Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites.

Dementia is caused by factors that damage neurons. We quantified small molecular markers in whole blood of dementia patients, using nontargeted liquid chromatography-mass spectroscopy (LC-MS). Thirty-three metabolites, classified into five groups (A to E), differed significantly in dementia patients, compared with healthy elderly subjects. Seven A metabolites present in plasma, including quinolinic acid, kynurenine, and indoxyl-sulfate, increased. Possibly they act as neurotoxins in the central nervous system (CNS). The remaining 26 compounds (B to E) decreased, possibly causing a loss of support or protection of the brain in dementia. Six B metabolites, normally enriched in red blood cells (RBCs), all contain trimethylated ammonium moieties. These metabolites include ergothioneine and structurally related compounds that have scarcely been investigated as dementia markers, validating the examination of RBC metabolites. Ergothioneine, a potent antioxidant, is significantly decreased in various cognition-related disorders, such as mild cognitive impairment and frailty. C compounds also include some oxidoreductants and are normally abundant in RBCs (NADP+, glutathione, adenosine triphosphate, pantothenate, S-adenosyl-methionine, and gluconate). Their decreased levels in dementia patients may also contribute to depressed brain function. Twelve D metabolites contains plasma compounds, such as amino acids, glycerophosphocholine, dodecanoyl-carnitine, and 2-hydroxybutyrate, which normally protect the brain, but their diminution in dementia may reduce that protection. Seven D compounds have been identified previously as dementia markers. B to E compounds may be critical to maintain the CNS by acting directly or indirectly. How RBC metabolites act in the CNS and why they diminish significantly in dementia remain to be determined.

[The Experience of Caring for a Child Suffering From Incontinent Dermatitis].

This paper describes the experience of caring for a child with incontinent dermatitis that was caused by improper family care. From March 27, 2015 to April 2, 2015, the authors used Gordon's 11 functional health parameters to collect subjective and objective data on the physical, mental and social conditions of the care recipient. To understand the nursing-related problems, including impaired skin integrity, acute pain, and caregiver anxiety, the data for this case and his mother were conducted by observation, physical assessment, the process of caring, and communication. For the three nursing problems, we established a good relationship with the family by providing individual care, continuously active care, listening, and companionship. In order to reduce the pain during wound dressing, we used game therapy and an attention-transfer technique that was based on the case's preferences. We encouraged family members to participate in treatment in order to ensure that the case continued to receive proper and continuous care after returning home. The authors taught the family members the correct information for treating incontinent dermatitis in order to reduce their concerns and to enhance their confidence and care abilities. We hope that this nursing experience may provide a reference for other nursing staffs when caring for similar cases in order to ensure appropriate quality of care.

Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet.

BACKGROUND: The high-fat and high-sugar Westernized diet that is popular worldwide is associated with increased body fat accumulation, which has been related to the development of nonalcoholic fatty liver disease (NAFLD). Without treatment, NAFLD may progress to hepatocellular carcinoma (HCC), a cancer with a high mortality rate. The consumption of broccoli in the United States has greatly increased in the last 2 decades. Epidemiologic studies show that incorporating brassica vegetables into the daily diet lowers the risk of several cancers, although, to our knowledge, this is the first study to evaluate HCC prevention through dietary broccoli. OBJECTIVE: We aimed to determine the impact of dietary broccoli on hepatic lipid metabolism and the progression of NAFLD to HCC. Our hypothesis was that broccoli decreases both hepatic lipidosis and the development of HCC in a mouse model of Western diet-enhanced liver cancer. METHODS: Adult 5-wk-old male B6C3F1 mice received a control diet (AIN-93M) or a Western diet (high in lard and sucrose, 19% and 31%, wt:wt, respectively), with or without freeze-dried broccoli (10%, wt:wt). Starting the following week, mice were treated once per week with diethylnitrosamine (DEN; 45 mg/kg body weight intraperitoneally at ages 6, 7, 8, 10, 11, and 12 wk). Hepatic gene expression, lipidosis, and tumor outcomes were analyzed 6 mo later, when mice were 9 mo old. RESULTS: Mice receiving broccoli exhibited lower hepatic triglycerides (P < 0.001) and NAFLD scores (P < 0.0001), decreased plasma alanine aminotransferase (P < 0.0001), suppressed activation of hepatic CD68(+) macrophages (P < 0.0001), and slowed initiation and progression of hepatic neoplasm. Hepatic Cd36 was downregulated by broccoli feeding (P = 0.006), whereas microsomal triglyceride transfer protein was upregulated (P = 0.045), supporting the finding that dietary broccoli decreased hepatic triglycerides. CONCLUSION: Long-term consumption of whole broccoli countered both NAFLD development enhanced by a Western diet and hepatic tumorigenesis induced by DEN in male B6C3F1 mice.

Nasal Tumorigenesis in B6C3F1 Mice Following Intraperitoneal Diethylnitrosamine.

