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The article reports a study on central venous catheter-associated bloodstream infections (BSI) that occurred in 32 intensive care hospital units in southwestern Pennsylvania during April 2001-March 2005. The Pittsburgh Regional Healthcare Initiative's advisory committee identified strategies for preventing nosocomial infections. The five components of the voluntary intervention included promoting evidence-based catheter insertion practices and measurement of central-line associated BSI rates. Methods from the National Nosocomial Infection Surveillance system were implemented. The CDC editorial note discusses central line-associated BSI rates and three limitations in this report.

Septic systems (SSs) have been shown to be a significant source of nitrogen and phosphorus to nutrient-sensitive coastal surface and groundwaters. However, few published studies have quantified the effects of SSs on nutrient inputs to water supply watersheds in the Piedmont region of the USA. This region consists of rolling hills at the surface underlain by clayey soils. There are nearly 1 million SSs in this region, which accounts for approximately 50% of all SSs in North Carolina. The goal of this study was to determine if significant differences in nutrient concentrations and exports exist between Piedmont watersheds with different densities of SSs. Water quality was assessed in watersheds with SSs (n = 11) and a sewer and a forested watershed, which were designated as controls. Stream flow and environmental readings were recorded and water samples were collected from the watersheds from January 2015–December 2016. Additional samples were collected from sand filter watersheds in April 2015–March 2016 to compare to septic and control watersheds. Samples were analyzed for total dissolved nitrogen (TDN) and orthophosphate (PO 4 -P). Results indicated that watersheds served by a high-density (HD) of SSs (4.9 kg-N yr −1 ha −1 ; 0.2 kg-P yr −1 ha −1 ) exported more than double the median masses of TDN and PO 4 -P, respectively, relative to low-density (1.0 kg-N yr −1 ha −1 ; <0.1 kg-P yr −1 ha −1 ) and control watersheds (1.4 kg-N yr −1 ha −1 ; <0.1 kg-P yr −1 ha −1 ) during baseflow. Isotopic analysis indicated that wastewater was the most likely source of nitrate-N in HD watersheds. In all other watersheds, isotopic results suggested non-wastewater sources as the dominant nitrate-N provider. These findings indicated that SS density was a significant factor in the delivery of septic-derived nutrients to these nutrient-sensitive, water supply watersheds of the North Carolina Piedmont. [ABSTRACT FROM AUTHOR]

Importance: Multiplex molecular syndromic panels for diagnosis of urinary tract infection (UTI) lack clinical data supporting their use in routine clinical care. They also have the potential to exacerbate inappropriate antibiotic prescribing., Objective: To describe the frequency of unspecified multiplex testing in administrative claims with a primary diagnosis of UTI in the Medicare population over time, to assess costs, and to characterize the health care professionals (eg, clinicians, laboratories, physician assistants, and nurse practitioners) and patient populations using these tests., Design, Setting, and Participants: This cohort study used Centers for Medicare & Medicaid Services (CMS) claims data for Medicare beneficiaries. The study included older community-dwelling adults and nursing home residents with fee-for-service Medicare Part A and Part B benefits from January 1, 2016, to December 31, 2023., Main Outcomes and Measures: Multiplex syndromic panels were identified using carrier claims (ie, claims for clinician office or laboratory services). The annual rate of claims was measured for multiplex syndromic panels with a primary diagnosis of UTI per 10 000 eligible Medicare beneficiaries. The performing and referring specialties of health care professionals listed on claims of interest and the proportion of claims that occurred among beneficiaries residing in a nursing home were described., Results: Between 31 110 656 and 36 175 559 Medicare beneficiaries with fee-for-service coverage annually (2016-2023) were included in this study. In this period, 1 679 328 claims for UTI multiplex testing were identified. The median age of beneficiaries was 77 (IQR, 70-84) years; 34% of claims were from male beneficiaries and 66% were from female beneficiaries. From 2016 to 2023, the observed rate of UTI multiplex testing increased from 2.4 to 148.1 claims per 10 000 fee-for-service beneficiaries annually, and the proportion of claims that occurred among beneficiaries residing in a nursing home ranged from 1% in 2016 to 12% in 2020. In addition to laboratories or pathologists, urology was the most common clinician specialty conducting this testing. The CMS-assigned referring clinician specialty was most frequently urology or advanced practice clinician for claims among community-dwelling beneficiaries compared with internal medicine or family medicine for claims among nursing home residents. In 2023, the median cost of a multiplex test in the US was $585 (IQR, $516-$695 for Q1-Q3), which was more than 70 times higher than the median cost of $8 for a urine culture (IQR, $8-$16 for Q1-Q3)., Conclusions and Relevance: This cohort study of Medicare beneficiaries with fee-for-service coverage from 2016 to 2023 found increasing use of emerging multiplex testing for UTI coupled with high costs to the Medicare program. Monitoring and research are needed to determine the effects of multiplex testing on antimicrobial use and whether there are clinical situations in which this testing may benefit patients.

