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Family caregivers of persons with mild cognitive impairment attempt to understand the behavioural and functional changes exhibited by their relative. However, how caregivers respond to initial changes and changes over time has not been explored. The purpose of this qualitative study was to explore the experience of family caregivers responding to changes in their relative's memory, behaviours, and physical functions over 2 years. Eleven family caregivers of a relative with mild cognitive impairment were purposively recruited from neurological clinics in Taiwan. Face-to-face semi-structured interviews were conducted within 6-months of referral; three follow-ups were conducted at 6-month intervals. Content analysis of 41 transcribed audio-recorded interviews revealed the longitudinal changes in their relative with cognitive impairment was made caregiving challenging. Three themes described the challenges: (1) Changes related to their relative's cognitive impairment, which included increases in mood fluctuations, erratic behaviours, and reductions in physical abilities; (2) changes in their relative's comorbidities, which included adapting to new symptoms and treatments for a chronic disease, monitoring medication adherence and drug interactions; and (3) changes in caregiver burden, which increased levels of stress, uncertainty, and anxiety resulting in greater role strain. Caregiving became more challenging with time, especially caregivers whose relative developed dementia during the study period. These findings offer insight into the trajectory of the experience of family caregivers attempting to understand changes in cognition, behaviours, and physical functions for their relative with mild cognitive impairment over 2 years, which could help mental healthcare providers develop support services to reduce caregiver role strain., (© 2024 John Wiley & Sons Australia, Ltd.)

To clarify the survival benefit of sequential curative treatment post transcatheter arterial chemoembolization (TACE) for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), we retrospectively analyzed HCC patients at a hospital. From July 2017 to July 2020, 787 treatment-naïve HCC patients underwent initial treatment; 77 (9.8%) meeting inclusion criteria were enrolled. Their initial treatments were TACE only (n = 68, 88.3%) or TACE with other treatments (n = 9, 11.7%). Median survival of the TACE-only group was 30 months. Treatment response was evaluated after 2 or 3 consecutive TACEs for patients (54/68, 79.4%) with available pre-/post-TACE computerized tomography (CT) or magnetic resonance imaging (MRI). Treatment responses was divided into 4 groups: complete (n = 14, 26%, group (Gr) 1), incomplete without new tumor growth (n = 28, 52.0%, Gr2), incomplete with new growth (n = 6, 11%, Gr3), and progression (n = 6, 11%, Gr4). Of Gr2, further treatment after TACE were had radiofrequency ablation (n = 13, Gr2a), TACE (n = 9, Gr2b), other modalities (n = 6, Gr2c. Gr2a's median survival was longer than Gr2b's (> 60 vs. 20 months, p = 0.007). Nine patients in Gr2a (69%, 9/13) achieved a complete response, but none in Gr2b (p = 0.001). Conclusively, in TACE-suitable BCLC stage B HCC patients, a partial response without new tumor growth can serve as an indicator of treatment effectiveness following initial TACE treatment. This can facilitate the selection of appropriate candidates to receive RFA, potentially resulting in improved patient survival., (© 2024. The Author(s).)

Pressure ulcers are a common problem among individuals who, for medical reasons, must spend most of their day in bed. Manually turning a person's body is labor intensive and can easily cause occupational injuries. To compare the effectiveness of a new assisted turning mattress in pressure management with that of a conventional air mattress. This is a single-session crossover trial study. Twenty-four participants confined to bed were transferred onto the selected mattress (assisted turning or conventional air mattresses) in the selected position. Average interface pressures of bony prominences were measured after the participants laid on the mattress in different positions. After the data collection, they were transferred to the second mattress, and the process was repeated. Subjective feedback from participants and caregivers was also acquired immediately following a one-week trial period of assisted turning mattresses. The mean interface pressures were comparable for most body parts between two mattresses. Subjective feedback showed that assisted turning mattresses could relieve caregivers' workload but at the cost of patients' decreased feelings of safety. Assisted turning mattresses are equal to conventional air mattresses in pressure distribution. Proper pressure management through scheduled positional changes is required in assisted turning mattresses.

Objectives: The purpose of this study was to examine the role of predictability in the relationship between caregiving demands and caregiving consequences., Design: This 2-year longitudinal survey study collected from self-report questionnaires. A convenience sample of family caregivers of older persons living with dementia were recruited from a neurology clinic., Results: A total of 200 family caregivers were recruited to participate. Analysis indicated predictability was a partial mediator between caregiving demand and caregiver consequences of role strain, depressive symptoms and both physical and mental components of health-related quality of life at the 2-year follow. Predictability accounted for 25 %, 28.8 %, 15.3 % and 46.5 % of the relationship between caregiving demand and caregiving consequences of role strain, depressive symptoms, physical- and mental-health related quality of life, respectively., Conclusions: The contributions of caregiving demand to outcomes of caregiver consequences were in part due family caregivers perceived predictability for caregiving., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The purpose of this study was to explore variables associated with rewarded caregiving for family caregivers of persons living with dementia over a 2-year follow-up. This correlational longitudinal study was comprised of 200 family caregivers of persons living with dementia from neurological clinics of a medical center was conducted. Dichotomous scoring of the Rewards of Caregiving Scale of the Family Caregiving Inventory resulted in 61 (30.5%) caregivers being assigned to the well-rewarded group and 139 (69.5%) to the poorly reward group at baseline. Variables included characteristics of family caregivers and their care receivers and assessments with validated scales of caregivers' social support and dyadic relational variables of mutuality, preparedness, and balance. Analysis at baseline showed significant predictors of well-rewarded family caregivers were being an adult child of the care receiver, having a high perceived level mutuality and having a high perceived level of preparedness. These three variables remained as significant predictors at the 1- and 2-year follow-up. Caregivers with high levels of perceived mutuality and preparedness at 2-years were seven times more likely to perceive themselves as well-rewarded. Based on the findings, developing clinical interventions that focus on promoting mutuality and preparedness for family caregivers of persons with dementia could allow caregivers to perceive their role as rewarding. Attention should also be paid to the relationship between the caregiver and care receiver to enhance the family caregiver's feelings of mutuality and preparedness., (© 2024 Wiley Periodicals LLC.)

