Notes

Recurred Sphenoethmoidal Mucocele Soon after Addressed with Basic Endoscopic Marsupialization.
SARS-CoV-2, declared a pandemic in March 2020, is the current global health challenge. selleck The global bioburden of this virus is increasing at a rapid pace. Many antiviral drugs and vaccines have been registered for clinical trials because of their inhibitory activity observed in vitro. Currently, five types of vaccines have successfully passed Phase IV clinical trial and are being administered in populations worldwide. A plethora of experimental designs have been proposed worldwide in order to find a safe and efficacious treatment option. Therefore, it is necessary to provide baseline data and information to clinicians and researchers so that they can review the current status of therapeutics and efficacy of already developed vaccines. This review article summarizes all therapeutic options that may help to combat SARS-CoV-2.Background The efficacy of osimertinib as a first-line treatment for patients with poor performance status (PS) remains unclear. Patients & methods This multicenter retrospective study evaluated patients treated with osimertinib between 2018 and 2020, with PS 2-4. Results Among 36 patients with PS 2, the median progression-free survival (PFS), 1-year PFS, median overall survival (OS) and 1-year OS were 14.5 months, 65.4%, 18.1 months and 72.7%, respectively. Among 20 patients with PS 3-4, the median PFS, 1-year PFS, median OS and 1-year OS were 3.0 months, 27.1%, 5.0 months and 46.1%, respectively. Conclusion Osimertinib was not as efficacious as other EGFR-tyrosine kinase inhibitors.Case presentation A 72-year-old man with non-small-cell lung cancer received four cycles of pembrolizumab-containing chemotherapy. He developed multiple immune-related adverse events (irAEs) and discontinued immune checkpoint inhibitors (ICIs); however, he developed immune-related hepatitis and grade 4 neutropenia at 92 days and 118 days, respectively, from discontinuation. He received G-CSF and methylprednisolone pulse therapy and recovered from neutropenia 12 days later. Discussion & conclusion ICI-induced neutropenia is a life-threatening condition. The longest recorded onset in one study cohort is 26 days after the final administration of ICIs. This case developed strikingly delayed immune-related neutropenia manifesting as a delayed irAE. Clinicians should pay close attention to delayed immune-related neutropenia as a possible life-threatening irAE after ICI treatment.Background The age-dependent prognostic impact of KRAS status in metastatic colorectal cancer (mCRC) is unknown. Materials & Methods We used the National Cancer Database to evaluate the survival by KRAS status for age-groups less then 50, 50-69 and ≥70, adjusting for relevant patient and tumor characteristics. Results mCRC patients (n = 26,095; 33.5%) had KRAS status reported, and 11,338 of these patients (43.4%) had mutations in the KRAS gene. Patients with KRAS mutations had worse overall survival than wild-type KRAS patients. In age-groups less then 50 years (23 vs 29 months; p less then 0.001) and 50-69 (21 vs 23.4 months; p less then 0.001), KRAS mutations were significantly associated with worse survival, whereas in the ≥70-year age-group, there was no significant association (14 vs 14 months; p = 0.34). Conclusion We conclude that the age of patients influences the prognostic value of KRAS mutation in metastatic colorectal cancer.
Animal models of atherosclerosis are used extensively to interrogate molecular mechanisms in serial fashion. We tested whether a novel systems biology approach to integration of preclinical data identifies novel pathways and regulators in human disease. Approach and Results Of 716 articles published in
from 1995 to 2019 using the apolipoprotein E knockout mouse to study atherosclerosis, data were extracted from 360 unique studies in which a gene was experimentally perturbed to impact plaque size or composition and analyzed using Ingenuity Pathway Analysis software. TREM1 (triggering receptor expressed on myeloid cells) signaling and liver×receptor/retinoid×receptor activation were identified as the top atherosclerosis-associated pathways in mice (both
<1.93×10

, TREM1 implicated early and liver×receptor/retinoid×receptor in late atherogenesis). The top upstream regulatory network in mice (sc-58125, a COX2 inhibitor) linked 64.0% of the genes into a single network. The pathways and networks identiges published preclinical investigations to identify high-confidence pathways, networks, and regulators of human disease.
