Therapeutic blockade of ER stress and inflammation prevents NASH and progression to HCC.

The incidence of hepatocellular carcinoma (HCC) is rapidly rising largely because of increased obesity leading to nonalcoholic steatohepatitis (NASH), a known HCC risk factor. There are no approved treatments to treat NASH. Here, we first used single-nucleus RNA sequencing to characterize a mouse model that mimics human NASH-driven HCC, the MUP-uPA mouse fed a high-fat diet. Activation of endoplasmic reticulum (ER) stress and inflammation was observed in a subset of hepatocytes that was enriched in mice that progress to HCC. We next treated MUP-uPA mice with the ER stress inhibitor BGP-15 and soluble gp130Fc, a drug that blocks inflammation by preventing interleukin-6 trans-signaling. Both drugs have progressed to phase 2/3 human clinical trials for other indications. We show that this combined therapy reversed NASH and reduced NASH-driven HCC. Our data suggest that these drugs could provide a potential therapy for NASH progression to HCC.

Association of feed efficiency with organ characteristics and fatty liver haemorrhagic syndrome in laying hens.

Poor feed efficiency (FE) in hens impacts body weight (BW) and may reflect suboptimal health. Fatty Liver Haemorrhagic Syndrome (FLHS) is mostly observed in laying hens and affects egg production and hen performance. The aim of this study was to investigate the relationships of FE and BW with organ characteristics, liver composition and incidence of FLHS of 150 individually housed ISA Brown hens ranked on the basis of feed conversion ratio (FCR) attained from early lay. At 45 weeks, 10 birds per FE group (HFE-High feed efficient; MFE-medium feed efficient; LFE-low feed efficient) were randomly selected and euthanized. Hen BW was positively associated with feed intake and FCR. The HFE hens had a lower abdominal fat pad and liver weight compared to LFE hens. FLHS lesion score was higher (worse) in the LFE than HFE hen group and was moderately positively associated with BW and abdominal fat pad, but strongly positively associated with liver weight. Liver pathology of LFE hens showed hepatocytes with abnormal retention of lipids causing distended cytoplasmic vacuoles compared to the HFE hens. Hens which exhibited poorer FE in early lay had heavier abdominal fat pads, heavier, fatter livers and were more prone to FLHS.

Differentiation of Livestock Internal Organs Using Visible and Short-Wave Infrared Hyperspectral Imaging Sensors.

Automatic identification and sorting of livestock organs in the meat processing industry could reduce costs and improve efficiency. Two hyperspectral sensors encompassing the visible (400-900 nm) and short-wave infrared (900-1700 nm) spectra were used to identify the organs by type. A total of 104 parenchymatous organs of cattle and sheep (heart, kidney, liver, and lung) were scanned in a multi-sensory system that encompassed both sensors along a conveyor belt. Spectral data were obtained and averaged following manual markup of three to eight regions of interest of each organ. Two methods were evaluated to classify organs: partial least squares discriminant analysis (PLS-DA) and random forest (RF). In addition, classification models were obtained with the smoothed reflectance and absorbance and the first and second derivatives of the spectra to assess if one was superior to the rest. The in-sample accuracy for the visible, short-wave infrared, and combination of both sensors was higher for PLS-DA compared to RF. The accuracy of the classification models was not significantly different between data pre-processing methods or between visible and short-wave infrared sensors. Hyperspectral sensors, particularly those in the visible spectrum, seem promising to identify organs from slaughtered animals which could be useful for the automation of quality and process control in the food supply chain, such as in abattoirs.

Dermatophilus congolensis associated bronchopneumonia in an alpaca.

A severe, chronic, locally extensive granulomatous bronchopneumonia was diagnosed on post-mortem and histopathological examination of an adult alpaca. Dermatophilus congolensis organisms were isolated from the lungs and genotypic identification of aerobic culture was confirmed by sequence analysis of the entire 16S rDNA gene. This is the first report of D. congolensis-associated bronchopneumonia in any species.

Postmortem detection and histopathological features of canine spirocercosis-induced putative esophageal chondrosarcoma.

AIM: The objective of this study was to describe and characterize the postmortem and histopathological findings of putative esophageal chondrosarcoma associated with Spirocerca lupi. MATERIALS AND METHODS: Spirocerca-associated esophageal nodules were collected from 54 dogs at postmortem examination and were stained with hematoxylin and eosin. Of the cases examined, 15 were selected randomly for further investigation, of which 11 were classified as non-neoplastic nodules while 4 had changes reflecting a neoplastic process. RESULTS: In all four neoplastic cases, the wall of the esophageal nodules contained islands and nests of highly proliferative atypical chondroblasts within a cartilaginous matrix. However, there was no statistically significant association between gender (p=0.228), age (p=0.568), and breeds (p>0.05) with the occurrence of spirocercosis. Moreover, all esophageal nodules identified were located near the caudal segment, and their diameters ranged from 1 to 6 cm (4.7±1.5 cm). A number of worms in each nodule varied from 5 to 25 (11.3±5). CONCLUSION: Histopathology and cytology revealed that the wall of the esophageal nodules contained islands and nests of highly proliferative atypical chondroblasts within a cartilaginous matrix, a rare finding, and clinical challenge in spirocercosis.

