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The ribosome is one of the largest complexes in the cell. Adding to its complexity are more than 200 RNA modification sites present on ribosomal RNAs (rRNAs) in a single human ribosome. These modifications occur in functionally important regions of the rRNA molecule, and they are vital for ribosome function and proper gene expression. Until recent technological advancements, the study of rRNA modifications and their profiles has been extremely laborious, leaving many questions unanswered. Small nucleolar RNAs (snoRNAs) are non-coding RNAs that facilitate and dictate the specificity of rRNA modification deposition, making them an attractive target for ribosome modulation. Here, we propose that through the mapping of rRNA modification profiles, we can identify cell-specific modifications with high therapeutic potential. We also describe the challenges of achieving the targeting specificity needed to implement snoRNAs as therapeutic targets in cancers.

Canine visceral leishmaniosis (CVL) caused by Leishmania infantum is a common endemic zoonotic disease in the Middle East, including Israel. The common clinical signs, include, among others, ocular lesions and epistaxis. This report describes a case of CVL in a Boxer dog, which was presented to the hospital due to severe epistaxis, retinal hemorrhage, detachment and uveitis. The platelet count and platelet-crit were increased, and the clotting times were normal. Thromboelastometry demonstrated marked hypercoagulability. The bleeding tendency in this dog was therefore present concurrently with a hypercoagulable state and was likely a result of vasculitis secondary to circulating immune complex (CIC) deposition, which probably interfered with the platelet-vascular endothelium interactions. The dog improved with systemic prednisone and allopurinol therapy, as well as topical ophthalmic treatment. No bleeding episodes were noted from the time treatment was initiated. Nevertheless, the dog remained hypercoagulable during the follow-up period. Epistaxis and retinal hemorrhages in dogs with CVL may result from platelet dysfunction and thrombocytopenia, as previously reported. Nevertheless, based on the present findings, we suggest that in a subset of such cases, when thrombocytopenia is absent and hypercoagulability is demonstrated, bleeding may occur secondary to vasculitis. Thromboelastomety is therefore indicated in dogs with CVL, even in cases showing a bleeding tendency. [ABSTRACT FROM AUTHOR]

The article focuses on the treatment of Feline Herpes Virus (FeHV-1) in cats, which is widespread in the domestic feline population. It is noted that antiviral medications including pyrimidine and purine nucleoside analogues are indicated in cats with active disease. It is mentioned that antivirals are only effective in treating actively replicating virus and are virostatic.

This case series describes four cats, tentatively diagnosed with eyelid apocrine hidrocystoma (AH), a relatively uncommon benign tumor of Moll's glands. All four were Persians, middle-aged or older (median age 7 years; range 4-11 years). In all cats, lesions initially appeared near the medial canthus as dark, round, fluid-filled, non-painful masses of variable size (1-10 mm) and number (up to 20 per cat). No discomfort was observed. In three cases, cyst-like lesions were aspirated for therapeutic or diagnostic reasons, yielding a dark-brown to black turbid fluid, which was examined microscopically in three cases. In two, cytology showed reactive macrophages, with intensive phagocytosis of black-colored debris. In one case, cytology showed numerous cholesterol clefts. Fine needle aspiration of AH allows differentiation of AH, a benign tumor, from other, potentially malignant eyelid lesions (e.g. melanoma). In addition, aspiration and drainage of the lesion content reduces mass size, and therefore has a temporary therapeutic effect. Although a definitive diagnosis of AH is based on histopathology of tissue biopsies, we believe that the signalment, history, the macroscopic appearance and location and the cytological findings of the lesions were highly suggestive of AH. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions This study describes the ocular findings in dogs and cats diagnosed with Florida spot keratopathy (FSK) at a single institution.Affected animals underwent a single comprehensive ophthalmic examination, with no follow‐ups conducted. Data on patient demographics and clinical findings were collected and analyzed.Based on the presence of round, white, fluorescein negative anterior stromal lesions, FSK was diagnosed in 84 dogs and 16 cats, with mean ± SD ages of 6.5 ± 3.7 and 5.9 ± 4.6 years, respectively. FSK was the presenting complaint in 18% of dogs and 12.5% of cats. Most patients had unilateral lesions, with 57% of dog eyes and 55% of cat eyes having more than three lesions per eye. Lesions varied in size (0.5–7.6 mm in dogs, pinpoint to 5 mm in cats) and were predominantly located in the central cornea of dogs, while scattered throughout the cornea of cats. Progression was reported in just 4% of dogs and 6% of cats, while transient irritation was reported in 18% of dogs and 12.5% of cats. Owners reported the presence of little fire ants (LFA) in the vicinity of 21% of dogs and 38% of cats.FSK should be considered a differential diagnosis for transient ocular irritation in dogs and cats, with most lesions being non‐progressive. While an association with LFA has been suggested in both animals and humans, this link remains speculative and has not been confirmed by rigorous academic research. [ABSTRACT FROM AUTHOR]

