Serum uric acid to serum creatinine ratio predicts neurological deterioration in branch atheromatous disease

Background and objectiveBranch atheromatous disease (BAD) makes patients prone to early neurological deterioration (END), resulting in poor prognosis. The aim of this study was to investigate the association between SUA/SCr and END in BAD stroke patients.MethodsWe conducted a retrospective study that included 241 patients with BAD-stroke within 48 h of symptom onset. We divided the patients into the END group and the no END group. END was defined as an NIHSS score increase of more than 2 points within 1 week. SUA/SCr was calculated by the concentration of serum uric acid and creatine (serum uric acid/serum creatine) on admission. Univariate and multivariate analyses were used to identify independent predictors of END in BAD-stroke patients.ResultsEND was observed in 24.1% (58/241) of the patients in our study. Multiple logistic regression analyses showed that SUA/SCr (aOR, 0.716; 95% CI, 0.538–0.952; P = 0.022) and female sex (aOR, 0.469; 95% CI, 0.245–0.898; P = 0.022) were associated with END after adjusting for confounding factors. The predicted value of SUA/Scr for END was a sensitivity of 79.3%, a specificity of 44.8%, and an AUC of 0.609 (95% CI, 0.527–0.691, P < 0.05). The optimal cut-off value was 4.76.ConclusionSUA/SCr was negatively associated with the risk of END in BAD stroke patients

A Recombinant Vaccine of H5N1 HA1 Fused with Foldon and Human IgG Fc Induced Complete Cross-Clade Protection against Divergent H5N1 Viruses

Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus

Convergent, Parallel and Correlated Evolution of Trophic Morphologies in the Subfamily Schizothoracinae from the Qinghai-Tibetan Plateau

Schizothoracine fishes distributed in the water system of the Qinghai-Tibetan plateau (QTP) and adjacent areas are characterized by being highly adaptive to the cold and hypoxic environment of the plateau, as well as by a high degree of diversity in trophic morphology due to resource polymorphisms. Although convergent and parallel evolution are prevalent in the organisms of the QTP, it remains unknown whether similar evolutionary patterns have occurred in the schizothoracine fishes. Here, we constructed for the first time a tentative molecular phylogeny of the schizothoracine fishes based on the complete sequences of the cytochrome b gene. We employed this molecular phylogenetic framework to examine the evolution of trophic morphologies. We used Pagel's maximum likelihood method to estimate the evolutionary associations of trophic morphologies and food resource use. Our results showed that the molecular and published morphological phylogenies of Schizothoracinae are partially incongruent with respect to some intergeneric relationships. The phylogenetic results revealed that four character states of five trophic morphologies and of food resource use evolved at least twice during the diversification of the subfamily. State transitions are the result of evolutionary patterns including either convergence or parallelism or both. Furthermore, our analyses indicate that some characters of trophic morphologies in the Schizothoracinae have undergone correlated evolution, which are somewhat correlated with different food resource uses. Collectively, our results reveal new examples of convergent and parallel evolution in the organisms of the QTP. The adaptation to different trophic niches through the modification of trophic morphologies and feeding behaviour as found in the schizothoracine fishes may account for the formation and maintenance of the high degree of diversity and radiations in fish communities endemic to QTP

The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates

Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant

The clinical prognostic significance of hs-cTnT elevation in patients with acute ischemic stroke

