Ganglioside Alters Phospholipase Trafficking, Inhibits NF-κB Assembly, and Protects Tight Junction Integrity

Background and Aims: Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. The objective of this study was to examine mechanisms by which dietary gangliosides exert beneficial effects on intestinal health. Methods: Studies were conducted in vitro using CaCo-2 intestinal epithelial cells. Gangliosides were extracted from milk powder and incubated with differentiated CaCo-2 cells after exposure to pro-inflammatory stimuli. Gut barrier integrity was assessed by electron microscopy, epithelial barrier function was examined by measuring transepithelial electric resistance, and content of HBD-2, IL-23, NF-κB, and sPLA2 was assessed by ELISA. Results: Ganglioside attenuated the decrease in integrity of tight junctions induced by pro-inflammatory stimuli and improved epithelial barrier function (P \u3c 0.05). Ganglioside decreased the basolateral secretion of sPLA2 (P ≤ 0.05), lowered HBD-2 and IL-23 levels (P ≤ 0.05), and inhibited NF-κB activation (P ≤ 0.05). Conclusions: In summary, the present study indicates that ganglioside GD3 improves intestinal integrity by altering sPLA2 trafficking, and the production of pro-inflammatory mediators is mitigated by decreasing assembly of the NF-κB complex. Dietary gangliosides may have promising potential beneficial effects in IBD as decreased inflammatory signaling, improved intestinal integrity, and maintenance of epithelial barrier function have been demonstrated in vitro

AA and DHA are Decreased in Paediatric AD/HD and Inattention is Ameliorated by Increased Plasma DHA

The purpose of this study was to assess long chain polyunsaturated fatty acid (LCPUFA) status in relation to socio-behavioral outcomes in children with Attention Deficit/Hyperactivity Disorder (AD/HD). In a case-control design, plasma phospholipid fatty acid content was assessed in children aged 5–12 years with AD/HD and in typically functioning children. Dietary intakes of LCPUFAs arachidonic acid (AA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) were quantified using a four-day food record, polymorphisms were determined in FADS1 and FADS2, and socio-behavioral outcomes were assessed using the Conners 3 Parent Rating Scales in a cross section of children with AD/HD. Compared to typically functioning children, plasma AA and DHA were 40% lower in children with AD/HD. Median intake of AA, but not DHA, was higher in children with AD/HD compared to typically functioning children. Polymorphisms in FADS1 (rs174546) and FADS2 (174575) were associated with higher plasma linoleic acid (LA; 18:2n6) level. Plasma DHA level was inversely associated with inattention score. Despite having an elevated intake of AA, children diagnosed with AD/HD have a reduction in plasma AA level which may be due in part to polymorphisms in the fatty acid desaturase (FADS) gene cluster or increased conversion to AA-derived metabolites. Increasing intake of DHA may ameliorate symptoms of inattention in AD/HD

Data for Improvement and Clinical Excellence: a report of an interrupted time series trial of feedback in home care

Abstract Background There is substantial evidence about the effectiveness of audit with feedback, but none that we know have been conducted in home care settings. The primary purpose of the Data for Improvement and Clinical Excellence – Home Care (DICE-HC) project was to evaluate the effects of an audit and feedback delivered to care providers on home care client outcomes. The objective of this paper is to report the effects of feedback on four specific quality indicators: pain, falls, delirium, and hospital visits. Methods A 10-month audit with feedback intervention study was conducted with care providers in seven home care offices in Alberta, Canada, which involved delivery of four quarterly feedback reports consisting of data derived from the Resident Assessment Instrument – Home Care (RAI-HC). The primary evaluation employed an interrupted time series design using segmented regression analysis to assess the effects of feedback reporting on the four quality indicators: pain, falls, delirium, and hospitalization. Changes in level and trend of the quality indicators were measured before, during, and after the implementation of feedback reports. Pressure ulcer reporting was analyzed as a comparator condition not included in the feedback report. Care providers were surveyed on responses to feedback reporting which informed a process evaluation. Results At initiation of feedback report implementation, the percentage of clients reporting pain and falls significantly increased. Though the percentage of clients reporting pain and falls tended to increase and reporting of delirium and hospital visits tended to decrease relative to the pre-intervention period, there was no significant effect of feedback reporting on quality indicators during the 10-month intervention. The percentage of clients reporting falls, delirium, and hospital visits significantly increased in the 6-month period following feedback reporting relative to the intervention period. About 50% of the care providers that read and understand the feedback reports found the reports useful to make changes to the way clients are cared for. Conclusions Routinely collected data used over time for feedback is feasible in home care settings. A high proportion of care providers find feedback reports useful for informing how they care for clients. Since reporting on the frequency of quality indicators increased in the post-intervention period, this study suggests that ongoing use of audit with feedback to enhance health outcomes in home care may promote improved reporting on standardized instruments.https://deepblue.lib.umich.edu/bitstream/2027.42/136777/1/13012_2017_Article_600.pd

