Published Science

Trace elements have an impact on numerous physiological processes. The monitoring of their levels in the organism allows you to detect not only their deficiencies, but also several illnesses. The aim of this study was to compare the levels of essential elements (calcium, magnesium, zinc, copper, iron, manganese) in hair, nails and serum of both patients with laryngeal cancer and healthy people. The determination of six metals was performed by an inductively coupled plasma mass spectrometry (ICP-MS) and an inductively coupled plasma optical emission spectrometry (ICP-OES). The concentration of essential elements in hair and nails of the control group was statistically significantly higher than in the group of patients with laryngeal cancer. In the case of serum, differences were found between the patients and controls in respect of the level of three metals. The results of principal component analysis (PCA) revealed the strong and similar clustering behavior of essential elements in hair and nails. The metals did not correlate between two alternative materials. The present study indicated that, using the level of essential elements in hair and nails as a basis, it is possible to distinguish cancer patients from healthy people. The alternative materials are independent of homeostasis and therefore seem to be more useful in the detection of diseases and mineral deficiencies in human than the classical biological materials, such as blood.

Recently, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis (DKA) with uncharacteristically mild to moderate glucose elevations (euglycemic DKA [euDKA]) associated with the use of all the approved sodium–glucose cotransporter 2 (SGLT2) inhibitors (1). This Communication was based on 20 clinical cases requiring hospitalization captured between March 2013 and June 2014 in the FDA Adverse Event Reporting System database. The scarce clinical data provided suggested that most of the DKA cases were reported in patients with type 2 diabetes (T2D), for whom this class of agents is indicated; most likely, however, they were insulin-treated patients, some with type 1 diabetes (T1D). The FDA also identified potential triggering factors such as intercurrent illness, reduced food and fluid intake, reduced insulin doses, and history of alcohol intake. The following month, at the request of the European Commission, the European Medicines Agency (EMA) announced on 12 June 2015 that the Pharmacovigilance Risk Assessment Committee has started a review of all of the three approved SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to evaluate the risk of DKA in T2D (2). The EMA announcement claimed that as of May 2015 a total of 101 cases of DKA have been reported worldwide in EudraVigilance in T2D patients treated with SGLT2 inhibitors, with an estimated exposure over 0.5 million patient-years. No clinical details were provided except for the mention that “all cases were serious and some required hospitalisation. Although [DKA] is usually accompanied by high blood sugar levels, in a number of these reports blood sugar levels were only moderately increased” (2).$\backslash$n$\backslash$nWith this background, it is very timely that in this issue of Diabetes Care there are two articles on this subject. Erondu et al. (3) report cases of DKA in T2D \ldots

AIM: To evaluate the hypothesis that measurement of fasting plasma triglyceride concentration identifies individuals at enhanced risk of statin-induced type 2 diabetes mellitus. METHODS: A retrospective analysis of data collected from routine health examinations in non-diabetic, East Asian individuals (n = 5790) with low-density lipoprotein cholesterol concentrations of 3.4 mmol/L. Subjects were stratified into those with or without a triglyceride concentration of 1.7 mmol/L, and comparisons made of risk factors for type 2 diabetes mellitus. RESULTS: Approximately 40% of men and 20% of women with elevations of both low-density lipoprotein cholesterol and triglyceride concentrations were more insulin resistant (homeostatic model assessment of insulin resistance), associated with higher plasma concentrations of HbA1c, glucose and insulin. CONCLUSION: Apparently, healthy, non-diabetic East Asian men and women with combined elevations of low-density lipoprotein cholesterol and triglyceride concentrations are glucose intolerant and insulin resistant, and thereby at enhanced risk of type 2 diabetes mellitus. Measurement of plasma triglyceride concentration can identify within a hypercholesterolemic population a subset of individuals at enhanced risk of statin-induced type 2 diabetes mellitus.

Consumers are making new choices, switching away from carbs to food containing fat such as red meat, butter and eggs. This trend offers powerful investment ideas, according to a study by the Credit Suisse Research Institute. Over the last 50 years, general nutritional wisdom has recommended a moderate consumption of fat. We have been told to dramatically lower our consumption of saturated fats (contained in butter, lard, milk, red meat, coconut oil\ldots) and cholesterol (found in eggs, poultry, beef\ldots). We have also been advised to increase our intake of polyunsaturated fats (contained in soybean, sunflower, corn, cottonseed oil\ldots) and carbohydrates (found in pasta, bread, sugar\ldots). But fat is a complex topic and these recommendations have been debated and questioned over the past 30 years. Some experts believe that these dietary recommendations-closely followed by the US population-are the main cause behind the country's high obesity levels and the rapidly growing number of people suffering from metabolic syndrome.

The benefits of the Mediterranean diet (MD) for protecting against chronic disorders such as cardiovascular disease are usually attributed to high consumption of certain food groups such as vegetables, and low consumption of other food groups such as meat. The influence of food processing techniques such as food preparation and cooking on the nutrient composition and nutritional value of these foods is not generally taken into consideration. In this narrative review, we consider the mechanistic and epidemiological evidence that food processing influences phytochemicals in selected food groups in the MD (olives, olive oil, vegetables and nuts), and that this influences the protective effects of these foods against chronic diseases associated with inflammation. We also examine how the pro-inflammatory properties of meat consumption can be modified by Mediterranean cuisine. We conclude by discussing whether food processing should be given greater consideration, both when recommending a MD to the consumer and when evaluating its health properties. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

Violence, degradation, abuse, and neglect characterize women's lives in prison today such that only few women, often with support of the external community of human rights and advocacy groups, are able to resist their degradation and humiliation. We will primarily examine changes that have occurred in the past two decades in the incarceration of women and address issues of classification and assessment, health care, education, employment, family responsibilities, and conditions of incarceration. (PsycINFO Database Record (c) 2012 APA, all rights reserved). (chapter)

Long before the appearance of flowering plants, early plants were infected by pathogenic microorganisms and challenged by herbivorous animals. Consequently, plants and animals evolved defenses and counterdefenses from the very beginning. Therefore, to cope with a huge diversity of unfavorable biotic conditions, plants developed several different defense strategies. In particular, defense strategies against feeding arthropods are highly diverse, including constitutive and inducible, direct and indirect defense mechanism. Among all types of defense, chemical defenses based on the synthesis and accumulation of a consistent number of natural bioactive compounds is a very successful and ubiquitously distributed strategy among the plant kingdom. Many of those compounds are toxic; others act as repellents or are attractive cues for organisms belonging to other trophic levels. Often, toxic compounds have specific targets; other compounds exhibit general toxicity. In such cases plants need to protect themselves. Within the plants’ reservoir of chemical defensive compounds, alkaloids, terpenoids, phenolic compounds, and many polypeptides can be found. Not only herbivorous insects but also mammalian organisms including human beings can be targeted by such plant-derived toxins, which will be demonstrated in selected examples.

