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Title:
THE ROLE OF VITAMIN D IN THE PATHOGENESIS OF THE ARTERIAL HYPERTENSION
Authors:
Lystsova, N.; Petelina, Tatiana; Gapon, L.; Avdeeva, K.; Bucova, S.; Suplotov, S.
Abstract:
In recent years, accumulated numerous data on the pathogenetic links of the formation of arterial hypertension. A number of studies have shown that vitamin D deficiency, associated with age, changes in sex hormonal status, increased tone of the renin-angiotensin-aldosterone system, endothelial dysfunction, and calcium metabolism, can be one of the mechanisms of development and progression of arterial hypertension. The purpose of the review was to summarize the results of the original domestic and foreign studies, prospective observations and meta-analyzes on the relationship between vitamin D deficiency and arterial hypertension.
Published:
January 15, 2020
Title:
Neanderthal mobile toolkit in short-term occupations at Teixoneres Cave (Moià, Spain)
Authors:
Picin, Andrea; María Gema, Chacón; Gómez de Soler, Bruno; Blasco, Ruth; Rivals, Florent; Rosell Ardèvol, Jordi
Abstract:
Hunter-gatherers have a nomadic lifestyle and move frequently on the landscape based on the seasonal distribution of resources. During these displacements, carrying capacities are limited, and the composition of the transported gear is generally planned ahead of the activity to perform. During the Pleistocene, prehistoric hunter-gatherers faced similar difficulties in exploiting the territory and employed different strategies for coping with their subsistence needs and the possible shortage of stone tools. The understanding of how these behaviors developed diachronically is pivotal for the reconstruction of the human trajectories of land use in different environments, orographic settings, and climates. Thus far, the identification of the mobile toolkit has been related to blanks produced with allochthonous rocks, whereas the recognition of the transported artefacts knapped in local and semi-local raw materials encounters more difficulties because of the possible association with the lithic production conducted at the site. In this paper, we present the mobile toolkit of sub-unit IIIb and IIIa of Teixoneres Cave, a Middle Paleolithic site where a clear differentiation between in-situ knapping activities in local quartz and the import of stone tools in other raw materials is documented. The analysis of these latter assemblages reveals that the bulk of the toolkit is composed of knapping by-products and that the number of curated artefacts, Levallois flakes, and cores is significantly lower. Results show that the main strategy of transport at Teixoneres Cave was a combination of hunting and cutting tools aiming toward a generalized set of gears instead of narrowing the equipment to few specialized items. These new data highlight the plasticity of Neanderthals' technological organization in the western Mediterranean.
Published:
January 8, 2020
Title:
Cholesterol metabolism drives regulatory B cell function
Authors:
Bibby, Jack A.; Purvis, Harriet A.; Hayday, Thomas; Chandra, Anita; Okkenhaug, Klaus; Wood, Michael; Lachmann, Helen J.; Kemper, Claudia; Cope, Andrew P.; Perucha, Esperanza
Abstract:
Regulatory B cells restrict immune and inflammatory responses across a number of contexts. This capacity is mediated primarily through the production of IL-10. Here we demonstrate that the induction of a regulatory program in human B cells is dependent on a metabolic priming event driven by cholesterol metabolism. Synthesis of the metabolic intermediate geranylgeranyl pyrophosphate (GGPP) was required to specifically drive IL-10 production, and to attenuate Th1 responses. Furthermore, GGPP-dependent protein modifications controlled signaling through PI3Kδ-AKT-GSK3, which in turn promoted BLIMP1-dependent IL-10 production. Inherited gene mutations in cholesterol metabolism result in a severe autoinflammatory syndrome, termed mevalonate kinase deficiency (MKD). Consistent with our findings, B cells from MKD patients induced poor IL-10 responses and were functionally impaired. Moreover, metabolic supplementation with GGPP was able to reverse this defect. Collectively, our data define cholesterol metabolism as an integral metabolic pathway for the optimal functioning of human IL-10 producing regulatory B cells.
