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PubMed2003

Characterization of chemical exposures in hairdressing salons.

Workers in hairdressing salons are exposed to several hundred chemicals, of which a few are possibly detrimental to pregnant workers or their fetuses. In Quebec, a government program provides protective reassignment for exposed pregnant workers. This study was set up to assist public health physicians by describing the exposure levels for ingredients that were measurable (i.e., airborne), selected from a list of possibly detrimental hairdressing ingredients. Twenty-six salons were sampled in Montreal, Canada, between June 1996 and December 1997. At the time of sampling, information on certain work conditions (e.g., chemical services offered, number of clients, average CO(2) level during the day) was also noted. Fifty percent of the salons provided additional services other than hairdressing, such as manicures, pedicures, or beauty treatments. Almost half of the salons were quite small, with less than 5 employees. Average temperature ranged between 17 and 26 degrees C, relative humidity between 18 and 59 percent and average CO(2) concentrations from 583 to 4301 mg/m(3). Duration of samples varied between 15 minutes and 8 hours. The most prevalent chemicals were alcohols: ethanol, at an average personal concentration of 39.9 mg/m(3), and isopropanol at an average personal concentration of 3.1 mg/m(3). Acetone, toluene, and acetates, all related to manicure services, were also measured in small quantities. An empirical mathematical model brought in evidence that CO(2) levels explained 46 percent of variation in the concentration of ethanol; when number of permanent waves done during the day and relative humidity and temperature were added, the resulting model explained 68 percent of the variations in ethanol. Thus, although the measured concentrations of chemicals were fairly low in this study, it appears possible that on very busy days, especially if other chemical services are performed in the salon, the total mixture of airborne chemicals could reach significant concentrations.

Air Pollutants, Occupational↗
PubMed2005

Iodine excretion in regions of Ukraine affected by the Chornobyl Accident: experience of the Ukrainian-American cohort study of thyroid cancer and other thyroid diseases.

Urinary iodine concentrations were measured in 11,926 subjects who are participants in the Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident. Measurements were made in two time periods corresponding to the first and second thyroid screening cycles (1998-2000, 2001-2003). These time periods fall before and after initiation of a government program to increase iodine sufficiency. Median urinary iodine concentrations did increase in the later time period compared to the earlier [47.5 microg/L, 95% confidence interval (CI) 46.5-48.9 microg/L versus 41.7 microg/L, 95% CI 40.4-42.5 microg/L], but levels remained in the mild-to-moderate iodine deficiency range as defined by the World Health Organization (WHO), indicating the need for further efforts at iodination. In both time periods, urinary iodine levels were found to vary by place of residence and were lower in rural compared to urban areas. Iodine status needs to be considered when evaluating risk of thyroid cancer and other thyroid diseases.

Adolescent↗
PubMed2026

RNA splicing and cardiovascular disease: a guide for cardiologists.

Alternative splicing (AS) is a fundamental RNA processing mechanism, which generates different RNA transcripts and consequently different protein isoforms from a single gene. This increases the diversity of proteins within an organism and can fine-tune biological processes. This review examines how cardiac-enriched RNA-binding proteins establish heart-specific splicing programs governing aspects of cardiac development, function, and disease. Developmentally, coordinated sarcomeric isoform switches underpin the foetal-to-adult transition and further isoform rewiring in ion channel and kinase genes determine electrophysiology and excitation-contraction coupling. AS contributes to the pathogenesis of several cardiomyopathies and emerging datasets suggest that pathological hypertrophy engages distinct splicing signatures compared with physiological hypertrophy. This review summarizes diagnostic and prognostic opportunities arising from bulk, long-read, and single-cell/nucleus transcriptomics, which resolve cell type-specific isoforms and disease-associated switches. Circulating RNA biomarkers (including splice ratios and circularRNAs) may signify myocardial remodelling and arrhythmic risk. Integrative approaches that link AS with proteomics and genomics improve variant interpretation, reveal previously unannotated protein isoforms, and enable tracking of disease progression and therapy response. Finally, an outline of therapeutic strategies to modulate AS in cardiovascular disease (CVD), including antisense oligonucleotides, small molecules, and genome-editing modalities (CRISPR, base, and prime editing), is provided. The major challenges that remain before splice-targeting therapeutics can be targeted to treat cardiovascular disease are highlighted. Lessons from neuromuscular indications establish clinical feasibility of splicing correction and motivate translation to cardiology. Together, mechanistic insight, biomarker development, and therapeutic innovation position RNA splicing as a tractable axis for precision cardiovascular medicine.

Humans↗
PubMed2001

Changing attitudes toward aging policy in the United States during the 1980s and 1990s: a cohort analysis.

