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Objective: To comprehensively describe the pathological features of neurons in patients with ovarian teratomas and paraneoplastic anti-NMDAR encephalitis (anti-NMDARE), emphasizing on NMDA-receptor expression and infiltrating lymphocytes. Methods: A retrospective study was performed in a large series of 159 patients from the West China Hospital. We retrospectively identified 12 patients with paraneoplastic anti-NMDARE (11 case with ovarian teratomas and 1 case with mixed germ cell tumor), which were compared to 35 patients with teratomas and no encephalitis and to 147 patients with anti-NMDARE and no evidence for tumors. Patient history and outcome were reviewed from the clinical charts and compared between all three groups. Histopathological examination, including double-immunofluorescence of NMDAR subunits and IgG was performed in all teratoma tissues. Magnetic Luminex Assay Human Premixed Multi-Analyte Kit was performed to investigate cytokines profile of CSF. Results: Patients with paraneoplastic anti-NMDARE had a more severe clinical presentation, i.e. they required more mechanical ventilation and intensive care (p < 0.001). Though immunotherapy was initiated earlier in this group, repeated intravenous immunoglobulin administration (IVIG) was more common (p = 0.002) and with higher cerebrospinal fluid (CSF) antibody titres (p = 0.004). Following tumor resection, the outcome did not differ between groups. A peculiar population of floating-frog like dysplastic neurons were observed only in teratomas of patients with paraneoplastic anti-NMDARE, co-expressing NR1, NR2A, NR2B subunits and IgG. Also, CD20 positive B-cells were more common in anti-NMDARE teratomas. In CSF of paraneoplastic anti-NMDARE patients, TNF-α, IL-10 and GM-CSF concentrations were higher than in negative symptom control and VEGF-A and IL-1a were lower than in anti-NMDARE patients (0.25 < p < 0.05). Conclusions: Patients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE. Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE. [ABSTRACT FROM AUTHOR]

Background and objective Allergy is a potential outcome of dysregulated immune system. Previous studies have shown the association of allergy and autoimmune diseases, however, there is few study to investigate the relationship between allergy and anti- N -methyl- d -aspartate receptor (anti-NMDAR) encephalitis. Thus, we investigate the rate of allergy in patients with anti-NMDAR encephalitis and analyze the risk factors. Method The rate of allergy was investigated in patients with anti-NMDAR encephalitis and was compared with patients with virus encephalitis. The clinical cutaneous characters were described in details. All patients with anti-NMDAR encephalitis were divided into allergic and nonallergic group. Clinical factors were compared in the two groups, and logistic regression model was also used to analyze possible risk factors of allergy. Results Patients with anti-NMDAR encephalitis had a higher rate of allergy than those with viral encephalitis (22.1% vs 9.2%, odds ratio (OR) = 3.23, confidence interval (CI) = 1.40–7.42, P = 0.006). In patients with anti-NMDAR encephalitis, allergic patients exhibited longer days in hospital (30 days vs 22 days, P = 0.005) and higher occurrence of decreased consciousness (81.5% vs 58.9%, P = 0.031), higher rate of complications (77.8% vs 57.9%, P = 0.046) and abnormal electroencephalography (EEG) (100% vs 78.6%, P = 0.021) than patients without allergy. Cerebrospinal fluid (CSF) antibody titers of allergic patients during the disease course were also higher than nonallergic patients (P = 0.004). However, further logistic regression analysis did not reveal independent predictors of allergy. Conclusions Patients with anti-NMDAR encephalitis show higher allergic rate than those with virus encephalitis. Patients with allergy show higher CSF antibody titers and greater illness severity. However, the final outcome of anti-NMDAR encephalitis was not influenced. [ABSTRACT FROM AUTHOR]

A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC50 values ranging from 4.07 μM to 9.71 μM against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism studies reveal that A8 induces apoptosis and ferroptosis in MCF-7 cells in a dose-dependent manner, and CYPs inhibition assays reveal that A8 has a moderate inhibitory effect on CYP1A2 and CYP3A4 in the human body at 10 μM. The present work indicates that hybrid A8 may merit further investigation as a potential therapeutic agent. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of timing interval to start AED withdraw (TIW) after surgery on the seizure outcome in non-neoplastic drug resistant epilepsy (DRE). TIW were divided into three groups (respectively,<1 year, 1-<2 years, and ≥2 years). The seizure outcome at the different time points after starting AED withdrawal were compared among three groups. Other factors that related to seizure recurrence and TIW were included into the multiple analysis to investigate the predictors of seizure-free. Altogether, 205 patients were involved in the study. 102 individuals (50%) had seizure recurrence and 127 (62%) had seizure-free at the final follow up. 115 of them have attempted AED reduction and had not seizure recurrence before AED reduction. The rate of seizure-free had no significant difference among people with different TIW. Multiple analysis indicated that temporal surgery is a favorable predictor of seizure-free at the first year after starting AED withdrawal, and preoperative secondary generalized seizures is an unfavorable predictor of seizure-free at the final follow up. In patients with non-neoplastic DRE, TIW is not the mainly influence factor on seizure outcome, however, preoperative secondary generalized seizures and extra-temporal surgery are negatively associated with seizure-free. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to summarize the clinical characteristics and outcome of late-onset anti- N -methyl- d -aspartate receptor (anti-NMDAR) encephalitis in China. Method All cases of people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and April 2017 were retrospectively reviewed. The demographics, clinical characteristics, and outcome of those patients (age ≥ 45 years old) were summarized. Comparisons were conducted between older (≥ 45 years old) and younger (18–44 years old) adults. Result Eighteen (12%) of 151 people were ≥ 45 years old, 9 of whom (50%) were female. Psychiatric symptoms were the most common clinical manifestations of older adults and presented in all individuals. At the last follow-up, 14 (78%) of them had a good outcome (modified Rankin Scale: 0–2) and one (6%) died. Compared with 121 younger adults, older adults had a higher proportion of presenting memory deficit as the initial symptom (17% vs. 2%, p = 0.023), longer interval from onset to admission (30 vs. 13 days, p = 0.013), and longer interval from onset to diagnosis (42.5 vs. 24 days, p = 0.045). No older adults' condition was accompanied with teratoma compared with 75% of younger adults with tumor (p = 0.032). And older adults had a tendency to have a lower rate of positive NMDAR antibody (Ab) in serum (28% vs. 52%, p = 0.053). Conclusion Delayed admission and diagnosis are more common in older adults than in younger adults. A comprehensive consideration of all symptoms and early screening of NMDAR Ab, especially in cerebrospinal fluid, is necessary and beneficial to differential diagnosis. [ABSTRACT FROM AUTHOR]