Human neutrophil elastase (HNE) overexpression has a crucial role in most acute inflammation and alpha1-antitrypsin deficiency syndromes observed in humans, triggering neutrophil invasion and activation of macrophage inflammatory and proteolytic effects, leading to tissue damage. Manipulating HNE level homeostasis could potentially help treat neutrophilic inflammation. Previous studies have shown that sirtinol (1) has a specific influence on HNE and potently attenuates acute lung injury and hepatic injury mediated by lipopolysaccharide or trauma hemorrhage. Therefore, 1 was chosen as the model structure to obtain more potent anti-HNE agents. In the present study, we synthesized a series of sirtinol analogues and determined their inhibitory effects on HNE. Structure-activity relationship (SAR) studies showed that swapping the imine and methyl groups of the sirtinol scaffold with diazene and carboxyl groups, respectively, enhances the HNE inhibiting potency. Compound 29 exhibited the highest potency in the SAR study and showed dual inhibitory effects on HNE and proteinase 3 with IC 50 values of 4.91 and 20.69 µM, respectively. Furthermore, 29 was confirmed to have dual impacts on inhibiting O 2•- generation and elastase release in cell-based assays with IC 50 values of 0.90 and 1.86 µM, respectively. These findings suggest that 29 is a promising candidate for developing HNE inhibitors in the treatment of neutrophilic inflammatory diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Chemical composition screening of an octocoral identified as Sinularia species led to the isolation of a novel diterpenoid, sinulariaone A (1), featuring a 13-membered carbocyclic skeleton. The structure of 1 was established by spectroscopic elucidation, computed calculation, and X-ray diffraction analysis. Moreover, a single-crystal X-ray diffraction analysis of chlorofurancembranoid B (2), obtained in our previous study from the same octocoral species, was reported for the first time to demonstrate the absolute configuration. Diterpenoid 1 showed cytotoxicity towards human promyelocytic leukemia HL-60 cells, with an IC 50 value of 38.01 μM., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Little is known regarding the effects of training programs on family caregivers of older persons with mild cognitive impairment because of the significant differences in outcome variables measured in the various studies in the literature., Purpose: This study was designed to examine the effects of an outpatient-based caregiver training program on the preparedness, health-related quality of life, and depressive symptoms of participants responsible for caring for older persons with mild cognitive impairment., Methods: A randomized clinical trial was implemented. Of the 54 family caregiver participants who provided complete and valid data, 28 and 26 were assigned to the experimental and control groups, respectively. The experimental group participated in a researcher-developed training program that provided information on mild cognitive impairment, strategies for maintaining and promoting cognitive function in persons with mild cognitive impairment, managing their own and their care recipients' healthcare, and managing their own emotional support and stress. Outcomes (caregiver preparedness, health-related quality of life, and depressive symptoms) were assessed before the start of the training program (baseline) and at 1, 3, and 6 months after completion of the program., Results: After controlling for baseline cognitive function of the care recipients and of caregiver preparedness, the experimental group was shown to be significantly less prepared than the control group at baseline (β = -1.41, p = .031) and better prepared than the control group at all three posttests (group differences: 1.3, 1.53, and 4.24, respectively), with the difference at the third posttest (6 months) reaching statistical significance (p = .008). No impact of the intervention on caregiver depressive symptoms or health-related quality of life was found at posttest., Conclusions: The training intervention in this study was found to increase the perceived preparedness of the family caregiver participants to handle various aspects of providing care to persons with mild cognitive impairment. However, no changes were found in depressive symptoms or health-related quality of life., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: 5-FU-induced intestinal mucositis (FUIIM) is a common gastrointestinal side effect of chemotherapy, leading to gastric pain in clinical cancer patients. In a previous study, we demonstrated that neutrophil elastase (NE) inhibitors could alleviate FUIIM and manipulate the homeostasis of the gut microbiota. The root of Melastoma malabathricum, also called Ye-Mu-Dan, has been used as a traditional Chinese medicine for gastrointestinal disease. Water extract of the roots of M. malabathricum exhibits an inhibitory effect on NE, with an IC 50 value of 9.13 μg/ml., Purpose: In this study, we aimed to isolate an anti-NE compound from the root of M. malabathricum and to determine the protective effect of the bioactive component on a mouse model of FUIIM with respect to tissue damage, inflammation, intestinal barrier dysfunction, and gut microbiota dysbiosis., Methods: A water extract of the roots of M. malabathricum was prepared and its major bioactive compound, was identified using bioactivity-guided fractionation. The effects of samples on the inhibition of NE activity were evaluated using enzymatic assays. To evaluate the effects of the bioactive compound in an FUIIM animal model, male C57BL/6 mice treated with or without casuarinin (50 and 100 mg/kg/day, p.o.), and then received of 5-fluorouracil (50 mg/kg/day) intraperitoneally for 5 days to induce FUIIM. Histopathological staining was used to monitor the tissue damage, proliferation of intestinal crypts, and expression of tight junction proteins. The inflammation score was estimated by determining the levels of oxidative stress, neutrophil-related proteases, and proinflammatory cytokines in tissue and serum. The ecology of the gut microbiota was evaluated using 16S rRNA gene sequencing., Results: Casuarinin had the most potent and selective effect against NE, with an IC 50 value of 2.79 ± 0.07 μM. Casuarinin (100 mg/kg/day, p.o.) significantly improved 5-FU-induced body weight loss together with food intake reduction, and it also significantly reversed villus atrophy, restored the proliferative activity of the intestinal crypts, and suppressed inflammation and intestinal barrier dysfunction in the mouse model of FUIIM. Casuarinin also reversed 5-FU-induced gut microbiota dysbiosis, particularly the abundance of Actinobacteria, Candidatus Arthromitus, and Lactobacillus murinus, and the Firmicutes-to-Bacteroidetes ratio., Conclusion: This study firstly showed that casuarinin isolated from the root part of M. malabathricum could be used as a NE inhibitor, whereas it could improve FUIIM by modulating inflammation, intestinal barrier dysfunction, and gut microbiota dysbiosis. In summary, exploring anti-NE natural product may provide a way to find candidate for improvement of FUIIM., (Copyright © 2022. Published by Elsevier GmbH.)

A novel chromone analogue, phyllomakin A ( 1 ), and a new flavonolignan, (-)-quiquelignan C ( 2 ), along with 18 phenolic and 2 triterpenoids, were isolated from the leaves of Phyllostachys makinoi Hayata. The structures of 1 - 22 were elucidated by an application of various spectroscopic analyses (1D & 2D NMR and MS) and compared with reported data. A biological evaluation showed that compound 3 had very potent anti-NO production activity (IC 50 = 4.80 µM), while compounds 2 , 6 , 11 , and 15 showed moderate inhibitory effects (IC 50 = 10.19, 13.26, 13.56, and 10.96 µM, respectively) without affecting cell viability at 20 μM.

Objectives: Computerised cognitive training programs can improve cognitive function in patients with moderate-to-severe dementia or brain injuries and healthy older adults. However, most previous studies were not randomised controlled trials and did not examine older adults with mild dementia. The current study sought to analyse the effects of a computerised cognitive training program using a randomised controlled trial., Methods: In a single-blinded randomised clinical trial, 30 older individuals with mild dementia were split into an experimental (n = 15) and a control (n = 15) group to analyse the effects of a computerised cognitive training program. Outcomes were assessed before and after each program session, and 1 and 3 months afterwards., Results: Participants in the experimental group had better overall subjective memory, subjective retrospective memory and global quality of life, with fewer depressive symptoms than those in the control group 3 months following the program., Conclusions: Our computerised cognitive training program improved subjective memory and quality of life in patients with mild dementia and decreased their depressive symptoms. These results may be useful for health-care providers caring for people with mild dementia., (© 2021 AJA Inc.)

Background: Dementia and hip fracture are both associated with substantial disability and mortality. However, few studies have explored the effects of intervention programs on post-operative recovery of older persons with hip fracture and cognitive impairment., Objective: To examine the effects of a family-centered care model for older persons with hip fracture and cognitive impairment and their family caregivers., Design: Single-blinded clinical trial., Setting: A 3000-bed medical center in Taiwan., Participants: Older persons hip fracture and cognitive impairment (N = 152); 76 in the intervention group, and 76 in the usual-care control group., Methods: A family-centered care model consisting of geriatric assessment, discharge planning, in-home rehabilitation, and family caregiver-training for dementia care. Outcomes were assessed 1-, 3-, 6- and 12-months following hospital discharge for older persons with hip fracture and cognitive impairment. Assessed outcomes were self-care ability (performance of activities of daily living and instrumental activities of daily living), nutritional status, self-rated health, health-related quality of life and self-efficacy, and competence of the family caregivers., Results: Relative to patients who received usual care, those who received the family-centered care intervention had a greater rate of improvement in self-rated health (β = 1.68, p < .05) and nutritional status (β = 0.23, p < .05), especially during the first 6 months following hospital discharge. Relative to family caregivers who received usual care, those who received family-centered care had a higher level of competence (β = 7.97, p < .01), a greater rate of improvement in competence (β = 0.57, p < .01), and a greater rate of improvement in self-efficacy (β = 0.74, p < .05) 3 months following hospital discharge., Conclusions: A family-centered care model enhanced family caregivers' self-efficacy and competence but did not improve the physical recovery of the participants with hip fracture and dementia. We suggest adding an educational component to include geriatric assessment, discharge planning, in-home rehabilitation, and family caregiver-training for dementia care and assessing family caregiver outcomes in interventions for older persons with hip fracture and cognitive impairment., Trial Registration: Registered with www.clinicaltrials.gov (NCT03894709) Tweetable abstract: A family-centered care model consisting of geriatric assessment, discharge planning, in-home rehabilitation, and family caregiver-training for dementia care of older persons with hip fracture and cognitive impairment enhanced family caregivers' self-efficacy and competence., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. The funding agency had no role in the study design, methods, subject recruitment, data collections, analysis, and preparation of this article., (Copyright © 2021. Published by Elsevier Ltd.)

