ABSTRACT
The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The DNA-only vaccine regimens were compared to a regimen that included co- immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques. Author summaryAnti-Spike neutralizing antibodies provide strong protection against SARS-CoV-2 infection in animal models, and correlate with protection in humans, supporting the notion that induction of strong humoral immunity is key to protection. We show induction of robust antibody and T cell responses by different Spike DNA-based vaccine regimens able to effectively mediate protection and to control SARS-CoV-2 infection in the rhesus macaque model. This study provides the opportunity to compare vaccines able to induce different humoral and cellular immune responses in an effort to develop durable immunity against the SARS-CoV-2. A vaccine regimen comprising simultaneous co-immunization of DNA and Protein at the same anatomical site showed best neutralizing abilities and was more effective than DNA alone in inducing protective immune responses and controlling SARS-CoV-2 infection. Thus, an expansion of the DNA vaccine regimen to include co-immunization with Spike protein may be of advantage also for SARS-CoV-2.
ABSTRACT
INTRODUCTION: Dapoxetine is considered a first-line treatment for patients with lifelong premature ejaculation (PE), and current researches have showed with functional magnetic resonance imaging (fMRI) that patients with lifelong PE might have abnormal brain function, but differences in brain function before and after administration have not been reported. AIM: The aim of this study was to determine some objective differences in brain function between patients with lifelong PE before and after administration and healthy individuals. METHODS: In this study, 17 patients with lifelong PE and 11 healthy controls underwent clinical assessments and resting-state fMRI examination. After 4 weeks of treatment with dapoxetine 30 mg as needed, patients with PE underwent the same fMRI examination again 3 hours after dapoxetine administration. MAIN OUTCOME MEASURE: The data were preprocessed using a data processing assistant for resting-state fMRI, and voxelwise amplitude of low-frequency fluctuation (ALFF) maps was calculated to identify abnormal neural activity in the brain. RESULTS: (a) The ALFF of patients with PE was significantly lower in the bilateral hippocampus and thalamus and higher in the left fusiform and lingual gyrus than that of healthy controls; (b) decreased and increased ALFF in patients with PE recovered after dapoxetine administration. CONCLUSION: We preliminarily identified the relevant sites by analyzing changes in the ALFF in patients with lifelong PE. Analyzing ALFF changes in the brain by resting-state fMRI is an effective method to study PE, and it might provide a reference for disease diagnosis and future research. Yubo M, Lianjia H, Cuiping M, et al. Changes in the Amplitude of Low-Frequency Fluctuation in Patients With Lifelong Premature Ejaculation by Resting-State Functional MRI. Sex Med 2021;9:100287.
ABSTRACT
Objective: To observe the effect of Turbohawk atherectomy combined with percutaneous transluminal angioplasty (PTA) using drug-coated balloon (DCB) for treatment of in-stent restenosis (ISR) after femoropopliteal artery stent implantation. Methods: Clinical data of 63 ISR patients after femoropopliteal artery stent implantation were retrospectively analyzed. The patients were divided into 2 groups, those in observation group (n=28) were treated with atherectomy combined with DCB, while in control group (n=35) were treated with DCB alone. The therapeutic effect and prognosis were compared between 2 groups. Results: All 63 patients were successfully treated without death nor amputation. There was no significant difference of ankle brachial index (ABI) before procedure, 7 days and 6 months after procedure between 2 groups. The difference of minimum lumen diameter (MLD) before procedure, immediately and 6 months after procedure were not statistically significant (all P> 0.05). ABI and MLD in the observation group were higher than those in control group 12 months after procedure, while the rate of late lumen loss (LLL) was lower than that in control group (both P 0.05), while primary patency rate of observation group was higher than that of control group 12 months after procedure (P=0.028). Conclusion: Atherectomy combined with DCB is effective in treatment of femoropopliteal artery ISR, especially in the near and middle terms.