• HHV-6B triggers immune modulatory factors in MTLE. • Increased IL-1a, IL-2 and IL-7 mRNA levels are associated with early antigen expression. • IL-1a and IL-7 may be taken as indirect biomarker of HHV-6B infection in CSF. • Co-localization of HHV-6B antigen with astrocytes and oligodendrocytes. Background: Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity. Methods: Nested polymerase chain reaction (nPCR), real-time PCR, immunohistochemistry (IHC) and suspension bead array for cytokines were performed. Results : Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (P < 0.001), but not in CSF. ICH showed HHV-6B early antigen (P41) positivity in 3 patients (6%), late antigen (gp116/54/64) positivity in 5 patients (10%), latent antigen (U94) positivity in 8 patients (16%), and multiple antigen (early and late or/and latent) positivity in 9 patients (18%). None of these HHV-6B related proteins were found positive in control brain tissue. PCR revealed significant up-regulation of IL-1a, IL-2 and IL-7 mRNA levels in the brain tissue from MTLE patients expressing early antigens compared to those expressing late, latent, multiple antigens, negative antigens and the controls. Suspension bead array of the CSF confirmed significant up-regulation of IL-1a and IL-7 protein expression from MTLE patients expressing early antigens compared to the other groups. Conclusions: Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection. [ABSTRACT FROM AUTHOR]

Species of the order Crocodylia are mostly large, predatory and semi-aquatic reptiles. Crocodylia, the closest living relatives of birds, first appeared in the Late Cretaceous period. In the present study, the complete mitochondrial (mt) genomes of 19 Crocodylia species, including two species (Melanosuchus niger and Caiman yacare) that have not been previously sequenced for mitogenomes, were processed through Illumina sequencing to offer genetic resources and compare with the mitogenomes of Crocodylia species reported previously. In addition, a high-resolution phylogenetic tree of nearly all current recognized species of Crocodylia is constructed based on mitogenomic data. Phylogenetic analyses support monophyly of three families: Alligatoridae (four genera: Alligator , Caiman , Melanosuchus and Paleosuchus), Crocodylidae (three genera: Crocodylus , Mecistops and Osteolaemus) and Gavialidae (two genera: Gavialis and Tomistoma). The tree topology is generally similar to previous studies. Molecular dating suggests that the first split within Crocodylia date back to the Upper Cretaceous (approx. 86.75 Mya). The estimated time to the most recent common ancestor (TMRCA) of Alligatoridae is 53.33 Mya and that of Crocodylidae and Gavialidae is 50.13 Mya, which might be closely linked to climate changes during the Late Palaeocene and Early Eocene. Additionally, this study proves that the diversification rate within Crocodylia began to increase from the Late Eocene (about 36 Mya) and two diversification peak periods of Crocodylia (0–10 Mya and 10–20 Mya) are disclosed, which is roughly consistent with the estimated crocodylian species richness through time. Combining all these clues, we can suggest that climate fluctuation may have played a decisive role in the speciation of Crocodylia. [ABSTRACT FROM AUTHOR]

We aimed to assess suicidality risk amongst people who had had anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis. All people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and February 2017 were identified and their notes were retrospectively reviewed. Demographic and clinical characteristics and risk predictors for suicidality were summarized; those with suicidality were compared to those without. 17 of 133 people (13%) presented with suicidality symptoms: 7 (5%) with suicidal ideation; 8 (6%) who attempted suicide; and 2 (1.5%) who completed suicide. Median age was 27 (16-78) years, most were female [13 (76%)]. Compared with those with no suicidality, psychiatric symptoms as the initial symptoms were more frequent in those who reported suicidality ( p = 0.039); insomnia, aggression, mania, depression and delusion were also more common ( p < 0.05). The use of antidepressants ( p < 0.001) and recurrence of encephalitis ( p = 0.020) were higher in people with suicidality than in those without. Other characteristics were not significantly different in those who had suicidality and those who did not. Suicidality is a common and potentially lethal risk for people with anti-NMDAR encephalitis. Those presenting with psychiatric symptoms as the initial symptom and with insomnia, aggression, mania, depression and delusion should be carefully screened for suicidality. Closely monitoring people who have been treated with antidepressants is necessary. [ABSTRACT FROM AUTHOR]