Anode-free lithium metal batteries are the most promising candidate to outperform lithium metal batteries due to higher energy density and reduced safety hazards with the absence of metallic lithium anode during initial cell fabrication. In general, researchers report capacity retention, reversible capacity, or rate capability of the cells to study the electrochemical performance of anode-free lithium metal batteries. However, evaluating the behavior of batteries from limited aspects may easily overlook other information hidden deep inside the meretricious results or even lead to misguided data interpretation. In this work, we present an integrated protocol combining different types of cell configuration to determine various sources of irreversible coulombic efficiency in anode-free lithium metal cells. The decrypted information from the protocol provides an insightful understanding of the behaviors of LMBs and AFLMBs, which promotes their development for practical applications.

Twelve undescribed lanostane-type triterpenes, and twenty-two known triterpenes were isolated and identified from a medicinal bracket fungus Fomitopsis pinicola (Sw.) P. Karst. The structures of these compounds were determined by spectroscopic and spectrometric analyses. The antiinflammatory potential of thirty-two triterpene compounds was evaluated using neutrophils as an assay model, and pinicolasin J was the most potent inhibitor of superoxide anion generation and elastase release, with IC 50 values of 1.81 ± 0.44 and 2.50 ± 0.64 μM, respectively. This study provides scientific insight into the nutritional supplement value and medicinal development of Fomitopsis pinicola., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: 5-Fluorouracil (5-FU)-based chemotherapy is first-line chemotherapy for colorectal cancer. However, 5-FU-induced intestinal mucositis (FUIIM) is a common adverse effect that severely impairs drug tolerance and results in poor patient health., Methods: Male C57BL/6 mice were given 5-FU (50 mg/kg/day, i.p.) and treated with MPH-966 (5 and 7.5 mg/kg/day, p.o.) for five days. The body weight loss and the amount of food intake, and histopathological findings were recorded and analyzed. In addition, the neutrophil infiltration, levels of neutrophil serine proteases and pro-inflammatory cytokines, and tight junction proteins expression in intestinal tissues were determined. The ecology of gut microbiota was performed through next-generation sequencing technologies., Results: Neutrophil elastase (NE) overexpression is a key feature in FUIIM. This study showed that treatment with the specific NE inhibitor MPH-966 (7.5 mg/kg/day, p.o.) significantly reversed 5-FU-induced loss in body weight and food intake; reversed villous atrophy; significantly suppressed myeloperoxidase, NE, and proteinase 3 activity; and reduced pro-inflammatory cytokine expression in an FUIIM mouse model. In addition, MPH-966 prevented 5-FU-induced intestinal barrier dysfunction, as indicated by the modulated expression of the tight junction proteins zonula occludin-1 and occludin. MPH-966 also reversed 5-FU-induced changes in gut microbiota diversity and abundances, specifically the Firmicutes-to-Bacteroidetes ratio; Muribaculaceae, Ruminococcaceae, and Eggerthellaceae abundances at the family level; and Candidatus Arthromitus abundance at the genus level., Conclusion: These data indicate that NE inhibitor is a key treatment candidate to alleviate FUIIM by regulating abnormal inflammatory responses, intestinal barrier dysfunction, and gut microbiota imbalance., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Aims: (a) To identify the frequencies and reasons for missed care by nursing aides in long-term care facilities and (b) to clarify the correlation between missed care and the characteristics of nursing aides and facilities., Background: Missed care by nursing aides in long-term care facilities affects the resident's quality of care and, therefore, requires attention., Methods: A cross-sectional study was conducted, wherein 184 nursing aides and 80 registered nurses were recruited from 10 long-term care facilities., Results: (a) The most frequently missed item of care by nursing aides was assistance with body cleaning (30.4%). (b) Among all participants, 90.2%, 89.8% and 64% indicated poor communication, labour shortages and material resource insufficiencies, respectively, as the reason for missed care. (c) Participants who perceived staff to be insufficient missed care tasks more frequently than those who perceived staff to be sufficient (p < .05)., Conclusions: Missed handover and insufficient nursing aides on duty were identified as the primary reasons for missed care., Implications for Nursing Management: Handover as a nursing process should be improved to promote accuracy and continuity. Flexibility in human resources should be maintained to respond adequately to resident's emergencies, thereby ensuring effective completion of the job., (© 2019 John Wiley & Sons Ltd.)

Activation of hepatic stellate cells (HSCs) is a critical pathogenic feature of liver fibrosis and cirrhosis. BAY 41-2272 is a canonical non-nitric oxide (NO)-based soluble guanylyl cyclase (sGC) stimulator that triggers cyclic guanosine monophosphate (cGMP) signaling for attenuation of fibrotic disorders; however, the impact of BAY 41-2272 on HSC activation remains ill-defined. Transforming growth factor (TGF)β and its downstream connective tissue growth factor (CTGF or cellular communication network factor 2, CCN2) are critical fibrogenic cytokines for accelerating HSC activation. Here, we identified that BAY 41-2272 significantly inhibited the TGFβ1-induced mRNA and protein expression of CTGF in mouse primary HSCs. Indeed, BAY 41-2272 increased the sGC activity and cGMP levels that were potentiated by two NO donors and inhibited by a specific sGC inhibitor, ODQ. Surprisingly, the inhibitory effects of BAY 41-2272 on CTGF expression were independent of the sGC/cGMP pathway in TGFβ1-activated primary HSCs. BAY 41-2272 selectively restricted the TGFβ1-induced phosphorylation of Akt but not canonical Smad2/3 in primary HSCs. Together, we illustrate a unique framework of BAY 41-2272 for inhibiting TGFβ1-induced CTGF upregulation and HSC activation via a noncanonical Akt-dependent but sGC/cGMP-independent pathway.

