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Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR "serotyped" (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

We are dealing with extensions of commutative rings R ⊆ S whose chains of the poset [ R , S ] of their subextensions are finite (i.e. R ⊆ S has the FCP property) and such that [ R , S ] is a distributive lattice, that we call distributive FCP extensions. Note that the lattice [ R , S ] of a distributive FCP extension is finite. This paper is the continuation of our earlier papers where we studied catenarian and Boolean extensions. Actually, for an FCP extension, the following implications hold: Boolean ⇒ distributive ⇒ catenarian. A comprehensive characterization of distributive FCP extensions actually remains a challenge, essentially because the same problem for field extensions is not completely solved. Nevertheless, we are able to exhibit a lot of positive results for some classes of extensions. A main result is that an FCP extension R ⊆ S is distributive if and only if R ⊆ R ¯ is distributive, where R ¯ is the integral closure of R in S. A special attention is paid to distributive field extensions. [ABSTRACT FROM AUTHOR]

Background Objective Animals Methods Results Conclusions and Clinical Importance Before the discovery of effective antiviral drugs, feline infectious peritonitis (FIP) was a uniformly fatal disease of cats. Multiple antiviral treatments have been recognized, but optimization of treatment protocols is needed.To evaluate the efficacy of PO molnupiravir (MPV; EIDD‐2801) to treat effusive FIP.Ten cats with naturally occurring effusive FIP and 10 historical control cats with effusive FIP treated with PO GS‐441524.A single‐center, prospective, open‐label longitudinal, non‐inferiority trial with historical controls. Ten cats with FIP were enrolled and treated with PO MPV (10‐15 mg/kg PO q12h) for 84 days. Cats were evaluated at 0, 6, and 16 weeks, and the proportion of cats in clinical remission at 16 weeks was determined. Survival and clinicopathologic features were compared with historical control cats with effusive FIP treated with PO GS‐441524.Eight of the 10 cats treated with MPV survived and were in remission at 16 weeks. The 2 non‐survivors died in the first 24 hours of treatment. No adverse events that necessitated discontinuation of treatment were observed. Survival of cats treated with PO MPV was non‐inferior to historic control cats treated with PO GS‐441524 (5/9 [55%] survived), with a difference in survival of 25% (90% confidence interval, −9.3% to 59.3%). Clinicopathologic features associated with FIP normalized during the study period, and no differences in clinicopathologic data at each study time point were observed when comparing cats treated with MPV and GS‐441524.Molnupiravir is an effective antiviral treatment for effusive FIP. [ABSTRACT FROM AUTHOR]

Simple Summary: Feline infectious peritonitis (FIP) is a deadly disease affecting cats, with very few effective treatments available. The disease is caused by a feline coronavirus, and once a cat develops FIP, it is almost always fatal. Researchers are constantly seeking new ways to treat or manage this disease. Vitamin E is known for its strong effects on the immune system, and scientists have now investigated whether certain forms of this vitamin could directly target the virus responsible for FIP. Specifically, different vitamin E analogs, particularly β-tocotrienol and δ-tocotrienol, interact with a key viral enzyme called the 3C-like protease (FIPV-3CLpro), which is essential for the virus's replication. The study used advanced computer simulations to find that these compounds could potentially inhibit the enzyme, suggesting they might help treat or manage FIP. While this research is still in its early stages, it opens up new possibilities for developing treatments that could improve the prognosis for cats suffering from this devastating disease. Feline infectious peritonitis (FIP) is a severe and invariably fatal disease affecting both domestic and wild felines with limited effective therapeutic options available. By considering the significant immunomodulatory effects of vitamin E observed in both animal and human models under physiological and pathological conditions, we have provided a full in silico investigation of vitamin E and related compounds and their effect on the crystal structure of feline infectious peritonitis virus 3C-like protease (FIPV-3CLpro). This work revealed the β-tocotrienol and δ-tocotrienol analogs as inhibitor candidates for this protein, suggesting their potential as possible drug compounds against FIP or their supplementary use with current medicines against this disease. [ABSTRACT FROM AUTHOR]

AbstractFeline infectious peritonitis (FIP) is a potentially fatal coronavirus-driven disease of cats. Treatment with nucleoside analogue GS-441524 and or prodrug remdesivir (RDV) have produced remission in both experimentally induced and naturally occurring FIP, yet information regarding metabolism of RDV into GS-441524 in cats is scarce. This study assessed possible phase I metabolism of RDV in cats, utilising an in vitro feline microsome model with in vitro t1/2 and in vitro Clint calculated using the substrate depletion method. A previously validated high-performance liquid chromatography (HPLC) fluorescence method was utilised for detection and analysis of RDV and GS-441524. Qualitative yield of RDV and intermediate metabolite GS-441524 were determined following microsome incubation, then compared to whole blood and plasma incubations. In vitro microsome incubation resulted in rapid depletion of RDV, though it did not appear to resemble a conventional phase I-dependent reaction in cats, as it is in humans and dogs. Depletion of RDV into GS-441524 was demonstrated in whole blood in vitro, suggesting cats convert RDV to GS-441524, likely via blood esterases, as observed in mice and rats. RDV metabolism is unlikely to be impacted by impaired liver function in cats. Furthermore, as RDV depletes within minutes, whereas GS-441524 is very stable, whole blood or plasma GS-441524 concentrations, rather than plasma RDV concentrations, are more appropriate for therapeutic drug monitoring (TDM) in cats receiving RDV.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective. [ABSTRACT FROM AUTHOR]

An extension of commutative rings R ⊆ S is called a Δ0-extension if any Rsubmodule of S containing R is an R-subalgebra of S. We characterize FCP Δ0-extensions, which are a special case of FCP Δ-extensions (the set of all subextensions is stable under the formation of sums) and that we studied in an earlier paper. Using Huckaba-Papick's result which say that a ring extension is a Δ0-extension if and only if it is a Δ-extension such that any element of S is quadratic over R, Δ0-extension is integral. If R ⊆ S is an FCP Δ0-extension such that R is a local ring, then any R-subalgebra of S is comparable to the seminormalization + SR and the t-closure t SR of the extension. The converse holds adding some conditions on + SR and t SR. The paper ends by considering Δ0-extensions satisfying another condition as Boolean extensions, pointwise minimal extensions, idealizations, and extensions of the form R ⊆ Rn. Aymen [ABSTRACT FROM AUTHOR]

