Updated assessment of occupational safety and health hazards of climate change.

Workers, particularly outdoor workers, are among the populations most disproportionately affected by climate-related hazards. However, scientific research and control actions to comprehensively address these hazards are notably absent. To assess this absence, a seven-category framework was developed in 2009 to characterize the scientific literature published from 1988-2008. Using this framework, a second assessment examined the literature published through 2014, and the current one examines literature from 2014-2021. The objectives were to present literature that updates the framework and related topics and increases awareness of the role of climate change in occupational safety and health. In general, there is substantial literature on worker hazards related to ambient temperatures, biological hazards, and extreme weather but less on air pollution, ultraviolet radiation, industrial transitions, and the built environment. There is growing literature on mental health and health equity issues related to climate change, but much more research is needed. The socioeconomic impacts of climate change also require more research. This study illustrates that workers are experiencing increased morbidity and mortality related to climate change. In all areas of climate-related worker risk, including geoengineering, research is needed on the causality and prevalence of hazards, along with surveillance to identify, and interventions for hazard prevention and control.

Weaning onto solid foods: some of the challenges.

Weaning--the transition from milk to solid food--influences life-long health. Dietary challenges during weaning include providing sufficient critical nutrients such as iron with minimal added sugar and fat and no added salt. This study assessed the inclusion of iron-containing red meat in infant diets before age one year, and the Irish commercial baby food environment. Of mothers with an infant under 30 months of age who were surveyed in shopping centres in Ireland (n195), 82% (n159) reported wanting more weaning information. A quarter (n24) of infants over age 12 months (n97) received no iron-containing red meat before age one year. A scan of commercial baby foods in Ireland identified 448 products. While all complied with baby food legislation, 15% (n69) were intrinsically high in sugar and fat, or contained added salt. This study indicates the need for specific guidance on best infant feeding practice in Ireland.

Prevalence of overweight and obesity in Irish school children, using four different definitions.

OBJECTIVE: To determine the prevalence of overweight and obesity in Irish children using four different weight-for-height methods and to examine secular trends from previous national data. DESIGN: A cross-sectional survey. Weight and height were measured according to standard procedures and used to determine the prevalence of overweight and obesity using four weight-for-height methods of assessment, actual relative weight, the Centers for Disease Control and Prevention body mass index (BMI) for age charts for boys and girls, the BMI reference curves for the UK 1990 and the International Obesity Task Force age- and sex-specific BMI cutoffs. SETTING: The survey was carried out between 2003 and 2004 in the Republic of Ireland. SUBJECTS: Random representative sample of 596 children aged 5-12 years. RESULTS: The prevalence of overweight and obesity in Irish children is high, but varies considerably with each method. The prevalence of obesity in boys ranged from 4.1 to 11.2 % and in girls from 9.3 to 16.3%. Between 1990 and 2005, depending on the method used, there was a two-to-fourfold increase in obesity in children aged 8-12 years. CONCLUSION: It is evident given the variation displayed in the prevalence of obesity when using the different methods, that there is a discernible need for a single definition to identify the obese child in Ireland. The findings show a high prevalence of overweight and obesity in Irish school children and the increase in the prevalence of obesity over the last 15 years highlights this growing public health issue.

Reducing obesity and related chronic disease risk in children and youth: a synthesis of evidence with 'best practice' recommendations.

