Published Science

Akkermansia muciniphila is a mucin-degrading bacterium that has shown the potential to provide anti-inflammatory and anti-obesity effects in mouse and man. We here focus on companion animals, specifically cats and dogs, and evaluate the microbial degradation of mucus and its health impact in the context of the worldwide epidemic of pet obesity. A literature survey revealed that the two presently known Akkermansia spp., A. muciniphila and A. glycaniphila, as well as other members of the phylum of Verrucomicrobia seem to be neither very prevalent nor abundant in the digestive tract of cats and dog. While this may be due to methodological aspects, it suggests that bacteria related to Akkermansia are not the major mucus degraders in these pets and hence other mucus-utilizing taxa may deserve attention. Hence, we will discuss the potential of these endogenous mucus utilizers and dietary interventions to boost these as well as the use of Akkermansia spp. related bacteria or their components as strategies to target feline and canine obesity.

Introduction: Medium-chain-triglycerides (MCT), formed by fatty acids with a length of 6–12 carbon atoms (C6–C12), constitute about two thirds of coconut oil (Coc). MCT have specific metabolic properties which has led them to be described as ketogenic even in the absence of carbohydrate restriction. This effect has mainly been demonstrated for caprylic acid (C8), which constitutes about 6–8% of coconut oil. Our aim was to quantify ketosis and blood glucose after intake of Coc and C8, with and without glucose intake. Sunflower oil (Suf) was used as control, expected to not break fasting ketosis, nor induce supply-driven ketosis., Method: In a 6-arm cross-over design, 15 healthy volunteers—age 65–73, 53% women—were tested once a week. After a 12-h fast, ketones were measured during 4 h after intake of coffee with cream, in combination with each of the intervention arms in a randomized order: 1. Suf (30 g); 2. C8 (20 g) + Suf (10 g); 3. C8 (20 g) + Suf (10 g) + Glucose (50 g); 4. Coc (30 g); 5. Coc (30 g) + Glucose (50 g); 6. C8 (20 g) + Coc (30 g). The primary outcome was absolute blood levels of the ketone β-hydroxybutyrate, area under the curve (AUC). ANOVA for repeated measures was performed to compare arms., Results: β-hydroxybutyrate, AUC/time (mean ± SD), for arms were 1: 0.18 ± 0.11; 2: 0.45 ± 0.19; 3: 0.28 ± 0.12; 4: 0.22 ± 0.12; 5: 0.08 ± 0.04; 6: 0.45 ± 0.20 (mmol/L). Differences were significant (all p ≤ 0.02), except for arm 2 vs. 6, and 4 vs. 1 & 3. Blood glucose was stable in arm 1, 2, 4, & 6, at levels slightly below baseline (p ≤ 0.05) at all timepoints hours 1–4 after intake., Conclusions: C8 had a higher ketogenic effect than the other components. Coc was not significantly different from Suf, or C8 with glucose. In addition, we report that a 16-h non-carbohydrate window contributed to a mild ketosis, while blood glucose remained stable. Our results suggest that time-restricted feeding regarding carbohydrates may optimize ketosis from intake of MCT., Clinical Trial Registration: The study was registered as a clinical trial on ClinicalTrials.gov, NCT03904433.

Innate lymphoid cells (ILCs) play an important role in the control and maintenance of barrier immunity. However, chronic activation of ILCs results in immune-mediated pathology. Here, we show that tissue-resident type 2 ILCs (ILC2s) display a distinct metabolic signature upon chronic activation. In the context of allergen-driven airway inflammation, ILC2s increase their uptake of both external lipids and glucose. Externally acquired fatty acids are transiently stored in lipid droplets and converted into phospholipids to promote the proliferation of ILC2s. This metabolic program is imprinted by interleukin-33 (IL-33) and regulated by the genes Pparg and Dgat1, which are both controlled by glucose availability and mTOR signaling. Restricting dietary glucose by feeding mice a ketogenic diet largely ablated ILC2-mediated airway inflammation by impairing fatty acid metabolism and the formation of lipid droplets. Together, these results reveal that pathogenic ILC2 responses require lipid metabolism and identify ketogenic diet as a potent intervention strategy to treat airway inflammation.

Neanderthals are often considered as less technologically advanced than modern humans. However, we typically only find faunal remains or stone tools at Paleolithic sites. Perishable materials, comprising the vast majority of material culture items, are typically missing. Individual twisted fibres on stone tools from the Abri du Maras led to the hypothesis of Neanderthal string production in the past, but conclusive evidence was lacking. Here we show direct evidence of fibre technology in the form of a 3-ply cord fragment made from inner bark fibres on a stone tool recovered in situ from the same site. Twisted fibres provide the basis for clothing, rope, bags, nets, mats, boats, etc. which, once discovered, would have become an indispensable part of daily life. Understanding and use of twisted fibres implies the use of complex multi-component technology as well as a mathematical understanding of pairs, sets, and numbers. Added to recent evidence of birch bark tar, art, and shell beads, the idea that Neanderthals were cognitively inferior to modern humans is becoming increasingly untenable.

The story of the origin of our species is being radically rewritten. Graham Lawton discovers the latest twists in the tale

Liam Hemsworth had long been a proponent of veganism after making the switch the plant-based eating back in 2015, but in this month's issue of Men's Health the Aussie actor revealed he's quit a vegan diet for health reasons. The first two years, I felt great,” he says. “I felt my energy was high. I felt like my body was strong, cardio was high, everything felt really good.” However, the 30-year-old says that began to change in early 2019. "February last year I was feeling really low and lethargic and wasn’t feeling good generally," he said. "And then I got a kidney stone." Hemsworth’s ailment was what is known in medical circles as a calcium oxalate stone. The painful stone formed due to an excessively high level of oxalate – a chemical compound found in nuts, spinach, legumes and bran – in his diet. These were foods Hemsworth was consuming in epic proportions. By the time he was hospitalised, the actor’s morning smoothie alone consisted of five handfuls of spinach, almond milk, almond butter and vegan protein. “That was what I considered super healthy and doing the right thing,” he says. “I had to completely rethink what I was putting in my body.” While Hemsworth now openly admits his vegan days are behind him, he’s quick to recognise that although it didn’t end well for him, others may have a different, more positive experience. “If something works for a period of time, great, keep doing it,” he advises. “If something changes and you’re not feeling great, then you’ve got to reassess it again and then figure it out.” The episode involved a complete overhaul of his diet as he took stock of what he put into his body. It included an almost six-month stint of sobriety. “I want to have optimal health at all times,” he says. “I want my mental health to be strong and I want my body to feel good.”

