Early-Stage IM Treatment with the Host-Derived Immunostimulant CPDI-02 Increases Curative Protection of Healthy Outbred Mice Against Subcutaneous Infection with Community-Acquired Methicillin-Resistant USA300.

: Community-acquired methicillin-resistant (CA-MRSA) greatly complicates the treatment of skin and soft tissue infections (SSTI). It was previously found that subcutaneous (SQ) treatment with the mononuclear phagocyte (MP)-selective activator complements peptide-derived immunostimulant-02 (CPDI-02; formerly EP67) and increases prophylaxis of outbred CD-1 mice against SQ infection with CA-MRSA. Here, we determined if treatment with CPDI-02 also increases curative protection.

Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC).

Background: A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce.

Methods: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation.

Fading SARS-CoV-2 humoral VOC cross-reactivity and sustained cellular immunity in convalescent children and adolescents.

Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-).

CD98hc is a target for brain delivery of biotherapeutics.

Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TV). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATV) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys.

Translatome analysis reveals microglia and astrocytes to be distinct regulators of inflammation in the hyperacute and acute phases after stroke.

Neuroinflammation is a hallmark of ischemic stroke, which is a leading cause of death and long-term disability. Understanding the exact cellular signaling pathways that initiate and propagate neuroinflammation after stroke will be critical for developing immunomodulatory stroke therapies. In particular, the precise mechanisms of inflammatory signaling in the clinically relevant hyperacute period, hours after stroke, have not been elucidated.

Establish a Pregnant Sow-Neonate Model to Assess Maternal Immunity of a Candidate Influenza Vaccine.

While it is well appreciated that maternal immunity can provide neonatal protection, the contribution of maternal vaccination toward generating such immunity is not well characterized. In our previous work, we created a candidate influenza vaccine using our chimeric hemagglutinin (HA) construct, HA-129. The HA-129 was expressed as part of a whole-virus vaccine that was built on the A/swine/Texas/4199-2/98-H3N2 backbone to generate the recombinant virus TX98-129.

Effects of Core Antigen Bacterin with an Immunostimulant on Piglet Health and Performance Outcomes When Challenged with Enteric and Respiratory Pathogens.

A total of 90 pigs, approximately one day of age, were used in a 42-day study to evaluate whether Endovac-Porci, a core antigen vaccine with an immunostimulant, provides piglets with broad-spectrum protection against the enteric and respiratory effects of Gram-negative bacteria. This study was a single-site, randomized, prospective, blinded, comparative placebo-controlled design. Individual pigs were randomly allocated to 1 of 2 treatments in a randomized design.

Translatome analysis reveals microglia and astrocytes to be distinct regulators of inflammation in the hyperacute and acute phases after stroke.

Neuroinflammation is a hallmark of ischemic stroke, which is a leading cause of death and long-term disability. Understanding the exact cellular signaling pathways that initiate and propagate neuroinflammation after stroke will be critical for developing immunomodulatory stroke therapies. In particular, the precise mechanisms of inflammatory signaling in the clinically relevant hyperacute period, hours after stroke, have not been elucidated.

A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models.

Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody.

Comparison of lidocaine alone or in combination with a local nerve block of ethanol, bupivacaine liposome suspension, or oral meloxicam to extend analgesia after scoop dehorning in Holstein calves.

The American Veterinary Medical Association recommends the use of practices that reduce or eliminate pain and discomfort associated with dehorning. Identification of an effective, long-acting local anesthetic that is practical for producers to implement and reduces pain from dehorning would benefit animal welfare. Thirty-two Holstein bulls and heifers were enrolled.

Efficacy of and -Based Feed Additives in Reducing -Associated Health and Performance Effects in Commercial Beef Calves.

Salmonella enterica, which causes typhoid fever, is one of the most prevalent food-borne pathogens. Salmonellosis in cattle can greatly impact a producer’s income due to treatment costs, decreased productivity of the herd, and mortality due to disease. Current methods of treatment and prevention for salmonellosis consist of antibiotics and vaccinations, but neither of these options are perfect.

Synovex ONE Grower improves growth performance for at least 200 days in growing beef steers and heifers fed in confinement for slaughter.

Growth-promoting implants are broadly used in the feedlot industry to improve growth performance and to increase production efficiencies. With cattle being fed longer and to heavier weights, there is demand for extended-release implants that payout for at least 200 d. Our objective was to evaluate feedlot growth of Synovex ONE Grower, a moderate potency (150 mg trenbolone acetate [TBA] and 21 mg estradiol benzoate [EB]), extended-release, growth-promoting implant for 200 d.

Comparison of two distinct arrival and treatment programs for bovine respiratory disease in high-risk feeder cattle entering a feedlot.

