Pharmacokinetics, biodistribution and toxicology of novel cell-penetrating peptides.

Cell-penetrating peptides (CPPs) have been used in basic and preclinical research in the past 30 years to facilitate drug delivery into target cells. However, translation toward the clinic has not been successful so far. Here, we studied the pharmacokinetic (PK) and biodistribution profiles of Shuttle cell-penetrating peptides (S-CPP) in rodents, combined or not with an immunoglobulin G (IgG) cargo. We compared two enantiomers of S-CPP that contain both a protein transduction domain and an endosomal escape domain, with previously shown capacity for cytoplasmic delivery. The plasma concentration versus time curve of both radiolabelled S-CPPs required a two-compartment PK analytical model, which showed a fast distribution phase (t1/2α ranging from 1.25 to 3 min) followed by a slower elimination phase (t1/2ß ranging from 5 to 15 h) after intravenous injection. Cargo IgG combined to S-CPPs displayed longer elimination half-life, of up to 25 h. The fast decrease in plasma concentration of S-CPPs was associated with an accumulation in target organs assessed at 1 and 5 h post-injection, particularly in the liver. In addition, in situ cerebral perfusion (ISCP) of L-S-CPP yielded a brain uptake coefficient of 7.2 ± 1.1 µl g-1 s-1, consistent with penetration across the blood-brain barrier (BBB), without damaging its integrity in vivo. No sign of peripheral toxicity was detected either by examining hematologic and biochemical blood parameters, or by measuring cytokine levels in plasma. In conclusion, S-CPPs are promising non-toxic transport vectors for improved tissue distribution of drug cargos in vivo.

[Vocal cord dysfunction in athletes: Interest of rehabilitation to effort]. / Dysfonction des cordes vocales chez le sportif : intérêt du reconditionnement à l'effort.

INTRODUCTION: Vocal Cord Dysfunction (VCD) is a syndrome characterized by paradoxical adduction of the vocal folds during breathing. Its non-specific clinical manifestations frequently lead to misdiagnosis and delay in its treatment. The treatment of VCD is not pharmacological but rehabilitative and remains poorly appreciated. OBSERVATION: In this clinical case we describe a 16-year-old female judoka who presented with effort intolerance associated with occasional dyspnea, which had suddenly worsened over the preceding few months so that in now produced sudden respiratory difficulty, mainly during intense and sudden efforts. After a period where her symptoms were confused with asthma, she was diagnosed with exercise-induced VCD. Her treatment was aimed to: (a) rehabilitate respiratory mechanics in order to eliminate abdominal-thoracic asynchrony, (b) rehabilitate naso-nasal breathing, (c) train her to control abdominal-diaphragmatic breathing at rest and then during effort, (d) train her to use ventilatory control as soon as prodromal symptoms appear in order to prevent the development of stridor or complete closure of the vocal folds (at rest and then progressively during exercise). CONCLUSION: Following the implementation of these rehabilitation strategies to correct her ventilatory and dyskinetic issues, the patient no longer develops respiratory discomfort during exercise, including during judo competitions.

Role of organic matter and microbial communities in mercury retention and methylation in sediments near run-of-river hydroelectric dams.

Run-of-river power plants (RoRs) are expected to triple in number over the next decades in Canada. These structures are not anticipated to considerably promote the mobilization and transport of mercury (Hg) and its subsequent microbial transformation to methylmercury (MeHg), a neurotoxin able to biomagnify in food webs up to humans. To test whether construction of RoRs had an effect on Hg transport and transformation, we studied Hg and MeHg concentrations, organic matter contents and methylating microbial community abundance and composition in the sediments of a section of the St. Maurice River (Quebec, Canada). This river section has been affected by the construction of two RoR dams and its watershed has been disturbed by a forest fire, logging, and the construction of wetlands. Higher total Hg (THg) and MeHg concentrations were observed in the surface sediments of the flooded sites upstream of the RoRs. These peaks in THg and MeHg were correlated with organic matter proportions in the sediments (r2 = 0.87 and 0.82, respectively). In contrast, the proportion of MeHg, a proxy for methylation potential, was best explained by the carbon to nitrogen ratio suggesting the importance of terrigenous organic matter as labile substrate for Hg methylation in this system. Metagenomic analysis of Hg-methylating communities based on the hgcA functional gene marker indicated an abundance of methanogens, sulfate reducers and fermenters, suggesting that these metabolic guilds may be primary Hg methylators in these surface sediments. We propose that RoR pondages act as traps for sediments, organic matter and Hg, and that this retention can be amplified by other disturbances of the watershed such as forest fire and logging. RoR flooded sites can be conducive to Hg methylation in sediments and may act as gateways for bioaccumulation and biomagnification of MeHg along food webs, particularly in disturbed watersheds.