Background: Residents of nursing homes remain an epidemiologically important population for COVID-19 prevention efforts, including vaccination. We aim to understand effectiveness of bivalent vaccination for preventing SARS-CoV-2 infections in this population., Methods: We used a retrospective cohort of nursing home residents from November 1, 2022, through March 31, 2023, to identify new SARS-CoV-2 infections. A Cox proportional hazards model was used to estimate hazard ratios comparing residents with a bivalent vaccination compared with residents not up to date with vaccination recommendations. Vaccine effectiveness was estimated as (1 - Hazard Ratio) * 100., Results: Among 6,916 residents residing in 76 nursing homes included in our cohort, 3,211 (46%) received a bivalent vaccine 7 or more days prior to censoring. Adjusted vaccine effectiveness against laboratory confirmed SARS-CoV-2 infection comparing receipt of a bivalent vaccine versus not up to date vaccine status was 29% (95% Confidence interval 18% to 39%). Vaccine effectiveness for receipt of a bivalent vaccine against residents who were unvaccinated or vaccinated more than a year prior was 32% (95% CI: 20% to 42%,) and was 25% compared with residents who were vaccinated with a monovalent vaccine in the past 61-365 days (95% CI:10% to 37%)., Conclusions: Bivalent COVID-19 vaccines provided additional protection against SARS-CoV-2 infections in nursing home residents during our study time-period, compared to both no vaccination or vaccination more than a year ago and monovalent vaccination 60 - 365 days prior. Ensuring nursing home residents stay up to date with vaccine recommendations remains a critical tool for COVID-19 prevention efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Parkinson's Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated in PD pathogenesis. Although alterations in circulating inflammatory cytokines and reactive oxygen species (ROS) have been associated with PD, no biomarkers have been identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, which involves perturbation of the underlying immune system, is an early and often-overlooked symptom that affects up to 80% of individuals living with PD. Interestingly, 50-70% of individuals with inflammatory bowel disease (IBD), a GI condition that has been epidemiologically linked to PD, display chronic illness-induced anemia - which drives toxic accumulation of iron in the gut. Ferroptotic (or iron loaded) cells have small and dysmorphic mitochondria-suggesting that mitochondrial dysfunction is a consequence of iron accumulation. In pro-inflammatory environments, iron accumulates in immune cells, suggesting a possible connection and/or synergy between iron dysregulation and immune cell dysfunction. Peripheral blood mononuclear cells (PBMCs) recapitulate certain PD-associated neuropathological and inflammatory signatures and can act as communicating messengers in the gut-brain axis. Additionally, this communication can be modulated by several environmental factors; specifically, our data further support existing literature demonstrating a role for non-steroidal anti-inflammatory drugs (NSAIDs) in modulating immune transcriptional states in inflamed individuals. A mechanism linking chronic gut inflammation to iron dysregulation and mitochondrial function within peripheral immune cells has yet to be identified in conferring risk for PD. To that end, we isolated PBMCs and simultaneously evaluated their directed transcriptome and bioenergetic status, to investigate if iron dysregulation and mitochondrial sensitization are linked in individuals living with PD or IBD because of chronic underlying remittent immune activation. We have identified shared features of peripheral inflammation and immunometabolism in individuals living with IBD or PD that may contribute to the epidemiological association reported between IBD and risk for PD.