Background: Dietary guidelines generally recommend increasing fish intake and reducing red meat intake for better long-term health. Few studies have compared the metabolic differences between eating meat and fish.Objective: The objective of this study was to determine whether there are differences in the postprandial plasma metabolic response to meals containing baked beef, baked herring, and pickled herring.Methods: Seventeen overweight men (BMI 25-30 kg/m(2), 41-67 y of age) were included in a randomized crossover intervention study. Subjects ate baked herring-, pickled herring-, and baked beef-based meals in a randomized order and postprandial blood plasma samples were taken over 7 h. Plasma metabolomics were measured with the use of gas chromatography-mass spectrometry and areas under the curve for detected metabolites were compared between meals.Results: The plasma postprandial response of 2-aminoadipic acid, a suggested marker of diabetes risk, was 1.6 times higher after the beef meal than after the baked herring meal (P < 0.001). Plasma β-alanine and 4-hydroxyproline both were markedly greater after beef intake than after herring intake (16 and 3.4 times the response of baked herring, respectively; P < 0.001). Herring intake led to a greater plasma postprandial response from docosahexaenoic acid (DHA) and cetoleic acid compared with beef (17.6 and 150 times greater, respectively; P < 0.001), whereas hippuric acid and benzoic acid were elevated after pickled herring compared with baked herring (5.4 and 43 times higher; P

"Making use of recently released Soviet archival materials, Hunger and War investigates state food supply policy and its impact on Soviet society during World War II. It explores the role of the state in provisioning the urban population, particularly workers, with food, and in feeding the Red army; the medicalization of hunger; hunger in blockaded Leningrad; and civilian mortality from hunger and malnutrition in other home front industrial regions. New research reported here challenges and complicates many of the narratives and counter-narratives about the war. The authors engage such difficult subjects as starvation mortality, bitterness over privation and inequalities in provisioning, and conflicts among state organizations. At the same time, they recognize the considerable role played by the Soviet state in organizing supplies of food to adequately support the military effort and defense production, and in developing policies that promoted social stability amid upheaval. The book makes a significant contribution to scholarship on the Soviet population's experience of World War II as well as to studies of war and famine"--Provided by publisher.

At the onset of the First World War, Germany was subject to a shipping embargo by the Allied forces. Ostensibly military in nature, the blockade prevented not only armaments but also food and fertilizers from entering Germany. The impact of that blockade on civilian populations has been debated ever since. Germans protested that the Allies had wielded hunger as a weapon against women and children with devastating results, a claim that was hotly denied by the Allies. The impact of what the Germans termed the Hungerblockade on childhood nutrition can now be assessed using a newly discovered dataset based on heights and weights of nearly 600,000 German schoolchildren measured between 1914 and 1924. Statistical analysis reveals a grim truth: German children suffered severe malnutrition due to the blockade. Social class impacted risk of deprivation, with working-class children suffering the most. Surprisingly, they were the quickest to recover after the war. Their rescue was fuelled by massive food aid organized by the former enemies of Germany, and delivered cooperatively with both government and civil society. The ability of former belligerents to work together after an exceptionally bitter war to feed impoverished children may hold hope for the future.

Objective: Several studies have shown decreased insulin clearance rate (ICR) in individuals with obesity, but it remains unclear whether this is predominately due to obesity-associated insulin resistance (IR) or obesity itself. This study aimed to clarify the complex interrelationship that exists between obesity, IR, and ICR. Methods: Healthy volunteers (n = 277) had measurement of IR and ICR using the insulin suppression test (IST). IR was quantified by determining the steady-state plasma glucose (SSPG) during the IST. ICR was estimated by dividing the insulin infusion rate by the steady-state plasma insulin concentration. We performed our analysis by stratifying the experimental population into four dichotomous categories, varying in obesity and IR. Obesity was defined as a body mass index (BMI) ≥ 30 kg/m², and IR was defined as SSPG ≥ 150 mg/dL. Results: Individuals with obesity had higher fasting insulin compared with individuals without obesity, regardless of IR. ICR was similar between individuals with and without obesity but was higher in insulin resistant individuals compared with insulin-sensitive individuals. In multivariate analysis, both fasting insulin and SSPG were significantly associated with ICR. No significant relationships were observed between BMI and ICR. Conclusions: Reduced ICR in obesity is secondary to IR, not excess adiposity. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

This paper examines the impact that single and interacting environmental stress factors have on tolerance mechanisms, molecular ecology and the relationship with secondary metabolite production by a group of mycotoxigenic species of economic importance. Growth of these fungi (Aspergillus flavus, A.ochraceus, A.carbonarius, Penicillium nordicum and P. verrucosum) is influenced by water and temperature interactions and type of solute used to induce water stress. Such abiotic stresses are overcome by the synthesis of increased amounts of low molecular weight sugar alcohols, especially glycerol and erythritol, to enable them to remain active under abiotic stress. This is accompanied by increased expression of sugar transporter genes, e.g., in A. flavus, which provides the nutritional means of tolerating such stress. The optimum conditions of water activity (a w ) × temperature stress for growth are often different from those for secondary metabolite production. The genes for toxin production are clustered together and their relative expression is influenced by abiotic interacting stress factors. For example., A. flavus synthesises aflatoxins under water stress in non-ionic solutes. In contrast, P. nordicum specifically occupies a high salt (0.87 a w  = 22 % NaCl) niche such as cured meats, and produces ochratoxin A (OTA). There is differential and temporal expression of the genes in the secondary metabolite clusters in response to a w  × temperature stress. We have used a microarray and integrated data on growth, relative expression of key genes in the biosynthetic pathways for secondary metabolite production and toxin production using a mixed growth model. This was used to correlate these factors and predict the toxin levels produced under different abiotic stress conditions. This system approach to integrate these different data sets and model the relationships could be a powerful tool for predicting the relative toxin production under extreme stress conditions, including climate change scenarios. This approach will facilitate a better functional understanding of the influence that environmental stress has on these mycotoxigenic fungi and enable better prevention strategies to be developed based on this system-based approach. © 2014, Springer-Verlag Berlin Heidelberg.

