Conventional anticancer chemotherapy has been historically thought to act through direct killing of tumor cells. This concept stems from the fact that cytotoxic drugs interfere with DNA synthesis and ...replication. Accumulating evidence, however, indicates that the antitumor activities of chemotherapy also rely on several off-target effects, especially directed to the host immune system, that cooperate for successful tumor eradication. Chemotherapeutic agents stimulate both the innate and adaptive arms of the immune system through several modalities: (i) by promoting specific rearrangements on dying tumor cells, which render them visible to the immune system; (ii) by influencing the homeostasis of the hematopoietic compartment through transient lymphodepletion followed by rebound replenishment of immune cell pools; (iii) by subverting tumor-induced immunosuppressive mechanisms and (iv) by exerting direct or indirect stimulatory effects on immune effectors. Among the indirect ways of immune cell stimulation, some cytotoxic drugs have been shown to induce an immunogenic type of cell death in tumor cells, resulting in the emission of specific signals that trigger phagocytosis of cell debris and promote the maturation of dendritic cells, ultimately resulting in the induction of potent antitumor responses. Here, we provide an extensive overview of the multiple immune-based mechanisms exploited by the most commonly employed cytotoxic drugs, with the final aim of identifying prerequisites for optimal combination with immunotherapy strategies for the development of more effective treatments against cancer.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Australian healthy food baskets are typically modelled off the Government Guidelines for healthy eating. However, these baskets have not been updated recently, nor has there been a Mediterranean Diet ...basket developed for an Australian population despite research suggesting high adherence is possible and subsequent health benefits observed. Food baskets typically only present the nutrition profile or the cost of a basket, seldom both.
Baskets were developed based on the Australian Guide to Healthy Eating, The Mediterranean Diet and typical Australian dietary intake (Western Diet). Four reference families were created based on data from Australian censuses and population statistics. Seven-day meal plans for reference families were entered into Foodworks software and aimed to meet 100% of nutrition and energy requirements. Basket costs were calculated from Coles Australia online.
The AGHE basket met all NRVs except for VLCN3 for the 7-year-old male (73% adequate intake). The Mediterranean Diet met all NRVs except zinc (44-year-old male) ranging from 98 to 257% of the RDI. The Western Diet failed to meet NRVs for numerous nutrients. The MedDiet baskets were generally cheaper ($78 for a one-person household to $285 for a four-person household) than AGHE and Western Diet.
Meeting nutrition requirements over seven days for zinc can be challenging for males. Fortified products provide an opportunity to improve nutrient profile; however, nutrient intake should equilibrate over time. Further, cost saving strategies can increase affordability. This research suggests a MedDiet is not more costly than a typical Western Diet or healthy AGHE diet.
Weight loss diets continue to rise in popularity; however, the associated costs are seldom reported. Certain weight loss diets may be unaffordable and differ from their traditional nutrition ...composition to include non-conventional premium products. In contrast, healthy eating principles such as the Australian Guide to Healthy Eating (AGHE) and the Mediterranean Diet (MedDiet) place an emphasis on fresh produce and staple foods but are sometimes thought to be unaffordable. A new methodology was piloted to assess the cost of weight loss diets using seven meal plans.
Seven meal plans were analysed to quantify the absolute grams required of all ingredients across seven days and multiplied by the cost of the ingredient per gram to determine the total cost of each ingredient based on unit size and price. The weekly grocery shopping cost was determined through summation of all ingredients and their entire unit size to compare weekly costs.
Weekly meal plans (absolute grams) cost between $93-193AUD. The AGHE meal plan was the least expensive and 8 Weeks to Wow was the most expensive. Weekly grocery shopping of entire units cost between $345-$625AUD, over $100AUD greater than the spending of an average Australian ($237AUD/week).
