Allied health professionals: A promising ally in the work against health inequalities- A rapid review.

Objectives: Allied Health Professionals (AHPs) have a crucial role in reducing health inequalities. However, there is a lack of evidence regarding the ways they can fulfil this role. This rapid review explores the ways in which AHPs can decrease health care or health outcome inequalities; address inequalities in the social determinants of health; and support disadvantaged groups at an individual, organisational and system level. Study design: Rapid review following Cochrane criteria and narrative synthesis. Methods: MEDLINE, EMBASE, CINAHL, Web of Science and AMED were searched combined with grey literature, to identify quantitative or qualitative review articles published between January 2010 and February 2021. Results: From 8727 references, 36 met the inclusion criteria. The methodological quality of the studies was assessed with the AMSTAR tool and was generally low. Meta-analysis was not possible due to the heterogeneity of the studies, and a narrative synthesis was produced. Three themes emerged at patient and organisational level: 1) access to AHP services; 2) quality of care; and 3) social determinants of health. Two themes emerged at system level: 1) unequal workforce distribution and 2) lack of inclusive clinical guidelines. Conclusions: This rapid review offers a broad range of evidence on the ways AHPs can contribute to the reduction of inequalities in health care, both in terms of access and quality of care and in health outcomes. More research is needed to further understand the impact of AHPs on inequalities affecting specific groups and their contribution to equitable distribution of social determinants of health.

Failed rib region prediction in a human body model during crash events with precrash braking.

OBJECTIVE: The objective of this study is 2-fold. We used a validated human body finite element model to study the predicted chest injury (focusing on rib fracture as a function of element strain) based on varying levels of simulated precrash braking. Furthermore, we compare deterministic and probabilistic methods of rib injury prediction in the computational model. METHODS: The Global Human Body Models Consortium (GHBMC) M50-O model was gravity settled in the driver position of a generic interior equipped with an advanced 3-point belt and airbag. Twelve cases were investigated with permutations for failure, precrash braking system, and crash severity. The severities used were median (17 kph), severe (34 kph), and New Car Assessment Program (NCAP; 56.4 kph). Cases with failure enabled removed rib cortical bone elements once 1.8% effective plastic strain was exceeded. Alternatively, a probabilistic framework found in the literature was used to predict rib failure. Both the probabilistic and deterministic methods take into consideration location (anterior, lateral, and posterior). The deterministic method is based on a rubric that defines failed rib regions dependent on a threshold for contiguous failed elements. The probabilistic method depends on age-based strain and failure functions. RESULTS: Kinematics between both methods were similar (peak max deviation: ΔXhead = 17 mm; ΔZhead = 4 mm; ΔXthorax = 5 mm; ΔZthorax = 1 mm). Seat belt forces at the time of probabilistic failed region initiation were lower than those at deterministic failed region initiation. The probabilistic method for rib fracture predicted more failed regions in the rib (an analog for fracture) than the deterministic method in all but 1 case where they were equal. The failed region patterns between models are similar; however, there are differences that arise due to stress reduced from element elimination that cause probabilistic failed regions to continue to rise after no deterministic failed region would be predicted. CONCLUSIONS: Both the probabilistic and deterministic methods indicate similar trends with regards to the effect of precrash braking; however, there are tradeoffs. The deterministic failed region method is more spatially sensitive to failure and is more sensitive to belt loads. The probabilistic failed region method allows for increased capability in postprocessing with respect to age. The probabilistic failed region method predicted more failed regions than the deterministic failed region method due to force distribution differences.

The differential short- and long-term effects of HIV-1 latency-reversing agents on T cell function.

Despite the extraordinary success of HIV-1 antiretroviral therapy in prolonging life, infected individuals face lifelong therapy because of a reservoir of latently-infected cells that harbor replication competent virus. Recently, compounds have been identified that can reverse HIV-1 latency in vivo. These latency- reversing agents (LRAs) could make latently-infected cells vulnerable to clearance by immune cells, including cytolytic CD8+ T cells. We investigated the effects of two leading LRA classes on CD8+ T cell phenotype and function: the histone deacetylase inhibitors (HDACis) and protein kinase C modulators (PKCms). We observed that relative to HDACis, the PKCms induced much stronger T cell activation coupled with non-specific cytokine production and T cell proliferation. When examining antigen-specific CD8+ T cell function, all the LRAs except the HDACi Vorinostat reduced, but did not abolish, one or more measurements of CD8+ T cell function. Importantly, the extent and timing of these effects differed between LRAs. Panobinostat had detrimental effects within 10 hours of drug treatment, whereas the effects of the other LRAs were observed between 48 hours and 5 days. These observations suggest that scheduling of LRA and CD8+ T cell immunotherapy regimens may be critical for optimal clearance of the HIV-1 reservoir.

Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation.

Current immunosuppressive/anti-inflammatory agents target the responding effector arm of the immune response and their nonspecific action increases the risk of infection and malignancy. These effects impact on their use in allogeneic haematopoietic cell transplantation and other forms of transplantation. Interventions that target activated dendritic cells (DCs) have the potential to suppress the induction of undesired immune responses (for example, graft versus host disease (GVHD) or transplant rejection) and to leave protective T-cell immune responses intact (for example, cytomegalovirus (CMV) immunity). We developed a human IgG1 monoclonal antibody (mAb), 3C12, specific for CD83, which is expressed on activated but not resting DC. The 3C12 mAb and an affinity improved version, 3C12C, depleted CD83(+) cells by CD16(+) NK cell-mediated antibody-dependent cellular cytotoxicity, and inhibited allogeneic T-cell proliferation in vitro. A single dose of 3C12C prevented human peripheral blood mononuclear cell-induced acute GVHD in SCID mouse recipients. The mAb 3C12C depleted CMRF-44(+)CD83(bright) activated DC but spared CD83(dim/-) DC in vivo. It reduced human T-cell activation in vivo and maintained the proportion of CD4(+) FoxP3(+) CD25(+) Treg cells and also viral-specific CD8(+) T cells. The anti-CD83 mAb, 3C12C, merits further evaluation as a new immunosuppressive agent in transplantation.

Impact of diet and exercise on lipid management in the modern era.

Unfortunately, many patients as well as the medical community, continue to rely on coronary revascularization procedures and cardioprotective medications as a first-line strategy to stabilize or favorably modify established risk factors and the course of coronary artery disease. However, these therapies do not address the root of the problem, that is, the most proximal risk factors for heart disease, including unhealthy dietary practices, physical inactivity, and cigarette smoking. We argue that more emphasis must be placed on novel approaches to embrace current primary and secondary prevention guidelines, which requires attacking conventional risk factors and their underlying environmental causes. The impact of lifestyle on the risk of cardiovascular disease has been well established in clinical trials, but these results are often overlooked and underemphasized. Considerable data also strongly support the role of lifestyle intervention to improve glucose and insulin homeostasis, as well as physical inactivity and/or low aerobic fitness. Accordingly, intensive diet and exercise interventions can be highly effective in facilitating coronary risk reduction, complementing and enhancing medications, and in some instances, even outperforming drug therapy.

Effects of an intensive short-term diet and exercise intervention: comparison between normal-weight and obese children.

Lifestyle intervention programs currently emphasize weight loss secondary to obesity as the primary determinant of phenotypic changes. We examined whether the effects of a short-term lifestyle intervention program differ in normal-weight versus overweight/obese children. Nineteen overweight/obese (O; BMI = 33.6 ± 1.9 kg/m(2)) and 14 normal-weight (N; BMI = 19.9 ± 1.5 kg/m(2)) children participated in a 2-wk program consisting of an ad libitum high-fiber, low-fat diet and daily exercise (2-2.5 h). Fasting serum samples were taken pre- and postintervention for determination of lipids, glucose homeostasis, inflammatory cytokines, and adipokines. Only the O group lost weight (3.9%) but remained overweight/obese (32.3 ± 1.9 kg/m(2)). Both groups exhibited significant intervention-induced decreases (P < 0.05) in serum insulin (N: 52.5% vs. O: 28.1%; between groups, P = 0.38), homeostatic model assessment for insulin resistance (N: 53.1% vs. O: 28.4%, P = 0.43), leptin (N: 69.3% vs. O: 44.1%, P = 0.10), amylin (N: 28.7% vs. O: 26.1%, P = 0.80), resistin (N: 40.0% vs. O: 35.1%, P = 0.99), plasminogen activator-inhibitor-1 (N: 30.8% vs. O: 25.6%, P = 0.59), IL-6 (N: 58.8% vs. O: 48.5%, P = 0.78), IL-8 (N: 46.0% vs. O: 42.2%, P = 0.49), and TNFα (N: 45.8% vs. O: 40.8%, P = 0.99). No associations between indices of weight change and phenotypic changes were noted. A short-term, intensive lifestyle modification program is effective in ameliorating metabolic risk factors in N and O children. These results suggest that obesity per se was not the primary driver of the phenotypes noted and that dietary intake and physical inactivity induce the phenotypic abnormalities. These data may have implications for the weight loss-independent management of cardiometabolic risk in pediatric populations.

Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training.

Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Regardless of the true definition, based on current population estimates, nearly 100 million have MS. It is often characterized by insulin resistance, which some have suggested is a major underpinning link between physical inactivity and MS. The purpose of this review is to: (i) provide an overview of the history, causes and clinical aspects of MS, (ii) review the molecular mechanisms of insulin action and the causes of insulin resistance, and (iii) discuss the epidemiological and intervention data on the effects of exercise on MS and insulin sensitivity.

Gene expression phenotypes for lipid metabolism and intramuscular fat in skeletal muscle of cattle.

Gene expression phenotypes were evaluated for intramuscular fat (IMF) in bovine skeletal muscle as an alternative to traditional estimates of IMF%. Gene expression data from a time course of LM development in high- and low-marbling Bos taurus cattle crosses were compared to identify genes involved in intramuscular adipocyte lipid metabolism with developmentally similar gene expression profiles. Three sets of genes were identified: triacylglyceride (TAG) synthesis and storage, fatty acid (FA) synthesis, and PPARγ-related genes. In an independent analysis in the LM of 48 Bos indicus cattle, TAG and FA gene sets were enriched in the top 100 genes of which expression was most correlated with IMF% (P = 1.2 × 10(-24) and 3.5 × 10(-9), respectively). In general, genes encoding enzymes involved in the synthesis of FA and TAG in the intramuscular adipocytes were present in the top 100 genes. In B. indicus, effects of a steroid hormone growth promotant (HGP), 2 experimental sites [New South Wales (NSW) and Western Australia (WA)], and 3 tenderness genotypes on the expression levels of genes in the TAG gene set and the correlation of gene expression with IMF% were investigated. Although correlation between expression of 12 individual TAG genes and IMF% was observed in HGP-treated animals in both experimental sites (mean r = 0.43), correlation was not observed for untreated animals at the NSW site (mean r = -0.07, P < 3 × 10(-6)). However, TAG genes showed an average 1.6-fold (P < 0.0004) reduction in expression in the LM of HGP-treated cattle relative to untreated cattle, an effect consistent across both experimental sites. Cattle possessing the favored tenderness calpain 1 and 3 and calpastatin alleles exhibited a greater (P = 0.008) reduction in expression in NSW (1.8-fold reduction, P = 0.0002) compared with WA (1.2-fold reduction, P = 0.03). Tenderness genotype had no impact (P > 0.05) on the correlation of TAG genes with IMF%. In general, the interactions among genotype, treatment and location, and TAG gene set gene expression were consistent with the interactions among the same factors and IMF% detected using 255 animals, of which the 48 in this study were a subset. Thus, the TAG gene set constitutes a gene expression phenotype able to predict effects of different genotypes and treatments on IMF% using much smaller groups than current approaches, even in animals with very low IMF%.

Soil nitrogen dynamics in a river floodplain mosaic.

In their natural state, river floodplains are heterogeneous and dynamic ecosystems that may retain and remove large quantities of nitrogen from surface waters. We compared the soil nitrogen dynamics in different types of habitat patches in a restored and a channelized section of a Thur River floodplain (northeast Switzerland). Our objective was to relate the spatiotemporal variability of selected nitrogen pools (ammonium, nitrate, microbial nitrogen), nitrogen transformations (mineralization, nitrification, denitrification), and gaseous nitrogen emission (NO) to soil properties and hydrological processes. Our study showed that soil water content and carbon availability, which depend on sedimentation and inundation dynamics, were the key factors controlling nitrogen pools and processes. High nitrogen turnover rates were measured on gravel bars, characterized by both frequent inundation and high sediment deposition rates, as well as in low-lying alluvial forest patches with a fine-textured, nutrient-rich soil where anaerobic microsites probably facilitated coupled nitrification-denitrification. In contrast, soils of the embankment in the channelized section had comparatively small inorganic nitrogen pools and low transformation rates, particularly those related to nitrate production. Environmental heterogeneity, characteristic of the restored section, favors nitrogen removal by creating sites of high sedimentation and denitrification. Of concern, however, are the locally high NO efflux and the possibility that nitrate could leach from nitrification hotspots.