New hominin cranial fossils highlight the early exploits of Homo erectus New hominin cranial fossils highlight the early exploits of Homo erectus

Health, the environment, and animal rights represent the three main reasons people cite for vegetarian diet in Western societies. However, it has not been shown that these motives can be distinguished empirically, and little is known about what kind of people are likely to be compelled by these different motives. This study had three goals. First, we aimed to use construct validation to test whether develop health, environmental, and animal rights motives for a vegetarian diet could be distinguished. Second, we evaluated whether these motivations were associated with different demographic, behavioral, and personality profiles in three diverse samples. Third, we examined whether peoples’ motivations were related to responses to vegetarian advocacy materials. We created the Vegetarian Eating Motives Inventory, a 15-item measure whose structure was invariant across three samples (N = 1006, 1004, 5478) and two languages (English and Dutch). Using this measure, we found that health was the most common motive for non-vegetarians to consider vegetarian diets and it had the broadest array of correlates, which primarily involved communal and agentic values. Correlates of environmental and animal rights motives were limited, but these motives were strong and specific predictors of advocacy materials in a fourth sample (N = 739). These results provide researchers with a useful tool for identifying vegetarian motives among both vegetarian and non-vegetarian respondents, offer useful insights into the nomological net of vegetarian motivations, and provide advocates with guidance about how to best target campaigns promoting a vegetarian diet.

Like human groups, carnivores are able to act on the same faunal accumulation and generate important bone assemblages with their prey remains. In addition, both predators can share the same habitable areas and alternate their occupations, producing the well-known palimpsest at archaeological sites. As a discipline, taphonomy helps us understand the formation of these sites and allows us to identify what occurred before and after the burial of the remains. In order to make an accurate taphonomic interpretation, knowledge of the carnivore ethology is necessary to understand the way that bone accumulations originate and to make inferences about their relationship with human behaviour or other living beings of the environment. In this work, a first taphonomic approach concerning the faunal assemblage of unit 2 of Tritons Cave (Lleida, Catalonia) has been carried out. This unit is characterized by the prevailing presence of the Iberian ibex (Capra pyrenaica) and, to a lesser extent, the brown bear (Ursus arctos) and cave bear (Ursus spelaeus). The survival profile of goats, the alterations observed on the bones, and the consumption patterns seem to indicate that the main agent accumulator is the leopard (Panthera pardus); nevertheless, the occasional intrusion and secondary activity of other predators, including hominins, cannot be ruled out. The presence of ursids and the alterations on their bones seem to be related to natural deaths and subsequent carnivore activity, which indicates the high complexity in the assemblage formation. The identification of the leopard as a main taphonomic agent sheds light about these kinds of dens, establishing guidelines to differentiate bone accumulations produced by other carnivores as well as the criteria to identify them within anthropic contexts. Thus, the goal here is to highlight the importance of these types of studies to better understand the relationships and differences between human and carnivore activities in the Iberian Peninsula during the Late Pleistocene age.

Objective To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese. Design Systematic review and network meta-analysis of randomised trials. Data sources Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews. Study selection Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet. Outcomes and measures Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up. Review methods Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets. Results 121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 v 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty v 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 v 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty v 7.08 mg/dL, moderate certainty v 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (−1.88 mg/dL, moderate certainty) and moderate macronutrient (−0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared. Conclusions Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear. Systematic review registration PROSPERO CRD42015027929.

Background The human gut microbiome is recognized as an important determinant of human health, yet little is known about how dietary habits are related to the microbiome in post-weaned, pre-pubescent children. Objective The goal of this work was to link quantitative dietary intake with microbiome features in a diverse population of children consuming a predominantly Western diet. Design This was a cross-sectional study. Participants/settings English- or Spanish-speaking families with healthy children between the ages of 2 and 9 years were recruited from a community-based, early childhood learning center in suburban Los Angeles, California between June and September 2014. Main outcome measures Children included in the analyses (n=75) contributed three fecal samples and three quantitative 24-hour dietary recalls using the multiple-pass method with an average of 5.7 days between samples. Microbial communities of each fecal sample were characterized using Illumina sequencing of the 16S ribosomal RNA gene. Dietary recalls were analyzed using the Automated Self-Administered 24-Hour Recall Dietary Assessment Tool. Statistical analysis performed Associations between dietary factors and microbiome features were assessed using the Kruskal-Wallis test, Spearman rank correlations, or permutational multivariate analysis of variance. For demographic and health-related variables, χ2 analyses were used to test for differences between age groups for categorical variables. Results Our results show that age is correlated with three metrics of microbiome diversity (P0.05). Likewise, the relative abundance of several bacterial taxa were linked to consumption of particular food groups and/or nutrients, as illustrated by the positive associations between total fruit (Pfalse discovery rate<0.05) and fiber (Pfalse discovery rate

Background Akkermansia muciniphila (AM) is a gram-negative, mucin-degrading bacteria inhabiting the gastrointestinal tract associated with host phenotypes and disease states. Objective Explore characteristics of overweight and obese female early-stage (0 to II) breast cancer patients with low AM relative abundance (LAM) vs high (HAM) enrolled in a presurgical weight-loss trial. Design Secondary analysis of pooled participants in a randomized controlled trial (NCT02224807). Participants/setting During the period from 2014 to 2017, 32 female patients with breast cancer were randomized to weight-loss or attention-control arms from time of diagnosis-to-lumpectomy (mean=30±9 days). Intervention All were instructed to correct nutrient deficiencies via food sources and on upper-body exercises. The weight-loss group received additional guidance to promote 0.5 to 1 kg/wk weight-loss via energy restriction and aerobic exercise. Main outcome measures At baseline and follow-up, sera, fecal samples, two-24 hour dietary recalls and dual x-ray absorptiometry were obtained. Bacterial DNA was isolated from feces and polymerase chain reaction (16S) amplified. Inflammatory cytokines were measured in sera. Statistical analyses performed Differences between LAM and HAM participants were analyzed using t tests and nonparametric tests. Spearman correlations explored relationships between continuous variables. Results Participants were aged 61±9 years with body mass index 34.8±6. Mean AM relative abundance was 0.02% (0.007% to 0.06%) and 1.59% (0.59% to 13.57%) for LAM and HAM participants, respectively. At baseline, women with HAM vs LAM had lower fat mass (38.9±11.2 kg vs 46.4±9.0 kg; P=0.044). Alpha diversity (ie, species richness) was higher in women with HAM (360.8±84.8 vs 282.4±69.6; P=0.008) at baseline, but attenuated after weight-loss (P=0.058). At baseline, interleukin-6 level was associated with species richness (ρ=–0.471, P=0.008) and fat mass (ρ=0.529, P=0.002), but not AM. Change in total dietary fiber was positively associated with AM in LAM (ρ=0.626, P=0.002), but not HAM (ρ=0.436, P=0.180) participants. Conclusions Among women with early-stage breast cancer, body composition is associated with AM, microbiota diversity, and interleukin-6 level. AM may mediate the effects of dietary fiber in improving microbiota composition.