Background: Effective immunotherapeutic agents for use in cats are needed to aid in the management of intractable viral diseases, including feline infectious peritonitis (FIP) infection. The objectives of this study were to compare two different immune stimulants for antiviral activity in cats: (1) TLR 2/6-activating compound polyprenyl immunostimulant; (PI) and (2) liposome Toll-like receptor 3/9 agonist complexes (LTCs) to determine relative abilities to stimulate the induction of type I (IFN-α, IFN-β) and type II (IFN-γ) interferon immune responses in vitro and to study the effects of treatment on immune responses in healthy cats. Methods: Cytokine and cellular immune responses to PI and LTC were evaluated using peripheral blood mononuclear cells (PBMCs) from healthy cats incubated with LTC and PI at indicated concentrations using reverse transcriptase polymerase chain reaction assays and ELISA assays. The effects of the immune stimulants on inhibiting FIPV replication were assessed using a feline macrophage cell line (fcwf-4). Cytokine and cellular immune responses to PI and LTC were evaluated in blood samples from healthy cats treated with PI and LTC, using reverse transcriptase polymerase chain reaction (RT-PCR) and ELISA assays. Results: In the in vitro studies, both compounds triggered the upregulated expression of IFN-α, IFN-γ, and IL-1β genes in cat PBMC, whereas treatment with LTC induced significantly greater expression of IFN-α and IFN-γ on Day 1 and IL-1b on Day 3. There was significant protection from FIPV-induced cytopathic effects when fcwf-4 cells were treated with conditioned medium from LTC-activated leukocytes. In the healthy cat study (in vivo), both PI and LTC increased the mRNA signal for IFN-α, IFN-γ, and IL-1β above baseline at multiple time points with statistically greater increases in the LTC group on either Day 1 (IFN-α, IFN-γ) or Day 3 (IL-1β). In addition, RANTES increased over time in cats treated with the LTC. Conclusions: Both LTC and PI protocols induced immune-enhancing effects, suggesting a possible clinical use for the management of chronic infectious diseases like FIP. Activating the TLR 3 and 9 pathways (LTC) induced superior broad interferon production in vitro than the activation of the TLR 2 and 6 pathways (PI). [ABSTRACT FROM AUTHOR]

Simple Summary: Feline infectious peritonitis (FIP) is a very common coronavirus (FCoV) infectious disease in the feline population. FIP infection is a cause of death in cats and is widespread in domestic cats. FIP can have an acute or chronic clinical form, also known as effusive or non-effusive FIP, respectively. The typical lesion found in the acute form is an effusion in the thoracic and/or abdominal cavities, while collection in the pericardial sac is rare. The chronic form is characterized by pyogranulomatous necrotizing lesions in organs such as the kidney, liver, intestine, lung, eyes, skin, and central nervous system. FIP does not represent a zoonotic risk. The reported case is an uncommon pyogranuloma found in the myocardium in a cat with clinical heart dysfunction. The most important histopathological finding was the myocarditis/myocardial necrosis associated with the presence of S gene-mutated FCoV (M1058L biotype). This is the first described case of myocarditis in an FCoV/FIP M1058L biotype-positive cat. An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP). FIP was confirmed in the effusive abdominal fluid by a molecular genetic test (real-time PCR for feline coronavirus RNA). The molecular genetic investigation also detected an FCoV S gene single-nucleotide mutation: biotype M1058L. At necropsy, an effusive collection was recorded in the abdomen, thoracic cavity, and pericardium sac. White parenchymal nodules, of about 1 mm diameter, were found on the surface and deep in the lungs, liver, kidneys, and heart. Histopathology revealed the typical FIP pyogranulomatous vasculitis and IHC confirmed the presence of the FIP virus (FIPV) antigen. The most relevant histopathological finding was the myocarditis/myocardial necrosis associated with the presence of the S gene-mutated FCoV (M1058L biotype). This is the first case of myocarditis in a cat positive for the FCoV/FIP M1058L biotype. Further studies are necessary to support the mutated FCoV M1058L biotype, as an uncommon, but possible, causative pathogen of myocarditis in FCoV/FIP-positive cats. Studies including several FCoV/FIP M1058L-positive cases could allow us to make a correlation with heart gross pathology, histopathology, and immunolocalization of the FCoV/FIP M1058L biotype in the myocardium. The investigation will potentially allow us to determine the effective tropism of the FCoV/FIP M1058L biotype for myocardiocytes or whether myocardiocyte lesions are evident in the presence of concomitant causes related to the patient, its poor condition, or external environmental distress such as cold season, and whether the aforementioned concomitant events are correlated. [ABSTRACT FROM AUTHOR]

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Coronavirus frequently infects humans and animals, showing the ability to recombine and cross over to different species. Cats can be considered a model for studying coronavirus infection, in which feline coronavirus (FCoV) represents a major enteric pathogen related to gastroenteric disease. In this animal, the virus can acquire tropism for macrophage cells, leading to a deadly disease called feline infectious peritonitis (FIP). In this study, monocyte-derived macrophages were isolated by CD14-positive selection in venous whole blood from 26 cats with FIP and 32 FCoV-positive healthy cats. Phagocytosis and respiratory burst activities were investigated and compared between the groups. This is the first study comparing macrophage activity in cats affected by FIP and healthy cats positive for FCoV infection. Our results showed that in cats with FIP, the phagocytic and respiratory burst activities were significantly lower. Our results support the possible role of host immunity in Coronaviridae pathogenesis in cats, supporting future research on the immune defense against this systemic disease. [ABSTRACT FROM AUTHOR]

Until recently, the diagnosis of feline infectious peritonitis (FIP) in cats usually led to euthanasia, but recent research has revealed that antiviral drugs, including the nucleoside analog GS-441524, have the potential to effectively cure FIP. Alpha-1-acid glycoprotein (AGP) has been suggested as a diagnostic marker for FIP. However, AGP quantification methods are not easily accessible. This study aimed to establish a Spatial Proximity Analyte Reagent Capture Luminescence (SPARCLTM) assay on the VetBio-1 analyzer to determine the AGP concentrations in feline serum and effusion samples. Linearity was found in serial dilutions between 1:2000 and 1:32,000; the intra-run and inter-run precision was <5% and <15%, respectively; and AGP was stable in serum stored for at least 8 days at room temperature, at 4 °C and at −20 °C. Cats with confirmed FIP had significantly higher serum AGP concentrations (median: 2954 µg/mL (range: 200–5861 µg/mL)) than those with other inflammatory diseases (median: 1734 µg/mL (305–3449 µg/mL)) and clinically healthy cats (median 235 µg/mL (range: 78–616 µg/mL); pKW < 0.0001). The AGP concentrations were significantly higher in the effusions from cats with FIP than in those from diseased cats without FIP (pMWU < 0.0001). The AGP concentrations in the serum of cats with FIP undergoing GS-441524 treatment showed a significant drop within the first seven days of treatment and reached normal levels after ~14 days. In conclusion, the VetBio-1 SPARCLTM assay offers a precise, fast and cost-effective method to measure the AGP concentrations in serum and effusion samples of feline patients. The monitoring of the AGP concentration throughout FIP treatment provides a valuable marker to evaluate the treatment's effectiveness and identify potential relapses at an early stage. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to evaluate the utility of clinicopathological and molecular findings on aqueous humor (AH) for the diagnosis of feline infectious peritonitis (FIP), a disease sustained by the feline coronavirus (FCoV). To this aim, we investigated the presence of viral genome or of cells potentially consistent with inflammation and the protein content in AH samples collected from cats with or without FIP. The results of this study demonstrated that although none of these tests were sensitive or specific enough to be used alone to diagnose FIP, the detection of inflammatory cells in the AH, especially if associated with positive PCR, may work as a supportive test when the probability of FIP is high, based on the additional information provided via physical examination or laboratory tests. Additionally, the concentration of intraocular protein in cats with FIP was very high, especially in the non-effusive form. However, the diagnostic role of protein measurement in ocular fluids needs to be further assessed in future studies. Background: This study was designed to assess the diagnostic utility for FIP of cytology, protein measurement and RT-PCR for feline coronaviruses (FCoV) on aqueous humor (AH), since little information is currently available. Methods: AH samples (n = 85) were collected post-mortem from 13 cats with effusive FIP (E-FIP), 15 with non-effusive FIP (NE-FIP) and 16 without FIP, to perform cytology (n = 83) and RT-PCR (n = 66) and to calculate their sensitivity, specificity and positive and negative likelihood ratios (LR+ and LR−). The protein concentration was measured on 80 fluids. Results: The proportion of RT-PCR positive samples did not differ among groups, while positive cytology was more frequent in samples with FIP (p = 0.042) or positive RT-PCR (p = 0.007). Compared with other groups, the protein concentration was higher in samples with NE-FIP (p = 0.017), positive RT-PCR (p = 0.005) or positive cytology (p < 0.001). The specificity of cytology together with RT-PCR, cytology alone, RT-PCR alone and cytological proteinaceous background were 90.0%, 84.6%, 70.0%, 61.5%, and the LRs 3.48, 2.65, 1.83, 1.64, respectively. However, their sensitivities were low (34.8–63.0%) and their LR− high (0.60–0.72). Conclusions: Based on the LR+, cytology and/or RT-PCR may support the diagnosis when the pre-test probability of FIP is high. The concentration of intraocular protein is a promising marker, especially in NE-FIP. [ABSTRACT FROM AUTHOR]

Background: Alpha-1 acid glycoprotein (AGP) may support a clinical diagnosis of feline infectious peritonitis (FIP). In this study, we assessed the analytical and diagnostic performances of a novel ELISA method to measure feline AGP. Methods: AGP was measured in sera and effusions from cats with FIP (n = 20) or with other diseases (n = 15). Precision was calculated based on the coefficient of variation (CV) of repeated testing, and accuracy was calculated by linearity under dilution (LUD). Results: The test is precise (intra-assay CVs: <6.0% in individual samples, <15.0% in pooled samples; inter-assay CVs <11.0% and <15.0%) and accurate (serum LUD r2: 0.995; effusion LUD r2: 0.950) in serum and in effusions. AGP is higher in cats with FIP than in other cats in both serum (median: 1968, I-III interquartile range: 1216–3371 μg/mL and 296, 246–1963 μg/mL; p = 0.009) and effusion (1717, 1011–2379 μg/mL and 233, 165–566 μg/mL; p < 0.001). AGP discriminates FIP from other diseases (area under the receiver operating characteristic curve: serum, 0.760; effusion, 0.877), and its likelihood ratio is high (serum: 8.50 if AGP > 1590 μg/mL; effusion: 3.75 if AGP > 3780 μg/mL). Conclusion: This ELISA method is precise and accurate. AGP in serum and in effusions is a useful diagnostic marker for FIP. [ABSTRACT FROM AUTHOR]

Simple Summary: This article describes the treatment course of three ferrets diagnosed with FSCD, a fatal disease in ferrets. An effective treatment for FSCD in ferrets has not been reported. The three ferrets were treated with the antiviral nucleoside analogue GS-441524 and monitored over the course of the 12-week treatment. Complete remission from the disease was achieved for all the three ferrets that remained disease-free months to 1 year after the treatment was terminated. Ferret Systemic Coronaviral Disease (FSCD) is a systemic disease caused by ferret systemic coronavirus, which is considered lethal in most of the ferrets that are affected by it. To our knowledge, no treatment has been shown to be effective against FSCD in vivo, and most of the ferrets are euthanized or die after the development of clinical disease. GS-441524 has been shown to be effective in successfully treating cats with Feline Infectious Peritonitis (FIP), a disease that shares similarities with FSCD. However, to our knowledge, treatment with GS-441524 has not been reported for the treatment of FSCD in ferrets. Here, we describe three cases of ferrets diagnosed with FSCD successfully cured utilizing oral GS-441524. FSCD may be effectively treated following similar protocols utilized for feline infectious peritonitis in cats. [ABSTRACT FROM AUTHOR]

With growing concerns about global overfishing, market‐based eco‐certification programs like the Marine Stewardship Council (MSC) can incentivise adoption of sustainable practices. Several studies investigated drivers of improvement in market‐driven Fisheries Improvement Projects, but failed to use detailed, standardised measures of progress, or considered small samples. We considered the relative influence market, governance and fishery‐specific drivers have on MSC certification speed and success in 208 fisheries. To evaluate improvement we compared pre‐certification scores from MSC pre‐assessments—rapid high‐level audits against the MSC Standard—to scores from full MSC audits. Drivers considered included measures of pre‐assessment quality, as this initial advice might contribute to later certification success. National fishery management capacity, percentage of MSC catch and landed value were the strongest drivers of successful and rapid certification. Environmental improvements occurred for stock management, ecosystem health and governance aspects. While only 48% of fisheries with favourable pre‐assessment outcomes went on to be certified, improvements in many fisheries with lower pre‐assessment scores were observed in their lead‐up to full assessment. Random forest analyses allowed for considering multiple interacting variables simultaneously and revealed influential drivers under specific fishery contexts. For example, higher certification probability was associated with greater percentage of MSC catch under the full dataset, but not under subsets representing fisheries facing more challenging contexts for certification. Fisheries from lower/middle‐income countries had lower overall probability of certification, but this increased with higher management capacity. This suggests multiple drivers interact in instigating fisheries improvements, and MSC pre‐assessments provide valuable resources to understand this journey. [ABSTRACT FROM AUTHOR]

OBJECTIVE Feline infectious peritonitis is fatal, and due to lack of approved treatments, unregulated antiviral drugs are used to treat this disease. This study set out to determine the purity of various batches of these drugs from several companies, characterize them, and note any impurities or other unusual characteristics. We also developed a method to qualitatively assess the primary components before administration. SAMPLES We tested 30 vials from 17 brands of GS-441524 and 5 vials from 1 brand of GC376. We compared the GS-441524 to a control standard from Ambeed and the GC376 to a standard from Cayman Chemical. METHODS We recorded physical appearance, pH, absorbance, HPLC retention times, and thin-layer chromatography retention factors for all of the samples. Some samples were used for nuclear magnetic resonance and mass spectrometric analysis. RESULTS Some of the GS-441524 vials were 10% to 25% more concentrated than advertised, but most of the GS-441524 samples tested were similar in purity and composition, both between batches and between brands. We also tested 5 vials of GC376 and found that 1 of the 5 vials contained GS-441524 rather than GC376 and the other 4 vials contained molnupiravir. CLINICAL RELEVANCE While all of the GS-441524 vials contained GS-441524, none of the GC376 vials tested contained GC376. GC376 is used in cats that are unresponsive to GS-441524, and use of the wrong antiviral can cause serious side effects. We provide suggested methods for distinguishing one drug from the other in new batches. [ABSTRACT FROM AUTHOR]

Abstract Feline infectious peritonitis (FIP) historically has been a fatal disease in cats. Recent unlicensed use of antiviral medication has been shown to markedly improve survival of this infection. An 8‐month‐old female spayed domestic short‐haired cat undergoing treatment for presumptive FIP with the antiviral nucleoside analog GS‐441524 developed acute progressive azotemia. Abdominal ultrasound examination identified multifocal urolithiasis including renal, ureteral, and cystic calculi. Unilateral ureteral obstruction progressed to suspected bilateral ureteral obstruction and subcutaneous ureteral bypass (SUB) was performed along with urolith removal and submission for analysis. A 2‐year‐old male neutered domestic medium‐haired cat undergoing treatment for confirmed FIP with GS‐441524 developed dysuria (weak urine stream, urinary incontinence, and difficulty expressing the urinary bladder). This cat also was diagnosed sonographically with multifocal urolithiasis requiring temporary tube cystostomy after cystotomy and urolith removal. In both cases, initial urolith analysis showed unidentified material. Additional testing confirmed the calculi in both cats to be 98% consistent with GS‐441524. Additional clinical studies are required to determine best screening practices for cats presented for urolithiasis during treatment with GS‐441524.

