Lesion Scores Research Articles

Efficacy of Bacillus subtilis to replace in-feed antibiotics of broiler chickens under necrotic enteritis-challenged experiments: a systematic review and meta-analysis

Necrotic enteritis (NE) and coccidiosis are among the most prevalent infectious diseases in broiler chickens, contributing to large profitability losses. Bacillus subtilis is a promising direct-fed probiotic to counter various pathogens infection in broiler chickens. Here, we performed a meta-analysis to investigate the effects of B. subtilis on broiler chickens performance. A total of 28 studies were selected according to a PRISMA checklist. Random-effect model and mixed-effect model of meta-analysis were fitted to estimate the overall effects of B. subtilis (BS) treatment compared to either the control group (CON) or NE-infected group (NEinf) as a baseline. Hedges' g effect size and its variance were used as estimators of standardized mean difference (SMD) calculation where the results were presented at a 95% confidence interval (95% CI) of the SMD. Overall, NEinf broiler chickens depressed (P < 0.01) body weight (BW), average daily gain (ADG), and feed intake, and elevated (P < 0.01) feed conversion ratio (FCR). Treatment with BS improved ADG and final BW of NEinf with no difference (P=0.15) between BS and antibiotics (AB), indicating that they had comparable efficacy to treat NE in broiler chickens. BS supplemented to uninfected CON (BSS) improved (P < 0.01) final BW, ADG, and FCR. Compared to CON, BS, and AB failed to recover the FCR but these treatments decreased (P < 0.01) FCR when compared to the NEinf group with similar efficacy (P=0.97). As expected, NEinf birds had a higher mortality rate (P < 0.01) and higher lesion score (P < 0.01) compared to CON, and treatment using AB and BS successfully decreased (P < 0.01) the mortality rate and lesion score. Compared to BS, AB was more effective to lower (P=0.01) mortality rate, but comparable (P=0.65) to minimize lesion score. To conclude, B. subtilis could be an effective natural additive to replace in-feed antibiotics in broiler chickens challenged with C. perfringens. However, the efficacy to reduce mortality rate was better with antibiotics treatment.

Molecular characterization and protective efficacy of vacuolar protein sorting 29 from Eimeria tenella.

Vacuolar protein sorting 29 (VPS29) is a core component of the retromer-retriever complex and is essential for recycling numerous cell-surface cargoes from endosomes. However, there are no reports yet on VPS29 of Eimeria spp. Here, we cloned and prokaryotically expressed a partial sequence of Eimeria tenella VPS29 (EtVPS29) with RT-PCR and engineered strain of Escherichia coli respectively. The localization of the VPS29 protein in E. tenella sporozoites was investigated with immunofluorescence (IFA) and overexpression assays. And its protective efficacy against E. tenella infection was investigated in chickens with the animal protection test. An EtVPS29 gene fragment with an ORF reading frame of 549 bp was cloned. The band size of the expressed recombinant protein, rEtVPS29, was approximately 39 kDa and was recognized by the chicken anti-E. tenella positive serum. EtVPS29 protein was observed widely distributing in the cytoplasm of E. tenella sporozoites in the IFA and overexpression assays. rEtVPS29 significantly increased average body weight gain and decreased mean lesion score and oocyst output in chickens. The relative weight gain rate in the rEtVPS29-immunized group was 62.9%, which was significantly higher than that in the unimmunized and challenged group (P < 0.05). The percentage of reduced oocyst output in the rEtVPS29 immunized group was 32.2%. The anticoccidial index of the rEtVPS29-immunized group was 144.2. Serum ELISA also showed that rEtVPS29 immunization induced high levels of specific antibodies in chickens. These results suggest that rEtVPS29 can induce a specific immune response and is a potential candidate for the development of novel vaccines against E. tenella infections in chickens.

Chimeric Antigen Receptor (CAR) T-Cell Therapy for Patients with Lung Cancer: Current Perspectives.