A short-term diet and exercise intervention ameliorates inflammation and markers of metabolic health in overweight/obese children.

The present study was designed to examine the effects of short-term diet and exercise on markers of metabolic health, serum-stimulated production of inflammatory biomarkers from cultured monocytes and adipocytes, and serum lipomics. Twenty-one overweight/obese children (9 boys and 12 girls, age 13.0 ± 0.5 yr, BMI 33.0 ± 1.8 kg/m(2)) were placed on a 2-wk ad libitum, high-fiber, low-fat diet and daily exercise regimen. Fasting serum samples were taken pre- and postintervention for determination of cytokines, metabolic risk markers, and lipomics. Monocytes and adipocytes were incubated with pre- and postintervention serum to investigate changes in cytokine secretion. Correlative associations were calculated, followed by hierarchical clustering to determine relationships between fatty acid (FA) species and clinical biomarkers. Despite remaining overweight/obese, interleukin (IL)-6, IL-8, TNFα, PAI-1, resistin, amylin, leptin, insulin, and IL-1ra decreased and adiponectin increased. Culture studies indicated decreases in monocyte secretion of IL-6, TNFα, and IL-1ß and adipocyte secretion of IL-6. Lipomic analysis revealed a decrease in total lipids and decreases in saturated FAs and an increase in 18:1/18:0. In general, Pearson's correlations revealed that inflammatory markers are negatively associated with a cluster of polyunsaturated FAs and positively correlated with several saturated FAs. These results indicate significant modification of multiple indices of metabolic health with short-term rigorous lifestyle modification in overweight/obese children prior to obesity reversal.

Effect of a low-fat diet combined with IGF-1 receptor blockade on 22Rv1 prostate cancer xenografts.

In preclinical models, both dietary fat reduction and insulin-like growth factor I receptor (IGF-1R) blockade individually inhibit prostate cancer xenograft growth. We hypothesized that a low-fat diet combined with IGF-1R blockade would cause additive inhibition of prostate cancer growth and offset possible untoward metabolic effects of IGF-1R blockade antibody therapy. Fifty severe combined immunodeficient mice were injected with 22Rv1 cells subcutaneously. Ten days postinjection, the animals were randomized to four groups: (i) high-fat diet + saline (HF); (ii) high-fat diet + IGF-1R blocking antibody, ganitumab (HF/Ab); (iii) low-fat diet + saline (LF); and (iv) low-fat diet + ganitumab (LF/Ab). After 19 days of treatment, the animals were euthanized, serum was collected, and tumors were weighed. Tumor Ki67, Akt and extracellular signal-regulated kinase (ERK) activation, serum insulin, IGF-I and TNF-α were measured. In vitro, ganitumab treatment inhibited growth and induced apoptosis in several prostate cancer cell lines. In vivo, tumor weights and volumes were unaffected by the different treatments. The LF/Ab therapy significantly reduced proliferation (Ki67) and ERK activation in tumors. The HF/Ab group had significantly higher serum insulin levels than the HF group. However, LF/Ab combination significantly reduced serum insulin back to normal levels as well as normalizing serum TNF-α level. Whereas the combination of low-fat diet and IGF-1R blockade did not have additive inhibitory effects on tumor weight, it led to reduced tumor cell proliferation and a reduction in serum insulin and TNF-α levels.

Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy.

Preclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control Western diet (omega-6:omega-3 ratio of 15:1) for four to six weeks prior to surgery. The primary endpoint was change in serum insulin-like growth factor I (IGF-1) between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E2 levels, omega-6:omega-3 fatty acid ratios, COX-2, and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil versus Western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki-67 index), and reduced proliferation in an ex vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, four to six weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses, the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology.

Global Igfbp1 deletion does not affect prostate cancer development in a c-Myc transgenic mouse model.

