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Sociodemographic and lifestyle-related risk factors for identifying vulnerable groups for type 2 diabetes: a narrative review with emphasis on data from Europe.
Kyrou, I, Tsigos, C, Mavrogianni, C, Cardon, G, Van Stappen, V, Latomme, J, Kivelä, J, Wikström, K, Tsochev, K, Nanasi, A, et al
BMC endocrine disorders. 2020;20(Suppl 1):134
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Type 2 diabetes mellitus (T2DM) results from progressive loss of insulin secretion, which is typically combined with various degrees of insulin resistance. The aim of this study is to provide a comprehensive overview of key sociodemographic and lifestyle-related risk factors for identifying vulnerable groups for T2DM with emphasis on data from Europe. This study is a narrative review which includes 101 publications. Literature shows that prevention of T2DM should be a collaborative effort which mobilizes multiple partners/ stakeholders at a national and international (e.g. European) level. In addition, a holistic approach is becoming increasingly essential in order to put into effect multidimensional public health programs and integrated interventions for effective T2DM prevention which will take into account both traditional and socioeconomic/socioecological factors. Authors conclude that a multidimensional approach for the prevention of T2DM may have a broader impact against the current diabesity epidemic within and across countries in Europe.
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) comprises the vast majority of all diabetes cases in adults, with alarmingly increasing prevalence over the past few decades worldwide. A particularly heavy healthcare burden of diabetes is noted in Europe, where 8.8% of the population aged 20-79 years is estimated to have diabetes according to the International Diabetes Federation. Multiple risk factors are implicated in the pathogenesis of T2DM with complex underlying interplay and intricate gene-environment interactions. Thus, intense research has been focused on studying the role of T2DM risk factors and on identifying vulnerable groups for T2DM in the general population which can then be targeted for prevention interventions. METHODS For this narrative review, we conducted a comprehensive search of the existing literature on T2DM risk factors, focusing on studies in adult cohorts from European countries which were published in English after January 2000. RESULTS Multiple lifestyle-related and sociodemographic factors were identified as related to high T2DM risk, including age, ethnicity, family history, low socioeconomic status, obesity, metabolic syndrome and each of its components, as well as certain unhealthy lifestyle behaviors. As Europe has an increasingly aging population, multiple migrant and ethnic minority groups and significant socioeconomic diversity both within and across different countries, this review focuses not only on modifiable T2DM risk factors, but also on the impact of pertinent demographic and socioeconomic factors. CONCLUSION In addition to other T2DM risk factors, low socioeconomic status can significantly increase the risk for prediabetes and T2DM, but is often overlooked. In multinational and multicultural regions such as Europe, a holistic approach, which will take into account both traditional and socioeconomic/socioecological factors, is becoming increasingly crucial in order to implement multidimensional public health programs and integrated community-based interventions for effective T2DM prevention.
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How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS.
Nacul, L, O'Boyle, S, Palla, L, Nacul, FE, Mudie, K, Kingdon, CC, Cliff, JM, Clark, TG, Dockrell, HM, Lacerda, EM
Frontiers in neurology. 2020;11:826
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A good understanding of the disease course is vital not only for the design of preventative and intervention studies, but also to assess the timing and type of intervention that minimizes disease risk or optimizes prognosis. The aim of this review was to explore the long-term course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and how presentation and pathophysiological abnormalities may vary with time. Literature shows that it is unknown how the initial host response to a stressor or insult compares in individuals who do or do not develop typical symptoms of ME/CFS. However, the return to good health, following exposure to mild or moderate levels of insult, seems to be impeded in ME/CFS when symptoms persist for longer than 3–6 months. Authors sought to provide a simple framework, similar to those of other chronic diseases, in an effort to extend the temporal perception of ME/CFS and better incorporate the less defined pre-illness stages of the disease. In fact, they conclude that by applying this framework to ME/CFS research efforts could better elucidate the pathophysiological mechanisms of the disease and identify potential therapeutic targets at distinct stages.
Abstract
We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS.
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The impact of educational attainment on cardiorespiratory fitness and metabolic syndrome in Korean adults.
