Chronic disease prevention and screening outcomes for patients with and without financial difficulty: a secondary analysis of the BETTER WISE cluster randomised controlled trial.

OBJECTIVE: Building on Existing Tools To improvE chronic disease pRevention and screening in primary care Wellness of cancer survIvorS and patiEnts (BETTER WISE) was designed to assess the effectiveness of a cancer and chronic disease prevention and screening (CCDPS) programme. Here, we compare outcomes in participants living with and without financial difficulty. DESIGN: Secondary analysis of a cluster-randomised controlled trial. SETTING: Patients of 59 physicians from 13 clinics enrolled between September 2018 and August 2019. PARTICIPANTS: 596 of 1005 trial participants who responded to a financial difficulty screening question at enrolment. INTERVENTION: 1-hour CCDPS visit versus usual care. OUTCOME MEASURES: Eligibility for a possible 24 CCDPS actions was assessed at baseline and the primary outcome was the percentage of eligible items that were completed at 12-month follow-up. We also compared the change in response to the financial difficulty screening question between baseline and follow-up. RESULTS: 55 of 265 participants (20.7%) in the control group and 69 of 331 participants (20.8%) in the intervention group reported living with financial difficulty. The primary outcome was 29% (95% CI 26% to 33%) for intervention and 23% (95% CI 21% to 26%) for control participants without financial difficulty (p=0.01). Intervention and control participants with financial difficulty scored 28% (95% CI 24% to 32%) and 32% (95% CI 27% to 38%), respectively (p=0.14). In participants who responded to the financial difficulty question at both time points (n=302), there was a net decrease in the percentage of participants who reported financial difficulty between baseline (21%) and follow-up (12%, p<0.001) which was similar in the control and intervention groups. The response rate to this question was only 51% at follow-up. CONCLUSION: The BETTER intervention improved uptake of CCDPS manoeuvres in participants without financial difficulty, but not in those living with financial difficulty. Improving CCDPS for people living with financial difficulty may require a different clinical approach or that social determinants be addressed concurrently with clinical and lifestyle needs or both. TRIAL REGISTRATION NUMBER: ISRCTN21333761.

The Programming Effect of Plant-Based DHA, Along with Equivalent AA, on Immune System and Oral Tolerance Development in Six-Week Allergy Prone BALB/c Pups.

BACKGROUND: Docosahexaenoic acid (DHA) and arachidonic acid (AA) on oral tolerance (OT) development in allergy-prone infants is less known. OBJECTIVES: We aim to determine the effects of early life DHA supplementation (1% of total fat, from novel canola oil), along with AA, on OT toward ovalbumin (ova, egg protein) in allergy-prone BALB/c pups at 6-wk. METHODS: Breastfeeding dams (n ≥ 10/diet) were fed DHA+AA (1% DHA, 1% AA wt/wt of total fat) or control (0% DHA, 0% AA) suckling period diet (SPD) during which pups consumed dam's milk. At 3-wk, pups from each SPD group were assigned to either the control or DHA+AA weaning diet. For OT, pups from each diet group were either orally fed ova or placebo daily from 21-25 d. Systemic immunization to ova was induced through intraperitoneal injections before euthanizing 6-wk pups. Ova-specific immunoglobulin (ova-Ig) and splenocytes ex-vivo cytokine response to different stimuli were analyzed using a 3-factor analysis of variance. RESULTS: OT-induced suppression was seen in ova-stimulated splenocyte ex-vivo response, where ova-tolerized pups showed significantly lower total immunoglobulin (Ig)G, IgG1, interleukin (IL)-2 and IL-6 production than sucrose (placebo) pups. DHA+AA SPD was associated with 3 times lower plasma concentrations of ova-IgE (P = 0.03) than controls. DHA+AA weaning diet resulted in lower T helper type-2 cytokines (IL-4 and IL-6) with ova stimulation than controls, which may benefit OT. DHA+AA SPD resulted in significantly higher T cell cytokine response [IL-2, interferon-gamma, (IFNγ) and IL-1ß] to anti-CD3/CD28 stimulation than controls. The splenocytes stimulated with lipopolysaccharide produced lower inflammatory cytokines (IFNγ, tumor necrosis factor-alpha, IL-6, and C-X-C motif ligand 1), which may be because of lower CD11b+CD68+ splenocytes proportion in pups from DHA+AA SPD than control (all P < 0.05). CONCLUSIONS: DHA and AA in early life may influence OT in allergy-prone BALB/c mouse offspring, as they effectively promote T helper type-1 immune responses.

Regulation of immune function in healthy adults: one-stop guide on the role of dietary fatty acids, gut microbiota-derived short chain fatty acids, and select micronutrients in combination with physical activity.

