Chronic Adolescent Δ9-Tetrahydrocannabinol Treatment of Male Mice Leads to Long-Term Cognitive and Behavioral Dysfunction, Which Are Prevented by Concurrent Cannabidiol Treatment.

Introduction: The high prevalence of adolescent cannabis use, the association between this use and later psychiatric disease, and increased access to high-potency cannabis highlight the need for a better understanding of the long-term effects of adolescent cannabis use on cognitive and behavioral outcomes. Furthermore, increasing Δ9-tetrahydrocannabinol (THC) in high-potency cannabis is accompanied by a decrease in cannabidiol (CBD), thus an understanding of the interactions between CBD and THC in the neurodevelopmental effects of THC is also important. The current study examined the immediate and long-term behavioral consequences of THC, CBD, and their combination in a mouse model of adolescent cannabis use. Materials and Methods: Male CD1 mice received daily injections of THC (3 mg/kg), CBD (3 mg/kg), CBD+THC (3 mg/kg each), vehicle, or remained undisturbed in their home cage (no handling/injections), either during adolescence (postnatal day [PND] 28-48) or during early adulthood (PND 69-89). Animals were then evaluated with a battery of behavioral tests 1 day after drug treatment, and again after 42 drug-free days. The tests included the following: open field (day 1), novel object recognition (NOR; day 2), marble burying (day 3), elevated plus maze (EPM; day 4), and Nestlet shredding (day 5). Results: Chronic administration of THC during adolescence led to immediate and long-term impairments in object recognition/working memory, as measured by the NOR task. In contrast, adult administration of THC caused immediate, but not long term, impairment of object/working memory. Adolescent chronic exposure to THC increased repetitive and compulsive-like behaviors, as measured by the Nestlet shredding task. Chronic administration of THC, either during adolescence or during adulthood, led to a delayed increase in anxiety as measured by the EPM. All THC-induced behavioral abnormalities were prevented by the coadministration of CBD+THC, whereas CBD alone did not influence behavioral outcomes. Conclusion: These data suggest that chronic exposure to THC during adolescence leads to some of the behavioral abnormalities common in schizophrenia. Interestingly, CBD appeared to antagonize all THC-induced behavioral abnormalities. These findings support the hypothesis that adolescent THC use can impart long-term behavioral deficits; however, cotreatment with CBD prevents these deficits.

Influence of Cattle Trails on Runoff Quantity and Quality.

Cattle trails in grazed pastures close to rivers may adversely affect surface water quality of the adjacent river by directing runoff to it. The objective of this 3-yr study (2013-2015) in southern Alberta, Canada, was to determine if cattle trails significantly increased the risk of runoff and contaminants (sediment, nutrients) compared with the adjacent grazed pasture (control). A portable rainfall simulator was used to generate artificial rainfall (140 mm h) and runoff. The runoff properties measured were time to runoff and initial abstraction (infiltration), total runoff depth and average runoff rates, as well as concentrations and mass loads of sediment, N, and P fractions. Cattle trails significantly ( ≤ 0.10) decreased time to runoff and initial abstraction (26-32%) in the 2 yr measured and increased total runoff depth, runoff coefficients, and average runoff rates (21-51%) in 2 of 3 yr. Concentrations of sediment, N, and P fractions in runoff were not significantly greater for cattle trails than for control areas. However, mass loads of total suspended solids (57-85% increase), NH-N (31-90%), and dissolved reactive P (DRP) (30-92%) were significantly greater because of increased runoff volumes. Overall, runoff quantity and loads of sediment, NH-N, and DRP were greater for cattle trails compared with the adjacent grazed pasture, and hydrologic connection with cattle-access sites on the riverbank suggests that this could adversely affect water quality in the adjacent river. Extrapolation of the study results should be tempered by the specific conditions represented by this rainfall simulation study.

Response of Soil Mesofauna to Long-Term Application of Feedlot Manure on Irrigated Cropland.

Long-term application of feedlot manure to cropland may influence soil mesofauna. These organisms affect the health, structure, and fertility of soils, organic matter decomposition, and crop growth. The objective was to study the long-term (16-17 yr) influence of feedlot manure type and bedding on soil mesofauna over 2 yr (2014-2015). Stockpiled or composted feedlot manure with straw (ST) or wood-chip (WD) bedding (plus unamended control) was annually applied (13 Mg ha dry wt.) to an irrigated clay loam soil with continuous barley (). Intact cores were taken from surface (0-5 cm) soil in the fall, and the densities of Acari (mites) suborders and Collembola (springtails) families were determined. Manure type had no significant ( > 0.05) effect on soil mesofauna density. In contrast, there was a significant two- to sixfold increase in density with WD- compared with ST-amended soils of total Acari in 2014 and 2015, as well as total Collembola, total Acari and Collembola, oribatid mites, and entomobryid springtails in 2014. The bedding effect was attributed to significantly greater soil water content and lower bulk density for WD than ST. Density of soil mesofauna was not significantly greater in amended soils than in unamended soils. A shift by feedlot producers from stockpiled to composted feedlot manure application should have no effect on soil mesofauna density, whereas a shift from ST to WD bedding may increase the density of certain soil mesofauna, which may have a beneficial effect on soil.