Four new sesquiterpenes (1-4), one new alkaloid (5), and one new benzenoid glycoside (6) were characterized from Lindera aggregata, and their structures were elucidated according to their spectrometric analytical data. Among these isolates, 3 and 4 were constructed as possessing unprecedented carbon skeletons from the natural source. Some of these purified constituents were examined for their anti-inflammatory bioactivity. Among the tested compounds, linderaggredin C (3), (+)-N-methyllaurotetanine, and (+)-isoboldine displayed the significant inhibition of superoxide anion generation in human neutrophils with IC 50 values of 7.45 ± 0.74, 8.36 ± 0.11, and 5.81 ± 0.59 μM, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to analyze the nutritional risk factors for postoperative complications following hepatic resection for hepatocellular carcinoma (HCC)., Methods: The preoperative nutritional status of patients with HCC who underwent hepatic resection was evaluated using the scored Patient-Generated Subjective Global Assessment (PG-SGA). The perioperative variables were compared between well-nourished and malnourished patients. Regression analysis was employed to identify the risk factors for postoperative complications., Results: The overall operative mortality and morbidity of 287 patients who underwent resection for HCC were 1.7% and 44.3%, respectively. Upon admission, 96 (33.4%) study participants were malnourished, which was associated with a significantly higher PG-SGA score (P < 0.001), higher frequency of comorbidity (P < 0.001), more postoperative complications (P < 0.001) and a longer length of hospital stay (P < 0.001). In addition, major complications (Clavien-Dindo classification ≥ IIIa) occurred significantly more frequently in the malnourished group (P < 0.01). Age ≥70 years (risk ratio [RR] = 2.50, P = 0.008) and PG-SGA score ≥ 4 ([RR] = 9.85, P < 0.001) were significant risk factors for postoperative complications., Conclusions: The PG-SGA score is an effective tool for predicting postoperative complications in patients with HCC following hepatic resection., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: To determine the feasibility of semi-quantitative haemodynamic parameters derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to assess liver fibrosis., Materials and Methods: Seventy-five patients with Child's A classification (males/females=24/51; average age, 58 years; range, 30-80 years) received DCE-MRI 3 days prior to hepatectomy. Semi-quantitative haemodynamic parameters, including the wash-in slope, wash-out slope, and time-to-peak, were calculated from DCE-MRI data. Liver fibrosis of the resected non-tumour liver was graded pathologically from F0 (no fibrosis) to F6 (cirrhosis) in the regions corresponding to those assessed by DCE-MRI., Results: The wash-out slope showed higher interobserver and intra-observer reliabilities than the wash-in slope and time-to-peak. There was a significant positive correlation between the wash-out slope and pathological grade of fibrosis (Spearman's correlation coefficient: r=0.5331, p<0.0001). The area under the receiver operating characteristic curve was 0.8066 when using the wash-out slope to differentiate cirrhosis (grade F6) from non-cirrhosis (grades F0-5). Using the cut-off point that maximised specificity, the sensitivity was 62.07%, specificity was 91.30%, positive predictive value was 81.81%, negative predictive value was 79.25%, and accuracy was 80%., Conclusions: The wash-out slope derived from DCE-MRI might be potentially useful in assessing liver cirrhosis in patients with Child's A classification before hepatectomy., (Copyright © 2019. Published by Elsevier Ltd.)

Objectives: This study investigated the associations of cognitive status with specific/overall health-related quality of life (HRQoL) in older stroke survivors in Taiwan., Method: A subsample of 592 older stroke survivors in a nationwide population-based survey of cognitive-dysfunction prevalencewas analyzed. HRQoL was assessed using the EuroQol five-dimension questionnaire (EQ-5D)., Results: Stroke survivors with dementia were 5.60 times more likely to have mobility problems, 12.20 times to have self-care problems, 16.61 times to have problems in usual activities, 4.31 times to have pain/discomfort, and 3.28 times to have anxiety/depression than stroke survivors with normal cognitive function. Stroke survivors with mild cognitive dysfunction (MCD) were 2.57 times more likely to have mobility problems, 3.17 times to have self-care problems, 3.31 times to have problems in usual activities, 2.11 times to have pain/discomfort, and 2.35 times to have anxiety/depression than those with normal cognitive function. Both dementia (b = -15.13, p < .001) and MCD (b = -6.24, p < .001) significantly contributed to lower EQ-5D VAS; both dementia (b = -.15, p < .001) and MCD (b = -.10, p < .001) significantly contributed to lower EQ-5D index., Conclusion: Dementia and MCD strongly predicted worse overall and specific HRQoL dimensions, especially self-care and usual activities for older stroke survivors.

Dementia is typically classified into mild, moderate, and severe stages based on symptom severity. Prevention and early diagnosis is one of the care goals for dementia. Mild cognitive impairment (MCI) is a transitional stage between the cognitive changes of normal aging and dementia. Initiating an appropriate treatment regimen and methods at a sufficiently early stage has been shown to be effective in postponing the onset of dementia. Previous studies have confirmed the effectiveness of non-pharmacological treatments in improving the cognitive functions, reducing the onset of the behavioral and psychological symptoms of dementia, and training the physical functions of daily living in patients diagnosed with MCI. Game therapy, in addition to reminiscence therapy, music therapy, cognitive training, cognitive stimulation, and aromatherapy, is one of these non-pharmacological treatments. Moreover, game therapy may be used as a tool to screen individuals for symptoms of dementia. Using easily accessible, user-friendly, and affordable games, patients with dementia and their caregivers may receive their therapy in a more relaxed and enjoyable manner. Patients and their caregivers who perceive a prescribed therapy as a game are expected to exhibit higher motivation to use, which should result in better treatment outcomes. This paper will introduce and compare several games for people with dementia, providing valuable information for caregivers and healthcare professionals who are responsible for caring for patients with dementia.

The prevalence of depressive symptoms among older residents in long-term care facilities (LTCFs) is high. Nurses are the main healthcare providers in LTCFs and also the persons responsible for detecting changes in residents' mental function and providing subsequent care. Therefore, it is necessary to understand nurses' knowledge, attitudes, and confidence regarding care for older residents with depressive symptoms or depression. This study aimed to understand nurses' level of knowledge of late-life depression, attitudes towards depression, and confidence levels in caring for older adults with depressive symptoms or depression in LTCFs. A cross-sectional descriptive and correlational research design was used. A nationwide self-report survey was conducted in 2016. Ultimately, 556 valid questionnaires were returned. The study found that LTCF nurses' knowledge about late-life depression was poor, and they also lacked confidence in managing and caring for older persons with depressive symptoms or depression, but nurses' attitudes towards depression were neutral or slightly positive. Moreover, nurses who had greater confidence in providing care for older persons with depression were those with more positive attitudes towards depression, a greater interest level in taking care of older adults with depression, less late-life depression knowledge, longer nursing experience in LTCFs, and a greater interest level in late-life depression issues, and who had read late-life depression pamphlets or taken courses or classes in late-life depression. The findings suggest an urgent need to develop strategies to improve nurses' late-life depression knowledge and increase their confidence in providing care to older residents with depressive symptoms or depression., (© 2018 Australian College of Mental Health Nurses Inc.)

The practical implementation of an anode-free lithium-metal battery with promising high capacity is hampered by dendrite formation and low coulombic efficiency. Most notably, these challenges stem from non-uniform lithium plating and unstable SEI layer formation on the bare copper electrode. Herein, we revealed the homogeneous deposition of lithium and effective suppression of dendrite formation using a copper electrode coated with a polyethylene oxide (PEO) film in an electrolyte comprising 1 M LiTFSI, DME/DOL (1/1, v/v) and 2 wt% LiNO3. More importantly, the PEO film coating promoted the formation of a thin and robust SEI layer film by hosting lithium and regulating the inevitable reaction of lithium with the electrolyte. The modified electrode exhibited stable cycling of lithium with an average coulombic efficiency of ∼100% over 200 cycles and low voltage hysteresis (∼30 mV) at a current density of 0.5 mA cm-2. Moreover, we tested the anode-free battery experimentally by integrating it with an LiFePO4 cathode into a full-cell configuration (Cu@PEO/LiFePO4). The new cell demonstrated stable cycling with an average coulombic efficiency of 98.6% and capacity retention of 30% in the 200th cycle at a rate of 0.2C. These impressive enhancements in cycle life and capacity retention result from the synergy of the PEO film coating, high electrode-electrolyte interface compatibility, stable polar oligomer formation from the reduction of 1,3-dioxolane and the generation of SEI-stabilizing nitrite and nitride upon lithium nitrate reduction. Our result opens up a new route to realize anode-free batteries by modifying the copper anode with PEO to achieve ever more demanding yet safe interfacial chemistry and control of dendrite formation.

