Non-Pharmacological Interventions for Feeding and Eating Disorders in Persons with Dementia: Systematic Review and Evidence Summary.

BACKGROUND: Feeding and eating disorders related to cognitive and psycho-behavioral symptoms are strongly associated with health status in persons with dementia (PWD). Non-pharmacological interventions have been the priority selection to address this significant issue. However, the direct targets of non-pharmacological interventions are unclear and there is no consistent evidence of recommendations on the intervention of different dementia stages and the settings of intervention practice. OBJECTIVE: To provide caregivers with a set of self-help non-pharmacological interventions for feeding and eating disorders in PWD. METHODS: Based on the process of evidence summary, a systematic literature search was performed on dementia websites and seven databases. Two researchers screened the studies independently and appraise the quality. The evidence was graded by Joanna Briggs Institute Grades of Recommendation. RESULTS: Twenty-eight articles were included. Twenty-three non-pharmacological intervention recommendations were categorized into six themes containing oral nutritional supplementation, assistance with eating and drinking, person-centered mealtime care, environmental modification, education or training, and multi-component intervention. These interventions corresponded to three direct targets including improving engagement, making up for loss ability, and increasing food intake directly. They were applied to different stages of dementia and most interventions were targeted at PWD in long-term care institutions. CONCLUSION: This article summarized the direct targets and the specific implementation of recommendations at different stages of dementia to provide caregivers with self-help non-pharmacological interventions. The practice of recommendations was more applicable to institutionalized PWD. When applied to PWD at home, caregivers need to identify the specific feeding and eating conditions at different stages and adopted the interventions in conjunction with the wishes of the PWD and professional advice.

Anti-Swelling, Robust, and Adhesive Extracellular Matrix-Mimicking Hydrogel Used as Intraoral Dressing.

Due to the wet and dynamic environment of the oral cavity, the healing of intraoral wounds, such as tooth extraction wounds, requires stable and firm wound dressings. In clinical practice, cotton balls and gauzes, sponge plugs, or sutures are used to treat extraction wounds, but none of these means can continuously isolate the wound from the intraoral environment and facilitate ideal healing conditions. Herein, inspired by the natural extracellular matrix, a family of wound dressings is developed for intraoral wound repair. Infiltrating a ductile long-chain hydrogel network into a prefabricated, sturdy macromolecular meshwork and in situ crosslinking endowed the composite hydrogel with controllable swelling behaviors and robust mechanical properties. The macromolecular meshwork functioned as the backbone to support the composite and restricts the swelling of the long-chain hydrogel network. In vitro tests verified that this wound dressing can provide durable protection for intraoral wounds against complex irritations. Furthermore, accelerated wound healing occurred when the wound dressing is applied in vivo on a canine tooth extraction model, due to the effective reduction of acute inflammation. These results suggest that this family of bioinspired hydrogels has great potential for application as intraoral wound dressing.

Identification of differentially expressed proteins in the gastric mucosal atypical hyperplasia tissue microenvironment.

In the present study, the interaction of proteins in the microenvironment of gastric mucosal atypical hyperplasia was analyzed. The stromata of normal gastric mucosa (NGM) and gastric mucosal atypical hyperplasia (GMAH) tissues were purified with laser capture microdissection (LCM). The differentially expressed GMAH proteins of the NGM and GMAH tissues were identified by quantitative proteomic techniques with isotope labeling. The cross-talk between differentially expressed proteins in NGM and GMAH tissues was then analyzed by bioinformatics. There were 165 differentially expressed proteins identified from the stromata of NGM and GMAH tissues. Among them, 99 proteins were upregulated and 66 were downregulated in GMAH tissue. The present study demonstrated that these proteins in gastric mucosal atypical hyperplasia were involved in cancer-associated signaling pathways, including the p53, mitogen-activated protein kinase (MAPK), cell cycle and apoptosis signaling pathways, and were involved in cellular growth, cellular proliferation, apoptosis and the humoral immune response. The results of the present study suggest that the 165 differentially expressed proteins, including S100 calcium-binding protein A6 (S100A6) and superoxide dismutase 3 (SOD3) in the microenvironment of gastric mucosal atypical hyperplasia, are involved in the p53, MAPK, cell cycle and apoptosis signaling pathways, and serve a function in the pathogenesis of gastric cancer.

[Expression and clinical significance of EMS1 gene in gastric carcinoma].

