Tenure and Turnover Among State Health Officials From the SHO-CASE Survey: Correlates and Consequences of Changing Leadership.

OBJECTIVE: To examine characteristics associated with tenure length of State Health Officials (SHOs) and examine reasons and consequences for SHO turnover. DESIGN: Surveys of current and former SHOs linked with secondary data from the United Health Foundation. SETTING: Original survey responses from SHOs in the United States. PARTICIPANTS: Respondents included SHOs who served between 1973 and 2017. MAIN OUTCOME MEASURES: Tenure length and consequences of SHO turnover. RESULTS: Average completed tenure among SHOs was 5.3 years (median = 4) and was shorter in recent time periods compared with decades prior. Older age at appointment (ß = -0.109, P = .005) and those holding a management degree (ß = -1.835, P = .017) and/or a law degree (ß = -3.553, P < .001) were each associated with shorter SHO tenures. State Health Officials from states in the top quartile for health rankings had significantly longer average tenures (ß = 1.717, P = .036). Many former SHOs believed that their tenure was too short and reported that their departure had either a significant or very large effect on their agency's ability to fulfill its mission. CONCLUSIONS: State Health Official tenures have become shorter over time and continue to be shorter than industry chief executive officers and best practice recommendations from organizational researchers. States have an opportunity to consider and address how factors within their control influence the stability of the SHO position.

Ontogenetic alterations in molecular and structural correlates of dendritic growth after developmental exposure to polychlorinated biphenyls.

OBJECTIVE: Perinatal exposure to polychlorinated biphenyls (PCBs) is associated with decreased IQ scores, impaired learning and memory, psychomotor difficulties, and attentional deficits in children. It is postulated that these neuropsychological deficits reflect altered patterns of neuronal connectivity. To test this hypothesis, we examined the effects of developmental PCB exposure on dendritic growth. METHODS: Rat dams were gavaged from gestational day 6 through postnatal day (PND) 21 with vehicle (corn oil) or the commercial PCB mixture Aroclor 1254 (6 mg/kg/day). Dendritic growth and molecular markers were examined in pups during development. RESULTS: Golgi analyses of CA1 hippocampal pyramidal neurons and cerebellar Purkinje cells indicated that developmental exposure to PCBs caused a pronounced age-related increase in dendritic growth. Thus, even though dendritic lengths were significantly attenuated in PCB-treated animals at PND22, the rate of growth was accelerated at later ages such that by PND60, dendritic growth was comparable to or even exceeded that observed in vehicle controls. Quantitative reverse transcriptase polymerase chain reaction analyses demonstrated that from PND4 through PND21, PCBs generally increased expression of both spinophilin and RC3/neurogranin mRNA in the hippocampus, cerebellum, and cortex with the most significant increases observed in the cortex. CONCLUSIONS: This study demonstrates that developmental PCB exposure alters the ontogenetic profile of dendritogenesis in critical brain regions, supporting the hypothesis that disruption of neuronal connectivity contributes to neuropsychological deficits seen in exposed children.

Increased [3H]phorbol ester binding in rat cerebellar granule cells and inhibition of 45Ca(2+) buffering in rat cerebellum by hydroxylated polychlorinated biphenyls.

Our previous structure-activity relationship (SAR) studies indicated that the effects of polychlorinated biphenyls (PCBs) on neuronal Ca(2+) homeostasis and protein kinase C (PKC) translocation were associated with the extent of coplanarity. Chlorine substitutions at ortho position on the biphenyl, which increase the non-coplanarity, are characteristic of the most active congeners in vitro. In the present study, we investigated the effects of selected hydroxylated PCBs, which are major PCB metabolites identified in mammals, on the same measures where PCBs had differential effects based on structural configuration. These measures include PKC translocation as determined by [3H]phorbol ester ([3H]PDBu) binding in cerebellar granule cells, and Ca(2+) sequestration as determined by 45Ca(2+) uptake by microsomes isolated from adult rat cerebellum. All the selected hydroxy-PCBs with ortho-chlorine substitutions increased [3H]PDBu binding in a concentration-dependent manner and the order of potency as determined by E(50) (concentration that increases control activity by 50%) is 2',4',6'-trichloro-4-biphenylol (32 +/- 4 microM), 2',5'-dichloro-4-biphenylol (70 +/- 9 microM), 2,2',4',5,5'-pentachloro-4-biphenylol (80 +/- 7 microM) and 2,2',5'-trichloro-4-biphenylol (93 +/- 14 microM). All the selected hydroxy-PCBs inhibited microsomal 45Ca(2+) uptake to a different extent. Among the hydroxy-PCBs selected, 2',4',6'-trichloro-4-biphenylol is the most active in increasing [3H]PDBu binding as well as inhibiting microsomal 45Ca(2+) uptake. 3,5-Dichloro-4-biphenylol and 3,4',5-trichloro-4-biphenylol did not increase [3H]PDBu binding, but inhibited microsomal 45Ca(2+) uptake. This effect was not related to ionization of these two hydroxy-PCBs. Hydroxylated PCBs seemed to be as active as parent PCBs in vitro. These studies indicate that PCB metabolites such as hydroxy-PCBs might contribute significantly to the neurotoxic responses of PCBs.

Morphological alterations and elevations in tumor necrosis factor-alpha, interleukin (IL)-1alpha, and IL-6 in mixed glia cultures following exposure to trimethyltin: modulation by proinflammatory cytokine recombinant proteins and neutralizing antibodies.

Trimethyltin (TMT), is a hippocampal neurotoxicant characterized by neuronal degeneration, astrogliosis, and microglia reactivity with an associated elevation in proinflammatory cytokine mRNA levels. To examine the role of proinflammatory cytokines in the TMT-induced glia response, mixed cortical glia cultures were exposed to TMT and morphological and cytokine responses were examined. Morphological changes in the glia monolayer, enlarged, rounded cell bodies and retraction of the monolayer into distinct GFAP+ dense processes, displayed a dose (1, 5, and 10 microM TMT) and temporal response (6-48 h), accompanied by clustering of OX-42+ microglia. Tumor necrosis factor-alpha (TNF), interleukin (IL)-1alpha, and IL-6 mRNA levels were elevated by 3 and 6 h of TMT (10 microM) and proteins by 24 h. Recombinant proteins for IL-1alpha (100 pg/ml) and IL-6 (10 ng/ml) exacerbated the morphological response to TMT while those for TNFalpha (150 pg/ml) did not. Neutralizing antibodies (1:100) to IL-1alpha and IL-6 showed a slight decrease in the severity of the morphological response to TMT while, at 24 h, TNFalpha antibodies (1:100) and an antibody cocktail offered a significant level of protection. At 6 h, the neutralizing antibodies to TNFalpha or IL-1alpha did not elevate basal cytokine mRNA levels, however, IL-6 and the cocktail of antibodies significantly elevated IL-1alpha, IL-1beta, and IL-6 mRNA levels. The specific elevation in IL-1alpha and IL-6 mRNA levels induced by TMT remained evident only in cells coexposed to anti-TNFalpha. Similar responses in cytokine mRNA levels were seen in cocultures of hippocampal neurons and glia exposed to TMT. These data suggest a relationship between microglia activation, proinflammatory cytokine release, and glia morphological responses, the significance of which remains to be determined, as well as, the impact on neuronal degeneration.