Biomolecular study and conjugation of two para-aminobenzoic acid derivatives with serum proteins: drug binding efficacy and protein structural analysis.

Two aminobenzoic acid derivatives DAB-0 and DAB-1 showed distinct biological properties on murine bladder cancer (BCa) cell line MB49-I. In contrast to DAB-1, DAB-0 does not possess any anti-inflammatory activity and is less toxic. Furthermore, DAB-0 does not interfere with INFγ-induced STAT1 activation and TNFα-induced IκB phosphorylation, while DAB-1 does. In order to rationalize these results, the binding efficacy of DAB-0 and DAB-1 with serum proteins such a human serum albumin (HSA), bovine serum albumin (BSA) and beta-lactoglobulin (ß-LG) was investigated in aqueous solution at physiological pH. Multiple spectroscopic methods and thermodynamic analysis were used to determine the binding efficacy of DAB-0 and DAB-1 with serum proteins. Drug-protein conjugation was observed via through ionic contacts. DAB-1 forms stronger adducts than DAB-0, while ß-LG shows more affinity with the order of stability ß-LG > BSA > HSA. The stronger complexation of DAB-1 with serum proteins might account for its biological potential and transport in the blood. The binding efficacy ranged from 40 to 60%. Major alterations of protein secondary structures were detected upon drug complexation. Serum proteins are capable of delivering DAB-1 in vitro.Communicated by Ramaswamy H. Sarma.

Hunters select for behavioral traits in a large carnivore.

Human harvest can induce selection on life history and morphological traits, leading to ecological and evolutionary responses. Our understanding of harvest-induced selection on behavioral traits is, however, very limited. Here, we assessed whether hunters harvest, consciously or not, individuals with specific behavioral traits. We used long-term, detailed behavioral and survival data of a heavily harvested brown bear (Ursus arctos) population in Sweden. We found that hunters harvested male bears that were less active during legal hunting hours and had lower movement rates. Also, hunters harvested male and female bears that used habitats closer to roads. We provide an empirical example that individual behavior can modulate vulnerability to hunting and that hunters could exert a selective pressure on wildlife behaviors. This study increases our understanding of the complex interactions between harvest method, human behavior, and animal behavior that are at play in harvest-induced selection and provides better insight into the full effects of human harvest on wild populations.

Review: Milking routines and cluster detachment levels in small ruminants.

Small ruminants not only differ on mammary gland anatomy, milk's properties and the amount of milk yielded comparable to those of dairy cattle, but also on the milking routine strategies and machine milking settings to maximize daily milk secretion. The udder compartment is proportionally larger in dairy sheep and goats, which requires modifications in the milking machine settings, milking procedures and allows the use of different milking strategies as they better tolerate extension of milking intervals. Depending on the breed, cisternal milk in goats varies from 70% to 90%, whereas in dairy sheep it varies from 50% to 78% of the total gland capacity. This explains why these species are commonly milked without pre-milking teat preparation, while in goats it is applied only in cases of high prevalence of intramammary infection in the herd. Recent French researchers observed that 40% of the goats presented an unbalanced udder as well as unbalanced morphology (21% to 30%) and functional milk flow (around 10% to 20% more) which could induce overmilking. In dairy sheep, selection for higher milk production increases teat angle insertion. Thus, to increase machine milk fraction, it is recommended to use either the 'Sagi hook' as an alternative for lifting up the 'pendulous' udder during milking or to perform machine stripping. There are three cluster removal strategies for small ruminants: manual, timed and milk flow driven automatic cluster removal (ACR). Automatic cluster removal reduces overmilking, improves teat condition, enables labour saving and provides a consistent milking routine in small ruminants. There are three to five main milk flow profiles in ewes and goats, which result in curves with one or two peaks (or plateau) and different patterns of the milk flow decreasing phase due to the degree of mammary gland imbalance and teat characteristics. When taking into account our current knowledge, ACR recommended take-off settings for goats are: 200 g/min+10 s delay time (DT) for a long decreasing phase or two plateau curves and 500 g/min+5 s DT for a short decreasing phase and one plateau curve. The ACR take-off settings for ewes are: 150 g/min +10 s DT for long decreasing phase and 200 g /min+5 s DT for a short decreasing phase. This review is intended to be useful for scientists and producers seeking basic knowledge of milking routines and cluster detachment settings for parlour performance and milk quality.