Published:
January 3, 2020
Title:
Cooked starchy rhizomes in Africa 170 thousand years ago
Authors:
Wadley, Lyn; Backwell, Lucinda; d’Errico, Francesco; Sievers, Christine
Abstract:
Middle Stone Age cooking Early evidence of cooked starchy plant food is sparse, yet the consumption of starchy roots is likely to have been a key innovation in the human diet. Wadley et al. report the identification of whole, charred rhizomes of plants of the genus Hypoxis from Border Cave, South Africa, dated up to 170,000 years ago. These archaeobotanical remains represent the earliest direct evidence for the cooking of underground storage organs. The edible Hypoxis rhizomes appear to have been cooked and consumed in the cave by the Middle Stone Age humans at the site. Hypoxis has a wide geographical distribution, suggesting that the rhizomes could have been a ready and reliable carbohydrate source for Homo sapiens in Africa, perhaps facilitating the mobility of human populations. Science, this issue p. 87 Plant carbohydrates were undoubtedly consumed in antiquity, yet starchy geophytes were seldom preserved archaeologically. We report evidence for geophyte exploitation by early humans from at least 170,000 years ago. Charred rhizomes from Border Cave, South Africa, were identified to the genus Hypoxis L. by comparing the morphology and anatomy of ancient and modern rhizomes. Hypoxis angustifolia Lam., the likely taxon, proliferates in relatively well-watered areas of sub-Saharan Africa and in Yemen, Arabia. In those areas and possibly farther north during moist periods, Hypoxis rhizomes would have provided reliable and familiar carbohydrate sources for mobile groups. Rhizomes cooked in a South African cave 90 to 170,000 years ago imply a reliable source of carbohydrate in the Middle Stone Age. Rhizomes cooked in a South African cave 90 to 170,000 years ago imply a reliable source of carbohydrate in the Middle Stone Age.
Published:
January 3, 2020
Title:
A descriptive and comparative study of two Early Pleistocene immature scapulae from the TD6.2 level of the Gran Dolina cave site (Sierra de Atapuerca, Spain)
Authors:
Bermúdez de Castro, José-María; Martínez de Pinillos, Marina; López-Polín, Lucía; Martín-Francés, Laura; Garcia, Cecilia; Modesto Mata, Mario; Rosell Ardèvol, Jordi; Martinón-Torres, María
Abstract:
Here we present the descriptive and comparative study of two immature scapulae recovered from the TD6.2 level of the Gran Dolina cave site (Sierra de Atapuerca, Spain) and assigned to Homo antecessor. This is the first time that data on the morphology and dimensions of the scapulae of a European late Early Pleistocene hominin population are provided. Considering the state of development and the linear dimensions, the scapula ATD6-116 could belong to a child of about 2-4 years. The morphology of ATD6-116 clearly departs from that of the Australopithecus afarensis juvenile specimen DIK-1-1, pointing to functional differences in locomotor behavior between Australopithecus and the late Early Pleistocene hominins. The immature scapula ATD6-118 belonged to an immature individual with a development of the scapula equivalent to that of adolescents of recent human populations. The scapulae ATD6-118 and KNM-WT 15000 present a similar state of development. Although the scapula KNM-WT 15000 is clearly larger than ATD6-118, these two specimens share some characteristics such as their relative narrowness and the value of the axilloglenoid and spinoglenoid angles. The glenoid fossa of ATD6-116 show a lateral orientation, whereas in ATD6-118 the glenoid fossa is slightly cranially oriented, but still within the range of variation of modern humans. The glenoid index of both ATD6-116 and ATD6-118 is low in accordance to the values usually observed in other early hominins, thus showing the primitive condition for this feature. Both scapulae show a ventrally placed axillary sulcus. The presence of this primitive feature in ATD-116 confirms that the shape of the axillary border has a genetic basis and it is not related to physical activity.
Published:
January 2, 2020
Title:
Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study
Authors:
Bahr, Lina Samira; Bock, Markus; Liebscher, Daniela; Bellmann-Strobl, Judith; Franz, Liane; Prüß, Alexandra; Schumann, Dania; Piper, Sophie K.; Kessler, Christian S.; Steckhan, Nico; Michalsen, Andreas; Paul, Friedemann; Mähler, Anja
Abstract:
Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression.
Published:
January 2, 2020
Title:
A comparative study of sulphated polysaccharide effects on advanced glycation end-product uptake and scavenger receptor class A level in macrophages
Authors:
Nishinaka, Takashi; Mori, Shuji; Yamazaki, Yui; Niwa, Atsuko; Wake, Hidenori; Yoshino, Tadashi; Nishibori, Masahiro; Takahashi, Hideo
Abstract:
Advanced glycation end-products, especially toxic advanced glycation end-products derived from glyceraldehyde (advanced glycation end-product-2) and glycolaldehyde (advanced glycation end-product-3), are biologically reactive compounds associated with diabetic complications. We previously demonstrated that toxic advanced glycation end-products were internalised into macrophage-like RAW264.7 cells through scavenger receptor-1 class A (CD204). Toxic advanced glycation end-product uptake was inhibited by fucoidan, a sulphated polysaccharide and antagonistic ligand for scavenger receptors, suggesting that sulphated polysaccharides are emerging candidates for treatment of advanced glycation end-product–related diseases. In this study, we compared the effects of six types of sulphated and non-sulphated polysaccharides on toxic advanced glycation end-product uptake in RAW264.7 cells. Fucoidan, carrageenan and dextran sulphate attenuated toxic advanced glycation end-product uptake. Fucoidan and carrageenan inhibited advanced glycation end-product-2–induced upregulation of SR-A, while advanced glycation end-product-3–induced upregulation of scavenger receptor-1 class A was only suppressed by fucoidan. Dextran sulphate did not affect scavenger receptor-1 class A levels in toxic advanced glycation end-product–treated cells. Chondroitin sulphate, heparin and hyaluronic acid failed to attenuate toxic advanced glycation end-product uptake. Heparin and hyaluronic acid had no effect on scavenger receptor-1 class A levels, while chondroitin sulphate inhibited advanced glycation end-product-3–induced upregulation of scavenger receptor-1 class A. Taken together, fucoidan and carrageenan, but not the other sulphated polysaccharides examined, had inhibitory activities on toxic advanced glycation end-product uptake and toxic advanced glycation end-product–induced upregulation of scavenger receptor-1 class A, possibly because of structural differences among sulphated polysaccharides.