Microglia play a critical role in maintaining brain homeostasis but become dysregulated in neurodegenerative diseases. Regulator of G-protein Signaling 10 (RGS10), one of the most abundant homeostasis proteins in microglia, decreases with aging and functions as a negative regulator of microglia activation. RGS10-deficient mice exhibit impaired glucose tolerance, and high-fat diet induces insulin resistance in these mice. In this study, we investigated whether RGS10 modulates microglia activation in response to hyperglycemic conditions, complementing our previous findings of its role in inflammatory stimuli. In RGS10 knockdown (KD) BV2 cells, TNF production increased significantly in response to high glucose, particularly under proinflammatory conditions. Additionally, glucose uptake and GLUT1 mRNA levels were significantly elevated in RGS10 KD BV2 cells. These cells produced higher ROS and displayed reduced sensitivity to the antioxidant N-Acetyl Cysteine (NAC) when exposed to high glucose. Notably, both BV2 cells and primary microglia that lack RGS10 exhibited impaired uptake of alpha-synuclein aggregates. These findings suggest that RGS10 acts as a negative regulator of microglia activation not only in response to inflammation but also under hyperglycemic conditions., Competing Interests: J-KL holds shares in Neuronity Therapeutics, Inc. and declares no competing interests. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chung, Jernigan, Menees and Lee.)

Background: Residents of nursing homes experience disproportionate morbidity and mortality related to coronavirus disease 2019 (COVID-19) and were prioritized for vaccine introduction. We evaluated COVID-19 vaccine effectiveness (VE) in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among nursing home residents., Methods: We used a retrospective cohort of 4315 nursing home residents during 14 December 2020-9 November 2021. A Cox proportional hazards model was used to estimate hazard ratios comparing residents with a completed vaccination series with unvaccinated among those with and without prior SARS-CoV-2 infection, by vaccine product, and by time period., Results: Overall adjusted VE was 58% (95% confidence interval [CI], 44% to 69%) among residents without a history of SARS-CoV-2 infection. During the pre-Delta period, the VE within 150 days of receipt of the second dose of Pfizer-BioNTech (67%; 95% CI, 40% to 82%) and Moderna (75%; 95% CI, 32% to 91%) was similar. During the Delta period, VE measured >150 days after the second dose was 33% (95% CI, -2% to 56%) for Pfizer-BioNTech and 77% (95% CI, 48% to 91%) for Moderna. Rates of infection were 78% lower (95% CI, 67% to 85%) among residents with prior SARS-CoV-2 infection and completed vaccination series compared with unvaccinated residents without a history of SARS-CoV-2 infection., Conclusions: COVID-19 vaccines were effective in preventing SARS-CoV-2 infections among nursing home residents, and history of prior SARS-CoV-2 infection provided additional protection. Maintaining high coverage of recommended doses of COVID-19 vaccines remains a critical tool for preventing infections in nursing homes., Competing Interests: Potential conflicts of interest. A. A. S., K. S. M., and S. J. report funding from their employer Base10 Genetics and report holding stocks with their employer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

In April 2021, we assessed mRNA vaccine effectiveness (VE) in the context of a COVID-19 outbreak in a skilled nursing facility. Among 28 cases, genomic sequencing was performed on 4 specimens on 4 different patients, and all were classified by sequence analysis as the Beta (B.1.351) variant. Adjusted VE among residents was 65% (95% confidence interval: 25-84%). These findings underscore the importance of vaccination for prevention of COVID-19 in skilled nursing facilities., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

