Chemotherapy is usually the subsequent treatment for non-small cell lung cancer patients with acquired radioresistance after long-term fractionated radiotherapy. However, few studies have focused on the selection of chemotherapeutic drugs to treat lung adenocarcinoma patients with radioresistance. Our study compared the sensitivity changes of lung adenocarcinoma cells to conventional chemotherapeutic drugs under radioresistant circumstances by using three lung adenocarcinoma cell models, which were irradiated with fractionated X-rays at a total dose of 60 Gy. The results showed that the toxicities of paclitaxel, docetaxel and SN-38 were increased in radioresistant cells. The IC50 values of docetaxel and SN-38 decreased 0 ~ 3 times and 3 ~ 36 times in radioresistant cells, respectively. Notably, the A549 radioresistant cells were approximately 36 times more sensitive to SN-38 than the parental cells. Further results revealed that the downregulation of the efflux transporter BCRP by long-term fractionated irradiation was an important factor contributing to the increased cytotoxicity of SN-38. In addition, the reported miRNAs and transcriptional factors that regulate BCRP did not participate in the downregulation. In conclusion, these results presented important data on the sensitivity changes of lung adenocarcinoma cells to chemotherapeutic drugs after acquiring radioresistance and suggested that irinotecan (the prodrug of SN-38) might be a promising drug candidate for lung adenocarcinoma patients with acquired radioresistance.This study investigates the association of comorbid disorders with gambling activity in a longitudinal follow-up study of younger and older adult subjects with DSM-IV pathological gambling (PG). The subjects included 57 younger adults with PG (≥ 18/  less then  40 years) and 48 older adults with PG (≥ 60 years). Subjects were assessed at baseline and every 6 months for a mean (SD) of 31.4 (13.1) months. Comorbidity was assessed using a modification of the Longitudinal Interval Follow-up Evaluation (LIFE). During follow-up, rates of problem severity were highest for anxiety disorders, mood disorders, and impulse control disorders. Among all subjects with PG, greater severity of depression or posttraumatic stress disorder was associated with increased gambling activity. In older subjects, greater severity of agoraphobia and social phobia were associated with lowered gambling activity. In younger subjects, greater severity of any substance use disorder, an alcohol use disorder, or compulsive computer use were associated with lowered gambling activity. The latter findings provide presumptive evidence for the substitute addiction hypothesis. We conclude that increased severity of several comorbid disorders could serve as triggers for increased gambling or predict lowered gambling activity. On the other hand, certain comorbid disorders could be triggered by increased gambling activity. Knowing these interrelationships is important to gaining a better understanding of PG and its clinical management.Whole body vibration (WBV) applications have been used in recent years to increase muscle strength, power, and postural control in healthy and various disease populations. This study aims to investigate the effects of WBV on postural control in patients with ataxia. Twenty-four patients were randomly allocated to two groups. In the first group, whole body vibration and exercise therapy (WBV + E) were applied together for the first 8 weeks; after 1 week washout, only exercise program (OE) was applied for the second 8 weeks. In the second group, the OE program was applied first followed by the WBV + E program. Outcome measures were Sensory Organization Test (SOT), Adaptation Test (ADT), Limits of Stability Test (LOS), International Classification Ataxia Ratio Scale (ICARS), Berg Balance Scale (BBS), and Timed Up and Go Test with cognitive task (TUG-C). Twenty patients (mean age ± SD, 34.00 ± 9.16 years) completed the study. The scores of SOT, ICARS, and BBS improved significantly after both OE and WBV + E program (p  0.05). This study demonstrated that exercise programs supported by WBV can play an important role in the improvement of all components of postural control in patients with ataxia. ClinicalTrial.gov Identifier NCT02977377.The non-structural protein nsp3 from SARS-CoV-2 plays an essential role in the viral replication transcription complex. Nsp3a constitutes the N-terminal domain of nsp3, comprising a ubiquitin-like folded domain and a disordered acidic chain. This region of nsp3a has been linked to interactions with the viral nucleoprotein and the structure of double membrane vesicles. Here, we report the backbone resonance assignment of both domains of nsp3a. The study is carried out in the context of the international covid19-nmr consortium, which aims to characterize SARS-CoV-2 proteins and RNAs, providing for example NMR chemical shift assignments of the different viral components. Our assignment will provide the basis for the identification of inhibitors and further functional and interaction studies of this essential protein.LEE-encoded effector EspF (EspF) is an effector protein part of enteropathogenic Escherichia coli’s (EPEC’s) arsenal for intestinal infection. This intrinsically disordered protein contains three highly conserved repeats which together compose over half of the protein’s complete amino acid sequence. EPEC uses EspF to hijack host proteins in order to promote infection. In the attack EspF is translocated, together with other effector proteins, to host cell via type III secretion system. Inside host EspF stimulates actin polymerization by interacting with Neural Wiskott-Aldrich syndrome protein (N-WASP), a regulator in actin polymerization machinery. It is presumed that EspF acts by disrupting the autoinhibitory state of N-WASP GTPase binding domain. In this NMR spectroscopy study, we report the 1H, 13C, and 15N resonance assignments for the complex formed by the first 47-residue repeat of EspF and N-WASP GTPase binding domain. These near-complete resonance assignments provide the basis for further studies which aim to characterize structure, interactions, and dynamics between these two proteins in solution.

