Cell death and autophagy after severe hypoxic-ischemic encephalopathy in term newborns

Introduction: Various studies from hypoxic-ischemic animals haveinvestigated neuroprotection by targeting necrosis and apoptosis with inconclusive results. Three types of cell death have been described: apoptosis, necrosis and more recently, autophagic cell death. While autophagy is a physiological process of degradation of cellular components, excessive autophagy may be involved in cell death. Recent studies showed that inhibition of autophagy is neuroprotective in rodent neonatal models of cerebral ischemia. Furthermore, neonatal hypoxia-ischemia strongly increased neuronal autophagic flux which is linked to cell death in a rat model of perinatal asphyxia. Following our observations in animals, the aim of the present study was to characterize the different neuronal death phenotypes and to clarify whether autophagic cell death could be also involved in neuronal death in the human newborns after perinatal asphyxia. Methods: we selected retrospectively and anonymously all newborns who died in our unit of neonatology between 2004 and 2009, with the following criteria: gestational age >36 weeks, diagnosis of perinatal asphyxia (Apgar <5 at 5 minutes, arterial pH <7.0 at 1 hour of life and encephalopathy Sarnat III) and performed autopsy. The brain of 6 cases in asphyxia group and 6 control cases matching gestational age who died of pulmonary or other malformations were selected. On histological sections of thalamus, frontal cortex and hippocampus, different markers of apoptosis (caspase 3, TUNEL), autophagosomes (LC3-II) and lysosomes (LAMP1, Cathepsin D) were tested by immunohistochemistry. Results: Preliminary studies on markers of apoptosis (TUNEL, caspase 3) and of autophagy (Cathepsin D, LC3II, LAMP1) showed an expected increase of apoptosis, but also an increase of neuronal autophagic flux in the selected areas. The distribution seems to be region specific. Conclusion: This is the first time that autophagic flux linked with cell death is shown in brain of human babies, in association with hypoxicischemic encephalopathy. This work leads to a better understanding of the mechanisms associated with neuronal death following perinatal asphyxia and determines whether autophagy could be a promising therapeutic target.

Cardiologie. Tests de réactivité plaquettaire: mise à jour pour le praticien [Cardiology. Platelet function testing for clinicians].

Platelet P2YI2 receptor inhibition with clopidogrel, prasugrel or ticagrelor plays a key role to prevent recurrent ischaemic events after percutaneous coronary intervention in acute coronary syndromes or elective settings. The degree of platelet inhibition depends on the antiplatelet medication used and is influenced by clinical and genetic factors. A concept of therapeutic window exists. On one side, efficient anti-aggregation is required in order to reduce cardio-vascular events. On the other side, an excessive platelet inhibition represents a risk of bleeding complications. This article describes the current knowledge about some platelet function tests and genetic tests and summarises their role in the clinical practice.

Road Safety Audit for US 6 from the ECL of Iowa City to the WCL of West Liberty in Johnson and Muscatine Counties, Iowa, 2008

Approximately 13.2 miles of US 6 in eastern Iowa extends from the east corporate limits of Iowa City, Iowa, to the west corporate limits of West Liberty, Iowa. This segment of US 6 is a service level B primary highway, with an annual daily traffic volume varying from 3,480 vehicles per day (vpd) to 5,700 vpd. According to 2001–2007 crash density data from the Iowa Department of Transportation (Iowa DOT), the corridor is currently listed among the top 5% of non-freeway Iowa DOT roads in several crash categories, including crashes involving excessive speed, impaired drivers, single-vehicle run-off-road, and multiple-vehicle crossed centerline. A road safety audit of this corridor was deemed appropriate by the Iowa Department of Transportation’s Office of Traffic and Safety. Staff and officials from the Iowa DOT, Iowa State Patrol, Governor’s Traffic Safety Bureau, Federal Highway Administration, Center for Transportation Research and Education, and several local law enforcement and transportation agencies met to review crash data and discuss potential safety improvements to this segment of US 6. This report outlines the findings and recommendations of the road safety audit team to address the safety concerns on this US 6 corridor and explains several selected mitigation strategies.

