Christiane V. Löhr

Adult salmon enteritis (ASE) is a severe intestinal disease affecting spring Chinook Salmon ( Oncorhynchus tshawytscha ) in the Pacific Northwest. ASE is strongly associated with prespawn mortality (PSM), a critical concern for endangered populations and continued Chinook Salmon management. This study characterizes the geographic distribution of ASE across Oregon and Washington watersheds, examines its association with two common parasites ( Ceratonova shasta and Enterocytozoon schreckii ), and provides detailed histopathological characterization of the disease. We examined intestinal tissues from 259 adult spring Chinook Salmon collected from multiple hatcheries across the Columbia River Basin and Puget Sound between 2022 and 2025 using routine histopathology, specific histochemical stains, and immunohistochemistry. ASE was highly prevalent in all Columbia Basin populations, with chronic ulcerative and necrotizing enteritis, but was absent in Puget Sound populations. C. shasta prevalence was high in most Columbia Basin locations (10%–100%), while E. schreckii prevalence was more variable (0%–67%). Consistent histopathological findings of ASE included ≥ 10% mucosal ulceration, mixed inflammation expanding the lamina propria and extending into surrounding intestinal layers, and dissolution of the stratum granulosum. In chronic ASE lesions, we further characterized granulation tissue formation. Cold water holding of spawning adults appears to slow disease progression and reduce PSM without preventing ASE development. These findings demonstrate that ASE is a geographically restricted disease of the Columbia Basin that may have associations with diverse environmental exposures including water temperature and pathogens.

Adult salmon enteritis (ASE) is a severe intestinal disease affecting spring Chinook Salmon ( Oncorhynchus tshawytscha ) in the Pacific Northwest. ASE is strongly associated with pre-spawn mortality (PSM), a critical concern for endangered populations and continued Chinook Salmon management. This study characterizes the geographic distribution of ASE across Oregon and Washington watersheds, examines its association with two common parasites ( Ceratonova shasta and Enterocytozoon schreckii ), and provides detailed histopathological characterization of the disease. We examined intestinal tissues from 256 adult spring Chinook Salmon collected from multiple hatcheries across the Columbia River Basin and Puget Sound between 2022 and 2025 using routine histopathology, specific histochemical stains, and immunohistochemistry. ASE was highly prevalent in all Columbia Basin populations, with chronic ulcerative and necrotizing enteritis, but was absent in Puget Sound populations. C. shasta prevalence was high in most Columbia Basin locations (10-100%), while E. schreckii prevalence was more variable (0-67%). Consistent histopathological findings of ASE included ≥ 10% mucosal ulceration, mixed inflammation expanding the lamina propria and extending into surrounding intestinal layers, and dissolution of the stratum granulosum. In chronic ASE lesions, we further characterized granulation tissue formation. Cold water holding of spawning adults appears to slow disease progression and reduce PSM without preventing ASE development. These findings demonstrate that ASE is a geographically restricted disease of the Columbia Basin that may have associations with diverse environmental exposures including water temperature and pathogens.

The efficacy of candidate drugs for neuroprotection is tested in rodent models of retinal atrophy where light-induced outer retinal atrophy (ORA) is quantified by manual or semi-automated measurements, analyses that are time-consuming and error-prone. We developed a quantitative, automated image analysis–based method of ORA assessment in whole-slide images (WSIs). A commercial, cloud-based, artificial intelligence image analysis platform (Aiforia) was used to train convolutional neural network (CNN)-based deep learning models for semantic segmentation of retina and object counts of outer nuclear layer (ONL) nuclei. Model development was an iterative process of establishing and fine-tuning the ground truth (manual annotations), adding training annotations, and increasing the number of CNN training iterations. Inter-observer concordance yielded F1-scores exceeding 0.98 for retina area and 0.92 for ONL counts. Performance of the developed algorithm in comparison with manual annotations by individual validators yielded F1-scores between 0.89 and 0.95. Analysis of WSIs by the algorithm was completed 50× faster compared with manual analysis on hematoxylin and eosin–stained sections; however, it required time to digitize the slides. Performance of the ORA quantification deep learning model is noninferior to that of current manual ORA scoring approaches and provides improved reproducibility and reduced time and cost of analysis.

Objective: To characterize an acquired carpal hyperextension syndrome reported by North American owners of Nigerian Dwarf goats and examine potential genetic associations. Methods: Affected (cases) and unaffected (controls) Nigerian Dwarf goats were recruited into this observational study from 2022 to 2023 through a small ruminant producer email list and social media. Animals with reported limb trauma, cases with mild carpal angulation, and controls under 2 years old were excluded. Physical examination, carpal goniometry and blood mineral analysis were performed on all animals. Husbandry and registration information were recorded by a standardized questionnaire. Imaging and histopathology were performed on a subset of cases. Pedigrees were analyzed for common ancestor(s) with Pedigraph. A genome-wide association study was performed with the Illumina GoatSNP50 array. Results: 36 cases (carpal angle > 187°) and 64 controls were included. Owners recognized cases at a median age of 12 months (IQR, 12 to 24 months; range, 3 to 36 months); lameness was common in cases. Median standing carpal angle of cases when bearing weight was 193.3° (IQR, 190.2° to 198.3°) versus 180.3° in controls (IQR, 180.0° to 180.7°). Imaging and histopathology did not identify a structural cause. Blood mineral concentrations were similar between groups. Pedigree analysis indicated all cases shared a single ancestor. Genome-wide analysis identified a region of interest (chr24:59,830,666-60,251,280) associated with the hyperextension phenotype. Conclusions: Carpal hyperextension in Nigerian Dwarf goats was often associated with lameness and appears heritable. Clinical Relevance: Small ruminant producers and veterinarians should be alert to this potentially heritable condition. Carpal goniometry of standing animals represents an inexpensive and minimally invasive diagnostic procedure.

