Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation.

Signals from the endothelium play a pivotal role in pancreatic lineage commitment. As such, the fate of the epithelial cells relies heavily on the spatiotemporal recruitment of the endothelial cells to the embryonic pancreas. Although it is known that VEGFA secreted by the epithelium recruits the endothelial cells to the specific domains within the developing pancreas, the mechanism that controls the timing of such recruitment is poorly understood. Here, we have assessed the role of focal adhesion kinase (FAK) in mouse pancreatic development based on our observation that the presence of the enzymatically active form of FAK (pFAK) in the epithelial cells is inversely correlated with vessel recruitment. To study the role of FAK in the pancreas, we conditionally deleted the gene encoding focal adhesion kinase in the developing mouse pancreas. We found that homozygous deletion of Fak (Ptk2) during embryogenesis resulted in ectopic epithelial expression of VEGFA, abnormal endothelial recruitment and a delay in endocrine and acinar cell differentiation. The heterozygous mutants were born with no pancreatic phenotype but displayed gradual acinar atrophy due to cell polarity defects in exocrine cells. Together, our findings imply a role for FAK in controlling the timing of pancreatic lineage commitment and/or differentiation in the embryonic pancreas by preventing endothelial recruitment to the embryonic pancreatic epithelium.

Fish consumption and awareness of fish advisories among Burmese refugees: A respondent-driven sampling study in Milwaukee, Wisconsin.

BACKGROUND: Since 2000, more than 6000 Burmese refugees were resettled in Wisconsin. The Burmese diet is traditionally rich in fish and fish products, and studies show that Burmese refugees continue to rely on local waterbodies for food. Given that Wisconsin has five Areas of Concern (AOC) that are severely affected by pollution, long-term exposure to contaminants in sport-caught fish is a health concern. To better understand fish consumption among Burmese refugees, we conducted a biomonitoring study in Milwaukee. The present study examined Burmese refugees' fish consumption habits and awareness of fish advisories. METHODS: We used respondent-driven sampling (RDS) methodology to recruit Burmese refugees in Milwaukee. RDS Analysis Tool 7.1 was used to obtain adjusted population estimates for demographic characteristics, fish consumption habits, and awareness of fish advisories. Homophily and equilibrium were investigated to evaluate the effectiveness of RDS in recruitment. RESULTS: Initiated by five active seeds, we recruited 103 respondents to participate in the study. Respondents had a strong preference to recruit those with the same ethnicity (Homophily-score: 0.614 to 0.699) and a relatively weak preference to recruit those with the same sex (Homophily-score: 0.188 to 0.222) to participate in our study. The majority (72.5%) of respondents were women of childbearing age (WCBA). Most (68.5%) had 8th grade or less education. Regarding sportfish consumption per month in the last year, 30.6% reported eating 1-3 meals and 21.2% reported eating more than 3 meals. When asked about purchased fish consumption per month, 26.3% reported eating 1-3 meals. The overwhelming majority were not aware of safe-eating sportfish guidelines for Wisconsin (88.3%) or Milwaukee waterbodies (96.6%). CONCLUSIONS: RDS is an effective methodology to recruit hard-to-reach populations, such as the Burmese surveyed in this study. High percentages of WCBA eating potentially contaminated sportfish meals, low awareness of consumption advisories, and limited economic resources make the Burmese population more likely to be exposed to contaminants. Health education efforts should be focused in this vulnerable population, particularly among Burmese WCBA.

Perfluoroalkyl substances and fish consumption.

BACKGROUND: Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and dyslipidemia. The major source of PFAS exposure in the general population is thought to be consumption of seafood. OBJECTIVES: In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported fish and shellfish consumption, using a representative sample of the U.S. METHODS: Data on PFAS levels and self-reported fish consumption over the past 30 days were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Ordinary least squares regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with serum PFAS concentrations. Additional models were further adjusted for other potential exposures including military service and consumption of ready-to-eat and fast foods. RESULTS: Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUA). The PFAS with the highest concentrations were PFOS, followed by PFOA, PFHxS and PFNA (medians of 8.3, 2.7, 1.5 and 1.0ng/mL). Fish consumption was generally low, with a median of 1.2 fish meals and 0.14 shellfish meals, reported over the past 30 days. After adjusting for demographic characteristics, total fish consumption was associated with reduced MPAH, and with elevated PFDE, PFNA and PFuDA. Shellfish consumption was associated with elevations of all PFAS examined except MPAH. Certain specific fish and shellfish types were also associated with specific PFAS. Adjustment for additional exposure variables resulted in little to no change in effect estimates for seafood variables. CONCLUSIONS: PFAS are emerging contaminants with widespread exposure, persistence, and potential for adverse health effects. In the general population, fish and shellfish consumption are associated with PFAS levels, which may indicate an avenue for education and outreach.