The immune system requires an adequate supply of nutrients, although current dietary recommendations may not account for optimal immune function in healthy adults. Nutrient inadequacies due to the growing influence of the western diet pose a risk for immune dysfunction. This review aims to determine the beneficial effects of supplementing dietary fats, nutrients that modulate gut microbiota, and specific micronutrients on systemic immune functions (concentrations of plasma cytokines, antibodies, and acute phase proteins) during health and acute inflammatory conditions, including COVID-19. We discussed micronutrients (selenium, zinc, and vitamin D) with compelling evidence supporting immunomodulatory properties. Additionally, the synergistic effects of physical activity and dietary interventions on systemic immune markers are explored. Briefly, evidence suggests that dietary consumption of monounsaturated (oleic and palmitoleic acids) and omega-3 polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic acids) promotes anti-inflammatory properties. Food sources (fiber, prebiotics, probiotics, omega-3) and patterns (Mediterranean diet) increase the production of short-chain fatty acids, beneficially altering gut microbiota composition, which subsequently enhances the immunomodulatory properties of circulating immune cells. A positive synergistic role of nutrient supplementation (omega-3 and fiber) and physical activity on circulating C-reactive protein and interleukin-6 levels has been observed. Lastly, omega-3 supplementation during COVID-19 infection may reduce circulating C-reactive protein and pro-inflammatory cytokines and improves pain and fatigue symptoms. This review highlights recent findings that support the beneficial role of specific nutrients in promoting systemic immune function in healthy adults. However, to establish specific dietary recommendations to support optimal immune function, more research is required. Key takeaway: Increasing dietary fats (fish and olive oils) and specific micronutrients may positively impact systemic immune function in healthy adults. Evidence suggests that these nutrients promote immunomodulatory properties useful in resolving acute infection.

Maternal diet supplementation with high-docosahexaenoic-acid canola oil, along with arachidonic acid, promotes immune system development in allergy-prone BALB/c mouse offspring at 3 weeks of age.

PURPOSE: To study the effects of feeding docosahexaenoic acid (DHA, derived from novel canola oil), with same amount of arachidonic acid (ARA), supplemented diet to lactating dams on the immune system development of suckled offspring using a T helper type-2 (Th2)-dominant BALB/c mouse. METHODS: Dams received nutritionally complete control (no ARA or DHA) or DHA + ARA diet (1% DHA and 1% ARA of total fatty acids) from 5 days pre-parturition to the end of 3-week suckling period. After euthanization, relevant tissues were collected to study fatty acids, splenocyte phenotype and function (ex vivo cytokines with/without lipopolysaccharide (LPS, bacterial challenge) or phorbol myristate acetate + ionomycin (PMAi) stimulation). RESULTS: Feeding dams a DHA diet significantly increased the mammary gland milk phospholipid concentration of DHA and ARA. This resulted in 60% higher DHA levels in splenocyte phospholipids of the pups although ARA levels showed no difference. In dams fed DHA diet, significantly higher proportion of CD27+ cytotoxic T cell (CTL) and CXCR3+ CCR6- Th (enriched in Th1) were observed than control, but there were no differences in the splenocyte function upon PMAi (non-specific lymphocyte stimulant) stimulation. Pups from DHA-fed dams showed significantly higher IL-1ß, IFN-γ and TNF-α (inflammatory cytokines) by LPS-stimulated splenocytes. This may be due to higher proportion of CD86+ macrophages and B cells (all p's < 0.05) in these pups, which may influence T cell polarization. CONCLUSION: Plant-based source of DHA in maternal diet resulted in higher ex vivo production of inflammatory cytokines by splenocytes due to change in their phenotype, and this can skew T cell towards Th1 response in a Th2-dominant BALB/c mouse.

Combined Supplementation with Arachidonic and Docosahexaenoic Acids in T Helper Type-2 Skewed Brown Norway Rat Offspring is Beneficial in the Induction of Oral Tolerance toward Ovalbumin and Immune System Development.