BACKGROUND & OBJECTIVE: EMS1 (chromosome eleven, band q13, mammary tumor and squamous cell carcinoma-associated gene 1) is correlated to the genesis, progression, invasion and metastasis of some malignancies. This study was to investigate the expression of EMS1 protein in gastric carcinoma, and to explore its correlation to the carcinogenesis of gastric carcinoma. METHODS: The expression of EMS1 protein in 20 specimens of normal gastric mucosa, 38 specimens of intraepithelial neoplasia, and 146 specimens of gastric carcinoma was detected by immunohistochemistry. RESULTS: EMS1 protein was expressed in cytoplasm. The positive rate of EMS1 protein was significantly higher in gastric carcinoma than in intraepithelial neoplasia and normal gastric mucosa (89.7% vs. 68.4% and 20.0%, P<0.001), and significantly higher in intraepithelial neoplasia than in normal gastric mucosa (P<0.001). The positive rate of EMS1 protein was significantly lower in the gastric carcinomas at early stages than in those at advanced stages (60.9% vs. 95.1%, P<0.001), and significantly higher in the gastric carcinomas with lymph node metastases than in those without lymph node metastases (96.8% vs. 77.0%, P<0.001). EMS1 protein expression had no correlations to sex, age, tumor differentiation and diameter. CONCLUSION: EMS1 protein expression is related to the carcinogenesis, lymph node metastasis and clinical stage of gastric carcinoma.

Direct evidence that Bcr-Abl tyrosine kinase activity disrupts normal synergistic interactions between Kit ligand and cytokines in primary primitive progenitor cells.

We previously reported that chronic myelogenous leukemia (CML) primitive granulocyte-monocyte (GM) progenitors have a greatly reduced requirement for kit ligand (KL) to achieve optimal growth with granulocyte colony-stimulating factor (G-CSF) + granulocyte-monocyte colony-stimulating factor (GM-CSF). Conversely, others have demonstrated that unlike normal, CML CD34+ progenitors can proliferate in response to KL as a sole stimulus. To address these seemingly paradoxical findings, we examined the growth responses of CML CD34+ GM progenitors to various cytokines with and without a potent inhibitor of Bcr-Abl tyrosine kinase activity, PD173955. The heightened growth responses of CML GM progenitors to KL alone and to G-CSF + GM-CSF were abrogated by 10 nM PD173955 while having no effect on normal GM progenitors. While normal GM progenitors exhibited the expected synergistic response when KL was added to G-CSF + GM-CSF, CML GM progenitors had a minimal response; however, some synergism was restored by 10 nM PD173955. Normal erythroid progenitors require the synergistic interaction between KL and a saturating amount of erythropoietin (EPO, 1 unit) for optimal growth. In contrast, CML erythroid progenitors had up to 50% of optimal growth in KL alone, and, only a subthreshold amount of EPO (0.1 unit) was needed with KL to achieve 85% of the optimal response; these heightened growth responses were largely abrogated by 10 nM PD173955. Thus, direct evidence is provided that constitutively activated Bcr-Abl kinase pathways in primitive CML progenitors cooperate with single growth factors producing a heightened growth response, and, in so doing, disrupt the normally required synergistic interactions between KL and other cytokines to achieve activation and optimal growth of primitive progenitors. Coupled with our previous findings that a larger than normal proportion of CML primitive progenitors are at a later stage of maturation, we propose that this disruption of normal synergistic responses leads to increased progenitor recruitment into a committed pool by a process of accelerated maturation.

Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinases.

The early stage of chronic myelogenous leukemia (CML) is caused by the tyrosine kinase Bcr-Abl. Imatinib mesylate (also known as STI-571 and Gleevec), a tyrosine kinase inhibitor, has shown encouraging results in CML clinical trials and has become a paradigm for targeted cancer therapeutics. Recent reports of resistance to imatinib argue for further development of therapies for CML. During studies of signal transduction, we observed that the pyrido[2,3-d]pyrimidine src tyrosine kinase inhibitor PD173955 inhibited Bcr-Abl-dependent cell growth. Subsequently, a related compound, PD180970, was reported as a potent inhibitor of Bcr-Abl. We have compared the potency of these two compounds and four other analogues with imatinib on Bcr-Abl-dependent cell growth, cytokine-dependent cell growth, and tyrosine kinase inhibition. PD173955 inhibited Bcr-Abl-dependent cell growth with an IC(50) of 2-35 nM in different cell lines. Fluorescence-activated cell-sorting analyses of cells treated with PD173955 showed cell cycle arrest in G(1). PD173955 has an IC(50) of 1-2 nM in kinase inhibition assays of Bcr-Abl, and in cellular growth assays it inhibits Bcr-Abl-dependent substrate tyrosine phosphorylation. Of the six pyrido[2,3-d]pyrimidine analogues studied, PD166326 was the most potent inhibitor of Bcr-Abl-dependent cell growth. PD173955 inhibited kit ligand-dependent c-kit autophosphorylation (IC(50) = approximately 25 nM) and kit ligand-dependent proliferation of M07e cells (IC(50) = 40 nM) but had a lesser effect on interleukin 3-dependent (IC(50) = 250 nM) or granulocyte macrophage colony-stimulating factor (IC(50) = 1 microM)-dependent cell growth. These compounds are potent inhibitors of both the Bcr-Abl and c-kit receptor tyrosine kinases and deserve further study as potential treatments for both CML and for diseases in which c-kit has a role.