A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis.

BackgroundThe ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus.MethodsTo meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA.ResultsWe found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8lo cells in blood prior to and at 3 months post-ASC therapy. CD8lo cells may serve as a potential "predictor" for response to systemic ASC therapy.ConclusionFresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases

Incidence of enamel defects on permanent canine teeth following extraction of linguoverted mandibular deciduous canine teeth in dogs

Interceptive orthodontics may be indicated in puppies exhibiting dental malocclusion with linguoverted deciduous mandibular canine teeth to alleviate pain and prevent teeth interlock, which may affect growth and development of the mandibles. Historically extraction of deciduous mandibular canine teeth has been recommended as soon as a malocclusion is identified, often as early as 6-8 weeks of age and no later than 12 weeks of age. This early surgical intervention of deciduous teeth extractions risks potential damage to the developing permanent canine teeth resulting in enamel defects often referred to as a Turner's tooth or Turner's hypoplasia. A search of medical records from five veterinary specialty dentistry practices was conducted to identify dogs 8-12 weeks of age who (a) underwent deciduous mandibular canine extractions for management of class 1 or class 2 malocclusion with linguoverted mandibular canine teeth, and (b) were seen for at least one recheck exam to assess for enamel defects on permanent mandibular canine teeth. Furthermore, data was collected to determine the number of dogs that required additional treatment after eruption of the permanent canine teeth due to linguoversion of the permanent canine teeth. All procedures were performed by a board-certified veterinary dentist™ or a supervised veterinary dentistry resident. Seventy-four dogs fit the inclusion criteria and had a total of 143 deciduous mandibular canine teeth extracted, out of which 13 dogs exhibited enamel defects affecting 21 permanent canine teeth. The 13 affected dogs represent a 17.5% cumulative incident rate 13/74 (95%CI 11-28%). Of all extracted teeth, 14.6% (21/143) had enamel defects affecting permanent canine teeth. Twenty-eight dogs required additional treatment to prevent the permanent mandibular canine teeth from causing trauma to the hard palate and gingiva which represented 37.8% (28/74) of all dogs in the study. Age and sex of the dog at the time of extraction were not found to be associated with the likelihood of incidence of enamel defects. This is the first reported rate of enamel defects on permanent mandibular canine teeth following extraction of deciduous mandibular canine teeth and is important to consider when advising or performing extraction of deciduous teeth in dogs

Cell Therapy in Veterinary Medicine as a Proof-of-Concept for Human Therapies: Perspectives From the North American Veterinary Regenerative Medicine Association

In the past decade, the potential to translate scientific discoveries in the area of regenerative therapeutics in veterinary species to novel, effective human therapies has gained interest from the scientific and public domains. Translational research using a One Health approach provides a fundamental link between basic biomedical research and medical clinical practice, with the goal of developing strategies for curing or preventing disease and ameliorating pain and suffering in companion animals and humans alike. Veterinary clinical trials in client-owned companion animals affected with naturally occurring, spontaneous disease can inform human clinical trials and significantly improve their outcomes. Innovative cell therapies are an area of rapid development that can benefit from non-traditional and clinically relevant animal models of disease. This manuscript outlines cell types and therapeutic applications that are currently being investigated in companion animals that are affected by naturally occurring diseases. We further discuss how such investigations impact translational efforts into the human medical field, including a critical evaluation of their benefits and shortcomings. Here, leaders in the field of veterinary regenerative medicine argue that experience gained through the use of cell therapies in companion animals with naturally occurring diseases represent a unique and under-utilized resource that could serve as a critical bridge between laboratory/preclinical models and successful human clinical trials through a One-Health approach

Categorical Dimensions of Human Odor Descriptor Space Revealed by Non-Negative Matrix Factorization

In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain unclear. Here, we use non-negative matrix factorization (NMF) – a dimensionality reduction technique – to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor dimensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures

Fatigue evaluation in maintenance and assembly operations by digital human simulation