BACKGROUND: A T helper type-2 (Th2) skewed immune response is associated with food allergies. DHA and arachidonic acid (ARA) have been shown to promote oral tolerance (OT) in healthy rodents. OBJECTIVES: We studied the effect of combined ARA + DHA supplementation during the suckling and weaning periods on OT and immune system development in Th2-skewed Brown Norway rat offspring. METHODS: Dams were fed ARA + DHA (0.45% ARA, 0.8% DHA wt/wt of total fat; n = 10) as a suckling period diet (SPD) or control SPD (0% ARA, 0% DHA, n = 8). At 3 wk, offspring from each SPD group received ARA + DHA (0.5% ARA, 0.5% DHA wt/wt of total fat) weaning diet (WD), or control until 8 wk. For OT, offspring were orally exposed to either ovalbumin (OVA) or placebo between 21 and 25 d, followed by systemic immunization with OVA + adjuvant at 7 wk. Primary outcomes, ex vivo cytokine production by splenocytes and plasma OVA-specific Igs, were analyzed using a 3-way ANOVA. RESULTS: At 8 wk, despite no lasting effect of SPD on splenocytes fatty acids, ARA + DHA WD resulted in 2× higher DHA in splenocyte phospholipid compositions without affecting ARA. OT development was observed in OVA-exposed groups with 15% lower plasma OVA-IgE (P = 0.04) and 35% lower OVA-IgG1 (P = 0.01) than placebo. ARA + DHA SPD resulted in 35% lower OVA-IgG1 and iIL-6 (P = 0.04) when stimulated with LPS, and a higher proportion of mature B cells (OX12+, P = 0.0004, and IgG+, P = 0.008). ARA + DHA WD resulted in 20% higher Th1 cytokines (TNF-α and IFN-γ) production to lymphocyte stimulant and higher splenocyte proportion of CD45RA+ (pan-B cells) and OX6+ (dendritic cells) than control WD (P values < 0.05). CONCLUSIONS: Combined supplementation of ARA and DHA is beneficial for OT development, especially in the suckling period. Further, ARA + DHA supplementation can also counteract the Th2-skewed immunity of Brown Norway rat offspring through higher Th1 cytokine production by lymphocytes.

AHP and TOPSIS based flood risk assessment- a case study of the Navsari City, Gujarat, India.

Flooding is one of the major natural catastrophic disasters that causes massive environmental and socioeconomic destruction. The magnitude of losses due to floods has prompted researchers to focus more on robust and comprehensive modeling approaches for alleviating flood damages. Recently developed multi-criteria decision making (MCDM) methods are being widely used to construct decision-making process more participatory, rational, and efficient. In this study, two statistical MCDM approaches, namely the analytical hierarchy process (AHP) and the technique for order preference by similarity to ideal solution (TOPSIS), have been employed to generate flood risk maps together with hazard and vulnerability maps in a GIS framework for Navsari city in Gujarat, India, to identify the vulnerable areas that are more susceptible to inundation during floods. The study area was divided into 10 sub areas (i.e., NC1 to NC10) to appraise the degree of flood hazard, vulnerability and risk intensities in terms of areal coverage and categorized under 5 intensity classes, viz., very low, low, moderate, high, and very high. A total of 14 flood indicators, seven each for hazard (i.e., elevation, slope, drainage density, distance to river, rainfall, soil, and flow accumulation) and vulnerability (i.e., population density, female population, land use, road network density, household, distance to hospital, and literacy rate) were considered for evaluating the flood risk. Flood risk coverage evaluated from the two approaches were compared with the flood extent computed from the actual flood data collected at 36 random locations. Results revealed that the TOPSIS approach estimated more precise flood risk coverage than the AHP approach, yielding high R2 values, i.e., 0.78 to 0.95 and low RMSE values, i.e., 0.95 to 0.43, for all the 5 risk intensity classes. The sub areas identified under "very high" and "high" risk intensity classes (i.e., NC1, NC4, NC6, NC7, NC8, and NC10) call for immediate flood control measures with a view to palliate the extent of flood risk and consequential damages. The study demonstrates the potential of AHP and TOPSIS integrated with GIS towards precise identification of flood-prone areas for devising effective flood management strategies.

Long Chain Polyunsaturated Fatty Acids Docosahexaenoic Acid and Arachidonic Acid Supplementation in the Suckling and the Post-weaning Diet Influences the Immune System Development of T Helper Type-2 Bias Brown Norway Rat Offspring.

Background: Dietary long chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) play an important role in the development of the infant immune system. The role of LCPUFA in the T helper type 2 (Th2) biased immune system is unknown. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring. Methods: Brown Norway dams were randomly assigned to nutritionally adequate maternal diet throughout the suckling period (0-3 weeks), namely, control diet (0% ARA, 0% DHA; n= 8) or ARA + DHA (0.45% ARA, 0.8% DHA; n = 10). At 3 weeks, offspring from each maternal diet group were randomized to either a control (0% ARA, 0% DHA; n = 19) or ARA+DHA post-weaning (0.5% ARA, 0.5% DHA; n = 18) diet. At 8 weeks, offspring were killed, and tissues were collected for immune cell function and fatty acid composition analyses. Results: ARA + DHA maternal diet resulted in higher (p < 0.05) DHA composition in breast milk (4×) without changing ARA levels. This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer's patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks. ARA+DHA post-weaning diet (3-8 weeks) resulted in 2 × higher DHA in splenocyte phospholipids compared to control. This also resulted in higher Th1 cytokines, ~50% higher TNF-α and IFNγ, by PMAi stimulated splenocytes ex vivo, with no differences in Th2 cytokines (IL-4, IL-13, and IL-10) compared to controls. Conclusion: Feeding dams a diet higher in DHA during the suckling period resulted in adaptive immune cell maturation in offspring at 8 weeks. Providing ARA and DHA during the post-weaning period in a Th2 biased Brown Norway offspring model may support Th1 biased immune response development, which could be associated with a lower risk of developing atopic diseases.