As of 2 September 2021, United States nursing homes have reported >675,000 COVID-19 cases and >134,000 deaths according to the Centers for Medicare & Medicaid Services (CMS). More than 205,000,000 persons in the United States had received at least one dose of a COVID-19 vaccine (62% of total population) as of 2 September 2021. We investigate the role of vaccination in controlling future COVID-19 outbreaks. We developed a stochastic, compartmental model of SARS-CoV-2 transmission in a 100-bed nursing home with a staff of 99 healthcare personnel (HCP) in a community of 20,000 people. We parameterized admission and discharge of residents in the model with CMS data, for a within-facility basic reproduction number (R 0 ) of 3.5 and a community R 0 of 2.5. The model also included: importation of COVID-19 from the community, isolation of SARS-CoV-2 positive residents, facility-wide adherence to personal protective equipment (PPE) use by HCP, and testing. We systematically varied coverage of mRNA vaccine among residents, HCP, and the community. Simulations were run for 6 months after the second dose in the facility, with results summarized over 1,000 simulations. Expected resident cases decreased as community vaccination increased, with large reductions at high HCP coverage. The probability of a COVID-19 outbreak was lower as well: at HCP vaccination coverage of 60%, probability of an outbreak was below 20% for community coverage of 50% or above. At high coverage, stopping asymptomatic screening and facility-wide testing yielded similar results. Results suggest that high coverage among HCP and in the community can prevent infections in residents. When vaccination is high in nursing homes, but not in their surrounding communities, asymptomatic and facility-wide testing remains necessary to prevent the spread of COVID-19. High adherence to PPE may increase the likelihood of containing future COVID-19 outbreaks if they occur., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Nursing home residents have experienced disproportionally high levels of COVID-19-associated morbidity and mortality and were prioritized for early COVID-19 vaccination (1). Following reported declines in vaccine-induced immunity after primary series vaccination, defined as receipt of 2 primary doses of an mRNA vaccine (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) or 1 primary dose of Ad26.COV2 (Johnson & Johnson [Janssen]) vaccine (2), CDC recommended that all persons aged ≥12 years receive a COVID-19 booster vaccine dose.* Moderately to severely immunocompromised persons, a group that includes many nursing home residents, are also recommended to receive an additional primary COVID-19 vaccine dose. † Data on vaccine effectiveness (VE) of an additional primary or booster dose against infection with SARS-CoV-2 (the virus that causes COVID-19) among nursing home residents are limited, especially against the highly transmissible B.1.1.529 and BA.2 (Omicron) variants. Weekly COVID-19 surveillance and vaccination coverage data among nursing home residents, reported by skilled nursing facilities (SNFs) to CDC's National Healthcare Safety Network (NHSN) § during February 14-March 27, 2022, when the Omicron variant accounted for >99% of sequenced isolates, were analyzed to estimate relative VE against infection for any COVID-19 additional primary or booster dose compared with primary series vaccination. After adjusting for calendar week and variability across SNFs, relative VE of a COVID-19 additional primary or booster dose was 46.9% (95% CI = 44.8%-48.9%). These findings indicate that among nursing home residents, COVID-19 additional primary or booster doses provide greater protection against Omicron variant infection than does primary series vaccination alone. All immunocompromised nursing home residents should receive an additional primary dose, and all nursing home residents should receive a booster dose, when eligible, to protect against COVID-19. Efforts to keep nursing home residents up to date with vaccination should be implemented in conjunction with other COVID-19 prevention strategies, including testing and vaccination of nursing home staff members and visitors., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Nursing home residents and staff were included in the first phase of coronavirus disease 2019 vaccination in the United States. Because the primary trial endpoint was vaccine efficacy (VE) against symptomatic disease, there are limited data on the extent to which vaccines protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the ability to infect others (infectiousness). Assumptions about VE against infection and infectiousness have implications for changes to infection prevention guidance for vaccinated populations, including testing strategies., Methods: We use a stochastic agent-based Susceptible-Exposed-Infectious (Asymptomatic/Symptomatic)-Recovered model of a nursing home to simulate SARS-CoV-2 transmission. We model 3 scenarios, varying VE against infection, infectiousness, and symptoms, to understand the expected impact of vaccination in nursing homes, increasing staff vaccination coverage, and different screening testing strategies under each scenario., Results: Increasing vaccination coverage in staff decreases total symptomatic cases in the nursing home (among staff and residents combined) in each VE scenario. In scenarios with 50% and 90% VE against infection and infectiousness, increasing staff coverage reduces symptomatic cases among residents. If vaccination only protects against symptoms, and asymptomatic cases remain infectious, increased staff coverage increases symptomatic cases among residents. However, this is outweighed by the reduction in symptomatic cases among staff. Higher frequency testing-more than once weekly-is needed to reduce total symptomatic cases if the vaccine has lower efficacy against infection and infectiousness, or only protects against symptoms., Conclusions: Encouraging staff vaccination is not only important for protecting staff, but might also reduce symptomatic cases in residents if a vaccine confers at least some protection against infection or infectiousness., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Objective: To evaluate if facility-level vaccination after an initial vaccination clinic was independently associated with COVID-19 incidence adjusted for other factors in January 2021 among nursing home residents., Design: Ecological analysis of data from the CDC's National Healthcare Safety Network (NHSN) and from the CDC's Pharmacy Partnership for Long-Term Care Program., Setting and Participants: CMS-certified nursing homes participating in both NHSN and the Pharmacy Partnership for Long-Term Care Program., Methods: A multivariable, random intercepts, negative binomial model was applied to contrast COVID-19 incidence rates among residents living in facilities with an initial vaccination clinic during the week ending January 3, 2021 (n = 2843), vs those living in facilities with no vaccination clinic reported up to and including the week ending January 10, 2021 (n = 3216). Model covariates included bed size, resident SARS-CoV-2 testing, staff with COVID-19, cumulative COVID-19 among residents, residents admitted with COVID-19, community county incidence, and county social vulnerability index (SVI)., Results: In December 2020 and January 2021, incidence of COVID-19 among nursing home residents declined to the lowest point since reporting began in May, diverged from the pattern in community cases, and began dropping before vaccination occurred. Comparing week 3 following an initial vaccination clinic vs week 2, the adjusted reduction in COVID-19 rate in vaccinated facilities was 27% greater than the reduction in facilities where vaccination clinics had not yet occurred (95% confidence interval: 14%-38%, P < .05)., Conclusions and Implications: Vaccination of residents contributed to the decline in COVID-19 incidence in nursing homes; however, other factors also contributed. The decline in COVID-19 was evident prior to widespread vaccination, highlighting the benefit of a multifaced approach to prevention including continued use of recommended screening, testing, and infection prevention practices as well as vaccination to keep residents in nursing homes safe., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood., Results: Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson's disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis., Conclusions: This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson's disease, where immune dysfunction is implicated in their etiology.

