Plasmodium falciparum alters the trophoblastic barrier and stroma villi organization of human placental villi explants.

BACKGROUND: The sequestration of Plasmodium falciparum infected erythrocytes in the placenta, and the resulting inflammatory response affects maternal and child health. Despite existing information, little is known about the direct impact of P. falciparum on the placental barrier formed by trophoblast and villous stroma. This study aimed to assess placental tissue damage caused by P. falciparum in human placental explants (HPEs). METHODS: HPEs from chorionic villi obtained of human term placentas (n = 9) from normal pregnancies were exposed to P. falciparum-infected erythrocytes (IE) for 24 h. HPEs were embedded in paraffin blocks and used to study tissue damage through histopathological and histochemical analysis and apoptosis using TUNEL staining. Culture supernatants were collected to measure cytokine and angiogenic factors and to determine LDH activity as a marker of cytotoxicity. A subset of archived human term placenta paraffin-embedded blocks from pregnant women with malaria were used to confirm ex vivo findings. RESULTS: Plasmodium falciparum-IE significantly damages the trophoblast layer and the villous stroma of the chorionic villi. The increased LDH activity and pathological findings such as syncytial knots, fibrin deposits, infarction, trophoblast detachment, and collagen disorganization supported these findings. The specific damage to the trophoblast and the thickening of the subjacent basal lamina were more pronounced in the ex vivo infection. In contrast, apoptosis was higher in the in vivo infection. This disparity could be attributed to the duration of exposure to the infection, which significantly varied between individuals naturally exposed over time and the 24-h exposure in the ex vivo HPE model. CONCLUSION: Exposure to P. falciparum-IE induces a detachment of the syncytiotrophoblast, disorganization of the stroma villi, and an increase in apoptosis, alterations that may be associated with adverse results such as intrauterine growth restriction and low birth weight.

Spindly is a nucleocytosolic O-fucosyltransferase in Dictyostelium and related proteins are widespread in protists and bacteria.

O-GlcNAcylation is a prominent modification of nuclear and cytoplasmic proteins in animals and plants and is mediated by a single O-GlcNAc transferase (OGT). Spindly (Spy), a paralog of OGT first discovered in higher plants, has an ortholog in the apicomplexan parasite Toxoplasma gondii, and both enzymes are now recognized as O-fucosyltransferases (OFTs). Here we investigate the evolution of spy-like genes and experimentally confirm OFT activity in the social amoeba Dictyostelium-a protist that is more related to fungi and metazoa. Immunofluorescence probing with the fucose-specific Aleuria aurantia lectin (AAL) and biochemical cell fractionation combined with western blotting suggested the occurrence of nucleocytoplasmic fucosylation. The absence of reactivity in mutants deleted in spy or gmd (unable to synthesize GDP-Fuc) suggested monofucosylation mediated by Spy. Genetic ablation of the modE locus, previously predicted to encode a GDP-fucose transporter, confirmed its necessity for fucosylation in the secretory pathway but not for the nucleocytoplasmic proteins. Affinity capture of these proteins combined with mass spectrometry confirmed monofucosylation of Ser and Thr residues of several known nucleocytoplasmic proteins. As in Toxoplasma, the Spy OFT was required for optimal proliferation of Dictyostelium under laboratory conditions. These findings support a new phylogenetic analysis of OGT and OFT evolution that indicates their occurrence in the last eukaryotic common ancestor but mostly complementary presence in its eukaryotic descendants with the notable exception that both occur in red algae and plants. Their generally exclusive expression, high degree of conservation, and shared monoglycosylation targets suggest overlapping roles in physiological regulation.

Post-Intensive Care Unit Multidisciplinary Approach in Patients with Severe Bilateral SARS-CoV-2 Pneumonia.

