Cadmium exposure and risk of breast cancer: A meta-analysis.

BACKGROUND: Cadmium is a heavy metal with carcinogenic properties, highly prevalent in industrialized areas worldwide. Prior reviews evaluating whether cadmium influences breast cancer have been inconclusive and not reflected several recent studies. OBJECTIVE: To evaluate the association between cadmium exposure and female breast cancer incidence, with an emphasis on separately estimating dietary vs. airborne vs. biomarker measures of cadmium and studies published until October 2022. METHODS: We evaluated risk of bias using set criteria and excluded one study judged to have high risk based on self-report of breast cancer and insufficient adjustment. We conducted a random effects meta-analysis of epidemiological studies, including subgroups by exposure route and by menopausal status. RESULTS: A total of 17 studies were eligible for our meta-analysis. Only 2 studies addressed airborne cadmium directly. Breast cancer risk was elevated in women exposed to higher levels of cadmium across all studies - pooled odds ratio: 1.13 (95% confidence interval: 1.00, 1.28), with notable heterogeneity between studies (I2 = 77%). When examining separately by exposure route, dietary cadmium was not linked with an elevated risk - (OR: 1.05; 95%CI: 0.91, 1.21; I2 = 69%), consistent with prior reviews, but biomarker-based studies showed an elevated but non-significant pooled measure (OR: 1.37; 95%CI: 0.96, 1.94; I2 = 84%). We did not observe any clear patterns of different risk by menopausal status. CONCLUSION: Findings from our meta-analysis suggest that exposure to higher cadmium increases the risk of breast cancer in women, but with remaining questions about whether non-dietary exposure may be more risky or whether residual confounding by constituents of tobacco smoke may be at play.

Cross-regulation of Hox genes in the Drosophila melanogaster embryo.

Cross-regulation of Homeotic Complex (Hox) genes by ectopic Hox proteins during the embryonic development of Drosophila melanogaster was examined using Gal4 directed transcriptional regulation. The expression patterns of the endogenous Hox genes were analyzed to identify cross-regulation while ectopic expression patterns and timing were altered using different Gal4 drivers. We provide evidence for tissue specific interactions between various Hox genes and demonstrate the induction of endodermal labial (lab) by ectopically expressed Ultrabithorax outside the visceral mesoderm (VMS). Similarly, activation and repression of Hox genes in the VMS from outside tissues seems to be mediated by decapentaplegic (dpp) gene activation. Additionally, we find that proboscipedia (pb) is activated in the epidermis by ectopically driven Sex combs reduced (Scr) and Deformed (Dfd); however, mesodermal pb expression is repressed by ectopic Scr in this tissue. Mutant analyses demonstrate that Scr and Dfd regulate pb in their normal domains of expression during embryogenesis. Ectopic Ultrabithorax and Abdominal-A repress only lab and Scr in the central nervous system (CNS) in a timing dependent manner; otherwise, overlapping expression in the CNS in tolerated. A summary of Hox gene cross-regulation by ectopically driven Hox proteins is tabulated for embryogenesis.

Homeotic Complex (Hox) gene regulation and homeosis in the mesoderm of the Drosophila melanogaster embryo: the roles of signal transduction and cell autonomous regulation.

In this paper we evaluate homeosis and Homeotic Complex (Hox) regulatory hierarchies in the somatic and visceral mesoderm. We demonstrate that both Hox control of signal transduction and cell autonomous regulation are critical for establishing normal Hox expression patterns and the specification of segmental identity and morphology. We present data identifying novel regulatory interactions associated with the segmental register shift in Hox expression domains between the epidermis/somatic mesoderm and visceral mesoderm. A proposed mechanism for the gap between the expression domains of Sex combs reduced (Scr) and Antennapedia (Antp) in the visceral mesoderm is provided. Previously, Hox gene interactions have been shown to occur on multiple levels: direct cross-regulation, competition for binding sites at downstream targets and through indirect feedback involving signal transduction. We find that extrinsic specification of cell fate by signaling can be overridden by Hox protein expression in mesodermal cells and propose the term autonomic dominance for this phenomenon.