Published:
January 1, 2020
Title:
Alternatively Activated Macrophages Are the Primary Retinoic Acid-Producing Cells in Human Decidua
Authors:
Rajakumar, Augustine; Kane, Maureen A.; Yu, Jianshi; Jones, Jace W.; Qu, Hongyan; Badell, Martina; Taylor, Robert N.; Sidell, Neil
Abstract:
In situ production and metabolism of all-trans retinoic acid (RA) in decidual tissue are critically important for endometrial stromal differentiation, embryo implantation, and healthy placentation. However, the cellular source(s) of RA in this tissue has yet to be determined. To identify the primary RA-producing cells in human term decidua, we isolated cells from decidua basalis of delivered placenta and quantified cellular retinal dehydrogenase (RALDH) activity, a major biosynthetic enzyme whose activity determines the synthesis of RA from retinol, using an Aldefluor assay and flow cytometry. RA production in decidual tissue and sorted cell subpopulations was evaluated by liquid chromatography-tandem mass spectrometry. CD14+ cells (macrophages/monocytes) showed > 4-fold higher RALDH activity than stromal cells (CD10+), T cells (CD3+), or non-T lymphocytes (CD3-negative). CD11c+ cells that did not co-express CD14 showed about one-third the RALDH activity of their CD14 co-expressing counterparts. The highest RALDH activity was found in “alternatively activated” M2 macrophages delineated by the simultaneous expression of CD14 and CD163. The greater RA synthesizing capacity of M2 versus CD14+CD163-ve (M1) cells was confirmed by direct quantitation of RA biosynthesis from retinol. RA levels in whole decidua were correlated with M2 cell density but not with stromal cell (CD10+) number, the major cell type comprising the decidua. These results identified M2 monocyte/macrophages as the primary source of RA in human term decidua. This finding may have implications for certain pregnancy complications that are known to be associated with reduced numbers of decidual M2 cells.
Published:
January 1, 2020
Title:
Dietary traits of ungulates in northeastern Iberian Peninsula: Did these Neanderthal preys show adaptive behaviour to local habitats during the Middle Palaeolithic?
Authors:
Sánchez-Hernández, Carlos; Gourichon, Lionel; Soler, Joaquim; Soler, Narcis; Blasco, Ruth; Rosell Ardèvol, Jordi; Rivals, Florent
Abstract:
Diet is closely connected to the habitat exploited by ungulates and is one of the main links between them and the surrounding environment. When climatic fluctuations modified the vegetal coverture and habitat, ungulates' dietary behaviours and ecological niches could have been impacted severely. During the Middle Palaeolithic, the Mediterranean peninsulas were known to be climatic refuges because they seemed less susceptible to these changes. However, the altitude or latitude of a given site may have resulted in local particularities that could have influenced the vegetal composition and therefore the feeding behaviour of ungulates from the same region. In the present research we investigate whether these variables necessitated adaptive changes in the feeding behaviours of ungulates hunted by Neanderthals through the study of two archaeological sites, Arbreda Cave (Serinyà, Girona, Spain) and Teixoneres Cave (Moià, Barcelona, Spain). We use a combined analysis of dental wear (meso- and microwear) and dental cementum analysis of Cervus elaphus, Equus ferus, and Equus hydruntinus teeth. Dental wear reflects the immediate and average annual dietary traits of ungulates as well as the environmental conditions in the surroundings. Dental cementum analysis allows accurately identifying the season of ungulate death and linking an individual's dietary preferences with the seasonal conditions in its last moments of life. As results, red deer at both sites were mixed-feeders in the annual cycle. A slight increase in grass consumption was identified during winter for populations from sub-unit IIIa of Teixoneres Cave. Horse and wild ass based their diet on grasses, but the latter showed seasonal adaptation toward a mixed consumption of grasses and concentrate resources (i.e. leaves, shrubs, forbs, and other woody plants). The seasonal feeding adaptations observed for some of the studied species did not strongly influence their general dietary trends because they kept feeding on the same resources annually.