Virtual human techniques have been used a lot in industrial design in order to consider human factors and ergonomics as early as possible. The physical status (the physical capacity of virtual human) has been mostly treated as invariable in the current available human simulation tools, while indeed the physical capacity varies along time in an operation and the change of the physical capacity depends on the history of the work as well. Virtual Human Status is proposed in this paper in order to assess the difficulty of manual handling operations, especially from the physical perspective. The decrease of the physical capacity before and after an operation is used as an index to indicate the work difficulty. The reduction of physical strength is simulated in a theoretical approach on the basis of a fatigue model in which fatigue resistances of different muscle groups were regressed from 24 existing maximum endurance time (MET) models. A framework based on digital human modeling technique is established to realize the comparison of physical status. An assembly case in airplane assembly is simulated and analyzed under the framework. The endurance time and the decrease of the joint moment strengths are simulated. The experimental result in simulated operations under laboratory conditions confirms the feasibility of the theoretical approach

PerBrain: a multimodal approach to personalized tracking of evolving state-of-consciousness in brain-injured patients: protocol of an international, multicentric, observational study

BACKGROUND: Disorders of consciousness (DoC) are severe neurological conditions in which consciousness is impaired to various degrees. They are caused by injury or malfunction of neural systems regulating arousal and awareness. Over the last decades, major efforts in improving and individualizing diagnostic and prognostic accuracy for patients affected by DoC have been made, mainly focusing on introducing multimodal assessments to complement behavioral examination. The present EU-funded multicentric research project “PerBrain” is aimed at developing an individualized diagnostic hierarchical pathway guided by both behavior and multimodal neurodiagnostics for DoC patients. METHODS: In this project, each enrolled patient undergoes repetitive behavioral, clinical, and neurodiagnostic assessments according to a patient-tailored multi-layer workflow. Multimodal diagnostic acquisitions using state-of-the-art techniques at different stages of the patients’ clinical evolution are performed. The techniques applied comprise well-established behavioral scales, innovative neurophysiological techniques (such as quantitative electroencephalography and transcranial magnetic stimulation combined with electroencephalography), structural and resting-state functional magnetic resonance imaging, and measurements of physiological activity (i.e. nasal airflow respiration). In addition, the well-being and treatment decision attitudes of patients’ informal caregivers (primarily family members) are investigated. Patient and caregiver assessments are performed at multiple time points within one year after acquired brain injury, starting at the acute disease phase. DISCUSSION: Accurate classification and outcome prediction of DoC are of crucial importance for affected patients as well as their caregivers, as individual rehabilitation strategies and treatment decisions are critically dependent on the latter. The PerBrain project aims at optimizing individual DoC diagnosis and accuracy of outcome prediction by integrating data from the suggested multimodal examination methods into a personalized hierarchical diagnosis and prognosis procedure. Using the parallel tracking of both patients’ neurological status and their caregivers’ mental situation, well-being, and treatment decision attitudes from the acute to the chronic phase of the disease and across different countries, this project aims at significantly contributing to the current clinical routine of DoC patients and their family members. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04798456. Registered 15 March 2021 – Retrospectively registered

Modeling the impact of melt on seismic properties during mountain building

Initiation of partial melting in the mid/lower crust causes a decrease in P-wave and S-wave velocities; recent studies imply that the relationship between these velocities and melt is not simple. We have developed a modelling approach to assess the combined impact of various melt and solid phase properties on seismic velocities and anisotropy. The modelling is based on crystallographic preferred orientation (CPO) data measured from migmatite samples, allowing quantification of the variation of seismic velocities with varying melt volumes, shapes, orientations, and matrix anisotropy. The results show non-linear behaviour of seismic properties as a result of the interaction of all of these physical properties, which in turn depend on lithology, stress regime, strain rate, pre-existing rock fabrics, and pressure-temperature conditions. This non-linear behaviour is evident when applied to a suite of samples from a traverse across a migmatitic shear zone in the Seiland Igneous Province, Northern Norway. Critically, changes in solid phase composition and CPO, and melt shape and orientation with respect to the wave propagation direction can result in huge variations in the same seismic property even if the melt fraction remains the same. A comparison with surface wave interpretations from tectonically active regions highlights the issues in current models used to predict melt percentages or partially molten regions. Interpretation of seismic data to infer melt percentages or extent of melting should, therefore, always be underpinned by robust modelling of the underlying geological parameters combined with examination of multiple seismic properties in order to reduce uncertainty of the interpretation

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment