Antimicrobial resistance of Pseudomonas aeruginosa isolated from patients with pneumonia during the COVID-19 pandemic and pre-pandemic periods in Northeast Brazil.

Healthcare-related infections caused by resistant microorganisms are a severe public health problem and are becoming increasingly prevalent in the hospital environment, especially Pseudomonas aeruginosa. This work aimed to evaluate the resistance profile of Pseudomonas aeruginosa to antimicrobials before the COVID-19 pandemic and during the pandemic period. Bacteria strains were obtained from tracheal aspiration, sputum, and bronchoalveolar lavage for diagnosis and phenotypic characterization. Matrix assisted laser-desorption ionization-time of flight mass spectrometry (MALD-TOF MS) was used to identify strains. Automated Phoenix and VITEK® 2 Compact system and the disc diffusion method were performed to determine the antimicrobial susceptibility profile. A total of 41,000 medical reports from adult patients with pneumonia were analyzed. Of these, 951 patients were positive for P. aeruginosa, of which 373 were related to the pre-pandemic period and 578 to the pandemic period. Older men (≥60 years) were more prevalent in both periods. P. aeruginosa strains were resistant to imipenem in both periods: 38.8 and 42.5%, respectively, followed by meropenem (34.2 and 39.2%), ciprofloxacin (33.6 and 36.7%), and levofloxacin (34.9 and 43.5%). Intensive care units had the highest percentage of affected patients (62 and 65%) compared with other sectors, with a prevalence of 71% in the public network before COVID-19 and 59% during the pandemic. Our data showed a prevalence of P. aeruginosa in elderly patients in both the pre-pandemic and pandemic periods. In addition, an increase in P. aeruginosa resistance to beta-lactams, quinolones, carbapenems, and cephalosporins was observed during the COVID-19 pandemic compared with the period before the pandemic, especially in ICUs.

Antimicrobial resistance of Pseudomonas aeruginosa isolated from patients with pneumonia during the COVID-19 pandemic and pre-pandemic periods in Northeast Brazil

Healthcare-related infections caused by resistant microorganisms are a severe public health problem and are becoming increasingly prevalent in the hospital environment, especially Pseudomonas aeruginosa. This work aimed to evaluate the resistance profile of Pseudomonas aeruginosa to antimicrobials before the COVID-19 pandemic and during the pandemic period. Bacteria strains were obtained from tracheal aspiration, sputum, and bronchoalveolar lavage for diagnosis and phenotypic characterization. Matrix assisted laser-desorption ionization-time of flight mass spectrometry (MALD-TOF MS) was used to identify strains. Automated Phoenix and VITEK® 2 Compact system and the disc diffusion method were performed to determine the antimicrobial susceptibility profile. A total of 41,000 medical reports from adult patients with pneumonia were analyzed. Of these, 951 patients were positive for P. aeruginosa, of which 373 were related to the pre-pandemic period and 578 to the pandemic period. Older men (≥60 years) were more prevalent in both periods. P. aeruginosa strains were resistant to imipenem in both periods: 38.8 and 42.5%, respectively, followed by meropenem (34.2 and 39.2%), ciprofloxacin (33.6 and 36.7%), and levofloxacin (34.9 and 43.5%). Intensive care units had the highest percentage of affected patients (62 and 65%) compared with other sectors, with a prevalence of 71% in the public network before COVID-19 and 59% during the pandemic. Our data showed a prevalence of P. aeruginosa in elderly patients in both the pre-pandemic and pandemic periods. In addition, an increase in P. aeruginosa resistance to beta-lactams, quinolones, carbapenems, and cephalosporins was observed during the COVID-19 pandemic compared with the period before the pandemic, especially in ICUs.

The need for European harmonization of Nutrivigilance in a public health perspective: a comprehensive review.

