[Genetic research in childhood and adolescent psychiatry]. / Genetisch onderzoek in de kinder- en jeugdpsychiatrie.

BACKGROUND: Childhood mental health problems are partly influence by genetic factors with heritability estimates varying between 40% and 90%. AIM: We provide examples of genetic research focusing on explaining the continuity of symptoms and the association between parental traits and offspring psychopathology. METHOD: We summarize two recently publish review papers RESULTS: There are significant genetic correlations between childhood and adult mental disorders. Genetic factors also explain part of the associations between parental traits and offspring psychopathology, because parents and children share 50% of their genetic material. CONCLUSION: The role of genetic factors is not restricted to influencing the risk to develop a mental disorder. They also play a role in persistence of symptoms and the associations with the environment.

Impacts on soil nitrogen availability of converting managed pine plantation into switchgrass monoculture for bioenergy.

Biofuels derived from lignocellulosic materials is one of the options in addressing issues on climate change and energy independence. One of the most promising bioenergy crops is switchgrass (Panicum virgatum L.), particularly in North America. Future advancement in large-scale conversion of lignocellulosic feedstocks and relatively more competitive price for biomass and other economic advantages could lead to landowners opting to venture on switchgrass monoculture (SWITCH) in lieu of loblolly pine monoculture (PINE). Therefore, we investigated the conversion of previously managed loblolly pine stand into SWITCH in eastern North Carolina, U.S.A. on soil N availability. Treatments included PINE, SWTICH, and mature loblolly pine stand (REF). Each treatment was replicated three times on 0.8 ha plots drained by open ditches dug 1.0-1.2 m deep and spaced at 100 m. Rates of net N mineralization (Nm) and nitrification (Nn) at the top 20 cm were measured using sequential in-situ techniques in 2011 and 2012 (the 3rd and 4th years of establishment, respectively) along with a one-time laboratory incubation. On average, PINE, SWITCH, and REF can have field net Nm rates up to 0.40, 0.34 and 0.44 mg N·kg soil-1·d-1, respectively, and net Nn rates up to 0.14, 0.08 and 0.10 mg N·kg soil-1·d-1, respectively. Annually, net Nm rates ranged from 136.98 to 167.21, 62.00 to 142.61, and 63.57 to 127.95 kg N·ha-1, and net Nn rates were 56.31-62.98, 16.45-30.45, 31.99-32.94 kg N·ha-1 in PINE, SWITCH, and REF, respectively. Treatment effect was not significant on field Nm rate (p = 0.091). However, SWITCH significantly reduced nitrate-N production (p < 0.01). Overall, results indicated that establishment of SWITCH on poorly drained lands previously under PINE is less likely to significantly impact total soil N availability and potentially has minimum N leaching losses since soil mineral N under this system will be dominated by ammonium-N.

Clinical Experiences: Navigating the Intricacies of Student Placement Requirements.

Clinical apprenticeships, also called clinical experiences, are integral to most allied health (AH) student professional education. Clinical experiences begin the process of enculturating students into a healthcare profession where higher cognitive mastery of learned skills is supported through social interaction and scaffolding with an AH professional. In AH programs, clinical experiences for students are a necessity for programmatic accreditation; however, clinical sites have developed a range of requirements for students, which lead to a myriad of issues. These requirements may include drug screens, criminal background checks, and HIPAA training prior to a student beginning their clinical experience. Because of differing interpretation of policy, there is variability of requirements imposed on students before beginning these clinical experiences. This variability can create a financial burden on the student, who likely pays out-of-pocket for criminal background checks, vaccines, or drug screens. It also creates an administrative burden for clinical coordinators, who must know what each of the hundreds of clinical sites require, and they must follow up with each site to determine if these requirements have changed. Some strategies exist that may help clinical coordinators to manage clinical site requirements for student placement.

Review: The compositional variation of the rumen microbiome and its effect on host performance and methane emission.