Comprehension of Fish Consumption Guidelines Among Older Male Anglers in Wisconsin.

Although awareness of Wisconsin's fish consumption guidelines is high among older male anglers, little is known about comprehension of guideline content, and many anglers have levels of contaminants high enough to be associated with adverse health outcomes. The Environmental Protection Agency Great Lakes Restoration Initiative supported evaluation and revision of Wisconsin's fish consumption guideline program, using a web based survey of male Wisconsin anglers over the age of 50. A total of 3740 men completed the online survey; the median age of respondents was 62 years, and nearly all had lived and fished in Wisconsin for over 10 years. Comprehension of guideline content was relatively high, although two knowledge gaps were identified, one relating to mercury exposures and fish preparation, and the other to polychlorinated biphenyl content of certain fish species. The fishing regulations booklet distributed with annual fishing licenses and warning signs posted at fishing locations were commonly reported sources of guideline information in Wisconsin. Residents of coastal counties and consumers of Great Lakes fish were more likely to report guideline knowledge and behavior changes reflective of guideline knowledge, when compared to inland residents and those not consuming Great Lakes fish, respectively. In general, Wisconsin's consumption guidelines do not appear to discourage men from eating the fish they catch; rather, the most common behavioral changes included modifying the species eaten or the water body source of their meals. Continued efforts to educate anglers about the risks and benefits of fish consumption are needed.

Mercury-impacted scrap metal: Source and nature of the mercury.

The reuse and recycling of industrial solid wastes such as scrap metal is supported and encouraged both internationally and domestically, especially when such wastes can be used as substitutes for raw material. However, scrap metal processing facilities, such as mini-mills, have been identified as a source of mercury (Hg) emissions in the United States. This research aims to better define some of the key issues related to the source and nature of mercury in the scrap metal waste stream. Overall, it is difficult to pinpoint the key mercury sources feeding into scrap metal recycling facilities, quantify their associated mercury concentrations, or determine which chemical forms are most significant. Potential sources of mercury in scrap metal include mercury switches from discarded vehicles, electronic-based scrap from household appliances and related industrial systems, and Hg-impacted scrap metal from the oil and gas industry. The form of mercury associated with scrap metal varies and depends on the source type. The specific amount of mercury that can be adsorbed and retained by steel appears to be a function of both metallurgical and environmental factors. In general, the longer the steel is in contact with a fluid or condensate that contains measurable concentrations of elemental mercury, the greater the potential for mercury accumulation in that steel. Most mercury compounds are thermally unstable at elevated temperatures (i.e., above 350 °C). As such, the mercury associated with impacted scrap is expected to be volatilized out of the metal when it is heated during processing (e.g., shredding or torch cutting) or melted in a furnace. This release of fugitive gas (Hg vapor) and particulates, as well as Hg-impacted bag-house dust and control filters, could potentially pose an occupational exposure risk to workers at a scrap metal processing facility. Thus, identifying and characterizing the key sources of Hg-impacted scrap, and understanding the nature and extent of associated releases, represent a practical research need that is essential for improving the environmental management of Hg-impacted scrap and assessing measures to protect workers from potential health and safety hazards that might be posed by mercury and Hg-impacted scrap.

Survey of nutrition screening practices in pediatric hospitals across the United States.