Immunotherapy using chimeric antigen receptor (CAR)-engineered T-cells has achieved unprecedented efficacy in selected hematological cancers. However, solid tumors such as lung cancer impose several additional challenges to the attainment of clinical success using this emerging therapeutic modality. Lung cancer is the biggest cause of cancer-related mortality worldwide, accounting for approximately 1.8 million deaths worldwide each year. Obstacles to the development of CAR T-cell immunotherapy for lung cancer include the selection of safe tumor-selective targets, accounting for the large number of candidates that have been evaluated thus far. Tumor heterogeneity is also a key hurdle, meaning that single target-based approaches are susceptible to therapeutic failure through the emergence of antigen null cancers. There is also a need to enable CAR T-cells to traffic efficiently to sites of disease, to infiltrate tumor deposits and to operate within the hostile tumor microenvironment formed by solid tumors, resisting the onset of exhaustion. Multiple immune, metabolic, physical and chemical barriers operate at the core of malignant lesions, with potential for further heterogeneity and evolution in the face of selective therapeutic pressures. Although the extraordinarily adaptable nature of lung cancers has recently been unmasked, immunotherapy using immune checkpoint blockade can achieve long-term disease control in a small number of patients, establishing clinical proof of concept that immunotherapies can control advanced lung carcinomas. This review summarizes pre-clinical CAR T-cell research that is specifically focused on lung cancer in addition to published and ongoing clinical trial activity. A number of advanced engineering strategies are also described which are designed to bridge the gap to the attainment of meaningful efficacy using genetically engineered T-cells.

Poster 290: Effect of Platelet-rich Plasma Injections on Cartilage T1rho in Knee Osteoarthritis

Poster 290: Effect of Platelet-rich Plasma Injections on Cartilage T1rho in Knee Osteoarthritis

Autologous exosome facilitates load and target delivery of bioactive peptides to repair spinal cord injury.

Spinal cord injury (SCI) causes motor, sensory and automatic impairment due to rarely axon regeneration. Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury, as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier. To develop an effective non-invasive treatment strategy for SCI in clinic, we generated an autologous plasma exosome (AP-EXO) based biological scaffold where AP-EXO was loaded with neuron targeting peptide (RVG) and growth-facilitating peptides (ILP and ISP). This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment, thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice. More importantly, in ex vivo, human plasma exosomes (HP-EXO) loaded with combinatory peptides of RVG, ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice. Combining the efficacy and safety, the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI. It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.

Evaluation of Three Vaccination Schemes Against Clostridium perfringens Alpha Toxin and Their Effects on the Performance, Level of Intestinal Lesions, and Serum Antibody Titers in Broilers.

The objective of the trial was to evaluate three vaccination schemes against Clostridium perfringens (CP) alpha-toxoid through drinking water to determine if they can protect against clinical signs of necrotic enteritis and coccidiosis in broiler chickens. Three hundred 1-day-old Cobb 500 male chicks were used in 4 treatments with 10 repetitions. Each group received 1 of the following treatments over the course of 29 days: T1, no vaccination; T2, vaccination on Day 1; T3, vaccination on Day 7; and T4, vaccination on Days 7 and 17. The birds were vaccinated with inactivated CP toxoid type A, administered via drinking water. During the first 14 days, a high-protein diet (27%) consisting of corn, soy, and fish meal was fed. On Day 14 Eimeria acervulina (EA), Eimeria maxima (EMx), Eimeria tenella (ET), Eimeria necatrix, and Eimeria brunetti were used in a coccidial challenge. The field isolate CP type A was then inoculated on Days 18, 19, and 20. Ten birds were slaughtered by treatment to obtain serology samples for antibody titers and intestine samples for CP and Eimeria lesion score and gut integrity indicators. Productive performance was assessed using complete randomized design and compared statistically using the Tukey test, whereas intestinal integrity variables and antibodies against CP alpha toxin were assessed using a Kruskal-Wallis nonparametric method. The results revealed that the treatments had an effect on productive performance (P < 0.05); T3 had better body weight and weight gain than T1. In terms of lesion score at Day 21, T4 had a lower lesion score by EA, EMx, and ET than T1. Cell desquamation in T2 was lower than in T4, and excess mucus (EM) in T1 was the worst in gut integrity indicators at Day 21. On the other hand, T2 had more EM than T3 and T4 at Day 25. In the measurement of antibodies, no statistical differences (P > 0.05) were found. These findings indicate that vaccination on Day 7 (T3) outperformed double vaccination on Days 7 and 17 (T4) and single on Day 1 (T2), in terms of productive performance, gut integrity, and lesion scores; and on the last day of the experiment T3 had the best performance in immunology response.