ABSTRACTBackground:To develop a theoretical model explaining the longitudinal changes in the caregiving process for family caregivers of persons with mild cognitive impairment (MCI) in Taiwan., Methods: A longitudinal, grounded theory approach using in-depth face-to-face interviews and an open-ended interview guide. We conducted 42 interviews over a two-year period; each participant was interviewed at least once every six months. All participants were interviewed in their home. The participants total of 13 family caregivers of persons with MCI., Results: One core theme emerged: "protective preparation." This reflected the family caregiving process of preparation for a further decline in cognitive function, and protection from the impact of low self-esteem, accidents, and symptoms of comorbidities for the family member with MCI. Protective preparation contained three components: ambivalent normalization, vigilant preparation, and protective management., Conclusions: Interventions to help family caregivers manage the changes in persons with MCI can reduce caregiver burden. Our findings could provide a knowledge base for use by healthcare providers to develop and implement strategies to reduce caregiver burden for family caregivers of persons with MCI.

The activation of hepatic stellate cells (HSCs) is a significant phenomenon during the pathogenesis of liver disorders, including liver cirrhosis and fibrosis. Here, we identified that the extract from a gorgonian coral Pinnigorgia sp. (Pin) induced apoptosis of HSC-T6 cells. Pin inhibited the viability of HSC-T6 cells and increased their subG1 population, DNA fragmentation, caspase-3 activation, and reactive oxygen species (ROS) production in a concentration-dependent manner. The Pin-induced ROS generation and apoptotic effects were significantly reversed by a thiol antioxidant, N -acetylcysteine (NAC). Additionally, Pin induced ERK/JNK phosphorylation and pharmacological inhibition of ERK/JNK rescued the Pin-induced cell death. Pin-activated ERK/JNK were significantly reduced after the administration of NAC; however, the inhibition of ERK/JNK failed to change the Pin-induced ROS production. Similarly, pinnigorgiol A, a pure compound isolated from Pin, elicited ROS production and apoptosis in HSC-T6 cells. The pinnigorgiol A-induced apoptosis was retrained by NAC. Together, it appears that Pin leads to apoptosis in HSC-T6 cells through ROS-mediated ERK/JNK signaling and caspase-3 activation. Pinnigorgiol A serves as a bioactive compound of Pin and may exhibit therapeutic potential by clearance of HSCs., Competing Interests: The authors declare no conflict of interest.

Aims: The aim of this study was to explore distinct trajectories of caregivers' depressive symptoms and the effects of a training programme on these trajectories over 18 months after the programme., Background: Overall effects of caregiver-training programmes on family caregivers' depressive symptoms have been reported, but few studies explored distinct courses of changes in caregivers' depressive symptoms and followed up intervention effects on these distinct courses., Design: Randomized clinical trial., Methods: Family caregivers (n = 116) were randomly assigned into experimental (n = 57) and control (n = 59) groups. The experimental group received the training programme with telephone consultation and the control group received written educational materials and social telephone follow-ups. Caregivers' depressive symptoms were assessed from June 2009 - March 2012 by self-completed questionnaires before, at 2 weeks and 3, 6, 12 and 18 months after the intervention. Groups of individual trajectories were distinguished using group-based trajectory modelling., Results: Caregivers' depressive symptoms fell into three stable trajectories: non-depressed, mildly blue and depressed. After controlling for covariates, caregivers who received the caregiver-training programme were less likely than those who did not experience persistent depressive symptoms (b = -1·92, odds ratio = 0·15, P < 0·05)., Conclusion: Depressive symptoms of family caregivers of persons with dementia were relatively stable and followed three distinct courses: non-depressed, mildly blue and depressed. Therefore, caregivers' depressive symptoms should be assessed as early as possible. Caregivers in the experimental group had a lower probability of persistent depressive symptoms than caregivers in the control group. Therefore, this training programme can be used by healthcare providers for persons with dementia and their caregivers., Trial Registration Number: NCT02667951., (© 2016 John Wiley & Sons Ltd.)

To determine distinct courses of change in health-related quality of life (HRQoL) among family caregivers of individuals with dementia and how participating in a home-based caregiver-training program affects the probability of belonging to each course. Sixty three caregivers were in the intervention group, and 66 caregivers were in the control group of a single-blinded randomized clinical trial. Two distinct trajectories of HRQoL were identified: a well-functioning trajectory and a poor-functioning trajectory. Caregivers who received the training program were more likely than those who did not have a well-functioning trajectory of HRQoL over 18 months. This trajectory included bodily pain (b = 1.02, odds ratio [OR] = 2.76), general health perception (b = 1.28, OR = 3.60), social functioning (b = 1.12, OR = 3.05), vitality (b = 1.51, OR = 4.49), general mental health (b = 1.08, OR = 2.94), and mental component summary (b = 1.27, OR = 3.55). Home-based caregiver training can be considered as part of the protocol for managing patients with dementia and their caregivers., Trial Registration Number: NCT02667951., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Seven new marine 11-acetoxy-9,11-secosterols, pinnisterols D-J ( 1 - 7 ), with a 1,4-quinone moiety, were discovered from the gorgonian coral Pinnigorgia sp. In this study, the structures of secosterols 1 - 7 were revealed by spectroscopic analysis. Bioactivity study showed that secosterol 1 treatment inhibited cell viability in a hepatic stellate cell line, HSC-T6, with an IC 50 value of 3.93 μM; and secosterols 2 , 5 , and 7 reduced elastase enzyme release, and 3 , 5 , and 7 decreased the production of superoxide anions from human neutrophils., Competing Interests: The authors declare no conflicts of interest.

Objective: This paper describes the trajectories of nutritional status and cognitive impairment and their correlation among older Taiwanese over 1 year after hip-fracture surgery., Design: Secondary analysis of data from a clinical trial evaluating the effects of three types of post-discharge care for 292 older hip-fracture patients (age >60 years)., Measurements: Nutritional status was assessed by the Mini Nutritional Assessment before and 1, 3, 6, 12 months after hospital discharge. Cognitive function was measured by the Mini-Mental State Examination before surgery, at hospital discharge, 6 and 12 months after discharge. Trajectories of nutritional status and cognitive impairment were depicted by latent class growth modeling, whereas linkages between nutritional-status and cognitive-impairment trajectories were assessed by multinomial logistic regression., Results: Nutritional status in general improved significantly, particularly during the first 3 months after discharge. We identified three trajectories of nutritional status: malnourished (15.4%), at risk for malnutrition (38.9%), and well-nourished (45.7%). In contrast, cognitive changes followed four largely linear but distinct trajectories: moderately impaired (12.2%), mildly impaired (27.8%), borderline impaired (21.8%), and cognitively intact (38.2%). Trajectories of nutritional status were significantly associated with cognitive-function trajectories. For instance, relative to malnourished patients, well-nourished patients were 95% less likely (OR=0.05, CI =0.01-0.24) to be moderately cognitively impaired., Conclusion: A good nutritional-status trajectory after hip fracture was associated with better cognitive function. To treat and care for elderly hip-fractured patients, specific interventions need to target those who are malnourished or at risk of malnutrition to decrease their risk for cognitive impairment.