OBJECTIVES: This research assessed how the attitudes of Americans toward government programs that serve older people changed between the mid-1980s and late 1990s and how much of the shift was dueto intracohort change and how much was due to cohort replacement. METHODS: Data come from three nationally representative cross-sectional samples, surveyed by telephone in 1986 (N = 1.209), 1990 (N = 1,500), and 1997 (N = 1,559). RESULTS: Attitudes of Americans have become less supportive of expanding entitlement programs for older people and more supportive of cutting their costs and benefits. Between 1986 and 1997, most cohorts, particularly older adults, grew more in favor of maintaining Social Security benefit levels but less in favor of expanding them. Young adults tended to be driving the societal shift in attitudes toward decreasing benefits. Intercohort change was more important than cohort replacement in this process. Analyses of change in 2 attitude domains between 1990 and 1997 revealed that the general population felt less strongly that older people are entitled to benefits and expressed greater opposition to the associated costs. However, young adults moderated their concerns about costs as they got older, although the young adults in the cohort replacing them had become more critical of the principle of entitlement. DISCUSSION: These findings enhance the understanding of the roles that historical conditions and aging play in shaping the attitudes of adult cohorts toward public programs for older citizens. Discrepant findings based on the intercohort change in younger age groups are reconciled by differentiating maturation effects from period effects on impressionable youth.

Adolescent↗
PubMed2003

Macro- and microlevel processes affect food choice and nutritional status in the republic of the marshall islands.

Despite its relative isolation from the world stage and lack of resources, the Marshall Islands serve as an example of the interaction between global political power, macroeconomic forces and local cultural factors. At the national level, patterns of food importation and government programs encourage the consumption of high fat foods. These factors have fostered dependency on Western foods and a loss of traditional food practices. Beliefs come into play as microlevel factors that influence food choice and aspects of lifestyle. Nearly three quarters of women are overweight or obese in this setting. Obesity in women is associated with greater age, higher education and more imported food consumption. Over a third of children ages 1-5 y are stunted, with stunting associated with worse economic status, less active feeding, increased consumption of imported foods and urban residence. What can be done at the microlevel is constrained by macrolevel factors of disempowerment. In this way, issues of power and belief are played out in the bodies of individuals.

Adult↗
PubMed2003

Diet, individual responsiveness and cancer prevention.

Dietary recommendations for the prevention of cancer have been based predominantly on large epidemiological studies of diet and lifestyle, conducted 20, and in some cases, almost 30 years ago. Government programs have been successful in educating the public about the benefits of eating fruits and vegetables, yet despite these efforts, Americans have become heavier, diabetes is more prevalent and general health indicators have not greatly improved. Individual response to dietary recommendations may be complicated by a variety of factors. Polymorphisms in genes related to drug activation and detoxification, folate metabolism, DNA repair, vitamin receptors and other cellular receptors could account for a lack of benefit at the level of the individual for consuming cancer preventive foods. Beyond consideration of genetic polymorphisms, the last half century has brought stark changes in lifestyle that depart from normal diurnal cycle and periodic fluctuations in food availability. Thus, modern times may be characterized as being constantly in a "feast" environment. The cellular consequences may be an increase in risk for several diseases including cancer.

Animals↗
PubMedDate not supplied

Moving further upstream: from toxics reduction to the precautionary principle.

Early policies to reduce the amount of toxic waste in the environment focused on cleaning up downstream sources of pollution, such as toxic disposal sites. Public attention in the 1980s encouraged both industry and government to develop an alternative to this command-and-control approach. This article describes the emergence of that alternative-pollution prevention-and its application in Massachusetts through the 1989 Toxics Use Reduction Act. Pollution prevention focuses on the sources of pollution, both metaphorically and physically, more upstream than its predecessors. The success of the Toxics Use Reduction Act in Massachusetts helped create an opportunity where an alternative pollution prevention paradigm could develop. That paradigm, the precautionary principle, is popular among environment activists because it focuses further upstream than pollution prevention by calling attention to the role the social construction of risk plays in decisions regarding the use of hazardous substances. The authors examine the evolution of the precautionary principle through an investigation of three major pathways in its development and expansion. The article concludes with a discussion of the increased potential for protecting public health and the environment afforded by this new perspective.

Community Participation↗
PubMed2004

Rapamycin attenuates vascular wall inflammation and progenitor cell promoters after angioplasty.