Randomized single-blinded prospective comparison between ozone therapy and electroacupuncture for canine thoracolumbar disk disease

Ozone therapy has been used to control pain in animals. Moreover, electroacupuncture (EA) has been effective in neurological recovery and pain control in dogs with thoracolumbar discopathy. EA was compared with Ozone applied at acupuncture points in dogs with signs of thoracolumbar disk disease. Chondrodystrophic mongrel dogs, with lesion scores between 1 and 4, were randomly divided into groups: EA (n = 13) - electroacupuncture at BL20, BL23, ST36, KID3 and BL60 and dry needle in lumbar Bai Hui, and OZO (n = 15) - paravertebral application of 3 mL ozone (20 μg / mL) at BL20, BL23, lumbar Bai Hui, ST36, and KID3/BL60, both groups with weekly applications. No significant differences were observed between groups in weekly blind pain assessments using a dynamic interactive visual analog scale, and neurological assessments using a numerical-functional scale. Both groups showed a progressive improvement in pain control and neurological condition, which was observed when comparing the group's EA and OZO in dogs with all lesion scores. The time of return to locomotion (days) of dogs scored 3 and 4, between groups EA (10.6 ± 5.4) and OZO (14.5 ± 15.7), had no significant differences. Ozone therapy was effective to control pain and motor rehabilitation and sensory functions of dogs with thoracolumbar discopathy signs, just as electroacupuncture. Ozone application was a quick and easy-to-handle treatment. Paravertebral and subcutaneous routes did not require anesthesia or other advanced imaging technology, besides being safe and effective.

Clinical, dermoscopic, and ultrasonic monitoring of the response to biologic treatment in patients with moderate-to-severe plaque psoriasis.

Assessment of therapeutic response of psoriasis has relied traditionally on clinical observation, and effective non-invasive tools are desirable. To investigate the value of dermoscopy and high-frequency ultrasound (HFUS) in the monitoring of psoriatic lesions treated with biologics. Patients with moderate-to-severe plaque psoriasis treated with biologics were evaluated by clinical, dermoscopic, and ultrasonic scores at weeks 0, 4, 8, and 12. Clinical scores, including Psoriasis Area Severity Index (PASI) and target lesion score (TLS), were evaluated at representative lesions. Dermoscopy was performed to assess the red background, vessels, and scales on a 4-point scale as well as the presence of hyperpigmentation, hemorrhagic spots, and linear vessels. HFUS was performed to measure the thicknesses of the superficial hyperechoic band and subepidermal hypoechoic band (SLEB). The correlation between clinical, dermoscopic, and ultrasonic evaluation was also analyzed. In total, 24 patients were analyzed and achieved 85.3 and 87.5% reduction of PASI and TLS, respectively, after 12 weeks of treatment. The red background, vessels, and scales scores under dermoscopy were reduced by 78.5, 84.1, and 86.5%, respectively. Some patients developed hyperpigmentation and linear vessels after treatment. Hemorrhagic dots slowly subside over the therapeutic course. Ultrasonic scores were significantly improved with an average reduction of 53.9% in superficial hyperechoic band thickness and 89.9% in SLEB thickness. TLS in the clinical variables, scales in dermoscopic variables, and SLEB in ultrasonic variables decreased the most significantly in the early stage of treatment (week 4) with 55.4, 57.7, and 59.1% (P > 0.05), respectively. Most of the variables, including the red background, vessels, scales, and SLEB thickness, were strongly correlated with TLS. High correlations were also found between the SLEB thickness and the red background or vessels scores, and between the superficial hyperechoic band thickness and the scales scores. Both dermoscopy and HFUS were useful in the therapeutic monitoring of moderate-to-severe plaque psoriasis.

Association of brain morphology and phenotypic profile in patients with unruptured intracranial aneurysm.