Published:
January 1, 2020
Title:
Distinct patterns of interleukin-12/23 and tumor necrosis factor α synthesis by activated macrophages are modulated by glucose and colon cancer metabolites
Authors:
Huang, Ching-Ying; Yu, Linda Chia-Hui
Abstract:
Chronic inflammation is a major risk factor for colitis-associated colorectal carcinoma (CRC). Macrophages play a key role in altering the tumor microenvironment by producing pro-inflammatory and anti-inflammatory cytokines. Our previous studies showed that glucose metabolism conferred death resistance for tumor progression and exerted anti-inflammatory effects in ischemic gut mucosa. However, the effect of glucose and cancer metabolites in modulating macrophage cytokine profiles remains poorly defined. We used an in vitro system to mimic intestinal microenvironment and to investigate the roles of glucose and cancer metabolites in the cross-talk between carcinoma cells and macrophages. Human monocyte-derived THP-1 macrophages were stimulated with bacterial lipopolysaccharide (LPS) in the presence of conditioned media (CM) collected from human CRC Caco-2 cells incubated in either glucose-free or glucose-containing media. Our results demonstrated that glucose modulated the macrophage cytokine production, including decreased LPS-induced pro-inflammatory cytokines (i.e., tumor necrosis factor [TNF]α and interleukin [IL]-6) and increased anti-inflammatory cytokine (i.e., IL-10), at resting state. Moreover, glucose-containing CM reduced the macrophage secretion of TNFα and IL-8 but elevated the IL-12 and IL-23 levels, showing an opposite pattern of distinct pro-inflammatory cytokines modulated by cancer glucose metabolites. In contrast, LPS-induced production of macrophage inflammatory protein-1 (a macrophage-derived chemoattractant for granulocytes) was not altered by glucose or CM, indicating that resident macrophages may play a more dominant role than infiltrating granulocytes for responding to cancer metabolites. In conclusion, glucose metabolites from CRC triggered distinct changes in the cytokine profiles in macrophages. The downregulation of death-inducing TNFα and upregulation of Th1/17-polarizing IL-12/IL-23 axis in macrophages caused by exposure to cancer-derived glucose metabolites may contribute to tumor progression.
Published:
January 1, 2020
Title:
High-protein diet with renal hyperfiltration is associated with rapid decline rate of renal function: a community-based prospective cohort study
Authors:
Jhee, Jong Hyun; Kee, Youn Kyung; Park, Seohyun; Kim, Hyoungnae; Park, Jung Tak; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun
Abstract:
BACKGROUND: The effect of a high-protein diet with renal hyperfiltration (RHF) on decline of kidney function has rarely been explored. We investigated the association between a high-protein diet, RHF and declining kidney function. METHODS: A total of 9226 subjects from the Korean Genome and Epidemiology Study, a community-based prospective study (2001-14), were enrolled and classified into quartiles according to daily amount of protein intake based on food frequency questionnaires. RHF was defined as estimated glomerular filtration rate (eGFR) with residuals of >95th percentile after adjustment for age, sex, history of hypertension or diabetes, height and weight. Rapid decline of renal function was defined as decline rate of eGFR >3 mL/min/1.73 m2/year. RESULTS: The relative risk of RHF was 3.48-fold higher in the highest than in the lowest protein intake quartile after adjustment for confounding factors [95% confidence interval (CI) 1.39-8.71]. The mean eGFR decline rate was faster as quartiles of protein intake increased. Furthermore, the highest quartile was associated with 1.32-fold increased risk of rapid eGFR decline (95% CI 1.02-1.73). When subjects were divided into two groups with or without RHF, the highest quartile was associated with a rapid decline in renal function only in RHF subjects (odds ratio 3.35; 95% CI 1.07-10.51). The sensitivity analysis using the Korean National Health and Nutrition Examination Survey (2008-15) data with 40 113 subjects showed that higher quartile was associated with increased risk for RHF. CONCLUSIONS: A high-protein diet increases the risk of RHF and a rapid renal function decline in the general population. These findings suggest that a high-protein diet has a deleterious effect on renal function in the general population.
