observed for SULT1A *1/2 genotype (1.0; 95% CI 0.7-1.5) and for SULT1A1 *2/2 genotype (0.9; 95% CI 0.5-1.7). CONCLUSIONS: These results are suggestive of a role of meat intake and NAT2 on bladder cancer risk. They support the hypothesis that among subjects with the rapid NAT2 acetylation genotype higher levels of HAAs exposure are a bladder cancer risk factor. We did not observe an effect of SULT1A1 allele variants on this cancer. The present study adds new information on the possible long-term adverse effects of diets with high meat intake.

Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers.

BACKGROUND: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). PATIENTS AND METHODS: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase II metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). RESULTS: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.

Trait impulsivity in patients with mood disorders.

BACKGROUND: Impulsivity is a key component of the manic behavior of bipolar disorder and is reported to occur in bipolar patients as a stable characteristic, i.e. a trait. Nevertheless, impulsivity has not been widely studied in depressed bipolar patients. We assessed impulsivity in depressed and euthymic bipolar and unipolar patients and healthy controls. We hypothesized that bipolar subjects would have higher levels of trait impulsivity than the comparison groups. METHODS: Twenty-four depressed bipolar, 24 depressed unipolar, 12 euthymic bipolar, and 10 euthymic unipolar patients, as well as 51 healthy subjects were evaluated with the Barratt Impulsiveness Scale (BIS). Analysis of covariance with age and sex as covariates was used to compare mean group differences. RESULTS: Depressed bipolar, euthymic bipolar, and depressed unipolar patients did not differ, and showed greater impulsivity than healthy controls on all of the BIS scales. Euthymic unipolar patients scored higher than healthy controls only on motor impulsivity. LIMITATIONS: Higher number of past substance abusers in the bipolar groups, and no control for anxiety and personality disorders, as well as small sample sizes, limit the reach of this study. CONCLUSIONS: This study replicates prior findings of stable trait impulsivity in bipolar disorder patients, and extends them, confirming that this trait can be demonstrated in depressed patients, as well as manic and euthymic ones. Trait impulsivity may be the result of repeated mood episodes or be present prior to their onset, either way it would influence the clinical presentation of bipolar disorder.

Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions.

It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n=124), lung cancer (n=116) and myeloid leukemia (n=169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P<0.001, mean CVC of 6.60, P=0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C>T (mean prediction error of 22%, P<0.001, mean CVC consistency of 7.40, P<0.037). For leukemia, a 3-loci model including RAD52-2259C>T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P<0.001) and a maximum CVC of 4.40 (P=0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.

Impulsivity and bipolar disorder.

Impulsivity is frequently associated with bipolar disorder (BD) during manic episodes, but may also be present in euthymic bipolar patients. Aggression is an impulsivity-related behavior also found during manic episodes. The objective of this review is to further clarify the relationship between impulsivity and BD. A search in Medline and Psycinfo databases, combined with a manual search of selected references, was conducted to identify available literature on BD and impulsivity-related features. Although few studies have directly measured impulsivity in BD, available findings suggest that impulsivity is not only state-related, but also a trait component of BD, which could represent a core feature of the illness. Further research exploring the neurobiology of the impulsivity/BD relationship may contribute to elucidate the pathophysiology and to improve the diagnosis and treatment of this severe illness.

Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder.

The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, there are few functional neuroimaging studies of MDD patients during working memory processing, and most of the available ones included medicated patients or patients with both MDD and bipolar disorder. We used functional magnetic resonance imaging (fMRI) to measure prefrontal cortex function during working memory processing in untreated depressed patients with MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition recurrent MDD (mean age+/-s.d.=34.3+/-11.5 years) and 15 healthy comparison subjects (37.7+/-12.1 years) matched for age, sex and race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back) was used to elicit frontal cortex activation. Data were analyzed with a multiple regression analysis using the FSL-FEAT software. MDD patients showed significantly greater left dorsolateral cortex activation during the n-back task compared to the healthy controls (P<0.01), although task performance was similar in the two groups. Furthermore, the patients showed significant anterior cingulate cortex activation during the task, but the comparison subjects did not (P<0.01). This study provides in vivo imaging evidence of abnormal frontolimbic circuit function during working memory processing in individuals with MDD.

DNA repair polymorphisms and cancer risk in non-smokers in a cohort study.

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

Reliability of bulky DNA adducts measurement by the nuclease P1 32P-post-labelling technique.