Studies have found a varying degree of cognitive, psychosocial, and functional impairments in patients with unruptured intracranial aneurysms (UIAs), whereas the neural correlates underlying these impairments remain unknown. To examine the brain morphological alterations and white matter lesions in patients with UIA, we performed a range of structural analyses to examine the brain morphological alterations in patients with UIA compared with healthy controls (HCs). Twenty-one patients with UIA and 23 HCs were prospectively enrolled into this study. Study assessment consisted of a brain magnetic resonance imaging (MRI) scan with high-resolution T1-weighted and T2-weighted imaging data, a Montreal Cognitive Assessment (MoCA), and laboratory tests including blood inflammatory markers and serum lipids. Brain MRI data were processed for cortical thickness, local gyrification index (LGI), volume and shape of subcortical nuclei, and white matter lesions. Compared to the HCs, patients with UIA showed no significant differences in cortical thickness but decreased LGI values in the right posterior cingulate cortex, retrosplenial cortex, cuneus, and lingual gyrus. In addition, decreased LGI values correlated with decreased MoCA score (r = 0.498, p = 0.021) and increased white matter lesion scores (r = -0.497, p = 0.022). The LGI values were correlated with laboratory values such as inflammatory markers and serum lipids. Patients with UIA also showed significant regional atrophy in bilateral thalami as compared to the HCs. Moreover, the LGI values were significantly correlated with thalamic volume in the HCs (r = 0.4728, p = 0.0227) but not in the patients with UIA (r = 0.11, p = 0.6350). The decreased cortical gyrification, increased white matter lesions, and regional thalamic atrophy in patients with UIA might be potential neural correlates of cognitive changes in UIA.

TSPO-Detectable Chronic Active Lesions Predict Disease Progression in Multiple Sclerosis.

In the multiple sclerosis (MS) brain, chronic active lesions can be detected using MRI- and PET-based methods. In this study, we investigated whether the frequency of TSPO-PET-detectable chronic active lesions associates with disease progression measured using the Expanded Disability Status Scale (EDSS) at 5-year follow-up. Chronic lesion-associated innate immune cell activation was evaluated using TSPO-PET in 82 patients with MS. Chronic lesions were categorized into rim-active, inactive, and overall active lesion subtypes based on innate immune cell activation patterns in the lesion core and at the 2-mm perilesional rim. Logistic regression was used to identify best predictors of progression. Twenty-one patients experienced disability progression during the follow-up. These patients had a significantly higher proportion of rim-active lesions (p < 0.001) and a significantly lower proportion of inactive lesions (p = 0.001) compared with nonprogressed patients. The results were similar in the patient group having no relapses during the follow-up (60 patients, 14 experienced progression). In logistic regression modeling, the categorized variable "patients with >10% rim-active lesions and ≤50% inactive lesions of all chronic lesions" predicted disease progression in the entire cohort (OR = 26.8, p < 0.001) and in the group free of relapses (OR = 34.8, p = 0.002). The results show that single TSPO-PET-based in vivo lesion phenotyping of chronic MS lesions provides a strong predictor for MS disease progression. This emphasizes the significance of chronic active lesions in disability accumulation in MS.

The impact of the experimental route of challenge on the host responses and pathogenesis of the Canadian Delmarva (DMV/1639) infectious bronchitis virus infection in laying chickens

Infectious bronchitis virus (IBV) infection can be associated with respiratory, renal, and/or reproductive diseases in chickens. Under natural conditions, conjunctiva, mucosa of upper respiratory tract, and cloaca are the main routes of IBV entry. Experimentally, the study of IBV infection involved various routes of inoculation. This study investigated the impact of adding the trachea as a potential route of viral entry to the oculo-nasal infection on the host responses, pathogenicity, and tissue tropism of the Canadian IBV Delmarva (DMV/1639) strain in laying chickens. Specific-pathogen-free laying chickens were divided into three experimental groups: control group (Con group), oculo-nasal challenged group (ON group), and oculo-nasal/intratracheal challenged group (ON/IT group); all groups were observed for 12 days post-infection (dpi). The clinical signs and reduction in egg production in the ON/IT group started slightly earlier compared to the ON group. At 12 dpi, the gross lesions in the ON/IT group were confined to the ovary, while the ON group showed regressed ovary and atrophied oviduct. Only the ON group showed significantly higher microscopic lesion scores in the lung, kidney, magnum, and uterus compared to the control group at 12 dpi. The oviduct tissues of the ON group showed a significant increase in B cells infiltration compared to ON/IT and control groups. The viral shedding (detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR)), tissue tropism (detected either by qRT-PCR or immunohistochemistry (IHC)), T/natural killer cells infiltration in reproductive tract (detected by IHC), and antibody-mediated immune responses (measured by enzyme-linked immunosorbent assay) showed similar patterns in the ON and ON/IT groups.