According to the European Union regulation, some countries have established a pre-market notification system for food supplements while others have not. As this regulation is unfulfilled, a notified and marketed food supplement ingredient in one country may be forbidden in another. Even though food supplements shall not be placed on the market if unsafe, some products may still expose the consumers to risks. The risk is increased by easier access due to worldwide dissemination fostered by the internet and free movement of goods in the European Union. The Rapid Alert System for Food and Feed and the Emerging Risks Exchange Network are described. To date, the European Union legislation does not include a provision to establish a dedicated vigilance system for food supplements (Nutrivigilance). Six European Union countries have nevertheless set up national systems, which are presented. The present lack of European Union data collection harmonization, does not allow easy cooperation between countries. This article advocates for creating a coordinated European Nutrivigilance System to detect and scrutinize adverse effects of food supplements. This, to help in directing science-based risk assessments and reinforce the science-based decision of policy makers to improve public health safety.

Evaluation of At-home Bleaching Times on Effectiveness and Sensitivity with 10% Hydrogen Peroxide: A Randomized Controlled Double-blind Clinical Trial.

OBJECTIVES: The aim of this randomized double-blind controlled clinical trial was to evaluate different protocols for at-home use of 10% hydrogen peroxide in whitening effectiveness and tooth sensitivity. METHODS: Seventy-two patients were selected according to the inclusion and exclusion criteria, with the upper central incisors having color A2 or darker according to the Vita Classical scale (VITA Zahnfabrik, Bad Säckingen, Germany) and randomized into two groups: 10% hydrogen peroxide applied once daily for 15 minutes (HP 15) or applied once daily for 30 minutes (HP 30). Bleaching was performed for 14 days in both groups. The color was evaluated before bleaching, during bleaching (1st and 2nd weeks), and 1 month after the bleaching treatment using the Vita Classical, Vita Bleachedguide 3D-MASTER, and Vita Easyshade spectrophotometer (VITA Zahnfabrik). Dental sensitivity was recorded by the patients using the numerical rating scale (0-4) and visual analogue scale (0-10 cm). Color data were evaluated by two-way analysis of variance (ANOVA) of repeated measures (group vs. treatment time). The Mann-Whitney test was performed to contrast the means (α=0.05). Tooth sensitivity was assessed by Fisher's exact test (p=1.00) and intensity of tooth sensitivity was evaluated by the Mann-Whitney test (α=0.05) for both scales. RESULTS: A significant whitening effect was observed after 2 weeks of bleaching for all color measurements (p=0.01), with no difference between HP 15 and HP 30 (p>0.05). Also, the absolute risk and intensity of tooth sensitivity were similar (47%; p>0.05). CONCLUSIONS: The effectiveness and tooth sensitivity of at-home bleaching carried out with 10% hydrogen peroxide applied for 15 minutes or 30 minutes are similar.

Early identification of keratoconus using pachymetric indexes obtained with spectral domain optical coherence tomography.

PURPOSE: To evaluate the diagnostic ability of pachymetric indexes obtained with Spectral Domain Optical Coherence Tomography (SD-OCT) for early detection of keratoconus (Kc). METHODS: 64 patients with Kc in at least one eye (95 eyes, 46 men and 18 women, average age 27.84 ±13.50), 59 healthy control subjects (100 eyes, 28 men and 31 women, average age 27.15 ±16.14). All patients underwent detailed clinical examination, topography and anterior segment OCT. 37 subjects (37 eyes, 27 men and 10 women, average age 24.23 ± 14.24) having one eye with manifest Kc and the fellow eye without clinical signs of Kc were identified. We studied two groups of pachymetric indexes: C1-C2, M1-M2, pCLMI, Pmin-P2 (Group 1 indexes) and PPD, PSD, PSSD and PASD (Group 2 indexes). A ROC (Receiver Operating Characteristic) curve was developed to compare the diagnostic accuracy, relative sensitivity and specificity for each index. RESULTS: In manifest keratoconus, C1-C2, M1-M2, and pCLMI are significantly higher compared to the control group (P<0.0001); for suspect keratoconus, all Group 1 indexes are significantly higher compared to healthy subjects (P<0.0001) excluding M1-M2 obtained using a constant area circle (P = 0.02). Furthermore, for manifest and suspect keratoconus, PPD, PSD, PSSD and PASD are significantly higher compared to the control group (P <0.0001). CONCLUSION: The studied pachymetric indexes in patients with Kc have high diagnostic accuracy and are statistically significant when compared with healthy subjects (p<0.0001) and can provide a useful tool for keratoconus screening.