Chang, M, Lee, HY, Seo, SM, Koh, YS, Park, HJ, Kim, PJ, Seung, KB
Medicine. 2020;99(17):e19865
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Lower socioeconomic status is associated with worse health outcomes, and in particular with cardiovascular disease and metabolic syndrome. This association is thought to be mediated through lifestyle factors such as physical activity, diet and smoking. Level of education is commonly used as an indicator for socioeconomic status. This Korean cross-sectional study, involving 988 healthy adults, evaluated the association between level of education (<12 years, 12-16 years, >16 years), cardiorespiratory fitness (CRF) and metabolic syndrome. People in the highest education group were more likely to be younger and male. There was no difference in the prevalence of metabolic syndrome, hypertension or diabetes mellitus between the three educational attainment groups, 36.1% overall had metabolic syndrome. There was also no difference in dyslipidaemia, physical activity or smoking status. Whilst BMI was similar in all groups, the higher the level of education, the lower the body fat and the higher lean mass and CRF were. Although education was not associated with metabolic syndrome, better CRF was associated with lower rates of metabolic syndrome. Limitations of the study as pointed out by the authors include the retrospective design and a potentially non-representative sample.
Abstract
The aim of this study was to evaluate the relationship between educational attainment and cardiorespiratory fitness (CRF) as a predictor of metabolic syndrome in a Korean population.In this single-center, retrospective cross-sectional study, 988 healthy adults (601 men and 387 women) who underwent regular health check-up in Seoul St. Mary's Hospital were analyzed. Educational attainment was categorized into 3 groups according to their final grade of educational course: middle or high school (≤12 years of education), college or university (12-16 years of education), and postgraduate (≥16 years of education). CRF was assessed by cardiopulmonary exercise testing, biceps strength, hand grip strength, bioelectrical impedance analysis, and echocardiography. Metabolic syndrome was diagnosed according to the 3rd report of the National Cholesterol Education Program.Among the subjects, 357 (36.1%) had metabolic syndrome. The postgraduate group had significantly higher peak oxygen consumption (VO2), biceps strength, hand grip strength, and peak expiratory flow than other groups (all P < .001). This group showed better left ventricular diastolic function, in terms of deceleration time of mitral inflow, maximal tricuspid valve regurgitation velocity, and left atrial volume index than other groups. Peak VO2 (%) was significantly correlated with all the parameters of metabolic syndrome, including insulin resistance (r = -0.106, P = .002), waist circumference (r = -0.387, P < .001), triglyceride (r = -0.109, P = .001), high density lipoprotein-cholesterol (r = 0.219, P < .001), systolic blood pressure (r = -0.143, P < .001), and diastolic blood pressure (r = -0.177, P < .001). And Peak VO2 (%) was found to be a predictor of metabolic syndrome (adjusted β = .988, P < .001). However, the level of education was not able to predict metabolic syndrome (postgraduate group; β = .955, P = .801).Although the postgraduate group had better CRF than other groups, the educational attainment could not exclusively predict metabolic syndrome in this study. Further research is needed to reveal the socioeconomic mechanism of developing metabolic syndrome.
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Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.
Kim, DH, Bang, E, Jung, HJ, Noh, SG, Yu, BP, Choi, YJ, Chung, HY
Nutrients. 2020;12(2)
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Low grade, systemic, chronic inflammation is a feature of ageing and underlies many age-related chronic diseases states. As cells age their capacity to proliferate declines, which is referred to as cell senescence. Such senescent cells release multiple inflammatory markers contributing to a pro-inflammatory state. This is further aggravated by elevated oxidative stress and a reduced capacity to manage it, eventually leading to improper gene regulation and DNA damage. To define this age-related, complex inflammatory phenomena the authors introduced the term senoinflammation. A well-established intervention to reverse or slow down the ageing process and many ageing-associated diseases is calorie restriction (CR), by means of reducing overall caloric intake without malnutrition. CR exhibits potent anti-inflammatory effects, reduces age-associated oxidative stress, improves age-related metabolic dysregulation and enhances favourable gene expression. This review summarises how CR and CR-mimicking substances exert their anti-inflammatory effect and some of the cellular mechanism involved and may be of interest to those who are looking to get a more detailed understanding on ageing, inflammation and the benefits of CR.