AbstractThe adenosine analogue GS-441524 has demonstrated efficacy in treatment of feline infectious peritonitis (FIP). With no commercially registered formulations of GS-441524 available, global focus shifted to its pro-drug remdesivir, as it became more accessible throughout the COVID-19 pandemic. This study developed and validated a simple liquid chromatography equipped with a fluorescence detector to quantify plasma concentrations of GS-441524 applicable for routine therapeutic monitoring of remdesivir or GS-441524 therapy for FIP infected cats. A Waters X-Bridge C18, 5 µm, 150 × 4.6 mm, column was used and mixtures of 20 mM ammonium acetate (pH 4.5) with acetonitrile of 5% and 70% were prepared for gradient mobile phase. With a simple protein precipitation using methanol to clean plasma sample, GS-441524 was monitored at excitation and emission wavelengths of 250 nm and 475 nm, respectively. Using an external standard, the lowest and highest limits of quantification were 19.5 ng/mL to 10,000 ng/mL, respectively. The intra- and inter day trueness of the quality controls (QCs) were within 10% of their nominal concentrations and intra- and inter day precision of the QCs (expressed as the coefficient of variation) ranged from 1.7 to 5.7%, This assay was able to quantify plasma trough levels of GS-441524 (23.7–190.1 ng/mL) after the administration of remdesivir (9.9–15.0 mg/kg BW, IV or SC) in FIP cats (n = 12). Accordingly, this study generated an alternative and cost-effective way to quantify GS-441524 in feline biological fluids at least up to 24 hr after administrations of remdesivir.

Feline infectious peritonitis (FIP) is a severe and invariably fatal disease affecting both domestic and wild felines with limited effective therapeutic options available. By considering the significant immunomodulatory effects of vitamin E observed in both animal and human models under physiological and pathological conditions, we have provided a full in silico investigation of vitamin E and related compounds and their effect on the crystal structure of feline infectious peritonitis virus 3C-like protease (FIPV-3CLpro). This work revealed the β-tocotrienol and δ-tocotrienol analogs as inhibitor candidates for this protein, suggesting their potential as possible drug compounds against FIP or their supplementary use with current medicines against this disease.

Feline infectious peritonitis (FIP) is a systemic disease manifestation of feline coronavirus (FCoV) and is the most important cause of infectious disease-related deaths in domestic cats. FIP has a variable clinical manifestation but is most often characterized by widespread vasculitis with visceral involvement and/or neurological disease that is typically fatal in the absence of antiviral therapy. Using an aptamer-based proteomics assay, we analyzed the plasma protein profiles of cats who were naturally infected with FIP (n = 19) in comparison to the plasma protein profiles of cats who were clinically healthy and negative for FCoV (n = 17) and cats who were positive for the enteric form of FCoV (n = 9). We identified 442 proteins that were significantly differentiable; in total, 219 increased and 223 decreased in FIP plasma versus clinically healthy cat plasma. Pathway enrichment and associated analyses showed that differentiable proteins were related to immune system processes, including the innate immune response, cytokine signaling, and antigen presentation, as well as apoptosis and vascular integrity. The relevance of these findings is discussed in the context of previous studies. While these results have the potential to inform diagnostic, therapeutic, and preventative investigations, they represent only a first step, and will require further validation. [ABSTRACT FROM AUTHOR]

Feline infectious peritonitis (FIP) historically has been a fatal disease in cats. Recent unlicensed use of antiviral medication has been shown to markedly improve survival of this infection. An 8‐month‐old female spayed domestic short‐haired cat undergoing treatment for presumptive FIP with the antiviral nucleoside analog GS‐441524 developed acute progressive azotemia. Abdominal ultrasound examination identified multifocal urolithiasis including renal, ureteral, and cystic calculi. Unilateral ureteral obstruction progressed to suspected bilateral ureteral obstruction and subcutaneous ureteral bypass (SUB) was performed along with urolith removal and submission for analysis. A 2‐year‐old male neutered domestic medium‐haired cat undergoing treatment for confirmed FIP with GS‐441524 developed dysuria (weak urine stream, urinary incontinence, and difficulty expressing the urinary bladder). This cat also was diagnosed sonographically with multifocal urolithiasis requiring temporary tube cystostomy after cystotomy and urolith removal. In both cases, initial urolith analysis showed unidentified material. Additional testing confirmed the calculi in both cats to be 98% consistent with GS‐441524. Additional clinical studies are required to determine best screening practices for cats presented for urolithiasis during treatment with GS‐441524. [ABSTRACT FROM AUTHOR]

Feline infectious peritonitis (FIP) is a lethal disease caused by a pathogenic coronavirus, feline infectious peritonitis virus (FIPV), in cats. Effective vaccines have been unsuccessful due to the frequent mutation of FIPV and antibody-dependent enhancement (ADE) caused by vaccine-induced IgG antibodies (Abs). This study examined the induction of pan-coronavirus IgM Ab in mice and its ameliorating effects in feline FIP using CoV-mMAP8, an octavalent dendrimer composed of multiple antigenic peptides. The 11-amino acid peptide (SAIEDLLFNKV) was designed as the highly conserved region of the fusion peptide at the N-terminus of S2’ subunit of the spike protein found in human and animal coronaviruses and was then conjugated to an octavalent dendrimer to form CoV-mMAP8. After a total of three injections of CoV-mMAP8 into Balb/c mice with α-galactosylceramide (α-GC) co-administered in the second injection, serum titers of IgM Abs increased against the peptide, recombinant spike proteins of SARS-CoV-2 and MERS-CoV, and crude viral antigens of canine coronavirus, porcine endemic diarrhea virus, and FIPV. In contrast, serum titers of IgG Abs did not significantly increase against any antigens. When CoV-mMAP8 was injected into three cats experimentally infected with FIPV, hyperthermia was improved within seven days after the injection with ameliorating inflammatory markers such as the platelet-to-lymphocyte ratio and the systemic immune-inflammatory index. One cat that showed recurrent hyperthermia received an additional injection of CoV-mMAP8, and clinical improvement was observed again. Postmortem examinations confirmed chronic lesions of FIP in all the cats, providing evidence that FIPV had been successfully infected and treated with CoV-mMAP8 in all the cats. Based on the induction of pan-coronavirus IgM Abs in mice and ameliorating effects in FIP of cats, it is assumed that CoV-mMAP8 has the potential to overcome the challenges posed by variants and ADE in FIPV. The mutational compatibility of CoV-mMAP8 can make it a viable universal vaccine for various coronaviruses beyond FIPV.