The rumen microbiome has the important task of supplying ruminants with most of their dietary requirements and is responsible for up to 90% of their metabolic needs. This tremendous feat is possible due to the large diversity of microorganisms in the rumen. The rumen is considered one of the most diverse ecosystems on the planet in terms of species diversity and functional richness. From the moment the feed is ingested, it enters a vast cascade in which specialized microorganisms degrade specific components of the feed turning them into molecules, which in turn are utilized as anabolic precursors and energy sources for the animal. The output of this degradation process not only affects the animal, but also has an extensive impact on the environment. Some of the byproducts that are emitted as waste from this process, such as methane, act as greenhouse gases which greatly contribute to global warming. Recent technological advances developed to study this community enabled a larger overview of its vast taxonomic and functional diversity, thus leading to a better understanding of its ecology and function. This deeper understanding of the forces affecting the microbiome includes the forces that shape composition, the variation among animals, the stability of its key components, the processes of succession on a short- and long-time scales such as primary colonization and diurnal oscillations. These collective understandings have helped to provide insights into the potential effects that these forces have on the outputs observed from the animal itself. Over the recent years, there has been a growing body of evidence demonstrating the link between the microbiome and its effect on productivity of the host animals and the environment, which has placed rumen microbiome studies in the forefront of animal agricultural research. In this review, we focus on the natural variations in community composition, which are not the results of different management or feed but rather intrinsic features of animals. We characterize the rumen microbiome, its potential impact on its host as well as the barriers in implementing the current knowledge to modulate the microbiome and point toward potential avenues to overcome these hurdles.

Effects of forest-based bioenergy feedstock production on shallow groundwater quality of a drained forest soil.

Managed forests in southern U.S. are a potential source of lignocellulosic biomass for biofuel production. Changes in management practices to optimize biomass production may impact the quality of waters draining to nutrient-sensitive waters in coastal plain regions. We investigated shallow groundwater quality effects of intercropping switchgrass (Panicum virgatum L.) with managed loblolly pine (Pinus taeda L.) to produce bioenergy feedstock and quality sawtimber in a poorly drained soil of eastern North Carolina, U.S.A. Treatments included PINE (traditional pine production), PSWITCH (pine-switchgrass intercropped), SWITCH (switchgrass monoculture) and REF (mature loblolly pine stand). Each treatment was replicated three times on 0.8ha plots drained by parallel-open ditches, 1.0-1.2m deep and 100m apart. Water samples were collected monthly or more frequently after fertilizer application. Water samples were analyzed for organic nitrogen (ON), ammonium N (NH4+- N), and nitrite+nitrate N (NO3-+ NO2-- N), ortohophosphate phosphorus (OP), and total organic carbon (TOC). Overall, PSWITCH did not significantly affect shallow groundwater quality relative to PINE and SWITCH. ON, NO3-+ NO2-- N, and TOC concentrations in PSWITCH, PINE and SWITCH were substantially elevated during the two years after tree harvest and site establishment. The elevated nutrient concentrations at the beginning of the study were likely caused by a combination of rapid organic matter decomposition of the abundant supply of post-harvest residues, warming of exposed soil surfaces and reduction of plant nutrient uptake that can occur after harvesting, and pre-plant fertilization. Nutrient concentrations returned to background levels observed in REF during the third year after harvest.

Pharmacist perceptions of competency: Identifying priority areas for a competency program development at an academic medical center.

BACKGROUND: Competency-based education models can serve as valuable resources for providing quality continuing education and professional development in healthcare. However, competency development programs can be stifled by scarce stakeholder involvement and insufficient recognition of resource challenges. Engaging pharmacists in program development can inform program design and prioritization of needs. OBJECTIVE: To describe a process to assess pharmacist perceptions about competency development and to inform program design by identifying high priority topic areas based on perceived value, confidence in abilities, and frequency of use by pharmacists. METHODS: Pharmacists at a large academic medical center were surveyed to examine opinions regarding competency development and identify perceived departmental value, personal confidence, and frequency of use for nine competency topic areas. Responses were aggregated to create scores for each of the three criteria related to the nine topics. Priority areas were topics with the highest relative scores in perceived value and frequency of use and lowest relative scores in confidence compared to the other areas. RESULTS: Survey responses were collected from 105 pharmacists (78.9% response rate). A majority indicated that competency assessment is a shared responsibility between the organization and individual pharmacists. Therapeutic knowledge was identified as the competency requiring the most immediate attention as it was perceived to have the highest departmental value and highest frequency of use, yet participants indicated low confidence regarding the topic. CONCLUSIONS: Competency development is a critical aspect of ensuring pharmacists are prepared for the rapidly evolving needs of the healthcare system. Organizations play an important role in identifying and developing pharmacist competencies aligned with institutional and individual needs. This study suggests that pharmacists and leaders at an academic medical center identified a shared responsibility for competency development. The process described here may provide a model for other medical centers with similar competency development needs.