Abstract
Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.
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A Systematic Review of Organic Versus Conventional Food Consumption: Is There a Measurable Benefit on Human Health?
Vigar, V, Myers, S, Oliver, C, Arellano, J, Robinson, S, Leifert, C
Nutrients. 2019;12(1)
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The demand for organic products has risen rapidly over the last decades. The reasons why consumers may favour organic over conventional products are varied. They may be for personal health and wellbeing, environmental considerations, animal welfare or perceived higher nutritional profile - which is true for some, but not all components. While the long-term safety of pesticide consumption through conventional food production has been questioned, organic foods clearly show lower levels of toxic metabolites, like heavy metals and synthetic fertilizer and pesticide residues. This systematic review aimed to assess the current evidence of organic diet consumption and human health compared to conventionally produced foods. Included were 35 papers on clinical trials and observational studies. The clinical trials studied pesticide and phytochemical excretion, antioxidant capacity, body composition, lipids and inflammatory markers. The observational studies were focused on fertility, foetal and childhood development, pregnancy, lactation and levels of pesticides in children and adults, as well as nutritional biomarkers and cancer risk in adults. An increased intake of organic produce in long-term studies appeared to reduce the incidence of infertility, birth defects, allergies, middle ear infection, pre-eclampsia, metabolic syndrome, high BMI, and non-Hodgkin lymphoma. Organic intake was also linked to reduced urinary levels of organophosphorus pesticides and herbicides. Yet, the author highlighted that organic consumers are more likely to be health conscious, physically active, eat a more plant-based diet, have higher education levels and income, and therefore are not representative of the general population. They also argue that the possible benefits from an organic diet may be partially due to the quality and composition of the diet rather than a direct effect of organic food consumption. Whereby a growing number of findings demonstrate the health benefits of organic food consumption, according to the authors, the current evidence does not yield a solid and definitive answer.
Abstract
The current review aims to systematically assess the evidence related to human health outcomes when an organic diet is consumed in comparison to its conventional counterpart. Relevant databases were searched for articles published to January 2019. Clinical trials and observational research studies were included where they provided comparative results on direct or indirect health outcomes. Thirty-five papers met the criteria for inclusion in the review. Few clinical trials assessed direct improvements in health outcomes associated with organic food consumption; most assessed either differences in pesticide exposure or other indirect measures. Significant positive outcomes were seen in longitudinal studies where increased organic intake was associated with reduced incidence of infertility, birth defects, allergic sensitisation, otitis media, pre-eclampsia, metabolic syndrome, high BMI, and non-Hodgkin lymphoma. The current evidence base does not allow a definitive statement on the health benefits of organic dietary intake. However, a growing number of important findings are being reported from observational research linking demonstrable health benefits with organic food consumption. Future clinical research should focus on using long-term whole-diet substitution with certified organic interventions as this approach is more likely to determine whether or not true measurable health benefits exist.
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Associations of Meal Timing and Frequency with Obesity and Metabolic Syndrome among Korean Adults.
Ha, K, Song, Y
Nutrients. 2019;11(10)
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The timing of food intake appears to affect the robustness of circadian rhythms in metabolic organs, and circadian rhythm disruption is emerging as a new risk factor for cardiovascular disease. As major risk factors for cardiovascular diseases, obesity and metabolic syndrome are critical worldwide issues. In Korea, 3 in 10 adults have obesity or the metabolic syndrome. The aim of this study was to explore meal timing and frequency using various variables, including nightly fasting duration and specific time periods such as morning and night, and to examine their associations with obesity and metabolic syndrome in Korean adults using national survey data. The study used data from the 2013–2017 Korea National Health and Nutrition Examination Survey (KNHANES), which is a continuous annual survey conducted by the Korea Centers for Disease Control and Prevention Results indicated that a greater number of eating episodes was associated with lower prevalence of metabolic abnormalities in men. Furthermore, the prevalence of metabolic syndrome was inversely associated with morning eating in both men and women, whereas it was positively associated with night eating in men. Authors conclude that having desirable eating patterns, including eating in the morning and avoiding eating after 21:00, and an appropriate sleep schedule may be helpful for reducing the risks of obesity and metabolic syndrome, independently of fasting duration.