Docosahexaenoic Acid Incorporation Is Not Affected by Doxorubicin Chemotherapy in either Whole Cell or Lipid Raft Phospholipids of Breast Cancer Cells in vitro and Tumor Phospholipids in vivo.

To better understand how docosahexaenoic acid (DHA) improves the effects of doxorubicin (DOX), we examined DHA ± DOX on changes in whole cell and lipid raft phospholipids (PL) of MDA-MB-231 and MCF-7 breast cancer cells. We sought to confirm whether the relative changes in PL DHA content of MDA-MB-231 cells could be extended to PL from MDA-MB-231 tumors grown in mice fed a DHA supplemented diet ±DOX. Treatment with DHA did not change PL composition yet DOX increased the proportion of phosphatidylserine in MCF-7 cell lipid rafts by two-fold (p < 0.001). Regardless of DOX, the relative percent incorporation of DHA was higher in MDA-MB-231 cells compared to MCF-7 cells in phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine (whole cell and lipid rafts); and higher in phosphatidylethanolamine vs. phosphatidylcholine (4.4-fold in MCF-7 and 6-fold in MDA-MB-231 cells respectively). DHA treatment increased eicosapentaenoic acid and docosapentaenoic acid in MDA-MB-231 cells but not MCF-7 cells. Increased DHA content in MDA-MB-231 cells, MCF-7 cells, and MDA-MB-231 tumors in all PL moieties (except sphingomyelin) corresponded with reduced arachidonic acid (p < 0.05). Feeding mice 2.8% (w/w of fat) DHA ± DOX increased tumor necrotic regions (p < 0.05). This study established differential incorporation of DHA into whole cell and lipid rafts between human breast cancer cell lines. However, within each cell line, this incorporation was not altered by DOX confirming that DOX does not change membrane lipid composition. Furthermore, our findings indicate that membrane changes observed in vitro are translatable to in vivo changes and that DHA + DOX could contribute to the anticancer effects through increased necrosis.

Feeding a Bioactive Oil Enriched in Stearidonic Acid during Early Life Influences Immune System Maturation in Neonatal Sprague-Dawley Rats.

BACKGROUND: Long-chain n-3 PUFAs (LCPUFAs) improve immune development and reduce atopic disease risk in infants. Stearidonic acid (SDA) can be a substrate for biosynthesis of n-3 LCPUFAs. OBJECTIVE: We aimed to determine the effect of feeding an SDA-enriched diet during suckling and weaning on offspring immunity and ability to develop oral tolerance (OT). METHODS: Pregnant Sprague-Dawley rats were randomly assigned to consume either SDA (3 g SDA/100 g fat) or a control (no SDA) diet, 5 d before parturition and through lactation (21 d). For the OT treatment, 10-d-old pups were fed ovalbumin (Ova; 200 µL of 8 mg/mL) or placebo daily for 5 d. At 21 d, pups (both sexes) were weaned to their respective maternal diet until 6 wk of age or killed. Systemic immunization was induced using Ova (in 3-wk-old pups) or Ova + adjuvant (in 6-wk-old pups). The effect of suckling diet (in 3-wk-old pups) or weaning diet (in 6-wk-old pups) and OT treatment on immune function (main outcome) in spleen and blood was compared using 2-factor ANOVA. RESULTS: An SDA-enriched maternal diet, compared with the control diet, resulted in higher plasma phospholipid (PL) EPA (15 times higher), docosapentaenoic acid (DPA; 3 times higher), and DHA (1.3 times higher) content in 3-wk-old pups, accompanied by higher B-cell function [plasma ovalbumin-specific IgG1 (Ova-IgG1), 2 times higher] ( P < 0.05). Compared with pups fed a control diet, the splenocytes from these pups had more (23%) helper T (Th) cells (CD3+CD4+) and activated (12%) Th cells (CD4+CD28+) (P < 0.02) than controls. At 6 wk, the SDA group had 30% more CD4+CD25+ splenocytes, and when stimulated ex vivo with LPS, produced less inflammatory IL-6 (50%) and TNF-α (30%) and more immunoregulatory IL-10 (45%) cytokines (P < 0.05) than the control group. The Ova-exposed group had less (30%) plasma Ova-IgG1 than the placebo group. Splenocytes and plasma PLs from the 6-wk-old SDA group had more EPA (2x) and DPA (3.5x) (P < 0.05), but not DHA, than the control group. CONCLUSIONS: Feeding SDA during lactation and weaning altered immune responses in directions believed to be beneficial.