Diethylnitrosamine (DEN) is a chemical broadly used in animal models as a hepatocarcinogen, reported to also cause pulmonary neoplasms in mice. The original objective was to evaluate the impact of a Western diet with or without 10% broccoli on DEN-induced on liver cancer. We administered DEN (45 mg/kg) intraperitoneally to young adult male B6C3F1 mice by 6 weekly injections and evaluated liver cancer 6 months after the DEN treatments. Here, we report unexpected primary tumorigenesis in nasal epithelium, independent of dietary treatment. More than 50% of DEN-treated B6C3F1 mice developed nasal neoplasm-related lesions, not reported previously in the literature. Only one of these neoplasms was visible externally prior to postmortem examination. Intraperitoneal DEN treatment used as a model for liver cancer can have a carcinogenic effect on the nasal epithelium in B6C3F1 mice, which should be carefully monitored in future liver cancer studies.

The relationships between motor skills and executive functions in children with and without autism spectrum disorder.

To date, information on associations between motor skills and executive functions (EF) in autistic children is limited. The purpose of this study was to compare motor skills and EF performance between autistic children and typically developing (TD) children and to examine the relationships between motor skills and EF in these two groups. Forty-eight autistic children and 48 TD children aged 6 to 12 years were recruited for this study. Motor skills were measured with the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). EF was assessed with the Stroop Color and Word Test, the Wisconsin Card Sorting Task (WCST), and the Test of Attentional Performance: Go/No-go test. Independent sample t-tests were used to compare the BOT-2 scores and EF measures between autistic children and TD children. Pearson product-moment correlation and regressions were conducted to assess the relationships between the BOT-2 scores and the EF measures for each group. Results showed that autistic children scored significantly lower than TD children on all four BOT-2 composite scores and a total motor composite. Autistic children also demonstrated significantly lower levels of performance on all EF measures than TD children. Further, autistic children showed more significant associations between motor skills and EF than TD children, particularly pronounced in the domains of fine manual control and manual coordination to cognitive flexibility, as well as manual coordination and inhibitory control. Continued development of motor skills and EF in autistic children is important. The relationships between motor skills and EF were significant among autistic children, suggesting future research on promoting EF through motor skill interventions in autistic children is required.

Dietary broccoli protects against fatty liver development but not against progression of liver cancer in mice pretreated with diethylnitrosamine.

Western-style high fat, high sugar diets are associated with non-alcoholic fatty liver disease (NAFLD) and increased liver cancer risk. Sulforaphane from broccoli may protect against these. Previously we initiated broccoli feeding to mice prior to exposure to the hepatocarcinogen diethylnitrosamine (DEN), and saw protection against NAFLD and liver cancer. Here we administered DEN to unweaned mice, initiating broccoli feeding two weeks later, to determine if broccoli protects against cancer progression. Specifically, male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months. Dietary broccoli decreased hepatic triacylglycerols, NAFLD, liver damage and tumour necrosis factor by month 5 without changing body weight or relative liver weight, but did not slow carcinogenesis, seen in 100% of mice. We conclude that broccoli, a good source of sulforaphane, slows progression of hepatic lipidosis, but not tumourigenesis in this robust model.

Dietary broccoli mildly improves neuroinflammation in aged mice but does not reduce lipopolysaccharide-induced sickness behavior.

Aging is associated with oxidative stress and heightened inflammatory response to infection. Dietary interventions to reduce these changes are therefore desirable. Broccoli contains glucoraphanin, which is converted to sulforaphane (SFN) by plant myrosinase during cooking preparation or digestion. Sulforaphane increases antioxidant enzymes including NAD(P)H quinone oxidoreductase and heme oxygenase I and inhibits inflammatory cytokines. We hypothesized that dietary broccoli would support an antioxidant response in brain and periphery of aged mice and inhibit lipopolysaccharide (LPS)-induced inflammation and sickness. Young adult and aged mice were fed control or 10% broccoli diet for 28 days before an intraperitoneal LPS injection. Social interactions were assessed 2, 4, 8, and 24 hours after LPS, and mRNA was quantified in liver and brain at 24 hours. Dietary broccoli did not ameliorate LPS-induced decrease in social interactions in young or aged mice. Interleukin-1ß (IL-1ß) expression was unaffected by broccoli consumption but was induced by LPS in brain and liver of adult and aged mice. In addition, IL-1ß was elevated in brain of aged mice without LPS. Broccoli consumption decreased age-elevated cytochrome b-245 ß, an oxidative stress marker, and reduced glial activation markers in aged mice. Collectively, these data suggest that 10% broccoli diet provides a modest reduction in age-related oxidative stress and glial reactivity, but is insufficient to inhibit LPS-induced inflammation. Thus, it is likely that SFN would need to be provided in supplement form to control the inflammatory response to LPS.