Abstract Objective To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection. Materials and methods A total of 40 cats with effusive FIP (30 with abdominal effusion, AE group; 10 with thoracic effusion, TE group) and 10 asymptomatic but FECV positive cats (FECV group), all were confirmed by reverse transcription polymerase chain reaction either in faeces or effusion samples. Physical examinations and effusion tests were performed. Trefoil factor‐3 (TFF‐3), intestinal alkaline phosphatase (IAP), intestinal fatty acid binding protein (I‐FABP), myeloperoxidase‐anti‐neutrophilic cytoplasmic antibody (MPO‐ANCA) and proteinase 3‐ANCA (PR3‐ANCA) concentrations were measured both in serum and effusion samples. Results Rectal temperature and respiratory rate were highest in the TE group (p

Abstract Background Feline infectious peritonitis (FIP) is a viral disease in cats, caused by certain strains of coronavirus and has a high case fatality rate. Objective This case series reports the outcomes of treatment of cats with FIP using molnupiravir. Animals Eighteen cats diagnosed with FIP at the You‐Me Animal Clinic, Sakura‐shi, Japan between January and August 2022, and whose owners gave informed consent to this experimental treatment. Methods For this prospective observational study, molnupiravir tablets were compounded in‐house at the You‐Me Animal Clinic. Owners administered 10‐20 mg/kg PO twice daily. Standard treatment duration was 84 days. Results Among 18 cats, 13 cats had effusive FIP and 5 had noneffusive FIP. Three cats had neurological or ocular signs of FIP before treatment. Four cats, all with effusive FIP, died or were euthanized within 7 days of starting treatment. The remaining 14 cats completed treatment and remained in remission at the time of writing (139‐206 days after starting treatment). Elevated serum alanine transaminase (ALT) activity was found in 3 cats, all at Days 7‐9, and all recovered without management. Two cats with jaundice were hospitalized, 1 during treatment (Day 37) and 1 with severe anemia at the start of treatment. Conclusions and Clinical Importance This case series suggests that molnupiravir might be an effective and safe treatment for domestic cats with FIP at a dose of 10‐20 mg/kg twice daily.

Abstract Background GS‐441524 has been successfully used to treat feline infectious peritonitis (FIP) in cats. However, the use of its prodrug, remdesivir, in combination with a PO GS‐441524 containing product for the treatment of FIP has not yet been described. Objectives Describe treatment protocols, response to treatment and outcomes in cats with FIP treated with a combination of PO GS‐441524 and injectable remdesivir. Animals Thirty‐two client‐owned cats diagnosed with effusive or non‐effusive FIP including those with ocular and neurological involvement. Methods Cats diagnosed with FIP at a single university hospital between August 2021 and July 2022 were included. Variables were recorded from time of diagnosis, and subsequent follow‐up information was obtained from the records of referring veterinarians. All surviving cats were observed for the entire 12‐week treatment period. Results Cats received treatment with different combinations of IV remdesivir, SC remdesivir, and PO GS‐441524 at a median (range) dosage of 15 (10‐20) mg/kg. Clinical response to treatment was observed in 28 of 32 cats (87.5%) in a median (range) of 2 (1‐5) days. Twenty‐six of 32 cats (81.3%) were alive and in clinical and biochemical remission at the end of the 12‐week treatment period. Six of 32 cats (18.8%) died or were euthanized during treatment with 4 of the 6 cats (66%) dying within 3 days of starting treatment. Conclusions We describe the effective use of injectable remdesivir and PO GS‐441524 for the treatment of FIP in cats. Success occurred using different treatment protocols and with different presentations of FIP including cats with ocular and neurological involvement.

Feline infectious peritonitis (FIP) is a disease of domestic cats caused by the genetic variant of the feline coronavirus (FCoV) and feline infectious peritonitis virus (FIPV), currently grouped into two serotypes, I and II. Although serotype I FIPV is more prevalent in cats with FIP, serotype II has been more extensively studied in vitro due to the relative ease in propagating this viral serotype in culture systems. As a result, more is known about serotype II FIPV than the more biologically prevalent serotype I. The primary cell receptor for serotype II has been determined, while it remains unknown for serotype I. The recent development of a culture-adapted feline cell line that more effectively propagates serotype I FIPV, FCWF-4 CU, derived from FCWF-4 cells available through the ATCC, offers the potential for an improved understanding of serotype I FIPV biology. To learn more about FIPV receptor biology, we determined targeted gene expression patterns in feline cells variably permissive to replication of serotype I or II FIPV. We utilized normal feline tissues to determine the immunohistochemical expression patterns of two known coronavirus receptors, ACE2 and DC-SIGN. Lastly, we compared the global transcriptomes of the two closely related FCWF-4 cell lines and identified viral transcripts with potential importance for the differential replication kinetics of serotype I FIPV.

Background: Effective immunotherapeutic agents for use in cats are needed to aid in the management of intractable viral diseases, including feline infectious peritonitis (FIP) infection. The objectives of this study were to compare two different immune stimulants for antiviral activity in cats: (1) TLR 2/6-activating compound polyprenyl immunostimulant; (PI) and (2) liposome Toll-like receptor 3/9 agonist complexes (LTCs) to determine relative abilities to stimulate the induction of type I (IFN-α, IFN-β) and type II (IFN-γ) interferon immune responses in vitro and to study the effects of treatment on immune responses in healthy cats. Methods: Cytokine and cellular immune responses to PI and LTC were evaluated using peripheral blood mononuclear cells (PBMCs) from healthy cats incubated with LTC and PI at indicated concentrations using reverse transcriptase polymerase chain reaction assays and ELISA assays. The effects of the immune stimulants on inhibiting FIPV replication were assessed using a feline macrophage cell line (fcwf-4). Cytokine and cellular immune responses to PI and LTC were evaluated in blood samples from healthy cats treated with PI and LTC, using reverse transcriptase polymerase chain reaction (RT-PCR) and ELISA assays. Results: In the in vitro studies, both compounds triggered the upregulated expression of IFN-α, IFN-γ, and IL-1β genes in cat PBMC, whereas treatment with LTC induced significantly greater expression of IFN-α and IFN-γ on Day 1 and IL-1b on Day 3. There was significant protection from FIPV-induced cytopathic effects when fcwf-4 cells were treated with conditioned medium from LTC-activated leukocytes. In the healthy cat study (in vivo), both PI and LTC increased the mRNA signal for IFN-α, IFN-γ, and IL-1β above baseline at multiple time points with statistically greater increases in the LTC group on either Day 1 (IFN-α, IFN-γ) or Day 3 (IL-1β). In addition, RANTES increased over time in cats treated with the LTC. Conclusions: Both LTC and PI protocols induced immune-enhancing effects, suggesting a possible clinical use for the management of chronic infectious diseases like FIP. Activating the TLR 3 and 9 pathways (LTC) induced superior broad interferon production in vitro than the activation of the TLR 2 and 6 pathways (PI).