Published:
January 1, 2020
Title:
Late Pleistocene to Holocene human palaeoecology in the tropical environments of coastal eastern Africa
Authors:
Roberts, Patrick; Prendergast, Mary E.; Janzen, Anneke; Shipton, Ceri; Blinkhorn, James; Zech, Jana; Crowther, Alison; Sawchuk, Elizabeth A.; Stewart, Mathew; Ndiema, Emmanuel; Petraglia, Michael; Boivin, Nicole
Abstract:
The ecological adaptations that stimulated the dispersal and technological strategies of our species during the Late Pleistocene remain hotly disputed, with some influential theories focusing on grassland biomes or marine resources as key drivers behind the rapid expansion and material culture innovations of Homo sapiens within and beyond Africa. Here, we present novel chronologically resolved, zooarchaeological taxonomic and taphonomic analysis, and stable isotope analysis of human and faunal tooth enamel, from the site of Panga ya Saidi (c. 78–0.4 ka), Kenya. Zooarchaeological data provide rare insights into the fauna associated with, and utilized by, Late Pleistocene-Holocene human populations in tropical coastal eastern Africa. Combined zooarchaeological and faunal stable isotope data provide some of the only dated, ‘on-site’ archives of palaeoenvironments beyond the arid interior of eastern Africa for this time period, while stable isotope analysis of humans provides direct snapshots of the dietary reliance of foragers at the site. Results demonstrate that humans consistently utilized tropical forest and grassland biomes throughout the period of site occupation, through a transition from Middle Stone Age to Later Stone Age technological industries and the arrival of agriculture in the region. By contrast, while coastal resources were obtained for use in symbolic material culture, there is limited evidence for consumption of marine resources until the Holocene. We argue that the ecotonal or heterogeneous environments of coastal eastern Africa may have represented an important refugium for populations during the increasing climatic variability of the Late Pleistocene and Holocene, and that tropical environments were one of a diverse series of ecosystems exploited by H. sapiens in Africa at the dawn of global migrations.
Published:
January 1, 2020
Title:
Long-term use of antipsychotics and antidepressants is not evidence-based
Authors:
Gøtzsche, Peter C.
Abstract:
BACKGROUND: The widespread use of psychiatric drugs does not appear to be evidence-based but seems to be driven mainly by commercial pressures. I studied whether two widely differing drug classes, antipsychotics and antidepressants, showed similar pa
Published:
January 1, 2020
Title:
Presentation of benefits and harms of antidepressants on websites: A cross sectional study
Authors:
Demasi, Maryanne; Gøtzsche, Peter C.
Abstract:
BACKGROUND: Many people use the Internet for obtaining information about their medications. OBJECTIVE: To investigate whether information about antidepressants on popular websites reflects the scientific evidence and enables people to make informed c
Published:
January 1, 2020
Title:
Self-Management of Type 2 Diabetes in Adult Haitian Immigrants: A Qualitative Study
Authors:
Magny-Normilus, Cherlie; Mawn, Barbara; Dalton, Joanne
Abstract:
Introduction: A large body of literature exists on self-management of type 2 diabetes (T2D) in a variety of populations. However, research is limited on how Haitian immigrants self-manage their T2D despite a prevalence of 6.9% in Haiti. The purpose of this study was to explore and describe the lived experience of adult Haitian immigrants managing T2D living in the United States. Methodology: Moustakas’s phenomenological approach guided this qualitative study. Adult Haitian immigrants diagnosed with T2D for at least 1 year were interviewed. Individual interviews were audio-recorded, transcribed verbatim, uploaded into NVivo, and analyzed using Moustakas’s existential data analysis process. Results: We interviewed 16 participants (mean age 56;12 females; an average of 11 years living in the United States; mean hemoglobin A1c 8.1%). Four themes emerged: self-reliance, spirituality, nostalgia for home, and a desire for positive patient–provider relationships. Cultural influences and health beliefs may affect individual self-management of T2D in this population. Conclusions: These results may assist clinicians in identifying factors that contribute to suboptimal self-management in Haitian immigrants and help patients reach glycemic control. Culturally competent assessment and interventions for Haitian immigrants with T2D may not be provided without considering these four themes.
Published:
January 1, 2020
Title:
Short-Term Neanderthal Occupations and Carnivores in the Northeast of Iberian Peninsula
Authors:
Picin, Andrea; Blasco, Ruth; Arilla, Maite; Rivals, Florent; María Gema, Chacón; Gómez de Soler, Bruno; Talamo, Sahra; Rosell Ardèvol, Jordi
Abstract:
Short-term human occupations could occur in very distinct places and be related to very different behaviours. The low number of items left by the human groups in these sites, usually, generates discrete assemblages, which often are difficult to disentangle. In the European Middle Palaeolithic, short-term human occupations in caves and rock-shelters, frequented by carnivores as hibernation places, dens or refuges, are common. From an archaeological perspective, the resulting assemblages are a mixture of anthropogenic and carnivore items (palimpsests) in which the intensity of human occupation(s) is usually measured by the quantity of recovered lithic artefacts, hearths or modified bones. The detailed study of these sites is pivotal to understand the development of the human communities in a landscape, their movements across the territory, the diversity of activities performed and the relationships stablished within the other biological entities (mainly carnivores). This paper aims to present data on four Middle Palaeolithic sites in the Northeast of the Iberian Peninsula characterized by short-term occupations in carnivore contexts. The results indicate a complex scenario in terms of settlement patterns and movements of Neanderthals in mountainous environments ranging from occasional visits to carnivore dens for hunting or active scavenging to full-scale, planned occupations during the course of seasonal foraging activities.