The financial feasibility for long-term sustainment of weight loss diets may be questionable for groups including low-income earners and low socioeconomic status. Further, when dietary patterns are adapted for weight loss, or followed by consumers, deviations from foundational principles tend to occur which may influence overall cost.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mediterranean populations enjoy the health benefits of a Mediterranean diet (MedDiet), but is it feasible to implement such a pattern beyond the Mediterranean region? The MedLey trial, a 6-month ...MedDiet intervention vs habitual diet in older Australians, demonstrated that the participants could maintain high adherence to a MedDiet for 6 months. The MedDiet resulted in improved systolic blood pressure (BP), endothelial dilatation, oxidative stress, and plasma triglycerides in comparison with the habitual diet. We sought to determine if 12 months after finishing the MedLey study, the participants maintained their adherence to the MedDiet principles and whether the reduction in the cardiovascular disease (CVD) risk factors that were seen in the trial were sustained. Participants completed a food frequency questionnaire, and a 15-point MedDiet adherence score (MDAS; greater score = greater adherence) was calculated. Home BP was measured over 6 days, BMI was assessed, and fasting plasma triglycerides were measured. The data were analysed using intention-to-treat linear mixed effects models with a group × time interaction term, comparing data at baseline, 2, 4, and 18 months (12 months post-trial). At 18 months (12 months after finishing the MedLey study), the MedDiet group had a MDAS of 7.9 ± 0.3, compared to 9.6 ± 0.2 at 4 months (p < 0.0001), and 6.7 ± 0.2 (p < 0.0001), at baseline. The MDAS in the HabDiet group remained unchanged over the 18-month period (18 months 6.9 ± 0.3, 4 months 6.9 ± 0.2, baseline 6.7 ± 0.2). In the MedDiet group, the consumption of olive oil, legumes, fish, and vegetables remained higher (p < 0.01, compared with baseline) and discretionary food consumption remained lower (p = 0.02) at 18 months. These data show that some MedDiet principles could be adhered to for 12 months after finishing the MedLey trial. However, improvements in cardiometabolic health markers, including BP and plasma triglycerides, were not sustained. The results indicate that further dietary support for behaviour change may be beneficial to maintaining high adherence and metabolic benefits of the MedDiet.
A multitude of weight loss diets exist. However, no one diet has been proven to be superior, despite their claims. Resultingly, this creates confusion amongst consumers and conflicting nutrition ...messages. The aim of the ranking system was to evaluate a range of dietary pattern’s nutrition profile and financial costs, as well as their potential long-term sustainability and associated adverse effects. Nutrition profile is typically the focal point of weight loss diets with less attention focused towards other factors that may affect their suitability. Five popular diets (Keto, Paleo, Intermittent Fasting, Optifast, and 8 Weeks to Wow) and two energy restricted healthy eating principles (Australian Guide to Healthy Eating and the Mediterranean Diet) were compared for diet quality, cost, adverse effects, and support for behaviour change. In general, healthy eating principles scored more favourably compared to popular weight loss diets in all categories. Lower carbohydrate diets tended to score lower for diet quality due to restricting multiple food groups, had more associated adverse effects and did not encourage behaviour change compared to the other weight loss diets. Optifast was the only weight loss diet to receive a negative score for cost. There should be considerations when undertaking a change to dietary patterns beyond nutrition profile. Diets indeed vary in terms of diet quality, and in addition can be costly, incur adverse effects, and disregard behaviour change which is important for sustainable weight loss and maintenance. This ranking system could create a reference point for future comparisons of diets.
Non-beneficial treatment affects a considerable proportion of older people in hospital, and some will choose to decline invasive treatments when they are approaching the end of their life. The ...Intervention for Appropriate Care and Treatment (InterACT) intervention was a 12-month stepped wedge randomised controlled trial with an embedded process evaluation in three hospitals in Brisbane, Australia. The aim was to increase appropriate care and treatment decisions for older people at the end-of-life, through implementing a nudge intervention in the form of a prospective feedback loop. However, the trial results indicated that the expected practice change did not occur. The process evaluation aimed to assess implementation using the Consolidated Framework for Implementation Research, identify barriers and enablers to implementation and provide insights into the lack of effect of the InterACT intervention.
Qualitative data collection involved 38 semi-structured interviews with participating clinicians, members of the executive advisory groups overseeing the intervention at a site level, clinical auditors, and project leads. Online interviews were conducted at two times: implementation onset and completion. Data were coded to the Consolidated Framework for Implementation Research and deductively analysed.
Overall, clinicians felt the premise and clinical reasoning behind InterACT were strong and could improve patient management. However, several prominent barriers affected implementation. These related to the potency of the nudge intervention and its integration into routine clinical practice, clinician beliefs and perceived self-efficacy, and wider contextual factors at the health system level.
An intervention designed to change clinical practice for patients at or near to end-of-life did not have the intended effect. Future interventions targeting this area of care should consider using multi-component strategies that address the identified barriers to implementation and clinician change of practice.
Australia New Zealand Clinical Trial Registry (ANZCTR), ACTRN12619000675123p (approved 06/05/2019).