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP). FIP was confirmed in the effusive abdominal fluid by a molecular genetic test (real-time PCR for feline coronavirus RNA). The molecular genetic investigation also detected an FCoV S gene single-nucleotide mutation: biotype M1058L. At necropsy, an effusive collection was recorded in the abdomen, thoracic cavity, and pericardium sac. White parenchymal nodules, of about 1 mm diameter, were found on the surface and deep in the lungs, liver, kidneys, and heart. Histopathology revealed the typical FIP pyogranulomatous vasculitis and IHC confirmed the presence of the FIP virus (FIPV) antigen. The most relevant histopathological finding was the myocarditis/myocardial necrosis associated with the presence of the S gene-mutated FCoV (M1058L biotype). This is the first case of myocarditis in a cat positive for the FCoV/FIP M1058L biotype. Further studies are necessary to support the mutated FCoV M1058L biotype, as an uncommon, but possible, causative pathogen of myocarditis in FCoV/FIP-positive cats. Studies including several FCoV/FIP M1058L-positive cases could allow us to make a correlation with heart gross pathology, histopathology, and immunolocalization of the FCoV/FIP M1058L biotype in the myocardium. The investigation will potentially allow us to determine the effective tropism of the FCoV/FIP M1058L biotype for myocardiocytes or whether myocardiocyte lesions are evident in the presence of concomitant causes related to the patient, its poor condition, or external environmental distress such as cold season, and whether the aforementioned concomitant events are correlated.

Objective: To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection. Materials and methods: A total of 40 cats with effusive FIP (30 with abdominal effusion, AE group; 10 with thoracic effusion, TE group) and 10 asymptomatic but FECV positive cats (FECV group), all were confirmed by reverse transcription polymerase chain reaction either in faeces or effusion samples. Physical examinations and effusion tests were performed. Trefoil factor‐3 (TFF‐3), intestinal alkaline phosphatase (IAP), intestinal fatty acid binding protein (I‐FABP), myeloperoxidase‐anti‐neutrophilic cytoplasmic antibody (MPO‐ANCA) and proteinase 3‐ANCA (PR3‐ANCA) concentrations were measured both in serum and effusion samples. Results: Rectal temperature and respiratory rate were highest in the TE group (p < 0.000). Effusion white blood cell count was higher in the AE group than TE group (p < 0.042). Serum TFF‐3, IAP and I‐FABP concentrations were higher in cats with effusive FIP than the cats with FECV (p < 0.05). Compared with the AE group, TE group had lower effusion MPO‐ANCA (p < 0.036), higher IAP (p < 0.050) and higher TFF‐3 (p < 0.016) concentrations. Clinical significance: Markers of intestinal and epithelial surface injury were higher in cats with effusive FIP than those with FECV. Compared to cats with abdominal effusions, markers of apoptosis inhibition and immunostimulation to the injured epithelium were more potent in cats with thoracic effusion, suggesting the possibility of a poorer prognosis or more advanced disease in these patients. [ABSTRACT FROM AUTHOR]

The current study deals with a reactivity-controlled compression ignition (RCCI) engine working with 1-pentanol as the LRF and JOBD as the HRF. The composition of the pilot fuel includes 20% Jatropha oil and 80% diesel, which nearly matches the heating value and cetane index of petroleum diesel. The research focuses on studying the impact of the pilot fuel injection angle on the engine characteristics at full load conditions, and the pilot fuel injection angle varies from 19, 21, 23, 25, to 27° bTDC at a constant injection pressure of 600 bar. The results revealed that increasing the pilot fuel injection angle increased the engine performance with a 13.36% rise in BTE, a reduction in CO emissions by 11.03%, and a decrease in HC emissions by 9.28% at a pilot fuel injection angle of 25° bTDC at 30% pentanol energy share (BD70P30). On the other hand, NOx emissions rise by 11.07%. The results indicate that the performance of the ternary fuelled RCCI engine can be improved by increasing the fuel injection angle of the pilot fuel. [ABSTRACT FROM AUTHOR]

Feline coronavirus (FCoV) is a ubiquitous RNA virus of cats, which is transmitted faeco-orally. In these guidelines, the European Advisory Board on Cat Diseases (ABCD) presents a comprehensive review of feline infectious peritonitis (FIP). FCoV is primarily an enteric virus and most infections do not cause clinical signs, or result in only enteritis, but a small proportion of FCoV-infected cats develop FIP. The pathology in FIP comprises a perivascular phlebitis that can affect any organ. Cats under two years old are most frequently affected by FIP. Most cats present with fever, anorexia, and weight loss; many have effusions, and some have ocular and/or neurological signs. Making a diagnosis is complex and ABCD FIP Diagnostic Approach Tools are available to aid veterinarians. Sampling an effusion, when present, for cytology, biochemistry, and FCoV RNA or FCoV antigen detection is very useful diagnostically. In the absence of an effusion, fine-needle aspirates from affected organs for cytology and FCoV RNA or FCoV antigen detection are helpful. Definitive diagnosis usually requires histopathology with FCoV antigen detection. Antiviral treatments now enable recovery in many cases from this previously fatal disease; nucleoside analogues (e.g., oral GS-441524) are very effective, although they are not available in all countries. [ABSTRACT FROM AUTHOR]

Sulfite auto-oxidation catalyzed by cobalt complexed with ammonia deposited on silica (CoNSi) was used to generate sulfate radicals. The material was characterized by ATR–FTIR, suggesting that the silica structure did not change, and SEM–EDS, indicating an uniform dispersion of cobalt across the material surface according with XRD results. BET analysis provided information on a mesoporous material (type IV isotherm) with regular morphology (H1 hysteresis). The DSC analysis showed that CoNSi is thermally stable under the studied conditions. Quantitative analysis of Fipronil (FIP) was performed by HPLC-DAD, where the applied method was selective and linear. The Box–Behnken experimental design (BBD) method was used to define the best condition for removing the analyte in water. It was found that in 60 min, 76% removal of 1.8 mg L−1 of FIP was reached by adding 0.30 g of the material and 0.30 g of the sulfite in a solution under stirring, aeration, pH 8.0, and room temperature and protected from radiation. However, analysis of cobalt leaching into the solution by FAAS showed a small amount of the metal (0.44 mg L−1) informing that the synthesis of the material must be improved. [ABSTRACT FROM AUTHOR]

Background: Feline infectious peritonitis (FIP) is a viral disease in cats, caused by certain strains of coronavirus and has a high case fatality rate. Objective: This case series reports the outcomes of treatment of cats with FIP using molnupiravir. Animals: Eighteen cats diagnosed with FIP at the You‐Me Animal Clinic, Sakura‐shi, Japan between January and August 2022, and whose owners gave informed consent to this experimental treatment. Methods: For this prospective observational study, molnupiravir tablets were compounded in‐house at the You‐Me Animal Clinic. Owners administered 10‐20 mg/kg PO twice daily. Standard treatment duration was 84 days. Results: Among 18 cats, 13 cats had effusive FIP and 5 had noneffusive FIP. Three cats had neurological or ocular signs of FIP before treatment. Four cats, all with effusive FIP, died or were euthanized within 7 days of starting treatment. The remaining 14 cats completed treatment and remained in remission at the time of writing (139‐206 days after starting treatment). Elevated serum alanine transaminase (ALT) activity was found in 3 cats, all at Days 7‐9, and all recovered without management. Two cats with jaundice were hospitalized, 1 during treatment (Day 37) and 1 with severe anemia at the start of treatment. Conclusions and Clinical Importance: This case series suggests that molnupiravir might be an effective and safe treatment for domestic cats with FIP at a dose of 10‐20 mg/kg twice daily. [ABSTRACT FROM AUTHOR]