Published:
January 1, 2020
Title:
The association of nativity/length of residence and cardiovascular disease risk factors in the United States
Authors:
Fryar, Cheryl D.; Fakhouri, Tala H.; Carroll, Margaret D.; Frenk, Steven M.; Ogden, Cynthia L.
Abstract:
Differences by nativity status for cardiovascular disease (CVD) risk factors have been previously reported. Recent research has focused on understanding how other acculturation factors, such as length of residence, affect health behaviors and outcomes. This study examines the association between CVD risk factors and nativity/length of US residence. Using cross-sectional data from 15,965 adults in the 2011–2016 National Health and Nutrition Examination Surveys (analyzed in 2018), prevalence ratios and predicted marginals from logistic regression models are used to estimate associations of CVD risk factors (i.e., hypertension, hypercholesterolemia, diabetes, overweight/obesity and smoking) with nativity/length of residence (<15 years, ≥15 years) in the US. In sex-, age-, education- and race and Hispanic origin- adjusted analyses, a higher percentage of US (50 states and District of Columbia) born adults (86.4%) had ≥1 CVD risk factor compared to non-US born residents in the US <15 years (80.1%) but not ≥15 years (85.1%). Compared to US born counterparts, regardless of length of residence, hypertension overall and smoking among non-Hispanic white and Hispanic adults were lower among non-US born residents. Overweight/obesity overall and diabetes among Hispanic adults were lower among non-US born residents in the US <15 years. In contrast, non-US born non-Hispanic Asian residents in the US
Published:
January 1, 2020
Title:
Edible Insects and Human Evolution (Book Review)
Authors:
Pobiner, Briana
Abstract:
book review of Edible Insects and Human Evolution by Julie Lesnik
Published:
December 30, 2019
Title:
Pharmacist-led therapeutic carbohydrate restriction as a treatment strategy for type 2 diabetes: the Pharm-TCR randomized controlled trial protocol
Authors:
Durrer, Cody; McKelvey, Sean; Singer, Joel; Batterham, Alan M.; Johnson, James D.; Wortman, Jay; Little, Jonathan P.
Abstract:
BACKGROUND: The current treatment paradigm for type 2 diabetes mellitus (T2D) typically involves use of multiple medications to lower glucose levels in hope of reducing long-term complications. However, such treatment does not necessarily address the underlying pathophysiology of the disease and very few patients achieve partial, complete, or prolonged remission of T2D after diagnosis. The therapeutic potential of nutrition has been highlighted recently based on results of clinical trials reporting remission of T2D with targeted dietary approaches. During the initial phase of such interventions that restrict carbohydrates and/or induce rapid weight loss, hypoglycemia presents a notable risk to patients. We therefore hypothesized that delivering very low-carbohydrate, low-calorie therapeutic nutrition through community pharmacies would be an innovative strategy to facilitate lowering of glycated hemoglobin (A1C) while safely reducing the use of glucose-lowering medications in T2D. METHODS: A community-based randomized controlled trial that is pragmatic in nature, following a parallel-group design will be conducted (N = 200). Participants will have an equal chance of being randomized to either a pharmacist-led, therapeutic carbohydrate restricted (Pharm-TCR) diet or guideline-based treatment as usual (TAU). Pharm-TCR involves a 12-week very low carbohydrate, calorie-restricted commercial diet plan led by pharmacists and lifestyle coaches with pharmacists responsible for managing medications in collaboration with the participants' family physicians. Main inclusion criteria are diagnosis of T2D, currently treated with glucose-lowering medications, age 30-75 years, and body mass index ≥ 30. The primary outcome is a binary measure of use of glucose-lowering medication. Secondary outcomes include A1C, anthropometrics and clinical blood markers. DISCUSSION: There are inherent risks involved if patients with T2D who take glucose-lowering medications follow very low carbohydrate diets. This randomized controlled trial aims to determine whether engaging community pharmacists is a safe and effective way to deliver therapeutic carbohydrate restriction and reduce/eliminate the need for glucose-lowering medications in people with T2D. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03181165. Registered on 8 June 2017.
Published:
December 27, 2019
Title:
Changes in Food Cravings and Eating Behavior after a Dietary Carbohydrate Restriction Intervention Trial
Authors:
Anguah, Katherene O.-B.; Syed-Abdul, Majid M.; Hu, Qiong; Jacome-Sosa, Miriam; Heimowitz, Colette; Cox, Vicki; Parks, Elizabeth J.