F-Specific RNA Bacteriophages, Especially Members of Subgroup II, Should Be Reconsidered as Good Indicators of Viral Pollution of Oysters.

Norovirus (NoV) is the leading cause of gastroenteritis outbreaks linked to oyster consumption. In this study, we investigated the potential of F-specific RNA bacteriophages (FRNAPH) as indicators of viral contamination in oysters by focusing especially on FRNAPH subgroup II (FRNAPH-II). These viral indicators have been neglected because their behavior is sometimes different from that of NoV in shellfish, especially during the depuration processes usually performed before marketing. However, a significant bias needs to be taken into account. This bias is that, in the absence of routine culture methods, NoV is targeted by genome detection, while the presence of FRNAPH is usually investigated by isolation of infectious particles. In this study, by targeting both viruses using genome detection, a significant correlation between the presence of FRNAPH-II and that of NoV in shellfish collected from various European harvesting areas impacted by fecal pollution was observed. Moreover, during their depuration, while the long period of persistence of NoV was confirmed, a similar or even longer period of persistence of the FRNAPH-II genome, which was over 30 days, was observed. Such a striking genome persistence calls into question the relevance of molecular methods for assessing viral hazards. Targeting the same virus (i.e., FRNAPH-II) by culture and genome detection in specimens from harvesting areas as well as during depuration, we concluded that the presence of genomes in shellfish does not provide any information on the presence of the corresponding infectious particles. In view of these results, infectious FRNAPH detection should be reconsidered as a valuable indicator in oysters, and its potential for use in assessing viral hazard needs to be investigated.IMPORTANCE This work brings new data about the behavior of viruses in shellfish, as well as about the relevance of molecular methods for their detection and evaluation of the viral hazard. First, a strong correlation between the presence of F-specific RNA bacteriophages of subgroup II (FRNAPH-II) and that of norovirus (NoV) in shellfish impacted by fecal contamination has been observed when both viruses are detected using molecular approaches. Second, when reverse transcription-PCR and culture are used to detect FRNAPH-II in shellfish, it appears that the genomes of the viruses present a longer period of persistence than infectious virus, and thus, virus genome detection fails to give information about the concomitant presence of infectious viruses. Finally, this study shows that FRNAPH persist at least as long as NoV does. These data are major arguments to reconsider the potential of FRNAPH as indicators of shellfish viral quality.

Hunting promotes spatial reorganization and sexually selected infanticide.

Harvest can affect the ecology and evolution of wild species. The removal of key individuals, such as matriarchs or dominant males, can disrupt social structure and exacerbate the impact of hunting on population growth. We do not know, however, how and when the spatiotemporal reorganization takes place after removal and if such changes can be the mechanism that explain a decrease in population growth. Detailed behavioral information from individually monitored brown bears, in a population where hunting increases sexually selected infanticide, revealed that adult males increased their use of home ranges of hunter-killed neighbors in the second year after their death. Use of a hunter-killed male's home range was influenced by the survivor's as well as the hunter-killed male's age, population density, and hunting intensity. Our results emphasize that hunting can have long-term indirect effects which can affect population viability.

Carbon dioxide fluxes from Tifway bermudagrass: early results.

This paper reports for the first time preliminary data on carbon uptake of warm-season turfgrass at a well-managed sod farm in south central Georgia. It examines the changes in carbon uptake from one of the most widely used warm-season turfgrass cultivars in the world, Tifway Bermudagrass. It elucidates the role of canopy density and light avalaibility on the net carbon uptake using the eddy-covariance technique.  Preliminary evidence suggests that turfgrass is effective  at sequestering carbon dioxide during the summer months even when the canopy is being reestablished following a grass harvest.

Prospective evaluation of a cutaneous stimulation technique to induce on-demand urination in non-toilet-trained infants.