Skilled nursing facilities (SNFs) are focal points of the coronavirus disease 2019 (COVID-19) pandemic, and asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19, among SNF residents and health care personnel have been described (1-3). Repeated point prevalence surveys (serial testing of all residents and health care personnel at a health care facility irrespective of symptoms) have been used to identify asymptomatic infections and have reduced SARS-CoV-2 transmission during SNF outbreaks (1,3). During March 2020, the Detroit Health Department and area hospitals detected a sharp increase in COVID-19 diagnoses, hospitalizations, and associated deaths among SNF residents. The Detroit Health Department collaborated with local government, academic, and health care system partners and a CDC field team to rapidly expand SARS-CoV-2 testing and implement infection prevention and control (IPC) activities in all Detroit-area SNFs. During March 7-May 8, among 2,773 residents of 26 Detroit SNFs, 1,207 laboratory-confirmed cases of COVID-19 were identified during three periods: before (March 7-April 7) and after two point prevalence surveys (April 8-25 and April 30-May 8): the overall attack rate was 44%. Within 21 days of receiving their first positive test results, 446 (37%) of 1,207 COVID-19 patients were hospitalized, and 287 (24%) died. Among facilities participating in both surveys (n = 12), the percentage of positive test results declined from 35% to 18%. Repeated point prevalence surveys in SNFs identified asymptomatic COVID-19 cases, informed cohorting and IPC practices aimed at reducing transmission, and guided prioritization of health department resources for facilities experiencing high levels of SARS-CoV-2 transmission. With the increased availability of SARS-CoV-2 testing, repeated point prevalence surveys and enhanced and expanded IPC support should be standard tools for interrupting and preventing COVID-19 outbreaks in SNFs., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. John Zervos and Tyler Prentiss report grants from the United Way of Southeastern Michigan, Vattikuti Foundation, and Abbott Laboratories during the conduct of the study. Marcus J. Zervos reports grants from Pfizer, Merck, and Serono, outside the submitted work. No other potential conflicts of interest were disclosed.