Abstract:
Compared to low-fat diets, low-carbohydrate (CHO) diets cause weight loss (WL) over a faster time frame; however, it is unknown how changes in food cravings and eating behavior contribute to this more rapid WL in the early phases of dieting. We hypothesized that reductions in food cravings and improved eating behaviors would be evident even after a relatively short (4-week) duration of CHO-restriction, and that these changes would be associated with WL. Adult participants (n = 19, 53% males, mean ± SD: BMI = 34.1 ± 0.8 kg/m2; age 40.6 ± 1.9 years) consumed a CHO-restricted diet (14% CHO, 58% fat, 28% protein) for 4 weeks. Before and after the intervention, specific and total cravings were measured with the Food Craving Inventory (FCI) and eating behaviors assessed with the Three-Factor Eating questionnaire. Food cravings were significantly reduced at week 4, while women had significantly greater reductions in sweet cravings than men. Dietary restraint was significantly increased by 102%, while disinhibiton and hunger scores were reduced (17% and 22%, respectively, p
Published:
December 24, 2019
Title:
38-Month Long Progression-Free and Symptom-Free Survival of a Patient With Recurrent Glioblastoma Multiforme: A Case Report of the Paleolithic Ketogenic Diet (PKD) Used As a Stand-Alone Treatment after Failed Standard Oncotherapy
Authors:
Tóth, Csaba; Dabóczi, Andrea; Chanrai, Madhvi; Schimmer, Mária; Clemens, Zsófia
Abstract:
Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 38 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.
Published:
December 20, 2019
Title:
Association Between Use of Multiple Classes of Antibiotic in Infancy and Allergic Disease in Childhood
Authors:
Zven, Sidney E.; Susi, Apryl; Mitre, Edward; Nylund, Cade M.
Abstract:
Antibiotic administration negatively affects the microbiome by decreasing bacterial diversity, and this has been associated with allergic disease. Exposure to multiple classes of antibiotics may lead to even greater perturbations to the gut biome than 1 class alone. The purpose of this study is to determine whether exposure to multiple antibiotic classes in infancy is associated with a higher risk of developing allergic disease in early childhood.
Published:
December 20, 2019
Title:
Association between diabetes and mood disorders and the potential use of anti-hyperglycemic agents as antidepressants.
Authors:
Grigolon, Ruth B.; Brietzke, Elisa; Mansur, Rodrigo B.; Idzikowski, Maia A.; Gerchman, Fernando; De Felice, Fernanda G.; McIntyre, Roger S.
Abstract:
Epidemiological and mechanistic studies support the association between Diabetes Mellitus and mood disorders, such as Major Depressive Disorder and Bipolar Disorder. This association is especially relevant in specific domains of depressive psychopathology, such as disturbances in reward systems and cognitive functions. Several anti-hyperglycemic agents have demonstrated effects on depressive symptoms and cognitive decline and this efficacy is probably the result of an action in shared brain targets between these two groups of conditions. These medications include subcutaneous insulin, intranasal insulin, metformin, and liraglutide. The study of the mechanisms involved in the relationship between Diabetes Mellitus and mood disorders offers a new avenue of investigation, and this understanding can be applied when examining whether antidiabetic agents can be repurposed as antidepressants and mood stabilizers. The objective of this narrative review is to critically appraise the literature surrounding drugs commonly used as anti-hyperglycemic agents and their effects on the brain, while discussing their potential as a new treatment for mental illnesses, and specifically, mood disorders.
Published:
December 20, 2019
Title:
Close to half of U.S. population projected to have obesity by 2030
Authors:
Communications, Nicole Rura Harvard Chan School
Abstract:
Researchers predict a marked rise in American adults with obesity or severe obesity in 10 years, leaving several states with obesity prevalence close to 60 percent.
Published:
December 18, 2019
Title:
Animal painting found in cave is 44,000 years old
Authors:
Abstract:
Experts say the art, found in an Indonesian cave, could be the world's oldest recorded story.
Published:
December 12, 2019
Title:
Deep learning and taphonomy: high accuracy in the classification of cut marks made on fleshed and defleshed bones using convolutional neural networks
Authors:
Cifuentes-Alcobendas, Gabriel; Domínguez-Rodrigo, Manuel
Abstract:
Accurate identification of bone surface modifications (BSM) is crucial for the taphonomic understanding of archaeological and paleontological sites. Critical interpretations of when humans started eating meat and animal fat or when they started using stone tools, or when they occupied new continents or interacted with predatory guilds impinge on accurate identifications of BSM. Until now, interpretations of Plio-Pleistocene BSM have been contentious because of the high uncertainty in discriminating among taphonomic agents. Recently, the use of machine learning algorithms has yielded high accuracy in the identification of BSM. A branch of machine learning methods based on imaging, computer vision (CV), has opened the door to a more objective and accurate method of BSM identification. The present work has selected two extremely similar types of BSM (cut marks made on fleshed an defleshed bones) to test the immense potential of artificial intelligence methods. This CV approach not only produced the highest accuracy in the classification of these types of BSM until present (95% on complete images of BSM and 88.89% of images of only internal mark features), but it also has enabled a method for determining which inconspicuous microscopic features determine successful BSM discrimination. The potential of this method in other areas of taphonomy and paleobiology is enormous.