The aim was to assess the reliability of bulky DNA adducts measurement by means of the 32P-post-labelling assay. The research design consisted of an intramethod reliability study. Buffy coats from 41 subjects were used to obtain two aliquots of 1-5 microg DNA for each subject; bulky DNA adducts were measured using the nuclease P1 32P-post-labelling technique. The reliability of the measurement was assessed by means of the intraclass correlation coefficient (ICC), the distribution of the differences between the two measurements and the limits of agreement. The estimated ICC was 0.977, with a 95% confidence interval between 0.921 and 0.977. The limits of agreement were +/- 0.44 (DNA adducts per 10(8) nucleotides). Only three subjects had differences lying out of such limits. Bulky DNA adduct levels measured by the 32P-post-labelling technique showed good reliability. Only one measurement is needed to use DNA adducts as a biomarker of exposure and, possibly, cancer risk. Besides, as a validation analysis, 32P-post-labelling measurements can be repeated in only 20-30% of samples.

Methodology of laboratory measurements in prospective studies on gene-environment interactions: the experience of GenAir.

Several large prospective investigations are under way or are planned in different parts of the world, aiming at the investigation of gene-environment interactions for chronic diseases. Technical, practical and ethical issues are raised by such large investigations. Here we describe how such issues were approached within a case-control study nested in EPIC, a large European cohort, and the kind of validation studies that have been set up. The GenAir investigation aimed at measuring the effects of air pollution and environmental tobacco smoke on human health in EPIC with a nested design and with biological measures. Validation studies included (a) comparisons between cotinine measurements, hemoglobin adducts and questionnaire data; (b) an analysis of the determinants of DNA adduct concentration; (c) comparison among different genotyping methods; (d) an analysis of the determinants of plasma DNA amounts. We also describe how the ethical issues were dealt with in our investigation.

Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study.

OBJECTIVES: To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death. DESIGN: Nested case-control study within the European prospective investigation into cancer and nutrition (EPIC). PARTICIPANTS: 303,020 people from the EPIC cohort (total 500,000) who had never smoked or who had stopped smoking for at least 10 years, 123,479 of whom provided information on exposure to environmental tobacco smoke. Cases were people who developed respiratory cancers or died from respiratory conditions. Controls were matched for sex, age (plus or minus 5 years), smoking status, country of recruitment, and time elapsed since recruitment. MAIN OUTCOME MEASURES: Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people. RESULTS: Over seven years of follow up, 97 people had newly diagnosed lung cancer, 20 had upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema. In the whole cohort exposure to environmental tobacco smoke was associated with increased risks (hazard ratio 1.30, 95% confidence interval 0.87 to 1.95, for all respiratory diseases; 1.34, 0.85 to 2.13, for lung cancer alone). Higher results were found in the nested case-control study (odds ratio 1.70, 1.02 to 2.82, for respiratory diseases; 1.76, 0.96 to 3.23, for lung cancer alone). Odds ratios were consistently higher in former smokers than in those who had never smoked; the association was limited to exposure related to work. Cotinine concentration was clearly associated with self reported exposure (3.30, 2.07 to 5.23, for detectable/non-detectable cotinine), but it was not associated with the risk of respiratory diseases or lung cancer. Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood (hazard ratio 3.63, 1.19 to 11.11, for daily exposure for many hours). CONCLUSIONS: This large prospective study, in which the smoking status was supported by cotinine measurements, confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases, particularly in ex-smokers.

Effects of Soy-derived diets on plasma and liver lipids, glucose tolerance, and longevity in normal, long-lived and short-lived mice.

We examined the effects of diets based on a low isoflavone or a high isoflavone soy protein isolates in normal, growth-hormone receptor knockout and Ames dwarf, and Prop 1 (df) mice that are hypoinsulinemic, insulin-sensitive, and exceptionally long-lived, as well as in growth hormone transgenic mice that are hyperinsulinemic, insulin-resistant, dyslipidemic, and short-lived. Soybean diets tended to normalize plasma cholesterol levels in dwarf and transgenic mice, while low isoflavone diet reduced plasma triglycerides in most of the examined genotypes. The effects of low isoflavone and high isoflavone diets on the levels of free and esterified cholesterol in the liver were strongly genotype-dependent. Fasting blood glucose levels were reduced and glucose tolerance improved by both low isoflavone and high isoflavone diets in growth hormone-transgenic mice and in their normal siblings. Glucose tolerance was also improved by high-isoflavone diet in growth hormone receptor knockout mice. Lifespan was increased by low isoflavone diet in normal mice from two of the examined stocks. High isoflavone diet increased lifespan in normal animals from one line, but reduced lifespan of normal mice from a different line. We conclude that dietary soy protein intake can improve plasma and hepatic lipid profiles, reduce fasting glucose, enhance capacity for glucose tolerance, and prolong life, but all of these effects are strongly genotype-dependent.