Rapamycin combines antiproliferative and antiinflammatory properties and reduces neointima formation after angioplasty in patients. Its effect on transcriptional programs governing neointima formation has not yet been investigated. Here, we systematically analyzed the effect of rapamycin on gene expression during neointima formation in a human organ culture model. After angioplasty, renal artery segments were cultured for 21 or 56 days in absence or presence of 100 ng/ml rapamycin. Gene expression analysis of 2312 genes revealed 264 regulated genes with a peak alteration after 21 days. Many of those were associated with recruitment of blood cells and inflammatory reactions of the vessel wall. Likewise, chemokines and cytokines such as M-CSF, IL-1beta, IL-8, beta-thromboglobulin, and EMAP-II were found up-regulated in response to vessel injury. Markers indicative for a facilitated recruitment and stimulation of hematopoetic progenitor cells (HPC), including BST-1 and SDF-1, were also induced. In this setting, rapamycin suppressed the coordinated proadhesive and proinflammatory gene expression pattern next to down-regulation of genes related to metabolism, proliferation, and apoptosis. Our study shows that mechanical injury leads to induction of a proinflammatory, proadhesive gene expression pattern in the vessel wall even in absence of leukocytes. These molecular events could provide a basis for the recruitment of leukocytes and HPC. By inhibiting the expression of such genes, rapamycin may lead to a reduced recruitment of leukocytes and HPC after vascular injury, an effect that may play a decisive role for its effectiveness in reducing restenosis.

Aged↗
PubMed1994

Radiocesium in the Savannah River Site environment.

The Savannah River Site has produced plutonium, tritium, and other special nuclear materials for national defense, other government programs, and some civilian purposes. Radiocesium, a waste product, has been released to the environment during the operation of five reactors, two radio-chemical processing facilities, and a high-level waste storage system. During the period 1955-1989, 130 GBq of 137Cs was released to the atmosphere and 2.2 x 10(4) GBq was released to site streams and ponds. Approximately 65% of the latter remained on the site. The maximum individual effective dose equivalent at the site boundary was estimated to be 3.3 microSv from atmospheric releases and 600 microSv from liquid releases. The 80-km population dose was 1.6 person-Sv.

Air Pollutants, Radioactive↗
PubMed1996

Plutonium in the Savannah River Site environment.

The Savannah River Site has produced plutonium, tritium, and other special nuclear materials for national defense, other government programs, and some civilian purposes. Plutonium has been released to the environment during the operation of five reactors, two radiochemical processing facilities, and other supporting facilities. During the period 1954-1989, 140 GBq of plutonium were released to the atmosphere and 23 GBq were released to site streams and ponds. The maximum individual effective dose equivalent at the site boundary was estimated to be 120 microSv from atmospheric releases and 2.4 microSv from liquid releases. The 80-km population dose was 7.1 person-Sv.

Humans↗
PubMed1999

Radiostrontium in the Savannah river site environment.

The Savannah River Site has produced plutonium, tritium, and other special nuclear materials for national defense, other government programs, and some civilian purposes. Strontium has been released to the environment during the operation of five reactors, two radiochemical processing facilities, and other supporting facilities. During the period 1954-1996, 110 GBq of 90Sr were released to the atmosphere and 5,400 GBq were released to site streams. The maximum individual effective dose equivalent at the site boundary was estimated to be 72 microSv from atmospheric releases and 25 microSv from liquid releases. The 80-km population dose was 0.3 person-Sv.

Air Pollutants, Radioactive↗
PubMed2003

The value of therapeutic communities in the treatment of personality disorder: a suitable place for treatment?

In the United Kingdom, a government program investigating the links between offending and personality disorder has stimulated renewed interest in the treatment of personality disorders. One psychosocial treatment option for patients with personality disorders is the therapeutic community (TC). In 2000, the authors conducted a small qualitative study with a sample of psychiatrists which suggested that TCs were not well understood and that the status of evidence on efficacy might be partly responsible for low referral numbers. This article reviews the evidence for the efficacy and cost-effectiveness of TCs as a treatment for personality disorders and considers which types of disorders are amenable to TC treatment. We conclude that there is a strong case for more rigorous evaluation and that some of the difficulties anticipated in applying randomized clinical trial (RCT) methodology to the study of TCs could be overcome.

Journal Article↗
PubMed2003

GATA-3: an unexpected regulator of cell lineage determination in skin.

Multipotent skin stem cells give rise to epidermis and its appendages, including the hair follicle. The Lef-1/Tcf family of Wnt-regulated transcription factors plays a major role in specification of the hair shaft, but little is known about how the equally important hair channel, the inner root sheath (IRS), develops in concert to shape and guide the hair. In a microarray screen to search for transcriptional regulators of hair follicle morphogenesis, we identified GATA-3, a key regulator of T-cell lineage determination. Surprisingly, this transcription factor is essential for stem cell lineage determination in skin, where it is expressed at the onset of epidermal stratification and IRS specification in follicles. GATA-3-null/lacZ knock-in embryos can survive up to embryonic day 18.5 (E18.5), when they fail to form the IRS. Skin grafting unveiled additional defects in GATA-3-null hairs and follicles. IRS progenitors failed to differentiate, whereas cortical progenitors differentiated, but produced an aberrant hair structure. Curiously, some GATA-3-null progenitor cells expressed mixed IRS and hair shaft markers. Taken together, these findings place GATA-3 with Lef-1/Wnts at the crossroads of the IRS versus hair shaft cell fate decision in hair follicle morphogenesis. This newfound function for GATA-3 in skin development strengthens the parallels between the differentiation programs governing hair follicle and lymphocyte differentiation.