Field Evaluation of Elliptical Steel Dowel Performance, 2006

Joints are always a concern in the construction and long-term performance of concrete pavements. Research has shown that we need some type of positive load transfer across transverse joints. The same research has directed pavement designers to use round dowels spaced at regular intervals across the transverse joint to distribute the vehicle loads both longitudinally and transversely across the joint. The goal is to reduce bearing stresses on the dowels and the two pavement slab edges and erosion of the underlying surface, hence improved long-term joint and pavement structure performance. Road salts cause metal corrosion in doweled joints, excessive bearing stresses hollow dowel ends, and construction processes are associated with cracking pavement at the end of dowels. Dowels are also a cost factor in the pavement costs when joint spacing is reduced to control curling and warping distress in pavements. Designers desire to place adequate numbers of dowels spaced at the proper locations to handle the anticipated loads and bearing stresses for the design life of the pavement. This interim report is the second of three reports on the evaluation of elliptical steel dowels. This report consists of an update on the testing and performance of the various shapes and sizes of dowels. It also documents the results of the first series of performance surveys and draws interim conclusions about the performance of various bar shapes, sizes, spacings, and basket configurations. In addition to the study of elliptical steel dowel performance, fiber reinforced polymers (FRP) are also tested as elliptical dowel material (in contrast to steel) on a section of the highway construction north of the elliptical steel test sections.

09032-017 Miller Creek Watershed Final Report

Miller Creek is on the 2006 Section 303d Impaired Waters List and has a 19,926 acre watershed. All indicators, as reported in the Miller Creek assessment, show that the impairment is due to sediment and nutrient delivery from upland runoff which contributes to elevated water temperatures, excessive algae, and low dissolved oxygen levels within the stream. In an effort to control these problems, the Miller Creek Water Quality Project will target areas of 5 tons per acre or greater soil loss or with 0.5 tons per acre or greater sediment delivery rates. The assessment revealed these targeted priority lands make up 32% or 6,395 acres of the Miller Creek watershed. Priority lands include cropland, pasture land, timber, and sensitive riparian areas. It is the goal of this project to reduce sediment delivery by 70% on 60% or 3,837 acres of these priority lands. This will be accomplished through installation of strategically placed structural practices, rotational grazing systems, and buffer strips. These practices will reduce soil loss, reduce sediment delivery, improve water quality, and improve wildlife habitat in the watershed. Utilizing partnerships with NRCS and IDALS-DSC will be important in making this project successful. In addition to using matching funds from EQIP, WHIP, and CRP, the Monroe SWCD is committed to prioritizing local cost share funds through IFIP and REAP for use in the Miller Creek Watershed.

Water-filtered infrared-A radiation (wIRA) is not implicated in cellular degeneration of human skin.