408 Dupilumab treatment in patients with atopic hand and foot dermatitis: results from a phase 3, randomized, double-blind, placebo-controlled trial

Abstract Atopic dermatitis (AD) of the hands and/or feet is often chronic, difficult to treat and substantially impacts patient quality of life. This study aims to report the effect of dupilumab treatment on signs, symptoms and quality of life in patients with atopic hand and foot dermatitis using dedicated clinical and patient reported instruments. The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients ≥12 years with moderate-to-severe [Investigator’s Global Assessment (IGA) 3/4] atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg q2w in adults; 200/300 mg every 2 weeks in adolescents, or placebo for 16 weeks. The primary endpoint was hand and foot IGA 0/1 score at Week 16. Safety/tolerability was assessed. The 133 patients enrolled were randomized to dupilumab (n = 67) or placebo (n = 66). At Week 16, the primary and all secondary endpoints were met. Significantly more patients in the dupilumab vs. placebo group achieved hand and foot IGA 0/1 (40.3% vs. 16.7%; P = 0.003; primary endpoint) and ≥4-point improvement in the hand and foot Peak Pruritus Numerical Rating Scale (52.2% vs. 13.6%; P &amp;lt; 0.0001; a key secondary endpoint). Dupilumab-treated patients experienced significant improvement in percent change from baseline in the modified Total Lesion Sign Score for hand and foot lesions vs. placebo [LS mean (SE) −69.4 (5.8) vs. −31.0 (5.9); P &amp;lt; 0.0001] and Hand Eczema Severity Index [HECSI; LS mean (SE) −74.8 (6.3) vs. −39.9 (6.2); P &amp;lt; 0.0001]. At Week 16, treatment with dupilumab also significantly increased the proportion of patients achieving a 75% improvement in HECSI (46.9% vs. 21.5%; P = 0.0028) and improved Quality of Life in Hand Eczema Questionnaire scores [LS mean (SE) −40.3 (4.0) vs. −16.2 (4.2); P &amp;lt; 0.0001]. The most common TEAEs (≥10%) were nasopharyngitis (16% vs. 11%) and dermatitis atopic (5% vs. 18%). Dupilumab significantly improved signs, symptoms and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis and had an acceptable safety profile.

High-Intensity Interval Training’s Effect on Cognitive Functions

HIIT has been known to improve cognitive function. In addition to its effect on the hippocampal area. After HIIT training, BDNF levels also increase in the spinal cord, cerebellum and several cortical areas through increasing levels of Insulin-like Growth Factor-1 (IGF-1). In neurons, BDNF is present not only in the cytoplasm, but also near the dendritic spines, which influences their development. BDNF stimulates the process of neuroplasticity, which is manifested in neurogenesis, stimulation of the plasticity of serotoninergic, dopaminergic, cholinergic or noradrenergic neurons, dendritogenesis, and synaptogenesis. Moreover, BDNF facilitates the growth and survival of neurons and microglial cells. It also participates in cell differentiation, potentiation of signal transmission, induction, and maintenance of long-term potentiation of the synapse enhancement. Because of these properties, BDNF enhances cognition and takes part in emotional processes, spatial orientation and learning, as well as body coordination. Evidence suggests that IGF-1 is a major determinant of the effect of physical exercise on BDNF levels and thus on cognition more generally. There is an upregulation of Fndc5 gene expression in skeletal muscle and an increase in irisin after prolonged resistance training in rats and humans following HIIT training. When hippocampal Fndc5 was upregulated during exercise, BDNF and other neuroprotective genes were also activated in the rat hippocampus. Exercise-induced adult hippocampal neurogenesis is associated with increased Fndc5 and BDNF genes thus enhancing cognition. Then, stroke is associated with neuroinflammation that affects the processes of neuroplasticity in the lesion core, penumbra and small areas such as the spinal cord.