Abstract Background Cardiac autonomic dysfunction caused by ischemic stroke might lead to an adverse outcome. Elevated high sensitivity cardiac troponin (hs-cTnT) is a marker of cardiac disease, it can elevate in acute stroke patients. The aim of the present study was to investigate association between serum hs-cTnT with prognosis among patients with acute ischemic stroke. Methods Five hundred and sixteen patients (mean age 66.19 ± 10.11) with acute ischemic stroke underwent a comprehensive clinical investigation and serum hs-cTnT activity test. All patients were followed up for 3 months. The prognosis was death or major disability (modified Rankin Scale score ≥ 3) at 3 months after acute ischemic stroke. Results 22.87% (118/516) of patients had serum hs-cTnT elevation (≥14 ng/l). Compared with normal hs-TnT group, the incidence of insular stroke (adjusted odds ratio, 2.84; 95% confidence interval, 1.48–4.17; P = 0.001) were more likely in patients with hs-cTnT elevation. In fully adjusted models, there was an association between serum hs-cTnT elevation and death (adjusted odds ratio, 3.14; 95% confidence interval, 1.16–8.49; P = 0.02) and major disability(adjusted odds ratio, 2.07; 95% confidence interval, 1.04–4.51; P = 0.04), and composite outcome(adjusted odds ratio,2.22;95% confidence interval,1.10–4.48; P = 0.03). Conclusions Higher levels of serum hs-cTnT were independently associated with increased risk of death or major disability after stroke onset, suggesting that serum hs-cTnT may have prognostic value in poor outcomes of ischemic stroke

Laryngeal myasthenia gravis following influenza vaccination: a case report and literature review

Background Myasthenia gravis (MG) is an autoimmune disease of acquired neuromuscular junction transmission disorder mediated by auto-antibodies. Extranophthalmic muscles are the most susceptible to MG, while the larynx muscle may also be affected. MG can be aggravated by various types of drugs. In the present study, a patient with laryngeal MG who received an influenza vaccination 5 days before onset was treated, which has not been previously reported. Case presentation A 58-year-old Asian woman developed mild dysphagia and severe dysarthria five days after receiving a trivalent inactivated influenza vaccine. The patient’s quantitative MG score was 4 (1 for swallowing and 3 for speech), and the patient’s neurological symptoms varied. The serum acetylcholine receptor (AChR) antibody titer was 0.67 nmol/L (normal range below 0.2 nmol/L), and other immunological and thyroid function tests were negative. As revealed by chest computed tomography (CT), there was no thymus abnormality. Based on the patient’s history, clinical features, and examination results, the patient was diagnosed with laryngeal MG. The patient received pyridostigmine oral administration (60 mg/d) and steroid therapy (Prednisone, oral, 60 mg/d). The patient’s symptoms began to improve after 7 days of treatment, and were significantly relieved after 2 weeks. Conclusion Influenza vaccination might cause an unexpected abnormal autoimmune response in MG as a very rare event. Further research is needed to assess the possible causal relationship between the influenza vaccine and neurological complications, also in addition to the safety of the vaccine

Predictive factors for early neurological deterioration after intravenous thrombolysis of single subcortical infarction in the territory of the middle cerebral artery

Abstract Introduction Patients with a single subcortical infarction (SSI) in the territory of the middle cerebral artery (MCA) often experience early neurological deterioration (END) despite receiving intravenous thrombolytic therapy (IVT). In this study, predictors of END were investigated in patients with SSI in the MCA after IVT. Methods Patients with SSI in the MCA territory who had received IVT between June 2020 and 2022 were included. END was defined as an increase in the total National Institutes of Health Stroke Scale (NIHSS) score by ≥2 or in the motor NIHSS score by ≥1 within the first 72 h of admission. Patients with proximal (pSSI) and distal SSI (dSSI) were analyzed to determine SSI type‐specific predictors for END. Results We evaluated 174 patients with SSI in the MCA territory who underwent IVT. Multivariable logistic regression analysis showed that pSSI (odds ratio [OR] = 0.242; 95% confidence interval [CI], 0.104–0.564; p = .001), lower high‐density lipoprotein cholesterol (HDL‐C) (OR = 0.150; 95% CI, 0.033–0.682; p = .014), higher blood glucose (OR = 0.858; 95% CI, 0.752–0.979; p = .023), and higher red blood cells count (OR = 1.966; 95% CI, 1.154–3.349; p = .013) were risk factors for END. In patients with pSSI, HDL‐C and blood glucose were associated with END. No variable related to END was found in the dSSI group. Conclusions The proportion of END in patients with SSI in the MCA territory after IVT was not low; therefore, pSSI, HDL‐C, blood glucose, and red blood cells should be monitored closely. The frequency and predictors of SSI in the MCA territory differed between pSSI and dSSI