miR-196a and/or miR-196b, involved in cancer initiation and progression, are frequently upregulated in tumour tissues. However, the clinical significance of these microRNAs in gastric cancer (GC) remains to be clarified. In the current study, we investigated the potential utility of circulating miR-196a/b as novel biomarkers for early detection and/or metastatic prognosis of GC. The quantitative real time-polymerase chain reaction data revealed markedly higher pre-operative circulating miR-196a and miR-196b levels in GC patients than healthy controls. Receiver-operating characteristics curve analysis showed that circulating miR-196a, miR-196b and combined miR-196a and miR-196b (miR-196a/b) are more effective than carcinoembryonic antigen or carbohydrate antigen 19-9 alone in distinguishing GC patients from healthy controls, with higher sensitivity and specificity. Circulating miR-196a exhibited higher diagnostic capacity than combined miR-196a/b or miR-196b alone, highlighting its potential as an effective plasma biomarker for GC. In clinicopathological analysis, elevated circulating miR-196a/b levels were highly correlated with metastatic potential or more advanced stages of disease and poorer survival. In addition, the expression levels of circulating miR-196a/b were reduced after surgical resection in GC patients. Taken together, we propose that circulating miR-196a/b serve as a more sensitive and specific novel biomarker than carbohydrate antigen 19-9 for GC monitor, diagnosis and prognosis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Patients with dementia differ in their behavioral and psychological symptoms according to their diagnosis with Alzheimer's disease (AD) or vascular dementia (VaD), requiring different symptom-management strategies. This study analyzed data from a sub-sample of a randomized clinical trial to determine the effects of a home-based training program on family caregivers of patients with dementia in northern Taiwan. Our sub-sample comprised patient-caregiver dyads (46 VaD and 68 AD patients) followed for 18 months. Caregivers of AD patients in the intervention group had better competence, preparedness, health-related quality of life, and fewer depressive symptoms than those in the control group. Caregivers of VaD patients in the intervention group had better competence and health-related quality of life than those in the control group. The training program benefited family caregivers of AD patients more than caregivers of VaD patients. Specific training programs need to be developed for family caregivers of VaD patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

MicroRNAs (miRNA) play an important role in carcinogenesis. Previously, we identified miR-26b as a significantly downregulated miRNA in gastric cancer (GC) tissues (n = 106) based on differential quantitative RT-PCR (RT-qPCR) miRNA expression profiles. In the current study, we aimed to clarify the potential role of miR-26b and related target genes in GC progression. Downregulation of miR-26b was associated with advanced tumor-node-metastasis stage (TNM stage) and poor 5-year survival rate. Forced expression of miR-26b led to inhibition of GC cell migration and invasion in vitro and lung metastasis formation in vivo. Conversely, depletion of miR-26b had stimulatory effects. Additionally, miR-26b affected GC cell behavior through negative regulation of the metastasis promoter, karyopherin alpha 2 (KPNA2). Ectopic expression of miR-26b induced a reduction in KPNA2 protein levels, confirmed by luciferase assay data showing that miR-26b directly binds to the 3' untranslated regions (UTR) of KPNA2 mRNA. Furthermore, miR-26b and KPNA2 mRNA/protein expression patterns were inversely correlated in GC tissues. Cag A of Helicobacter pylori (Hp) enhanced miR-26b levels through regulation of the KPNA2/c-jun pathway. Taken together, our data indicate that miR-26b plays an anti-metastatic role and is downregulated in GC tissues via the KPNA2/c-jun pathway. Based on the study findings, we propose that miR-26b overexpression or KPNA2/c-jun suppression may have therapeutic potential in inhibiting GC metastasis., Competing Interests: The authors declare no conflicting financial interests.

Adhesion molecules expressed on cerebral endothelial cells (ECs) mediate leukocyte recruitment and play a significant role in cerebral inflammation. Increased levels of adhesion molecules on the EC surface induce leukocyte infiltration into inflammatory areas and are thus hallmarkers of inflammation. Honokiol, isolated from the Chinese medicinal herb Magnolia officinalis, has various pharmacological activities, including anti-inflammatory effects, yet the nature of honokiol targeting molecules remains to be revealed. Here, we investigated the inhibitory effect of honokiol on neutrophil adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression, which underlie its molecular target, and mechanisms for inactivating nuclear factor κ enhancer binding protein (NF-κB) in mouse cerebral ECs. Honokiol inhibited tumour necrosis factor-α (TNF-α)-induced neutrophil adhesion and VCAM-1 gene expression in cerebral ECs. The inflammatory transcription factor NF-κB was downregulated by honokiol. Honokiol significantly blocked TNF-α-induced NF-κB p65 nuclear translocation and degradation of the proteasome-dependent inhibitor of NF-κB α (IκBα). From docking model prediction, honokiol directly targeted the ubiquitin-ubiquitin interface of Lys48-linked polychains. Moreover, honokiol prevented the TNF-α-induced Lys48-linked polyubiquitination, including IκBα-polyubiquitin interaction. Honokiol has protective anti-inflammatory effects on TNF-α-induced neutrophil adhesion and VCAM-1 gene expression in cerebral ECs, at least in part by directly inhibiting ubiquitination-mediated IκBα degradation and then preventing NF-κB nuclear translocation.

The expression of cancer stemness is believed to reduce the efficacy of current therapies against hepatocellular carcinoma (HCC). Understanding of the stemness-regulating signaling pathways incurred by a specific etiology can facilitate the development of novel targets for individualized therapy against HCC. Niche environments, such as virus-induced inflammation, may play a crucial role. However, the mechanisms linking inflammation and stemness expression in HCC remain unclear. Here we demonstrated the distinct role of inflammatory mediators in expressions of stemness-related properties involving the pluripotent octamer-binding transcription factor 4 (OCT4) in cell migration and drug resistance of hepatitis B virus-related HCC (HBV-HCC). We observed positive immunorecognition for macrophage chemoattractant protein 1 (MCP-1)/CD68 and OCT4/NANOG in HBV-HCC tissues. The inflammation-conditioned medium (inflamed-CM) generated by lipopolysaccharide-stimulated U937 human leukemia cells significantly increased the mRNA and protein levels of OCT4/NANOG preferentially in HBV-active (HBV+HBsAg+) HCC cells. The inflamed-CM also increased the side population (SP) cell percentage, green fluorescent protein (GFP)-positive cell population, and luciferase activity of OCT4 promoter-GFP/luciferase in HBV-active HCC cells. Furthermore, the inflamed-CM upregulated the expressions of insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) and activated IGF-IR/Akt signaling in HBV-HCC. The IGF-IR phosphorylation inhibitor picropodophyllin (PPP) suppressed inflamed-CM-induced OCT4 and NANOG levels in HBV+HBsAg+ Hep3B cells. Forced expression of OCT4 significantly increased the secondary sphere formation and cell migration, and reduced susceptibility of HBV-HCC cells to cisplatin, bleomycin, and doxorubicin. Taking together, our results show that niche inflammatory mediators play critical roles in inducing the expression of stemness-related properties involving IGF-IR activation, and the upregulation of OCT4 contributes to cancer migration and drug resistance of HBV-HCC cells. Findings in this paper would provide potential targets for a therapeutic strategy targeting on inflammatory environment for HBV-HCC.

Three new 9,11-secosterols, pinnisterols A-C (1-3), were isolated from a gorgonian coral Pinnigorgia sp., collected off the waters of Taiwan. The structures of these compounds were elucidated on the basis of spectroscopic methods. The new sterols 1 and 3 displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils, and sterol 1 was found to show moderate cytotoxicity in hepatic stellate cells (HSCs).