A 5‐year‐old female alpaca was presented with respiratory distress and lethargy. Thoracic radiographs revealed a cranioventrally distributed alveolar pattern, caudodorsal bronchial pattern, cardiomegaly, increased soft tissue opaque content in the ventral thorax, and rounded soft tissue opaque structures craniodorsal to the carina. Cardiac gated CT demonstrated a patent ductus arteriosus, ventricular septal defect, complete left atrioventricular valve atresia, partial anomalous venous connections from the cranial pulmonary veins to the azygous and cranial vena cava, severe right‐sided cardiomegaly, pleural and peritoneal fluid, and severe hepatic congestion. These findings were confirmed with necropsy.

Antitumor effects of BFC1108 in an orthotopic breast cancer model. A, BFC1108 inhibits growth of high Bcl-2–expressing MDA-MB-231 TNBC cells in vivo. A total of 106 MDA-MB-231/Bcl-2 cells were implanted in the mammary fat pad of NOD.SCID mice (n = 8 per group). Once palpable tumors were detected, mice were randomized and treated with vehicle or BFC1108 at 100 mg/kg twice a week by intraperitoneal route. Tumor measurements were made with digital calipers twice a week. *, P < 0.05 from day 18 onward. B, The body weights of mice treated with vehicle or BFC1108 in A were measured twice a week. C, Induction of apoptosis of tumor cells by BFC1108 in vivo. Immunofluorescence was performed on frozen tumor sections to determine apoptosis by TUNEL staining. D, BFC1108 induces conformation change of Bcl-2 in tumor tissues. Bcl-2 conformational change was detected by staining with Bcl-2 BH3 antibody. E, Bax activation by BFC1108. Activated Bax was detected using Bax 6A7 antibody in tumor tissues from animals treated with vehicle or BFC1108. F, Activation of caspase-3 by BFC1108. Activated caspase-3 was detected using cleaved caspase-3 antibody in tumor tissues from animals treated with vehicle or BFC1108.

Bioluminescent imaging of data in Figure 7 for individual mouse treated with vehicle or BFC1108 is shown.

Interaction of BFC1108 with Bcl-2. A, Limited proteolysis of Bcl-2 loop domain in the presence of BFC1108. Purified GST-tagged Bcl-2 loop domain and GST only control were incubated with 50 µmol/L BFC1108. The proteolysis pattern of loop domain was determined at the indicated times upon coincubation with trypsin. B, BFC1108 stabilizes and increases melting temperature (Tm) of Bcl-2 full-length protein. Thermal unfolding of Bcl-2 full-length protein in the presence of BFC1108 was monitored by SYPRO Orange fluorescence. Z-tag and no protein control samples were included to confirm BFC1108 specific interaction with Bcl-2. Two-way ANOVA with Sidak multiple comparisons post hoc test, **, P < 0.01; ****, P < 0.0001. C, BFC1108 stabilizes and increases Bcl-2 loop domain melting temperature (Tm). Thermal unfolding of Bcl-2 loop domain in the presence of BFC1108 monitored by SYPRO Orange fluorescence. One-way ANOVA with Dunnett multiple comparisons post hoc test, ****, P < 0.0001. D, MDA-MB-231/Bcl-2, H460 cells were exposed to BFC1108 at 10 µmol/L concentration for 48 hours in a medium containing 10% serum. Change in conformation of Bcl-2 was determined by using Bcl-2 BH3 antibody followed by flow cytometric analysis.

Inhibition of breast cancer lung metastasis by BFC1108. A, BFC1108 suppresses the growth of lung metastasis in vivo. LMD-231 cells (200,000) stably expressing luciferase were injected into the tail vein of 6-week-old nude mice. Lung metastasis was detected in 2 weeks. Mice were randomized and were treated four times a week with vehicle or 100 mg/kg BFC1108 by intraperitoneal route (n = 8 for vehicle treatment and n = 9 for BFC1108 treatment). Bioluminescent imaging was performed once a week and quantified. *, P < 0.05; **, P < 0.01; ***, P < 0.001. Bioluminescent imaging data for individual mouse treated with vehicle or BFC1108 are shown in Supplementary Fig. S2. B, Representative mouse image from vehicle and BFC treatment is shown. C, Treatment with BFC1108 does not alter body weight of mice. Body weights were measured each time the mice were imaged. D, Suppression of lung metastasis by BFC1108. H&E staining showed increased number of tumor cells in lung tissue of mice with vehicle treatment, compared with BFC1108 treatment, at the end of the study. E, BFC1108 reduces proliferation of lung metastatic TNBC cells. Detection of Ki-67 indicating proliferating tumor cells in lung tissue from vehicle and BFC1108-treated mice.