CONTEXT: When a urinary tract infection is suspected, it is recommended to capture a midstream sample of urine for analysis, but this strategy is difficult to apply before successful toilet training. A cutaneous stimulation technique has been reported to be effective in provoking micturition in newborns. OBJECTIVE: To evaluate the feasibility and the efficacy of this technique in a population of non-toilet-trained infants. DESIGN AND METHODS: Fifty infants were enrolled in this prospective non-controlled study in three pediatric emergency departments. The bladder was stimulated through suprapubic and paravertebral cutaneous stimulation as previously reported in newborns. The evaluation criterion was the proportion of patients from whom urine had been collected within the first 5min of the procedure. RESULTS: Forty-eight patients (21 boys) were evaluated. The procedure was successful in 27% of the cases overall, but reached 46% for children aged less than 3 months. Elevated weight was associated with failure of the procedure. CONCLUSION: Despite promising results in newborns, the cutaneous stimulation technique to provoke micturition appears to encounter limitations in older children. Nevertheless, the technique is an attractive alternative to urethral catheterization or suprapubic aspiration for infants younger than 3 months.

Human shields mediate sexual conflict in a top predator.

Selecting the right habitat in a risky landscape is crucial for an individual's survival and reproduction. In predator-prey systems, prey often can anticipate the habitat use of their main predator and may use protective associates (i.e. typically an apex predator) as shields against predation. Although never tested, such mechanisms should also evolve in systems in which sexual conflict affects offspring survival. Here, we assessed the relationship between offspring survival and habitat selection, as well as the use of protective associates, in a system in which sexually selected infanticide (SSI), rather than interspecific predation, affects offspring survival. We used the Scandinavian brown bear (Ursus arctos) population with SSI in a human-dominated landscape as our model system. Bears, especially adult males, generally avoid humans in our study system. We used resource selection functions to contrast habitat selection of GPS-collared mothers that were successful (i.e. surviving litters, n = 19) and unsuccessful (i.e. complete litter loss, n = 11) in keeping their young during the mating season (2005-2012). Habitat selection was indeed a predictor of litter survival. Successful mothers were more likely to use humans as protective associates, whereas unsuccessful mothers avoided humans. Our results suggest that principles of predator-prey and fear ecology theory (e.g. non-consumptive and cascading effects) can also be applied to the context of sexual conflict.

Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery.

OBJECTIVES: Preventing postoperative recurrence after ileocolonic resection (ICR) for Crohn's disease (CD) is challenging. Defining the disturbances of the microbial composition and community structure after ICR and their link with early disease recurrence is crucial. DESIGN: Microbiota composition (fingerprinting and 16S rDNA sequencing) and community structure (correlation networks of bacterial species) were assessed from ileal mucosa sampled in 20 patients undergoing ICR and 6 months later during endoscopy from above (neoterminal ileum) and below (subanastomotic colon) the surgical anastomosis. RESULTS: ICR had a dramatic effect on gut microbial ecosystem. At surgery, CD mucosa harboured a dysbiotic microbiota with high proportions of α/ß Proteobacteria and Bacilli. Six months later, half of the patients had recurrent lesions at ileocolonoscopy and presented higher numbers of Lachnospiraceae. Recurrence of endoscopic lesions was associated with enrichment in Enterococcus durans while patients in remission had increased proportions of Dorea longicatena and Bacteroides plebeius. Structural differences were striking between recurrence and remission microbiota; while the microbiota of patients with CD recurrence exhibited a loose community structure, the microbiota of patients in remission displayed communities that were robustly correlated to each other. Microbiota colonising the neoterminal ileum and subanastomotic colon 6 months after ICR only differed in patients with recurrence. CONCLUSIONS: ICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern.

Combination of C-reactive protein, infliximab trough levels, and stable but not transient antibodies to infliximab are associated with loss of response to infliximab in inflammatory bowel disease.

