Sex Differences of Acute Stroke Treatment and in Hospital Outcomes After Intravenous Thrombolysis in Patients With Ischemic Stroke.

Background: Many studies have suggested that the clinical features of male patients with ischemic stroke are different from those of female patients, but related data on Chinese patients are scarce. Therefore, this study aimed to identify the differences in treatment delays, complications related to intravenous thrombolysis, and prognosis between male and female patients with ischemic stroke in China. Methods: The data of patients with ischemic stroke who received intravenous thrombolysis were retrospectively analyzed. The data were obtained from the China Hospital Stroke Registry from January 2017 to April 2019. The general clinical characteristics, onset-to-door time, door-to-needle time, complications related to thrombolysis, National Institute of Health Stroke Scale (NIHSS) scores, and in-hospital mortality were compared between male and female patients to identify any sex differences in these factors. A multi-factorial analysis was conducted to explore whether sex is associated with in-hospital mortality and complications of intracerebral hemorrhage after thrombolysis. Results: A total of 26,475 patients with ischemic stroke who received intravenous thrombolysis were involved in the study. The data were collected from 902 hospitals in 29 provinces, autonomous regions, and municipalities in China. The door-to-needle time was longer in female than in male patients (49 [35, 67] vs. 48 [35, 65], P = 0.008). Furthermore, the frequencies of intracerebral hemorrhage (4.1 vs. 3.2%, P < 0.001) and in-hospital mortality (2.55 vs. 1.83%, P < 0.001) were higher in female vs. male patients. However, sex was not associated with intracerebral hemorrhage and in-hospital mortality according to the adjusted multi-factorial analysis. In addition, improvement in NIHSS scores was greater in female patients than in male patients [-3 (-6, -1) vs. -3 (-5, -1), P = 0.036]. Conclusions: After adjusting for other predictors sex was not associated with intracerebral hemorrhage after thrombolysis or in-hospital mortality. Further study is warranted to evaluate the long-term outcomes in the different sexes.

Systemic infection and limited replication of SHIV vaccine virus in brains of macaques inoculated intracerebrally with infectious viral DNA.

SHIV deleted in two accessory genes, DeltavpuDeltanef SHIV(PPC), functioned well as a vaccine against later challenge with highly pathogenic SHIV(KU), and it was able to reach the brain after oral inoculation of live virus. In this study, the proviral genome cloned into a plasmid was inoculated as DNA intracerebrally and spread systemically. Few regions of the brain had detectable proviral DNA by real-time PCR. Two measures of virus replication, detection of viral mRNA expression and circular proviral DNA, were negative for those brain regions, with the exception of the infection site in the right parietal lobe, whereas lymphoid tissues were positive by both measures. Histopathological analyses of all the sampled brain and spinal cord regions did not reveal any abnormalities. Despite intracerebral inoculation of the viral DNA, the brain was not targeted for high levels of virus replication.

Presence of Intact vpu and nef genes in nonpathogenic SHIV is essential for acquisition of pathogenicity of this virus by serial passage in macaques.

Use of the macaque model of human immunodeficiency virus (HIV) pathogenesis has shown that the accessory genes nef and vpu are important in the pathogenicity of simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV). We examined the ability of two nonpathogenic SHIVs, SHIV(PPC) and DeltavpuDeltanefSHIV(PPC), to gain pathogenicity by rapid serial passage in macaques. In this study, each virus was passaged by blood intravenously four times at 4-week intervals in macaques. Animals were monitored for 40 weeks for levels of CD4 T cells and quantitative measures of virus infection. DeltavpuDeltanefSHIV(PPC) maintained a limited phase of productive replication in the four animals, with no loss of CD4(+) T cells, whereas SHIV(PPC) became more pathogenic in later passages, judging by plasma viral load and viral mRNA in lymph nodes, infectious peripheral blood mononuclear cells and CD4(+) T cell loss. The nef, LTR, and env of the SHIV(PPC) viruses underwent numerous mutations, compared to DeltavpuDeltanefSHIV(PPC). This study confirms the seminal role that nef, LTR, and vpu could play in regulation of pathogenesis of HIV infection.