Antimicrobial metaphylaxis of high-risk cattle entering the feedlot is a common management strategy implemented against bovine respiratory disease (). Typically, following a prescribed postmetaphylactic interval (), animals displaying clinical signs of BRD are pulled from the feedlot pen and treated with antimicrobials when treatment criteria are met. The objective of this study was to compare 2 distinct sequential BRD treatment protocols each consisting of a metaphylactic antimicrobial plus 2 potential subsequent as-needed treatment antimicrobials.

Disruption of anthrax toxin receptor 1 in pigs leads to a rare disease phenotype and protection from senecavirus A infection.

Senecavirus A (SVA) is a cause of vesicular disease in pigs, and infection rates are rising within the swine industry. Recently, anthrax toxin receptor 1 (ANTXR1) was revealed as the receptor for SVA in human cells. Herein, the role of ANTXR1 as a receptor for SVA in pigs was investigated by CRISPR/Cas9 genome editing.

Behavioral and performance response associated with administration of intravenous flunixin meglumine or oral meloxicam immediately prior to surgical castration in bull calves.

The objective of this study was to determine the effects of flunixin meglumine or meloxicam on behavioral response and performance characteristics associated with surgical castration in crossbred bulls. Intact male Bos taurus calves (n = 252; averaging 176 kg) were randomly allocated into one of three treatment groups within pen: control (CON), flunixin meglumine (FLU; 2.2 mg/kg intravenous injection), or meloxicam (MEL; 2.

Assessment of bovine respiratory disease progression in calves challenged with bovine herpesvirus 1 and using point-of-care and laboratory-based blood leukocyte differential assays.

Blood leukocyte differentials can be useful for understanding changes associated with bovine respiratory disease (BRD) progression. By improving turnaround time, point-of-care leukocyte differential assays (PCLD) may provide logistical advantages to laboratory-based assays. Our objective was to assess BRD progression in steers challenged with bovine herpesvirus 1 and using point-of-care and laboratory-based blood leukocyte differentials.

Evaluation of Antimicrobial or Non-antimicrobial Treatments in Commercial Feedlot Cattle With Mild Bovine Respiratory Disease Based on a Refined Case-Definition.

The study objective was to compare clinical and performance outcomes among feedlot steers treated for bovine respiratory disease (BRD) with tildipirosin (TIL), flunixin transdermal solution (FTS; topical application), or both, based on a refined BRD case-definition. Crossbred steer calves ( = 2,380) were enrolled based on a clinical illness score (CIS) of 1-3; a rectal temperature between >102.5° F and ≤103.

Evaluating the utility of a CO2 surgical laser for piglet castration to reduce pain and improve wound healing: a pilot study.

CO2 surgical lasers are widely used for procedures in veterinary and human medicine. There is evidence to suggest surgery using a CO2 laser reduces pain and swelling and improves healing time compared with surgery with a scalpel. Millions of piglets in North America are surgically castrated each year using a scalpel.

Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis.

Background: B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE).

Histologic evaluation of activation of acute inflammatory response in a mouse model following ultrasound-mediated blood-brain barrier using different acoustic pressures and microbubble doses.

Localized blood-brain barrier (BBB) opening can be achieved with minimal to no tissue damage by applying pulsed focused ultrasound alongside a low microbubble (MB) dose. However, relatively little is known regarding how varying treatment parameters affect the degree of neuroinflammation following BBB opening. The goal of this study was to evaluate the activation of an inflammatory response following BBB opening as a function of applied acoustic pressure using two different microbubble doses.

Obesity Drives Delayed Infarct Expansion, Inflammation, and Distinct Gene Networks in a Mouse Stroke Model.

Obesity is associated with chronic peripheral inflammation, is a risk factor for stroke, and causes increased infarct sizes. To characterize how obesity increases infarct size, we fed a high-fat diet to wild-type C57BL/6J mice for either 6 weeks or 15 weeks and then induced distal middle cerebral artery strokes. We found that infarct expansion happened late after stroke.

Augmented β2-adrenergic signaling dampens the neuroinflammatory response following ischemic stroke and increases stroke size.

Background: Ischemic stroke provokes a neuroinflammatory response and simultaneously promotes release of epinephrine and norepinephrine by the sympathetic nervous system. This increased sympathetic outflow can act on β2-adrenergic receptors expressed by immune cells such as brain-resident microglia and monocyte-derived macrophages (MDMs), but the effect on post-stroke neuroinflammation is unknown. Thus, we investigated how changes in β2-adrenergic signaling after stroke onset influence the microglia/MDM stroke response, and the specific importance of microglia/MDM β2-adrenergic receptors to post-stroke neuroinflammation.

Transmammary delivery of firocoxib to piglets reduces stress and improves average daily gain after castration, tail docking, and teeth clipping1.

Painful processing procedures in piglets such as tail docking, castration, and teeth clipping are an emerging animal welfare concern. We hypothesized that transmammary delivery of a nonsteroidal anti-inflammatory drug, firocoxib, would reduce pain associated with processing in piglets. This study compared the pharmacokinetics, efficacy, safety, and tissue residue concentrations of 4 doses of firocoxib (0.