Assessing diagnostic certainty for scurvy and rickets in human skeletal remains.

Identifying scurvy and rickets has important implications for understanding adaptations and variability among past communities, and bioarchaeologists now regularly evaluate these conditions. Due to the increased number of studies, cases with less clear-cut lesions and variable preservation are now frequently reported. Despite an improved understanding of the biological mechanisms for disease expression, there is a lack of consensus on the language used to express diagnostic certainty, limiting comparability. This article aims to address these issues and provide recommendations on more consistent diagnostic terminology using widely accepted diagnostic methodology based on biological mechanisms. We review diagnostic terms used in bioarchaeology by considering published cases of rickets, scurvy and co-occurrence alongside M.B.B.'s past project notes. We also consider differences in the diagnosis of rickets and scurvy in living and archeological individuals. We provide recommendations on a framework that can be used to show diagnostic certainty in cases of rickets, scurvy, and co-occurrence. Core lesions of rickets and scurvy are used alongside a limited lexicon of diagnostic terminology based on the Istanbul protocol. It is not the number of lesions that determines whether an individual is assigned to a particular diagnosis category, but rather the range and expression of lesions present. Avoiding a "tick-list" approach to core lesions of these diseases will be critical to ensure that identifying rickets and scurvy continues to contribute to understanding adaptations and variability among past communities. The framework allows more consistency in diagnostic certainty, facilitating greater comparability in research.

Effects of dietary nano-selenium supplementation on Riemerella anatipestifer vaccinated and challenged Pekin ducklings (Anas platyrhynchos)

Riemerella anatipestifer (RA) is a common disease causing economic losses to duck farms worldwide. Novel supplements are crucially needed to control this bacterium, enhance poultry performance, and produce synergistic effects with vaccines in stimulating the immune system. This study investigated the effect of nano-selenium (Nano-Se) on the vaccinated (VAC) and challenged (Ch) Pekin ducklings (Anas platyrhynchos) with RA. Five experimental groups (G1-G5) were included in this study: G1 was the control group, G2 was the RA-challenged group, G3 was the Nano-Se+Ch group, G4 was the VAC+Ch group, and G5 was the Nano-Se+VAC+Ch group. The Nano-Se (0.3 mg/kg diet) was supplemented for 5 weeks post-vaccination (PV). The ducklings were vaccinated subcutaneously with the RA vaccine at 7 days of age and challenged with RA at the 3rd week PV. Blood, pharyngeal swabs and tissue samples were collected at the 3rd week PV and at different times post-challenge (PC). The growth performance (weight gain and feed conversion ratio), clinical signs, gross lesions, mortality, bacterial shedding, haematological, immunological, and biochemical parameters, cytokines production, and histopathological lesion scores showed significant differences (P < 0.05) between the challenged (G2) group and the supplemented (G3 & G5) groups. G5 showed the highest (P < 0.05) growth performance, phagocytic activity, IgM and IgG, splenic interleukin-2 (IL-2), IL-10, and interferon-gamma (IFN-γ) gene expressions, and the lowest mortality, bacterial shedding, hepatic and renal damage, heterophil/lymphocyte ratio and lesion scores compared to the other groups. In conclusion, the supplementation of nano-selenium for five weeks in the diet can improve the growth performance, immune status, and cytokines production in ducklings vaccinated and challenged with RA.

Trehalose-Guanosine Glycopolymer Hydrogels Direct Adaptive Glia Responses in CNS Injury.