In medical practice, almost every clinician may encounter patients with skin disease. However, it is not always easy for physicians of all specialties to face the daily task of determining the nature and clinical implication of dermatologic manifestations. Are they confined to the skin, representing a pure dermatologic event? Or are they also markers of internal conditions relating to the patient's overall health? In this review, we will discuss the principal cutaneous conditions which have been linked to metabolic alterations. Particularly, since insulin has an important role in homeostasis and physiology of the skin, we will focus on the relationships between insulin resistance (IR) and skin diseases, analyzing strongly IR-associated conditions such as acanthosis nigricans, acne, and psoriasis, without neglecting emerging and potential scenarios as the ones represented by hidradenitis suppurativa, androgenetic alopecia, and hirsutism.

OBJECTIVE To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015, supplemented by bibliographies of retrieved articles and previous reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Observational studies reporting associations of saturated fat and/or trans unsaturated fat (total, industrially manufactured, or from ruminant animals) with all cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes. DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted data and assessed study risks of bias. Multivariable relative risks were pooled. Heterogeneity was assessed and quantified. Potential publication bias was assessed and subgroup analyses were undertaken. The GRADE approach was used to evaluate quality of evidence and certainty of conclusions. RESULTS For saturated fat, three to 12 prospective cohort studies for each association were pooled (five to 17 comparisons with 90,501-339,090 participants). Saturated fat intake was not associated with all cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97, 0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to 1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10). For trans fats, one to six prospective cohort studies for each association were pooled (two to seven comparisons with 12,942-230,135 participants). Total trans fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD mortality (1.28, 1.09 to 1.50), and total CHD (1.21, 1.10 to 1.33) but not ischemic stroke (1.07, 0.88 to 1.28) or type 2 diabetes (1.10, 0.95 to 1.27). Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18 (1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05 to 1.92) v 0.93 (0.73 to 1.18)). Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes (0.58, 0.46 to 0.74). The certainty of associations between saturated fat and all outcomes was "very low." The certainty of associations of trans fat with CHD outcomes was "moderate" and "very low" to "low" for other associations. CONCLUSIONS Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats. Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats.

Some evidence from previous randomized controlled trials and systematic reviews has demonstrated a positive association between hypertension and transcendental meditation (TM). However, other trials and reviews showed the effect of TM on blood pressure (BP) was unclear but did not use subgroup analysis to rigorously investigate this relationship. The American Heart Association has stated that TM is potentially beneficial but did not give a standard indication. The present study explored several subgroup analyses in systematic reviews to investigate the effect of TM on BP. Medline, Embase, Cochrane Library, Web of Science and Chinese BioMedical Literature Database were searched through August 2014. Randomized controlled trials of TM as a primary intervention for BP were included. Two reviewers independently used the Cochrane Collaboration's quality assessment tool to assess each study's quality. Twelve studies with 996 participants indicated an approximate reduction of systolic and diastolic BP of -4.26 mm Hg (95% CI=-6.06, -2.23) and -2.33 mm Hg (95% CI=-3.70, -0.97), respectively, in TM groups compared with control groups. Results from subgroup analysis suggested that TM had a greater effect on systolic BP among older participants, those with higher initial BP levels, and women, respectively. In terms of diastolic BP, it appears that TM might be more efficient in a short-term intervention and with individuals experiencing higher BP levels. However, some biases may have influenced the results, primarily a lack of information about study design and methods of BP measurement in primary studies.Journal of Human Hypertension advance online publication, 12 February 2015; doi:10.1038/jhh.2015.6.

ABSTRACT: Sleep is essential for optimal health. The American Academy of Sleep Medicine (AASM) and Sleep Research Society (SRS) developed a consensus recommendation for the amount of sleep needed to promote optimal health in adults, using a modified RAND Appropriateness Method process. The recommendation is summarized here. A manuscript detailing the conference proceedings and evidence supporting the final recommendation statement will be published in SLEEP and the Journal of Clinical Sleep Medicine.

DISCUSSION: The positive effects of KD on the health of children and adolescents with refractory epilepsy are unquestionable. Conversely, this positive role is associated with significant and negative changes in lipid metabolism. Moreover, the positive effects are possibly related to oxidative reactions and unbalance of antioxidants that can contribute to an increased cardiometabolic risk. Therefore, this review invites clinicians and researchers to investigate the lipid and oxidative metabolism in their clinical practice and trials, respectively.

Objective Ketone bodies (KB) are products of fatty acid oxidation and serve as essential fuels during fasting or treatment with the high-fat antiseizure ketogenic diet (KD). Despite growing evidence that KB exert broad neuroprotective effects, their role in seizure control has not been firmly demonstrated. The major goal of this study was to demonstrate the direct antiseizure effects of KB and to identify an underlying target mechanism. Methods We studied the effects of both the KD and KB in spontaneously epileptic Kcna1-null mice using a combination of behavioral, planar multielectrode, and standard cellular electrophysiological techniques. Thresholds for mitochondrial permeability transition (mPT) were determined in acutely isolated brain mitochondria. Results KB alone were sufficient to: (1) exert antiseizure effects in Kcna1-null mice, (2) restore intrinsic impairment of hippocampal long-term potentiation and spatial learning–memory defects in Kcna1-null mutants, and (3) raise the threshold for calcium-induced mPT in acutely prepared mitochondria from hippocampi of Kcna1-null animals. Targeted deletion of the cyclophilin D subunit of the mPT complex abrogated the effects of KB on mPT, and in vivo pharmacological inhibition and activation of mPT were found to mirror and reverse, respectively, the antiseizure effects of the KD in Kcna1-null mice. Interpretation The present data reveal the first direct link between mPT and seizure control, and provide a potential mechanistic explanation for the KD. Given that mPT is increasingly being implicated in diverse neurological disorders, our results suggest that metabolism-based treatments and/or metabolic substrates might represent a worthy paradigm for therapeutic development. Ann Neurol 2015;78:77–87

Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (K\textlessinf\textgreaterATP\textless/inf\textgreater) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of K\textlessinf\textgreaterATP\textless/inf\textgreater channel activation. Ketones dose-dependently reversed oxidative impairment of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity, and this action was mirrored by the K\textlessinf\textgreaterATP\textless/inf\textgreater channel activator diazoxide. Inhibition of K\textlessinf\textgreaterATP\textless/inf\textgreater channels reversed ketoneevoked hippocampal protection, and genetic ablation of the inwardly rectifying K\textlesssup\textgreater+\textless/sup\textgreater channel subunit Kir6.2, a critical component of K\textlessinf\textgreaterATP\textless/inf\textgreater channels, partially negated the synaptic protection afforded by ketones. This partial protection was completely reversed by co-application of the K\textlessinf\textgreaterATP\textless/inf\textgreater blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of oxidative injury, ketones induce synaptic protection in part through activation of K\textlessinf\textgreaterATP\textless/inf\textgreater channels.

Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.

Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer's disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined.

BACKGROUND: The cerebral metabolic rate of glucose (CMRg) is lower in specific brain regions in Alzheimer's disease (AD). The ketones, acetoacetate and β-hydroxybutyrate, are the brain's main alternative energy substrates to glucose. OBJECTIVE: To gain insight into brain fuel metabolism in mild AD dementia by determining whether the regional CMR and the rate constant of acetoacetate (CMRa and Ka, respectively) reflect the same metabolic deficit reported for cerebral glucose uptake (CMRg and Kg). METHODS: Mild AD dementia (Mild AD; n = 10, age 76 y) patients were compared with gender- and age-matched cognitively normal older adults (Controls; n = 29, age 75 y) using a PET/MRI protocol and analyzed with both ROI- and voxel-based methods. RESULTS: ROI-based analysis showed 13% lower global CMRg in the gray matter of mild AD dementia versus Controls (34.2 ± 5.0 versus 38.3 ± 4.7 μmol/100 g/min, respectively; p = 0.015), with CMRg and Kg in the parietal cortex, posterior cingulate, and thalamus being the most affected (p ≤ 0.022). Neither global nor regional CMRa or Ka differed between the two groups (all p ≥ 0.188). Voxel-based analysis showed a similar metabolic pattern to ROI-based analysis with seven clusters of significantly lower CMRg in the mild AD dementia group (uncorrected p ≤ 0.005) but with no difference in CMRa. CONCLUSION: Regional brain energy substrate hypometabolism in mild AD dementia may be specific to impaired glucose uptake and/or utilization. This suggests a potential avenue for compensating brain energy deficit in AD dementia with ketones.

Seafood poisoning in humans is caused by consumption of toxin-containing seafood that is contaminated with marine dinoflagellates. This has been a concern for many years. There are a number of dinoflagellate species that produce strong neurotoxins, which are often associated with the phenomenon called red tide. Outbreaks of red tide are caused by harmful algal blooms (HABs). HABs are not a new phenomenon, with written references dating back to biblical times. The most common type of HAB is referred to as a red tide because the bloom discolors the water, making it appear red. Humans eating seafood from infested areas during dinoflagellate bloom can become poisoned. With respect to the contaminants of toxic dinoflagellates in seafood, there are two main types of poisoning in humans. The terms fish and shellfish are associated with these illnesses because the toxins are concentrated in fish and shellfish that ingest the harmful dinoflagellates. According to the species of toxigenic dinoflagel-lates the poisoning syndromes have been given the names paralytic (PSP), diarrhetic (DSP), neurotoxic (NSP), and azaspiracid shellfish poisoning (AZP). Another human illness, ciguatera fish poisoning (CFP) is caused by the ciguatoxins produced by di-noflagellates that attach to surfaces in many coral reef communities [33.1]. Besides these well-known poisoning types, several new poisoning syndromes resulting from newly appearing dinoflagellate toxins, such as yessotoxin (YTX) and palytoxin (PTX), have been reported and characterized recently, and this has increased global public concerns regarding dinoflagellates associated with humans poisoning. © Springer-Verlag Berlin Heidelberg 2015.

Attention Deficit Hyperactivity Disorder (ADHD) mainly affects the academic performance of children and adolescents. In addition to bringing physical and mental health benefits, physical activity has been used to prevent and improve ADHD comorbidities; however, its effectiveness has not been quantified. In this study, the effect of physical activity on children's attention was measured using a computer game. Intense physical activity was promoted by a relay race, which requires a 5-min run without a rest interval. The proposed physical stimulus was performed with 28 volunteers: 14 with ADHD (GE-EF) and 14 without ADHD symptoms (GC-EF). After 5 min of rest, these volunteers accessed the computer game to accomplish the tasks in the shortest time possible. The computer game was also accessed by another 28 volunteers: 14 with ADHD (GE) and 14 without these symptoms (GC). The response time to solve the tasks that require attention was recorded. The results of the four groups were analyzed using D'Agostino statistical tests of normality, Kruskal-Wallis analyses of variance and post-hoc Dunn tests. The groups of volunteers with ADHD who performed exercise (GE-EF) showed improved performance for the tasks that require attention with a difference of 30.52% compared with the volunteers with ADHD who did not perform the exercise (GE). The (GE-EF) group showed similar performance (2.5% difference) with the volunteers in the (GC) group who have no ADHD symptoms and did not exercise. This study shows that intense exercise can improve the attention of children with ADHD and may help their school performance.

"In his new, must-read history of food, acclaimed historian Massimo Montanari traces the development of medieval tastes -- both culinary and cultural -- from raw materials to market and their reflections in today's food trends. He immerses readers in the passionate debates and bold inventions that transformed food from a simple staple to a potent factor in health and symbol of social and ideological standing, tying the ingredients of its fascinating evolution to the growth of human civilization. Montanari returns to the prestigious Salerno school of medicine, the 'mother of all medical schools, ' to plot the theory of food that took shape in the twelfth century. He reviews the influence of the Near Eastern spice routes, which introduced new flavors and cooking techniques to European kitchens, and reads Europe's earliest cookbooks, which took cues from old Roman practices valuing artifice and mixed flavors. Dishes were largely low-fat, and meats and fish were seasoned with vinegar, citrus juices, and wine. Other dishes, habits, and battles that mirror contemporary culinary identity involve the refinement of pasta, polenta, bread, and other flour-based preparations; the transition to more advanced cooking tools and formal dining implements; the controversy over cooking with oil, lard, or butter; dietary regimens; and the consumption and cultural meaning of water and wine. As people became more cognizant of their physicality, individuality, and philosophical place in the cosmos, Montanari shows, they adopted a new attitude toward food as well, investing as much in its pleasure and possibilities as in its basic acquisition"--Provided by publisher.

This work describes a metabolic profiling study of non-irradiated and irradiated beef (at 2.5, 4.5 and 8kGy) using 1H NMR and chemometrics. The assignment of all major NMR signals of the aqueous/methanolic extracts was performed. A comprehensive multivariate data analysis proved the ability to distinguish between the irradiated and non-irradiated beef. Classification trees revealed that three metabolites (glycerol, lactic acid esters and tyramine or a p-substituted phenolic compound) are important biomarkers for classification of the irradiated and non-irradiated beef samples. Overall, the achieved metabolomic results show that the changes in the metabolic profile of meat provide a valuable insight to be used in detecting irradiated beef. The use of the NMR-based approach simplifies sample preparation and decrease the time required for analysis, compared to available official analytical procedures. © 2015 Elsevier Ltd.

Nitrate is a natural constituent of the human diet and an approved food additive. It can be partially converted to nitrogen monoxide, which induces vasodilation and thereby decreases blood pressure. This effect is associated with a reduced risk regarding cardiovascular disease, myocardial infarction, and stroke. Moreover, dietary nitrate has been associated with beneficial effects in patients with gastric ulcer, renal failure, or metabolic syndrome. Recent studies indicate that such beneficial health effects due to dietary nitrate may be achievable at intake levels resulting from the daily consumption of nitrate-rich vegetables. N-nitroso compounds are endogenously formed in humans. However, their relevance for human health has not been adequately explored up to now. Nitrate and nitrite are per se not carcinogenic, but under conditions that result in endogenous nitrosation, it cannot be excluded that ingested nitrate and nitrite may lead to an increased cancer risk and may probably be carcinogenic to humans. In this review, the known beneficial and detrimental health effects related to dietary nitrate/nitrite intake are described and the identified gaps in knowledge as well as the research needs required to perform a reliable benefit/risk assessment in terms of long-term human health consequences due to dietary nitrate/nitrite intake are presented. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

We apply nutritional geometry, a framework for modelling the interactive effects of nutrients on animals, to help understand the role of modern environments in the obesity pandemic. Evidence suggests that humans regulate the intake of protein energy (PE) more strongly than non-protein energy (nPE), and consequently will over- and under-ingest nPE on diets with low or high PE, respectively. This pattern of macronutrient regulation has led to the protein leverage hypothesis, which proposes that the rise in obesity has been caused partly by a shift towards diets with reduced PE:nPE ratios relative to the set point for protein regulation. We discuss potential causes of this mismatch, including environmentally induced reductions in the protein density of the human diet and factors that might increase the regulatory set point for protein and hence exacerbate protein leverage. Economics – the high price of protein compared with fats and carbohydrates – is one factor that might contribute to the reduction of dietary protein concentrations. The possibility that rising atmospheric CO 2 levels could also play a role through reducing the PE:nPE ratios in plants and animals in the human food chain is discussed. Factors that reduce protein efficiency, for example by increasing the use of ingested amino acids in energy metabolism (hepatic gluconeogenesis), are highlighted as potential drivers of increased set points for protein regulation. We recommend that a similar approach is taken to understand the rise of obesity in other species, and identify some key gaps in the understanding of nutrient regulation in companion animals.

Protein oxidation, the process caused especially by reactive oxygen and nitrogen species, is thought to play a major role in various oxidative processes within cells and is implicated in the development of many human diseases. This review provides a brief overview of the protein oxidation with the emphasis on the types of oxidation (oxidation of protein backbone and amino acid residues side chains, site-specific metal-catalysed protein oxidation), oxidation-dependent generation of protein hydroperoxides, carbonyl derivatives and protein–protein cross-linkages. Non-enzymatic glycoxidation (also known as Maillard reaction) as an important factor of protein damage, consequences of oxidative protein impairment and related diseases as well as means of monitoring and assessment of protein modifications are discussed. © 2015, Indian Academy of Sciences.

Background Bariatric surgery is effective treatment for weight loss, but demand continuous nutritional care and physical activity. They regain weight happens with inadequate diets, physical inactivity and high alcohol consumption. Aim To investigate in patients undergoing Roux-Y-of gastroplasty weight regain, nutritional deficiencies, candidates for the treatment with endoscopic argon plasma, the diameter of the gastrojejunostomy and the size of the gastric pouch at the time of treatment with plasma. Methods A prospective 59 patients non-randomized study with no control group undergoing gastroplasty with recurrence of weight and candidates for the endoscopic procedure of argon plasma was realized. The surgical evaluation consisted of investigation of complications in the digestive system and verification of the increased diameter of the gastrojejunostomy. Nutritional evaluation was based on body mass index at the time of operation, in the minimum BMI achieved after and in which BMI was when making the procedure with plasma. The laboratory tests included hemoglobin, erythrocyte volume, ferritin, vitamin D, B12, iron, calcium, zinc and serum albumin. Clinical analysis was based on scheduled follow-up. Results Of the 59 selected, five were men and 51 women; were included 49 people (four men and 44 women) with all the complete data. The exclusion was due to the lack of some of the laboratory tests. Of this total 19 patients (38.7%) had a restrictive ring, while 30 (61.2%) did not. Iron deficiency anemia was common; 30 patients (61.2%) were below 30 with ferritin (unit); 35 (71.4%) with vitamin B12 were below 300 pg/ml; vitamin D3 deficiency occurred in more than 90%; there were no cases of deficiency of protein, calcium and zinc; glucose levels were above 99 mg/dl in three patients (6.12%). Clinically all had complaints of labile memory, irritability and poor concentration. All reported that they stopped treatment with the multidisciplinary team in the first year after the operation. Conclusions The profile of patients submitted to argon plasma procedure was: anastomosis in average with 27 mm; multiple nutritional deficiencies with predominance of iron deficiency anemia; ferritin below 30; vitamin B12 levels below 300 pg/ml; labile memory complaints, irritability and poor concentration.

Perna canaliculus (Green-Lippped Mussel) is found only in New Zealand waters and is cultivated and manufactured for both the food and nutraceutical industry world-wide. P. canaliculus has traditionally been used as a therapeutic to treat various arthralgias in both humans and animals; however, clinical research reports provide conflicting results. Numerous in vitro studies have reported anti-inflammatory activity of the mussel under various conditions and also demonstrated a synergistic effect with pharmaceutical medications such as non-steroidal anti-inflammatory drugs (NSAIDs) with P. canaliculus protecting the gastrointestinal mucosal lining against such medications. It is proposed that the anti-inflammatory activity demonstrated by P. canaliculus is predominantly due to the lipid fraction, however, among the major classes of compounds found in mussel meat, proteins and peptides are the largest with isolates demonstrating various anti-microbial, anti-inflammatory, anti-oxidant, bioadhesive and anti-hypertensive activities. A review of the bioactive components, their function and therapeutic application is outlined in this chapter. Furthermore, we hypothesise and provide supportive evidence that the gastrointestinal microbiota play an important role in disease processes such as Rheumatoid arthritis and Osteoarthritis and also in the efficacy of P. canaliculus in chronic inflammatory conditions. The metabolic capacity of intestinal microbiota can modify bioactive food components altering the hosts’ exposure to these components, potentially enhancing or diminishing their health effects. Understanding the interaction of the bioactive compounds in P. canaliculus with commensal and pathogenic bacteria may facilitate the development of novel interventions to control intestinal and extraintestinal inflammation. © 2015, Progress in Drug Research, All rights Reserved.

Reduced food intake, avoiding malnutrition, can ameliorate aging and aging-associated diseases in invertebrate model organisms, rodents, primates, and humans. Recent findings indicate that meal timing is crucial, with both intermittent fasting and adjusted diurnal rhythm of feeding improving health and function, in the absence of changes in overall intake. Lowered intake of particular nutrients rather than of overall calories is also key, with protein and specific amino acids playing prominent roles. Nutritional modulation of the microbiome can also be important, and there are long-term, including inter-generational, effects of diet. The metabolic, molecular, and cellular mechanisms that mediate both improvement in health during aging to diet and genetic variation in the response to diet are being identified. These new findings are opening the way to specific dietary and pharmacological interventions to recapture the full potential benefits of dietary restriction, which humans can find difficult to maintain voluntarily.

This paper begins by exploring the role of fermented and deliberately rotted (putrefied) meat, fish, and fat in the diet of modern hunters and gatherers throughout the arctic and subarctic. These practices partially ‘pre-digest’ the high protein and fat content typical of northern forager diets without the need for cooking, and hence without the need for fire or scarce fuel. Because of the peculiar properties of many bacteria, including various lactic acid bacteria (LAB) which rapidly colonize decomposing meat and fish, these foods can be preserved free of pathogens for weeks or even months and remain safe to eat. In addition, aerobic bacteria in the early stages of putrefaction deplete the supply of oxygen in the tissues, creating an anaerobic environment that retards the production of potentially toxic byproducts of lipid autoxidation (rancidity). Moreover, LAB produce B-vitamins, and the anaerobic environment favors the preservation of vitamin C, a critical but scarce micronutrient in heavily meat-based northern diets. If such foods are cooked, vitamin C may be depleted or lost entirely, increasing the threat of scurvy. Psychological studies indicate that the widespread revulsion shown by many Euroamericans to the sight and smell of putrefied meat is not a universal hard-wired response, but a culturally learned reaction that does not emerge in young children until the age of about five or later, too late to protect the infant from pathogens during the highly vulnerable immediate-post-weaning period. Ethnohistoric and ethnographic evidence clearly show that putrefied meat and fish were not used solely as starvation foods, but served instead as ubiquitous, desirable, and nutritionally important components of forager diets throughout these northern environments. In the second part of the paper, I extend these arguments to suggest that putrefied meat, fish, and fat are likely to have been equally important to the lifeways and adaptations of Eurasian Paleolithic hominins inhabiting analogous environments. If such food practices were in fact widespread during the midto late Pleistocene, they may help account for aspects of the archaeological record that are presently difficult to comprehend, such as the ‘on again, off again’ evidence for fire use (and hence cooking) during the Eurasian Middle Paleolithic. Putrefaction also may alter the isotopic composition of the diet. As meat and fish decompose, a variety of volatile compounds are produced, including ammonia. Loss of NH3, along with lesser amounts of two other nitrogenous gases—cadaverine and putrescine—would very likely leave rotted meat and fish enriched in 15N by comparison to the isotopic composition of these foods in their fresh state. Such enrichment may have contributed to the elevated values seen in many Neanderthals, values that are widely taken as prima facie evidence of Neanderthal’s status as a ‘top predator.’ Finally, if Paleolithic foragers relied upon putrefaction to prepare and store meat, archaeologists may have to rethink the way they interpret a number of widely used taphonomic signatures, including the number and distribution of cutmarks, the extent of carnivore damage, the incidence of burning on both animal bones and stone tools, and the frequency and scale of hearths, ash lenses, and other features of combustion. “When we fix salmon head we put it in bucket in ground and we take it out and eat it. We leave it in ten days only because it will spoil in summer.... Stinkfish, oooh, I love that stinkfish. Smell funny, but it sure taste good....“ (Mary Tyone, quoted in Godduhn and Kostick 2016: 30) INTRODUCTION B nature most Paleolithic archaeologists—myself included—are empiricists. We want facts and, understandably, we build our interpretations closely around them. After all, what good are interpretations in archaeology if their aim is to account for domains of behavior in the past that we cannot ‘see’ in the material record? Without the facts, we may be doing little more than weaving fanciful stories out of whole cloth—creating archaeological ‘fairy tales’ or ‘just-so’ stories. PaleoAnthropology 2017: 44−72. © 2017 PaleoAnthropology Society. All rights reserved. ISSN 1545-0031 doi:10.4207/PA.2017.ART105 JOHN D. SPETH Department of Anthropology, 101 West Hall, 1085 South University Avenue, University of Michigan, Ann Arbor, MI 48109-1107, USA; jdspeth@umich.edu submitted: 21 February 2017; revised 2 April 2017; accepted 4 April 2017 Putrid Meat and Fish in the Paleolithic • 45 tundras, arctic steppes, and boreal forests that are, or were, home to northern foragers of the ‘ethnographic present.’ More to the point, these are precisely the kinds of environments in which modern foragers routinely relied on fermented and deliberately rotted meat, fish, fat, fish roe, and stomach contents. In fact, many explorers, ethnographers, ethnohistorians, and nutritionists over the years have concluded that life in northern environments might not have been possible without frequent recourse to fermented animal foods (Kozlov and Zdor 2003: 129). So, is it not likely, or at least plausible, that Neanderthals, and perhaps even their predecessors, as well as Upper Paleolithic foragers, might have done likewise? WHY DOES IT MATTER TO PALEOLITHIC ARCHAEOLOGISTS? There is much more at stake in the answer to this question than merely adding some offensive smelling oddities to the culinary repertoire of our Pleistocene forebears. For reasons to be discussed shortly, if fermentation of the type seen historically in the northern latitudes was also practiced as an alternative to cooking on a more-than-occasional basis by Eurasian Neanderthals and Upper Paleolithic hominins, we may have to modify, in some cases quite radically, the way we go about reconstructing many aspects of their behavior and lifeways, including, among others: (1) estimating the metabolic costs of digesting and assimilating the large amounts of protein in a heavily meat-based diet (Churchill 2014: 325; Speth and Spielmann 1983); (2) accounting for the on-again, off-again evidence for fire (and hence cooking) in the European Middle Paleolithic, and in particular the seemingly counterintuitive decline in the incidence of fire use (in at least some sites) during colder climatic episodes (Sandgathe et al. 2011; see also Sorensen 2017); (3) broadening our view of the potential range of hominin food preservation and storage capabilities and consequent patterns of site occupancy and mobility; (4) assessing what impact, if any, the repeated consumption of millions upon millions of bacteria and their complex metabolites, together with the normal postmortem biochemical products of endogenous muscle and lipid decomposition, might have had on the carbon and nitrogen stable isotope values of Neanderthals and Upper Paleolithic peoples (Bocherens 2011; Richards and Trinkaus 2009); and, (5) developing taphonomic signatures that take into account the impact that non-thermal fermentation and putrefaction are likely to have had on signs of anthropogenic involvement in assemblage formation (e.g., the frequency of charred bones, the abundance and anatomical distribution of cutmarks), the survivorship of fish bones and other fragile faunal remains, and the extent to which discarded bones from deliberately fermented or rotted carcasses would have remained attractive to predators and scavengers. Fermentation may be like gender—frustratingly intractable yet fundamentally important to our understanding of the behavior and adaptations of our Pleistocene ancestors. On the other hand, there are a number of behavioral domains that for all practical purposes remain archaeologically invisible, or at least frustratingly intractable, despite the fact that we know they are present, even universal, among modern foragers. Gender provides a classic case in point. Gender distinctions are central to hunting and gathering societies across the globe and play a fundamental role in the daily lives of these peoples (e.g., Brumbach and Jarvenpa 2006; Frink 2009). They must therefore have a prehistory, one that very likely extends well back into the Paleolithic. But we remain all but helpless when it comes to ‘seeing’ gender in the Paleolithic record, where stone tools are just about the only artifacts with which we have to work. Given the male-centric biases that we standardly bring to lithic studies, coupled with the inadequacies of the methods at our disposal and the almost total lack of suitable middle range theory (Gero 1991), we are compelled to pay little more than lip service to the issue. As a consequence, there is considerable risk that a portion—quite likely a substantial portion—of the variability that we are trying to explain in Paleolithic stone tool assemblages derives from gendered behavior, not from the usual list of ‘suspects’ to which we almost invariably turn (e.g., differences in raw material, site function, cultural tradition). Unlike gender distinctions, which most Paleolithic archaeologists are at least well aware of, there are potentially important domains of past behavior that are not only archaeologically invisible, but have almost never received even so much as lip service. One such domain—the focus of the present endeavor—concerns the use of deliberately fermented (often literally rotted or putrefied) meat, fish, fat, and stomach contents. Ubiquitous today and in the recent past in the foodways of foragers throughout the circumpolar regions (Yamin-Pasternak et al. 2014), and important even well beyond the northern latitudes (Audubon 1897: 496–497; Barnes et al. 1973; Buck et al. 2016; Budack 1977; Cawthorn 1997; Coues 1897: 356–357; Darwin 1860: 213– 214; Dirar 1992; Dornan 1925: 115; Ealy 1880: 134–135; Grey 1841: 276–278; Griffiths 1975; Johnston 1908: 627; Kelsey 1997: 204; Marlowe 2004a: 191; Newcomb 1961: 41; Oyewole 1997; Selous 1881: 436; Winship 1896: 528), fermented and rotted animal foods are—or at least we

During the period 1985-2005, studies examined the proposal that adaptation to a low-carbohydrate (\textless25 % energy), high-fat (\textgreater60 % energy) diet (LCHF) to increase muscle fat utilization during exercise could enhance performance in trained individuals by reducing reliance on muscle glycogen. As little as 5 days of training with LCHF retools the muscle to enhance fat-burning capacity with robust changes that persist despite acute strategies to restore carbohydrate availability (e.g., glycogen supercompensation, carbohydrate intake during exercise). Furthermore, a 2- to 3-week exposure to minimal carbohydrate (\textless20 g/day) intake achieves adaptation to high blood ketone concentrations. However, the failure to detect clear performance benefits during endurance/ultra-endurance protocols, combined with evidence of impaired performance of high-intensity exercise via a down-regulation of carbohydrate metabolism led this author to dismiss the use of such fat-adaptation strategies by competitive athletes in conventional sports. Recent re-emergence of interest in LCHF diets, coupled with anecdotes of improved performance by sportspeople who follow them, has created a need to re-examine the potential benefits of this eating style. Unfortunately, the absence of new data prevents a different conclusion from being made. Notwithstanding the outcomes of future research, there is a need for better recognition of current sports nutrition guidelines that promote an individualized and periodized approach to fuel availability during training, allowing the athlete to prepare for competition performance with metabolic flexibility and optimal utilization of all muscle substrates. Nevertheless, there may be a few scenarios where LCHF diets are of benefit, or at least are not detrimental, for sports performance.

This article provides an overview of the recent developments in the diagnosis, treatment, and prevention of cancer-related lymphedema. Lymphedema incidence by tumor site is evaluated. Measurement techniques and trends in patient education and treatment are also summarized to include current trends in therapeutic and surgical treatment options as well as longer-term management. Finally, an overview of the policies related to insurance coverage and reimbursement will give the clinician an overview of important trends in the diagnosis, treatment, and management of cancer-related lymphedema.

The knowledge of the molecular organization of living organisms evolved considerably during the last years. The methodologies associated also progressed with the development of the high-throughput sequencing (SNP array, RNAseq, etc.) and of genomic tools allowing the simultaneous analysis of hundreds or thousands of genes, proteins or metabolites. In farm animals, some proteins, mRNAs or metabolites whose abundance has been associated with meat quality traits have been detected in pig, cattle, chicken. They constitute biomarkers for the assessment and prediction of qualities of interest in each species, with potential biomarkers across species. The ongoing development of rapid methods will allow their use for decision-making and management tools in slaughterhouses, to better allocate carcasses or cuts to the appropriate markets. Besides, their application on living animals will help to improve genetic selection and to adapt a breeding system to fulfill expected quality level. The ultimate goal is to propose effective molecular tools for the management of product quality in meat production chains. © 2015 Elsevier Ltd.

Glucokinase-maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in approximately 1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10-60%): persistent incidental childhood hyperglycemia (10-60%) and gestational diabetes mellitus (1-2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4-8.3 mmol/L, HbA1c range 5.8-7.6% [40-60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes.

Background: The influence of diet on metabolic syndrome and oxidative stress are not completely known. Design: This cross-sectional study assessed the association of red meat and white meat consumption with metabolic syndrome, insulin resistance and lipid peroxidation in Brazilian middle-aged men. Methods: A total of 296 subjects (age: 50.5±5.0 years, body mass index: 25.8±3.5 kg/m2) were evaluated. Anthropometry, lifestyle features, blood biochemical parameters, diagnosis of metabolic syndrome, homeostatic model assessment for insulin resistance, a lipid peroxidation marker (oxidized low-density lipoprotein) and triglycerides: high-density lipoprotein cholesterol ratio were assessed. Dietary intake was estimated by a food frequency questionnaire. Results: The subjects included in the highest tertile red meat (≥81.5 g/d) and saturated fatty acid from red meat consumption (≥4.3 g/d) had higher occurrence of central obesity (nearly 60%, p<0.01), hypertriglyceridaemia (nearly 43%, p<0.01) and metabolic syndrome (35%, p0.05). Conclusions: Red meat consumption was cross-sectionally associated with the occurrence of central obesity, hypertriglyceridaemia, and metabolic syndrome as well as with higher homeostatic model assessment for insulin resistance, oxidized low-density lipoprotein concentrations and triglycerides:high-density lipoprotein cholesterol ratio. The content of saturated fatty acid from red meat consumption may be a factor that contributed to this relationship, while white meat consumption was not associated with metabolic syndrome and the assessed biomarkers. © The European Society of Cardiology 2013.

BACKGROUND Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally it is unclear whether the energy from saturated fats that are lost in the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. This review is part of a series split from and updating an overarching review. OBJECTIVES To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA) or monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. SEARCH METHODS We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and EMBASE (Ovid) on 5 March 2014. We also checked references of included studies and reviews. SELECTION CRITERIA Trials fulfilled the following criteria: 1) randomised with appropriate control group; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) not multifactorial; 4) adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 5) intervention at least 24 months; 6) mortality or cardiovascular morbidity data available. DATA COLLECTION AND ANALYSIS Two review authors working independently extracted participant numbers experiencing health outcomes in each arm, and we performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses and funnel plots. MAIN RESULTS We include 15 randomised controlled trials (RCTs) (17 comparisons, ˜59,000 participants), which used a variety of interventions from providing all food to advice on how to reduce saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of cardiovascular events by 17% (risk ratio (RR) 0.83; 95% confidence interval (CI) 0.72 to 0.96, 13 comparisons, 53,300 participants of whom 8% had a cardiovascular event, I² 65%, GRADE moderate quality of evidence), but effects on all-cause mortality (RR 0.97; 95% CI 0.90 to 1.05; 12 trials, 55,858 participants) and cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 12 trials, 53,421 participants) were less clear (both GRADE moderate quality of evidence). There was some evidence that reducing saturated fats reduced the risk of myocardial infarction (fatal and non-fatal, RR 0.90; 95% CI 0.80 to 1.01; 11 trials, 53,167 participants), but evidence for non-fatal myocardial infarction (RR 0.95; 95% CI 0.80 to 1.13; 9 trials, 52,834 participants) was unclear and there were no clear effects on stroke (any stroke, RR 1.00; 95% CI 0.89 to 1.12; 8 trials, 50,952 participants). These relationships did not alter with sensitivity analysis. Subgrouping suggested that the reduction in cardiovascular events was seen in studies that primarily replaced saturated fat calories with polyunsaturated fat, and no effects were seen in studies replacing saturated fat with carbohydrate or protein, but effects in studies replacing with monounsaturated fats were unclear (as we located only one small trial). Subgrouping and meta-regression suggested that the degree of reduction in cardiovascular events was related to the degree of reduction of serum total cholesterol, and there were suggestions of greater protection with greater saturated fat reduction or greater increase in polyunsaturated and monounsaturated fats. There was no evidence of harmful effects of reducing saturated fat intakes on cancer mortality, cancer diagnoses or blood pressure, while there was some evidence of improvements in weight and BMI. AUTHORS' CONCLUSIONS The findings of this updated review are suggestive of a small but potentially important reduction in cardiovascular risk on reduction of saturated fat intake. Replacing the energy from saturated fat with polyunsaturated fat appears to be a useful strategy, and replacement with carbohydrate appears less useful, but effects of replacement with monounsaturated fat were unclear due to inclusion of only one small trial. This effect did not appear to alter by study duration, sex or baseline level of cardiovascular risk. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturated fats. The ideal type of unsaturated fat is unclear.

OBJECTIVE: To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. MATERIALS AND METHODS: Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. RESULTS: The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. CONCLUSIONS: The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

Regulation of taste is important for improving meat quality and glutamate (Glu) is one of the important taste-active components in meat. Here, the effects of dietary lysine (Lys) content on taste-active components in meat, especially free Glu, were investigated. Fourteen-day-old broiler chicks (Gallus gallus) were fed on diets containing 100% or 150% of the recommended Lys content for 10 days. Concentrations of free amino acids in plasma, muscle and liver were measured. The levels of messenger RNAs (mRNAs) for enzymes related to Glu metabolism were determined in muscle and liver. The concentration of muscle metabolites was also determined. The free Glu content in muscle of chicks fed the Lys150% diet was increased by 44.0% compared with that in chicks fed the Lys100% diet (P<0.01). The mRNA level of lysine α-ketoglutarate reductase, which is involved in Lys degradation and Glu production, was significantly increased (P

CONCLUSIONS: Overall, we show that an isocaloric switch from a diet rich in saturated fat to a diet rich in unsaturated fat can attenuate NAFLD and atherosclerosis development. Phytochemical-rich virgin pumpkin seed oil exerts additional anti-inflammatory effects resulting in more pronounced health effects.

The effects of saturated fatty acids (SFAs) on cardiovascular disease (CVD) risk are modulated by the nutrients that replace them and their food matrices. Replacement of SFAs with polyunsaturated fatty acids has been associated with reduced CVD risk, although there is heterogeneity in both fatty acid categories. In contrast, replacement of SFAs with carbohydrates, particularly sugar, has been associated with no improvement or even a worsening of CVD risk, at least in part through effects on atherogenic dyslipidemia, a cluster of traits including small, dense low-density lipoprotein particles. The effects of dietary SFAs on insulin sensitivity, inflammation, vascular function, and thrombosis are less clear. There is growing evidence that SFAs in the context of dairy foods, particularly fermented dairy products, have neutral or inverse associations with CVD. Overall dietary patterns emphasizing vegetables, fish, nuts, and whole versus processed grains form the basis of heart-healthy eating and should supersede a focus on macronutrient composition.