Failure of early mycological clearance in HIV-negative cryptococcal meningitis

BACKGROUND: Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood. METHODS: We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for RESULTS: Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log CONCLUSIONS: EMC failure in HIV-negative CM is attributed to non-AmB-based therapy and is associated with lo

Predictors of lung adenocarcinoma with leptomeningeal metastases: A 2022 targeted-therapy-assisted molGPA model

Objective: To explore prognostic indicators of lung adenocarcinoma with leptomeningeal metastases (LM) and provide an updated graded prognostic assessment model integrated with molecular alterations (molGPA). Methods: A cohort of 162 patients was enrolled from 202 patients with lung adenocarcinoma and LM. By randomly splitting data into the training (80%) and validation (20%) sets, the Cox regression and random survival forest methods were used on the training set to identify statistically significant variables and construct a prognostic model. The C-index of the model was calculated and compared with that of previous molGPA models. Results: The Cox regression and random forest models both identified four variables, which included KPS, LANO neurological assessment, TKI therapy line, and controlled primary tumor, as statistically significant predictors. A novel targeted-therapy-assisted molGPA model (2022) using the above four prognostic factors was developed to predict LM of lung adenocarcinoma. The C-indices of this prognostic model in the training and validation sets were higher than those of the lung-molGPA (2017) and molGPA (2019) models. Conclusions: The 2022 molGPA model, a substantial update of previous molGPA models with better prediction performance, may be useful in clinical decision making and stratification of future clinical trials

Penaeid shrimp genome provides insights into benthic adaptation and frequent molting

Crustacea, the subphylum of Arthropoda which dominates the aquatic environment, is of major importance in ecology and fisheries. Here we report the genome sequence of the Pacific white shrimp Litopenaeus vannamei, covering similar to 1.66 Gb (scaffold N50 605.56 Kb) with 25,596 protein-coding genes and a high proportion of simple sequence repeats (>23.93%). The expansion of genes related to vision and locomotion is probably central to its benthic adaptation. Frequent molting of the shrimp may be explained by an intensified ecdysone signal pathway through gene expansion and positive selection. As an important aquaculture organism, L. vannamei has been subjected to high selection pressure during the past 30 years of breeding, and this has had a considerable impact on its genome. Decoding the L. vannamei genome not only provides an insight into the genetic underpinnings of specific biological processes, but also provides valuable information for enhancing crustacean aquaculture

Elevated Plasma Homocysteine Levels in Anti-N-methyl-D-aspartate Receptor Encephalitis

Objective: Homocysteine (Hcy) levels have been investigated in many diseases, such as neurodegenerative and autoimmune diseases. However, changes in Hcy levels in anti-N-Methyl-D-aspartate receptor (anti-NMDAR) encephalitis have not been investigated thus far.Methods: Case data were collected from 45 patients with anti-NMDAR encephalitis and 179 age- and sex-matched healthy controls (HCs). Clinical characteristics, Hcy levels, C reactive protein (CRP) levels, and cerebrospinal fluid (CSF) parameters were determined. Association of Hcy and clinical parameters were evaluated in these patients. Among these 45 patients, 15 had a follow-up evaluation at 3 months after treatment.Results: Hcy levels (p < 0.001) and CRP levels (p = 0.005) from the patients with anti-NMDAR encephalitis were significantly higher than those from HCs. Hcy levels from male patients were significantly lower than those from male HCs (p < 0.001). Comparing anti-NMDAR encephalitis patients after treatment with before treatment, the former has significantly higher Hcy levels (p = 0.004), CRP levels (p = 0.041) and mRS scores (p = 0.002). Furthermore, a significant negative correlation between the changes in Hcy levels and the changes in mRS scores (r = −0.534, p = 0.040) was observed.Conclusion: Elevated plasma homocysteine occurs in anti-NMDAR encephalitis, and seems associated with male sex

Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells

Microglial activation plays an important role in neuroinflammation, which contributes to neuronal damage, and inhibition of microglial activation may have therapeutic benefits that could alleviate the progression of neurodegeneration. Recent studies have indicated that the antimalarial agent artemisinin has the ability to inhibit NF-κB activation. In this study, the inhibitory effects of artemisinin on the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated primary microglia. Our results show that artemisinin significantly inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO). Artemisinin significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) and increased the protein levels of IκB-α, which forms a cytoplasmic inactive complex with the p65-p50 heterodimeric complex. Artemisinin treatment significantly inhibited basal and LPS-induced migration of BV-2 microglia. Electrophoretic mobility shift assays revealed increased NF-κB binding activity in LPS-stimulated primary microglia, and this increase could be prevented by artemisinin. The inhibitory effects of artemisinin on LPS-stimulated microglia were blocked after IκB-α was silenced with IκB-α siRNA. Our results suggest that artemisinin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The data provide direct evidence of the potential application of artemisinin for the treatment of neuroinflammatory diseases