Background: Short and long-term sequelae after admission to the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19) are to be expected, which makes multidisciplinary care key in the support of physical and cognitive recovery. Objective: To describe, from a multidisciplinary perspective, the sequelae one month after hospital discharge among patients who required ICU admission for severe COVID-19 pneumonia. Design: Prospective cohort study. Environment: Multidisciplinary outpatient clinic. Population: Patients with severe COVID-19 pneumonia, post- ICU admission. Methods: A total of 104 patients completed the study in the multidisciplinary outpatient clinic. The tests performed included spirometry, measurement of respiratory muscle pressure, loss of body cell mass (BCM) and BCM index (BCMI), general joint and muscular mobility, the short physical performance battery (SPPB or Guralnik test), grip strength with hand dynamometer, the six-minute walk test (6-MWT), the functional assessment of chronic illness therapy-fatigue scale (FACIT-F), the European quality of life-5 dimensions (EQ-5D), the Barthel index and the Montreal cognitive assessment test (MoCA). While rehabilitation was not necessary for 23 patients, 38 patients attended group rehabilitation sessions and other 43 patients received home rehabilitation. Endpoints: The main sequelae detected in patients were fatigue (75.96%), dyspnoea (64.42%) and oxygen therapy on discharge (37.5%). The MoCA showed a mean score compatible with mild cognitive decline. The main impairment of joint mobility was limited shoulder (11.54%) and shoulder girdle (2.88%) mobility; whereas for muscle mobility, lower limb limitations (16.35%) were the main dysfunction. Distal neuropathy was present in 23.08% of patients, most frequently located in lower limbs (15.38%). Finally, 50% of patients reported moderate limitation in the EQ-5D, with a mean score of 60.62 points (SD 20.15) in perceived quality of life. Conclusions: Our findings support the need for a multidisciplinary and comprehensive evaluation of patients after ICU admission for COVID-19 because of the wide range of sequelae, which also mean that these patients need a long-term follow-up. Impact on clinical rehabilitation: This study provides data supporting the key role of rehabilitation during the follow-up of severe patients, thus facilitating their reintegration in society and a suitable adaptation to daily living.

Clinical outcomes of long-term corneas preserved frozen in Eusol-C used in emergency tectonic grafts.

To report the clinical results on the use of corneas frozen in Eusol-C as tectonic corneal grafts.Retrospective review of medical records of patients who received frozen corneas as emergency tectonic grafts from 2013 to 2020. Corneas had been stored in Eusol-C preservation media at - 78 °C for a mean time of 6.9 months. Diagnosis, transplant characteristics, microbial culture results, anatomic integrity, epithelial healing, neovascularization, transparency, infection and need for additional surgeries were registered. Fifty corneas were used in 40 patients (mean age 60.5 years, 20 males) with a median follow-up of 27.3 months after surgery. Need for tectonic graft was due to: perforation secondary to immune diseases (6, 12%), neurotrophic ulcer (11, 22%), trauma (3, 6%), corneal infection (11, 22%), chronic disorders of the ocular surface (9, 18%) and previous corneal graft failure (10, 22%). Mean size of grafts was 5.6 mm and 36 cases (72%) also received an amniotic membrane graft. Thirty-eight corneas achieved epithelization (76%), 25 (50%) were clear and 19 (38%) developed neovascularization. None of the corneas were rejected. Seventeen corneas (34%) failed: 7 (14%) due to reactivation of baseline disease and 10 (20%) due to primary graft failure. Four corneas (8%) had positive microbial cultures suggestive of contamination and 2 (4%) developed a cornea abscess non-related to a positive microbial culture. Long-term preservation of donor corneas in Eusol-C at - 78 °C is a viable technique to meet the needs of emergency grafts with minimal equipment.

Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.

FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.

[Social networks use and risk factors for the development of eating disorders: A systematic review]. / Uso de redes sociales y factores de riesgo para el desarrollo de trastornos relacionados con la alimentación en España: una revisión sistemática.

