Development of an adaptive, personalized, and scalable dementia care program: Early findings from the Care Ecosystem.

Katherine Possin and colleagues report on the implementation, development, and early findings of the Care Ecosystem, an adaptive, personalized, and scalable dementia care program.

Implications of the colonic deposition of free hemoglobin-α chain: a previously unknown tissue by-product in inflammatory bowel disease.

BACKGROUND: We analyzed inflamed mucosal/submucosal layers of ulcerative colitis (UC = 63) and Crohn's colitis (CC = 50), and unexpectedly, we unveiled a pool of free hemoglobin alpha (Hb-α) chain. Patients with colitides have increased reactive oxidative stress (ROS), DNA oxidation products, free iron in mucosa, in preneoplastic, and in colitis-cancers and increased risks of developing colorectal cancer. All inflammatory bowel disease-related colorectal cancer lesions are found in segments with colitis. Linking this information, we investigated whether free Hb-α is key transformational stepping that increases colitis-related colorectal cancer vulnerability. METHODS: UC/CC samples were profiled using matrix-assisted laser desorption/ionization mass spectrometry; protein identification was made by liquid chromatography. Diverticulitis was used as control (Ctrl). The presence of Hb(n) (n = α, ß, or hemin)/Hb was validated by Western blotting and immunohistochemistry. We tested for DNA damage (DNAD) by exposing normal colonic epithelial cell line, NCM460, to 10 µM and 100 µM of Hb(n)/Hb, individually for 2, 6, and 12 hours. Quantification of Hb-α staining was done by Nikon Elements Advance Research Analysis software. ROS was measured by the production of 8-OHdG. DNAD was assessed by Comet assay. Colonic tissue homogenate antioxidants Nrf2-, CAT-, SOD-, and GPx-expressions were analyzed densitometrically/normalized by ß-actin. RESULTS: Immunohistochemistry of CC/UC mucosal/submucosal compartments stained strongly positive for Hb-α and significantly higher versus Ctrl. NCM460 exposed to Hb(n)/Hb exhibited steadily increasing ROS and subsequent DNAD. DNAD was higher in 10 µM than 100 µM in Hb-ß/hemin the first 2 hours then plateaued followed by DNAD repair. This may be likely due to apoptosis in the later concentration. Nrf2 enzyme activities among UC, CC, and ulcerative colitis-associated colon cancer (UCAC) were observed impaired in all inflammatory bowel disease subjects. Decreased levels of Nrf2 among patients with UC versus patients with CC with active disease were insignificant as well as versus Ctrls but significantly lower in UCAC versus Ctrl. SOD was decreased in UC and UCAC and GPx in CC but statistically not significant. Comparing CC versus UC, SOD was significantly lower in CC (P < 0.05). CAT was observed increased among patients with CC/UC/UCAC and GPx in UC and UCAC versus Ctrl, respectively, and significantly increased in CC versus Ctrl (P < 0.01). CONCLUSIONS: In the colitides, mucosal/submucosal tissue microenvironments demonstrated pool of free Hb-α chain. In vitro exposure of NCM460 cells to Hb(n)/Hb induced ROS and DNAD. Toxic effect of free Hb-α, in colonic epithelial cells, is therefore through production of ROS formation modulated by impairment of antioxidant effects. Targeting reduction-oxidation-sensitive pathways and transcription factors may offer options for inflammatory bowel disease-management and colitis-related cancer prevention.

Adenocarcinomas After Prophylactic Surgery For Familial Adenomatous Polyposis.

The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000 live births. Virtually, all surgically untreated patients with FAP inevitably develop colorectal-cancer in their lifetime because they carry the adenomatous polyposis coli gene. Thus prophylactic proctocolectomy is indicated. Surgical treatment of FAP is still controversial. There are however, four surgical options: ileorectal anastomosis, restorative proctocolectomy with ileal pouch-anal anastomosis, proctocolectomy with ileostomy, and proctocolectomy with continent-ileostomy. Conventional proctocolectomy options largely lie between colectomy with ileorectal anastomosis or ileal pouch-anal anastomosis. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis because of better functional results and quality of life. The functional outcome of total colectomy with ileorectal anastomosis is undoubtedly far superior to that of the ileoanal pouch; however, the risk for rectal cancer is increased by 30%. Even after mucosectomy, inadvertent small mucosal residual islands remain. These residual islands carry the potential for the development of subsequent malignancy. We reviewed the literature (1975-2012) on the incidence, nature, and possible etiology of subsequent ileal-pouch and anal transit zone adenocarcinoma after prophylactic surgery procedure for FAP. To date there are 24 studies reporting 92 pouch-related cancers; 15 case reports, 4 prospective and 5 retrospective studies. Twenty three of 92 cancers (25%) developed in the pouch mucosa and 69 (75%) in anal transit zone (ATZ). Current recommendation for pouch surveillance and treatment are presented. Data suggest lifetime surveillance of these patients.

Uptake of all-trans retinoic acid-containing aerosol by inhalation to lungs in a guinea pig model system--a pilot study.

Systemic therapies with retinoic acid (RA) can result in toxic side effects without yielding biologically effective levels in target tissues such as lung. The authors adapted a PARI LC Star nebulizer to create a tubular system for short-term inhalation treatment of guinea pigs using a water-miscible formulation of all-trans RA (ATRA) or vehicle. Based on the initial average weight, animals received an estimated average ATRA doses of either 0.32 mg·kg(-1) (low dose, 1.4 mM), or 0.62 mg·kg(-1) (medium dose, 2.8 mM), or 1.26 mg·kg(-1) (high dose, 5.6 mM) 20 minutes per day for 6 consecutive days. This system led to a rise of ATRA levels in lung, but not liver or plasma. Cellular lung levels of retinol, retinyl palmitate, and retinyl stearate also appeared to be unaffected (245.6 ± 10.7, 47.4 ± 3.4, and 132.8 ± 7.7 ng·g(-1) wet weight, respectively). The application of this aerosolized ATRA also induced a dose-dependent protein expression of the cellular retinol-binding protein 1 (CRBP-1) in lung, without apparent harmful side effects.

Qualitative and quantitative analysis of retinol, retinyl esters, tocopherols and selected carotenoids out of various internal organs form different species by HPLC.

We report the validation of a reversed-phase gradient HPLC method allowing simultaneous quantification of retinol, retinyl esters, tocopherols and selected carotenoids in lung, liver and plasma of mouse, rat and guinea pig (gp) using a diode array detector. A significant species difference was observed regarding the distribution of retinol and retinyl esters. The levels of total retinol in lung, liver and plasma were in the following order: mouse >> rat > gp; rat >mouse > gp; and gp >> rat > mouse, respectively. Furthermore, comparison studies revealed similarities between the vitamin A profiles of human and gp lung samples.

Identification of lutein, a dietary antioxidant carotenoid in guinea pig tissues.

Lutein, a dietary carotenoid, is a well known antioxidant. The major source of this carotenoid in humans is diet. We report here the presence of lutein, a dietary carotenoid in several guinea pig tissues (in decreasing order: liver>spleen>lung>>testis>kidney>plasma>eye but not in white adipose tissue). The presence of lutein in lung and other tissues may be significant in term of its antioxidant capacity of these organs.