Relations of income inequality and family income to chronic medical conditions and mental health disorders: national survey

ObjectivesTo analyse the relation between geographical inequalities in income and the prevalence of common chronic medical conditions and mental health disorders, and to compare it with the relation between family income and these health problems.Design Nationally representative household telephone survey conducted in 1997-8.Setting 60 metropolitan areas or economic areas of the United States.Participants 9585 adults who participated in the community tracking study.Results A strong continuous association was seen between health and education or family income. No relation was found between income inequality and the prevalence of chronic medical problems or depressive disorders and anxiety disorders, either across the whole population or among poorer people. Only self reported overall health, the measure used in previous studies, was significantly correlated with inequality at the population level, but this correlation disappeared after adjustment for individual characteristics.Conclusions This study provides no evidence for the hypothesis that income inequality is a major risk factor for common disorders of physical or mental health.

What is already known on this topic

Several studies have found a relation between income inequality and self reported health or mortality

What this study adds

There is a strong social gradient in health, as measured by the prevalence of chronic medical conditions and specific mental health disorders, by income or educationNo such association is seen between income inequality and health     

Siglec-9 defines and restrains a natural killer subpopulation highly cytotoxic to HIV-infected cells

Siglec-9 is an MHC-independent inhibitory receptor expressed on a subset of natural killer (NK) cells. Siglec-9 restrains NK cytotoxicity by binding to sialoglycans (sialic acid-containing glycans) on target cells. Despite the importance of Siglec-9 interactions in tumor immune evasion, their role as an immune evasion mechanism during HIV infection has not been investigated. Using in vivo phenotypic analyses, we found that Siglec-9⁺ CD56^dim NK cells, during HIV infection, exhibit an activated phenotype with higher expression of activating receptors and markers (NKp30, CD38, CD16, DNAM-1, perforin) and lower expression of the inhibitory receptor NKG2A, compared to Siglec-9^- CD56^dim NK cells. We also found that levels of Siglec-9⁺ CD56^dim NK cells inversely correlate with viral load during viremic infection and CD4⁺ T cell-associated HIV DNA during suppressed infection. Using in vitro cytotoxicity assays, we confirmed that Siglec-9⁺ NK cells exhibit higher cytotoxicity towards HIV-infected cells compared to Siglec-9^- NK cells. These data are consistent with the notion that Siglec-9⁺ NK cells are highly cytotoxic against HIV-infected cells. However, blocking Siglec-9 enhanced NK cells’ ability to lyse HIV-infected cells, consistent with the known inhibitory function of the Siglec-9 molecule. Together, these data support a model in which the Siglec-9⁺ CD56^dim NK subpopulation is highly cytotoxic against HIV-infected cells even whilst being restrained by the inhibitory effects of Siglec-9. To harness the cytotoxic capacity of the Siglec-9⁺ NK subpopulation, which is dampened by Siglec-9, we developed a proof-of-concept approach to selectively disrupt Siglec/sialoglycan interactions between NK and HIV-infected cells. We achieved this goal by conjugating Sialidase to several HIV broadly neutralizing antibodies. These conjugates selectively desialylated HIV-infected cells and enhanced NK cells’ capacity to kill them. In summary, we identified a novel, glycan-based interaction that may contribute to HIV-infected cells’ ability to evade NK immunosurveillance and developed an approach to break this interaction.     

TREK-1 Regulates Cytokine Secretion from Cultured Human Alveolar Epithelial Cells Independently of Cytoskeletal Rearrangements

BackgroundTREK-1 deficient alveolar epithelial cells (AECs) secrete less IL-6, more MCP-1, and contain less F-actin. Whether these alterations in cytokine secretion and F-actin content are related remains unknown. We now hypothesized that cytokine secretion from TREK-1-deficient AECs was regulated by cytoskeletal rearrangements.MethodsWe determined F-actin and α-tubulin contents of control, TREK-1-deficient and TREK-1-overexpressing human A549 cells by confocal microscopy and western blotting, and measured IL-6 and MCP-1 levels using real-time PCR and ELISA.ResultsCytochalasin D decreased the F-actin content of control cells. Jasplakinolide increased the F-actin content of TREK-1 deficient cells, similar to the effect of TREK-1 overexpression in control cells. Treatment of control and TREK-1 deficient cells with TNF-α, a strong stimulus for IL-6 and MCP-1 secretion, had no effect on F-actin structures. The combination of TNF-α+cytochalasin D or TNF-α+jasplakinolide had no additional effect on the F-actin content or architecture when compared to cytochalasin D or jasplakinolide alone. Although TREK-1 deficient AECs contained less F-actin at baseline, quantified biochemically, they contained more α-tubulin. Exposure to nocodazole disrupted α-tubulin filaments in control and TREK-1 deficient cells, but left the overall amount of α-tubulin unchanged. Although TNF-α had no effect on the F-actin or α-tubulin contents, it increased IL-6 and MCP-1 production and secretion from control and TREK-1 deficient cells. IL-6 and MCP-1 secretions from control and TREK-1 deficient cells after TNF-α+jasplakinolide or TNF-α+nocodazole treatment was similar to the effect of TNF-α alone. Interestingly, cytochalasin D decreased TNF-α-induced IL-6 but not MCP-1 secretion from control but not TREK-1 deficient cells.ConclusionAlthough cytochalasin D, jasplakinolide and nocodazole altered the F-actin and α-tubulin structures of control and TREK-1 deficient AEC, the changes in cytokine secretion from TREK-1 deficient cells cannot be explained by cytoskeletal rearrangements in these cells.     