Microglia transform from homeostatic to disease-associated-microglia (DAM) profiles in neurodegeneration. Within DAM, we recently identified distinct pro-inflammatory and anti-inflammatory sub-profiles although transcriptional regulators of homeostatic and distinct DAM profiles remain unclear. Informed by these studies, we nominated CEBPα, IRF1, and LXRβ as likely regulators of homeostatic, pro-inflammatory and anti-inflammatory DAM states and performed in-vitro siRNA studies in primary microglia to identify roles of each transcriptional factor (TF) in regulating microglial activation, using an integrated transcriptomics, bioinformatics and experimental validation approach. Efficient (>70%) silencing of TFs in microglia revealed reciprocal regulation between each TF specifically following pro-inflammatory activation. Neuroinflammatory transcriptomic profiling of microglia coupled with qPCR validation revealed distinct gene clusters with unique patterns of regulation by each TF, which were independent of LPS stimulation. While all three TFs (especially IRF1 and LXRβ) positively regulated core DAM genes (Apoe, Axl, Clec7a, Tyrobp, and Trem2) as well as homeostatic and pro-inflammatory DAM genes, LPS, and IFNγ increased pro-inflammatory DAM but suppressed homeostatic and anti-inflammatory DAM gene expression via an Erk1/2-dependent signaling pathway. IRF1 and LXRβ silencing suppressed microglial phagocytic activity for polystyrene microspheres as well as fAβ42 while IRF1 silencing strongly suppressed production of pro-inflammatory cytokines in response to LPS. Our studies reveal complex transcriptional regulation of homeostatic and DAM profiles whereby IRF1, LXRβ, and CEBPα positively regulate both pro- and anti-inflammatory DAM genes while activating stimuli independently augment pro-inflammatory DAM responses and suppress homeostatic and anti-inflammatory responses via Erk signaling. This framework can guide development of therapeutic immuno-modulatory strategies for neurodegeneration., (© 2019 Wiley Periodicals, Inc.)