Synthesis, biological activity, and four-dimensional quantitative structure-activity analysis of 2-arylidene indan-1,3-dione derivatives tested against Daphnia magna.

A series of 18 2-arylidene indan-1,3-dione derivatives was synthesized and tested against Daphnia magna to assess the environmental toxicity of these compounds. Aiming to investigate the toxicity mechanism for this series of compounds, a four-dimensional quantitative structure-activity analysis (4D-QSAR) was performed through the partial least square regression (PLS). The best PLS model was built with two factors and the selected field descriptors, of Coulomb (C) and Lennard-Jones (L) nature, describing 77.43% of variance and presenting the following statistics: r 2 = 0.89; SEC = 0.30; Q 2 = 0.81; SEV = 0.36. According to the literature, the bioactivity of α,ß-unsaturated ketones, a functionality present in the series of compounds under investigation, is related to the conjugated double bond with the carbonyl group. The presence of a positive Coulomb descriptor nearby the carbonyl moieties, obtained as a result of the regression model, indicates that these polar groups are also related to the toxicity on D. magna. From the PLS regression model, the toxicity EC50-48 h values increases with the positive Coulomb descriptor and diminishes with the negative Lennard-Jones descriptors. It could be concluded that the presence of small polar groups in the aromatic ring of the arylidene moiety tends to increase the toxicity, while bulkier apolar substituents lead to a decrease of the toxicity.

Effect of size and location of simulated lytic lesions on the structural properties of human vertebral bodies, a micro-finite element study.

Currently, the Spinal Instability Neoplastic Score system is used in clinics to evaluate the risk of fracture in patients with spinal metastases. This method, however, does not always provide a clear guideline due to the complexity in accounting for the effect of metastatic lesions on vertebral stability. The aim of this study was to use a validated micro Finite Element (microFE) modelling approach to analyse the effect of the size and location of lytic metastases on the mechanical properties of human vertebral bodies. Micro Computed Tomography based microFE models were generated with and without lytic lesions simulated as holes within a human vertebral body. Single and multiple lytic lesions were simulated with four different sizes and in five different locations. Bone was assumed homogenous, isotropic and linear elastic, and each vertebra was loaded in axial compression. It was observed that the size of lytic lesions was linearly related with the reduction in structural properties of the vertebral body (reduction of stiffness between 3% and 30% for lesion volume between 4% and 35%). The location of lytic lesions did not show a clear effect on predicted structural properties. Single or multiple lesions with the same volume provided similar results. Locally, there was a homogeneous distribution of axial principal strains among the models with and without lytic lesions. This study highlights the potential of microFE models to study the effect of lesions on the mechanical properties of the human vertebral body.

Biomechanical assessment of vertebrae with lytic metastases with subject-specific finite element models.