Childhood obesity is a global epidemic and rising trends in overweight and obesity are apparent in both developed and developing countries. Available estimates for the period between the 1980s and 1990s show the prevalence of overweight and obesity in children increased by a magnitude of two to five times in developed countries (e.g. from 11% to over 30% in boys in Canada), and up to almost four times in developing countries (e.g. from 4% to 14% in Brazil). The goal of this synthesis research study was to develop best practice recommendations based on a systematic approach to finding, selecting and critically appraising programmes addressing prevention and treatment of childhood obesity and related risk of chronic diseases. An international panel of experts in areas of relevance to obesity provided guidance for the study. This synthesis research encompassed a comprehensive search of medical/academic and grey literature and the Internet covering the years 1982-2003. The appraisal approach developed to identify best practice was unique, in that it considered not only methodological rigour, but also population health, immigrant health and programme development/evaluation perspectives in the assessment. Scores were generated based on pre-determined criteria with programmes scoring in the top tertile of the scoring range in any one of the four appraisal categories included for further examination. The synthesis process included identification of gaps and an analysis and summary of programme development and programme effectiveness to enable conclusions to be drawn and recommendations to be made. The results from the library database searches (13,158 hits), the Internet search and key informant surveys were reduced to a review of 982 reports of which 500 were selected for critical appraisal. In total 158 articles, representing 147 programmes, were included for further analysis. The majority of reports were included based on high appraisal scores in programme development and evaluation with limited numbers eligible based on scores in other categories of appraisal. While no single programme emerged as a model of best practice, synthesis of included programmes provided rich information on elements that represent innovative rather than best practice under particular circumstances that are dynamic (changing according to population subgroups, age, ethnicity, setting, leadership, etc.). Thus the findings of this synthesis review identifies areas for action, opportunities for programme development and research priorities to inform the development of best practice recommendations that will reduce obesity and chronic disease risk in children and youth. A lack of programming to address the particular needs of subgroups of children and youth emerged in this review. Although immigrants new to developed countries may be more vulnerable to the obesogenic environment, no programmes were identified that specifically targeted their potentially specialized needs (e.g. different food supply in a new country). Children 0-6 years of age and males represented other population subgroups where obesity prevention programmes and evidence of effectiveness were limited. These gaps are of concern because (i) the pre-school years may be a critical period for obesity prevention as indicated by the association of the adiposity rebound and obesity in later years; and (ii) although the growing prevalence of obesity affects males and females equally; males may be more vulnerable to associated health risks such as cardiovascular disease. Other gaps in knowledge identified during synthesis include a limited number of interventions in home and community settings and a lack of upstream population-based interventions. The shortage of programmes in community and home settings limits our understanding of the effectiveness of interventions in these environments, while the lack of upstream investment indicates an opportunity to develop more upstream and population-focused interventions to balance and extend the current emphasis on individual-based programmes. The evidence reviewed indicates that current programmes lead to short-term improvements in outcomes relating to obesity and chronic disease prevention with no adverse effects noted. This supports the continuation and further development of programmes currently directed at children and youth, as further evidence for best practice accumulates. In this synthesis, schools were found to be a critical setting for programming where health status indicators, such as body composition, chronic disease risk factors and fitness, can all be positively impacted. Engagement in physical activity emerged as a critical intervention in obesity prevention and reduction programmes. While many programmes in the review had the potential to integrate chronic disease prevention, few did; therefore efforts could be directed towards better integration of chronic disease prevention programmes to minimize duplication and optimize resources. Programmes require sustained long-term resources to facilitate comprehensive evaluation that will ascertain if long-term impact such as sustained normal weight is maintained. Furthermore, involving stakeholders in programme design, implementation and evaluation could be crucial to the success of interventions, helping to ensure that needs are met. A number of methodological issues related to the assessment of obesity intervention and prevention programmes were identified and offer insight into how research protocols can be enhanced to strengthen evidence for obesity interventions. Further research is required to understand the merits of the various forms in which interventions (singly and in combination) are delivered and in which circumstances they are effective. There is a critical need for the development of consistent indicators to ensure that comparisons of programme outcomes can be made to better inform best practice.

Contribution of foods to trans unsaturated fatty acid intake in a group of Irish adults.

OBJECTIVE: To assess fat intake with particular focus on trans unsaturated fatty acid (TUFA) intake and the major sources of TUFA among Irish individuals using a Fat Intake Questionnaire (FIQ), designed specifically for an Irish context. SUBJECTS AND METHODS: A total of 105 healthy volunteers (43 females, 62 males; aged 23-63 years) were recruited from Dublin Airport Medical centre, Republic of Ireland. Dietary intake was assessed using an 88 food item/food group semi-quantitative FIQ, which was developed and validated for the Irish population. RESULTS: Mean energy intake was 10.6 MJ day(-1), and 34% was provided by fat. Saturated, monounsaturated, polyunsaturated, trans unsaturated fatty acids and linoleic acid contributed 13%, 10%, 6%, 2% and 5% of energy respectively. Mean TUFA intake was 5.4 g day(-1) (range 0.3-26). Margarine spreads provided the majority of TUFAs (1.93 g day(-1)), but the contribution was significantly greater for men compared with women (2.35 g day(-1) versus 1.33 g day(-1); P = 0.024). Milk and meat also contributed more to TUFA intake for men compared with women, but confectionery was a significantly greater contributor for women (8.6% versus 3.1% respectively, P = 0.01). CONCLUSIONS: Although the mean TUFA intake of the total group was 5.4 g day(-1) and was within current dietary recommendations (2% energy intake), some individuals had intakes as high as 26 g day(-1). Public health efforts are therefore required to reduce TUFA intake in those individuals with high intakes.