Animals↗
PubMed2004

Hoxb1 functions in both motoneurons and in tissues of the periphery to establish and maintain the proper neuronal circuitry.

Formation of neuronal circuits in the head requires the coordinated development of neurons within the central nervous system (CNS) and neural crest-derived peripheral target tissues. Hoxb1, which is expressed throughout rhombomere 4 (r4), has been shown to be required for the specification of facial branchiomotor neuron progenitors that are programmed to innervate the muscles of facial expression. In this study, we have uncovered additional roles for Hoxb1-expressing cells in the formation and maintenance of the VIIth cranial nerve circuitry. By conditionally deleting the Hoxb1 locus in neural crest, we demonstrate that Hoxb1 is also required in r4-derived neural crest to facilitate and maintain formation of the VIIth nerve circuitry. Genetic lineage analysis revealed that a significant population of r4-derived neural crest is fated to generate glia that myelinate the VIIth cranial nerve. Neural crest cultures show that the absence of Hoxb1 function does not appear to affect overall glial progenitor specification, suggesting that a later glial function is critical for maintenance of the VIIth nerve. Taken together, these results suggest that the molecular program governing the development and maintenance of the VIIth cranial nerve is dependent upon Hoxb1, both in the neural crest-derived glia and in the facial branchiomotor neurons.

Animals↗
PubMed1992

America's children: economic perspectives and policy options.

American children are worse off than those in the previous generation in several important dimensions of mental, physical, and emotional well-being. During the 1960s cultural changes adversely affected children while their material condition improved substantially. By contrast, material conditions deteriorated in the 1980s, especially among children at the lower end of the income distribution. Public policies to improve the material condition of children require a transfer of resources from households that do not have children to those that do. Government programs such as tax credits and child allowances are more efficient and equitable than employer-mandated programs.

Adult↗
PubMed2001

The health of U.S. hired farm workers.

Despite a recent surge in knowledge about U.S. hired farm workers, little is known about the health of this population. No national data are available on the size of the population, mortality or morbidity data, or on chronic health indicators. Demographic data show that these workers are mostly Mexican immigrant or migrant males, and nearly two thirds live in poverty. At least half of all current hired farm workers are undocumented. Fewer than one in five have health insurance, either through their employer or through government programs. However, programs targeting women farm workers, such as WIC or, in California, emergency MediCal, are more effective in helping them obtain needed services. The federal Migrant Health Program serves about 13% of the total of workers plus dependent family members. This paper reviews what is known in the following topical areas: (a) mortality and morbidity; (b) access to health care services; (c) control of infectious diseases; (d) maternal and child care; (e) occupational health; (f) violence; and (g) chronic health indicators. It is suggested that future research incorporate a minimal physical examination of all patients or subjects in order to establish baseline information for the population. Such information will be helpful in targeting interventions and measuring their effectiveness.

Agriculture↗
PubMed2004

Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner.

Recent evidence has identified the peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) as a regulator of cardiac energy metabolism and mitochondrial biogenesis. We describe the development of a transgenic system that permits inducible, cardiac-specific overexpression of PGC-1alpha. Expression of the PGC-1alpha transgene in this system (tet-on PGC-1alpha) is cardiac-specific in the presence of doxycycline (dox) and is not leaky in the absence of dox. Overexpression of PGC-1alpha in tet-on PGC-1alpha mice during the neonatal stages leads to a dramatic increase in cardiac mitochondrial number and size coincident with upregulation of gene markers associated with mitochondrial biogenesis. In contrast, overexpression of PGC-1alpha in the hearts of adult mice leads to a modest increase in mitochondrial number, derangements of mitochondrial ultrastructure, and development of cardiomyopathy. The cardiomyopathy in adult tet-on PGC-1alpha mice is characterized by an increase in ventricular mass and chamber dilatation. Surprisingly, removal of dox and cessation of PGC-1alpha overexpression in adult mice results in complete reversal of cardiac dysfunction within 4 weeks. These results indicate that PGC-1alpha drives mitochondrial biogenesis in a developmental stage-dependent manner permissive during the neonatal period. This unique murine model should prove useful for the study of the molecular regulatory programs governing mitochondrial biogenesis and characterization of the relationship between mitochondrial dysfunction and cardiomyopathy and as a general model of inducible, reversible cardiomyopathy.

Adenosine Triphosphate↗