BACKGROUND: Nutrition screening on admission is critically important to systematically identify patients with undernutrition given the known relationship with deleterious clinical outcomes. Limited data exist regarding optimal processes and criteria for pediatric nutrition screening. Therefore, we sought to characterize nutrition screening practices in pediatric hospitals. METHODS: A total of 365 inpatient pediatric hospitals in the United States were identified, eligible, and contacted. Eligible hospitals included general pediatric hospitals, adult hospitals with pediatric units, and specialty pediatric hospitals. One respondent at each eligible hospital was asked to complete a 33-question survey of admission nutrition screening practices. RESULTS: Of 268 survey respondents, 37% represented pediatric units in adult hospitals, 35% general pediatric hospitals, and 28% pediatric specialty or psychiatric hospitals. A total of 98.5% endorsed the existence of a screening process on admission. Anthropometrics (eg, body mass index z score, 84%) and nutrition status (eg, change in intake, 67%) were the most common screening criteria applied. A nutrition screening instrument was used in 37% of institutions, and only 31% of institutions reported using pediatric-specific screening instruments. Pediatric units within adult hospitals were 1.38 times more likely to use a screening instrument validated in any population. Barriers to nutrition screening included the lack of a standard screening procedure and insufficient staff to conduct screening. Fifty-four percent of respondents reported a desire to change their hospital's nutrition screening process. CONCLUSION: Most pediatric hospitals screen for nutrition risk on admission. However, methods and criteria varied widely across pediatric hospitals, highlighting the importance of standardized best practices.

Improving anthropometric measurements in hospitalized children: A quality-improvement project.

BACKGROUND: The objective of this quality-improvement project was to increase documentation rates of anthropometrics (measured weight, length/height, and body mass index [BMI], which are critical to identify patients at malnutrition (undernutrition) risk) from <50% to 80% within 24 hours of hospital admission for pediatric patients. METHODS: Multidisciplinary champion teams on surgical, cardiac, and intensive care (ICU) pilot units were established to identify and iteratively test interventions addressing barriers to documentation from May 2016 to June 2018. Percentage of patients with documented anthropometrics <24 h of admission was assessed monthly by statistical process control methodology. Percentage of patients at malnutrition (undernutrition) risk by anthropometrics was compared by χ2 for 4 months before and after intervention. RESULTS: Anthropometric documentation rates significantly increased (P < 0.001 for all): BMI, from 11% to 89% (surgical), 33% to 57% (cardiac), and 16% to 51% (ICU); measured weight, from 24% to 88% (surgical), 69% to 83% (cardiac), and 51% to 67% (ICU); and length/height, from 12% to 89% (surgical), 38% to 57% (cardiac), and 26% to 63% (ICU). Improvement hospital-wide was observed (BMI, 42% to 70%, P < 0.001) with formal dissemination tactics. For pilot units, moderate/severe malnutrition (undernutrition) rates tripled (1.2% [24 of 2081] to 3.4% [81 of 2374], P < 0.001). CONCLUSION: Documentation of anthropometrics on admission substantially improved after establishing multidisciplinary champion teams. Goal rate (80%) was achieved within 26 months for all anthropometrics in the surgical unit and for weight in the cardiac unit. Improved documentation rates led to significant increase in identification of patients at malnutrition (undernutrition) risk.

Fish consumption and advisory awareness in the Great Lakes basin.

BACKGROUND: Fish is a dietary staple in the United States. Risk of exposure to persistent contaminants through fish consumption is a significant health concern. Great Lakes basin states, along with the US Environmental Protection Agency and the Great Lakes Consortium for Fish Consumption Advisories, have developed and continuously updated fish consumption advisories specifically for the Great Lakes basin residents. OBJECTIVES: To characterize Great Lakes basin residents' fish consumption and advisory awareness, we conducted a point-in-time survey to describe fish consumption habits and awareness of state and EPA/FDA fish advisories. METHODS: We used a randomized, address-based sampling approach to recruit respondents from the eight Great Lakes basin states. Weighted survey analysis procedures were used to estimate population prevalence of fish consumption habits, state and EPA/FDA advisory awareness, and demographic and background characteristics. Logistic regression models were used to assess the associations between demographic and background factors and fish consumption and awareness of advisories, respectively. RESULTS: About 92% of respondents, representing an estimated 61 million adults, reported eating fish in the last 12 months. About 64% of respondents only consumed commercial fish, and an estimated 5 million fish consumers exceeded the EPA/FDA recommended limit for fish meals. Minorities were more likely to exceed the EPA/FDA recommended limit. About half of the respondents were aware of state or EPA/FDA advisories; however, minorities and women were less aware of the EPA/FDA advisory. After adjusting for demographic characteristics, sportfish consumption was significantly associated with state advisory awareness; commercial fish consumption was significantly associated with EPA/FDA awareness. DISCUSSION: Most respondents only consumed commercial fish, but an estimated 18.6 million adults consumed sportfish. While half of the fish consumers were aware of state or EPA/FDA advisories, minorities and women continue to be less aware of fish advisories. Improved outreach strategies are needed to inform them about safe fish-consumption guidelines.

