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An 82-year-old Japanese man with alcoholic liver cirrhosis was referred to our hospital for treatment of advanced esophageal cancer. A protruding tumor was endoscopically observed in the middle thoracic esophagus, and pathological findings of the biopsy specimens revealed a squamous cell carcinoma. The clinical tumor staging was stage II (T3N0M0). The patient received two courses of neoadjuvant chemotherapy with 5-fluorouracil and nedaplatin. After the treatments, computed tomography showed significant reductions in the size of the target tumor. However, radical esophagectomy was not performed because the patient refused major invasive treatments. this website Instead, endoscopic resection was performed using a combination of polypectomy and endoscopic submucosal resection (ESD). To prevent bleeding during endoscopic treatment, we applied a detachable snare to the base of the tumor and cut the stalk using by an SB knife Jr, without hemorrhage. The pathohistology of the resected specimen was positively showed cancer cells on the margin of the esophageal carcinoma stalk. At 4 weeks after the initial operation, an additional ESD was successfully performed, which pathologically led to radical removal. The patient survived for more than 18 months after beginning the initial treatment. We describe a successful treatment using endoscopic resection after chemotherapy for advanced esophageal cancer with high surgical treatment risks.The antiviral agent remdesivir (Veklury®; Gilead Sciences), nucleotide analogue prodrug, has broad-spectrum activity against viruses from several families. Having demonstrated potent antiviral activity against coronaviruses in preclinical studies, remdesivir emerged as a candidate drug for the treatment of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, during the current global pandemic. Phase III evaluation of remdesivir in the treatment of COVID-19 commenced in early 2020 and has thus far yielded promising results. In late May 2020, Taiwan conditionally approved the use of remdesivir in patients with severe COVID-19. This was followed by a rapid succession of conditional approvals in various countries/regions including the EU and Canada. Preceding these conditional approvals, an emergency use authorization for remdesivir had been granted in the USA (on 1 May 2020) and a special approval for emergency use was granted in Japan (on 7 May 2020). This article summarizes the milestones in the development of remdesivir leading to its first conditional approval for the treatment of COVID-19.Endoplasmic reticulum stress (ER stress) can be induced by virus infection. In this part, we explored whether Hantaan virus (HTNV) infection could induce ER stress in differentiated THP-1 (dTHP-1) cells. It showed that the mRNA and protein levels of ER stress-related 78 kDa glucose-regulated protein (GRP78, HSPA5) and mRNA levels of X box-binding protein 1 (XBP-1), activating transcription factor 6(ATF6) and PKR-like ER kinase (PERK) after HTNV infection, were significantly higher than that in uninfected control group. However, the mRNA levels of C/EBP homologous protein (CHOP), glucose-regulated protein 94 (GRP94, HSPC4), and inositol-requiring enzyme1 (IRE1) were not significantly different between the infected group and the untreated group in 2 h after virus infection. It is unusual in activating GRP78 but not GRP94. Meanwhile, dTHP-1 cells infected with HTNV at 12 h did not show obvious apoptosis. These results indicated that the HTNV infection could induce the unfolded protein response (UPR) in dTHP-1 cells, without directly leading to cell apoptosis during 12 h after virus infection.Ischaemic stroke is an acute interruption of the blood supply to the brain, which leads to rapid irreversible damage to nerve tissue. Ischaemic stroke is accompanied by the development of neuroinflammation and neurodegeneration observed around the affected brain area. Heat shock protein 70 (Hsp70) facilitates cell survival under a variety of different stress conditions. Hsp70 may be secreted from cells and exhibits cytoprotective activity. This activity most likely occurs by decreasing the levels of several proinflammatory cytokines through interaction with a few receptors specific to the innate immune system. Herein, we demonstrated that intranasal administration of recombinant human Hsp70 shows a significant twofold decrease in the volume of local ischaemia induced by photothrombosis in the mouse prefrontal brain cortex. Our results revealed that intranasal injections of recombinant Hsp70 decreased the apoptosis level in the ischaemic penumbra, stimulated axonogenesis and increased the number of neurons producing synaptophysin. Similarly, in the isolated crayfish stretch receptor, consisting of a single sensory neuron surrounded by the glial envelope, exogenous Hsp70 significantly decreased photoinduced apoptosis and necrosis of glial cells. The obtained data enable one to consider human recombinant Hsp70 as a promising compound that could be translated from the bench into clinical therapies.
To evaluate the efficacy of Chinese medicine acupoint application (CMAA) combined with Western medicine for perennial allergic rhinitis (PAR) in children.
In this prospective, parallel, randomized, placebo-controlled and single-blind trial from August to September, 2017, 180 children with PAR were randomly assigned to an integrative group (CMAA and Montelukast), CMAA group (CMAA and placebo tablet), or Montelukast group (placebo CMAA and Montelukast). Participants were applied with CMAA for 6 sessions over 2 weeks, and/or Montelukast Chewable Tablet orally once daily for 12 weeks. The changes in severity of symptoms were measured by Visual Analog Scale (VAS) and rhinitis control assessment test (RCAT) at 0, 2, 4 and 12 weeks of treatment. Blood samples were collected for serum interleukin-4, interferon gamma γ and T helper type 1 (Th1)/Th2 flow cytometric analysis at the time points of 0, 4 and 12 weeks.
