Nitric oxide (NO) is an important molecule in cell communication that also plays an important role in many biological processes. Given the dual role of NO in nerve degeneration and regeneration after facial nerve injury, we sought to delve deeper into its role through a systematic literature review. A comprehensive review of the literature employing SCOPUS, PubMed, Cochrane Library, EMBASE, and Google Scholar databases was conducted to evaluate the induction and role of NO in neurodegeneration and regeneration after facial nerve injury. From the 20 papers ultimately reviewed, the central findings were that neuronal nitric oxide synthase(nNOS), endothelial nitric oxide synthase (eNOS), and induced nitric oxide synthase (iNOS) increased or decreased depending on the method of facial nerve damage, damaged area, harvested area, and animal age, and were correlated with degeneration and regeneration of the facial nerve. Research conducted on rats and mice demonstrated that NO, nNOS, eNOS, and iNOS play significant roles in nerve regeneration and degeneration. However, the relationship between nerve damage and NO could not be defined by a simple causal relationship. Instead, the involvement of NOS depends on the type of nerve cell, source of NO, timing, and location of expression, age of the target animal, and proximity of the damage location to the brainstem. Consequently, nNOS, eNOS, and iNOS expression levels and functions may vary significantly.

The retina, a tissue of the central nervous system, is vital for vision as its photoreceptors capture light and transform it into electrical signals, which are further processed before they are sent to the brain to be interpreted as images. The retina is unique in that it is continuously exposed to light and has the highest metabolic rate and demand for energy amongst all the tissues in the body. Consequently, the retina is very susceptible to oxidative stress. VDAC, a pore in the outer membrane of mitochondria, shuttles metabolites between mitochondria and the cytosol and normally protects cells from oxidative damage, but when a cell\'s integrity is greatly compromised it initiates cell death. There are three isoforms of VDAC, and existing evidence indicates that all three are expressed in the retina. However, their precise localization and function in each cell type is unknown. It appears that most retinal cells express substantial amounts of VDAC2 and VDAC3, presumably to protect them from oxidative stress. Photoreceptors express VDAC2, HK2, and PKM2-key proteins in the Warburg pathway that also protect these cells. Consistent with its role in initiating cell death, VDAC is overexpressed in the retinal degenerative diseases retinitis pigmentosa, age related macular degeneration (AMD), and glaucoma. Treatment with antioxidants or inhibiting VDAC oligomerization reduced its expression and improved cell survival. Thus, VDAC may be a promising therapeutic candidate for the treatment of these diseases.

Management of breeding stallions is crucial to equine reproduction. The longevity of the breeding career is the ultimate objective, whether the stallion is used for natural cover or for semen collection and artificial insemination. Stud farm veterinarians should be aware of the techniques used to evaluate testicular function and the diagnostic approach to testicular disorders in cases of emergency. This paper presents the clinical methods used to evaluate testicular health, including palpation, ultrasonography, biopsy, and fine-needle aspiration. The discussion of testicular disorders is broken down into four categories: congenital disorders (cryptorchidism, monorchidism, and testicular hypoplasia), differential diagnosis of scrotal enlargement, differential diagnosis of causes of progressive testicular enlargement, and differential diagnosis of testicular asymmetry or reduction in size with an emphasis on testicular degeneration. The sudden increase in testicular size is often accompanied by severe clinical signs and is a major cause for referral of stallion for surgery. Testicular disorders are illustrated with clinical cases seen by the authors.

Paraneoplastic neurologic degeneration (PND) manifests as a sudden or subacute neurological syndrome often linked to underlying cancer, either overt or subclinical. Within the spectrum of PND, subacute paraneoplastic cerebellar degeneration (PCD) represents a distinctive subset. While rare, prompt diagnosis holds the potential to ameliorate both neurological and oncological outcomes. Herein, we present the case of a 61-year-old patient diagnosed with subacute cerebellar degeneration, ultimately unveiling non-small cell lung carcinoma.

Muscular dystrophies are a devastating class of diseases that result in a progressive loss of muscle integrity. Duchenne Muscular Dystrophy, the most prevalent form of Muscular Dystrophy, is due to the loss of functional Dystrophin. While much is known regarding destruction of muscle tissue in these diseases, much less is known regarding the synaptic defects that also occur in these diseases. Synaptic defects are also among the earliest hallmarks of neurodegenerative diseases, including the neuromuscular disease Amyotrophic Lateral Sclerosis (ALS). Our current study investigates synaptic defects within adult muscle tissues as well as presynaptic motor neurons in Drosophila dystrophin mutants. Here we demonstrate that the progressive, age-dependent loss of flight ability in dystrophin mutants is accompanied by disorganization of Neuromuscular Junctions (NMJs), including impaired localization of both presynaptic and postsynaptic markers. We show that these synaptic defects, including presynaptic defects within motor neurons, are due to the loss of Dystrophin specifically within muscles. These results should help to better understand the early synaptic defects preceding cell loss in neuromuscular disorders.

