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However, multiple primary survivors were more likely to report severe limitations in physical function than the single primary (PR = 1.48 (95% CI, 1.28-1.71)) and no-cancer (PR = 1.64 (95% CI, 1.42-1.88)) groups. Using a cane or walker and balance difficulties were also significantly more common among multiple primary survivors. CONCLUSIONS Despite a similar prevalence of comorbid medical conditions, severe functional limitations were significantly more common among multiple primary survivors than single primary survivors or individuals without cancer. IMPLICATIONS FOR CANCER SURVIVORS Assessment of functional status and treatment of physical deficits may be an especially critical component of care for older patients with a history of multiple cancer diagnoses.PURPOSES Cancer-related distress is known to persist long after completion of treatment. Factors related to distress are largely unexplored in colorectal cancer (CRC) survivors. We examined changes over time and risk factors for distress in CRC patients over the first year after surgery. METHODS We included 212 CRC patients with data at 6 and 12 months post-surgery from the ColoCare Study in Heidelberg, Germany. Sociodemographic and lifestyle factors, social support, and health-related quality of life (HrQOL) prior to surgery were evaluated as predictors of cancer-related distress. Distress was measured with the Cancer and Treatment Distress instrument (CTXD). Linear regression analyses examined associations between risk factors and distress. RESULTS Distress subscale scores varied significantly over time health burden subscale score increased (P  less then  .001), while finances (P = .004), medical demands (P  less then  .001), and identity (P  less then  .001) subscale scores decreased over time. Uncertainty and family strain subscale scores did not change. Younger age, lower income, advanced tumor stage, poorer social support, and poorer baseline HrQOL predicted higher level distress at 6 and 12 months. CONCLUSION Cancer-related distress continues unresolved after surgery. Although some risk factors are difficult to alter, those at highest risk can be identified earlier for possible preventive strategies. IMPLICATIONS FOR CANCER SURVIVORS Screening for risk factors pre-surgery would allow for targeted interventions including strategies to improve resources for those with low support, thereby reducing long-term distress in CRC survivors.BACKGROUND Nicotine, the pharmacologically active substance in both tobacco and many electronic cigarette (e-cigarette) liquids, is responsible for the addiction that sustains cigarette smoking. With 8 million deaths worldwide annually, smoking remains one of the major causes of disability and premature death. However, nicotine also plays an important role in smoking cessation strategies. OBJECTIVES The aim of this study was to develop a comprehensive, whole-body, physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model of nicotine and its major metabolite cotinine, covering various routes of nicotine administration, and to simulate nicotine brain tissue concentrations after the use of combustible cigarettes, e-cigarettes, nicotine gums, and nicotine patches. METHODS A parent-metabolite, PBPK/PD model of nicotine for a non-smoking and a smoking population was developed using 91 plasma and brain tissue concentration-time profiles and 11 heart rate profiles. Among others, cytochrome P450 (CYP) 2A6 nding of the recent increase in youth e-cigarette use.PURPOSE Early squamous cell neoplasia (ESCN) in the oesophagus is a highly treatable condition. Lesions confined to the mucosal layer can be curatively treated endoscopically. We build a computer-assisted detection system that can classify still images or video frames as normal or abnormal with high diagnostic accuracy. METHODS We present a new benchmark dataset containing 68K binary labelled frames extracted from 114 patient videos whose imaged areas have been resected and correlated to histopathology. Our novel convolutional network architecture solves the binary classification task and explains what features of the input domain drive the decision-making process of the network. RESULTS The proposed method achieved an average accuracy of 91.7% compared to the 94.7% achieved by a group of 12 senior clinicians. Our novel network architecture produces deeply supervised activation heatmaps that suggest the network is looking at intrapapillary capillary loop patterns when predicting abnormality. CONCLUSION We believe that this dataset and baseline method may serve as a reference for future benchmarks on both video frame classification and explainability in the context of ESCN detection. A future work path of high clinical relevance is the extension of the classification to ESCN types.Swelling of astrocytes represents a major component of the brain edema associated with many neurological conditions, including acute hepatic encephalopathy (AHE), traumatic brain injury (TBI) and ischemia. It has previously been reported that exposure of cultured astrocytes to ammonia (a factor strongly implicated in the pathogenesis of AHE), oxygen/glucose deprivation, or to direct mechanical trauma results in an increase in cell swelling. Since dietary polyphenols have been shown to exert a protective effect against cell injury, we examined whether resveratrol (RSV, 3,5,4'-trihydroxy-trans-stilbene, a stilbenoid phenol), has a protective effect on astrocyte swelling following its exposure to ammonia, oxygen-glucose deprivation (OGD), or trauma in vitro. Ammonia increased astrocyte swelling, and pre- or post-treatment of astrocytes with 10 and 25 µM RSV displayed an additive effect, while 5 µM did not prevent the effect of ammonia. However, pre-treatment of astrocytes with 25 µM RSV slightly, but significantsporter-1 (NKCC1), factors known to induce astrocytes swelling, when the cells were treated with ammonia or after trauma or ischemia. Further, inhibition of ERK1/2, and p38MAPK diminished the RSV-induced exacerbation of cell swelling post-ammonia, trauma and OGD treatment. These findings strongly suggest that treatment of cultured astrocytes with RSV enhanced the ammonia, ischemia and trauma-induced cell swelling, likely through the exacerbation of intercellular signaling kinases and ion transporters. U0126 concentration Accordingly, caution should be exercised when using RSV for the treatment of these neurological conditions, especially when brain edema is also suspected.