BACKGROUND: Antibodies to infliximab [ATI] and trough levels to infliximab [TRI] are associated with loss of response in inflammatory bowel diseases [IBD]. The best way to predict loss of response [LOR] to infliximab [IFX] is unknown. METHODS: We conducted a prospective observational cohort study enrolling all IBD patients who were in clinical remission at Week 14 after IFX treatment initiation. TRI, ATI and C-reactive protein [CRP] level were measured at Week 22 [T1] and thereafter at every other IFX infusion. Loss of clinical response was defined by a flare requiring therapeutic change [IFX dose intensification, initiation of another drug class, and/or surgery]. RESULTS: A total of 93 patients [59 Crohn's disease, mean duration of follow-up 17.2 months] were included; 32 patients [34.4%] lost clinical response during follow-up. Cumulative probability of LOR was 50% at 20 months. Mean TRI at T1 was significantly lower in IBD patients with stable ATI as compared with those with transient ATI or without ATI [0.052, 3.34 ,and 4.29 µg/ml, respectively; p = 0.001 between no ATI vs stable ATI, and p = 0.005 between stable and transient ATI] [p = 0.0001]. Three independent factors were predictive of LOR after Cox proportional hazards modelling: TRI > 5.5 µg/ml (hazard ratio [HR]: 0.21; 95% confidence interval [CI]: 0.05-0.89;p = 0.034) at T1, CRP > 5mg/l [HR: 2.5; 95% CI: 1.16-5.26; p = 0.019] at T1, and stable ATI defined by two consecutive ATI > 20ng/ml [HR: 3.77; 95% CI: 1.45-10.0; p = 0.007]. Transient ATI did not influence LOR. CONCLUSIONS: LOR can be predicted based on a combination of CRP, TRI and stable ATI with a high degree of accuracy.

Laboratory-confirmed HIV and sexually transmitted infection seropositivity and risk behavior among sexually active transgender patients at an adolescent and young adult urban community health center.

The sexual health of transgender adolescents and young adults who present for health care in urban community health centers is understudied. A retrospective review of electronic health record (EHR) data was conducted from 180 transgender patients aged 12-29 years seen for one or more health-care visits between 2001 and 2010 at an urban community health center serving youth in Boston, MA. Analyses were restricted to 145 sexually active transgender youth (87.3% of the sample). Laboratory-confirmed HIV and sexually transmitted infections (STIs) seroprevalence, demographics, sexual risk behavior, and structural and psychosocial risk indicators were extracted from the EHR. Analyses were descriptively focused for HIV and STIs. Stratified multivariable logistic regression models were fit for male-to-female (MTF) and female-to-male (FTM) patients separately to examine factors associated with any unprotected anal and/or vaginal sex (UAVS). The mean age was 20.0 (SD=2.9); 21.7% people of color, 46.9% white (non-Hispanic), 21.4% race/ethnicity unknown; 43.4% MTF, and 56.6% FTM; and 68.3% were on cross-sex hormones. Prevalence of STIs: 4.8% HIV, 2.8% herpes simplex virus, 2.8% syphilis, 2.1% chlamydia, 2.1% gonorrhea, 2.8% hepatitis C, 1.4% human papilloma virus. Only gonorrhea prevalence significantly differed by gender identity (MTF 2.1% vs. 0.0% FTM; p=0.046). Nearly half (47.6%) of the sample engaged in UAVS (52.4% MTF, 43.9% FTM, p=0.311). FTM more frequently had a primary sex partner compared to MTF (48.8% vs. 25.4%; p=0.004); MTF more frequently had a casual sex partner than FTM (69.8% vs. 42.7% p=0.001). In multivariable models, MTF youth who were younger in age, white non-Hispanic, and reported a primary sex partner had increased odds of UAVS; whereas, FTM youth reporting a casual sex partner and current alcohol use had increased odds of UAVS (all p<0.05). Factors associated with sexual risk differ for MTF and FTM youth. Partner type appears pivotal to understanding sexual risk in transgender adolescents and young adults. HIV and STI prevention efforts, including early intervention efforts, are needed in community-based settings serving transgender youth that attend to sex-specific (biological) and gender-related (social) pathways.

Mental health of transgender youth in care at an adolescent urban community health center: a matched retrospective cohort study.

PURPOSE: Transgender youth represent a vulnerable population at risk for negative mental health outcomes including depression, anxiety, self-harm, and suicidality. Limited data exist to compare the mental health of transgender adolescents and emerging adults to cisgender youth accessing community-based clinical services; the present study aimed to fill this gap. METHODS: A retrospective cohort study of electronic health record data from 180 transgender patients aged 12-29 years seen between 2002 and 2011 at a Boston-based community health center was performed. The 106 female-to-male (FTM) and 74 male-to-female (MTF) patients were matched on gender identity, age, visit date, and race/ethnicity to cisgender controls. Mental health outcomes were extracted and analyzed using conditional logistic regression models. Logistic regression models compared FTM with MTF youth on mental health outcomes. RESULTS: The sample (N = 360) had a mean age of 19.6 years (standard deviation, 3.0); 43% white, 33% racial/ethnic minority, and 24% race/ethnicity unknown. Compared with cisgender matched controls, transgender youth had a twofold to threefold increased risk of depression, anxiety disorder, suicidal ideation, suicide attempt, self-harm without lethal intent, and both inpatient and outpatient mental health treatment (all p < .05). No statistically significant differences in mental health outcomes were observed comparing FTM and MTF patients, adjusting for age, race/ethnicity, and hormone use. CONCLUSIONS: Transgender youth were found to have a disparity in negative mental health outcomes compared with cisgender youth, with equally high burden in FTM and MTF patients. Identifying gender identity differences in clinical settings and providing appropriate services and supports are important steps in addressing this disparity.