Biases such as the preference of a particular response for no obvious reason, are an integral part of psychophysics. Such biases have been reported in the common two-alternative forced choice (2AFC) experiments, where participants are instructed to compare two consecutively presented stimuli. However, the principles underlying these biases are largely unknown and previous studies have typically used ad-hoc explanations to account for them. Here we consider human performance in the 2AFC tone frequency discrimination task, utilizing two standard protocols. In both protocols, each trial contains a reference stimulus. In one (Reference-Lower protocol), the frequency of the reference stimulus is always lower than that of the comparison stimulus, whereas in the other (Reference protocol), the frequency of the reference stimulus is either lower or higher than that of the comparison stimulus. We find substantial interval biases. Namely, participants perform better when the reference is in a specific interval. Surprisingly, the biases in the two experiments are opposite: performance is better when the reference is in the first interval in the Reference protocol, but is better when the reference is second in the Reference-Lower protocol. This inconsistency refutes previous accounts of the interval bias, and is resolved when experiments statistics is considered. Viewing perception as incorporation of sensory input with prior knowledge accumulated during the experiment accounts for the seemingly contradictory biases both qualitatively and quantitatively. The success of this account implies that even simple discriminations reflect a combination of sensory limitations, memory limitations, and the ability to utilize stimuli statistics.

There is accumulating evidence that prior knowledge about expectations plays an important role in perception. The Bayesian framework is the standard computational approach to explain how prior knowledge about the distribution of expected stimuli is incorporated with noisy observations in order to improve performance. However, it is unclear what information about the prior distribution is acquired by the perceptual system over short periods of time and how this information is utilized in the process of perceptual decision making. Here we address this question using a simple two-tone discrimination task. We find that the "contraction bias", in which small magnitudes are overestimated and large magnitudes are underestimated, dominates the pattern of responses of human participants. This contraction bias is consistent with the Bayesian hypothesis in which the true prior information is available to the decision-maker. However, a trial-by-trial analysis of the pattern of responses reveals that the contribution of most recent trials to performance is overweighted compared with the predictions of a standard Bayesian model. Moreover, we study participants' performance in a-typical distributions of stimuli and demonstrate substantial deviations from the ideal Bayesian detector, suggesting that the brain utilizes a heuristic approximation of the Bayesian inference. We propose a biologically plausible model, in which decision in the two-tone discrimination task is based on a comparison between the second tone and an exponentially-decaying average of the first tone and past tones. We show that this model accounts for both the contraction bias and the deviations from the ideal Bayesian detector hypothesis. These findings demonstrate the power of Bayesian-like heuristics in the brain, as well as their limitations in their failure to fully adapt to novel environments.

A 14 year old, 6 kg, domestic short hair, spayed female cat was presented with bilateral uveitis, iris bombe, glaucoma, and blindness. Conventional treatment did not resolve the glaucoma, thus a bilateral enucleation was scheduled. Methadone was administered intravenously for anesthetic premedication, and anesthesia was induced with etomidate and midazolam given intravenously to effect, and maintained with isoflurane in 100% oxygen. Atropine was administered intramuscularly after induction. Preoperatively, a peribulbar anesthesia with 9 mg of bupivacaine 0.5% diluted with 1.8 mL of saline 0.9% was performed on the left eye, and a retrobulbar anesthesia with 2.5 mg of bupivacaine 0.5% diluted with 0.5 mL of saline 0.9% was performed on the right eye. During enucleation of the left eye, the cat did not move, and had low isoflurane vaporizer settings; however, during surgery of the right eye, the cat moved several times, and required higher isoflurane vaporizer settings, and additional methadone. After extubation the cat did not react to manual pressure on the left eye incision, but moved its head when the right eye incision was touched. Postoperative analgesia was provided with methadone. The cat recovered uneventfully, and had an increase in appetite several hours after surgery. The administration of peribulbar anesthesia was more likely to decrease inhalant requirements, and provide postoperative analgesia of the incision site. Additional research is indicated to investigate whether peribulbar anesthesia is preferable in cases of feline enucleation. [ABSTRACT FROM AUTHOR]

