Deep Learning-Based Survival Analysis for Receiving a Steatotic Donor Liver Versus Waiting for a Standard Liver.

BACKGROUND: An emerging strategy to expand the donor pool is the use of a steatotic donor liver (SDLs; ≥ 30% macrosteatosis on biopsy). With the obesity epidemic and prevalence of nonalcoholic fatty liver disease, SDLs have been reported in 59% of all deceased donors. Many potential candidates need to decide whether to accept an SDL offer or remain on the waitlist for a nonsteatotic donor liver (non-SDL). The objective of this study was to compare the survival of accepting an SDL vs using a non-SDL after waiting various times. METHODS: Using data from the United States' organ procurement and transplantation network, deep survival learning predictive models were built to compare post-decision survival after accepting an SDL vs waiting for a non-SDL. The comparison subjects contain simulated 20,000 different scenarios of a candidate either accepting an SDL immediately or receiving a non-SDL after waiting various times. The research variables were selected using the LASSO-Cox and Random Survival Forest (RSF) models. The Cox proportional hazards and RSF models were also comparatively included for survival prediction. In addition, personalized survival curves for randomly selected candidates were generated. RESULT: Deep survival learning outperformed Cox proportional hazards and RSF in predicting the survival of liver transplants. Among the simulations, 25% to 30% of scenarios demonstrated a higher 3-year survival post-decision for candidates accepting an SDL than waiting and receiving a non-SDL. The difference was only 1.43% in 3-year survival post-decision between accepting an SDL and waiting 260 days (mean waitlist time) for a non-SDL. As the number of days on the waitlist increases, the difference in survival between accepting SDLs and waiting for non-SDLs decreases. CONCLUSIONS: Appropriately used SDLs could expand the donor pool and relieve the candidates' unmet need for donor livers, which presents long-term survival benefits for recipients.

The role of microglial LRRK2 kinase in manganese-induced inflammatory neurotoxicity via NLRP3 inflammasome and RAB10-mediated autophagy dysfunction.

Chronic manganese (Mn) exposure can lead to manganism, a neurological disorder sharing common symptoms with Parkinson's disease (PD). Studies have shown that Mn can increase the expression and activity of leucine-rich repeat kinase 2 (LRRK2), leading to inflammation and toxicity in microglia. LRRK2 G2019S mutation also elevates LRRK2 kinase activity. Thus, we tested if Mn-increased microglial LRRK2 kinase is responsible for Mn-induced toxicity, and exacerbated by G2019S mutation, using WT and LRRK2 G2019S knock-in mice and BV2 microglia. Mn (30 mg/kg, nostril instillation, daily for 3 weeks) caused motor deficits, cognitive impairments, and dopaminergic dysfunction in WT mice, which were exacerbated in G2019S mice. Mn induced proapoptotic Bax, NLRP3 inflammasome, IL-1ß, and TNF-α in the striatum and midbrain of WT mice, and these effects were more pronounced in G2019S mice. BV2 microglia were transfected with human LRRK2 WT or G2019S, followed by Mn (250 µM) exposure to better characterize its mechanistic action. Mn increased TNF-α, IL-1ß, and NLRP3 inflammasome activation in BV2 cells expressing WT LRRK2, which was elevated further in G2019S-expressing cells, while pharmacological inhibition of LRRK2 mitigated these effects in both genotypes. Moreover, the media from Mn-treated G2019S-expressing BV2 microglia caused greater toxicity to the cath.a-differentiated (CAD) neuronal cells compared to media from microglia expressing WT. Mn-LRRK2 activated RAB10 which was exacerbated in G2019S. RAB10 played a critical role in LRRK2-mediated Mn toxicity by dysregulating the autophagy-lysosome pathway and NLRP3 inflammasome in microglia. Our novel findings suggest that microglial LRRK2 via RAB10 plays a critical role in Mn-induced neuroinflammation.

The role of microglial LRRK2 in manganese-induced inflammatory neurotoxicity via NLRP3 inflammasome and RAB10-mediated autophagy dysfunction.