Phosphorus and nitrogen in runoff after phosphorus- or nitrogen-based manure applications.

Application of beef cattle () manure based on nitrogen (N) requirements of crops has resulted in elevated concentrations of soil test phosphorus (P) in surface soils, and runoff from this cropland can contribute to eutrophication of surface waters. We conducted a 3-yr field study (2005-2007) on a Lethbridge loam soil cropped to dryland barley () in southern Alberta, Canada to evaluate the effect of annual and triennial P-based and annual N-based feedlot manure on P and N in runoff. The manure was spring applied and incorporated. There was one unamended control plot. A portable rainfall simulator was used to generate runoff in the spring of each year after recent manure incorporation, and the runoff was analyzed for total P, total dissolved P, total particulate P, dissolved reactive P, total N, total dissolved N, total particulate N, NO-N, and NH-N. Annual or triennial P-based application resulted in significantly ( ≤ 0.05) lower (by 50 to 94%) concentrations or loads of mainly dissolved P fractions in runoff for some years compared with annual N-based application, and this was related to lower rates of annual manure P applied. For example, mean dissolved reactive P concentrations in 2006 and 2007 were significantly lower for the annual P-based (0.12-0.20 mg L) than for the annual N-based application (0.24-0.48 mg L), and mean values were significantly lower for the triennial P-based (0.06-0.13 mg L) than for the annual N-based application. In contrast, other P fractions in runoff were unaffected by annual P-based application. Our findings suggested no environmental benefit of annual P-based application over triennial P-based application with respect to P and N in runoff. Similar concentrations and loads of N fractions in runoff for the P- and N-based applications indicated that shifting to a P-based application would not significantly influence N in runoff.

Requirement of cannabinoid CB(1) receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections.

A role for endocannabinoid signaling in neuronal morphogenesis as the brain develops has recently been suggested. Here we used the developing somatosensory circuit as a model system to examine the role of endocannabinoid signaling in neural circuit formation. We first show that a deficiency in cannabinoid receptor type 1 (CB(1)R), but not G-protein-coupled receptor 55 (GPR55), leads to aberrant fasciculation and pathfinding in both corticothalamic and thalamocortical axons despite normal target recognition. Next, we localized CB(1)R expression to developing corticothalamic projections and found little if any expression in thalamocortical axons, using a newly established reporter mouse expressing GFP in thalamocortical projections. A similar thalamocortical projection phenotype was observed following removal of CB(1)R from cortical principal neurons, clearly demonstrating that CB(1)R in corticothalamic axons was required to instruct their complimentary connections, thalamocortical axons. When reciprocal thalamic and cortical connections meet, CB(1)R-containing corticothalamic axons are intimately associated with elongating thalamocortical projections containing DGLß, a 2-arachidonoyl glycerol (2-AG) synthesizing enzyme. Thus, 2-AG produced in thalamocortical axons and acting at CB(1)Rs on corticothalamic axons is likely to modulate axonal patterning. The presence of monoglyceride lipase, a 2-AG degrading enzyme, in both thalamocortical and corticothalamic tracts probably serves to restrict 2-AG availability. In summary, our study provides strong evidence that endocannabinoids are a modulator for the proposed 'handshake' interactions between corticothalamic and thalamocortical axons, especially for fasciculation. These findings are important in understanding the long-term consequences of alterations in CB(1)R activity during development, a potential etiology for the mental health disorders linked to prenatal cannabis use.

Physical and chemical changes during composting of wood chip-bedded and straw-bedded beef cattle feedlot manure.