Perfluoroalkyl substances and metabolic syndrome.

BACKGROUND: Perfluoroalkyl substances (PFAS) are a class of contaminants used in many industrial applications and consumer products. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects. OBJECTIVES: In this analysis we examine PFAS levels and their association with metabolic syndrome and its components, using a representative sample of the U.S. METHODS: Data on PFAS levels and metabolic syndrome components were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Logistic regression models were used to identify associations between metabolic syndrome, its individual components, and serum PFAS concentrations. RESULTS: Over one-third (37%) of participants met the definition for metabolic syndrome, with increased waist circumference and elevated glucose being the most commonly reported components. Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUnDA). The PFAS with the highest concentrations was PFOS (median 8.4 ng/mL), followed by PFOA, PFHxS and PFNA. After adjusting for potential confounders, PFNA was associated with increased risk of metabolic syndrome and well as several individual components, while the highest levels of PFHxS were associated with elevated triglycerides. Other PFAS were associated with decreased risk of at least one outcome. CONCLUSIONS: Associations between PFAS and metabolic syndrome are inconsistent within and across studies. PFNA was consistently associated with increased risk for components of the syndrome, a finding that warrants further investigation.

An Occupational Legacy: Malignant Mesothelioma Incidence and Mortality in Wisconsin.

OBJECTIVES: The aim of the study was to describe mesothelioma occurrence in Wisconsin from 1997 to 2013 by usual industry and occupation (I&O), including occupations generally considered low risk. METHODS: Population-based rates and standardized incidence and mortality ratios were calculated. Two case-control analyses were designed to compare mesothelioma incidence and mortality in specific I&O groups with occurrence of (1) brain and central nervous system cancers and (2) other causes of death, using logistic regression. RESULTS: Mesothelioma incidence and mortality were elevated in Wisconsin (SIRadj = 1.20 [1.13 to 1.28]; SMRadj = 1.30 [1.22 to 1.38]). Certain industry (construction, manufacturing) and occupation (construction and extraction) groups were associated with increased odds of mesothelioma, with some evidence of increased risk among teachers. CONCLUSIONS: Forty years after the Occupational and Safety Health Act, mesothelioma incidence and mortality remain elevated in Wisconsin, with increased risk continuing for certain I&O groups.

Changes in Hair Mercury Levels Among Women of Child-Bearing Age Following an Educational Intervention.

OBJECTIVE: Describe mercury exposures among women of childbearing age before and after an educational intervention. METHODS: Women age 18 to 45 were recruited to participate in an educational intervention concerning fish consumption. Fish consumption habits and total mercury concentration in hair were assessed pre- and post-intervention. Regression models examined associations between mercury, fish consumption, and demographics. RESULTS: Overall, 234 women completed the study. On average, mercury concentrations increased by 0.01 ppm (parts per million) following the intervention, despite declines in fish consumption; however, women in the 90th percentile for mercury at baseline decreased concentrations significantly while maintaining high rates of fish consumption. Mercury concentrations were positively correlated with fish consumption and certain demographic characteristics. CONCLUSIONS: The intervention reached individuals most at-risk. Healthcare providers should discuss fish consumption habits with women to encourage consumption of low-risk fish, and identify women needing education and counseling.

Associations Between Fish Consumption and Contaminant Biomarkers With Cardiovascular Conditions Among Older Male Anglers in Wisconsin.