Effectiveness of a Community Program for Older Adults with Type 2 Diabetes and Multimorbidity: A Pragmatic Randomized Controlled Trial

Background Type II diabetes mellitus (T2DM) affects upwards of 25% of Canadian older adults and is associated with high comorbidity and burden. Studies show that lifestyle factors and self-management are associated with improved health outcomes, but many studies lack rigour or exclude older adults, particularly those with multimorbidity. More evidence is needed on the effectiveness of community-based self-management programs in older adults with T2DM and multimorbidity. The study purpose is to evaluate the effect of a community-based intervention versus usual care on physical functioning, mental health, depressive symptoms, anxiety, self-efficacy, self-management, and healthcare costs in older adults with T2DM and 2 or more comorbidities. Methods Community-living older adults with T2DM and two or more chronic conditions were recruited from three Primary Care Networks (PCNs) in Alberta, Canada. Participants were randomly allocated to the intervention or control group in this pragmatic randomized controlled trial comparing the intervention to usual care. The intervention involved up to three in-home visits, a monthly group wellness program, monthly case conferencing, and care coordination. The primary outcome was physical functioning. Secondary outcomes included mental functioning, anxiety, depressive symptoms, self-efficacy, self-management, and the cost of healthcare service use. Intention-to-treat analysis was performed using ANCOVA modeling. Results Of 132 enrolled participants (70-Intervention, 62-Control), 42% were 75 years or older, 55% were female, and over 75% had at least six chronic conditions (in addition to T2DM). No significant group differences were seen for the baseline to six-month change in physical functioning (mean difference: -0.74; 95% CI: − 3.22, 1.74; p-value: 0.56), mental functioning (mean difference: 1.24; 95% CI: − 1.12, 3.60; p-value: 0.30), or other secondary outcomes.. Conclusion No significant group differences were seen for the primary outcome, physical functioning (PCS). Program implementation, baseline differences between study arms and chronic disease management services that are part of usual care may have contributed to the modest study results. Fruitful areas for future research include capturing clinical outcome measures and exploring the impact of varying the type and intensity of key intervention components such as exercise and diet

Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer

<div><p>Background</p><p>This study aimed to assess whether feeding a diet containing fish oil was efficacious in reducing tumor- and subsequent chemotherapy-associated myosteatosis, and improving tumor response to treatment.</p><p>Methods</p><p>Female Fischer 344 rats were fed either a control diet for the entire study (control), or switched to a diet containing fish oil (2.0 g /100 g of diet) one week prior to tumor implantation (long term fish oil) or at the start of chemotherapy (adjuvant fish oil). Chemotherapy (irinotecan plus 5-fluorouracil) was initiated 2 weeks after tumor implantation (cycle-1) and 1 week thereafter (cycle-2). Reference animals received no tumor or treatment and only consumed the control diet. All skeletal muscle measures were conducted in the gastrocnemius. To assess myosteatosis, lipids were assessed histologically by Oil Red O staining and total triglyceride content was quantified by gas chromatography. Expression of adipogenic transcription factors were assessed at the mRNA level by real-time RT-PCR.</p><p>Results</p><p>Feeding a diet containing fish oil significantly reduced tumor- and subsequent chemotherapy-associated increases in skeletal muscle neutral lipid (p<0.001) and total triglyceride content (p<0.03), and expression of adipogenic transcription factors (p<0.01) compared with control diet fed animals. The adjuvant fish oil diet was as effective as the long term fish oil diet in mitigating chemotherapy-associated skeletal muscle fat content, and in reducing tumor volume during chemotherapy compared with control fed animals (p<0.01).</p><p>Conclusion</p><p>Long term and adjuvant fish oil diets are equally efficacious in reducing chemotherapy-associated myosteatosis that may be occurring by reducing expression of transcription factors involved in adipogenesis/lipogenesis, and improving tumor-response to chemotherapy in a neoplastic model.</p></div

Total triglyceride content in the rat gastrocnemius muscle quantified using gas chromatography.

<p>Values are means ± SD. Statistical symbols indicate: *different from Reference; ^‡different from tumor-bearing and cycle-1 control diet groups; ^§different from relative control diet group (p<0.05).</p

Relative tumor volume of tumor-bearing rats who underwent one or two cycles of CPT-11/5-FU treatment.

<p>Relative tumor volume was compared to the baseline volume when chemotherapy was initiated (Day 0). Black arrows show the days when single CPT-11 injections (50 mg/kg) occurred (Days 0, 7); white arrows show the days when single 5-FU injections (50 mg/kg) occurred (Days 1, 8). Values are means ± SD. *Indicates significant differences between the control and each fish oil diet group at each time point (p<0.01).</p