The leaves of Perilla frutescens (L.) Britt. have been traditionally used as an herbal medicine in East Asian countries to treat a variety diseases. In this present study, we investigated the inhibitory effects of P. frutescens extract (PFE) on N-formyl-Met-Leu-Phe (fMLF)-stimulated human neutrophils and the underlying mechanisms. PFE (1, 3, and 10 μg/ml) inhibited superoxide anion production, elastase release, reactive oxygen species formation, CD11b expression, and cell migration in fMLF-activated human neutrophils in dose-dependent manners. PFE inhibited fMLF-induced phosphorylation of the Src family kinases (SFKs), Src (Tyr416) and Lyn (Tyr396), and reduced their enzymatic activities. Both PFE and PP2 (a selective inhibitor of SFKs) reduced the phosphorylation of Burton's tyrosine kinases (Tyr223) and Vav (Tyr174) in fMLF-activated human neutrophils. Additionally, PFE decreased intracellular Ca(2+) levels ([Ca(2+)]i), whereas PP2 prolonged the time required for [Ca(2+)]i to return to its basal level. Our findings indicated that PFE effectively regulated the inflammatory activities of fMLF-activated human neutrophils. The anti-inflammatory effects of PFE on activated human neutrophils were mediated through two independent signaling pathways involving SFKs (Src and Lyn) and mobilization of intracellular Ca(2+).

Oxidative stress caused by neutrophils is an important pathogenic factor in trauma/hemorrhagic (T/H)-induced acute lung injury (ALI). Osthol, a natural coumarin found in traditional medicinal plants, has therapeutic potential in various diseases. However, the pharmacological effects of osthol in human neutrophils and its molecular mechanism of action remain elusive. In this study, our data showed that osthol potently inhibited the production of superoxide anion (O2(•-)) and reactive oxidants derived therefrom as well as expression of CD11b in N-formylmethionylleucylphenylalanine (FMLP)-activated human neutrophils. However, osthol inhibited neutrophil degranulation only slightly and it failed to inhibit the activity of subcellular NADPH oxidase. FMLP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) was inhibited by osthol. Notably, osthol increased the cAMP concentration and protein kinase A (PKA) activity in activated neutrophils. PKA inhibitors reversed the inhibitory effects of osthol, suggesting that these are mediated through cAMP/PKA-dependent inhibition of ERK and Akt activation. Furthermore, the activity of cAMP-specific phosphodiesterase (PDE) 4, but not PDE3 or PDE7, was significantly reduced by osthol. In addition, osthol reduced myeloperoxidase activity and pulmonary edema in rats subjected to T/H shock. In conclusion, our data suggest that osthol has effective anti-inflammatory activity in human neutrophils through the suppression of PDE4 and protects significantly against T/H shock-induced ALI in rats. Osthol may have potential for future clinical application as a novel adjunct therapy to treat lung inflammation caused by adverse circulatory conditions., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To unravel the role of interleukin (IL)-6 and insulin-like growth factor (IGF)-I receptor (IGFIR) in expressing stemness-related properties and to evaluate the prognostic values of pluripotent transcription factor OCT4/NANOG, and IGFIR in hepatocellular carcinoma (HCC)., Experimental Design: Serum levels of IL6 were detected using ELISA assays (n = 120). The effects of IL6/IGFI on stemness expression in HCC were examined using OCT4/NANOG promoter luciferase reporter, RNA interference, secondary sphere formation, side population, and xenograft animal models. The OCT4/NANOG protein and phospho-IGFI receptor (p-IGFIR) in tissues were detected by Western blotting (n = 8) and immunohistochemical staining (n = 85). OCT4, NANOG, and IGFIR expression levels in tissues (n = 191) were analyzed by real-time qRT-PCR and was correlated with early tumor recurrence using the Kaplan-Meier survival analysis., Results: A high positive correlation between the expression levels of OCT4/NANOG and IGFIR/p-IGFIR in human HCC tissues was observed. The concurrent expression of OCT4/NANOG/IGFIR was mostly confined to hepatitis B virus (HBV)-related HCC (HBV-HCC) and was significantly correlated with early tumor recurrence. High serum levels of IL6 were significantly correlated with high OCT4/NANOG expression. IL6 stimulated an autocrine IGFI/IGFIR expression STAT3 dependently, which stimulated stemness-related properties in both the cell lines and the xenografted mouse tumors. The inhibition of IGFIR activation by either RNA interference or by treatment with the inhibitor picropodophyllin (PPP) significantly suppressed the IL6-induced stemness-related properties both in vitro and in vivo., Conclusions: The expression of pluripotency-related genes is associated with early tumor recurrence and is regulated by IL6-induced IGF/IGFIR activation, particularly in HBV-HCC., (©2014 American Association for Cancer Research.)

Proliferation of hepatic stellate cells (HSCs) plays a key role in the pathogenesis of liver fibrosis. Induction of HSC apoptosis by natural products is considered an effective strategy for treating liver fibrosis. Herein, the apoptotic effects of 7,20-epoxy-ent-kaurane (oridonin), a diterpenoid isolated from Rabdosia rubescens, and its underlying mechanisms were investigated in rat HSC cell line, HSC-T6. We found that oridonin inhibited cell viability of HSC-T6 in a concentration-dependent manner. Oridonin induced a reduction in mitochondrial membrane potential and increases in caspase 3 activation, subG1 phase, and DNA fragmentation. These apoptotic effects of oridonin were completely reversed by thiol antioxidants, N-acetylcysteine (NAC) and glutathione monoethyl ester. Moreover, oridonin increased production of reactive oxygen species (ROS), which was also inhibited by NAC. Significantly, oridonin reduced intracellular glutathione (GSH) level in a concentration- and time-dependent fashion. Additionally, oridonin induced phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). NAC prevented the activation of MAPKs in oridonin-induced cells. However, selective inhibitors of MAPKs failed to alter oridonin-induced cell death. In summary, these results demonstrate that induction of apoptosis in HSC-T6 by oridonin is associated with a decrease in cellular GSH level and increase in ROS production.

Background: Malnutrition has been associated with poor health outcomes in hospitalized patients. This study assessed the validity of the scored patient-generated subjective global assessment (PG-SGA) in adult patients who had undergone an open appendectomy, and examined the association of this assessment tool with length of hospital stay., Methods: Nutritional status was determined by using the scored PG-SGA in adult patients (n = 86) who had undergone an open appendectomy within 24 hours of admission. Variables were compared between well-nourished and malnourished participants. Regression analysis was used to identify potential predictors for length of hospital stay. Receiver operator characteristic (ROC) analysis was used to examine the validity of the PG-SGA score to predict the nutritional status., Results: On admission, 17% of the study subjects were malnourished and associated with a significantly older age (53.0 vs. 39.5), greater PG-SGA score (8 vs. 2), higher comorbidity (67% vs. 27%), and longer length of hospital stay (6.9 d vs. 4.1 d). The PG-SGA score and comorbidity were the determined risk factors for length of hospital stay after performing multiple regression analysis. Furthermore, the PG-SGA score had a significantly positive correlation with length of hospital stay (Spearman's rho = 0.378, p < 0.001). The area under the ROC curve indicating the PG-SGA score, compared with nutritional status, is 0.9751., Conclusions: The scored PG-SGA in adults receiving an appendectomy is significantly associated with length of hospital stay, and is an effective tool for assessing the nutritional status of patients with cancer and chronic illness, as well as of patients with acute surgical abdomen.