Effects of timber harvests and silvicultural edges on terrestrial salamanders.

Balancing timber production and conservation in forest management requires an understanding of how timber harvests affect wildlife species. Terrestrial salamanders are useful indicators of mature forest ecosystem health due to their importance to ecosystem processes and sensitivity to environmental change. However, the effects of timber harvests on salamanders, though often researched, are still not well understood. To further this understanding, we used artificial cover objects to monitor the relative abundance of terrestrial salamanders for two seasons (fall and spring) pre-harvest and five seasons post-harvest in six forest management treatments, and for three seasons post-harvest across the edge gradients of six recent clearcuts. In total, we recorded 19,048 encounters representing nine species of salamanders. We observed declines in mean encounters of eastern red-backed salamanders (Plethodon cinereus) and northern slimy salamanders (P. glutinosus) from pre- to post-harvest in group selection cuts and in clearcuts. However, we found no evidence of salamander declines at shelterwoods and forested sites adjacent to harvests. Edge effects induced by recent clearcuts influenced salamanders for approximately 20 m into the forest, but edge influence varied by slope orientation. Temperature, soil moisture, and canopy cover were all correlated with salamander counts. Our results suggest silvicultural techniques that remove the forest canopy negatively affect salamander relative abundance on the local scale during the years immediately following harvest, and that the depth of edge influence of clearcuts on terrestrial salamanders is relatively shallow (<20 m). Small harvests (<4 ha) and techniques that leave the forest canopy intact may be compatible with maintaining terrestrial salamander populations across a forested landscape. Our results demonstrate the importance of examining species-specific responses and monitoring salamanders across multiple seasons and years. Long-term monitoring will be necessary to understand the full impacts of forest management on terrestrial salamanders.

Effects of including NaOH-treated corn straw as a substitute for wheat hay in the ration of lactating cows on performance, digestibility, and rumen microbial profile.

This study measured the effects of including 5% NaOH-treated corn straw (T-CS) as a substitute for 15% wheat hay in the control total mixed ration (TMR) of lactating cows on performance, digestibility, and rumen microbial profile. Two groups of 21 cows each, similar in initial performance, were fed individually 1 of the 2 TMR examined. Voluntary dry matter intake of cows fed the control TMR was 4.3% higher than that of the T-CS cows, but in vivo dry matter and organic matter digestibilities of both groups were similar. Crude protein digestibility was higher in the control cows but digestibility of neutral detergent fiber polysaccharides (cellulose and hemicelluloses) was higher in the T-CS TMR. This was followed by 4.6% reduction in rumination time of the T-CS group. A slightly higher milk yield was observed in the control cows compared with the T-CS group; however, milk fat and milk protein content were higher in cows fed the T-CS TMR. This was reflected in 1.3% increase in energy-corrected milk yield and 5.34% increase in production efficiency (energy-corrected milk yield/intake) of the T-CS cows compared with the control. Welfare of the cows, as assessed by length of daily recumbence time, was improved by feeding the T-CS TMR relative to the control group. As a whole, the rumen bacterial community was significantly modulated in the T-CS group in the experimental period compared with the preexperimental period, whereas the bacterial community of the control group remained unchanged during this period. Out of the 8 bacterial species that were quantified using real-time PCR, a notable decrease in cellulolytic bacteria was observed in the T-CS group, as well as an increase in lactic acid-utilizing bacteria. These results illustrate the effect of T-CS on the composition of rumen microbiota, which may play a role in improving the performance of the lactating cow.

Effects of adding a concentrated pomegranate-residue extract to the ration of lactating cows on in vivo digestibility and profile of rumen bacterial population.