Chronic exposure to manganese (Mn) can lead to manganism, a neurological disorder sharing common symptoms with Parkinson's disease (PD). Studies have shown that Mn can increase the expression and activity of leucine-rich repeat kinase 2 (LRRK2), leading to inflammation and toxicity in microglia. LRRK2 G2019S mutation also elevates LRRK2 kinase activity. Thus, we tested if Mn-increased microglial LRRK2 kinase is responsible for Mn-induced toxicity, and exacerbated by G2019S mutation, using WT and LRRK2 G2019S knock-in mice, and BV2 microglia. Mn (30 mg/kg, nostril instillation, daily for 3 weeks) caused motor deficits, cognitive impairments, and dopaminergic dysfunction in WT mice, which were exacerbated in G2019S mice. Mn induced proapoptotic Bax, NLRP3 inflammasome, IL-1ß and TNF-α in the striatum and midbrain of WT mice, and these effects were exacerbated in G2019S mice. BV2 microglia were transfected with human LRRK2 WT or G2019S, followed by Mn (250 µM) exposure to better characterize its mechanistic action. Mn increased TNF-α, IL-1ß, and NLRP3 inflammasome activation in BV2 cells expressing WT LRRK2, which was exacerbated in G2019S-expressing cells, while pharmacological inhibition of LRRK2 mitigated these effects in both genotypes. Moreover, the media from Mn-treated BV2 microglia expressing G2019S caused greater toxicity to cath.a-differentiated (CAD) neuronal cells compared to media from microglia expressing WT. Mn-LRRK2 activated RAB10, which was exacerbated in G2019S. RAB10 played a critical role in LRRK2-mediated Mn toxicity by dysregulating the autophagy-lysosome pathway, and NLRP3 inflammasome in microglia. Our novel findings suggest that microglial LRRK2 via RAB10 plays a critical role in Mn-induced neuroinflammation.

Emerging Pharmacotherapy to Reduce Elevated Lipoprotein(a) Plasma Levels.

Lipoprotein(a) is a unique form of low-density lipoprotein. It is associated with a high incidence of premature atherosclerotic disease such as coronary artery disease, myocardial infarction, and stroke. Plasma levels of this lipoprotein and its activities are highly variable. This is because of a wide variability in the size of the apolipoprotein A moiety, which is determined by the number of repeats of cysteine-rich domains known as "kringles." Although the exact mechanism of lipoprotein(a)-induced atherogenicity is unknown, the lipoprotein has been found in the arterial walls of atherosclerotic plaques. It has been implicated in the formation of foam cells and lipid deposition in these plaques. Pharmacologic management of elevated levels of lipoprotein(a) with statins, fibrates, or bile acid sequestrants is ineffective. The newer and emerging lipid-lowering agents, such as the second-generation antisense oligonucleotides, cholesteryl ester transfer protein inhibitors, and proprotein convertase subtilisin/kexin type 9 inhibitors offer the most effective pharmacologic therapy.

Evaluation of Rapid Syphilis Testing Using the Syphilis Health Check in Florida, 2015-2016.

The Syphilis Health Check (SHC) had low estimated specificity (91.5%) in one Florida county. We investigated use of SHC by a range of Florida publicly-funded programs between 2015 and 2016 to estimate specificity, positive predictive value (PPV), field staff acceptance, and impacts on programmatic outcomes. All reported SHC results were extracted from routinely collected program data. Field staff were surveyed about SHC's utility. Analyses investigated differences between SHC and traditional syphilis testing outcomes. Of 3,630 SHC results reported, 442 were reactive; 92 (20.8%) had prior diagnoses of syphilis; 7 (1.6%) had no further testing. Of the remaining 343; 158 (46.0%) were confirmed cases, 168 (49.0%) were considered false-positive, and 17 (5.0%) were not cases but not clearly false-positive. Estimated specificity of SHC was 95.0%. Overall, 48.5% of positives became confirmed cases (PPV). PPV varied according to prevalence of syphilis in populations tested. Staff (90%) thought SHC helped identify new cases but expressed concern regarding discordance between reactive SHC and lab-based testing. Programmatic outcomes assessment showed shorter time to treatment and increased numbers of partners tested for the SHC group; these enhanced outcomes may better mitigate the spread of syphilis compared to traditional syphilis testing alone, but more research is needed.

Community-Based Participatory Research at Jacksonville Florida Superfund Ash Site: Toxicology Training to Improve the Knowledge of the Lay Community.