Background: Little is known about the differences in patients' behavioral problems and health outcomes of family caregivers of patients with vascular dementia (VaD) and Alzheimer's disease (AD)., Methods: A secondary analysis of baseline data on a subsample of caregiver-dementia patient dyads in a randomized clinical trial., Results: Family caregivers of VaD patients reported higher self-efficacy than caregivers of AD patients in handling verbally nonaggressive and verbally aggressive behaviors. Caregivers of VaD patients had poorer health-related quality of life (HRQoL) than caregivers of AD patients considering role disability due to physical health problems, bodily pain, social function, and physical component summary. Greater self-efficacy was associated with better mental health-related outcomes for family caregivers of VaD patients, and better self-care ability of VaD patients was associated with better caregiver mental health-related outcomes. Caring for a patient with more severe dementia predicted poor physical health-related outcomes in role disability due to physical health problems, but better overall mental health (mental component summary) for caregivers., Conclusion: This study is the first to examine and compare the behavioral problems of AD and VaD patients in a Chinese population, along with their family caregivers' self-efficacy and health outcomes. Family caregivers of patients with VaD might warrant specific attention to their HRQoL, with interventions developed to enhance their self-efficacy.

A new benzo[c]phenanthridine, oxynorchelerythrine (1), and two new benzenoid derivatives, methyl 4-(2-hydroxy-4-methoxy-3-methyl-4-oxobutoxy)benzoate (2) and (E)-methyl 4-(4-((Z)-3-methoxy-3-oxoprop-1-enyl)phenoxy)-2-methylbut-2-enoate (3), have been isolated from the twigs of Zanthoxylum ailanthoides, together with 11 known compounds (4-14). The structures of these new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, decarine (4), (-)-syringaresinol (6), (+)-episesamin (8), glaberide I (9), (-)-dihydrocubebin (10), and xanthyletin (11) exhibited potent inhibition (IC50 values ≤ 4.79 µg/mL) of superoxide anion generation by human nutrophils in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 4, 8, and 11 also inhibited fMLP/CB-induced elastase release with IC50 values ≤ 5.48 µg/mL.

Objective: To investigate the effects of an individualized, home-based caregiver-training program for caregivers of elderly patients with dementia and behavioral problems., Methods: Using a randomized clinical trial in the neurologic clinics of two hospitals and a community care management center in northern Taiwan, we tested an individualized home-based caregiver-training program for managing behavioral problems, with referrals to community services and telephone consultation. Participants were patients with dementia and their caregivers (N = 129): 63 in the intervention group and 66 in the control group. The control group received only written instructions and social telephone follow-ups. Behavioral problems of elderly dementia patients were assessed by the Chinese version of the Cohen-Mansfield Agitation Inventory, community form. Family caregivers' outcomes were measured by the Agitation Management Self-efficacy Scale and the Preparedness and Competence Scales. These instruments were administered before the program and 2 weeks, 3 months, and 6 months afterward., Results: Family caregivers who received the individualized home-based training program had better preparedness (t = 2.72, df = 127, p <0.01), competence (t = 4.77, df = 126, p <0.001), and overall self-efficacy (t = 3.81, df = 127, p <0.001) at 3 months than those in the control group. Moreover, the growth rate by treatment interaction effect was significant for caregiver competence (t = 2.25, df = 127, p <0.05) and overall self-efficacy for managing behavioral problems (t = 2.16, df = 127, p <0.05). The probability of physically aggressive behavior for patients in the intervention group decreased from 0.27 to 0.12., Conclusion: Our individualized home-based caregiver-training program improved caregivers' preparedness, competence, and self-efficacy for managing problematic behaviors and decreased physical aggressiveness of elderly patients with dementia., (Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: Little is known about the longitudinal effects of training programs on family caregivers' health-related quality of life (HRQoL) and depressive symptoms over time. Therefore, the purpose of this study was to examine the effects of a home-based caregiver training program on HRQoL and depressive symptoms for family caregivers of older persons with dementia., Methods: Outcomes (caregivers' HRQoL and depressive symptoms) were assessed before the training program (baseline), and at 2 weeks, 3 months, and 6 months afterwards. HRQoL was measured using the Medical Outcomes Study 36-item Short Form Survey, Taiwan version. Depressive symptoms were measured using the Chinese version Center for Epidemiologic Studies Depression Scale., Results: Family caregivers who received the individualized home-based training program had better health outcomes in bodily pain (b = 12.37, p < 0.013), role disability due to emotional problems (b = 17.74, p < 0.013), vitality (b = 12.40, p < 0.001), better mental summary score (b = 5.14, p < 0.003), and decreased risk for depression (odds ratio = 0.15, confidence interval = 0.04-0.65, p < 0.013) than those in the control group during the 6 months following the training program., Conclusion: Our home-based caregiver training program improved caregivers' HRQoL, especially role limitations due to emotional problems, and decreased their risk for depression., (Copyright © 2012 John Wiley & Sons, Ltd.)

Four new 8,8',7,2'-lignans, (+)-ovafolinin B-9'-O-β-d-glucopyranoside (1), (-)-ovafolinin B-9'-O-β-d-glucopyranoside (2), (+)-ovafolinin E-9'-O-β-d-glucopyranoside (3), and (-)-ovafolinin E-9'-O-β-d-glucopyranoside (4), two neolignans, eusiderin N (5) and (7S,8R)-3,5,5'-trimethoxy-4',7-epoxy-8,3'-neolignan-9,9'-diol-4-O-β-d-xylopyranoside (6), and two new chromone glycosides, 5,7-dihydroxy-4H-chromen-4-one-3-O-β-d-glucopyranoside (7) and 5,7-dihydroxy-4H-chromen-4-one-3-O-β-d-xylopyranoside (8), together with 25 known compounds, were isolated from the stems of Eurya japonica. Structural elucidation of compounds 1-8 was established by spectroscopic methods, especially 2D NMR techniques, electronic circular dichroism data, and comparison with reported data. The isolates were evaluated for antioxidant and anti-NO production activities. Compounds 1, 2, 12-20, and 29 (ED50 23.40 μM for 1) demonstrated potent antioxidant activity compared to the positive control α-tocopherol (ED50 27.21 μM). On the other hand, compounds 1, 2, 7-9, 12-20, and 32 showed only weak anti-NO production activity when compared to the positive control quercetin.

Six new triterpenoids, euscaphic acids G-L (1-6), along with nine known triterpene acids, and two known lignans were isolated from the ethanolic extract of the twigs of Euscaphis japonica. This is the first report concerning 1α,3β-dihydroxy-12-oleanen-28-oic acid isolated from a natural source. The structures of the new compounds were established by spectroscopic analysis. The cytotoxic and anti-NO production activities for the isolates are also evaluated and discussed; compound 1, hederagenin (11), and arjunic acid (12) showed significant cytotoxicity against NCI-H460 cells, HT-29 cells, and CEM cells (IC₅₀ = 1.64 ± 0.87, 2.11 ± 1.54, 1.73 ± 0.64 µM, respectively). Some of the isolated triterpenoids showed marginal inhibitions on NO production induced by LPS., (Georg Thieme Verlag KG Stuttgart · New York.)

Bioassay-guided fractionation of the EtOH extract of the dried twigs of Podocarpus nakaii Hayata (Podocarpaceae), endemic plant in Taiwan has resulted in isolation of four [3'→8″]-biflavonoid derivatives, amenotoflavone (AF), podocarpusflavone-A (PF), II-4″,I-7-dimethoxyamentoflavone (DAF), and heveaflavone (HF). Their structures were determined by physical and extensive spectroscopic analyses such as (1)H, (13)C, (1)H-(1)H COSY, HMQC, and HMBC, as well as comparison with literature values. Compounds PF and DAF showed significant inhibitions against DLD, KB, MCF-7, HEp-2 tumor cell lines (ED50 ca. 4.56-16.24 μg/mL) and induced cell apoptosis in MCF-7 via mainly sub-G1/S phase arrest. Furthermore, these compounds exhibited moderate Topoisomerase I inhibitory activity.