This study characterizes the effects of concentrated pomegranate-peel extract (CPE) addition to the TMR at levels of 1, 2, or 4% on voluntary intake, in vivo digestibility, milk yield and composition, and profile of rumen bacterial and archaeal populations in lactating Holstein cows. Supplementation of CPE significantly affected the abundance of methanogenic archaea and specific ruminal bacterial species related to cellulolytic activities and soluble sugar and lactic acid fermentation, as revealed by real-time PCR quantification. Furthermore, CPE supplementation had a significant dose-dependent effect on the whole ruminal bacterial community, as determined by automated ribosomal intergenic spacer analysis. These changes were accompanied by a significant increase in digestibility of dry matter, crude protein, and neutral detergent fiber, as well as milk and energy-corrected milk yields in cows fed the 4% CPE supplement. These results suggest that CPE supplementation significantly affects the rumen bacterial communities, which in turn may be related to a beneficial effect on dairy cow performance.

Impacts of fertilization on water quality of a drained pine plantation: a worst case scenario.

Intensive plantation forestry will be increasingly important in the next 50 yr to meet the high demand for domestic wood in the United States. However, forest management practices can substantially influence downstream water quality and ecology. This study analyses, the effect of fertilization on effluent water quality of a low gradient drained coastal pine plantation in Carteret County, North Carolina using a paired watershed approach. The plantation consists of three watersheds, two mature (31-yr) and one young (8-yr) (age at treatment). One of the mature watersheds was commercially thinned in 2002. The mature unthinned watershed was designated as the control. The young and mature-thinned watersheds were fertilized at different rates with Arborite (Encee Chemical Sales, Inc., Bridgeton, NC), and boron. The outflow rates and nutrient concentrations in water drained from each of the watersheds were measured. Nutrient concentrations and loadings were analyzed using general linear models (GLM). Three large storm events occurred within 47 d of fertilization, which provided a worst case scenario for nutrient export from these watersheds to the receiving surface waters. Results showed that average nutrient concentrations soon after fertilization were significantly (alpha = 0.05) higher on both treatment watersheds than during any other period during the study. This increase in nutrient export was short lived and nutrient concentrations and loadings were back to prefertilization levels as soon as 3 mo after fertilization. Additionally, the mature-thinned watershed presented higher average nutrient concentrations and loadings when compared to the young watershed, which received a reduced fertilizer rate than the mature-thinned watershed.

CD11c+ cells are required to prevent progression from local acute lung injury to multiple organ failure and death.

To investigate the role of CD11c(+) cells in endotoxin-induced acute lung injury, wild-type or CD11c-diphtheria toxin receptor transgenic mice were treated with intraperitoneal diphtheria toxin (5 ng/g b.wt.) in the presence or absence of intratracheal lipopolysaccharide (51 microg). Lipopolysaccharide treatment resulted in 100% mortality in CD11c-depleted animals but not in control animals. Analysis of local lung tissue revealed no differences in acute lung injury severity; however, analysis of distal tissues revealed severe damage and necrosis to multiple organs (liver, spleen, and kidneys) in CD11c-diphtheria toxin receptor mice but not in wild-type mice. In addition, dramatic increases in systemic levels of liver enzymes (alanine aminotransferase, 657 U/L, aspartate aminotransferase, 1401 U/L), blood urea (53 mg/dl), and 8-iso-prostaglandin F(2alpha), a marker of oxidative stress (350 pg/ml), were observed. These data demonstrate that CD11c(+) cells play a critical role in protecting the organs from systemic injury caused by a pulmonary endotoxin challenge.

Role of dendritic cells and alveolar macrophages in regulating early host defense against pulmonary infection with Cryptococcus neoformans.