Until the late 1960's, Jacksonville, Florida incinerated its solid waste with the resultant ash deposited in landfills or used to fill flood-prone areas. These filled areas were later developed into parks, school sites and residential areas. Lead in soil at these sites was the major toxicant of concern and driver of clean-up actions. During the period of assessment of lead-levels in soil, there were no established lines of communication between the City and residents of affected neighborhoods resulting in mistrust in the community. To address communication issues, a community-based, culturally sensitive Community Environmental Toxicology Curriculum (CETC) and a short video were developed for community stakeholders to inform them of risks, health effects, remediation processes and preventive measures. Pre-and post-tests were developed to measure knowledge gained from the toxicology training. Learning gains averaged 47% and 24% for the community leaders and residents respectively. Most participants strongly agreed that the community toxicology curriculum was a useful tool for promoting awareness of environmental risks in their community and addressing the gap in trust between residents and agencies involved in site remediation.

The Role of Historically Black College and University Medical Schools in Academic Medicine.

INTRODUCTION: Although less than 3% of medical schools are considered Historically Black Colleges and Universities (HBCU), they have played a significant role in the education of Black physicians. METHODS: The Association of American Medical Colleges (AAMC) databases were used to obtain faculty and student demographic data from 2003-2013. We analyzed racial distributions of faculty and students at HBCU medical schools compared with all other medical schools and calculated correlations between rates of Black chairs, faculty, and students. RESULTS: Although HBCUs represent 2.4% of medical colleges, they house 31% of Black chairs, 10% of Black faculty and 14% of Black students. A significant (a* < .002) positive correlation was found between rates of Black chairs and students. CONCLUSIONS: Black chairs are associated with higher percentages of Black students. Medical colleges may find that increasing the number of Black chairs increases the number of Black medical students.

Does Place of Residence or Time of Year Affect the Risk of Stroke Hospitalization and Death? A Descriptive Spatial and Temporal Epidemiologic Study.

BACKGROUND: Identifying geographic areas with significantly high risks of stroke is important for informing public health prevention and control efforts. The objective of this study was to investigate geographic and temporal patterns of stroke hospitalization and mortality risks so as to identify areas and seasons with significantly high burden of the disease in Florida. The information obtained will be useful for resource allocation for disease prevention and control. METHODS: Stroke hospitalization and mortality data from 1992 to 2012 were obtained from the Florida Agency for Health Care Administration. Age-adjusted stroke hospitalization and mortality risks for time periods 1992-94, 1995-97, 1998-2000, 2001-03, 2004-06, 2007-09 and 2010-12 were computed at the county spatial scale. Global Moran's I statistics were computed for each of the time periods to test for evidence of global spatial clustering. Local Moran indicators of spatial association (LISA) were also computed to identify local areas with significantly high risks. RESULTS: There were approximately 1.5 million stroke hospitalizations and over 196,000 stroke deaths during the study period. Based on global Moran's I tests, there was evidence of significant (p<0.05) global spatial clustering of stroke mortality risks but no evidence (p>0.05) of significant global clustering of stroke hospitalization risks. However, LISA showed evidence of local spatial clusters of both hospitalization and mortality risks with significantly high risks being observed in the north while the south had significantly low risks of stroke deaths. There were decreasing temporal trends and seasonal patterns of both hospitalization and mortality risks with peaks in the winter. CONCLUSIONS: Although stroke hospitalization and mortality risks have declined in the past two decades, disparities continue to exist across Florida and it is evident from the results of this study that north Florida may, in fact, be part of the stroke belt despite not being in any of the traditional stroke belt states. These findings are useful for guiding public health efforts to reduce/eliminate inequities in stroke outcomes and inform policy decisions. There is need to continually identify populations with significantly high risks of stroke to better guide the targeting of limited resources to the highest risk populations.

Perspectives of Stakeholders on Implementing a Farm-to-University Program at an HBCU.

