Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected ...patients.
We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.
The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.
During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
Multimodal treatment of postoperative pain using adjuncts such as gabapentin is becoming more common. Pregabalin has anti-hyperalgesic properties similar to gabapentin. In this systematic review, we ...evaluated randomized, controlled trials (RCTs) for the analgesic efficacy and opioid-sparing effect of pregabalin in acute postoperative pain. A systematic search of Medline (1966–2010), the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was performed. We identified 11 valid RCTs that used pregabalin for acute postoperative pain. Postoperative pain intensity was not reduced by pregabalin. Cumulative opioid consumption at 24 h was significantly decreased with pregabalin. At pregabalin doses of <300 mg, there was a reduction of 8.8 mg weighted mean difference (WMD). At pregabalin doses ≥300 mg, cumulative opioid consumption was even lower (WMD, −13.4 mg). Pregabalin reduced opioid-related adverse effects such as vomiting risk ratio (RR) 0.73; 95% confidence interval (CI) 0.56–0.95. However, the risk of visual disturbance was greater (RR 3.29; 95% CI 1.95–5.57). Perioperative pregabalin administration reduced opioid consumption and opioid-related adverse effects after surgery.
The possibility that a fraction of dark matter is comprised of massive compact halo objects (MACHOs) remains unclear, especially in the 20–100 M⊙ window. MACHOs could make up binaries, whose mergers ...may be detected by LIGO as gravitational wave events. On the other hand, the cosmological origin of fast radio burst (FRBs) has been confirmed. We investigate the possibility of detecting FRBs gravitational lensed by MACHO binaries to constrain their properties. Since lensing events could generate more than one image, lensing by binaries could cause multiple-peak FRBs. The angular separation between these images is roughly 10−3 mas, which is too small to be resolved. The typical time interval between different images is roughly 1 millisecond (ms). The flux ratio between different images is from approximately 10 to 103. With the expected detection rate of 104 FRBs per year by the upcoming experiments, we could expect five multi-peak FRBs observed per year with a time interval larger than 1 ms and flux ratio less than 103 if the fraction of dark matter in MACHOs is f ~ 0.01. A null search of multiple-peak FRBs for time intervals larger than 1 ms and flux ratio less than 103 with 104 FRBs would constrain the fraction f of dark matter in MACHOs to f < 0.001.
Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
Background
Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the ...pathogenesis of CRS with nasal polyps (CRSwNP).
Methods
The expression of autophagic proteins microtubule‐associated protein 1 light chain 3B (LC3B)‐II, autophagy‐related proteins (Atg), and Beclin 1, substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules cysteine‐aspartic protease‐3 and cysteine‐aspartic protease‐8, and poly‐ADP‐ribose polymerase in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting. Autophagic vacuoles were observed with transmission electron microscopy. BEAS‐2B cells and NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some experiments, cultured NECs were transfected with small interfering RNA targeting p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting and flow cytometry.
Results
Although autophagic protein expression and autophagic vacuole formation were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in NECs, there was also an up‐regulation of substrate proteins and apoptotic signaling molecules. IFN‐γ, but not IL‐4, IL‐13, or IL‐17A, simultaneously enhanced LC3B‐II and p62 levels as well as cell apoptosis in BEAS‐2B cells and/or normal NECs. Bafilomycin A1 up‐regulated the levels of LC3B‐II and p62 in polyp NECs and IFN‐γ‐treated normal NECs. IFN‐γ‐induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN‐γ‐treated NECs. IFN‐γ protein levels were increased in both eosinophilic and noneosinophilic CRSwNP.
Conclusions
IFN‐γ induces activated but insufficient autophagy and thus contributes to a degree to p62‐dependent apoptosis of NECs in CRSwNP.
Because of its distinctive compositional properties and variability, low-speed ( 450 km s−1) solar wind is widely believed to originate from coronal streamers, unlike high-speed wind, which comes ...from coronal holes. An alternative scenario is that the bulk of the slow wind (excluding that in the immediate vicinity of the heliospheric current sheet) originates from rapidly diverging flux tubes rooted inside small coronal holes or just within the boundaries of large holes. This viewpoint is based largely on photospheric field extrapolations, which are subject to considerable uncertainties and do not include dynamical effects, making it difficult to be certain whether a source is located just inside or outside a hole boundary, or whether a high-latitude hole will be connected to Earth. To minimize the dependence on field-line extrapolations, we have searched for cases where equatorial coronal holes at central meridian are followed by low-speed streams at Earth. We describe 14 examples from the period 2014-2017, involving Fe xiv 21.1 nm coronal holes located near active regions and having equatorial widths of ∼3°-10°. The associated in situ wind was characterized by speeds v ∼ 300-450 km s−1 and by O7+/O6+ ratios of ∼0.05-0.15, with v showing the usual correlation with proton temperature. In addition, consistent with other recent studies, this slow wind had remarkably high Alfvénicity, similar to that in high-speed streams. We conclude that small coronal holes are a major contributor to the slow solar wind during the maximum and early post-maximum phases of the solar cycle.
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