Background: The authors' aim in this systematic review was to evaluate the validity of using preoperative serum C-terminal cross-linking telopeptide (CTX) levels as a predictive factor of increased risk of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving bisphosphonate (BP) therapy who underwent invasive dental procedures., Types of Studies Reviewed: The authors searched PubMed, MEDLINE, and Web of Science and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The authors conducted a meta-analysis on the risk ratio. The authors used the methodological index for nonrandomized studies and Quality Appraisal of Reliability Studies checklist to assess quality., Results: The authors included 18 clinical trials involving 2,301 patients. Most patients received alendronate or risedronate for an average of 62.14 months. The average serum CTX level in patients who received BP before surgery was 198.25 picograms per milliliter. Meta-analysis results showed that the cutoff in CTX level (150 pg/mL) was not predictive of MRONJ risk. The sensitivity of CTX values lower than 150 pg/mL was 34.26%, and the specificity was 77.08%., Conclusions and Practical Implications: The use of CTX levels to diagnose MRONJ risk after dental procedures in patients receiving BP is not justified. The cutoff of 150 pg/mL in serum CTX levels is not predictive of MRONJ. Further studies are needed to develop other reliable biomarkers., (Copyright © 2019 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Staphylococcus aureus is one of the most common pathogens in health care facilities and in the community, and can cause invasive infections, sepsis, and death. Despite progress in preventing methicillin-resistant S. aureus (MRSA) infections in health care settings, assessment of the problem in both health care and community settings is needed. Further, the epidemiology of methicillin-susceptible S. aureus (MSSA) infections is not well described at the national level., Methods: Data from the Emerging Infections Program (EIP) MRSA population surveillance (2005-2016) and from the Premier and Cerner Electronic Health Record databases (2012-2017) were analyzed to describe trends in incidence of hospital-onset and community-onset MRSA and MSSA bloodstream infections and to estimate the overall incidence of S. aureus bloodstream infections in the United States and associated in-hospital mortality., Results: In 2017, an estimated 119,247 S. aureus bloodstream infections with 19,832 associated deaths occurred. During 2005-2012 rates of hospital-onset MRSA bloodstream infection decreased by 17.1% annually, but the decline slowed during 2013-2016. Community-onset MRSA declined less markedly (6.9% annually during 2005-2016), mostly related to declines in health care-associated infections. Hospital-onset MSSA has not significantly changed (p = 0.11), and community-onset MSSA infections have slightly increased (3.9% per year, p<0.0001) from 2012 to 2017., Conclusions and Implications for Public Health Practice: Despite reductions in incidence of MRSA bloodstream infections since 2005, S. aureus infections account for significant morbidity and mortality in the United States. To reduce the incidence of these infections further, health care facilities should take steps to fully implement CDC recommendations for prevention of device- and procedure-associated infections and for interruption of transmission. New and novel prevention strategies are also needed., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Recent findings show that national childhood obesity prevalence overall is improving among some age groups, but that disparities continue to persist, particularly among populations that have historically been at higher risk of obesity and overweight. Over the past several years, many jurisdictions at the city or county level across the nation have also reported declines. Little evaluation has focused on understanding the factors that influence the implementation of efforts to reduce childhood obesity rates. This article summarizes the rationale, aims, and overall design of the Childhood Obesity Declines Project (COBD), which was the first of its kind to systematically study and document the what, how, when, and where of community-based obesity strategies in four distinct communities across the nation., Methods: COBD was initiated by the National Collaborative on Childhood Obesity Research (NCCOR), was led by a subset of NCCOR advisors and a research team at ICF, and was guided by external advisors made up of researchers, decision makers, and other key stakeholders. The research team used an adapted version of the Systematic Screening and Assessment method to review and collect retrospective implementation data in four communities., Results: COBD found that sites implemented strategies across the many levels and environments that impact children's well being (akin to the social-ecological framework), building a Culture of Health in their communities., Conclusions: COBD demonstrates how collaboratives of major funders with the support of other experts and key stakeholders, can help to accelerate progress in identifying and disseminating strategies that promote healthy eating and physical activity.

Background: The evidence for and our understanding of community-level strategies such as policies, system, and environmental changes that support healthy eating and active living is growing. However, researchers and evaluation scientists alike are still not confident in what to recommend for preventing or sustaining declines in the prevalence of obesity., Methods: The Systematic Screening and Assessment (SSA) methodology was adapted as a retrospective process to confirm obesity declines and to better understand what and how policies and programs or interventions may contribute as drivers. The Childhood Obesity Declines (COBD) project's adaptation of the SSA methodology consisted of the following components: (1) establishing and convening an external expert advisory panel; (2) identification and selection of sites reporting obesity declines; (3) confirmation and review of what strategies occurred and contextual factors were present during the period of the obesity decline; and (4) reporting the findings to sites and the field., Results/discussion: The primary result of the COBD project is an in-depth examination of the question, "What happened and how did it happen in communities where the prevalence of obesity declined?" The primary aim of this article is to describe the project's methodology and present its limitations and strengths., Conclusions: Exploration of the natural experiments such that occurred in Anchorage, Granville County, New York City, and Philadelphia is the beginning of our understanding of the drivers and contextual factors that may affect childhood obesity. This retrospective examination allows us to: (1) describe targeted interventions; (2) examine the timeline and summarize intervention implementation; (3) document national, state, local, and institutional policies; and (4) examine the influence of the reach and potential multisector layering of interventions.

Background: The social ecological model (SEM) is a framework for understanding the interactive effects of personal and environmental factors that determine behavior. The SEM has been used to examine childhood obesity interventions and identify factors at each level that impact behaviors. However, little is known about how those factors interact both within and across levels of the SEM., Methods: The Childhood Obesity Declines (COBD) project was exploratory, attempting to capture retrospectively policies and programs that occurred in four communities that reported small declines in childhood obesity. It also examined contextual factors that may have influenced initiatives, programs, or policies. Data collection included policy and program assessments, key informant interviews, and document reviews. These data were aggregated by the COBD project team to form a site report for each community (available at www.nccor.org/projects/obesity-declines ). These reports were used to develop site summaries that illustrate how policies, programs, and activities worked to address childhood obesity in each study site., Results/conclusions: Site summaries for Anchorage, AK; Granville County, NC; Philadelphia, PA; and New York City, NY, describe those policies and programs implemented across the levels of the SEM to address childhood obesity and examine interactions both across and within levels of the model to better understand what factors appear important for implementation success.