Highlighting new phylogenetic specificities of Crohn's disease microbiota.

BACKGROUND: Recent studies suggest that gastrointestinal (GI) microbes play a part in the pathogenesis of Crohn's disease (CD). METHODS: Fecal samples were collected from 16 healthy individuals and 16 CD patients (age- and sex-matched). The DNA extracted from these samples were subjected to two different methods of microbiome analysis. Specific bacterial groups were quantified by real-time polymerase chain reaction (PCR) methods using primers designed using a high-throughput in-house bioinformatics pipeline. The same DNA extracts were also used to produce fluorescently labeled cRNA amplicons to interrogate a custom-designed phylogenetic microarray for intestinal bacteria. RESULTS: Even though the intersubject variability was high, differences in the fecal microbiomes of healthy and CD patients were detected. Faecalibacterium prausnitzii and Escherichia coli were more represented in healthy and ileal CD patients, respectively. Additionally, probes specific for Ruminococcus bromii, Oscillibacter valericigenes, Bifidobacterium bifidum, and Eubacterium rectale produced stronger hybridization signals with the DNA samples from healthy subjects. Conversely, species overrepresented in CD patients were E. coli, Enterococcus faecium, and species from the Proteobacteria not normally found in the healthy human GI tract. Furthermore, we detected "healthy specific" molecular species or operational taxonomic units (OTUs) that are not closely related to any known species (Faecalibacterium, Subdoligranulum, and Oscillospora species), indicating that the phylogenetic dysbiosis is broader than at strain or species level. CONCLUSIONS: These two techniques of microbiome analysis provided a statistically robust new picture of the dysbiosis in fecal microbiota from ileal CD patients. Specifically, we identified a set of six species discriminant for CD, which provides a preliminary diagnostic tool.

Flux and concentration footprint modelling: state of the art.

Since early 1990s, the development of footprint models has been rapid with presently four different approaches being available: (i) analytical models, (ii) Lagrangian stochastic particle dispersion models, (iii) large-eddy simulations, and (iv) closure models. Parameterizations of some of these approaches have been developed, simplifying the original algorithms for use in practical applications. The paper provides a review of the footprint modelling. It also discusses our present understanding of the theoretical background, the most successful modelling approaches, as well as the usage and benefits of the footprint concept as it relates to flux measurements. There has recently been a trend emerging in modelling the behavior of the footprint functions using a less idealized, more realistic description of inhomogeneities, vegetation structure and topography, ultimately for reactive compounds. The estimation of footprints for application in the real world, complete with a multitude of interesting gaseous and particulate substances, remains a complex problem.

Indicator of risk of water contamination by phosphorus from Canadian agricultural land.

The indicator of risk of water contamination by phosphorus (IROWC_P) is designed to estimate where the risk of water P contamination by agriculture is high, and how this risk is changing over time based on the five-year period of data Census frequency. Firstly developed for the province of Quebec (2000), this paper presents an improved version of IROWC_P (intended to be released in 2008), which will be extended to all watersheds and Soil Landscape of Canada (SLC) polygons (scale 1:1, 000, 000) with more than 5% of agriculture. There are three objectives: (i) create a soil phosphorus saturation database for dominant and subdominant soil series of SLC polygons--the soil P saturation values are estimated by the ratio of soil test P to soil P sorption capacity; (ii) calculate an annual P balance considering crop residue P, manure P, and inorganic fertilizer P--agricultural and manure management practices will also be considered; and (iii) develop a transport-hydrology component including P transport estimation by runoff mechanisms (water balance factor, topographic index) and soil erosion, and the area connectivity to water (artificial drainage, soil macropores, and surface water bodies).