The assessment of risk of vertebral fracture in patients with lytic metastases is challenging, due to the complexity in modelling the mechanical properties of this heterogeneous material. Currently clinical assessment of patients at high risk of fracture is based on the Spinal Instability Neoplastic Score (SINS), which however in many cases does not provide clear guidelines. The goal of this study was to develop a computational approach to provide a comparative biomechanical assessment of vertebrae with lytic lesions with respect to the adjacent controls and highlight the critical vertebrae. The computed tomography images of the thoracolumbar spine of eight patients suffering of vertebral lytic metastases with SINS between 7 and 12 (indeterminate unstable) were analysed. For each patient one or two vertebrae with lytic lesions were modelled and the closest vertebrae without lesions were considered as control. Metastatic vertebrae (N = 12) and controls (N = 18) were converted to subject-specific, heterogeneous, isotropic, nonlinear finite element models for simulating uniaxial compression. Densitometric and mechanical properties were computed for each vertebra. In average, similar mechanical properties were found for vertebrae with lytic lesions and controls (e.g. ultimate force equal to 6.2 ±â€¯2.7 kN for vertebrae with lytic lesions and to 6.2 ±â€¯3.0 kN for control vertebrae). Only in three patients the vertebrae with lytic lesions were found to be mechanically weaker (-19% to -75% difference for ultimate stress) than the controls. In conclusion, in this study we presented an approach to estimate the mechanical competence of vertebrae with lytic metastases. It remains to be investigated in a clinical study if this method, together with the SINS, can better classify patients with vertebrae with lytic lesions at high risk of fracture.

Social, environmental and microbiologic aspects of endemic mycoses in Brazil.

Many factors that lead to host immunosuppression are clearly known to predispose the host to fungal diseases, significantly influencing the occurrence of mycoses. However, little or nothing has been discussed regarding social or economic factors that can influence the occurrence of diseases caused by fungi. In this minireview, we discuss several factors that may affect the occurrence of mycoses in Brazil, a continentally extended country that is marked by large climatic variations and severe socioeconomic distortions that may limit access to health services for the population.

Natural vertical infection by dengue virus serotype 4, Zika virus and Mayaro virus in Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus.

Vertical transmission to progeny ensures the maintenance of arboviruses in their natural vectors. This mechanism is largely reported for dengue virus (DENV) and yellow fever virus (YFV). Few studies have addressed this mechanism for Zika virus (ZIKV), Mayaro virus (MAYV) and other arboviruses. The present study investigated the natural infection rate by arboviruses in 4490 Aedes (Stegomyia) aegypti and 296 Aedes (Stegomyia) albopictus (Diptera: Culicidae) reared from eggs collected with ovitraps in Cuiabá, Mato Grosso State, from February to July, 2017. After viral RNA extraction and reverse transcriptase-polymerase chain reaction protocols for 10 flaviviruses and five alphaviruses, nucleotide sequencing and three passages in C6/36 cells, eight pools of Ae. aegypti positive for DENV-4 genotype II, seven for ZIKV Asian genotype and two for MAYV genotype L were found. In addition, two Ae. albopictus pools were positive for DENV-4 genotype II and two were positive for ZIKV Asian genotype. Infection was confirmed by viral isolation in all positive pools for DENV-4 and for MAYV and in eight of nine for ZIKV. This mechanism may contribute to the spread of arboviruses during epidemics and also to their maintenance in natural vectors during interepidemic periods.

Arbovirus investigation in patients from Mato Grosso during Zika and Chikungunya virus introdution in Brazil, 2015-2016.