OBJECTIVE: Review the available scientific literature on the relationship between the use of social networks and risk factors for the development of eating disorders, such as low self-esteem, body dissatisfaction and/or idealization of thinness, in the Spanish population. DESIGN: A systematic review of scientific literature published between 2010 and 2022 was carried out. DATA SOURCES: PubMed, Scopus and Web of Science. SELECTION OF STUDIES: Only original articles were included, published in Spanish or English, that measured at least one variable of use of social networks and at least one risk factor for eating disorders in the Spanish population. DATA EXTRACTION: The PRISMA 2009 statement was used as a guide. The quality of selected articles was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. RESULTS: Twelve cross-sectional studies that met the inclusion criteria were identified. Evidence suggests that the use and frequency of use of social networks is significantly associated with body dissatisfaction (p≤0,01), drive for thinness (p≤0,001), and low self-esteem (p≤0,05) in adolescents and young adults in the Spanish population. CONCLUSIONS: Users of social networks, mainly those based on images, are exposed to factors that could increase their risk of developing an eating disorder.

Regional variability of glycemic control among adults with diabetes mellitus in Colombia.

Not available.

The effect of comorbidities on glycemic control among Colombian adults with diabetes mellitus: a longitudinal approach with real-world data.

BACKGROUND: Achieving an optimal glycemic control has been described to reduce the incidence of diabetes mellitus (DM) related complications. The association between comorbidities and glycemic control remains unclear. Our aim is to evaluate the effect of comorbidities on glycemic control in people living with DM. METHODS: A retrospective longitudinal study on data from the National Registry of Chronic Kidney Disease from 2014 to 2019 in Colombia. The outcome was poor glycemic control (PGC = HbA1c ≥7.0%). The association between each comorbidity (hypertension (HTN), chronic kidney disease (CKD) or obesity) and PGC was evaluated through multivariate mixed effects logistic regression models. The measures of effect were odds ratios (OR) and their 95% confidence intervals (CI). We also evaluated the main associations stratified by gender, insurance, and early onset diabetes as well as statistical interaction between each comorbidity and ethnicity. RESULTS: From 969,531 people at baseline, 85% had at least one comorbidity; they were older and mostly female. In people living with DM and CKD, the odds of having a PGC were 78% (OR: 1.78, CI 95%: 1.55-2.05) higher than those without CKD. Same pattern was observed in obese for whom the odds were 52% (OR: 1.52, CI 95%: 1.31-1.75) higher than in non-obese. Non-significant association was found between HTN and PGC. We found statistical interaction between comorbidities and ethnicity (afro descendant) as well as effect modification by health insurance and early onset DM. CONCLUSIONS: Prevalence of comorbidities was high in adults living with DM. Patients with concomitant CKD or obesity had significantly higher odds of having a PGC.

Antifungal activity of boric acid, triclosan and zinc oxide against different clinically relevant Candida species.

BACKGROUND: The genus Candida includes about 200 different species, but only a few are able to produce disease in humans. The species responsible for the highest proportion of human infections is Candida albicans. However, in the last two decades there has been an increase in the proportion of infections caused by other Candida species, including C. glabrata (Nakaseomyces glabrata), C. parapsilosis, C. tropicalis, C. krusei (Pichia kudriavzevi) and more recently C. auris. Decolonisation of patients has been used as an infection control strategy for bacterial infections, but information about decolonisation products used in clinical practice for Candida and other fungal pathogens is limited. Compounds with antimicrobial activity, such as triclosan (TR), boric acid (BA) and zinc oxide (ZO), are mainly used in personal care products. These products can be used for long periods of time without an abrasive skin effect and are a possible alternative for patient decolonisation in healthcare settings. OBJECTIVE: The aim of this study was to evaluate the antifungal activity of boric acid (BA), triclosan (TR) and zinc oxide (ZO), individually and combined, against clinically relevant Candida species. MATERIALS AND METHODS: Compounds to be screened for antifungal activity were evaluated at different concentrations, alone, and combined, using a well diffusion assay. The statistical evaluation was performed using analysis of variance (ANOVA) and a post hoc analysis using the multiple comparisons method. RESULTS: Individually, BA and TR showed antifungal activity against all Candida species evaluated but ZO did not show any antifungal activity. Mixtures of BA [5%]-TR [0.2%]; BA [5%]-TR [0.3%]; BA [5%]-TR [0.2%]-ZO [8.6%]; and BA [5%]-TR [0.2%]-ZO [25%] yielded the highest antifungal activity. An increased antifungal effect was observed in some mixtures when compared with individual compounds. CONCLUSIONS: We demonstrated antifungal activity of BA and TR against multiple Candida species, including against a clade of the emerging healthcare-associated pathogen C. auris. Additionally, this study shows enhancement of the antifungal effect and no antagonism among the mixtures of these compounds. Further research is needed to determine whether these compounds can reduce the burden of Candida on skin.