Uterine fibroid degeneration is a rare cause of abdominal pain during pregnancy. It can cause complications during pregnancy, including placental abruption, fetal growth restriction, and preterm delivery. Myxoid degeneration is an unusual form of fibroid degeneration. We present a case of a 38-year-old female, G1P0, who presented at 13 weeks gestation to the emergency department at the request of her obstetrician due to abdominal pain with concern about appendicitis. A diagnosis of myxoid degeneration was made. The patient was treated with analgesics and discharged to continue her management in the outpatient setting.

Ophthalmic imaging instruments, including the confocal scanning laser ophthalmoscope and spectral-domain optical coherence tomography system, originally intended for revealing ocular microstructures in the human eye, have been deployed by vision researchers to evaluate the eyes of numerous small and large animal species for more than two decades. In this study, we have used these two instruments to obtain imaging data sequentially from the retinas of three prominent, widely used experimental mouse models to document changes induced by two contrasting vivarium lighting conditions. Mice studied include albino BALB/cJ and B6(Cg)-Tyrc-2J/J and pigmented C57Bl/6J. Mice were reared under dim light conditions until ~8 weeks of age where they underwent baseline imaging. Following, mice were returned to the dim vivarium or relocated to the top rack cage position in a standard vivarium. Mice were then followed for several months by ocular imaging to catalog the retinal dynamics as a function of long-term dim vs. elevated, standard vivarium lighting exposure levels. Upon exposure to elevated light levels, B6(Cg)-Tyrc-2J/J underwent similar changes as BALB/cJ in regard to photoreceptor outer segment shortening, photoreceptor layer proximal aspect hyperreflective changes, and the development of retinal infoldings and autofluorescent sub-retinal inflammatory monocyte infiltrate. Noteworthy, however, is that infoldings and infiltrate occurred at a slower rate of progression in B6(Cg)-Tyrc-2J/J vs. BALB/cJ. The photoreceptor outer nuclear layer thickness of BALB/cJ degenerated steadily following elevated light onset. In contrast, B6(Cg)-Tyrc-2J/J degeneration was unremarkable for many weeks before experiencing a noticeable change in the rate of degeneration that was concomitant with a plateau and decreasing trend in number of retinal infoldings and monocyte infiltrate. Pathological changes in C57Bl/6J mice were unremarkable for all imaging biomarkers assessed with exception to autofluorescent sub-retinal inflammatory monocyte infiltrate, which showed significant accumulation in dim vs. elevated light exposed mice following ~1 year of observation. These data were evaluated using Spearman\'s correlation and Predictive Power Score matrices to determine the best imaging optophysiological biomarkers for indicating vivarium light stress and light-induced photoreceptor degeneration. This study suggests that changes in proximal aspect hyperreflectivity, outer segment shortening, retinal infoldings and autofluorescent sub-retinal inflammatory monocyte infiltrate are excellent indicators of light stress and light-induced degeneration in albino B6(Cg)-Tyrc-2J/J and BALB/cJ mouse strains.

(1) Background: Intervertebral disc degeneration has been linked to obesity; its potential mechanical effects on the intervertebral disc remain unknown. This study aimed to develop and validate a patient-specific model of L3-L4 vertebrae and then use the model to estimate the impact of increasing body weight on disc degeneration. (2) Methods: A three-dimensional model of the functional spinal unit of L3-L4 vertebrae and its components were developed and validated. Validation was achieved by comparing the range of motions (RoM) and intradiscal pressures with the previous literature. Subsequently, the validated model was loaded according to the body mass index and estimated stress, deformation, and RoM to assess disc degeneration. (3) Results: During validation, L3-L4 RoM and intradiscal pressures: flexion 5.17° and 1.04 MPa, extension 1.54° and 0.22 MPa, lateral bending 3.36° and 0.54 MPa, axial rotation 1.14° and 0.52 MPa, respectively. When investigating the impact of weight on disc degeneration, escalating from normal weight to obesity reveals an increased RoM, by 3.44% during flexion, 22.7% during extension, 29.71% during lateral bending, and 33.2% during axial rotation, respectively. Also, stress and disc deformation elevated with increasing weight across all RoM. (4) Conclusions: The predicted mechanical responses of the developed model closely matched the validation dataset. The validated model predicts disc degeneration under increased weight and could lay the foundation for future recommendations aimed at identifying predictors of lower back pain due to disc degeneration.

UNASSIGNED: Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment.
UNASSIGNED: Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed.
UNASSIGNED: CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells.
UNASSIGNED: There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

UNASSIGNED: Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients.
UNASSIGNED: MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images.
UNASSIGNED: The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades.
UNASSIGNED: The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.