Arboviruses have become a major public health concern in Brazil, especially after Zika virus (ZIKV) and Chikungunya virus (CHIKV) introduction, leading to massive epidemics. We conducted an investigation of arboviruses in patients with acute febrile illness for less than five days in Mato Grosso state (MT) during the period of ZIKV and CHIKV dissemination in Brazil. To achieve that, 453 human serum samples of patients suspected of Dengue (DENV), Yellow Fever (YFV), ZIKV or CHIKV collected in health units of 31 cities of MT were subjected to RT-PCR protocols for 10 flaviviruses, 5 alphaviruses and orthobunyaviruses from Simbu serogroup, nucleotide sequencing and viral isolation. Regarding flaviviruses, five (1.1%) patients were infected with DENV-1 genotype V, 22 (4.4%) with DENV-4 genotype II, 3 (0.7%) with YFV South American genotype II and five (1.1%) with ZIKV Asian genotype. The first human case of ZIKV in MT was detected in this study during August, 2015 in Tapurah. Alphaviruses were detected in 2 (0.4%) patients infected with CHIKV genotype ECSA, 1 (0.2%) with Madariaga (EEEV) lineage III and 34 (7.5%) with Mayaro (MAYV) genotype L. Four (11.4%) patients presented dual infections with DENV-1/ZIKV, DENV-1/DENV4, DENV-4/MAYV and ZIKV/MAYV. The majority - 13/34 positive for MAYV, one for Madariaga virus - are residents in Várzea Grande (VG), metropolitan region of Cuiabá, capital of MT. The first CHIKV infection in MT was detected in this study in Mirassol D'Oeste, during July, 2015. In addition, 20 (4.4%) patients were positive for OROV Segment S genotype IA. These results reinforce the variation in arboviruses frequency and distribution during outbreaks, highlinghing the importance of differential diagnosis to identify agents silently co-circulating with major health problem arboviruses.

Speech and language therapy service delivery: overcoming limited provision for children.

OBJECTIVES: To test an alternative Speech and Language Therapy (SLT) service delivery model based on partnerships between a University and local schools and charities, and to report on the impact and feasibility of intervention based on long-term outcome measures and three case studies with individual analysis of Reliable Change. STUDY DESIGN: The following six-step model was tested: 1-establishing partnerships; 2-flagging children; 3-pre-treatment SLT assessment; 4-reporting and discussion with parents and teachers; 5-treatment; 6-post-treatment assessment. Case studies are presented. METHODS: A partnership was established with one kindergarten in a pre-test and a total of 25 kindergartens during the second phase of the process. A group of 139 children were then flagged and assessed. The following long-term outcomes (18 months post-therapy) were investigated: phonetic-phonological standardised test percentiles and raw scores; receptive and expressive language percentiles and raw scores according to a standardised language test; percentage of syllables stuttered; duration of stuttering moments; academic achievement in norm-tests' core areas (mathematics, Portuguese language and social studies). Case studies and a 95% credible interval analysis to assess Reliable Change are presented. RESULTS: Seventy five (54%) children needed SLT support. Fifty (67%) of those children returned to the clinic for long-term assessments and the analysis of all outcome measures showed significant improvements in their performance, 18 months post-therapy. Case Studies Reliable Change analysis revealed a statistically significant improvement, which also clearly shows the feasibility and the positive impact of the intervention. CONCLUSIONS: This specialised and differentiated care network constitutes an alternative delivery system of SLT services that addresses the lack of support currently experienced by children and their families. The long-term outcome measures and the 95% credible interval analysis are reliable methods to determine the impact of interventions.

Profiling of antioxidant potential and phytoconstituents of Plantago coronopus / Avaliação do potencial antioxidante e perfil fitoquímico do Plantago coronopus

Abstract The halophyte species Plantago coronopus has several described ethnomedicinal uses, but few reported biological activities. This work carried out for the first time a comparative analysis of P. coronopus organs in terms of phenolic composition and antioxidant activity of organic and water extracts from roots, leaves and flowers. The leaves contents in selected nutrients, namely amino acids and minerals, are also described. Roots (ethyl acetate and methanol extracts) had the highest radical scavenging activity (RSA) towards 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, while leaves (hexane extract) had higher RSA on nitric oxide radical and iron chelating ability. High performance liquid chromatography (HPLC) analysis identified eighteen phenolics from which salicylic acid and epicatechin are here firstly described in Plantago species. Leaves had mineral levels similar to those of most vegetables, proving to be a good source for elements like calcium, sodium, iron and magnesium, and also for several of the essential amino acids justifying it use as food. Our results, especially those regarding the phenolics composition, can explain the main traditional uses given to this plantain and, altogether, emphasize the potential of P. coronopus as a source of bioactive molecules particularly useful for the prevention of oxidative stress-related diseases.