Longitudinal study of effects of alcohol use and/or personal exercise on high density lipoprotein cholesterol in aging humans.

Self-controlled alcohol use and/or personal physical exercise is generally believed to be advantageous in extending good health in aging humans. We investigated whether data collected over 31 years in the same subjects (369 men, 75 women) in our Longitudinal Aging Study of humans (1969-2000) showed strong relationship between alcohol and/or physical exercise with High Density Lipoprotein Cholesterol (HDLC). Women s HDLC interactions among age, diet, alcohol use and/or exercise were not found to be statistically significant in our study. Men, however, showed a strong positive statistical significance (p

Facile entry to the tetracyclic 5-7-6-3 tigliane ring system.

[figure: see text] A tandem anionic 5-exo-dig cyclization/Claisen rearrangement sequence was used to effect a facile, "one-pot" conversion of an appropriately substituted 4-alkyn-1-ol to the tetracyclic carbon core structure of phorbol. The synthesis was conducted using readily available nonracemic starting materials to provide the target structure as a single enantiomer in high chemical yield.

Cardiovascular complications of weight reduction diets.

Weight reduction diets may reduce the severity of risk factors for coronary heart disease such as diabetes mellitus, hypertension, and dyslipidemia. Several case reports and small studies of patients receiving starvation diets have reported hypotension and sudden cardiac death. Myofibrillar damage was documented in 1 case. Very-low-calorie diets are generally safe and well-tolerated. However, low QRS voltage, QT interval prolongation, and both nonsustained ventricular arrhythmias and sudden cardiac death have been described in subjects treated with such diets. Orthostatic hypotension may complicate very-low-calorie protein diets because of sodium depletion and depressed sympathetic nervous system activity. Bariatric surgery is associated with disproportionately high mortality rates in both the perioperative and postoperative periods.

Use of fluorescent microspheres to localize in vivo gene transfer injection sites.

The potential for using gene therapy to treat a variety of disease states is growing rapidly. Many vector types and delivery systems have been developed that allow the optimization of protein production levels and kinetics for a given therapeutic gene product. In cases in which a transient, localized delivery of gene product is desired, any determination of the locale of transfected tissue by non-marker genes is problematic. We describe a technique by which the use of fluorescent microspheres can help in identifying potentially transfected tissue. Adenovirus containing the gene for beta-galactosidase (beta-gal) was mixed with fluorescent microspheres and injected into rat skeletal muscle and porcine myocardium. The injection sites could be visualized under ultraviolet light and correlated with beta-gal enzyme expression. This method is simple, inexpensive and generally useful for in vivo gene transfer experiments.

Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models.

