Pathogenicity and immunogenicity of gI/gE/TK-gene-deleted Felid herpesvirus 1 variants in cats.

BACKGROUND: Felid herpesvirus 1 (FHV-1) is a major pathogenic agent of upper respiratory tract infections and eye damage in felines worldwide. Current FHV-1 vaccines offer limited protection of short duration, and therefore, do not reduce the development of clinical signs or the latency of FHV-1. METHODS: To address these shortcomings, we constructed FHV ∆gIgE-eGFP, FHV ∆TK mCherry, and FHV ∆gIgE/TK eGFP-mCherry deletion mutants (ΔgI/gE, ΔTK, and ΔgIgE/TK, respectively) using the clustered regularly interspaced palindromic repeats (CRISPR)/CRISP-associated protein 9 (Cas9) system (CRISPR/Cas9), which showed safety and immunogenicity in vitro. We evaluated the safety and efficacy of the deletion mutants administered with intranasal (IN) and IN + subcutaneous (SC) vaccination protocols. Cats in the vaccination group were vaccinated twice at a 4-week interval, and all cats were challenged with infection 3 weeks after the last vaccination. The cats were assessed for clinical signs, nasal shedding, and virus-neutralizing antibodies (VN), and with postmortem histological testing. RESULTS: Vaccination with the gI/gE-deleted and gI/gE/TK-deleted mutants was safe and resulted in significantly lower clinical disease scores, fewer pathological changes, and less nasal virus shedding after infection. All three mutants induced virus-neutralizing antibodies after immunization. CONCLUSIONS: In conclusion, this study demonstrates the advantages of FHV-1 deletion mutants in preventing FHV-1 infection in cats.

Correlation study between multiplanar reconstruction trigeminal nerve angulation and trigeminal neuralgia.

OBJECTIVES: Neurovascular compression (NVC) produces morphological changes on the trigeminal nerve root is considered the cause of trigeminal neuralgia (TN), but there were some patients with TN found no NVC, and also NVC was found in asymptomatic individuals. Many studies found tight relationships of TN and morphological structures of trigeminal nerve. We designed this study to explore the correlation between multiplanar reconstruction (MPR) trigeminal nerve angulation (TNA) and TN. METHODS: Patients with classical symptoms of TN were recruited as observation group (OG) in this study, 50 healthy controls were enrolled as control group (CG), the OG was further subtyped into young patients (YP), middle-aged patients (MP) and old patients (OP) based to the onset age of symptoms, and also divided into patients with or without trigger maneuvers (TM) based on the presence of TM or not. All the participants underwent magnetic resonance (MR) examinations in same device, bilateral TNA measurements were carried out in OG and CG, then TNA was compared between different groups or subgroups. All images were interpreted by two radiologists who were blinded to the study, diagnosis of TN was made by two senior neurosurgery professors. RESULT: Ultimately, 95 patients with primary TN were recruited in OG, aged from 25 to 84 (61.15 ± 12.70) years with a course of 0.5 to 30 (5.03 ± 5.41) years, their onset age ranged from 24 to 82 (56.13 ± 11.98) years. There were 34 males and 61 females in OG, and 58 cases involved right side. The CG aged from 22 to 85 (61.86 ± 13.03) years. No statistical difference was found between the age of OG and CG(p = 0.76), and also the bilateral TNA of CG (154.92 ± 16.90° vs 155.55 ± 17.03°, p > 0.05), while TNA of OG was significantly smaller than CG (150.78 ± 11.29° vs 155.24 ± 16.88°, p = 0.019). In OG, TNA on the affected side was significantly smaller than the unaffected side (149.29 ± 12.44° vs 152.27 ± 9.85°, p = 0.014). TNA showed a positive correlation with onset age of patients with TN, as TNA on the affected side of YP was significantly smaller than MP and OP (139.00 ± 11.64° vs 148.86 ± 11.54°, 139.00 ± 11.64° vs 152.18 ± 12.61°, p = 0.004 and 0.026). Furthermore, patients with TM showed smaller TNA than those without TM (147.05 ± 11.30° vs 164.75 ± 8.39°, p < 0.001). CONCLUSIONS: This study suggested that TNA might play a role in TN, small TNA could be a risk factor of TN. Furthermore, patients with small TNA are more likely to combine with TM, but more studies are needed to explore the exact role of TNA in TN.

Microvascular decompression for trigeminal neuralgia caused by persistent trigeminal artery associated with craniosynostosis: a case report.

BACKGROUND: Persistent trigeminal artery (PTA) is a rare arterial anastomosis between the basilar artery (BA) and internal carotid artery (ICA). It plays an indispensable role in a number of neurological disorders, including trigeminal neuralgia (TN). CASE PRESENTATION: We report a unique case of a 58-year-old Han female patient with TN caused by PTA associated with craniosynostosis. Preoperative three-dimensional time-of-flight (3D-TOF) magnetic resonance (MR) and 3D constructive inference in steady state (3D-CISS) imaging showed that the PTA run though Meckel's cave. Complete pain relief was immediately achieved after microvascular decompression (MVD), without facial numbness and other complications. No recurrence was recorded at the 1-year follow up. CONCLUSIONS: Microvascular decompression is a feasible option for the treatment of complex TN combined with other abnormalities. For patients deemed suitable for percutaneous balloon compression, PTA should be ruled out. Preoperative 3D-TOF and 3D-CISS MR imaging were essential to identify PTA neurovascular conflicts.

Selection of glucocorticoid-sensitive patients in interstitial lung disease secondary to connective tissue diseases population by radiomics.

PURPOSE: The effect of glucocorticoid(s) on connective tissue disease (CTD)-related interstitial lung disease (ILD) is controversial. This multicenter study aimed to identify glucocorticoid-sensitive patients using a radiomics approach. METHODS: A total of 416 CTD-ILD patients who began glucocorticoid treatment at the discretion of the attending physician, with or without cyclophosphamide, were included in this study. High doses were defined as pulsed intravenous methylprednisolone, an initial dose of 1 mg/kg/day of prednisolone or 0.8 mg/kg/day of methylprednisolone. Low doses were defined as those less than high doses. Radiomics features were manually extracted from primary lung lesions delineated on computed tomography images, and selected by variance, univariate feature selection, and least absolute shrinkage and selection operator regression model. The prediction models were developed using data from 309 patients from two centers and externally validated in 107 patients from four other hospitals. RESULTS: Treatment response in the training and validation groups was 38.5% and 36.4%, respectively. Eleven radiomics features were selected from 1,029 features with predictive value. Random forest models built for radiomics features to predict treatment response yielded a sensitivity of 0.897. The calibration curve of a nomogram demonstrated good agreement between prediction and observation. Decision curve analysis indicated that glucocorticoid was beneficial if the predicted response rate was 50%-60% for an individual. High doses of glucocorticoids and cyclophosphamide yielded superior efficacy. CONCLUSION: Radiomics-based predictive models reliably identified glucocorticoid-sensitive CTD-ILD patients. Short-term, high-dose glucocorticoid with cyclophosphamide yielded promising results as a potential therapy.