Background: GS‐441524 has been successfully used to treat feline infectious peritonitis (FIP) in cats. However, the use of its prodrug, remdesivir, in combination with a PO GS‐441524 containing product for the treatment of FIP has not yet been described. Objectives: Describe treatment protocols, response to treatment and outcomes in cats with FIP treated with a combination of PO GS‐441524 and injectable remdesivir. Animals: Thirty‐two client‐owned cats diagnosed with effusive or non‐effusive FIP including those with ocular and neurological involvement. Methods: Cats diagnosed with FIP at a single university hospital between August 2021 and July 2022 were included. Variables were recorded from time of diagnosis, and subsequent follow‐up information was obtained from the records of referring veterinarians. All surviving cats were observed for the entire 12‐week treatment period. Results: Cats received treatment with different combinations of IV remdesivir, SC remdesivir, and PO GS‐441524 at a median (range) dosage of 15 (10‐20) mg/kg. Clinical response to treatment was observed in 28 of 32 cats (87.5%) in a median (range) of 2 (1‐5) days. Twenty‐six of 32 cats (81.3%) were alive and in clinical and biochemical remission at the end of the 12‐week treatment period. Six of 32 cats (18.8%) died or were euthanized during treatment with 4 of the 6 cats (66%) dying within 3 days of starting treatment. Conclusions: We describe the effective use of injectable remdesivir and PO GS‐441524 for the treatment of FIP in cats. Success occurred using different treatment protocols and with different presentations of FIP including cats with ocular and neurological involvement. [ABSTRACT FROM AUTHOR]

While there has been much research on cooperatives, research focused on the benefits and services that cooperatives provide their members, and how those benefits help strengthen cooperative success, has been sparse. This research aimed to address this gap and identify common types of benefits and services utilized by cooperatives around the world. Findings were generated to inform members of a Fisheries Improvement Project (FIP+) within the Belize spiny lobster fishery. Using a mix of informal interviews and a literature review of cooperative benefits, a pattern finding analysis was conducted. It was found that benefits fell into three main categories: social, economic, and environmental. A total of 32 benefit categories were identified and described. The categories showed varying levels of complexity. Many benefits occurred across sectors, while other benefits appeared to be more common within one or two sectors. The analysis also highlighted the importance of certain enabling conditions as necessary steps to implementing a robust and successful benefits program. Cooperatives are a uniquely positioned business model to address a rapidly changing environment. The variety of benefits found in this research highlight the creativity and adaptability of cooperatives around the world. Future research on cooperative benefits could be an important step in increasing adaptability, but also resiliency in the face of a changing world.

Coronavirus frequently infects humans and animals, showing the ability to recombine and cross over to different species. Cats can be considered a model for studying coronavirus infection, in which feline coronavirus (FCoV) represents a major enteric pathogen related to gastroenteric disease. In this animal, the virus can acquire tropism for macrophage cells, leading to a deadly disease called feline infectious peritonitis (FIP). In this study, monocyte-derived macrophages were isolated by CD14-positive selection in venous whole blood from 26 cats with FIP and 32 FCoV-positive healthy cats. Phagocytosis and respiratory burst activities were investigated and compared between the groups. This is the first study comparing macrophage activity in cats affected by FIP and healthy cats positive for FCoV infection. Our results showed that in cats with FIP, the phagocytic and respiratory burst activities were significantly lower. Our results support the possible role of host immunity in Coronaviridae pathogenesis in cats, supporting future research on the immune defense against this systemic disease.

Background: This study was designed to assess the diagnostic utility for FIP of cytology, protein measurement and RT-PCR for feline coronaviruses (FCoV) on aqueous humor (AH), since little information is currently available. Methods: AH samples (n = 85) were collected post-mortem from 13 cats with effusive FIP (E-FIP), 15 with non-effusive FIP (NE-FIP) and 16 without FIP, to perform cytology (n = 83) and RT-PCR (n = 66) and to calculate their sensitivity, specificity and positive and negative likelihood ratios (LR+ and LR−). The protein concentration was measured on 80 fluids. Results: The proportion of RT-PCR positive samples did not differ among groups, while positive cytology was more frequent in samples with FIP (p = 0.042) or positive RT-PCR (p = 0.007). Compared with other groups, the protein concentration was higher in samples with NE-FIP (p = 0.017), positive RT-PCR (p = 0.005) or positive cytology (p < 0.001). The specificity of cytology together with RT-PCR, cytology alone, RT-PCR alone and cytological proteinaceous background were 90.0%, 84.6%, 70.0%, 61.5%, and the LRs 3.48, 2.65, 1.83, 1.64, respectively. However, their sensitivities were low (34.8–63.0%) and their LR− high (0.60–0.72). Conclusions: Based on the LR+, cytology and/or RT-PCR may support the diagnosis when the pre-test probability of FIP is high. The concentration of intraocular protein is a promising marker, especially in NE-FIP.

Until recently, the diagnosis of feline infectious peritonitis (FIP) in cats usually led to euthanasia, but recent research has revealed that antiviral drugs, including the nucleoside analog GS-441524, have the potential to effectively cure FIP. Alpha-1-acid glycoprotein (AGP) has been suggested as a diagnostic marker for FIP. However, AGP quantification methods are not easily accessible. This study aimed to establish a Spatial Proximity Analyte Reagent Capture Luminescence (SPARCLTM) assay on the VetBio-1 analyzer to determine the AGP concentrations in feline serum and effusion samples. Linearity was found in serial dilutions between 1:2000 and 1:32,000; the intra-run and inter-run precision was pKW < 0.0001). The AGP concentrations were significantly higher in the effusions from cats with FIP than in those from diseased cats without FIP (pMWU < 0.0001). The AGP concentrations in the serum of cats with FIP undergoing GS-441524 treatment showed a significant drop within the first seven days of treatment and reached normal levels after ~14 days. In conclusion, the VetBio-1 SPARCLTM assay offers a precise, fast and cost-effective method to measure the AGP concentrations in serum and effusion samples of feline patients. The monitoring of the AGP concentration throughout FIP treatment provides a valuable marker to evaluate the treatment’s effectiveness and identify potential relapses at an early stage.

Background: Alpha-1 acid glycoprotein (AGP) may support a clinical diagnosis of feline infectious peritonitis (FIP). In this study, we assessed the analytical and diagnostic performances of a novel ELISA method to measure feline AGP. Methods: AGP was measured in sera and effusions from cats with FIP (n = 20) or with other diseases (n = 15). Precision was calculated based on the coefficient of variation (CV) of repeated testing, and accuracy was calculated by linearity under dilution (LUD). Results: The test is precise (intra-assay CVs: 2: 0.995; effusion LUD r2: 0.950) in serum and in effusions. AGP is higher in cats with FIP than in other cats in both serum (median: 1968, I-III interquartile range: 1216–3371 μg/mL and 296, 246–1963 μg/mL; p = 0.009) and effusion (1717, 1011–2379 μg/mL and 233, 165–566 μg/mL; p < 0.001). AGP discriminates FIP from other diseases (area under the receiver operating characteristic curve: serum, 0.760; effusion, 0.877), and its likelihood ratio is high (serum: 8.50 if AGP > 1590 μg/mL; effusion: 3.75 if AGP > 3780 μg/mL). Conclusion: This ELISA method is precise and accurate. AGP in serum and in effusions is a useful diagnostic marker for FIP.