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.

FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.

Aggregation and Amyloidogenicity of the Nuclear Coactivator Binding Domain of CREB-Binding Protein.

The nuclear coactivator binding domain (NCBD) of transcriptional co-regulator CREB-binding protein (CBP) is an example of conformationally malleable proteins that can bind to structurally unrelated protein targets and adopt distinct folds in the respective protein complexes. Here, we show that the folding landscape of NCBD contains an alternative pathway that results in protein aggregation and self-assembly into amyloid fibers. The initial steps of such protein misfolding are driven by intermolecular interactions of its N-terminal α-helix bringing multiple NCBD molecules into contact. These oligomers then undergo slow but progressive interconversion into ß-sheet-containing aggregates. To reveal the concealed aggregation potential of NCBD we used a chemically synthesized mirror-image d-NCBD form. The addition of d-NCBD promoted self-assembly into amyloid precipitates presumably due to formation of thermodynamically more stable racemic ß-sheet structures. The unexpected aggregation of NCBD needs to be taken into consideration given the multitude of protein-protein interactions and resulting biological functions mediated by CBP.

A spatial analysis of childhood cancer and industrial air pollution in a metropolitan area of Colombia.

BACKGROUND: Air pollutants are considered carcinogenic to humans. In some European countries, an association between industrial air pollution and childhood cancer has been established. This relationship has not been addressed in Latin America, despite the spatial variability of air pollutants that may limit the extrapolation of the results to other geographical areas. OBJECTIVE: To conduct a spatial analysis of the relationship between childhood cancer and proximity to industrial sources of air pollution in a metropolitan area of Colombia. METHODS: Incident cases of childhood cancers were obtained from the Population-based Cancer Registry of the Metropolitan Area of Bucaramanga during 2000-2015. Local and focused cluster tests were used for the detection of spatial clusters, and the Poisson multivariable model was used to evaluate the combined effects of spatial variables. RESULTS: The Kulldorff's focused test found a significant spatial cluster (P < 0.001) around one industrial agglomerate and the multivariable model results suggests that the distance effect is modified by the directional effect of the wind. CONCLUSION: A spatial cluster of incident cases of childhood cancer occurred in the municipality of Bucaramanga, Colombia. Our finding supports the hypothesis that childhood cancer might be related with industrial air pollution exposure in a Latin American city.

Exposure to bisphenol A: current levels from food intake are toxic to human cells.

In the present work, cell lines of different origin were exposed to BPA levels from food intake reported elsewhere. Specifically, we used an in vitro assay to determine cytotoxicity of BPA in three cell lines: MCF7 (breast cancer), PC3 (prostate cancer) and 3T3-L1 (mouse fibroblast). Cytotoxic effects were observed at concentrations higher than 50 µg/mL which is above the involuntary exposure level of BPA described before in fresh, canned and frozen foods and beverages. Furthermore, medial inhibitory concentrations (IC50) of 85.17 µg/mL and 88.48 µg/mL were observed for PC3 and 3T3-L1, respectively, and a slightly lower IC50 of 64.67 µg/mL for MCF7. These results highlight BPA's toxicity potential at current levels from food intake. The cell line-dependent divergent response to BPA reported herein is discussed.