BACKGROUND: Excessive exposure to solar ultraviolet radiation is involved in the complex biologic process of cutaneous aging. Wavelengths in the ultraviolet-A and -B range (UV-A and UV-B) have been shown to be responsible for the induction of proteases, e. g. the collagenase matrix metalloproteinase 1 (MMP-1), which are related to cell aging. As devices emitting longer wavelengths are widely used in therapeutic and cosmetic interventions and as the induction of MMP-1 by water-filtered infrared-A (wIRA) had been discussed, it was of interest to assess effects of wIRA on the cellular and molecular level known to be possibly involved in cutaneous degeneration. OBJECTIVES: Investigation of the biological implications of widely used water-filtered infrared-A (wIRA) radiators for clinical use on human skin fibroblasts assessed by MMP-1 gene expression (MMP-1 messenger ribonucleic acid (mRNA) expression).Methods: Human skin fibroblasts were irradiated with approximately 88% wIRA (780-1400 nm) and 12% red light (RL, 665-780 nm) with 380 mW/cm(2) wIRA(+RL) (333 mW/cm(2) wIRA) on the one hand and for comparison with UV-A (330-400 nm, mainly UV-A1) and a small amount of blue light (BL, 400-450 nm) with 28 mW/cm(2) UV-A(+BL) on the other hand. Survival curves were established by colony forming ability after single exposures between 15 minutes and 8 hours to wIRA(+RL) (340-10880 J/cm(2) wIRA(+RL), 300-9600 J/cm(2) wIRA) or 15-45 minutes to UV-A(+BL) (25-75 J/cm(2) UV-A(+BL)). Both conventional Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and quantitative real-time RT-PCR techniques were used to determine the induction of MMP-1 mRNA at two physiologic temperatures for skin fibroblasts (30 degrees C and 37 degrees C) in single exposure regimens (15-60 minutes wIRA(+RL), 340-1360 J/cm(2) wIRA(+RL), 300-1200 J/cm(2) wIRA; 30 minutes UV-A(+BL), 50 J/cm(2) UV-A(+BL)) and in addition at 30 degrees C in a repeated exposure protocol (up to 10 times 15 minutes wIRA(+RL) with 340 J/cm(2) wIRA(+RL), 300 J/cm(2) wIRA at each time). RESULTS: Single exposure of cultured human dermal fibroblasts to UV-A(+BL) radiation yielded a very high increase in MMP-1 mRNA expression (11 +/-1 fold expression for RT-PCR and 76 +/-2 fold expression for real-time RT-PCR both at 30 degrees C, 75 +/-1 fold expression for real-time RT-PCR at 37 degrees C) and a dose-dependent decrease in cell survival. In contrast, wIRA(+RL) did not produce cell death and did not induce a systematic increase in MMP-1 mRNA expression (less than twofold expression, within the laboratory range of fluctuation) detectable with the sensitive methods applied. Additionally, repeated exposure of human skin fibroblasts to wIRA(+RL) did not induce MMP-1 mRNA expression systematically (less than twofold expression by up to 10 consecutive wIRA(+RL) exposures and analysis with real-time RT-PCR). CONCLUSIONS: wIRA(+RL) even at the investigated disproportionally high irradiances does not induce cell death or a systematic increase of MMP-1 mRNA expression, both of which can be easily induced by UV-A radiation. Furthermore, these results support previous findings of in vivo investigations on collagenase induction by UV-A but not wIRA and show that infrared-A with appropriate irradiances does not seem to be involved in MMP-1 mediated photoaging of the skin. As suggested by previously published studies wIRA could even be implicated in a protective manner.

1012-007 Yellow River Headwaters Final Report

The Yellow River Headwaters Watershed (YRHW) drains 26,730 acres of rural land within Winneshiek and Allamakee Counties. While portions of the river have been designated as a High Quality Resource by the State of Iowa, other portions appear on the State's 303(d) List of Impaired Waters due to excessive nutrients, sediment and other water quality issues. The Winneshiek SWCD was fortunate enough to secure WSPF/WPF funds for FY2009 to begin addressing many of the sources of the identified problems, especially along the all-to-critical stream corridor. Initial landowner I producer interest has exceeded expectations and several key BMPs have been installed within the identified critical areas. Yet due to the current budget constraints in the WSPF/WPF programs, we currently have greater landowner I producer interest than we do funds, which is why the District is applying for WIRB funding, to provide supplemental incentives to continue the installation of needed Grade Stabilization Structures, Terraces and Manure Management Systems in identified critical areas. Other funding, currently available to the District, will cover the remaining portions of the project's budget, including staff and our outreach efforts.

1233-015IJ Miller Creek Watershed Final Report

Miller Creek, a 19,926 acre watershed, is listed on the 2008 Section 303d Impaired Waters List. All indicators, as reported in the Miller Creek assessment, show that the impairment is due to nutrient and sediment delivery from upland runoff which contributes to elevated water temperatures, excessive algae, and low dissolved oxygen levels within the stream. The WIRB board provided implementation grant funds in 2010 for a three year project to treat targeted areas of 5 tons per acre or greater soil loss with an estimated reduction of 2,547 tons. As of December 1, 2012, with 95% of the funds allocated, the final results are estimated to provide a sediment delivery reduction of 4,500 tons and an estimated phosphorus reduction of 5,700 lbs per year. These accomplishments and the completion of the three year Miller Creek WIRB project represent "Phase I" of the SWCD's goals to treat the Miller Creek watershed. This application represents "Phase II" or the final phase of the Miller Creek water quality project. The Monroe SWCD plans to reduce sediment delivery by 70% on an additional 245 acres of priority land. This goal will be accomplished through installation of strategically placed structural practices, BMPs, and grazing systems. These practices will reduce soil loss, nutrient runoff, and sediment delivery as well as improve water quality and wildlife habitat in the watershed. Utilization of partnerships with NRCS and IDALS-DSC will continue to be an important part to the success of the project. Project goals will be achieved by utilizing matching funds from EQIP, and the Monroe SWCD has approved the use of District IFIP cost share funds specifically for use in the Miller Creek Watershed.