Resumo A espécie halófita Plantago coronopus tem vários usos etnomedicinais já descritos, mas em relação à bioatividade a informação é escassa. Este trabalho efetuou, pela primeira vez, uma análise comparativa dos órgãos de P. coronopus em termos de compostos fenólicos e atividade antioxidante de extratos orgânicos e aquosos provenientes das raízes, folhas e flores da planta, bem como o conteúdo de determinados nutrientes, aminoácidos e minerais, nas folhas da planta. As raízes (extratos de acetato de etila e metanol) apresentaram a maior atividade de captação para os radicais 1,1-difenil-2-picril hidrazil (DPPH) e 2,2'-azino-bis(3-etilbenzotiazolina-6-ácido sulfónico) (ABTS), enquanto as folhas (extrato de hexano) mostraram maior atividade captadora para o radical óxido nítrico bem como maior capacidade quelante do ferro. A análise por cromatografia liquida de alta eficiência (CLAE) identificou dezoito compostos fenólicos e, destes, o ácido salicílico e a epicatequina são aqui descritos pela primeira vez em espécies de Plantago. As folhas desta planta halófita mostraram ainda conter minerais em níveis semelhantes aos da maioria dos vegetais, provando ser uma boa fonte de elementos como o cálcio, sódio, ferro e magnésio, bem como de vários dos aminoácidos essenciais o que justifica seu uso na alimentação. Os resultados, particularmente aqueles relacionados à composição fenólica, podem justificar os principais usos medicinais atribuídos a esta espécie e, na sua totalidade, demonstram o potencial de P. coronopus como fonte de moléculas bioativas particularmente úteis na prevenção de doenças relacionadas com estresse oxidativo.

Two-dimensional quantitative structure-activity relationship study of 1,4-naphthoquinone derivatives tested against HL-60 human promyelocytic leukaemia cells.

A series of 50 derivatives of 1,4-naphthoquinone tested against human HL-60 leukaemic cells showed activity at a wide range of concentrations. A multivariate quantitative structure-activity relationship (QSAR) study of 45 compounds was performed through principal component analysis (PCA) and partial least squares (PLS) regression. A good PLS regression model was obtained with two factors describing 60.1% of the total variance, and the selected descriptors were partial atomic charge at carbons 1 and 10 (C1 and C10) and total dipole moment (DIP). The calibration model exhibited the determination coefficient r2 = 0.78 and the standard error of calibration = 0.29. For external validation, r2 and the standard error of prediction were 0.74 and 0.32, respectively. DIP and C1 were the main descriptors for PCA, as well as for PLS, such that the pIC50 value increases when C1 increases and DIP diminishes. The selected descriptors are in accordance with the literature, once C10 and C1 are bound or close to the quinone oxygens involved in the production of radical anions (O2-∙). From the QSAR analysis, the structures of two new naphthoquinones were proposed and their estimated IC50 values were 1.42 and 1.13 µmol L-1.

Characterization of the Fecal Bacterial Microbiota of Healthy and Diarrheic Dairy Calves.