Background: Although childhood obesity rates have been high in the last few decades, recent national reports indicate a stabilization of rates among some subpopulations of children. This study examines the implementation of initiatives, policies, and programs (referred to as strategies) in four communities that experienced declines in childhood obesity between 2003 and 2012., Methods and Results: The Childhood Obesity Decline project verified obesity declines and identified strategies that may have influenced and supported the decline in obesity. The project used an adaptation of the Systematic Screening and Assessment method to identify key informants in each site. Four settings were highlighted related to childhood: (1) communities, (2) schools, (3) early care and education, and (4) healthcare. The findings indicate that programs and policies were implemented across local settings (primarily in schools and early childhood settings) and at the state level, during a timeframe of supportive federal policies and initiatives., Conclusions: Multilevel approaches were aimed to improve the nutrition and physical activity environments where children spend most of their time. We hypothesized that other, more distal strategies amplified and reinforced the impact of the efforts that more directly targeted children. The simultaneous public health messaging and multilayered initiatives, supported by cross-sector partnerships and active, high-level champions, were identified as likely important contributors to success in attaining declines in rates of childhood obesity.

Background: State- and local-level policies can influence children's diet quality and physical activity (PA) behaviors. The goal of this article is to understand the enacted state and local policy landscape in four communities reporting declines in childhood obesity., Methods and Results: State-level policies were searched within the CDC's online Chronic Disease State Policy Tracking System. Local level policies were captured during key informant interviews in each of the sites. Policies were coded by setting [i.e., early care and education (ECE) also known as child care, school, community], jurisdictional level (i.e., state or local) and policy type (i.e., legislation or regulation). The time period for each site was unique, capturing enacted policies 5 years before the reported declines in childhood obesity in each of the communities. A total of 39 policies were captured across the 4 sites. The majority originated at the state level. Two policies pertaining to ECE, documented during key informant interviews, were found to be adopted at the local level., Conclusion: Similarities were noted between the four communities in the types of polices enacted. All four communities had state- and/or local-level policies that aimed to improve the nutrition environment and increase opportunities for PA in both the ECE and K-12 school settings. This article is a step in the process of determining what may have contributed to obesity declines in the selected communities.

Background: Childhood obesity remains prevalent and is increasing in some disadvantaged populations. Numerous research, policy and community initiatives are undertaken to impact this pandemic. Understudied are natural experiments. The need to learn from these efforts is paramount. Resulting evidence may not be readily available to inform future research, community initiatives, and policy development/implementation., Methods: We discuss the implications of using an adaptation of the Systematic Screening and Assessment (SSA) method to evaluate the Childhood Obesity Declines (COBD) project. The project examined successful initiatives, programs and policies in four diverse communities which were concurrent with significant declines in child obesity. In the context of other research designs and evaluation schemas, rationale for use of SSA is presented. Evidence generated by this method is highlighted and guidance suggested for evaluation of future studies of community-based childhood obesity prevention initiatives. Support for the role of stakeholder collaboratives, in particular the National Collaborative on Childhood Obesity Research, as a synergistic vehicle to accelerate research on childhood obesity is discussed., Results/discussion: SSA mapped active processes and provided contextual understanding of multi-level/component simultaneous efforts to reduce rates of childhood obesity in community settings. Initiatives, programs and policies were not necessarily coordinated. And although direct attribution of intervention/initiative/policy components could not be made, the what, by who, how, to whom was temporally associated with statistically significant reductions in childhood obesity., Conclusions: SSA provides evidence for context and processes which are not often evaluated in other data analytic methods. SSA provides an additional tool to layer with other evaluation approaches.