OBJECTIVES: To test the feasibility of myocardial angiogenic gene expression using a novel catheter-based transendocardial injection system. BACKGROUND: Angiogenesis has been induced by direct injection of growth factors into ischemic myocardium during open-heart surgery. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without need of surgery. METHODS: A new guidance system for intramyocardial therapy utilizes magnetic fields and catheter-tip sensors to locate a position in space and reconstruct three-dimensional left ventricular (LV) electromechanical maps without using fluoroscopy. A retractable 27G needle was coupled with the guidance system for LV transendocardial injection. In 12 pigs, the catheter was used to inject 0.1 ml of methylene-blue (MB) dye and 8 pigs had myocardial injections of adenoviral vector (1 x 10(10) particles per site) containing the LacZ transgene. Ten pigs underwent catheter-based transendocardial injection and six pigs were injected using transepicardial approach with the gene encoding adenovirus vascular endothelial growth factor-121 (Ad.VEGF121; 1 x 10(10) viral particles x 6 sites) and sacrificed at 24 h. Injection sites were identified with ultraviolet light by coinjection of fluorescent beads. RESULTS: Overall, 138 of 152 attempted injection MB tracks (91%) were found after sacrifice. Tissue staining was 7.1+/-2.1 mm in depth and 2.3+/-1.8 mm in width. No animal had pericardial effusion or tamponade. In Ad.LacZ injected animals, gross pathology showed positive staining in injected zones, and histology confirmed positive myocyte staining. Adenovirus vascular endothelial growth factor-121 injected sites showed high levels of VEGF121 production that was of similar magnitude whether injected using the transendocardial (880.4+/-412.2 pg VEGF121/mg protein) or transepicardial (838.3+/-270 pg VEGF121/mg protein) delivery approach (p = 0.62). CONCLUSIONS: Using this magnetic guidance catheter-based navigational system, transgenes can effectively be transfected into designated myocardial sites. Thus, if it is determined that direct intramyocardial injection of angiogenic factors enhances collateral function in patients, this less invasive catheter-based system offers a similar gene delivery efficiency and, thus, may have clear advantages compared with the surgically-based transepicardial injection approach.

Butenolide endothelin antagonists with improved aqueous solubility.

Continued development around our ETA-selective endothelin (ET) antagonist 1 (CI-1020) has led to the synthesis of analogues with improved aqueous solubility profiles. Poor solubility characteristics displayed by 1 required a complex buffered formulation in order to conduct iv studies. To overcome the use of specific iv formulations for preclinical studies on additional drug candidates, analogues with improved aqueous solubility were desired. Several analogues were synthesized with substitution patterns that allowed for the formation of either acid or base addition salts. These derivatives had dramatically improved aqueous solubility. In addition, these analogues retained equivalent or improved ETA receptor selectivity and antagonist potency, versus 1, both in vitro and in vivo. Compound 29, which contains as a substituent the sodium salt of a sulfonic acid, has an ETA IC50 = 0.38 nM, ETA selectivity of 4200-fold, and ETA functional activity of KB = 7.8, all of which are similar or superior to those of 1. Compound 29 also has vastly superior aqueous solubility and solubility duration, compared to 1. Furthermore, 29 after iv infusion displays improved activity to 1 in preventing acute hypoxia-induced pulmonary hypertension in rats with an ED50 = 0.3 microg/kg/h.

Dehydroepiandrosterone replacement in aging humans.

Because so much medical and media attention has been drawn to the alleged benefits of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS), it is important to evaluate the effects of replacement therapy objectively using double blind, cross-over, randomized research methodology. In this 9-month study, healthy older men (n = 39) received replacement dose DHEA. Lean body mass, blood hematology, chemistry and endocrine values, as well as urological and psychological data were measured. Data showed some mild and temporary, but significant, changes during oral use of 100 mg DHEA for 3 months compared with placebo taken for 3 months. Body composition did not change during the 6 months of treatment, nor did any urological parameters. Concomitant with the endocrine changes, some small but, significant, variations in blood values (blood urea nitrogen, creatinine, uric acid, alanine transaminase, cholesterol, high density lipoprotein, and potassium) were found. After cessation of DHEA and placebo, followed by 3 months of no treatment, all values previously found to be altered returned to entry baseline. Well publicized effects of the drug reported by others, such as a sense of well-being or improved sexual function, were not found in this study.

Avian osteoclast cells are stimulated to resorb calcified matrices by and possess receptors for leukotriene B4.