Neural tissue damaged after central nervous system (CNS) injury does not naturally regenerate but is instead replaced by non-neural fibrotic scar tissue that serves no neurological function. Scar-free repair to create a more permissive environment for regeneration requires altering the natural injury responses of glial cells. In this work, glycopolymer-based supramolecular hydrogels are synthesized to direct adaptive glia repair after CNS injury. Combining poly(trehalose-co-guanosine) (pTreGuo) glycopolymers with free guanosine (fGuo) generates shear-thinning hydrogels through stabilized formation of long-range G-quadruplex secondary structures. Hydrogels with smooth or granular microstructures and mechanical properties spanning three orders of magnitude are produced through facile control of pTreGuo hydrogel composition. Injection of pTreGuo hydrogels into healthy mouse brains elicits minimal stromal cell infiltration and peripherally derived inflammation that is comparable to a bioinert methyl cellulose benchmarking material. pTreGuo hydrogels alter astrocyte borders and recruit microglia to infiltrate and resorb the hydrogel bulk over 7d. Injections of pTreGuo hydrogels into ischemic stroke alter the natural responses of glial cells after injury to reduce the size of lesions and increase axon regrowth into lesion core environments. These results support the use of pTreGuo hydrogels as part of neural regeneration strategies to activate endogenous glia repair mechanisms.

#4154 CIRCULATING BETA-TRACE PROTEIN VERSUS CREATININE AS MARKERS OF EARLY KIDNEY (DYS)FUNCTION IN THE NX-INDUCED RAT MODEL OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Beta trace protein (BTP) is a low molecular weight protein that has been proposed as an earlier biomarker of decreased glomerular filtration rate (GFR) and renal damage, than the traditional biomarkers, particularly in the creatinine blind range. Early biomarkers of renal (dys)function are needed to allow, in due time, the detection and treatment, to prevent worsening of the disease. To the authors’ knowledge, neither urine nor serum BTP has been assessed in animals with kidney disease. In the present study, we aimed to concomitantly evaluate BTP and creatinine circulating levels, to compare their value as early biomarkers of renal dysfunction, by performing the studies in rat models of mild and moderate chronic renal failure (CRF) induced by nephrectomy. Method Male Wistar rats, 12 weeks old, were randomly divided in three groups: Sham (n = 8, subjected to surgical process without kidney mass reduction), Mild CRF (n = 8, subjected to 1/2 nephrectomy), and Moderate CRF (n = 7, subjected to 5/6 nephrectomy). After five weeks, rats were sacrificed, blood and kidneys were collected. We analysed the circulating levels of BTP and creatinine and studied the association of BTP concentration with the glomerular and tubulointerstitial lesions, and with the traditional biomarkers of renal (dys)function, eGFR and creatinine. Results The serum levels of BTP were correlated with serum levels of creatinine (r = 0.575, p = 0.004) and also with eGFR (r = -0.453, p = 0.030); additionally, we found positive correlations with the total score of mild and advanced tubular lesions (r = 0.610, p = 0.02 and r = 0.517, p = 0.011, respectively), observed in kidney sections. The circulating levels of BTP increased with disease severity; Mild CRF showed a higher value of BTP than Sham group, although without statistical significance that was reached in Moderate CRF group, as observed for serum creatinine. The combined use of BTP and creatinine did not improve the discriminatory power in early disease detection. Though, the combination showed stronger correlations with the total score of tubular lesions (r = 0.849, p &amp;lt; 0.001 for mild tubular lesions and r = 0.774, p &amp;lt; 0.01 for advanced tubular lesions). Conclusion In rat models of mild and moderate CRF induced by nephrectomy, serum BTP levels increased with kidney function worsening, and correlated with disease severity, assessed by GFR and the degree of histopathological alterations. However, the earlier diagnostic value of BTP does not outperform serum creatinine in this model.

Research progress on deep learning in magnetic resonance imaging-based diagnosis and treatment of prostate cancer: a review on the current status and perspectives.