Surgical resection of intracranial meningiomas in patients that are 80years old and older, i.e. very old patients, is increasingly considered. Meningiomas with a largest diameter of at least 5cm-’giant meningiomas’-form a distinct entity, and their surgical resection is considered more difficult and prone to complications. Here, we evaluated functional outcome, morbidity and mortality, and the prognostic value of tumor size in very old patients who underwent resection of giant supratentorial meningiomas.

We retrospectively reviewed clinical and radiological data, functional performance (Karnofsky Performance Score), histopathological diagnosis and complications of very old patients who underwent surgery of a supratentorial meningioma at the Helsinki University Hospital between 2010 and 2018.

We identified 76 very old patients, including 28 with a giant meningioma. Patients with a giant meningioma suffered from major complications more commonly than those with a non-giant meningioma (36% vs. 17%, p = 0.0ing the surgical strategy.The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Autism Diagnostic Interview, Revised (ADI-R) have high accuracy as diagnostic instruments in research settings, while evidence of accuracy in clinical settings is less robust. This meta-analysis focused on efficacy of these measures in research versus clinical settings. Articles (n = 22) were analyzed using a hierarchical summary receiver operating characteristics (HSROC) model. ADOS-2 performance was stronger than the ADI-R. ADOS-2 sensitivity and specificity ranged from .89-.92 and .81-.85, respectively. ADOS-2 accuracy in research compared with clinical settings was mixed. ADI-R sensitivity and specificity were .75 and .82, respectively, with higher specificity in research samples (Research = .85, Clinical = .72). A small number of clinical studies were identified, indicating ongoing need for investigation outside research settings.The literature has shown the beneficial effects of microcurrent (MC) therapy on tissue repair. We investigated if the application of MC at 10 μA/90 s could modulate the expression of remodeling genes transforming growth factor beta (Tgfb), connective tissue growth factor (Ctgf), insulin-like growth factor 1 (Igf1), tenascin C (Tnc), Fibronectin (Fn1), Scleraxis (Scx), Fibromodulin (Fmod) and tenomodulin in NIH/3T3 fibroblasts in a wound healing assay. The cell migration was analyzed between days 0 and 4 in both fibroblasts (F) and fibroblasts + MC (F+MC) groups. On the 4th day, cell viability and gene expression were also analyzed after daily MC application. Higher expression of Ctgf and lower expression of Tnc and Fmod, respectively, were observed in the F+MC group in relation to F group (p  less then  0.05), and no difference was observed between the groups for the genes Tgfb, Fn1 and Scx. In cell migration, a higher number of cells in the scratch region was observed in group F+MC (p  less then  0.05) compared to group F on the 4th day, and the cell viability assay showed no difference between the groups. In conclusion, MC therapy at an intensity/time of 10 μA/90 s with 4 daily applications did not affect cell viability, stimulated fibroblasts migration with the involvement of Ctgf, and reduced the Tnc and Fmod expression.

Little is known about the association between immune-related adverse events (irAEs) and the efficacy and survival outcomes of nivolumab in patients with advancedgastric cancer(AGC).

The present study examined the association between irAEs and the prognosis of patients with AGC treated with nivolumab.

From July 2017 to November 2020, patients who had been diagnosed with advanced unresected gastric cancer and treated with nivolumab at our institution were included in this analysis. We compared the clinical and survival outcomes between the irAE and non-irAE groups. We also evaluated the factors associated with better survival in patients treated with nivolumab.

A total of 52 patients were included in the present study, and irAEs were observed in 13 (25%). Among the patients with measurable lesions (n = 29), the disease control rates were significantly higher in the irAE group than in the non-irAE group (88 vs. 24%; P = 0.0033). At the 8- and 12-week landmark analyses, the median overall survival (OS) in the irAE group was significantly longer than that in the non-irAE group, whereas the median progression-free survival was comparable between the groups. A multivariate analysis by Cox proportional hazard regression at the 8-week landmark revealed that the development of irAEs (hazard ratio 0.18; 95% confidence interval 0.0099-0.86) alone was positively associated with a longer OS.

The development of irAEs might be associated with survival outcomes with nivolumab treatment in patients withAGC.

The development of irAEs might be associated with survival outcomes with nivolumab treatment in patients with AGC.