A comparison of health care experiences for medicaid and commercially enrolled children in a large, nonprofit health maintenance organization.

BACKGROUND: Proponents of Medicaid managed care have argued that this type of care offers the potential to provide mainstream health care for poor children and the elimination of the 2-tier system of care that has long existed for poor and nonpoor children. However, few studies have attempted to assess whether differences in access, utilization, and satisfaction exist between Medicaid and commercially sponsored children who are enrolled in the same managed care plan. OBJECTIVE: To systematically answer the following research question: Within the same large, nonprofit, group-model health maintenance organization (HMO), how do children enrolled in Medicaid compare with children enrolled commercially across the domains of access, utilization, and satisfaction with care? METHODS: We compared access, satisfaction, and utilization of services between Medicaid and commercially sponsored children enrolled in Kaiser Permanente of Northern California during 1998 through use of a telephone survey and administrative data. Kaiser Permanente is a nonprofit, integrated, group HMO that serves 2.8 million members in more than 15 counties in northern California. The sample for this survey included 510 Medicaid-enrolled children and 512 commercially enrolled children. An overall response rate of 82% was achieved. Bivariate and multivariate analyses were used to compare Medicaid and commercially enrolled children. RESULTS: We found few differences between commercial and Medicaid enrollees across the domains of access, utilization, and satisfaction. Where access differences were present (problems in finding a personal care provider, problems getting care overall, and experiencing 1 or more barriers to care), the differences favored Medicaid-enrolled children. That is, Medicaid enrollees were reported to experience significantly fewer access problems and barriers than commercial enrollees, even after adjustment for confounding factors. Only one difference was found between Medicaid and commercial enrollees across the 6 utilization variables examined (volume of emergency department visits), and no differences were found among the 4 satisfaction and 2 global assessments of care received. Taken together, our results suggest that Medicaid-enrolled children experience as good as or better care than their commercially enrolled counterparts. However, there are other possible explanations for our findings. It may be that families of Medicaid-enrolled children hold their care providers to a lower standard than families of commercially enrolled children, given historic inequities in care between poor and nonpoor families. In addition, some degree of selection bias may be present in our sample, although that is true for both the Medicaid and commercial populations. CONCLUSIONS: Our findings suggest that large commercial HMOs are capable of eliminating the access barriers and stigma traditionally associated with the Medicaid program. However, this conclusion must be tempered with the knowledge that other explanations for our findings may also be at play.

Changes in dendritic morphology of rat spinal motoneurons during development and after unilateral target deletion.

During normal development, motoneuron dendrites in the spinal nucleus of the bulbocavernosus (SNB) grow exuberantly to almost twice their adult length and then retract. In this study, we retrogradely labeled SNB motoneurons with cholera toxin B-conjugated horseradish peroxidase (BHRP) to examine the maturation of SNB dendritic arbors in more detail, particularly with regard to its spatial distribution and reorganization. The number and orientation of SNB motoneuron primary processes did not change over the first ten weeks of life. In contrast, total dendritic length, radial extent and arbor area increased significantly through the first four postnatal weeks and declined thereafter. The declines in length and extent were restricted to particular portions of the arbor, specifically the dorsal, ipsi- and contralateral projections. Estimates of the degree of overlap between the dendritic arbors from both sides of the SNB reflected these changes, with overlap initially increasing and then decreasing as the SNB established its adult dendritic morphology. To determine if dendritic interactions facilitated by this arbor overlap might be involved in regulating the normal retraction of SNB dendrites, we reduced SNB motoneuron numbers unilaterally by target muscle removal on the day of birth. Somal size, number and orientation of primary processes developed normally in unilateral muscle-extirpated animals. The dendritic morphology of surviving SNB motoneurons in unilateral muscle extirpated males was altered, with significant increases in dendritic length, extent and arbor area relative to those of normal males. These results indicate that substantial changes in dendritic organization of SNB motoneurons occur in normal development and may be influenced by interactions between dendrites from the two halves of the SNB.