Relative D3 vitamin deficiency and consequent cognitive impairment in an animal model of Alzheimer's disease: Potential involvement of collapsin response mediator protein-2.

Alzheimer's disease (AD) starts with memory impairments that can be observed before the appearance of significant neuropathology; thus, identifying mechanisms to stop AD progression is an urgent priority. Epidemiological and clinical data show that the consequences of vitamin D deficiency are relevant to disease risk and can be observed in the progression of many diseases, especially AD, whereas higher serum levels of vitamin D are associated with better cognitive test performance. However, the potential therapeutic strategy and underlying mechanisms of vitamin D supplementation against AD still need to be further investigated. In the present study, we found that 3xTg-AD mice with vitamin D supplementation exhibited an increase in serum vitamin D concentrations and improved cognition. We measured serum vitamin D binding protein (VDBP) concentrations and found that serum VDBP levels were increased in 3xTg-AD mice compared to B6129S control mice, but there was no significant difference between control- and vitamin D-treated 3xTg-AD groups. The vitamin D-mediated memory improvement may be accompanied by the suppression of increased hippocampal collapsin response mediator protein-2 (CRMP2) phosphorylation, and the restoration of CRMP2 phosphorylation by okadaic acid (OA) could abolish the beneficial effects of vitamin D. In addition, we found that CRMP2 was associated with NR2B and PSD-95 in 3xTg-AD mice with vitamin D supplementation. This CRMP2-NR2B interaction could be disrupted by a TAT-CBD3 peptide or OA, leading to attenuated memory protection in vitamin D-treated 3xTg-AD mice. Therefore, CRMP2 may be involved in vitamin D-mediated memory improvement in AD.

Colorectal cancer in Taiwan: A case-control retrospective analysis of the impact of a case management programme on refusal and discontinuation of treatment.

AIMS: The purposes of this study were to identify the impact of a case management programme on the related factors of refusing treatment or discontinuing treatment in Taiwanese colorectal cancer patients. BACKGROUND: Side effects of anti-cancer treatments are associated with refusing treatment and discontinuing treatment. DESIGN: This case-control study, longitudinal database and secondary analysis of population-based data was conducted from 2009-2012. METHODS: Logistic regression was used to reveal the factors related to refusing or discontinuing treatment. RESULTS: Of the 68 patients who refused treatment, the top reasons for refusing treatment were patients or their family considered the patients poor physical condition, difficulty in enduring any condition likely to cause physical discomfort from the disease treatment, selected complementary and alternative medicine, patients or their families or friends experienced negative treatment effects and worried about the side effects of treatment, older age, poor family support and lost contact. Of the 278 patients who discontinued treatment, the most common reasons for discontinuing treatment were patients or their families or friends experienced negative treatment effects and worried about the side effects of treatment, inconvenient transportation, patients or their family considered the patients poor physical condition, difficulty in enduring any condition likely to cause physical discomfort from the disease treatment, poor treatment effect and selected complementary and alternative medicine. CONCLUSION: Case managers can provide positive communication and available resources in relation to cancer treatment. A case management programme can help patients cope with the difficulties encountered during the treatment period.

Three-dimensional spheroid culture targeting versatile tissue bioassays using a PDMS-based hanging drop array.

Biomaterial-based tissue culture platforms have emerged as useful tools to mimic in vivo physiological microenvironments in experimental cell biology and clinical studies. We describe herein a three-dimensional (3D) tissue culture platform using a polydimethylsiloxane (PDMS)-based hanging drop array (PDMS-HDA) methodology. Multicellular spheroids can be achieved within 24 h and further boosted by incorporating collagen fibrils in PDMS-HDA. In addition, the spheroids generated from different human tumor cells exhibited distinct sensitivities toward drug chemotherapeutic agents and radiation as compared with two-dimensional (2D) cultures that often lack in vivo-like biological insights. We also demonstrated that multicellular spheroids may enable key hallmarks of tissue-based bioassays, including drug screening, tumor dissemination, cell co-culture, and tumor invasion. Taken together, these results offer new opportunities not only to achieve the active control of 3D multicellular spheroids on demand, but also to establish a rapid and cost-effective platform to study anti-cancer therapeutics and tumor microenvironments.

[Clinical Trials for Treatment of Allergic Rhinitis with Heat Sensitive Moxibustion and Its Regularity of Heat-sensitization Acupoint Distribution].

OBJECTIVE: To observe the clinical effect of heat sensitive moxibustion (HSM) and its regularity of acupoint heat-sensitization in the treatment of allergic rhinitis (AR) patients. METHODS: Seventy patients with AR were randomly divided into HSM and manual acupuncture groups (n＝35/group). For patients of the HSM group, acupoints Yintang (EX-HN 3), bilateral Yingxiang (LI 20), Shangxing (GV 23), Tongtian (BL 7), Feishu (BL 13), Hegu (LI 4), etc. were used, and for patients of the manual acupuncture group, bilateral LI 20 and LI 4, Bitong (EX-HN 8) and EX-HN 3 were needled and stimulated with uniform reinforcing-reducing needling method. The treatment was conducted once every other day, for 20 days, with 3 days' interval between two 10 days. The symptoms of sneezing, running nose, nasal obstruction, and nasal itching were scored as 1, 2 and 3 points according to their severity. The signs of turbinate-nose cavity bottom/nasal septum correlation, morphological state (swelling or not) of inferior nasal concha and color of nasal mucosa, appearance (deviation or polyp) of the middle turbinate and nasal septum were scored as 1, 2 and 3 points according to their severity. The total score equaled to symptom score plus nasal sign score. The distribution of heat sensitization acupoints for effectively improving AR were recorded. RESULTS: The total effective rate of 82.86%(29/35) in the HSM group had no marked difference in comparison with that of 74.29%(26/35) in the manual acupuncture group (P>0.05). After the treatment, the total scores of symptoms and nasal signs of both HSM and manual acupuncture groups were significantly reduced in comparison with their own individual pre-treatment (P<0.01), and those in the HSM group were significantly decrased than those in the manual acupuncture group (P<0.05). In 35 patients of the HSM group, among the detected 57 acupoints, the most frequently sensitive acupoints were LI 20, EX-HN 3, EX-HN 8, Shangyintang, BL 13, Shenque(CV 8), GV 23, Fengchi(GB 20), Die'e and Dazhui (GV 14) in sequence, mainly covering the Governor Vessel, Large Intestine Meridian of Hand-yangming(LI), and Bladder Meridian of Foot-taiyang(BL), and characterized by heat conduction, heat diffusion, diathermancy, non-thermal (mainly itching) sensation, thermal sensation mainly in the deep tissue and in the distant part rather than in the body surface and the local part. CONCLUSIONS: HSM has a positive effect on improvement of AR, when applied, acupoints LI 20, EX-HN 3, EX-HN 8, Shangyintang, BL 13, CV 8, GV 23, GB 20, Die'e and GV 14 are highly recommended.