Circulating insulin-like growth factor binding protein 1 (IGFBP1) levels vary in response to nutritional status, and pre-clinical studies suggest that elevated IGFBP1 may be protective against the development and progression of prostate cancer. We hypothesized that global deletion of Igfbp1 would accelerate the development of prostate cancer in a c-Myc transgenic mouse model. To test our hypothesis, c-Myc transgenic mice (Myc/BP-1 wild-type (WT)) were crossed and interbred with the Igfbp1 knockout mice (Myc/BP-1 KO). The animals were placed on a high-protein diet at weaning, weighed every 2 weeks, and euthanized at 16 weeks of age. Prostate histopathology was assessed and proliferation status was determined by Ki-67 and proliferating cell nuclear antigen analyses. IGF-related serum biomarkers and body composition were measured. No significant difference in the incidence of prostate cancer was observed between the Myc/BP-1 KO and the Myc/BP-1 WT mice (65 and 80% respectively, P=0.48). Proliferation was significantly decreased by 71% in prostate tissue of Myc/BP-1 KO mice compared with Myc/BP-1 WT mice. Myc/BP-1 KO mice exhibited a significant 6.7% increase in body weight relative to the Myc/BP-1 WT mice that was attributed to an increase in fat mass. Fasting insulin levels were higher in the Myc/BP-1 KO mice without any difference between the groups in fasting glucose concentrations. Thus, contrary to our hypothesis, global deletion of Igfbp1 in a c-Myc transgenic mouse model did not accelerate the development of prostate cancer. Global Igfbp1 deletion did result in a significant increase in body weight and body fat mass. Further studies are required to understand the underlying mechanisms for these metabolic effects.

Effectiveness of once-weekly gym-based exercise programmes for older adults post discharge from day rehabilitation: a randomised controlled trial.

OBJECTIVE: To determine whether high-intensity, progressive gym-based exercise performed once a week is as effective as twice weekly for maintaining both subjective and objective outcomes in older adults post discharge from a metropolitan day rehabilitation centre (DRC). DESIGN: Randomised controlled trial. SETTING: Community-based exercise centre for older adults, located in Metropolitan Adelaide, South Australia. PARTICIPANTS: 21 men and 85 women who completed the DRC programme were assessed and randomly allocated to a study group. INTERVENTION: The two experimental interventions were gym-based exercise programmes (including resistance, aerobic, flexibility and balance training) varying only in frequency of delivery: either once or twice a week, directly compared with usual care (control). MAIN OUTCOME MEASURES: Lower limb strength (one-repetition maximum), balance (Berg Balance Scale), physical function (gait speed, 30-s chair stand test, timed up and go test (primary outcome) and 6-min walk test), self-reported pain (Glasgow Pain Questionnaire), activities of daily living (Barthel Index and Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire), perceived benefits of and barriers to exercise (Exercise Benefits Barriers Scale), quality of life (Assessment of Quality of Life Questionnaire) and exercise frequency preference. RESULTS: Most of the outcomes (69%, 11/16) were maintained over the intervention period with no significant group effects detected between the two intervention groups or compared to the control group. Physical activity levels recorded in the control group showed a significant proportion of participants were actively exercising once weekly. A per-protocol analysis was undertaken to take this potential contamination effect into account. This showed that the control group participants, who did not exercise, did not maintain outcomes to the extent of the intervention groups, with significant group-by-time effects detected between the two intervention groups and the control group. Most of all participants (66%, 62/94) nominated once a week as their preferred exercise frequency. CONCLUSIONS: The overall finding of no significant differences between the two intervention groups for all outcomes measured gives support to the effectiveness of once-a-week exercise in maintaining outcomes at 3 months post rehabilitation. Further research is warranted given the once-a-week exercise intervention should cost less, had higher compliance and was nominated as the preferred exercise frequency by most of the participants.

Analyzing serum-stimulated prostate cancer cell lines after low-fat, high-fiber diet and exercise intervention.

Serum from men undergoing a low-fat, high-fiber diet and exercise intervention has previously been shown to decrease growth and increase apoptosis in serum-stimulated, androgen-dependent LNCaP cells associated with a reduction in serum IGF-I. Here we sought to determine the underlying mechanisms for these anticancer effects. Again, the intervention slowed growth and increased apoptosis in LNCaP cells; responses that were eliminated when IGF-I was added back to the post-intervention samples. The p53 protein content was increased and NFκB activation reduced in the post serum-stimulated LNCaP cells. Similar results were observed when the IGF-I receptor was blocked in the pre-intervention serum. In androgen-independent PC-3 cells, growth was reduced while none of the other factors were changed by the intervention. We conclude that diet and exercise intervention might help prevent clinical PCa as well as aid in the treatment of PCa during the early stages of development.

Growth inhibitory effect of low fat diet on prostate cancer cells: results of a prospective, randomized dietary intervention trial in men with prostate cancer.