The effect of Glisson's capsule on the superficial elasticity measurements of the liver

In the past decade, novel tools for surgical planning and disease diagnosis have been developed to detect the liver's mechanical properties. Some tools utilize superficial indentation type measurements to determine the elasticity of the liver parenchyma and to assume material homogeneity. In fact, the liver is a soft tissue covered with a connective sheathing that is called Glisson's capsule. This article quantifies the effect of this capsule on the measured or "effective" elastic modulus obtained by indentation with a spherical geometry. Two sets of parametric computational studies in which the Glisson capsule thickness and elasticity were varied, demonstrated the relationship between the measured elastic response and the underlying parenchymal elastic response. Previously reported in vivo indentation data on the human liver were utilized to determine the elasticity of its parenchyma. The results indicated a linear relationship between the effective (measured) elastic response and the underlying parenchyma for the Glisson capsule thicknesses considered. When previously published human liver indentation data were analyzed, the measured elastic modulus was nearly 6.9% greater than the underlying parenchyma elastic modulus. Although the analyzed data were obtained from a single liver and yet displayed a significant variation, the Glisson capsule elasticity induced a significant but systematic error as well. The Glisson capsule thickness error was negligible for capsule parameters associated with a normal liver. Based on this work, an emphasis on the Glisson capsule's contribution to the mechanical response of the liver would enhance the clinical potential of indentation-based novel tools for liver care.     

Antigen-specific CD8+ T cells respond to Chlamydia trachomatis in the genital mucosa

Following sexual transmission, Chlamydia trachomatis specifically targets genital tract epithelial cells. Because epithelial cells are readily recognized by CD8+ T cells, the response of CD8+ T cells to Chlamydia infection has been explored in a number of studies. It has been shown that CD8+ T cells are present in the genital tracts of mice following C. trachomatis infection, but the specificity of these T cells has remained undefined. To determine whether Chlamydia-specific CD8+ T cells migrate to the genital tract in response to Chlamydia infection, we generated retrogenic mice that express a TCR specific for a Chlamydia-specific T cell Ag CrpA. T cells from the retrogenic mice were transferred into naive recipient animals to increase the frequency of Chlamydia-specific T cells to a level at which they could be tracked during primary infection. We observed that the Chlamydia-specific retrogenic T cells proliferated in lymph nodes draining the genital tract in response to genital infection with C. trachomatis. Furthermore, we found that these cells acquired the ability to produce IFN-gamma and migrated into the genital mucosa of the infected mice.     

Aberrant BCAA and glutamate metabolism linked to regional neurodegeneration in a mouse model of Leigh syndrome

The dysfunction of respiratory chain complex I (CI) is the most common form of mitochondrial disease that most often presents as Leigh syndrome (LS) in children — a severe neurometabolic disorder defined by progressive focal lesions in specific brain regions. The mechanisms underlying this region-specific vulnerability to CI deficiency, however, remain elusive. Here, we examined brain regional respiratory chain enzyme activities and metabolic profiles in a mouse model of LS with global CI deficiency to gain insight into regional vulnerability to neurodegeneration. One lesion-resistant and three lesion-prone brain regions were investigated in Ndufs4 knockout (KO) mice at the late stage of LS. Enzyme assays confirmed significantly decreased (60–80%) CI activity in all investigated KO brain regions, with the lesion-resistant region displaying the highest residual CI activity (38% of wild type). A higher residual CI activity, and a less perturbed NADH/NAD⁺ ratio, correlate with less severe metabolic perturbations in KO brain regions. Moreover, less perturbed BCAA oxidation and increased glutamate oxidation seem to distinguish lesion-resistant from -prone KO brain regions, thereby identifying key areas of metabolism to target in future therapeutic intervention studies.     

Type I interferon is required for T helper (Th) 2 induction by dendritic cells

Type 2 inflammation is a defining feature of infection with parasitic worms (helminths), as well as being responsible for widespread suffering in allergies. However, the precise mechanisms involved in T helper (Th) 2 polarization by dendritic cells (DCs) are currently unclear. We have identified a previously unrecognized role for type I IFN (IFN‐I) in enabling this process. An IFN‐I signature was evident in DCs responding to the helminth Schistosoma mansoni or the allergen house dust mite (HDM). Further, IFN‐I signaling was required for optimal DC phenotypic activation in response to helminth antigen (Ag), and efficient migration to, and localization with, T cells in the draining lymph node (dLN). Importantly, DCs generated from Ifnar1^?/? mice were incapable of initiating Th2 responses in vivo. These data demonstrate for the first time that the influence of IFN‐I is not limited to antiviral or bacterial settings but also has a central role to play in DC initiation of Th2 responses.     

Immune-mediated control of Chlamydia infection

Infection with the bacterium Chlamydia trachomatis can lead to a variety of diseases, including ectopic pregnancy, infertility and blindness. Exposure of the host to C. trachomatis stimulates multiple innate and adaptive immune effectors that can contribute towards controlling bacterial replication. However, these effectors are often insufficient to resolve the infection and prevent re-infection, and the continued presence of C. trachomatis within the host may induce immune effectors to chronically produce inflammatory cytokines. This may eventually lead to the tissue pathologies associated with the infection. Reducing the incidence and sequelae of infection will ultimately require the development of a C. trachomatis vaccine that can stimulate sterilizing immunity while avoiding immune-mediated pathology.