Background Irritable bowel syndrome (IBS) is the most common functional digestive condition in the industrialized world. The gut microbiota plays a key role in disease pathogenesis. Objective A systematic review and meta-analysis on case–control studies was conducted to determine whether there is gut microbial dysbiosis in participants with IBS in comparison with healthy controls and, if so, whether the dysbiosis pattern differs among IBS subtypes and geographic regions. Methods This review was conducted and reported according to the MOOSE (Meta-Analysis of Observational Studies in Epidemiology) 2000 and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines. Research articles published up to May 9, 2018 were identified through MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (Cochrane Library), ClinicalTrials.gov, EMBASE, and Web of Science. Study quality was assessed using the Newcastle-Ottawa Scale. Case–control studies of participants with IBS who had undergone quantitative gut microbial stool analysis were included. The primary exposure measure of interest is log10 bacterial counts per gram of stool. Meta-analyses were performed to estimate the mean difference (MD) in gut microbiota between participants with IBS and healthy controls using the random-effects model with inverse variance in Revman 5.3 and R 3.5.1. Publication bias was assessed with funnel plots and Egger’s test. Between-study heterogeneity was analyzed using Higgins I2 statistic with 95% CIs. Results There were 6,333 unique articles identified; 52 qualified for full-text screening. Of these, 23 studies were included for analysis (n=1,340 participants from North America, Europe, and Asia). Overall, the studies were moderate in quality. Comparing participants with IBS to healthy controls, lower fecal Lactobacillus (MD= –0.57 log10 colony-forming unit [CFU]/g; P<0.01) and Bifidobacterium (MD= –1.04 log10CFU/g; P<0.01), higher Escherichia coli (MD=0.60 log10CFU/g; P<0.01), and marginally higher Enterobacter (MD=0.74 log10CFU/g; P=0.05). No difference was found between participants with IBS and healthy controls in fecal Bacteroides and Enterococcus (P=0.18 and 0.68, respectively). Publication bias was not observed except in Bifidobacterium (P=0.015). Subgroup analyses on participants with diarrhea-predominant and constipation-predominant IBS showed consistent results with the primary results. A subgroup analysis of Chinese studies was consistent with the primary results, except for fecal Bacteroides, which was increased in participants with IBS vs healthy controls (MD=0.29; 95% CI 0.13 to 0.46; P75%) in most comparisons, the direction of the effect estimates is relatively consistent across studies. Conclusions IBS is characterized by gut microbial dysbiosis. Prospective, large-scale studies are needed to delineate how gut microbial profiles can be used to guide targeted therapies in this challenging patient population.

Background Higher protein intakes may help reduce sarcopenia and facilitate recovery from illness and injury in older adults. However, high-protein diets (HPDs) including animal-sourced foods may negatively perturb the microbiota, and provision of probiotics and prebiotics may mitigate these effects. Objective The aim of this study was to examine the effects of HPD, with and without a probiotic and/or prebiotic, on gut microbiota and wellness in older women. Design We conducted an 18-week, double-blind, placebo-controlled, crossover study. Participants/setting Participants were healthy, older women (mean age±standard deviation=73.7±5.6 years; n=26) recruited from Florida. Intervention Participants received a weight-maintenance HPD for 2-week periods and the following, in random order: HPD alone (1.5 to 2.2 g/kg/day protein); HPD plus multistrain probiotic formulation (1.54×109 Bifidobacterium bifidum HA-132, 4.62×109 Bifidobacterium breve HA-129, 4.62×109 Bifidobacterium longum HA-135, 4.62×109 Lactobacillus acidophilus HA-122, and 4.62×109 Lactobacillus plantarum HA-119), HPD plus prebiotic (5.6 g inulin), and HPD plus synbiotic (probiotic plus inulin), separated by 2-week washouts. Stools were collected per period for quantitative polymerase chain reaction (strain recovery) and 16S ribosomal RNA gene amplicon sequencing analyses (microbiota profile). Measures of gastrointestinal and general wellness were assessed. Main outcome measures Microbiota composition and probiotic strain recovery were measured. Statistical analyses Microbiota composition was analyzed by Wilcoxon signed-rank test and t test. Secondary outcomes were analyzing using generalized linear mixed models. Results The microbiota profile demonstrated relative stability with the HPD; representation of Lactobacillus, Lactococcus, and Streptococcus were enhanced, whereas butyrate producers, Roseburia and Anaerostipes, were suppressed. Lactococcus was suppressed with synbiotic vs other HPD periods. Recovery was confirmed for all probiotic strains. Indicators of wellness were unchanged, with the exception of a minimal increase in gastrointestinal distress with inulin. Fat-free mass increased from baseline to study end. Conclusions An HPD adhering to the recommended acceptable macronutrient distribution ranges maintains wellness in healthy older women and exerts minor perturbations to the microbiome profile, a group that may benefit from a higher protein intake. ClinicalTrials.gov ID: NCT #02445560.

Background Individuals with irritable bowel syndrome (IBS) may modify their diet, which may pose nutritional risk. Further, some dietary approaches, such as a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), are restrictive and may contribute to nutritional inadequacy. Objective Our aim was to evaluate habitual nutrient intake, diet quality, and diversity in IBS and the effect of a 4-week low FODMAP diet on these parameters compared with controls. Design Data from two randomized controlled trials were included for this secondary analysis. Participants were randomized to low FODMAP diet (n=63) or control diet (sham diet n=48, habitual diet n=19). Participants/setting Participants included 130 individuals with IBS referred to a tertiary center in London, UK between January 2010 to June 2011 and January 2013 to November 2014. Intervention Participants in one trial were randomized to receive either low FODMAP dietary counseling or sham control dietary counseling. In the other, they were randomized to receive low FODMAP dietary counseling or to continue habitual diet. All advice was provided by a specialist dietitian. Main outcome measures Habitual (usual) dietary intake at baseline (n=130) and after a 4-week intervention period was measured using 7-day food records. Statistical analyses performed Analysis of covariance and χ2 tests evaluated differences across groups at 4 weeks. Results When examining habitual intake of individuals with IBS, fiber intake was low, with only 6 (5%) achieving the target (30 g/day). In those receiving low FODMAP advice, there was no difference in intake of most nutrients compared with controls. However, there was lower intake of starch (109 g/day) vs habitual control diet (128 g/day; P=0.030), and higher intake of vitamin B-12 (6.1 μg/day) vs habitual (3.9 μg/day) and sham control diets (4.7 μg/day; P<0.01). Overall scores for diet quality were lower after low FODMAP advice vs habitual control diet (P

Malnutrition is common in patients with Crohn’s disease and negatively influences immunity and quality of life. The optimal tools for nutrition assessment in patients with Crohn’s disease are not clearly defined and lead to variations in practice. With this review, we aimed to appraise the existing evidence for nutrition assessment of patients with Crohn’s disease compared with healthy controls and provide a comprehensive guide with relevant measures applicable to clinical practice. A literature search using Medline, Embase, and Scopus from inception to October 1, 2018, was conducted. Forty-one articles that assessed body composition, muscle strength, micronutrient status and/or dietary intake in adults with Crohn’s disease compared with an age- and sex-matched healthy individuals were included. There were heterogeneous findings on nutritional status in patients with Crohn’s disease compared with healthy controls. Only one article reported a clinically significant difference for body mass index; however, significant deficits in fat mass, fat-free mass, and muscle strength were observed in patients with Crohn’s disease compared with healthy controls, with more pronounced differences with increasing disease activity and length of diagnosis. Most research reported significantly lower serum micronutrients in patients with Crohn’s disease compared with healthy controls. Half of studies measuring micronutrient intake reported lower intakes in patients with Crohn’s disease compared with healthy controls. Fruit and vegetable intake was also lower in patients with Crohn’s disease. Difficulties characterizing the type and prevalence of malnutrition exist due to the heterogeneous nature of Crohn’s disease and warrants continued investigation. As a result of this review, we advocate that a nutrition assessment should include more parameters than weight and body mass index.

Background A main mechanism of action proposed for oral probiotic supplementation is immunomodulation, which is expected to impart health benefits in the host by influencing circulating immune and inflammatory factors. To date, the effectiveness of probiotic supplementation for immunomodulation in healthy adults without disease has not been evaluated in a systematic review. Objective The objective of this systematic review was to evaluate the effect of probiotic supplementation on circulating immune and inflammatory markers of healthy adults compared to placebo. Methods PubMed, SCOPUS, ISI Web of Science, ProQuest, and Cochrane databases were searched for English articles up to May 15, 2019. Additional papers were identified by checking references of relevant papers. Only randomized controlled trials studying the administration of probiotic supplements compared to placebo on immune and inflammatory markers in healthy adults (aged 18 to 65 years), without acute or chronic disease, and in generally good health were examined. Independent extraction of articles was conducted by two authors using predefined search terms and restrictions/filters. The methodologic quality of each study was appraised using the Academy of Nutrition and Dietetics Evidence Analysis Library Quality Rating Worksheet and the body of evidence was assessed using the Academy of Nutrition and Dietetics Grade Definitions and Conclusion Grading Table. Results Eighteen articles, including 819 subjects, met eligibility criteria and were included in the present systematic review. Five articles were rated neutral in quality and 13 were rated high in quality. Eight articles reported a significant effect on immune and/or inflammatory parameters including increases in natural killer cells, lymphocytes, and monocytes, and decreases in proinflammatory cytokine concentrations. Conclusions Based on the 18 articles extracted in this systemic review, probiotic supplementation was concluded to have a limited effect on immune and inflammatory markers in healthy adults. Overall, the evidence was heterogenous, precluding a meta-analysis, and difficult to aggregate and conclude on effect size. Systematic review registration number PROSPERO ref CRD42018110856.

Background Intestinal bacteria composition and prebiotics may play a role in the management of type 2 diabetes mellitus (T2DM). Objective The objective of this systematic review was to evaluate the effect of prebiotics and substances with prebiotic properties on the metabolic and inflammatory biomarkers of individuals with T2DM compared with placebo. Methods A literature search to identify articles published up to March 31, 2018, was conducted utilizing PubMed, Science Direct, and Cochrane Central Register of Controlled Trials. Individuals at aged 18 years or older with T2DM from randomized controlled trials investigating prebiotics or substances with prebiotic properties were included. Metabolic and inflammatory biomarkers associated with T2DM were the primary outcome measures. Results Twenty-seven publications were analyzed. All but seven of these publications reported a beneficial effect on metabolic and/or inflammatory biomarkers. Interventions included mostly women, lasted 4 days to 12 weeks, and diabetes duration ranged from 6 months to 11 years. Nineteen publications reported improvements in glycemia, 15 in cardiovascular markers, nine in body weight, and nine in inflammatory markers. Benefits from resistant starch, resistant dextrin, and oligofructose-enriched inulin were most frequent. A smaller number of studies utilizing other substances with prebiotic properties also yielded improvements. Conclusions Based on these results, there is fair evidence that prebiotics and substances with prebiotic properties may improve metabolic and inflammatory biomarkers related to T2DM in women aged 18 years at least. Interventions with resistant starch, resistant dextrin, and oligofructose-enriched inulin exhibited the strongest evidence for improvements due to the quantity of publications and quality grades. Other prebiotics and substances with prebiotic properties show promise but the number of studies is few. Additional studies that are longer in duration, include both sexes, and include other prebiotics or substances with prebiotic properties are needed.

Background A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) has gained increasing acceptance for the treatment of irritable bowel syndrome but safety concerns have been raised regarding nutritional adequacy. Changes in nutrient intake during the elimination phase of the low-FODMAP diet remain predominantly unknown. Objective To determine changes in the mean reported daily nutrient content before and after 4 weeks of a low-FODMAP diet vs modified National Institute for Health and Clinical Excellence (mNICE) dietary intervention and to identify nutritional inadequacies based on comparison to the Dietary Reference Intakes in patients with irritable bowel syndrome-diarrhea subtype. Design Post hoc analysis of a randomized controlled trial entailing a 4-week trial period comparing the low-FODMAP and mNICE diets. Participants and setting A total of 78 patients (41 low FODMAP and 37 mNICE) meeting the Rome III criteria for irritable bowel syndrome-diarrhea subtype were consecutively recruited from gastroenterology and primary care clinics at the University of Michigan Medical Center between October 2012 and November 2015. Methods Participants randomized to the low-FODMAP arm were instructed to decrease their dietary intake of FODMAPs, whereas participants randomized to the mNICE intervention arm were instructed to eat small frequent meals, avoid trigger foods, and avoid excess alcohol and caffeine. Main outcome measures Post hoc evaluation for presence of micronutrient deficiencies per Dietary Reference Intakes when implementing low-FODMAP vs mNICE dietary interventions. Dietary intake was analyzed via 3-day food diaries at baseline and during the final week of the assigned diet. Statistical analyses performed A post hoc analysis utilizing either a t test or χ2 analysis was conducted between before and after data. Results Both diets resulted in fewer daily kilocalories consumed, fewer number of daily meals consumed, and less daily carbohydrate intake. Among the patients following the low-FODMAP diet, there was a statistically significant decrease from baseline in several micronutrients, which was not observed in the mNICE cohort. However, these differences in the low-FODMAP group remained significant only for riboflavin after correcting for calorie-adjusted nutrient intake. Comparing Dietary Reference Intakes of participants pre- and postintervention, fewer patients met the Dietary Reference Intakes for thiamin and iron in the low FODMAP group, and for calcium and copper in the mNICE group. Conclusions During a 4-week dietary intervention, the mean daily intake of most micronutrients remained stable and within the Recommended Dietary Allowances for both diets. Although decrease in several micronutrients was observed with implementation of the low-FODMAP diet relative to the mNICE diet, most of these disappeared after adjusting for energy intake.

Dietary intake is a key determinant of gastrointestinal microbiota composition. Studies have considered the relationship between gut microbiota and dietary patterns. It is likely that certain plant foods that contain fiber and other bioactive matter may be more likely to drive microbial changes than others; however, study design and other factors can make interpretation of the literature difficult. Fifteen well-controlled, well-defined diet interventions published between 2008 and 2018 using whole, plant foods were evaluated for their influence on gut microbiota. There was limited effect on microbial diversity across studies and modest microbial changes were noted in 10 of 15 studies. More research is needed before specific plant foods can be recommended to improve gut microbiota and ultimately health. Methodologic considerations for future diet and microbiome studies are discussed. Additional research to better understand how specific whole, plant foods influence microbe composition, functionality, and metabolite production is needed, as are mechanistic studies linking diet-induced gut microbe changes to health.

Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.

A few single-nucleotide polymorphisms (SNPs) have been identified to be associated with cutaneous melanoma (CM) survival through genome-wide association studies, but stringent multiple testing corrections required for the hypothesis-free testing may have masked some true associations. Using a hypothesis-driven analysis approach, we sought to evaluate associations between SNPs in ketone body metabolic pathway genes and CM survival. We comprehensively assessed associations between 4196 (538 genotyped and 3658 imputed) common SNPs in 44 ketone body metabolic pathway genes and CM survival, using a dataset of 858 patients of a case-control study from The University of Texas M.D. Anderson Cancer Center as the discovery set and another dataset of 409 patients from the Nurses' Health Study and the Health Professionals Follow-up Study as the replication set. There were 95/858 (11.1%) and 48/409 (11.7%) patients who died of CM, respectively. We identified two independent SNPs (ie, PDSS1 rs12254548 G>C and SLC16A6 rs71387392 G>A) that were associated with CM survival, with allelic hazards ratios of 0.58 (95% confidence interval [CI] = 0.44-0.76, P = 9.00 × 10-5 ) and 1.98 (95% CI = 1.34-2.94, P = 6.30 × 10-4 ), respectively. Additionally, associations between genotypes of the SNPs and messenger RNA expression levels of their corresponding genes support the biologic plausibility of a role for these two variants in CM tumor progression and survival. Once validated by other larger studies, PDSS1 rs12254548 and SLC16A6 rs71387392 may be valuable biomarkers for CM survival.

Based on international literature and clinical experience we argue that there are some simple solutions that can be applied quickly and effectively in everyday life to slow the spread of the SARS-CoV-2 virus and to drastically reduce the severity of complications.

Postnatal administration of high-fat, low-carbohydrate ketogenic diets (KDs) is an established and effective treatment option for refractory epilepsy, with more recently identified therapeutic potential across a wide range of preclinical models of neurological and psychiatric disorders. However, the impact of gestational exposure to a KD (GKD) on offspring development remains unclear. Previous work has found that GKD exposure reduces depression- and anxiety-like behaviors in CD-1 mice, whereas postnatal KD improves sociability in several different rodent models of autism. Here we examined how sociability is impacted by GKD. Given that the neuropeptide oxytocin positively regulates affect, anxiety, and sociability, we also examined the effects of GKD on brain oxytocin expression. Male and female CD-1 mice exposed to either a standard diet (SD) or a KD gestationally were cross-fostered with SD dams at birth and remained on a SD from that point onward. These offspring were then tested for sociability and social novelty (three-chambered test) and depressive-like behaviors (forced swim test) at 10 weeks of age. At the conclusion of testing, brain tissue was collected and immunohistochemically processed for oxytocin expression in hypothalamic and limbic areas. We found that GKD increased sociability and reduced depressive-like symptoms, without affecting oxytocin expression in quantified areas. By expanding the scope of the lasting impact of gestational exposure to a ketogenic diet to include positive effects on sociability, these results indicate that GKDs may have novel therapeutic applications for individuals at risk for developmental disorders of social behavior, including autism and schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Colobinae are a subfamily of the Old World monkey family that includes 61 species in 11 genera, including the black-and-white colobus, the large-nosed proboscis monkey, and the gray langurs. Some classifications split the colobine monkeys into two tribes, while others split them into three groups. Both classifications put the three African genera Colobus, Piliocolobus, and Procolobus in one group; these genera are distinct in that they have stub thumbs (Greek κολοβός kolobós = "docked"). The various Asian genera are placed into another one or two groups. Analysis of mtDNA confirms the Asian species form two distinct groups, one of langurs and the other of the "odd-nosed" species, but are inconsistent as to the relationships of the gray langurs; some studies suggest that the gray langurs are not closely related to either of these groups, while others place them firmly within the langur group.

BACKGROUND AND AIMS: We performed a retrospective study of diabetic patients undergoing a targeted multimodal prehabilitation programme to assess changes in their diabetic control and functional capacity prior to surgery. As part of the programme, patients were encouraged to follow a low-carbohydrate, high-fat (LCHF) dietary approach. We aimed to assess the feasibility and effects of this programme on our cohort of patients. METHODS: From 79 patients attending prehabilitation, 17 (13 males, age (median [interquartile range]): 71 [63-79] years) had Type 2 diabetes and none had Type 1. Patients had undergone a targeted multimodal prehabilitation programme prior to surgery, which comprised supervised exercise sessions (aerobic or resistance training), nutritional education (LCHF suggestion, correct protein intake, and avoidance of processed food), psychological support and medical optimization. Weight, body mass index (BMI), glycosylated haemoglobin (HbA1c), fasting glucose, and functional capacity were measured prior to and after prehabilitation. Data were compared with a Wilcoxon signed-rank test. RESULTS: There were significant improvements in HbA1c (P = 0.000), fasting glucose (P = 0.006), weight (P = 0.002), and BMI (P = 0.002). There were no significant improvements in functional capacity. CONCLUSIONS: We have shown that in the preoperative period, a targeted multimodal prehabilitation programme incorporating a LCHF diet improves diabetes control in patients with T2D awaiting elective surgery. Our approach is novel as a LCHF diet has not previously been utilized in patients with diabetes within this context. Prospective studies are required in the context of post-operative outcomes.

Fruits of the sea The origins of marine resource consumption by humans have been much debated. Zilhão et al. present evidence that, in Atlantic Iberia's coastal settings, Middle Paleolithic Neanderthals exploited marine resources at a scale on par with the modern human–associated Middle Stone Age of southern Africa (see the Perspective by Will). Excavations at the Figueira Brava site on Portugal's Atlantic coast reveal shell middens rich in the remains of mollusks, crabs, and fish, as well as terrestrial food items. Familiarity with the sea and its resources may thus have been widespread for residents there in the Middle Paleolithic. The Figueira Brava Neanderthals also exploited stone pine nuts in a way akin to that previously identified in the Holocene of Iberia. These findings add broader dimensions to our understanding of the role of aquatic resources in the subsistence of Paleolithic humans. Science, this issue p. eaaz7943; see also p. 1422 Structured Abstract INTRODUCTIONA record of the regular exploitation of aquatic foods has been lacking in Neandertal Europe. By contrast, marine resources feature prominently—alongside personal ornaments, body painting, and linear-geometric drawings—in the archeology of Last Interglacial Africa. A competitive advantage scenario of human origins is that the habitual consumption of aquatic foods and the fatty acids they contain, which favor brain development, underpins the acquisition of modernity in cognition and behavior. The resulting innovations in technology, demographic growth, and enhanced prosociality would therefore explain modern humans’ out-of-Africa expansion with regard to both dispersal process (along coastal routes and to southern Asia first) and outcome (the demise of coeval non-modern Eurasians). A corollary of this view is that the paucity of marine foods at Neandertal coastal sites is a genuine reflection of their subsistence behavior. RATIONALEEurope’s Atlantic façade boasts resource-rich coastal waters comparable to those of South Africa. From Scandinavia to France, however, any evidence for the Last Interglacial exploitation of marine resources would have been lost to subsequent icecap advances and postglacial submersion of the wide continental platform. Conversely, the very steep shelf off Arrábida, a littoral mountain range 30 km south of Lisbon, Portugal, has enabled extant and submerged shorelines to be preserved short distances apart. Gruta da Figueira Brava, one of Arrábida’s erosion-protected, seaside cave sites, provides a singular opportunity to investigate whether any considerable Last Interglacial accumulations of marine food debris ever existed in Europe. RESULTSThe Figueira Brava archeological sequence dates to ~86 to 106 thousand years ago (kya). Throughout, there is evidence of a settlement-subsistence system based on regular exploitation of all animal resources offered by the coastal environment: large crabs, marine mollusks, fish, marine birds and mammals, tortoise, waterfowl, and hoofed game. The composition of the food basket and the structure of the deposit vary as a function of the following: (i) sea-level oscillation, with implications for the ecosystems that were preferentially targeted; (ii) frequency of human occupation; (iii) site-formation process; and (iv) position of the archeological trenches relative to the changing configuration of the inhabited space. The initial occupations (phases FB1 and FB2), when the sea was closer to the cave (~750 m), include shell-supported accumulations. These occupations were followed by a period of infrequent use (phase FB3) and a final phase (FB4), when the shoreline was ~2000 m away but shellfish were again discarded at the site in substantial amounts. The density of marine food remains compares well to that seen in the regional Mesolithic and the Last Interglacial of South Africa and the Maghreb and exceeds the latter two in the case of crabs and fish. Figueira Brava also documents a stone pine economy featuring seasonal harvesting and on-site storage of the cones for deferred consumption of the nuts. The stability of this subsistence system suggests successful long-term adaptation. CONCLUSIONFigueira Brava provides the first record of significant marine resource consumption among Europe’s Neandertals. Taphonomic and site-preservation biases explain why this kind of record has not been previously found in Europe on the scale seen among coeval African populations. Consistent with rapidly accumulating evidence that Neandertals possessed a fully symbolic material culture, the subsistence evidence reported here further questions the behavioral gap once thought to separate them from modern humans. Download high-res image Open in new tab Download Powerpoint Gruta da Figueira Brava, Arrábida, Portugal.Note the Mediterranean vegetation, like at the time of the Last Interglacial occupation, the MIS 5e marine abrasion terrace, and, under the overhang, the brecciated remnant dated to ~86 to 106 kya. Neandertal use of this cave space, which is currently unroofed due to Holocene erosion, has left an archeological record rich in fish, shellfish, and other coastal resources.PHOTOS: PEDRO SOUTO/JOÃO ZILHÃO. Marine food–reliant subsistence systems such as those in the African Middle Stone Age (MSA) were not thought to exist in Europe until the much later Mesolithic. Whether this apparent lag reflects taphonomic biases or behavioral distinctions between archaic and modern humans remains much debated. Figueira Brava cave, in the Arrábida range (Portugal), provides an exceptionally well preserved record of Neandertal coastal resource exploitation on a comparable scale to the MSA and dated to ~86 to 106 thousand years ago. The breadth of the subsistence base—pine nuts, marine invertebrates, fish, marine birds and mammals, tortoises, waterfowl, and hoofed game—exceeds that of regional early Holocene sites. Fisher-hunter-gatherer economies are not the preserve of anatomically modern people; by the Last Interglacial, they were in place across the Old World in the appropriate settings. The subsistence base of coastal Portugal’s Last Interglacial Neandertals was as broad as that of present-day humans. The subsistence base of coastal Portugal’s Last Interglacial Neandertals was as broad as that of present-day humans.

Humans share a deep bond with coasts and oceans. More than 500 million people live in coastal communities, and beaches and seafood attract tourists from around the world. Archaeological research in southern Africa revealed early human coastal adaptations that occurred at least as far back as ∼160,000 years ago (1) in the Middle Stone Age (MSA)—the cultural period of the earliest Homo sapiens. Paleolithic sites across Africa and elsewhere support the hypothesis that coastal adaptations have a long and lasting history. Yet, scientists still debate the importance of coastal adaptations for the evolution and dispersal of H. sapiens during the Pleistocene (Ice Age) (2). On page 1443 of this issue, Zilhão et al. (3) tackle an even more contentious issue with wide-ranging implications for human evolution: Did Neanderthals share our species' interest in oceans and their inhabitants? Did our closest ancestors adapt to the sea in the same way as early Homo sapiens? Did our closest ancestors adapt to the sea in the same way as early Homo sapiens?