OBJECTIVE: The aim of this study was to determine fish consumption habits and contaminant exposures associated with adverse cardiovascular outcomes among older male anglers. METHODS: One hundred fifty-four men aged 50 years and older living and fishing in Wisconsin completed a detailed survey and provided hair and blood samples. Associations between fish consumption and body burdens of several contaminants, with self-reported cardiovascular outcomes, were evaluated. RESULTS: Consuming fish species with higher methyl mercury content was positively associated with odds of angina, coronary heart disease (CHD), or heart attack, while consuming fattier species was negatively associated with high blood pressure or high cholesterol. Total mercury in blood was associated with 27% higher odds of heart attack, and certain classes of polychlorinated biphenyls were positively associated with CHD. CONCLUSION: Total mercury exposures may affect cardiovascular outcomes. Educational interventions promoting consumption of fish low in methyl mercury among older male anglers are needed.

Fish Consumption, Levels of Nutrients and Contaminants, and Endocrine-Related Health Outcomes Among Older Male Anglers in Wisconsin.

OBJECTIVE: The aim of this study was to examine associations between endocrine disorders, fish consumption habits, and biomarkers of contaminants and nutrients METHODS: : Male anglers aged at least 50 years living in Wisconsin (n = 154) completed a questionnaire and provided biological samples. Adjusted logistic regression models were used to evaluate risk factors for endocrine outcomes. RESULTS: Nineteen percent of anglers reported either pre-diabetes or diabetes, while 4.6% reported thyroid disease. There were few associations between endocrine disease and fish consumption, fish meal source, or species, aside from a notable increase in diabetes risk with lake trout consumption. Docosahexaenoic acid, certain polychlorinated biphenyls (PCBs), and perfluorinated compounds were associated with an increased risk of diabetes or pre-diabetes. PCBs were associated with a decreased risk of thyroid disease. CONCLUSION: Fish consumption patterns may affect risk for endocrine outcomes, but direction and magnitude of association may depend on the balance of the contaminants and nutrients in the individual diet.

Perfluoroalkyl substances in older male anglers in Wisconsin.

BACKGROUND: Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and to dyslipidemia. The major source of PFAS exposure in the general population is seafood. OBJECTIVES: In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported health outcomes, in a group of older male anglers in Wisconsin with high fish consumption. METHODS: A biomonitoring study of male anglers aged 50 and older living in Wisconsin collected detailed information on fish consumption, demographics and self-reported health outcomes, along with hair and blood samples for biomarker analysis. Sixteen different PFAS were extracted from serum samples. Regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with PFAS biomarker levels in blood, as well as associations between PFAS and self-reported health outcomes, adjusting for potential confounders. RESULTS: Seven PFAS were detected in at least 30% of participants and were used in subsequent analyses (PFDA, PFHpS, PFHxS, PFNA, PFOA, PFOS, PFuDA). The PFAS with the highest levels were PFOS, followed by PFOA, PFHxS and PFNA (medians of 19.0, 2.5, 1.8 and 1.4ng/mL). In general, increasing age was associated with higher PFAS levels, while increasing BMI were associated with lower PFAS levels. Greater alcohol consumption was associated with higher levels of PFHpS, PFHxS and PFOA. Associations with smoking and employment did not show a consistent pattern. Associations between fish consumption and PFAS were generally weak, with the exception of notably higher PFDA and PFHpS with both other locally-caught fish, and restaurant-purchased fish. Regarding associations with health outcomes, PFuDA, PFNA and PFDA were all associated with increased risk of pre-diabetes and/or diabetes. PFHpS was associated with a significantly increased risk of high cholesterol; PFDA and PFuDA also showed notable, though non-significant associations. All PFAS evaluated were associated with lower risk of hypertension although the only significant odds ratio was that for PFNA. There were no associations between any of the PFAS examined and either coronary heart disease, or the grouped outcome of any cardiovascular condition. CONCLUSIONS: PFAS are emerging contaminants with widespread exposure, persistence, and potential for adverse health effects. In this study population, demographic patterns may reflect differences in exposure sources, or possibly differences in adsorption and metabolism. PFAS were associated mainly with endocrine related outcomes, with a general trend towards increased risk of glucose intolerance and high cholesterol. Continued research on the risks and benefits of fish consumption is important due to potential exposure to PFAS and noted associations with highly prevalent adverse health outcomes.