In the 1990s, restrictions on incineration encouraged the forest industry in western Canada to develop new uses for their wood residuals by product. One such use was as a replacement for cereal straw bedding in southern Alberta's beef cattle (Bos taurus) feedlot industry. However, use of carbon (C)-rich bedding, such as wood chips, had implications for subsequent composting of the feedlot manure, a practice that was being increasingly adopted. In a 3-yr study, we compared composting of wood chip-bedded manure (WBM) and barley (Hordeum vulgare L.) straw-bedded manure (SBM). There were no significant differences in temperature regimes of SBM and WBM, indicating similar rates of successful composting. Of 17 physical and chemical parameters, five showed significant (P < 0.10) differences due to bedding at the outset of composting (Day 0), and 11 showed significant differences at final sampling (Day 124). During composting (10 sampling times), seven parameters showed significant bedding effects, 16 showed significant time effects, and four showed a Bedding x Time interaction. Significantly lower (P < 0.10) losses of nitrogen (N) occurred with WBM (19%) compared with SBM (34%), which has positive implications for air quality and use as a soil amendment. Other advantages of WBM compost included significantly higher total C (333 vs. 210 kg Mg(-1) for SBM) and inorganic N (1.3 vs. 1.0 kg Mg(-1) for SBM) and significantly lower total phosphorus (4.5 vs. 5.3 kg Mg(-1) for SBM). Our results showed that wood chip bedding should not be a problem for subsequent composting of the manure after pen cleaning. In combination with other benefits, our findings should encourage the adoption of wood chips over straw as a bedding choice for southern Alberta feedlots.

LFA-1-mediated T cell costimulation through increased localization of TCR/class II complexes to the central supramolecular activation cluster and exclusion of CD45 from the immunological synapse.

T cell activation is associated with a dramatic reorganization of cell surface proteins and associated signaling components into discrete subdomains within the immunological synapse in T cell:APC conjugates. However, the signals that direct the localization of these proteins and the functional significance of this organization have not been established. In this study, we have used wild-type and LFA-1-deficient, DO11.10 TCR transgenic T cells to examine the role of LFA-1 in the formation of the immunological synapse. We found that coengagement of LFA-1 is not required for the formation of the central supramolecular activation cluster (cSMAC) region, but does increase the accumulation of TCR/class II complexes within the cSMAC. In addition, LFA-1 is required for the recruitment and localization of talin into the peripheral supramolecular activation cluster region and exclusion of CD45 from the synapse. The ability of LFA-1 to increase the amount of TCR engaged during synapse formation and segregate the phosphatase, CD45, from the synapse suggests that LFA-1 might enhance proximal TCR signaling. To test this, we combined flow cytometry-based cell adhesion and calcium-signaling assays and found that coengagement of LFA-1 significantly increased the magnitude of the intracellular calcium response following Ag presentation. These data support the idea that in addition to its important role on regulating T cell:APC adhesion, coengagement of LFA-1 can enhance T cell signaling, and suggest that this may be accomplished in part through the organization of proteins within the immunological synapse.

Phosphorus losses in simulated rainfall runoff from manured soils of Alberta.

Manure applied to agricultural land at rates that exceed annual crop nutrient requirements can be a source of phosphorus in runoff. Manure incorporation is often recommended to reduce phosphorus losses in runoff. A small plot rainfall simulation study was conducted at three sites in Alberta to evaluate the effects of manure rate and incorporation on phosphorus losses. Treatments consisted of three solid beef cattle manure application rates (50, 100, and 200 kg ha(-1) total phosphorus), an unmanured control, and two incorporation methods (nonincorporated and incorporated with one pass of a double disk). Simulated rain was applied to soils with freshly applied and residual (1 yr after application) manure at 70 mm h(-1) to produce 30 min of runoff. Soil test phosphorus (STP), total phosphorus (TP), and dissolved reactive phosphorus (DRP) concentrations in runoff increased with manure rate for fresh and residual manure. Initial abstraction and runoff volumes did not change with manure rate. Initial abstraction, runoff volumes, and phosphorus concentrations did not change with manure incorporation at Lacombe and Wilson, but initial abstraction volumes increased and runoff volumes and phosphorus concentrations decreased with incorporation of fresh manure at Beaverlodge. Phosphorus losses in runoff were directly related to phosphorus additions. Extraction coefficients (slopes of the regression lines) for the linear relationships between residual manure STP and phosphorus in runoff were 0.007 to 0.015 for runoff TP and 0.006 to 0.013 for runoff DRP. While incorporation of manure with a double disk had no significant effect on phosphorus losses in runoff from manure-amended soils 1 yr after application, incorporation of manure is still recommended to control nitrogen losses, improve crop nutrient uptake, and potentially reduce odor concerns.

Phosphorus and nitrogen in rainfall simulation runoff after fresh and composted beef cattle manure application.