Bipedalism is a defining trait of the hominin lineage, associated with a transition from a more arboreal to a more terrestrial environment. While there is debate about when modern human-like bipedalism first appeared in hominins, all known South African hominins show morphological adaptations to bipedalism, suggesting that this was their predominant mode of locomotion. Here we present evidence that hominins preserved in the Sterkfontein Caves practiced two different locomotor repertoires. The trabecular structure of a proximal femur (StW 522) attributed to Australopithecus africanus exhibits a modern human-like bipedal locomotor pattern, while that of a geologically younger specimen (StW 311) attributed to either Homo sp. or Paranthropus robustus exhibits a pattern more similar to nonhuman apes, potentially suggesting regular bouts of both climbing and terrestrial bipedalism. Our results demonstrate distinct morphological differences, linked to behavioral differences between Australopithecus and later hominins in South Africa and contribute to the increasing evidence of locomotor diversity within the hominin clade.

Summary Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, characterized by hepatic fat accumulation and possible development of inflammation, fibrosis, and cancer. The ketogenic diet (KD), with its drastic carbohydrate reduction, is a now popular weight loss intervention, despite safety concerns on a possible association with fatty liver. However, KDs were also reported to be beneficial on hepatic pathology, with ketone bodies recently proposed as effective modulators of inflammation and fibrosis. If the beneficial impact of weight loss on NAFLD is established, less is known on the effect of macronutrient distribution on such outcome. In a hypocaloric regimen, the latter seems not to be crucial, whereas at higher calorie intake, macronutrient ratio and, theoretically, ketosis, may become important. KDs could positively impact NAFLD for their very low carbohydrate content, and whether ketosis plays an additional role is unknown. Indeed, several mechanisms may directly link ketosis and NAFLD improvement, and elucidating these aspects would pave the way for new therapeutic strategies. We herein aimed at providing an accurate revision of current literature on KDs and NAFLD, focusing on clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, characterized by hepatic fat accumulation and possible development of inflammation, fibrosis, and cancer. The ketogenic diet (KD), with its drastic carbohydrate reduction, is a now popular weight loss intervention, despite safety concerns on a possible association with fatty liver. However, KDs were also reported to be beneficial on hepatic pathology, with ketone bodies recently proposed as effective modulators of inflammation and fibrosis. If the beneficial impact of weight loss on NAFLD is established, less is known on the effect of macronutrient distribution on such outcome. In a hypocaloric regimen, the latter seems not to be crucial, whereas at higher calorie intake, macronutrient ratio and, theoretically, ketosis, may become important. KDs could positively impact NAFLD for their very low carbohydrate content, and whether ketosis plays an additional role is unknown. Indeed, several mechanisms may directly link ketosis and NAFLD improvement, and elucidating these aspects would pave the way for new therapeutic strategies. We herein aimed at providing an accurate revision of current literature on KDs and NAFLD, focusing on clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions.

This study uses public employee salary data from 14 US public medical schools and the Open Payments database from the US Centers for Medicare & Medicaid Services to examine the ratio of academic oncologists’ reported salaries to their general payments from the medical industry.

Background Circulating lipoprotein lipids cause coronary heart disease (CHD). However, the precise way in which one or more lipoprotein lipid-related entities account for this relationship remains unclear. Using genetic instruments for lipoprotein lipid traits implemented through multivariable Mendelian randomisation (MR), we sought to compare their causal roles in the aetiology of CHD. Methods and findings We conducted a genome-wide association study (GWAS) of circulating non-fasted lipoprotein lipid traits in the UK Biobank (UKBB) for low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoprotein B to identify lipid-associated single nucleotide polymorphisms (SNPs). Using data from CARDIoGRAMplusC4D for CHD (consisting of 60,801 cases and 123,504 controls), we performed univariable and multivariable MR analyses. Similar GWAS and MR analyses were conducted for high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. The GWAS of lipids and apolipoproteins in the UKBB included between 393,193 and 441,016 individuals in whom the mean age was 56.9 y (range 39–73 y) and of whom 54.2% were women. The mean (standard deviation) lipid concentrations were LDL cholesterol 3.57 (0.87) mmol/L and HDL cholesterol 1.45 (0.38) mmol/L, and the median triglycerides was 1.50 (IQR = 1.11) mmol/L. The mean (standard deviation) values for apolipoproteins B and A-I were 1.03 (0.24) g/L and 1.54 (0.27) g/L, respectively. The GWAS identified multiple independent SNPs associated at P < 5 × 10−8 for LDL cholesterol (220), apolipoprotein B (n = 255), triglycerides (440), HDL cholesterol (534), and apolipoprotein A-I (440). Between 56%–93% of SNPs identified for each lipid trait had not been previously reported in large-scale GWASs. Almost half (46%) of these SNPs were associated at P < 5 × 10−8 with more than one lipid-related trait. Assessed individually using MR, LDL cholesterol (odds ratio [OR] 1.66 per 1-standard-deviation–higher trait; 95% CI: 1.49–1.86; P < 0.001), triglycerides (OR 1.34; 95% CI: 1.25–1.44; P < 0.001) and apolipoprotein B (OR 1.73; 95% CI: 1.56–1.91; P < 0.001) had effect estimates consistent with a higher risk of CHD. In multivariable MR, only apolipoprotein B (OR 1.92; 95% CI: 1.31–2.81; P < 0.001) retained a robust effect, with the estimate for LDL cholesterol (OR 0.85; 95% CI: 0.57–1.27; P = 0.44) reversing and that of triglycerides (OR 1.12; 95% CI: 1.02–1.23; P = 0.01) becoming weaker. Individual MR analyses showed a 1-standard-deviation–higher HDL cholesterol (OR 0.80; 95% CI: 0.75–0.86; P < 0.001) and apolipoprotein A-I (OR 0.83; 95% CI: 0.77–0.89; P

Background: Insulin resistance (IR), considered a hallmark of diabetes at the cellular level, is implicated in pre-diabetes, results in type 2 diabetes, and negatively affects mitochondrial function. Diabetes is increasingly associated with enhanced risk of developing Parkinson's disease (PD); however, the underlying mechanism remains unclear. This study investigated the probable culpability of IR in the pathogenesis of PD. Methods: Using MitoPark mice in vivo models, diabetes was induced by a high-fat diet in the in vivo models, and IR was induced by protracted pulse-stimulation with 100 nM insulin treatment of neuronal cells, in vitro to determine the molecular mechanism(s) underlying altered cellular functions in PD, including mitochondrial dysfunction and α-synuclein (SNCA) aberrant expression. Findings: We observed increased SNCA expression in the dopaminergic (DA) neurons of both the wild-type and diabetic MitoPark mice, coupled with enhanced degeneration of DA neurons in the diabetic MitoPark mice. Ex vivo, in differentiated human DA neurons, IR was associated with increased SNCA and reactive oxygen species (ROS) levels, as well as mitochondrial depolarization. Moreover, we demonstrated concomitant hyperactivation of polo-like kinase-2 (PLK2), and upregulated p-SNCA (Ser129) and proteinase K-resistant SNCA proteins level in IR SH-SY5Y cells, however the inhibition of PLK2 reversed IR-related increases in phosphorylated and total SNCA. Similarly, the overexpression of peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC)-1α suppressed ROS production, repressed PLK2 hyperactivity, and resulted in downregulation of total and Ser129-phosphorylated SNCA in the IR SH-SY5Y cells. Conclusions: These findings demonstrate that IR-associated diabetes promotes the development and progression of PD through PLK2-mediated mitochondrial dysfunction, upregulated ROS production, and enhanced SNCA signaling, suggesting the therapeutic targetability of PLK2 and/or SNCA as potential novel disease-modifying strategies in patients with PD.