Successful pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requires a T1 adaptive immune response. This response takes up to 3 weeks to fully develop. The role of the initial, innate immune response against the organism is uncertain. In this study, an established model of diphtheria toxin-mediated depletion of resident pulmonary dendritic cells (DC) and alveolar macrophages (AM) was used to assess the contribution of these cells to the initial host response against cryptococcal infection. The results demonstrate that depletion of DC and AM one day prior to infection results in rapid clinical deterioration and death of mice within 6 days postinfection; this effect was not observed in infected groups of control mice not depleted of DC and AM. Depletion did not alter the microbial burden or total leukocyte recruitment in the lung. Mortality (in mice depleted of DC and AM) was associated with increased neutrophil and B-cell accumulation accompanied by histopathologic evidence of suppurative neutrophilic bronchopneumonia, cyst formation, and alveolar damage. Collectively, these data define an important role for DC and AM in regulating the initial innate immune response following pulmonary infection with C. neoformans. These findings provide important insight into the cellular mechanisms which coordinate early host defense against an invasive fungal pathogen in the lung.

Cryptococcal urease promotes the accumulation of immature dendritic cells and a non-protective T2 immune response within the lung.

Urease, a major virulence factor for Cryptococcus neoformans, promotes lethal meningitis/encephalitis in mice. The effect of urease within the lung, the primary site of most invasive fungal infections, is unknown. An established model of murine infection that utilizes either urease-producing (wt and ure1::URE1) or urease-deficient (ure1) strains (H99) of C. neoformans was used to characterize fungal clearance and the resultant immune response evoked by these strains within the lung. Results indicate that mice infected with urease-producing strains of C. neoformans demonstrate a 100-fold increase in fungal burden beginning 2 weeks post-infection (as compared with mice infected with urease-deficient organisms). Infection with urease-producing C. neoformans was associated with a highly polarized T2 immune response as evidenced by increases in the following: 1) pulmonary eosinophils, 2) serum IgE levels, 3) T2 cytokines (interleukin-4, -13, and -4 to interferon-gamma ratio), and 4) alternatively activated macrophages. Furthermore, the percentage and total numbers of immature dendritic cells within the lung-associated lymph nodes was markedly increased in mice infected with urease-producing C. neoformans. Collectively, these data define cryptococcal urease as a pulmonary virulence factor that promotes immature dendritic cell accumulation and a potent, yet non-protective, T2 immune response. These findings provide new insights into mechanisms by which microbial factors contribute to the immunopathology associated with invasive fungal disease.

Sepsis-induced inhibition of neutrophil chemotaxis is mediated by activation of peroxisome proliferator-activated receptor-{gamma}.

Neutrophils (polymorphonuclear leukocytes [PMNs]) are critical to the immune response, including clearance of infectious pathogens. Sepsis is associated with impaired PMN function, including chemotaxis. PMNs express peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a ligand-activated nuclear transcription factor involved in immune and inflammatory regulation. The role of PPAR-gamma in PMN responses, however, is not well characterized. We report that freshly isolated human PMNs constitutively express PPAR-gamma, which is up-regulated by the sepsis-induced cytokines TNF-alpha and IL-4. PMN chemotactic responses to formylmethionyl-leucyl-phenylalanine (fMLP) and IL-8 were dose-dependently inhibited by treatment with the PPAR-gamma ligands troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and by transfection of PMN-like HL-60 cells with a constitutively active PPAR-gamma construct. Inhibition of chemotaxis by PPAR-gamma ligands correlated with decreases in extracellular signal-regulated kinase-1 and -2 activation, actin polymerization, and adherence to a fibrinogen substrate. Furthermore, PMN expression of PPAR-gamma was increased in sepsis patients and mice with either of 2 models of sepsis. Finally, treatment with the PPAR-gamma antagonist GW9662 significantly reversed the inhibition of PMN chemotaxis and increased peritoneal PMN recruitment in murine sepsis. This study indicates that PPAR-gamma activation is involved in PMN chemotactic responses in vitro and may play a role in the migration of these cells in vivo.