1011-006 Competine Creek Watershed Final Report

The Competine Creek watershed is a 24,956 acre sub-watershed of Cedar Creek. The creek traverses portions of three counties, slicing through rich and highly productive Southern lowa Drift Plain soils. The watershed is suffering from excessive sediment delivery and frequent flash floods that have been exacerbated by recent high rainfall events. Assessment data reveals soil erosion estimated to be 38,435 tons/year and sediment delivery to the creek at 15,847 tons/year. The Competine Creek Partnership Project is seeking WIRB funds to merge with IDALS-DSC funds and local funds, all targeted for structural Best Management Practices (BMPs) within the 2,760 acres of High Priority Areas (HPAs) identified by the assessment process. The BMPs will include grade stabilization structures, water and sediment basins, tile-outlet terraces, CRP, and urban storm water conservation practices. In addition, Iowa State University Extension-Iowa Learning Farm is investing in the project by facilitating a crop sampling program utilizing fall stalk nitrate, phosphorous index, and soil conditioning index testing. These tests will be used by producers as measures of performance to refine nutrient and soil loss management and to determine effective alternatives to reduce sediment and nutrient delivery to Competine Creek.

07003-001 Clear Lake Watershed Final Report

Clear Lake, Iowa's third largest natural lake, is a premier natural resource and popular recreational destination in north central Iowa. Despite the lake's already strong recreational use, water quality concerns have not allowed the lake to reach its full potential. Clear Lake is listed on Iowa's 2004 303(d) Impaired Waters List due to excessive levels of phosphorus, bacteria, and turbidity. Urban storm water runoff from the 8,600 acre watershed is a significant contributor to Clear Lake's impairment. Local communities have been working towards the goal of making improvements at all 30 storm water outlets that have a drainage area of five acres or more and have a cost effective solution. Many improvements have already been made, and now there are only seven storm water outlet sites remaining that still need protection in order to meet the goal. The storm water improvements have been very effective in reducing contaminants in urban runoff, achieving reduction levels in the 50-80% range. The proposed Clear Lake Storm Water Improvement Project will address the remaining seven outlet sites and take place over three years. The first year will consist of performing engineering and design of storm water best management practices (BMPs) at the seven outlet sites to determine if a cost effective solution exists for each. Years two and three will consist of installing two storm water improvements each year to implement the most cost effective BMPs at a minimum of four of the seven sites. The grant request addresses one of the main priorities of the Iowa Watershed Improvement Grant: storm water runoff.

Increased male offspring's risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother.

An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and Western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis or digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49-60 d), and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life.

07032-012 Lake MacBride Watershed Final Report

Lake Macbride is considered to be one of the top four lakes for fishing in the state of Iowa. It is widely used by the public and contributes significant economic benefits to the county. Lake Macbride is situated in the North Corridor which is one of the fastest growing areas in the state. The lake has a surface area of 940 acres and drains 16,205 acres. Lake Macbride is on the Iowa 303(d) list for excessive sediments and nutrients. In 2001, Lake Macbride State Park received over 2.5 million dollars from the Marine Fuel Tax and Fish and Wildlife Trust to install 2 silt basins and stabilize over 12 miles of shoreline in the lake. Also in 2001, the Johnson County SWCD received a WSPF allocation from DSC to address agriculture and urban runoff issues in the watershed. Section 319 funding was received in 2002 to continue watershed efforts to the present. A watershed assessment was completed in 2003 to guide watershed activities. In 2005, a TMDL was completed for the lake. Since 2001, over $645,000 dollars has been spent by landowners and funding partners to install conservation practices in the watershed. Watershed efforts have resulted in the reduction of over 4200 tons of soils from being delivered into Lake Macbride. Nutrient reductions have also occurred from the development of nutrient management plans on 2000 acres. The District is in the process of wrapping up watershed efforts on private land. A series of 13 structures is planned to be installed in the State Park over the next several years. One of the last remaining items that still needs addressed is 1,400 feet of eroding shoreline adjacent to Lake Macbride along Cottage Reserve Road. The road is under the jurisdiction of the Johnson County Board of Supervisors. Both the Board of Supervisors and the IDNR are willing to contribute substantial dollars to address the 250 tons of soil that are being directly delivered to Lake Macbride each year.