Eight cases dropped out from the trial, 3 in the integrative group, 2 in the CMAA group and 3 in theith Montelukast might be more effective and appropriate than either option alone for children with PAR. (Registered at Chinese Clinical Trial Register, registration No. ChiCTR-IOR-17012434).Chronic neurocognitive impairments, commonly associated with pediatric human immunodeficiency virus type 1 (PHIV), are a detrimental consequence of early exposure to HIV-1 viral proteins. Strong evidence supports S-Equol (SE) as an efficacious adjunctive neuroprotective and/or neurorestorative therapeutic for neurocognitive impairments in adult ovariectomized female HIV-1 transgenic (Tg) rats. There remains, however, a critical need to assess the therapeutic efficacy of SE when treatment occurs at an earlier age (i.e., resembling a therapeutic for children with PHIV) and across the factor of biological sex. Utilization of a series of signal detection operant tasks revealed prominent, sex-dependent neurocognitive deficits in the HIV-1 Tg rat, characterized by alterations in stimulus-reinforcement learning, the response profile, and temporal processing. Early (i.e., postnatal day 28) initiation of SE treatment precluded the development of chronic neurocognitive impairments in all (i.e., 100%) HIV-1 Tg animals, albeit not for all neurocognitive domains. Most notably, the therapeutic effects of SE are generalized across the factor of biological sex, despite the presence of endogenous hormones. Results support, therefore, the efficacy of SE as a neuroprotective therapeutic for chronic neurocognitive impairments in the post-cART era; an adjunctive therapeutic that demonstrates high efficacy in both males and females. Optimizing treatment conditions by evaluating multiple factors (i.e., age, neurocognitive domains, and biological sex) associated with PHIV and HIV-1 associated neurocognitive disorders (HAND) affords a key opportunity to improve the therapeutic efficacy of SE.
It is important to identify which older patients attending the emergency department are at risk of adverse outcomes to introduce preventive interventions. This study aimed to assess the prognostic value of a shortened screening instrument based on the Dutch national Safety Management System [Veiligheidsmanagementsysteem (VMS)] guidelines for adverse outcomes in older emergency department patients.
A cohort study was performed including patients aged 70years or older who visited the emergency department. Adverse outcomes included hospital admission, return emergency department visits within 30days, and 90-day mortality. The prognostic value of the VMS-score was assessed for these adverse events and, in addition, a prediction model was developed for 90-day mortality.
A high VMS-score was independently associated with an increased risk of hospital admission [OR 2.26 (95% CI 1.32-3.86)] and 90-day mortality [HR 2.48 (95% CI 1.31-4.71)]. The individual VMS-questions regarding history of delirium and help in activities of daily living were associated with these outcomes as well. A prediction model for 90-day mortality was developed and showed satisfactory calibration and good discrimination [AUC 0.80 (95% CI 0.72-0.87)]. A cut-off point that selected 30% of patients at the highest risk yielded a sensitivity of 67.4%, a specificity of 75.3%, a positive predictive value of 28.5%, and a negative predictive value of 94.1%.
The shortened VMS-based screening instrument showed to be of good prognostic value for hospitalization and 90-day mortality. The prediction model for mortality showed promising results and will be further validated and optimized.
The shortened VMS-based screening instrument showed to be of good prognostic value for hospitalization and 90-day mortality. The prediction model for mortality showed promising results and will be further validated and optimized.
This study aimed to establish which determinants had an effect on frailty among acutely admitted patients, where frailty was identified at discharge. In particular, our study focused on associations of sex with frailty.
A cross-sectional study was designed using a sample of 1267 people aged 65years or older. The Tilburg Frailty Indicator (TFI), a user-friendly self-report questionnaire was used to measure multidimensional frailty (physical, psychological, social) and determinants of frailty (sex, age, marital status, education, income, lifestyle, life events, multimorbidity).
The mean age of the participants was 76.8years (SD 7.5; range 65-100). The bivariate regression analyses showed that all determinants were associated with total and physical frailty, and six determinants were associated with psychological and social frailty. Using multiple linear regression analyses, the explained variances differed from 3.5% (psychological frailty) to 20.1% (social frailty), with p values < 0.001. Of the independent variables age, income, lifestyle, life events, and multimorbidity were associated with three frailty variables, after controlling for all the other variables in the model. At the level of both frailty domains and components, females appeared to be more frail than men.
The present study showed that sociodemographic characteristics (sex, age, marital status, education, income), lifestyle, life events, and multimorbidity had a different effect on total frailty and its domains (physical, psychological, social) in a sample of acute admitted patients.
The present study showed that sociodemographic characteristics (sex, age, marital status, education, income), lifestyle, life events, and multimorbidity had a different effect on total frailty and its domains (physical, psychological, social) in a sample of acute admitted patients.
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