Exposures to perfluoroalkyl substances (PFAS) including perfluoroalkyl acids (PFAAs) are associated with increased liver enzymes in cohort studies including the C8 Health Study. In animal models, PFAAs disrupt hepatic lipid metabolism and induce apoptosis to cause nonalcoholic fatty liver disease (NAFLD). PFAAs are immunotoxic and inhibit pro-inflammatory cytokine release from stimulated leukocytes in vitro. This cross-sectional study tests the hypothesis that environmental PFAAs are associated with increased hepatocyte apoptosis and decreased proinflammatory cytokines in serum. Biomarkers previously associated with PFAS exposures and/or NAFLD were evaluated as secondary endpoints. Two hundred adult C8 Health Study participants

BackgroundMutations affecting cilia proteins have an established role in renal cyst formation. In mice, the rate of cystogenesis is influenced by the age at which cilia dysfunction occurs and whether the kidney has been injured. Disruption of cilia function before postnatal day 12–14 results in rapid cyst formation; however, cyst formation is slower when cilia dysfunction is induced after postnatal day 14. Rapid cyst formation can also be induced in conditional adult cilia mutant mice by introducing renal injury. Previous studies indicate that macrophages are involved in cyst formation, however the specific role and type of macrophages responsible has not been clarified.MethodsWe analyzed resident macrophage number and subtypes during postnatal renal maturation and after renal injury in control and conditional Ift88 cilia mutant mice. We also used a pharmacological inhibitor of resident macrophage proliferation and accumulation to determine the importance of these cells during rapid cyst formation.ResultsOur data show that renal resident macrophages undergo a phenotypic switch from R2b (CD11clo) to R2a (CD11chi) during postnatal renal maturation. The timing of this switch correlates with the period in which cyst formation transitions from rapid to slow following induction of cilia dysfunction. Renal injury induces the reaccumulation of juvenile-like R2b resident macrophages in cilia mutant mice and restores rapid cystogenesis. Loss of primary cilia in injured conditional Ift88 mice results in enhanced epithelial production of membrane-bound CSF1, a cytokine that promotes resident macrophage proliferation. Inhibiting CSF1/CSF1-receptor signaling with a CSF1R kinase inhibitor reduces resident macrophage proliferation, R2b resident macrophage accumulation, and renal cyst formation in two mouse models of cystic disease.ConclusionsThese data uncover an important pathogenic role for resident macrophages during rapid cyst progression.

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Introduction: The healthcare industry has begun seeing a new hazard develop against them-the threat of cyberattack. Beginning in 2016, healthcare organizations in the United States have been targeted for malware attacks, a specific type of cyberattack. During malware incidents hackers can lock users out of their own network to gain access to information or to hold the organization for ransom. With the increase in medical technology and the need for access to this information to provide critical care, this type of incident has the potential to put patient lives and safety at risk. Methods: A content analysis was conducted to assess the trend of attacks on healthcare organizations. U.S. Healthcare IT News and Becker's Hospital Review were used to collect all publicly reported malware attacks against U.S. healthcare organizations between 2016 and 2017. A logic diagram was also developed to illustrate how hackers gain access to a healthcare network using malware. Results: There were 49 cases of malware attacks against U.S. HCOs identified. The attacks occurred across 27 states, and they took place during 18 out of 24 months. Six of the organizations reported paying ransom, whereas 43 organizations did not pay or did not report payment to the press. Impacts of these attacks range from network downtime to patient and staff records being breached. Discussion: Malware attacks have the potential to impact care delivery as well as the healthcare facility itself. Even though this study identified 49 malware attacks, we know this number is significantly higher based on data from HIMSS and the FBI. A reporting loophole exists in that hospitals are only required to report attacks in the case of breached protected health or financial data. For HCOs to fully understand the risk cyberthreats pose, it is important for attacks to become public information and for lessons learned to be shared. Future research reviewing identified attacks could help identify best practices for the healthcare industry to better prepare for cyberattacks.

The authors use tombstones from Investment Dealers' Digest to develop continuous and bracket prestige measures of underwriters in the municipal bond market. The measures are used in multivariate analysis of 409 offerings to examine the relationship between net interest cost to the issuer and prestige of the lead underwriter. Multiple regression analysis reveals that issuers in the sample do not receive statistically significant positive benefits from using prestigious underwriters. The authors note that their results are consistent with segmentation of the market for municipal bonds.