BACKGROUND: Neonatal diarrhea accounts for more than 50% of total deaths in dairy calves. Few population-based studies of cattle have investigated how the microbiota is impacted during diarrhea. OBJECTIVES: To characterize the fecal microbiota and predict the functional potential of the microbial communities in healthy and diarrheic calves. METHODS: Fifteen diarrheic calves between the ages of 1 and 30 days and 15 age-matched healthy control calves were enrolled from 2 dairy farms. The Illumina MiSeq sequencer was used for high-throughput sequencing of the V4 region of the 16S rRNA gene (Illumina, San Diego, CA). RESULTS: Significant differences in community membership and structure were identified among healthy calves from different farms. Differences in community membership and structure also were identified between healthy and diarrheic calves within each farm. Based on linear discriminant analysis effect size (LEfSe), the genera Bifidobacterium, Megamonas, and a genus of the family Bifidobacteriaceae were associated with health at farm 1, whereas Lachnospiraceae incertae sedis, Dietzia and an unclassified genus of the family Veillonellaceae were significantly associated with health at farm 2. The Phylogenetic Investigation of Communities Reconstruction of Unobserved States (PICRUSt) analysis indicated that diarrheic calves had decreased abundances of genes responsible for metabolism of various vitamins, amino acids, and carbohydrate. CLINICAL RELEVANCE: The fecal microbiota of healthy dairy calves appeared to be farm specific as were the changes observed during diarrhea. The differences in microbiota structure and membership between healthy and diarrheic calves suggest that dysbiosis can occur in diarrheic calves and it is associated with changes in predictive metagenomic function.

Genetic profile of Brazilian patients with dystrophinopathies.

Different types of mutations in the DMD gene underlie Duchenne muscular dystrophies (DMD) and Becker muscular dystrophies (BMD). Large deletions and duplications are the most frequent causative genetic alterations worldwide, but little is known about DMD/BMD genetic profile in Brazil. Hence, we recruited patients with DMD and BMD from 8 neuromuscular reference centers along the country, and performed a comprehensive molecular investigation that included Multiplex Ligation-dependent Probe Amplification and Next generation sequencing (NGS) analyses. We evaluated 199 patients from 177 unrelated families: 166 with DMD, 32 with BMD and 1 1.5 years old asymptomatic patient with persistent hiperCKemia. Overall, large deletions (58.2%) followed by nonsense mutations (12.4%) and large duplications (11.3%) were the most frequent variants in Brazilian families. Large deletions were less frequent in BMD than in DMD (44.8% vs 60.8%). We identified 19 new DMD variants. Nonsense mutations were significantly more frequent in patients from northeastern region than from southern/southeastern regions of Brazil (27.7% vs 8.5%, P < .05). Genetic profile of Brazilian patients with DMD/BMD is similar to previously reported cohorts, but it is not uniform across the country. This information is important to plan rational clinical care for patients in face of the new coming mutation-specific therapies.

Duodenitis-Proximal Jejunitis in Horses After Experimental Administration of Clostridium difficile Toxins.

BACKGROUND: Duodenitis-proximal jejunitis (DPJ) is an acute sporadic gastrointestinal disorder of horses of unknown cause. HYPOTHESIS/OBJECTIVES: We hypothesize that Clostridium difficile toxins are involved in the pathogenesis of DPJ in horses. The objective of this study was to determine whether experimentally delivered C. difficile toxins cause clinical signs and histologic lesions similar to those of naturally occurring DPJ. ANIMALS: Six healthy mature mixed breed horses. METHODS: Experimental study: animal model of animal disease. Fasted horses were administered crude C. difficile toxins via gastroscopy and monitored for up to 48 hour. Blood was collected for complete blood cell count, biochemistry profile, and plasma fibrinogen assay, and abdominal fluid was collected for cytologic analysis and total solids before and after toxin administration. Physical examination and abdominal ultrasonography were performed throughout the study period. Tissues were collected from the gastrointestinal tract and processed for routine histologic analysis, and lesions were scored. RESULTS: Clinical signs were observed in 2 of 6 horses that are typical although not specific for horses with naturally occurring DPJ. Histopathologic lesions were observed in 6 of 6 horses and were similar to those reported in horses with naturally occurring DPJ. Two horses were severely affected. CONCLUSIONS AND CLINICAL IMPORTANCE: Duodenitis-proximal jejunitis is likely a syndrome with multiple causes that result in the same clinical and pathologic findings, and our data suggest that the toxins of C. difficile represent one cause of this syndrome. Toxin dose and variation in individual animal susceptibility might affect the clinical signs and lesions after administration of C. difficile toxins.