Ferret Systemic Coronaviral Disease (FSCD) is a systemic disease caused by ferret systemic coronavirus, which is considered lethal in most of the ferrets that are affected by it. To our knowledge, no treatment has been shown to be effective against FSCD in vivo, and most of the ferrets are euthanized or die after the development of clinical disease. GS-441524 has been shown to be effective in successfully treating cats with Feline Infectious Peritonitis (FIP), a disease that shares similarities with FSCD. However, to our knowledge, treatment with GS-441524 has not been reported for the treatment of FSCD in ferrets. Here, we describe three cases of ferrets diagnosed with FSCD successfully cured utilizing oral GS-441524. FSCD may be effectively treated following similar protocols utilized for feline infectious peritonitis in cats.

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR “serotyped” (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

Objectives: Feline infectious peritonitis (FIP), a common disease in cats caused by feline coronavirus (FCoV), is usually fatal once clinical signs appear. Successful treatment of FIP with oral GS-441524 for 84 days was demonstrated recently by this research group. The aim of this study was to evaluate the long-term outcome in these cats. Methods: A total of 18 successfully treated cats were followed for up to 1 year after treatment initiation (9 months after completion of the antiviral treatment). Follow-up examinations were performed at 12-week intervals, including physical examination, haematology, serum biochemistry, abdominal and thoracic ultrasound, FCoV ribonucleic acid (RNA) loads in blood and faeces by reverse transciptase-quantitative PCR and anti-FCoV antibody titres by indirect immunofluorescence assay. Results: Follow-up data were available from 18 cats in week 24, from 15 cats in week 36 and from 14 cats in week 48 (after the start of treatment), respectively. Laboratory parameters remained stable after the end of the treatment, with undetectable blood viral loads (in all but one cat on one occasion). Recurrence of faecal FCoV shedding was detected in five cats. In four cats, an intermediate short-term rise in anti-FCoV antibody titres was detected. In total, 12 cats showed abdominal lymphadenomegaly during the follow-up period; four of them continuously during the treatment and follow-up period. Two cats developed mild neurological signs, compatible with feline hyperaesthesia syndrome, in weeks 36 and 48, respectively; however, FCoV RNA remained undetectable in blood and faeces, and no increase in anti-FCoV antibody titres was observed in these two cats, and the signs resolved. Conclusions and relevance: Treatment with GS-441524 proved to be effective against FIP in both the short term as well as the long term, with no confirmed relapse during the 1-year follow-up period. Whether delayed neurological signs could be a long-term adverse effect of the treatment or associated with a 'long FIP syndrome' needs to be further evaluated. [ABSTRACT FROM AUTHOR]

Researchers are examining the possibilities for alternative fuel research as a fossil fuel replacement in light of global energy insecurity and other urgent challenges like global warming, severe emissions, and growing industrialization. This research uses 1-pentanol as a low reactivity fuel and Jatropha biodiesel as a high reactivity fuel to explore the reactivity-controlled compression ignition engine characteristics. A water-cooled single-cylinder engine is used in an experiment with varied loads of 25%, 50%, and 75% at a constant speed of 2000 rpm to examine the effects of operational parameters (i.e., (23 bTDC, 25 bTDC, and 27 bTDC) and (400 bar, 500 bar, and 600 bar)). The fuzzy-based Taguchi approach predicts operational parameters, including fuel injection time, fuel injection pressure, and engine load. Utilizing this ideal model, one may increase brake thermal efficiency and braking power while minimizing unburned hydrocarbon and nitrogen oxide emissions. An L20 orthogonal array is used to analyze the effects of various variables on an engine running on B20/1-pentanol fuel, including engine load, fuel injection timing, and fuel injection pressure. Multiple models are generated and verified with the use of experimental findings. Compared to other operating parameters, for reducing oxides of nitrogen, hydrocarbons, and brake-specific energy consumption maximally, engine load of 75%, FIP of 400 bar, and FIT of 23 bTDC are optimal based on the greatest MPCI value of 0.802. [ABSTRACT FROM AUTHOR]

(1) Background: In households in which feline coronavirus (FCoV) is present, three patterns of FCoV shedding are described: non-shedders, intermittent (low-intensity) shedders, or persistent (high-intensity) shedders. It was the aim of this study to describe FCoV shedding patterns in cats from catteries in which FCoV infection is endemic. Additionally, risk factors for high-intensity FCoV shedding or non-shedding were analyzed. (2) Methods: Four fecal samples of 222 purebred cats from 37 breeding catteries were examined for FCoV RNA by quantitative reverse transcription polymerase chain reaction (RT-qPCR). High-intensity shedders were defined as cats positive for FCoV RNA in at least 3/4 fecal samples; non-shedding cats were defined as cats negative in all four fecal samples. Risk factor analysis was performed using information obtained by questionnaire. (3) Results: Of the 222 cats, 125 (56.3%) were considered high-intensity shedders, while 54/222 cats (24.3%) were FCoV non-shedders. The Persian breed was associated with a higher risk of high-intensity shedding in multivariable analysis, while Birman and Norwegian Forest Cats were more likely to be FCoV non-shedders. Cats living together with other cats were more likely to be FCoV shedders. (4) Conclusions: The proportion of both high-intensity shedders and non-shedding cats was higher than previously reported, which possibly can be explained by housing conditions, different genetic susceptibility, or differences in the study period. The risk of high-intensity shedding is higher in certain breeds. However, it cannot be excluded that the individual hygiene procedure of each breeder influenced FCoV-shedding frequency. A smaller group size is a protective factor against FCoV shedding. [ABSTRACT FROM AUTHOR]

Feline infectious peritonitis (FIP) is a systemic disease manifestation of feline coronavirus (FCoV) and is the most important cause of infectious disease-related deaths in domestic cats. FIP has a variable clinical manifestation but is most often characterized by widespread vasculitis with visceral involvement and/or neurological disease that is typically fatal in the absence of antiviral therapy. Using an aptamer-based proteomics assay, we analyzed the plasma protein profiles of cats who were naturally infected with FIP (n = 19) in comparison to the plasma protein profiles of cats who were clinically healthy and negative for FCoV (n = 17) and cats who were positive for the enteric form of FCoV (n = 9). We identified 442 proteins that were significantly differentiable; in total, 219 increased and 223 decreased in FIP plasma versus clinically healthy cat plasma. Pathway enrichment and associated analyses showed that differentiable proteins were related to immune system processes, including the innate immune response, cytokine signaling, and antigen presentation, as well as apoptosis and vascular integrity. The relevance of these findings is discussed in the context of previous studies. While these results have the potential to inform diagnostic, therapeutic, and preventative investigations, they represent only a first step, and will require further validation.