Abstract Background Nonketotic hyperglycinemia is a severe form of early onset epileptic encephalopathy caused by disturbances in the glycine cleavage system; the neurological damage is mainly attributed to overstimulation of the N-methyl-D-aspartate receptor. Case The patient presented with a severe form of nonketotic hyperglycinemia and experienced frequent epileptic spasms and focal seizures, which were resistant to vigabatrin, adrenocorticotropic hormone therapy, and combined dextromethorphan and sodium benzoate treatments. By 9 months of age, perampanel reduced epileptic spasms by >50%. At 14 months of age, the ketogenic diet markedly reduced focal seizures and glycine levels in the cerebrospinal fluid. Conclusion Perampanel reduced fast excitatory neuronal activity, which was induced by an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, followed by prolonged electrical depolarizations due to an N-methyl-D-aspartate receptor. Furthermore, the ketogenic diet may have modulated the excessive neurotoxic cascade through the N-methyl-D-aspartate receptor. Perampanel and ketogenic diet were effective for seizure control in our patient.

Objectives: To describe and interpret previously unreported marks on the dry cranium of an adult chimpanzee (Pan troglodytes verus) from Côte d'Ivoire at the Smithsonian's National Museum of Natural History (USNM 450071). Materials and methods: All marks on the cranium were documented and assessed through physical examination of the specimen, photography, micro-computed tomography (micro-CT), and 3D laser scanning. Pits and punctures were measured with digital calipers for comparison with published carnivore tooth mark measurements. Results: The cranium shows perimortem or postmortem damage to the temporal, occipital, and maxillary regions that is not recent. Size and color variation in the marks suggest two damage events, possibly involving chewing by different animals, at least one of which was a large-bodied mammal. The 22 tooth pits and punctures (0.89-8.75 mm in maximum length and 0.88-6.63 mm in breadth) overlap in size with those inflicted by wild leopards, the most significant predators of common chimpanzees due to their largely overlapping ecological distributions. Conclusions: Based on qualitative and quantitative evidence, we conclude that leopards are the most likely cause of the most prominent marks on the cranium. However, we cannot rule out the additional possibility of other chimpanzees, although there are no published studies of chimpanzee tooth marks for direct comparison. This study is the most extensive documentation to date of a modern adult chimpanzee skull exhibiting tooth marks by a large mammal, thus providing new evidence to help identify and interpret other events of predation and scavenging of large-bodied apes in the modern and fossil records.

Dendritic cells play a key role in activation of the immune system as potent antigen-presenting cells. This pivotal position, along with the ability to generate dendritic cells from monocytes and ready uptake of antigen, makes them an intriguing vehicle for immunotherapy for a variety of indications. Since the first reported trial using dendritic cells in 1995, they have been used in trials all over the world for a plethora of indications. Monocyte-derived dendritic cells are generated from whole blood or apheresis products by culturing enriched monocytes in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). A variety of methods can be used for enrichment of monocytes for generation of clinical-grade dendritic cells and are summarized herein.

Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D7]glucose, [13C4]β-hydroxybutyrate and [3-13C]lactate before and after a 6-d KD. IHTG was determined by proton magnetic resonance spectroscopy (1H-MRS). The KD diet decreased IHTG by 31% in the face of a 3% decrease in body weight and decreased hepatic insulin resistance (−58%) despite an increase in NEFA concentrations (+35%). These changes were attributed to increased net hydrolysis of IHTG and partitioning of the resulting fatty acids toward ketogenesis (+232%) due to reductions in serum insulin concentrations (−53%) and hepatic citrate synthase flux (−38%), respectively. The former was attributed to decreased hepatic insulin resistance and the latter to increased hepatic mitochondrial redox state (+167%) and decreased plasma leptin (−45%) and triiodothyronine (−21%) concentrations. These data demonstrate heretofore undescribed adaptations underlying the reversal of NAFLD by KD: That is, markedly altered hepatic mitochondrial fluxes and redox state to promote ketogenesis rather than synthesis of IHTG.

The Greater Cape Floristic Region of South Africa was critical to the evolution of early modern humans (Homo sapiens) during the Pleistocene. The now submerged continental shelf formed its own ecosystem, the Palaeo-Agulhas Plain (PAP), where early humans lived and foraged. Grazing animals living on the plain might have migrated east and west tracking seasonally varying rains—a hypothesis tested here by examining δ13C and δ18O of serially-drilled teeth from seven ungulate genera: Alcelaphus, Connochaetes, Antidorcus, Redunca, Damaliscus, and Hippotragus. Modern observations and paleoecological reconstructions indicate that summer rainfall areas to the east have more C4 grasses while the winter rainfall areas to the west have more C3 grasses, and that summer and winter rains differ in δ18O. Thus, we analyze δ13C and δ18O preserved in herbivore teeth from the site of PP30 (a hyena den dating to ∼151 ka) to infer diet and water source throughout tooth formation. On a generic level, none of the samples exhibit δ13C or δ18O values that differ significantly from a taxon that likely foraged locally through the year (Southern reedbuck, Redunca arundium). Overall, results indicate that the PAP could support herbivore populations year-round without substantial migration, providing an ecosystem ideal for human inhabitants.

The use of ketogenic diet therapies (KDT) in adults has expanded in the last two decades and has been accompanied by a surge of new retrospective as well as prospective studies evaluating its efficacy in adults with epilepsy. In this review article, we will highlight the recent clinical trials and advances in the use of the ketogenic diet therapy (KDT) in adult patients with epilepsy. We will analyze the responder rate in regard to the epilepsy syndrome (focal vs generalized) to identify adults who are optimal to consider for KDT. In addition to its role in treating patients with chronic epilepsy, we will explore the emerging use of the KDT in the critical care setting in adults with refractory and super-refractory status epilepticus as well as other neurologic disorders. Finally, we will discuss special considerations for the use of KDT in adults with epilepsy including its potential long-term effects on bone and cardiovascular health, and its use in pregnancy.