Leukotriene B4 (LTB4) is elevated in inflammatory conditions and appears to be a potential mediator of inflammation. We have recently shown that this 5-lipoxygenase metabolite of arachidonic acid stimulates bone resorption in vitro and in vivo. In order to determine the mechanism whereby LTB4 causes bone resorption, avian osteoclasts were examined for the effects of LTB4 and for the presence of LTB4 receptors. Isolated avian osteoclast mononuclear precursor cells, which fuse in culture to form multinucleated cells, were chosen for receptor binding studies because this population is a morphologically similar source of osteoclasts, and large numbers of these cells can be obtained from egg-laying hens. Binding of LTB4 and activation would support the hypothesis of a direct effect of this compound on osteoclasts. LTB4 stimulated isolated avian osteoclasts to form resorption lacunae on calcified matrices and to increase their content of tartrate-resistant acid phosphatase (TRAP), a marker of activated osteoclasts. Receptor binding studies were performed at day 1, when the cells were mononuclear, at day 4, when mononuclear precursors were actively fusing, and at day 7, when fusion has slowed. Scatchard analysis of saturation binding data showed two classes of binding sites, a high- and low-affinity binding site with dissociation constants (KD) of 0.2-0.4 nM and 5. 6-24 nM. Association studies showed rapid binding of LTB4 to the cells within 10 minutes. These data show that LTB4 accelerates fusion and activates highly enriched populations of avian osteoclasts and that LTB4 receptors are present in this cell population.

An approach to the development of food-based dietary guidelines for Ireland.

The aim of the present study was to analyse the different food and nutrient intakes of the adult Irish population from the lowest and highest quartiles of intake for total fat (%energy) dietary fibre (g/MJ) and fruit and vegetables (g/day). Data on Irish adults (n = 715) from the Irish National Nutrition Survey conducted in 1989 were used for the analyses and showed that the average diet is low in dietary fibre, with fruit and vegetables being only half the recommended level of 400 g. Comparisons of people with low or high intakes (from lowest and highest quartiles) of total fat (%energy), dietary fibre (g/MJ) and fruit and vegetables (g/day) show patterns of food intake differing in both the percentage of consumers and in the mean intakes among consumers only. This analysis provides data which may be useful as a first step towards the development of food-based dietary guidelines for Ireland. In particular, the low intake of fruit and vegetables in the adult Irish population deserves special attention.

Endothelin B receptors on human endothelial and smooth-muscle cells show equivalent binding pharmacology.

We have described the pharmacologic profiles of endothelin B receptors in human endothelial cells and vascular and nonvascular smooth-muscle cells. First, by amplifying endothelin B receptor numbers through the use of phosphoramidon and intact cell-binding techniques, we demonstrated the presence of these receptors in human umbilical vein endothelial cells (100% endothelin B receptors), human aortic smooth-muscle cells (22% endothelin B, 78% endothelin A receptors), and human bronchial smooth-muscle cells (55% endothelin B, 45% endothelin A receptors) by using [125I]-endothelin-1 radioligand binding. The typical binding profiles of the endothelin B receptors were established through competition binding curve analysis with endothelin-1, endothelin-3, sarafotoxin 6c, and the endothelin A receptor-selective antagonist BQ-123. In the presence of BQ-123, a diverse group of antagonists, including PD 142893, BQ-788, SB 209670, and Ro 47-0203, were used to probe for binding differences indicative of multiple endothelin B-receptor subtypes. The results indicate a rank order of potency for the antagonists of BQ-788 > SB 209670 > PD 142893 > Ro 47-0203 for each cell line, and that between any of these human cell lines, measurements of [125I]-endothelin-1-binding antagonism for each of the four test compounds differed by less than twofold. Although this study cannot discount the possibility of more than one endothelin B-receptor subtype in humans, it does indicate that these tissues express receptors that show equivalent binding pharmacology.

The pursuit of thinness: a study of Dublin schoolgirls aged 15 y.

Despite increasing trends in the prevalence of overweight and obesity, fatness phobia is common during female adolescence. This study has demonstrated a high level of dissatisfaction with body weight in a sample of Dublin schoolgirls aged 15 y. Of 420 subjects, 59% reported that they wanted to be slimmer and 68% had previously tried to lose weight. Contrary to expectations, overweight girls were not found to hold the monopoly on such dissatisfactions. Normal weight and even underweight girls also expressed a desire to be thinner and reported using unhealthy weight control practices including random avoidance of staple foods, fasting, smoking and purging, in their pursuit of the 'perfect' female figure. Obesity prevention programmes which target adolescent girls 'at risk' of overweight and obesity, must take cognizance of their profound fear of fatness, otherwise the use of harmful slimming strategies may be further increased as teenage girls frantically try to lose weight and to avoid the stigma associated with female fatness.

Atherogenesis and the homocysteine-folate-cobalamin triad: do we need standardized analyses?