Prevention and management of musculoskeletal pain in nursing staff by a multifaceted intervention in the workplace: design of a cluster randomized controlled trial with effectiveness, process and economic evaluation (INTEVAL_Spain).

BACKGROUND: Musculoskeletal pain (MSP) is the leading cause of years lived with disability. In consequence, to reduce MSP and its associated sickness absence is a major challenge. Previous interventions have been developed to reduce MSP and improve return to work of workers with MSP, but combined approaches and exhaustive evaluation are needed. The objective of the INTEVAL_Spain project is to evaluate the effectiveness of a multifaceted intervention in the workplace to prevent and manage MSP in nursing staff. METHODS: The study is designed as a two-armed cluster randomized controlled trial with a late intervention control group. The hospital units are the clusters of randomization and participants are nurses and aides. An evidence-based multi-component intervention was designed combining participatory ergonomics, case management and health promotion. Both the intervention and the control groups receive occupational health care as usual. Data are collected at baseline, and after six and 12 months. The primary outcomes are prevalence of MSP and incidence and duration of sickness absence due to MSP. Secondary outcomes are work role functioning and organizational preventive culture. The intervention process will be assessed through quantitative indicators of recruitment, context, reach, dose supplied, dose received, fidelity and satisfaction, and qualitative approaches including discussion groups of participants and experts. The economic evaluation will include cost-effectiveness and cost-utility, calculated from the societal and the National Health System perspectives. DISCUSSION: Workplace health programs are one of the best options for the prevention and control of non-communicable diseases. The main feature of this study is its multifaceted, multidisciplinary and de-medicalized intervention, which encompasses three evidence-based interventions and covers all three levels of prevention, which have not been previously unified in a single intervention. Also, it includes a comprehensive quantitative and qualitative evaluation of the intervention process, health results, and economic impact. This study could open the possibility of a new paradigm for the prevention and management of MSP and associated sickness absence approach at the workplace. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15780649 Retrospectively registered 13th July 2018.

Leveraging Big Data Towards Functionally-Based, Catchment Scale Restoration Prioritization.

The persistence of freshwater degradation has necessitated the growth of an expansive stream and wetland restoration industry, yet restoration prioritization at broad spatial extents is still limited and ad-hoc restoration prevails. The River Basin Restoration Prioritization tool has been developed to incorporate vetted, distributed data models into a catchment scale restoration prioritization framework. Catchment baseline condition and potential improvement with restoration activity is calculated for all National Hydrography Dataset stream reaches and catchments in North Carolina and compared to other catchments within the river subbasin to assess where restoration efforts may best be focused. Hydrologic, water quality, and aquatic habitat quality conditions are assessed with peak flood flow, nitrogen and phosphorus loading, and aquatic species distribution models. The modular nature of the tool leaves ample opportunity for future incorporation of novel and improved datasets to better represent the holistic health of a watershed, and the nature of the datasets used herein allow this framework to be applied at much broader scales than North Carolina.

Influence of paid maternity leave on return to work after childbirth.