PPAR-gamma agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is characterized by alterations in fibroblast phenotypes resulting in excessive extracellular matrix accumulation and anatomic remodeling. Current therapies for this condition are largely ineffective. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear hormone receptor superfamily, the activation of which produces a number of biological effects, including alterations in metabolic and inflammatory responses. The role of PPAR-gamma as a potential therapeutic target for fibrotic lung diseases remains undefined. In the present study, we show expression of PPAR-gamma in fibroblasts obtained from normal human lungs and lungs of patients with idiopathic interstitial pneumonias. Treatment of lung fibroblasts and myofibroblasts with PPAR-gamma agonists results in inhibition of proliferative responses and induces cell cycle arrest. In addition, PPAR-gamma agonists, including a constitutively active PPAR-gamma construct (VP16-PPAR-gamma), inhibit the ability of transforming growth factor-beta1 to induce myofibroblast differentiation and collagen secretion. PPAR-gamma agonists also inhibit fibrosis in a murine model, even when administration is delayed until after the initial inflammation has largely resolved. These observations indicate that PPAR-gamma is an important regulator of fibroblast/myofibroblast activation and suggest a role for PPAR-gamma ligands as novel therapeutic agents for fibrotic lung diseases.

Modulation of the pulmonary type 2 T-cell response to Cryptococcus neoformans by intratracheal delivery of a tumor necrosis factor alpha-expressing adenoviral vector.

C57BL/6 mice develop an allergic bronchopulmonary mycosis following intratracheal inoculation of Cryptococcus neoformans 24067. We determined that only low levels of tumor necrosis factor alpha (TNF-alpha) are produced in the lungs following infection. Thus, the objective of the present studies was to determine whether treatment with a TNF-alpha-expressing adenoviral vector (adenoviral vector with the murine TNF-alpha transgene under the control of the human cytomegalovirus promoter [AdTNFalpha]) could switch the type 2 (T2) T-cell response/T1 T-cell response balance toward the T1 T-cell response. AdTNFalpha induced an increase in TNF-alpha expression at days 3 and 7. At days 7 to 14, the number of cryptococcal lung CFU continued to increase in both untreated and control adenoviral vector (empty adenovirus type 5 backbone)-treated mice, but the number was ultimately 100-fold lower following AdTNFalpha treatment. AdTNFalpha markedly increased neutrophil and macrophage numbers, and pulmonary eosinophilia did not develop. CXCL1, CXCL2, and gamma interferon were also up-regulated, while eotaxin, interleukin-4 (IL-4), and IL-5 were down-regulated. AdTNFalpha treatment also increased the number of CD80(+) and CD40(+) cells and decreased the number of CD86(+) cells (CD11b(+) and CD11c(+)) in the lungs. Major histocompatibility complex class II levels on CD11b(+) cells were increased. Whole-lung expression of inducible nitric oxide synthase was increased, while YM2 expression and acidic mammalian chitinase expression were decreased. None of these effects were observed with the control (empty) adenoviral vector. Overall, these results support the hypothesis that early TNF-alpha expression promotes a shift in T-cell and macrophage polarization from T2/alternatively activated macrophages toward T1/classically activated macrophages, resulting in control of the fungal infection and prevention of the allergic response.

Facile syntheses of acyl dihydroxyacetone phosphates and lysophosphatidic acids having different acyl groups.

In this study, we report novel and simple chemical syntheses of acyl dihydroxyacetone phosphate (DHAP) and 1-acyl glycero-3-phosphate [lysophosphatidic acid (LPA)], key intermediaries in the formation of glycerolipids containing ester and ether bonds. The synthesis of acyl DHAPs involved acylating the dimethyl ketal of DHAP by acid anhydride using 4-pyrrolidinopyridine as the catalyst, and the resulting product was deketalized by HClO(4) in acetone to produce acyl DHAP. The acid anhydride was either added directly or generated in the reaction mixture from the corresponding fatty acid using dicyclohexylcarbodiimide as the condensing agent. Using these methods, a number of acyl DHAPs having short-, medium-, and long-chain saturated and unsaturated acyl groups were synthesized, with overall yields from 37% to 75%. The activities of these acyl DHAPs as substrates for guinea pig liver peroxisomal acyl DHAP:NADPH reductase and alkyl DHAP synthase were then determined. Next, starting from these acyl DHAPs, a variety of LPAs were synthesized by chemical reduction of the ketone group. Biological activities of these LPAs were determined by measuring their relative abilities to release intracellular Ca(2+) via the LPA receptor. A combined chemical-enzymatic method is also described to prepare the natural LPA from the racemic mixture.