05035-012 Clear Lake Watershed Final Report

Clear Lake, Iowa's third largest natural lake, is located in Cerro Gordo County in north-central Iowa. The lake is a premier natural resource and popular recreational destination in north central Iowa, providing more than $40 million dollars annually to the local economy. Despite the lake's already strong recreational use, water quality concerns have not allowed the lake to reach its full recreational potential. Clear Lake is listed on Iowa's 2004 303(d) Impaired Waters List due to excessive levels of phosphorus, bacteria, and turbidity. Urban storm water runoff from the 8,600 acre watershed is a significant contributor to Clear Lake's impairment. There are over 68 storm water outlet points in the Clear Lake watershed that allow untreated urban runoff to empty directly into Clear Lake. Local governments have been very active in installing storm water Best Management Practices (BMPs) at as many of the outlets that current funding allows. To date, 11 of the 68 sites (16%) have been protected. These improvements have been very effective in reducing contaminants in the storm water runoff, but the remaining outlets still need protection. The first phase of this grant request is for an investigation of 10 storm water outlet sites to determine the most cost effective BMP for each site. The second phase of the grant request is to implement the BMPs deemed most cost effective at 5 of the 10 sites investigated. The grant request addresses one of the main priorities of the Iowa Watershed Improvement Grant: storm water runoff.

Large differences in the prevalence of normal weight obesity using various cut-offs for excess body fat

BACKGROUND AND AIMS: Normal weight obesity (NWO) has been defined as an excessive body fat (BF) associated with a normal body mass index (BMI). Still, little is known regarding the effect of differing cut-offs for %BF on the prevalence of NWO. We thus conducted a study to assess the effect of modifying the cut-offs for excessive %BF on the prevalence of NWO. METHODS: We examined a convenience sample of 1523 Portuguese adults. BF was measured by validated hand-held bioimpedance. NWO was defined as a BMI < 25 kg/m2 and a %BF >30% or according to sex- and age-specific %BF cut-offs. RESULTS: Prevalence of NWO was 10.1% in women and 3.2% in men. In women, prevalence of NWO increased considerably with age, and virtually all women aged over 55 with a BMI < 25 kg/m2 were actually considered as NWO. Using sex-specific cut-offs for BF (men: 29.1%; women: 37.2%) led to moderately lower prevalence of NWO in women. Using sex and age-specific cut-offs for %BF considerably decreased the prevalence of NWO in women, i.e. 0.5e2.5% (depending on the criterion) but not in men, i.e. 1.9e3.4%. CONCLUSIONS: In women, the prevalence of NWO varies considerably according to the cut-off used to define excess BF, whereas a much smaller variation is found in men. While further studies are needed to describe the risk associated with NWO using various %BF cut-offs, this study suggests that sex- and age-specific cut-offs may be preferred.

Cyanogenesis and the onset of tapping panel dryness in rubber tree

The objective of this work was to study the influence of cyanogenesis on the onset of irreversible tapping panel dryness (TPD) and the physiological and histological aspects of secondary phloem in the trunk (tapping panel) of rubber trees (Hevea spp.). Two cyanogenic compounds, linamarin and KCN, were applied separately on the trunk bark of healthy mature trees belonging to two Brazilian clones (Fx 4098 and Fx 3899). Changes in histology, latex pressure potential (ΨP) and cyanogenic potential (HCNp) were followed in the trunk inner barks. In addition, the HCNp levels were determined in TPD-affected plants of both clones. The applications of linamarin or KCN in healthy plants decreased latex ΨP, and formed tylosoids associated with in situ coagulation of latex. The clone Fx 4098 had the higher HCNp and showed the quicker and stronger responses to the cyanogenic compounds. Plants with TPD syntoms had a higher HCNp than the untreated healthy ones. Since histological changes are also structural markers of early TPD, it can be inferred that excessive release of cyanide can induce it in sensitive rubber clones