Fresh beef cattle (Bos taurus) manure has traditionally been applied to cropland in southern Alberta, but there has been an increase in application of composted manure to cropland in this region. However, the quality of runoff under fresh manure (FM) versus composted manure (CM) has not been investigated. Our objective was to compare runoff quality under increasing rates (0, 13, 42, 83 Mg ha(-1) dry wt.) of FM and CM applied for two consecutive years to a clay loam soil cropped to irrigated barley (Hordeum vulgare L.). We determined total phosphorus (TP), particulate phosphorus (PP), dissolved reactive phosphorus (DRP), total nitrogen (TN), NH4-N, and NO3-N concentrations and loads in runoff after one (1999) and two (2000) applications of FM and CM. We found significantly (P < or = 0.05) higher TP, DRP, and NH4-N concentrations, and higher DRP and TN loads under FM than CM after 2 yr of manure application. The TP loads were also higher under FM than CM at the 83 Mg ha(-1) rate in 2000, and DRP loads were higher for FM than CM at this high rate when averaged over both years. Application rate had a significant effect on TP and DRP concentrations in runoff. In addition, the slope values of the regressions between TP and DRP in runoff versus application rate were considerably higher for FM in 2000 than for FM in 1999, and CM in both 1999 and 2000. Significant positive relationships were found for TP and DRP in runoff versus soil Kelowna-extractable P and soil water-extractable P for FM and CM in 2000, indicating that interaction of runoff with the soil controlled the release of P. Total P and DRP were the variables most affected by the treatments. Overall, our study found that application of CM rather than FM to cropland may lower certain forms of P and N in surface runoff, but this is dependent on the interaction with year, application rate, or both.

Bedding and within-pen location effects on feedlot pen runoff quality using a rainfall simulator.

Soluble salts, nutrients, and pathogenic bacteria in feedlot-pen runoff have the potential to cause pollution of the environment. A 2-yr study (1998-1999) was conducted at a beef cattle (Bos taurus) feedlot in southern Alberta, Canada, to determine the effect of bedding material [barley (Hordeum vulgare L.) straw versus wood chips] and within-pen location on the chemical and bacterial properties of pen-floor runoff. Runoff was generated with a portable rainfall simulator and analyzed for chemical content (nitrogen [N], phosphorus [P], soluble salts, electrical conductivity [EC], sodium adsorption ratio [SAR], dissolved oxygen [DO], and pH) and populations of three groups of bacteria (Escherichia coli, total coliforms, total aerobic heterotrophs at 27 degrees C) in 1998 and 1999. Bedding had a significant (P < or = 0.05) effect on NH4-N concentration and load in 1999, SO4 load in 1998, SO4 concentration and load in 1999, and total coliforms in both years; where these three variables were higher in wood than straw pens. Location had a significant effect on EC and concentrations of total Kjeldahl nitrogen (TKN), Na, K, SO4, and Cl in 1998, and total coliforms in both years. These seven variables were higher at the bedding pack than pen floor location, indicating that bedding packs were major reservoirs of TKN, soluble salts, and total coliforms. Significantly higher dissolved reactive phosphorus (DRP), total P, and NH4-N concentrations and loads at the bedding pack location in wood pens in 1998, and a similar trend for TKN concentration in 1999, indicated that this bedding-location treatment was a greater source of nutrients to runoff than the other three bedding-location treatments. Bedding, location, and their interaction may therefore be a potential tool to manage nutrients, soluble salts, and bacteria in feedlot runoff.

Chemical and physical changes following co-composting of beef cattle feedlot manure with phosphogypsum.

Nitrogen (N) loss during beef cattle (Bos taurus) feedlot manure composting may contribute to greenhouse gas emissions and increase ammonia (NH(3)) in the atmosphere while decreasing the fertilizer value of the final compost. Phosphogypsum (PG) is an acidic by-product of phosphorus (P) fertilizer manufacture and large stockpiles currently exist in Alberta. This experiment examined co-composting of PG (at rates of 0, 40, 70, and 140 kg PG Mg(-1) manure plus PG dry weight) with manure from feedlot pens bedded with straw or wood chips. During the 99-d composting period, PG addition reduced total nitrogen (TN) loss by 0.11% for each 1 kg Mg(-1) increment in PG rate. Available N at the end of composting was significantly higher for wood chip-bedded (2180 mg kg(-1)) than straw-bedded manure treatments (1820 mg kg(-1)). Total sulfur (TS) concentration in the final compost increased by 0.19 g kg(-1) for each 1 kg Mg(-1) increment in PG rate from 5.2 g TS kg(-1) without PG addition. Phosphogypsum (1.6 g kg(-1) P) addition had no significant effect on total phosphorus (TP) concentration of the final composts. Results from this study demonstrate the potential of PG addition to reduce overall N losses during composting. The accompanying increase in TS content has implications for use of the end-product on sulfur-deficient soils. Co-composting feedlot manure with PG may provide an inexpensive and technologically straightforward solution for managing and improving the nutrient composition of composted cattle manure.