Purpose: Assess aqueous tear production when measured with the dogs' eyelids open or closed., Methods: Thirty healthy dogs (15 Shih Tzus, 15 Labrador retrievers) were recruited. With the order of testing randomized for each dog, two sessions (separated by 30 min) of STT-1 testing were performed with the dogs' eyelids closed or open. Schirmer strip wetness (every 10 s for 60 s) and number of time(s) the strip dislodged during testing were recorded in each eye. Preferred STT-1 method was surveyed via a global Listserv of the veterinary ophthalmology community., Results: STT-1 values were significantly higher in closed versus open eyes in Shih Tzus (18.6 ± 2.7 mm/min vs. 16.3 ± 2.5 mm/min; p = .002) and Labrador retrievers (21.6 ± 2.9 mm/min vs. 17.8 ± 3.2 mm/min, p < .001), findings that were also significant at times <60 s for either breed (p ≤ .004). Schirmer strips dislodged from six dogs with open eyelids and no dogs with closed eyelids. Maximal STT-1 difference with closed versus open eyelids was 13 mm/min in Labrador retrievers and 7 mm/min in Shih Tzus. Survey results from 275 veterinarians showed STT-1 performed with "closed eyelids" (38.5%), "open eyelids" (26.9%), or "never paid attention, sometimes closed, sometimes open" (34.6%)., Conclusions: Eyelids status (closed or open) during STT-1 testing had a significant impact on aqueous tear secretion in brachycephalic and nonbrachycephalic dogs, highlighting the importance of consistency when repeating STT-1 in a canine patient. STT-1 differences are likely due to sustained reflex tearing throughout the test duration when the dogs' eyelids are closed., (© 2024 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Objectives: In equine glaucoma, topical treatment with carbonic anhydrase inhibitors (CAIs) is recommended. Oral acetazolamide, a systemic CAI, is used in horses with hyperkalemic periodic paralysis. Information regarding its effect on equine intraocular pressure (IOP) is scarce. The aim of the study was to determine the effect of oral acetazolamide treatment on IOP in horses, in a case-control study., Animals: Ten healthy horses., Procedures: Horses were treated with oral acetazolamide (4.4 mg/kg) BID for 1 week. Serum acetazolamide concentrations were determined by liquid chromatography/tandem mass spectrometry, and IOP were measured before treatment, daily during treatment, and at 48 and 72 h after treatment., Results: Acetazolamide serum levels reached steady state at 72 h after the first oral dose. In a mixed effect model logistic regression, there was a significant decrease in IOP on the third treatment day, of 2.4 mmHg (p = .012) and 2.7 mmHg (p = .006) in the left (OS) and right eye (OD), respectively. On the seventh day, there was a decrease in 2.5 mmHg (p = .008) and 2.7 mmHg (p = .007) OS and OD, respectively. A significant increase occurred 48 h following treatment discontinuation (3.6 mmHg, p < .001 and 3.5 mmHg, p < .001 OS and OD, respectively). The area under the concentration versus time curve (AUC (0-10h) ) was 1.1 ± 0.5 μg/mL*h, mean residence time 6.7 ± 4.3 h, peak plasma concentration (C max ) 0.4 ± 0.4 μg/mL and time to reach C max 1.8 h. There was a significant increase in serum concentrations 1, 2, 48, 72, and 156 h following the first drug administration (p < .05)., Conclusions: Further studies are required to determine whether acetazolamide is a potential treatment for equine glaucoma., (© 2024 The Author(s). Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Background: Haws syndrome is a relatively common yet poorly understood disorder in cats., Methods: Ten cats with acute haws syndrome underwent ophthalmic and physical examinations, bloodwork, faecal analysis and pharmacological testing with 1% phenylephrine. The cats were discharged with broad-spectrum deworming (with or without metronidazole) as well as topical tetrahydrozoline., Results: Cats were 17.6 ± 9.1 (2‒36) months old. All eyes had bilateral third eyelid protrusion and ptosis but no miosis or other ocular abnormalities. Diarrhoea was noted in four of 10 cats; otherwise, the cats were systemically healthy. A newly adopted kitten with haws syndrome and diarrhoea caused the condition to develop in the other three cats (from the same multicat household) within 4‒11 days. All cats tested negative for feline immunodeficiency virus and feline leukaemia virus. Serum amyloid A levels were elevated in two of eight tested cats. Tests for the presence of Giardia were positive in four of nine tested cats. Clinical signs transiently resolved within 20 minutes of the application of topical phenylephrine or tetrahydrozoline. Haws syndrome resolved in nine of the 10 cats within 37.7 ± 23 (12‒95) days but recurred in three of the nine cats 156‒182 days later., Limitations: The small sample size limits the conclusions that can be drawn., Conclusions: Haws syndrome occurs in generally healthy cats, with or without diarrhoea, and is characterised by a sympathetic neuropathy causing bilateral third eyelid protrusion and ptosis. Clinical signs are possibly triggered by contagious gastrointestinal pathogen(s) that presumably affect(s) the gut microbiota and influence(s) the gut‒brain axis., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Gene augmentation therapy is a promising treatment for incurable, blinding inherited retinal diseases, and intravitreal delivery is being studied as a safe alternative to subretinal injections. Adeno-Associated Viruses (AAV) are commonly-used vectors for ocular gene augmentation therapy. Naturally occurring pre-operative exposure and infection with AAV could result in presence of neutralizing antibodies (NAB's) in patients' serum, and may affect the safety and efficacy of treatment. Our aim was to characterize the humoral response against AAV pre- and post-intravitreal delivery of AAV2.7m8 vectors in a naturally-occurring sheep model of CNGA3 achromatopsia. Serial serum neutralization assays were performed to screen sheep for pre-exiting anti-AAV2 NAB's, and to assess the effect of intravitreal AAV2.7m8 injection on post-operative NAB titers and intraocular inflammation in sheep. The effect of viral dose and transgene type were also assessed. Serological screening revealed pre-operative seropositivity in 21.4% of animals, with age being a risk factor for the presence of anti-AAV2 NAB's. NAB titers increased following intravitreal AAV administration in the majority of sheep. There was no significant difference in the degree of post-operative serum neutralization between pre-operatively seronegative sheep and those with pre-existing antibodies. However, only sheep with pre-existing antibodies presented with signs of post-operative inflammation. We conclude that pre-existing anti-AAV2 NAB's do not affect the level of post-operative NAB titers; however, they increase the risk of post-operative ocular inflammation. Our results could have implications for the management of AAV-mediated ocular gene therapies, a technology being increasingly studied and used in patients., Competing Interests: Competing interests M. Ross, none; K. Sade, none; A. Obolensky none; E. Averbukh, none; M. Desrosiers, None A. Rosov, none; H. Dvir, none; E. Gootwine, none; E. Banin, none; D. Dalkara reports grants from Foundation Fighting Blindness, USA and European Research Council, during the conduct of the study; DD is a co-inventor on patent #9193956 (Adeno-associated virus virions with variant capsid and methods of use thereof), with royalties paid to Adverum Biotechnologies and on pending patent applications on noninvasive methods to target cone photoreceptors (EP17306429.6 and EP17306430.4) licensed to Gamut Tx now Sparing- Vision. DD also has personal financial interests in Tenpoint Tx. and SparingVision, outside the scope of the submitted work; R. Ofri, none. Ethical approval Experimental protocols were approved by the Agricultural Research Organization, Volcani Center, Animal Experimentation Ethics Committee, Permit 643/16, (© 2024. The Author(s).)