BACKGROUND: Paid maternity leave (ML) has been associated with better health outcomes in mothers and newborns. However, its protective role in mothers' employment after childbirth remains unclear. OBJECTIVE: To assess the association between paid ML and being employed 1-year after childbirth. METHODS: As part of the INfancia y Medio Ambiente (INMA) cohort study, 507 Spanish women employed at 12th week of pregnancy, were asked about their employment status and job characteristics at 32nd week of pregnancy. One year after childbirth, they were re-interviewed about their employment status and if they had taken paid ML. Incidence of maternal employment 1-year after childbirth was estimated. Crude and adjusted associations with paid ML were assessed by logistic regression, and characterized by odds ratios (ORs) with associated 95% CIs. RESULTS: Information was obtained from 398 women. Of those, 290 (72.9%) were employed 1-year after childbirth. Incidence of maternal employment was lower for those who: i) didn't take paid ML, ii) were younger than 27 years; iii) had temporary contract, iv) had part-time jobs, v) reported less-favoured familiar social class, and vi) left the job before 32 weeks of pregnancy. Being employed 1-year after childbirth was more common in those who took paid ML (OR 2.7, 95%CI 1.6-4.5), also after adjusting for staying at work until advanced stages of pregnancy (OR 1.8, 95%CI 1.0-3.1). CONCLUSIONS: Taking paid ML seems to be associated with higher maternal employment rates 1-year after childbirth. Therefore, our findings suggest that protection of maternity might positively influence women's labour market participation after childbirth.

Mutilating Purpura Fulminans in an Adult with Meningococcal Sepsis.

We report a dramatic case of meningococcal sepsis manifesting as purpura fulminans in an elderly diabetic woman. Hemodynamic instability and severe bilateral cutaneous lesions involving her hands and feet developed rapidly. Specific antibiotic therapy and the administration of inotropic and vasopressor drugs were initiated. The severity and extension of the cutaneous lesions (attributed to purpura fulminans) worsened because of the need for vasoconstrictors for the treatment of septic shock. Bilateral transmetatarsal and metacarpal amputations were required to stabilize the patient.

Silkomics: Insight into the Silk Spinning Process of Spiders.

The proteins from the silk-producing glands were identified using both a bottom-up gel-based proteomic approach as well as from a shotgun proteomic approach. Additionally, the relationship between the functions of identified proteins and the spinning process was studied. A total of 125 proteins were identified in the major ampullate, 101 in the flagelliform, 77 in the aggregate, 75 in the tubuliform, 68 in the minor ampullate, and 23 in aciniform glands. On the basis of the functional classification using Gene Ontology, these proteins were organized into seven different groups according to their general function: (i) web silk proteins-spidroins, (ii) proteins related to the folding/conformation of spidroins, (iii) proteins that protect silk proteins from oxidative stress, (iv) proteins involved in fibrillar preservation of silks in the web, (v) proteins related to ion transport into and out of the glands during silk fiber spinning, (vi) proteins involved in prey capture and pre-digestion, and (vii) housekeeping proteins from all of the glands. Thus, a general mechanism of action for the identified proteins in the silk-producing glands from the Nephila clavipes spider was proposed; the current results also indicate that the webs play an active role in prey capture.

Regional Effects of Agricultural Conservation Practices on Nutrient Transport in the Upper Mississippi River Basin.

Despite progress in the implementation of conservation practices, related improvements in water quality have been challenging to measure in larger river systems. In this paper we quantify these downstream effects by applying the empirical U.S. Geological Survey water-quality model SPARROW to investigate whether spatial differences in conservation intensity were statistically correlated with variations in nutrient loads. In contrast to other forms of water quality data analysis, the application of SPARROW controls for confounding factors such as hydrologic variability, multiple sources and environmental processes. A measure of conservation intensity was derived from the USDA-CEAP regional assessment of the Upper Mississippi River and used as an explanatory variable in a model of the Upper Midwest. The spatial pattern of conservation intensity was negatively correlated (p = 0.003) with the total nitrogen loads in streams in the basin. Total phosphorus loads were weakly negatively correlated with conservation (p = 0.25). Regional nitrogen reductions were estimated to range from 5 to 34% and phosphorus reductions from 1 to 10% in major river basins of the Upper Mississippi region. The statistical associations between conservation and nutrient loads are consistent with hydrological and biogeochemical processes such as denitrification. The results provide empirical evidence at the regional scale that conservation practices have had a larger statistically detectable effect on nitrogen than on phosphorus loadings in streams and rivers of the Upper Mississippi Basin.