Nutrient and sediment losses under simulated rainfall following manure incorporation by different methods.

Incorporation of manure into cultivated soils is generally recommended to minimize nutrient losses. A 3-yr study was conducted to evaluate sediment and nutrient losses with different tillage methods (moldboard plow, heavy-duty cultivator, double disk, and no-incorporation) for incorporation of beef cattle manure in a silage barley (Hordeum vulgare L.) cropping system. Runoff depths, sediment losses, and surface and subsurface nutrient transfers were determined from manured and unmanured field plots at Lethbridge, Alberta, Canada. A Guelph rainfall simulator was used to generate 30 min of runoff. Sediment losses among our tillage treatments (137.4-203.6 kg ha(-1)) were not significantly different due to compensating differences in runoff depths. Mass losses of total phosphorus (TP) and total nitrogen (TN) in surface runoff were greatest from the no-incorporation (NI) treatments, with reductions in TP loads of 14% for double disk (DD), 43% for cultivator (CU), and 79% for moldboard plow (MP) treatments. Total N load reductions in 2002 were 26% for DD, 70% for CU, and 95% for MP treatments compared to the NI treatments. Nutrient losses following incorporation of manure with the DD or CU methods were not significantly different from the NI treatments. Manure treatments generally had lower runoff depths and sediment losses, and higher phosphorus and nitrogen losses than the control treatments. Subsurface concentrations of NH4-N, NO3-N, and TN were greatest from the MP treatments, whereas subsurface phosphorus concentrations were not affected by tillage method. Tillage with a cultivator or double disk minimized combined surface and subsurface nutrient losses immediately after annual manure applications.

The Initial Health Assessment: an intervention to identify the supportive care needs of cancer patients.

BACKGROUND: The first step in effective supportive care delivery is an assessment of patient needs. The Initial Health Assessment Form (IHA) was developed to aid clinicians in recognition and documentation of a patient's supportive care needs during their first visit to a comprehensive cancer centre. The purpose of this study was to determine the relative effectiveness of this instrument as compared to routine practice. METHODS: A before-after study was performed. Charts of consecutive patients with newly diagnosed cancer attending the Hamilton Regional Cancer Centre were selected randomly. Each chart was reviewed to determine the documentation at the initial patient assessment of 22 supportive care items under eight domains of need: physical, psychological, daily living, social, financial, informational, special needs and personal resources. The pre-intervention evaluation (T1) occurred over a 3-month period followed by the introduction of the IHA into clinical practice. Three months after its introduction, the post-intervention (T2) evaluation took place over the ensuing 3 months. RESULTS: A total of 306 charts were evaluated (153 each in T1 and T2). Patients from the two time periods were comparable with respect to background demographic variables. Introduction of the IHA increased the mean documentation of supportive care needs and resources from 26% in T1 to 49% in T2 ( p=0.001). Significant improvements were found in all domains of need. Despite improvements, documentation of assessment continued to remain low for daily living, social, financial, and informational needs. CONCLUSIONS: The IHA improved documentation of supportive care needs and resources. There is still room for improvement.

Bedding and seasonal effects on chemical and bacterial properties of feedlot cattle manure.

Nutrients, soluble salts, and pathogenic bacteria in feedlot-pen manure have the potential to cause pollution of the environment. A three-year study (1998-2000) was conducted at a beef cattle (Bos taurus) feedlot in southern Alberta, Canada to determine the effect of bedding material [barley (Hordeum vulgare L.) straw versus wood chips] and season on the chemical and bacterial properties of pen-floor manure. Manure was sampled for chemical content (N, P, soluble salts, electrical conductivity, and pH) and populations of four groups of bacteria (Escherichia coli, total coliforms, and total aerobic heterotrophs at 27 and 39 degrees C). More chemical parameters of manure were significantly (P < or = 0.05) affected by season (SO4, Na, Mg, K, Ca, sodium adsorption ratio [SAR], total C, NO3-N, NH4-N, total P, and available P) than by bedding (K, pH, total C, C to N ratio, NH4-N, and available P). Bedding had no significant (P > 0.05) effect on the four bacterial groups whereas season affected all four groups. Numbers of E. coli and total coliforms (TC) were significantly higher by 1.72 to 2.02 log10 units in the summer than the other three seasons, which was consistent with a strong positive correlation of E. coli and TC with air temperature. The low ratio of bedding to manure in the pens was probably the major cause of the lack of significant bedding effects. Bedding material and seasonal timing of cleaning feedlot pens and land application of manure may be a potential tool to manage nutrients, soluble salts, and pathogens in manure.