Objective: Investigate the tolerance, stability, and efficacy of topical 0.1% and 1% atropine in cats., Procedures: Six cats underwent two trials separated by a 2-week washout period. One drop of artificial tears was placed in one randomly selected eye (control), and one drop of either 0.1% atropine (Trial I) or 1% atropine (Trial II) was placed in the other eye. Immediate adverse effects were recorded for severity (0-3) and duration (seconds). Horizontal pupil diameter (HPD), pupillary light reflexes (PLRs), intraocular pressure (IOP), Schirmer tear test-1 (STT-1), and heart rate (HR) were monitored at baseline then 8 h post-administration. PLRs were assessed for a total of 72 h. Stability was assessed weekly for 1 month in room temperature and refrigerated conditions, evaluating solution clarity, pH, and drug concentrations., Results: Adverse effects had a significantly lower severity score and shorter duration with 0.1% versus 1% atropine (severity 1.2 ± 0.4 vs. 2.5 ± 0.5, p = .010; duration 107.5 ± 53.3 vs. 293.3 ± 106.5 s, p = .009). HPD was significantly greater than baseline measurements as early as 40 min for both atropine formulations. Pupils were non-responsive for a significantly shorter duration with 0.1% versus 1% atropine (median 7 h vs. 47.5 h, p = .031). Compared with control eyes, IOP was significantly elevated by 1% atropine (p = .021) but not 0.1% atropine (p = .502). No significant differences were noted in STT-1 and HR measurements. Both solutions were stable in room temperature and refrigerated conditions for 1 month., Conclusions: Diluted 0.1% atropine was stable and better tolerated by cats, offering a potential alternative to feline patients that experience adverse effects from topical 1% atropine., (© 2024 The Author(s). Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Retinitis pigmentosa (RP) is a heterogeneous inherited retinal disorder. Mutations in KIZ cause autosomal recessive (AR) RP. We aimed to characterize the genotype, expression pattern, and phenotype in a large cohort of KIZ cases. Sanger and whole exome sequencing were used to identify the KIZ variants. Medical records were reviewed and analyzed. Thirty-one patients with biallelic KIZ mutations were identified: 28 homozygous for c.226C>T (p.R76*), 2 compound heterozygous for p.R76* and c.3G>A (p.M1?), and one homozygous for c.247C>T (p.R83*). c.226C>T is a founder mutation among patients of Jewish descent. The clinical parameters were less severe in KIZ compared to DHDDS and FAM161A cases. RT-PCR analysis in fibroblast cells revealed the presence of four different transcripts in both WT and mutant samples with a lower percentage of the WT transcript in patients. Sequence analysis identified an exonic sequence enhancer (ESE) that includes the c.226 position which is affected by the mutation. KIZ mutations are an uncommon cause of IRD worldwide but are not rare among Ashkenazi Jews. Our data indicate that p.R76* affect an ESE which in turn results in the pronounced skipping of exon 3. Therefore, RNA-based therapies might show low efficacy since the mutant transcripts are spliced.

Background: Ophthalmoscopy is a valuable tool in clinical practice. We report the use of a novel smartphone-based handheld device for visualisation and photo-documentation of the ocular fundus in veterinary medicine., Methods: Selected veterinary patients of a referral ophthalmology service were included if one or both eyes had clear ocular media, allowing for examination of the fundus. Following pharmacological mydriasis, fundic images were obtained with a handheld fundus camera (Volk VistaView). For comparison, the fundus of a subset of animals was also imaged with a veterinary-specific fundus camera (Optomed Smartscope VET2)., Results: The large field of view achieved by the Volk VistaView allowed for rapid and thorough observation of the ocular fundus in animals, providing a tool to visualise and record common pathologies of the posterior segment. Captured fundic images were sometimes overexposed, with the tapetal fundus artificially appearing hyperreflective when using the Volk VistaView camera, a finding that was less frequent when activating a 'veterinary mode' that reduced the sensitivity of the camera's sensor. The Volk VistaView compared well with the Optomed Smartscope VET2., Limitation: The main study limitation was the small sample size., Conclusions: The Volk VistaView camera was easy to use and provided good-quality fundic images in veterinary patients with healthy or diseased eyes, offering a wide field of view that was ideal for screening purposes., (© 2024 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)