Abstract
Emerging studies indicate that meal timing is linked to cardiometabolic risks by deterioration of circadian rhythms, however limited evidence is available in humans. This large-scale cross-sectional study explored the associations of meal timing and frequency with obesity and metabolic syndrome among Korean adults. Meal timing was defined as nightly fasting duration and morning, evening, and night eating, and meal frequency was estimated as the number of daily eating episodes using a single-day 24-hour dietary recall method. Meal frequency was inversely associated with prevalence of abdominal obesity, elevated blood pressure, and elevated triglycerides in men only. Independent of the nightly fasting duration and eating episodes, morning eating was associated with a lower prevalence of metabolic syndrome (odds ratio (OR), 0.73; 95% confidence interval (CI), 0.57-0.93 for men and OR, 0.69; 95% CI, 0.54-0.89 for women) than no morning eating, whereas night eating was associated with a 48% higher prevalence of metabolic syndrome (OR, 1.48; 95% CI, 1.15-1.90) than no night eating in men only. Longer fasting duration and less sleep were associated with obesity and metabolic syndrome. These findings suggest that overall eating patterns, including energy distribution across the day, eating frequency, and sleep duration, rather than fasting duration alone, are related to cardiometabolic risks in free-living Korean adults.
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Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Nagy-Szakal, D, Williams, BL, Mishra, N, Che, X, Lee, B, Bateman, L, Klimas, NG, Komaroff, AL, Levine, S, Montoya, JG, et al
Microbiome. 2017;5(1):44
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, swollen lymph glands and irritable bowel syndrome (IBS). It is associated with gut bacterial dysbiosis, systemic inflammation and both gastro intestinal (GI) and neurological disturbances. The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. This experiment looked at fecal bacterial samples and metabolic pathway markers in 50 ME/CFS patients and 50 healthy controls. In ME/CFS subgroups, measures of symptom severity including pain, fatigue, and reduced motivation were correlated with the amounts and types of gut bacteria and certain metabolic pathways. Future prospective studies should consider more detailed exploration of IBS subtypes, associated GI symptoms, and their relationship to ME/CFS dysbiosis. This may enable more accurate diagnosis and the development of specific therapeutic strategies.
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.
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Impact of Mediterranean diet on metabolic syndrome, cancer and longevity.
Di Daniele, N, Noce, A, Vidiri, MF, Moriconi, E, Marrone, G, Annicchiarico-Petruzzelli, M, D'Urso, G, Tesauro, M, Rovella, V, De Lorenzo, A
Oncotarget. 2017;8(5):8947-8979
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There is a growing link between being overweight or obese and the onset of certain cancers. The latest research shows that 30-35% of cancers may have a link to diet, and that metabolic syndromes involving obesity encourage the body to store metabolically active ‘sick fats’ in adipose tissue, which in turn causes inflammation and creates an environment for cancer to thrive. The Mediterranean diet (MD) is considered one of the healthiest in the world and rates of cancer and metabolic syndrome are lower in the Mediterranean region versus Northern Europe suggesting it may be helpful in prevention of obesity and cancer. The MD is characterised as a balanced combination of fruit and vegetables, fish, cereals, and polyunsaturated fats (such as olive oil), with a reduced consumption of meat and dairy products and moderate intake of alcohol, primarily red wine. The nutrients that are found in abundance in the MD have a mixture of anti-cancer, anti-inflammatory, and anti-obesity properties thanks to antioxidant elements, fibre and healthy polyunsaturated fats. Studies show these nutrients can help support multiple metabolic markers such as blood pressure, cholesterol, inflammation, and insulin sensitivity. In 2010, UNESCO proclaimed the MD as “World Cultural Heritage”. This diet represents a behavioural model, a “way of life”, that can ensure longer life expectancy and improve quality of life itself.