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a first-line screening and diagnostic tool for prostate cancer, aiding in treatment selection and noninvasive radiotherapy guidance. However, the manual interpretation of MRI data is challenging and time-consuming, which may impact sensitivity and specificity. With recent technological advances, artificial intelligence (AI) in the form of computer-aided diagnosis (CAD) based on MRI data has been applied to prostate cancer diagnosis and treatment. Among AI techniques, deep learning involving convolutional neural networks contributes to detection, segmentation, scoring, grading, and prognostic evaluation of prostate cancer. CAD systems have automatic operation, rapid processing, and accuracy, incorporating multiple sequences of multiparametric MRI data of the prostate gland into the deep learning model. Thus, they have become a research direction of great interest, especially in smart healthcare. This review highlights the current progress of deep learning technology in MRI-based diagnosis and treatment of prostate cancer. The key elements of deep learning-based MRI image processing in CAD systems and radiotherapy of prostate cancer are briefly described, making it understandable not only for radiologists but also for general physicians without specialized imaging interpretation training. Deep learning technology enables lesion identification, detection, and segmentation, grading and scoring of prostate cancer, and prediction of postoperative recurrence and prognostic outcomes. The diagnostic accuracy of deep learning can be improved by optimizing models and algorithms, expanding medical database resources, and combining multi-omics data and comprehensive analysis of various morphological data. Deep learning has the potential to become the key diagnostic method in prostate cancer diagnosis and treatment in the future.

Efficacy and tolerance of a novel topical TRPV-1 channel antagonist in dogs with allergic pododermatitis.

Pruritus due to allergic skin disease is one of the most common reasons for dermatological consultations in the veterinary clinic. Treatment is usually multimodal and requires continuous monitoring and reassessment. New therapies are needed to broaden the therapeutic arsenal. The aim of this study was to evaluate the efficacy of a novel transient receptor potential vanilloid 1 (TRPV1) channel antagonist for allergic pododermatitis in dogs. Twenty-four client-owned dogs with allergic pododermatitis. The study was an open, prospective, multi-centreclinical trial with client-owned dogs. All dogs were treated twice daily with a spray containing hydroxymethoxyiodobenzyl glycolamide pelargonate for 28 days. Clinical assessments included pruritus Visual Analog Scale (PVAS), pedal skin lesion score, evaluation of quality of life (QoL), presence of secondary infections and a four-point subjective efficacy assessment by the veterinarian and the dog owner. There was more than 50% improvement in all scores by the conclusion of the study. Secondary infections were reduced (p < 0.001). Both the veterinarians and dog owners evaluated the efficacy of the product positively. The product was well-tolerated. This study demonstrated the tolerability and efficacy of a TRPV1 antagonist on pruritic pododermatitis in 24 dogs.

Hyperimmune egg yolk antibodies developed against Clostridium perfringens antigens protect against necrotic enteritis

Necrotic enteritis (NE) is a widespread infectious disease caused by Clostridium perfringens that inflicts major economic losses on the global poultry industry. Due to regulations on antibiotic use in poultry production, there is an urgent need for alternative strategies to mitigate the negative effects of NE. This paper presents a passive immunization technology that utilizes hyperimmune egg yolk immunoglobulin Y (IgY) specific to the major immunodominant antigens of C. perfringens. Egg yolk IgYs were generated by immunizing hens with 4 different recombinant C. perfringens antigens, and their protective effects against NE were evaluated in commercial broilers. Six different spray-dried egg powders were produced using recombinant C. perfringens antigens: α-toxin, NE B-like toxin (NetB; EB), elongation factor-Tu (ET), pyruvate:ferredoxin oxidoreductase, a mixture of 4 antigens (EM-1), and a nonimmunized control (EC). The challenged groups were either provided with different egg powders at a 1% level or no egg powders (EN). The NE challenge model based on Eimeria maxima and C. perfringens dual infection was used. In Experiments 1 and 2, the EB and ET groups exhibited increased body weight gain (BWG; P < 0.01), decreased NE lesion scores (P < 0.001), and reduced serum NetB levels (P < 0.01) compared to the EN and EC groups. IgY against NetB significantly reduced Leghorn male hepatocellular cytotoxicity in an in vitro test (P < 0.01). In Experiment 3, the protective effect of the IgYs mixture (EM-2) against C. perfringens antigens (NetB and EFTu) and Eimeria antigens (elongation factor-1-alpha: EF1α and Eimeria profilin: 3-1E) was tested. The EM-2 group showed similar body weight, BWG, and feed intake from d 7 to 22 compared to the NC group (P < 0.05). On d 20, the EM-2 group showed comparable intestinal permeability, NE lesion scores, and jejunal NetB and collagen adhesion protein levels to the NC group (P < 0.05). In conclusion, dietary mixture containing antibodies to NetB and EFTu provides protection against experimental NE in chickens through passive immunization.