PURPOSE: A high fat Western diet and sedentary lifestyle may predispose men to prostate cancer through changes in serum hormones and growth factors. We evaluated the effect of a low fat diet on serum factors affecting prostate cancer cell growth by performing a prospective, randomized dietary intervention trial in men with prostate cancer. MATERIALS AND METHODS: We randomized 18 men with prostate cancer who did not receive prior therapy to a low fat (15% kcal), high fiber, soy protein supplemented diet or a Western (40% kcal fat) diet for 4 weeks. Fasting serum was collected at baseline and after the intervention to measure prostate specific antigen, sex hormones, insulin, insulin-like growth factor I and II, insulin-like growth factor binding proteins, lipids and fatty acids. LNCaP cells (ATCC(R)) were cultured in medium containing pre-intervention and post-intervention human serum to assess the in vitro effect of the diet on prostate cancer cell proliferation. RESULTS: Subjects in each group were highly compliant with the dietary intervention. Serum from men in the low fat group significantly decreased the growth of LNCaP cells relative to Western diet serum (p = 0.03). There were no significant between group changes in serum prostate specific antigen, sex hormones, insulin, insulin-like growth factor I and II, and insulin-like growth factor binding proteins. Serum triglyceride and linoleic acid (omega-6) levels were decreased in the low fat group (p = 0.034 and 0.005, respectively). Correlation analysis revealed that decreased omega-6 and increased omega-3 fatty acid correlated with decreased serum stimulated LNCaP cell growth (r = 0.64, p = 0.004 and r = -0.49, p = 0.04, respectively). CONCLUSIONS: In this prospective, randomized dietary intervention trial a low fat diet resulted in changes in serum fatty acid levels that were associated with decreased human LNCaP cancer cell growth. Further prospective trials are indicated to evaluate the potential of low fat diets for prostate cancer prevention and treatment.

Benign prostatic hyperplasia: does lifestyle play a role?

Benign prostatic hyperplasia (BPH) is a very common condition in older men, affecting up to 80% of men aged >or= 80 years in the United States. It typically leads to lower urinary tract symptoms, which often require medical management. The exact cause of BPH is unknown, and the only 2 established factors associated with BPH are age and the presence of androgens. Although the presence of testosterone is required for the development of BPH, testosterone is not thought to be the underlying factor causing BPH because testosterone levels decrease in older men. Recent studies have reported that BPH is associated with elevations in plasma estradiol/testosterone ratio, insulin, and insulin-like growth factor-I. Daily aerobic exercise can reduce all of these plasma factors, particularly when combined with a low-fat, high-fiber diet consisting of whole grains, fruits, and vegetables. In cell culture studies, this type of lifestyle regimen has recently been shown to reduce the growth of serum-stimulated prostate epithelial cells and the growth of androgen-dependent prostate cancer cell lines.

Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model.

This study evaluated the effect of dietary fat on prostate cancer development by using the Hi-Myc mouse transgenic prostate cancer model. Hi-Myc mice develop murine prostatic intraepithelial neoplasia (mPIN) as early as 2 to 4 weeks and invasive adenocarcinoma between 6 and 9 months due to the overexpression of human c-Myc in the mouse prostate. Three-week-old male Hi-Myc mice were placed on high-fat (HF; 42% Kcal) or low-fat (LF; 12% Kcal) diets, and equal caloric intake was maintained until euthanasia at 7 months. The number of mice that developed invasive adenocarcinoma at 7 months was 27% less in the LF diet group (12/28) compared with the HF diet group (23/33, P < 0.05). Epithelial cells in mPIN lesions in the LF group had a significantly lower proliferative index compared with epithelial cells in the HF group (21.7% versus 28.9%, P < 0.05). During the mPIN phase of carcinogenesis (4 months), the LF group had higher serum insulin-like growth factor (IGF) binding protein-1 levels (21.0 +/- 8.9 ng/mL versus 3.2 +/- 0.8 ng/mL, P < 0.05) relative to the HF group. Akt (Ser(473)) phosphorylation, Akt kinase activity, and phosphorylation of downstream targets of Akt in prostates were significantly reduced in the LF diet group compared with the HF group. We conclude that dietary fat reduction delays transition from mPIN to invasive cancer in this Myc-driven transgenic mouse model, possibly through suppression of the IGF-Akt pathway and decreased proliferation of mPIN epithelial cells.