BACKGROUND: Bioscientists, physicians and nutritionists are newly interested in the homocysteine-folate-cobalamin triad, in part because homocysteine may be important both in atherogenesis and thrombogenesis. Homocysteine imbalance may be an early marker for cobalamin disorders because cobalamin is a cofactor in remethylation of homocysteine to methionine. METHODS: In 139 men and 32 women of similar mean age of 65 years, we measured markers which have been cited as risk for atherosclerosis: serum homocysteine, folate, total cobalamin, holotranscobalamin I and II, (TCI and TCII), total serum cholesterol (SCHOL), high density lipoprotein cholesterol (HDLC), triglycerides (STG) as well as red blood cell (RBC) folate, food records and body composition by whole body counting of potassium-forty (40K). RESULTS: Statistical relationships among the data showed healthy women had lower mean serum homocysteine and their mean RBC folate and TCI and TCII were higher than men. Eighty-three subjects had TCII much lower than 60 pg/ml (subnormal), yet only 11 of these men and two women had total cobalamin < 200 pg/ml (abnormal). Fifty-two subjects with serum homocysteine greater than 17.5 nmol/ml had TCII less than 60 pg/ml, suggesting serum homocysteine may be a marker for early cobalamin negative balance. None of the subjects in the study had serum folate below abnormal values, i.e., less than 1.6 mg/ml. All subjects had RBC folate within normal range. Serum homocysteine showed inverse relationship with RBC folate and serum total cobalamin, TCI and TCII. CONCLUSIONS: 1) importance of using serum holotranscobalamin TCI and TCII as markers of cobalamin deficiency, 2) necessity to use documented quantitative components of dietary intake if strong comparisons are to be made among quantitative values of serum or plasma homocysteine, folate, cobalamin, and nutrients in food intake.

Risk factors for recurrence of hemorrhagic endovasculitis of the placenta.

OBJECTIVE: To assess the potential for recurrence of placental hemorrhagic endovasculitis and to identify clinical or pathologic cofactors that might influence recurrence of this lesion or subsequent pregnancy outcome. METHODS: Ninety-seven women with a placenta affected by hemorrhagic endovasculitis, who also had at least one placenta referred to the Michigan Placental Tissue Registry from a subsequent pregnancy, were identified from 10,531 referrals between 1978 and 1988. Histologic slides from 209 placentas and clinical data from 211 infants (two sets of twins) from initial (first) and subsequent referrals were analyzed. Placentas were graded for the presence, extent, and severity of hemorrhagic endovasculitis and chronic villitis of unknown etiology; for placental lesions indicative of hypertensive maternal vessel disease; and for intravascular nucleated erythrocytes and chorionic thrombi. Maternal data included age, gravidity, number of previous losses, and history of toxemia or hypertension. All data were analyzed for significance using chi2 and t tests. Outcome assessment was based on recurrence of hemorrhagic endovasculitis and infant viability with the second referral. RESULTS: With first referrals, 80 of 98 infants (81.6%) were stillborn. Among second referrals, 26 of 98 infants (26.5%) were stillborn. Hemorrhagic endovasculitis recurred in 28 second placentas (28.9%); of these, 18 infants (64.3%) were stillborn. Higher rates of recurrence were found with progressively higher first-referral chronic villitis severity scores (P < .02), higher hypertensive placental lesion scores (P < .001), and first referrals with a history of toxemia or hypertension (P < .02). Recurrence of hemorrhagic endovasculitis was higher in patients with two or more of these factors in first referrals (P < .001). Subsequent stillbirth was more frequent with progressively higher first-referral hypertensive placental lesion scores (P < .01) and in first placentas with two or more risk factors (P = .064). Hemorrhagic endovasculitis severity scores, intravascular nucleated erythrocytes, and chorionic thrombi were associated with stillbirth in index pregnancies only. Maternal age, gravidity, or history of prior losses were not predictive. CONCLUSIONS: Placental hemorrhagic endovasculitis is associated with pregnancy loss and can recur in some patients. Interrelations among placental hemorrhagic endovasculitis, chronic villitis, maternal hypertension, and adverse outcomes in subsequent pregnancies are apparent. This information may be useful in patient counseling.