Treatment of experimentally induced osteoarthritis in horses using an intravenous combination of sodium pentosan polysulfate, N-acetyl glucosamine, and sodium hyaluronan.

OBJECTIVE: To assess the effects of sodium pentosan polysulfate (PPS), N-acetyl glucosamine (NAG), and sodium hyaluronan (HA) in horses with induced osteoarthritis (OA). STUDY DESIGN: Experimental. ANIMALS: Adult Standard bred horses (n = 16). METHODS: OA was induced arthroscopically in 1 intercarpal joint; 8 horses were administered 3 mg/kg PPS, 4.8 mg/kg NAG, and 0.12 mg/kg HA (PGH), intravenously (IV), weekly and 8 horses were administered an equivalent volume of saline IV until study completion (day 70). Horses underwent a standardized treadmill exercise program. Clinical and radiographic findings and synovial fluid analysis were evaluated throughout the study. Macroscopic, histologic, histochemical, and biochemical findings were evaluated after necropsy. Comparisons of interest included OA and non-OA joints of saline treated horses and OA joints of PGH treated horses and OA joints of saline treated horses. Results were statistically analyzed with significance set at P < .05. RESULTS: OA caused increases in clinical assessment scores, synovial fluid variables, radiographic, macroscopic, and histologic cartilage scores, synovial fluid and cartilage chondroitin sulfate 846-epitope and glycosaminoglycan concentration. Total radiographic scores, total macroscopic joint pathology and macroscopic cartilage pathology scores were significantly reduced in horses treated with PGH compared with saline treated horses. Synovial fluid total protein concentration and white blood cell count were higher in OA joints of PGH treated horses compared with saline treated horses. There were no other significant differences between treatment groups. CONCLUSIONS: Improvements in macroscopic variables were not supported by other outcomes. Further evidence is needed before PGH can be recommended as a therapeutic option for osteoarthritis in horses.

Prevalence of cryptosporidium and other enteric parasites among wild non-human primates in Polonnaruwa, Sri Lanka.

Cryptosporidiosis is a rapidly emerging disease in the tropics. This is the first report of Cryptosporidium and other protozoan infections (Entamoeba spp., Iodamoeba, Chilomastix, and Balantidium spp.) in wild primates that inhabit the natural forest of Sri Lanka. It is unclear if non-human primates serve as a reservoir for these parasites under certain conditions. A cross-sectional coprologic survey among 125 monkeys (89 toque macaques, 21 gray langurs, and 15 purple-faced langurs) indicated that Cryptosporidium was detected in all three primate species and was most common among monkeys using areas and water that had been heavily soiled by human feces and livestock. Most macaques (96%) shedding Cryptosporidium oocysts were co-infected with other protozoans and important anthropozoonotic gastrointestinal parasites (e.g., Enterobius and Strongyloides). The transmission of these parasites among primates in the wild may have important implications for public health as well as wildlife conservation management.

Hematology of a natural population of toque macaques (Macaca sinica) at polonnaruwa, Sri Lanka.

Hematological studies were conducted in three wild groups of toque macaques (Macaca sinica) inhabiting the Polonnaruwa Sanctuary in northeastern Sri Lanka. The macaques were temporarily trapped and anesthetized, and femoral blood was drawn from 35 males and 37 females (age range: 0.33-24.5 yr). Statistically significant (P<0.05) differences were observed by sex for total plasma proteins (PP), and by age for red blood cell (RBC) counts, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC), PP, erythrocyte sedimentation rate (ESR), differential and absolute neutrophil counts, differential lymphocyte counts, and absolute eosinophil counts. In general, the results were similar to those reported for other species of colony-bred and free-ranging macaques. However, there also were differences. First, in contrast to earlier studies of nonhuman primates, we examined the hematology of infants. Compared to other age classes, infants (<1 yr old) had lower RBC, Hb, MCHC, and ESR values, and a higher MCV. These findings were similar to those obtained in human infants. Second, we observed variations in hematology among social groups in relation to their ecology. Two groups (IH3 and M3) had ready access to water throughout the dry season (the period of sampling), whereas the third group (J) did not. The Hb, RBC, and PP values obtained in groups IH3 and M3 were similar to those reported in other macaque species. However, these parameters in group J were significantly (P<0.01) higher, which suggests that this group (representing about 26% of the sample) had been dehydrated during the dry season. Finally, two indices indicative of injury and infection--the ESR and leukocyte counts--were higher in the wild toque macaques than has been reported for other species of macaques held in captivity, and about 15% of the toque macaques sampled had extreme outlier values for these parameters; however, none were visibly ill or died. These results suggest that wild toque macaques are subject to a wide array of physical and biological insults that are unique to natural populations.