Abstract
Obesity symbolizes a major public health problem. Overweight and obesity are associated to the occurrence of the metabolic syndrome and to adipose tissue dysfunction. The adipose tissue is metabolically active and an endocrine organ, whose dysregulation causes a low-grade inflammatory state and ectopic fat depositions. The Mediterranean Diet represents a possible therapy for metabolic syndrome, preventing adiposopathy or "sick fat" formation.The Mediterranean Diet exerts protective effects in elderly subjects with and without baseline of chronic diseases. Recent studies have demonstrated a relationship between cancer and obesity. In the US, diet represents amount 30-35% of death causes related to cancer. Currently, the cancer is the second cause of death after cardiovascular diseases worldwide. Furthermore, populations living in the Mediterranean area have a decreased incidence of cancer compared with populations living in Northern Europe or the US, likely due to healthier dietary habits. The bioactive food components have a potential preventive action on cancer. The aims of this review are to evaluate the impact of Mediterranean Diet on onset, progression and regression of metabolic syndrome, cancer and on longevity.
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Inhalational Alzheimer's disease: an unrecognized - and treatable - epidemic.
Bredesen, DE
Aging. 2016;8(2):304-13
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Alzheimer’s disease (AD) is the third leading cause of death in the USA, with around 5.2 million Americans diagnosed with AD. Effective treatment with medications has yet to be found. A recent multiple therapy programme (originally known as MEND, now called ReCODE) proposed by Professor Bredesen and team, has shown some promising anecdotal results. Identifying sub-types of AD has been proposed as a means to develop targeted protocols for treatment. Recently, 3 sub-types of AD have been described: Type 1 (inflammatory), Type 2 (non-inflammatory or decreasing brain size) and Type 3 (damage to the outer layer of the cerebrum). This report describes 7 patients with Type 3 AD. Type 3 AD is characterised by exposure to specific toxins (usually inhaled) and is often associated with Chronic Inflammatory Response Syndrome (CIRS). The report provides the symptoms, signs and laboratory values representative of Type 3 AD and could be used by Nutrition Practitioners to help with implementation of appropriate nutrition protocols when working with clients with AD.
Abstract
Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave.
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Risk factors for pancreatic cancer: a summary review of meta-analytical studies.
Maisonneuve, P, Lowenfels, AB
International journal of epidemiology. 2015;44(1):186-98
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Pancreatic cancer (PC) is one of the four or five most common causes of cancer mortality in developed countries. The aim of this review was to summarize results from pooled analyses and meta-analyses to estimate the fraction of PCs attributable to many different risk factors. A comprehensive review of the literature was carried out by searching for meta-analytical studies on the association between specific risk factors and PC risk or multiple cancer sites. Results indicate that PC has a multifactorial aetiology. All identified factors can be combined into a specific aetiological (the philosophy or study of causation) pathway for PC. The main pathways include insulin resistance (central adiposity, diabetes, metabolic syndrome), inflammation (tobacco, alcohol, pancreatitis), DNA damage (tobacco, red meat) and haemostasis (blood group, history of thrombosis). Authors conclude that about two-thirds of the major risk factors associated with PC are potentially modifiable, affording a unique opportunity for preventing one of our deadliest cancers.
Abstract
BACKGROUND The aetiology of pancreatic cancer (PC) has been extensively studied and is the subject of numerous meta-analyses and pooled analyses. We have summarized results from these pooled and meta-analytical studies to estimate the fraction of PCs attributable to each of the identified risk factors. METHODS Using a comprehensive strategy, we retrieved 117 meta-analytical or pooled reports dealing with the association between specific risk factors and PC risk. We combined estimates of relative risk and estimates of exposure to calculate the fraction of PCs caused or prevented by a particular exposure. RESULTS Tobacco smoking ('strong' evidence) and Helicobacter pylori infection ('moderate' evidence) are the major risk factors associated with PC, with respective estimated population attributable fractions of 11-32% and 4-25%. The major protective factors are history of allergy ('strong' evidence) and increasing fruit or folate intake ('moderate' evidence), with respective population preventable fractions of 3-7% and 0-12%. CONCLUSIONS We summarized results of 117 meta-analytical or pooled data reports dealing with 37 aetiological exposures, to obtain robust information about the suspected causes of PC. By combining these estimates with their prevalences in the population, we calculated population attributable or population preventable fractions. About two-thirds of the major risk factors associated with PC are potentially modifiable, affording a unique opportunity for preventing one of our deadliest cancers.