OBJECTIVE: To explore the perspectives of various stakeholders on whether an HBCU has the resources to establish a farm-to-university program that can improve fruits and vegetables intake among African American students. Additionally, this study assessed students' satisfaction with fruits and vegetables served in University dining halls, and their desire for changes in policies to increase local fruits and vegetables access on campus. METHODS: This study employed a mixed method data collection strategy. Semi-structured interviews were used to explore the stakeholders' perspectives and self-administered questionnaires were used to assess students' satisfaction with fruits and vegetables and desire for policy changes. RESULTS: Barriers reported by both food service administrators and farmers were cost and variation in supply and demand. Students expressed lack of satisfaction with fresh produce served in campus dining halls and a desire for change in policies to increase local fruits and vegetables access on campus. CONCLUSION: While there is student desire for improved access to fresh produce on campus, there are perceived barriers to overcome. University partnerships are needed to address the desired nutritional improvements.

Florida county health department, environmental health 2006 survey: do rural counties know "what to do' in a chemical or all-hazards event?

The objective of the study described here was to determine basic plans and collaboration with first responder stakeholders and to identify perceived roles and responsibilities in preparing for and responding to a chemical disaster. A survey was developed and provided to environmental health personnel at county health departments (CHDs) in Florida. Most of the counties had good collaborative relationships with first responder stakeholders. A little more than half of the respondents had access to a resource manual with contact information and had developed and maintained a chemical plan. Rural counties were less likely to know "what to do" or their responsibility in a chemical disaster; however, both rural and nonrural counties were equally likely not to have a written plan. Public health agencies at the local CHD must be the communicators of public health messages in coordination with the incident commander and the state communications office in a chemical disaster, so it is important to strengthen collaboration and cooperation with chemical response stakeholders.

Racial Differences in Length of Stay for Patients Who Leave Against Medical Advice from U.S. General Hospitals.

There is a paucity of published literature on the length of hospital stays (LOS) for patients who leave against medical advice (AMA) and on the factors that predict their LOS. The purpose of the study is to examine the relationship between race and the LOS for AMA patients after adjusting for patient and hospital characteristics. National Hospital Discharge Survey (NHDS) data were used to describe LOS for AMA patients aged 18 years or older. Patient characteristics included age, sex, race, marital status, insurance, and diagnosis (ICD-9-CM). Hospital characteristics consisted of ownership, region and bed size. LOS was the major outcome measure. Using data from all years 1988-2006, the expected time to AMA discharge was first examined as a function of race, then adjusting for year terms, patient and hospital characteristics, and major medical diagnoses and mental illness. The unadjusted effect of race on the expected time of leaving AMA was about twice the adjusted effect. After controlling for the other covariates, the expected time to AMA discharge is 20% shorter for Blacks than Whites. The most significant predictors included age, insurance coverage, mental illness, gender, and region. Factors identified in this study offer insights into directions for evidence based- health policy to reduce AMA discharges.

The role of the wound care nurse: an integrative review.

The role of the wound care nurse has developed to meet the need for expert wound care advice. Internationally, the role has developed with a variety of different titles. Although all positions have some common tasks and obligations, there remain gaps in knowledge around the role of the wound care nurse. This article aims to determine the state of knowledge in relation to the context of practice, scope of practice and impact of the wound care nurse. An integrative review design was used to allow a broad search strategy and to gather papers from a variety of sources. A multi-method search strategy of the literature published between 1980-2011 was undertaken. This included 5 electronic databases, a thesis search and manual search. It was found that the characteristics of the patients wound care nurses care for reflect an ageing population and disease processes, including diabetes and obesity. Internationally, there is little consensus on the level of competence, educational requirements and qualifications required to practise as a wound care nurse. There was some evidence that the wound care nurse improved healing times and decreased pressure injury prevalence.

Obesity literacy and culture among African American women in Florida.

OBJECTIVE: To explore causal explanations of obesity among African-American women of diverse weight across the life spectrum. METHODS: In-depth interviews were conducted with adult African-American women of healthy weight (N = 10), overweight (N = 10), and obese weight (N = 20) to evaluate the relationship between causal explanations of obesity and weight. RESULTS: Generally overlooked dimensions of health definitions were discovered. Differences in weight definitions were detected between women of different weights. Terminology, symptoms, and solutions to obesity were detected between the women of different weights and public health recommendations. CONCLUSION: Identified causal discrepancies will help bridge the disconnection between public health recommendations and African-American women's perceptions with tailored interventions.