Antibody blockade of the do not eat me signal CD47 enhances efferocytosis and reduces lesion size and necrotic core formation in murine atherosclerosis. TNF (Tumor necrosis factor)-α expression directly enhances
expression, and elevated TNF-α is observed in the absence of the proefferocytosis receptor LRP1 (low-density lipoprotein receptor-related protein 1), a regulator of atherogenesis and inflammation. Thus, we tested the hypothesis that CD47 blockade requires the presence of macrophage LRP1 to enhance efferocytosis, temper TNF-α-dependent inflammation, and limit atherosclerosis. Approach and Results Mice lacking systemic apoE (apoE
), alone or in combination with the loss of macrophage LRP1 (double knockout), were fed a Western-type diet for 12 weeks while receiving anti-CD47 antibody (anti-CD47) or IgG every other day. In apoE
mice, treatment with anti-CD47 reduced lesion size by 25.4%, decreased necrotic core area by 34.5%, and decreased the ratio of freemacrophage-associated apoptotic bodies bynhance efferocytosis, limit atherogenesis, and decrease necrotic core formation in the apoE-/- model of atherosclerosis.Aim The subsequent treatments for patients with hepatocellular carcinoma (HCC) resistant to immunotherapy remain unclear. This study aimed to identify optimal treatments for HCC patients with progression after anti-PD-1 therapy. Methods The authors retrospectively analyzed 197 HCC patients with progressive disease after anti-PD-1 treatment. These patients were classified into initial resistant and secondary resistant groups. Results In the initial resistant group, subsequent treatment with PD-1 antibody plus locoregional therapy prolonged post-progression survival and overall survival (p = 0.025 and 0.029, respectively). In the secondary resistant group, subsequent treatment did not improve the prognosis of patients. Conclusion Subsequent PD-1 antibody plus locoregional therapy could achieve survival benefits in HCC patients initially resistant to anti-PD-1 immunotherapy.Aim To report the experience of chronic pain participants after a well-formulated ketogenic diet (WFKD) or whole-food diet (WFD). The quantitative outcomes for this trial have been published separately (clinical trial registration number ACTRN12620000946910). Patients & methods The experience of 24 participants was evaluated after 12 and 24 weeks of dietary intervention using survey responses and open questions. Results & conclusion Retention rates for the WFKD and WFD groups were 93 and 89%, respectively. Average adherence to the WFKD was 82% and to the WFD was 87%. The WFKD enjoyment was rated at 66 and 81% for the WFD group. The ease of adhering to the diet varied more widely for the WFKD group. Barriers included knowledge integration, time management, navigating social food environments and emotional attachment to eliminated foods. Facilitators included structured support and coaching, and comprehensive learning materials. The WFKD was shown to be a feasible and effective treatment option for chronic pain.Prior to clinical development, a comprehensive pharmacokinetic characterization of a novel drug is required to understand its exposure at the site of action and elimination. Accordingly, in vitro assays and animal pharmacokinetic studies are regularly employed to predict drug exposure in humans, which is often costly and time-consuming. For this reason, the prediction of human pharmacokinetics at the point of design would be of high value for drug discovery. Therefore, we have established a comprehensive data curation protocol that enables machine learning evaluation of 12 human in vivo pharmacokinetic parameters using only chemical structure information and available doses for 1001 unique compounds. These machine learning models were thoroughly investigated and validated using both an independent hold-out test set and AstraZeneca clinical data. In addition, the availability of preclinical predictions for a subset of internal clinical candidates allowed us to compare our in silico approach with state-of-the-art pharmacokinetic predictions. Based on this evaluation, three fit-for-purpose models for AUC PO (Rtest2 = 0.63; RMSEtest = 0.76), Cmax PO (Rtest2 = 0.68; RMSEtest = 0.62), and Vdss IV (Rtest2 = 0.47; RMSEtest = 0.50) were identified. Based on the findings, our machine learning models have considerable potential for practical applications in drug discovery, such as influencing decision-making in drug discovery projects and progression of drug candidates toward the clinic.Textile-based stretchable electronic devices are one of the best candidates for future wearable applications, as they can simultaneously provide high compliance and wearing comfort to the human body. Stretchable conductive textile is the fundamental building block for constructing high-performance textile-based stretchable electronic devices. Here, we report a simple strategy for the fabrication of stretchable conductive fabric using commercial knitted cloth as a substrate. Briefly, we coated the fibers of the fabric with a thin layer of poly(styrene-block-butadiene-block-styrene) (SBS) by dip-coating. Then, silver nanoparticles (AgNPs) were loaded on the fabric by sequential absorption and in situ reduction. After loading AgNPs, the conductivity of the fabric could be as high as ∼800 S/m, while its maximal strain at break was higher than 540%. Meanwhile, such fabric also possesses excellent permeability, robust endurance to repeated stretching, long-time washing, and mechanical rubbing or tearing. We further approve that the fabric is less cytotoxic to mammalian skin and antibacterial to microbial, making it safe for on-skin applications. With these multifarious advantages, the fabric developed here is promising for on-skin wearable applications. As a proof-of-concept, we demonstrate its use as an electrode for collecting electrocardiograph signals and electrothermal therapy.The potential of microplastics to act as a vector for micropollutants of natural or anthropogenic origin is of rising concern. Cyanobacterial toxins, including microcystins, are harmful to humans and wildlife. In this study, we demonstrate for the first time the potential of microplastics to act as vectors for two different microcystin analogues. A concentration of up to 28 times from water to plastic was observed for the combination of polystyrene and microcystin-LF achieving toxin concentrations on the plastic of 142 ± 7 μg g-1. Based on the experimental results, and assuming a worst-case scenario, potential toxin doses for daphnids are calculated based on published microplastic ingestion data. Progressing up through trophic levels, theoretically, the concentration of microcystins in organisms is discussed. The experimental results indicate that adsorption of microcystins onto microplastics is a multifactorial process, depending on the particle size, the variable amino acid composition of the microcystins, the type of plastic, and pH.
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