The impact of a Mediterranean diet on the intestinal microbiome has been linked to its health benefits. We aim to evaluate the effects of a Mediterranean diet supplemented with dairy foods on the gut ...microbiome in Australians at risk of cardiovascular disease. In a randomised controlled cross-over study, 34 adults with a systolic blood pressure ≥120 mmHg and with risk factors for cardiovascular disease were randomly allocated to a Mediterranean diet with 3–4 daily serves of dairy foods (Australian recommended daily intake (RDI) of 1000–1300 mg per day (MedDairy)) or a low-fat (LFD) control diet. Between each 8-week diet, participants underwent an 8-week washout period. Microbiota characteristics of stool samples collected at the start and end of each diet period were determined by 16S rRNA amplicon sequencing. MedDairy-associated effects on bacterial relative abundance were correlated with clinical, anthropometric, and cognitive outcomes. No change in the overall faecal microbial structure or composition was observed with either diet (p > 0.05). The MedDairy diet was associated with changes in the relative abundance of several bacterial taxa, including an increase in Butyricicoccus and a decrease in Colinsella and Veillonella (p < 0.05). Increases in Butyricicoccus relative abundance over 8 weeks were inversely correlated with lower systolic blood pressure (r = −0.38, p = 0.026) and positively correlated with changes in fasting glucose levels (r = 0.39, p = 0.019), specifically for the MedDairy group. No significant associations were observed between the altered taxa and anthropometric or cognitive measures (p > 0.05). Compared to a low-fat control diet, the MedDairy diet resulted in changes in the abundance of specific gut bacteria, which were associated with clinical outcomes in adults at risk of CVD.
Objectives. To investigate the ability of bone marrow (BM)-derived mesenchymal stromal cells (BM-MSCs) in suppressing the proliferation of stimulated lymphocytes across a range of conditions ...including autologous BM-MSCs derived from autoimmune disease (AD) patients.
Methods.
In vitro cultures of BM-MSCs from healthy donors and AD patients were established and characterized by their differentiation potential into adipocytes and osteoblasts, and their fibroblast-colony-forming unit (CFU-F) ability and phenotype by flow cytometry.
BM-MSCs (irradiated and non-irradiated) from healthy and AD patients were tested for their ability to suppress the in vitro proliferation of autologous and allogeneic peripheral blood mononuclear cells (PBMC) (from healthy donors and patients suffering from various ADs) stimulated with anti-CD3ε antibody alone or in combination with anti-CD28 antibody. The anti-proliferative effect of the BM-MSCs from healthy donors was tested also on transformed B-cell lines as a model of non-antigen-stimulated lymphocytes.
Results. BM-MSCs from healthy donors and AD patients reduced the proliferation of autologous and allogeneic PBMCs by up to 90% in a cell dose-dependent fashion. The immunosuppression was independent of the proliferation of the BM-MSCs and was also effective on already proliferating cells. It was independent also of the clinical activity of AD.
An MSC dose-dependent pattern of suppression of proliferation was observed also with transformed B-cell lines, similar to that observed with proliferating PBMC.
Conclusions.The BM-MSCs exhibit extensive anti-proliferative properties against lymphocytes under different conditions. This property might offer a form of immunomodulatory cellular therapy for AD patients if further confirmed in animal models.
There is limited information regarding the nutrition profile and diet quality of meal plans from currently popular weight loss (WL) diets in Australia. This includes the energy content (kilojoules), ...the macronutrient distribution and the micronutrient composition. Further, these diets have not been compared with current government guidelines and healthy eating principles (HEP) for nutritional adequacy. Popular diets were identified through grey literature, trending searches and relative popularity in Australia. Meal plans for each diet were analysed using Foodworks Dietary Software to determine food group intake, micronutrient and macronutrient distribution. The results indicated that all popular diets assessed deviated from government recommended HEP such as the Australian Guide to Healthy Eating and the Mediterranean diet. In most cases, both popular diets and the HEP had low intakes of multiple food groups, low intakes of essential micronutrients and a distorted macronutrient distribution. Popular diets may not provide adequate nutrition to meet needs, particularly in the long term and potentially resulting in micronutrient deficiency. When energy restricting for WL, meal plans should be highly individualised in conjunction with a qualified nutrition professional to ensure adequate dietary intake.
In previous papers, we observed that dendrimers of peptide mimotopes of the nicotinic receptor ligand site are strong antidotes against the lethality of the nicotinic receptor ligand α-bungarotoxin. ...Although their in vitro activity is identical to that of dendrimers, the corresponding monomeric peptide mimotopes are not effective in vivo. Because the higher in vivo efficiency of dendrimers could not in this case be related to polyvalent interaction, the stability to blood protease activity of monomeric versus tetrabranched dendrimeric mimotope peptides was compared here by incubating three different mimotopes with human plasma and serum. Unmodified peptides and cleaved sequences were followed by high pressure liquid chromatography and mass spectrometry. Tetrabranched peptides were shown to be much more stable in plasma and also in serum. To assess the notable stability of multimeric peptides, different bioactive neuropeptides, including enkephalins, neurotensin and nociceptin, were synthesized in monomeric and tetrabranched forms and incubated with human plasma and serum and with rat brain membrane extracts. All the tetrabranched neuropeptides fully retained biological activity and generally showed much greater stability to blood and brain protease activity. Some tetrabranched peptides were also resistant to trypsin and chymotrypsin. Our findings provide new insights into the possible therapeutic use of bioactive peptides.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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