Published:
December 12, 2019
Title:
Psoriasis and Metabolic Syndrome: Comorbidities and Environmental and Therapeutic Implications
Authors:
Peralta, Cesar; Hamid, Pousette; Batool, Humera; Al Achkar, Zeina; Maximus, Pierre
Abstract:
Psoriasis (PS) is an incessant, fiery skin sickness characterized by erythematous plaques with thick silvery scales, white or red patches of the skin, which encompasses several immunological, biomolecular, genetic, and environmental factors that may lead to further development of metabolic syndrome (MS) and vice versa. Metabolic syndrome is composed of multiple components (high blood pressure, abdominal obesity, glucose intolerance, and dyslipidemia) of risk factors that arise primarily from insulin resistance, mostly mediated by inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) together with leptin and adiponectin, which are molecules also found in PS. The incidence, severity, and poor prognosis of the psoriatic diseases could be influenced by cardiometabolic diseases, which are controllable or preventable with intense lifestyle modification such as diet, exercise, and weight control. We performed a far-reaching writing search of different databases as part of this review; 47 investigations were regarded as important based on our search. Fasting, proper weight management, and special diet modifications seemed to have a positive impact on the management of PS. This review agrees with previous literature that nutritionists and specialists of preventive medicine should play a central role in the evaluation and management of psoriatic patients. We recommended that the management of this disease should focus on the environmental factors first instead of the genetic and immunologic pathways.
Published:
December 12, 2019
Title:
The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed
Authors:
Ludwig, David S.
Abstract:
For >50 y, dietary guidelines in the United States have focused on reducing intakes of saturated and total fat. However, rates of obesity and diabetes rose markedly throughout this period, with potentially catastrophic implications for public health and the economy. Recently, ketogenic diets have received substantial attention from the general public and nutrition research community. These very-low-carbohydrate diets, with fat comprising >70% of calories, have been dismissed as fads. However, they have a long history in clinical medicine and human evolution. Ketogenic diets appear to be more effective than low-fat diets for treatment of obesity and diabetes. In addition to the reductions in blood glucose and insulin achievable through carbohydrate restriction, chronic ketosis might confer unique metabolic benefits of relevance to cancer, neurodegenerative conditions, and other diseases associated with insulin resistance. Based on available evidence, a well-formulated ketogenic diet does not appear to have major safety concerns for the general public and can be considered a first-line approach for obesity and diabetes. High-quality clinical trials of ketogenic diets will be needed to assess important questions about their long-term effects and full potential in clinical medicine.
Published:
December 11, 2019
Title:
38-month long progression-free and symptom-free survival of a patient with recurrent glioblastoma multiforme: A case report of the Paleolithic Ketogenic Diet (PKD) used as a stand-alone treatment after failed standard oncotherapy
Authors:
Tóth, Csaba; Dabóczi, Andrea; Chanrai, Madhvi; Schimmer, Mária; Clemens, Zsofia
Abstract:
Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 38 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.
Published:
December 9, 2019
Title:
Differential Responses of Blood Essential Amino Acid Levels Following Ingestion of High-Quality Plant-Based Protein Blends Compared to Whey Protein—A Double-Blind Randomized, Cross-Over, Clinical Trial
Authors:
Brennan, Jessica L.; Keerati-u-rai, Maneephan; Yin, Huaixia; Daoust, Julie; Nonnotte, Emilie; Quinquis, Laurent; St-Denis, Thierry; Bolster, Douglas R.
Abstract:
This study assessed the bio-equivalence of high-quality, plant-based protein blends versus Whey Protein Isolate (WPI) in healthy, resistance-trained men. The primary endpoint was incremental area under the curve (iAUC) of blood essential Amino Acids (eAAs) 4 hours after consumption of each product. Maximum concentration (Cmax) and time to maximum concentration (Tmax) of blood leucine were secondary outcomes. Subjects (n = 18) consumed three plant-based protein blends and WPI (control). An analysis of Variance model was used to assess for bio-equivalence of total sum of blood eAA concentrations. The total blood eAA iAUC ratios of the three blends were [90% CI]: #1: 0.66 [0.58–0.76]; #2: 0.71 [0.62–0.82]; #3: 0.60 [0.52–0.69], not completely within the pre-defined equivalence range [0.80–1.25], indicative of 30–40% lower iAUC versus WPI. Leucine Cmax of the three blends was not equivalent to WPI, #1: 0.70 [0.67–0.73]; #2: 0.72 [0.68–0.75]; #3: 0.65 [0.62–0.68], indicative of a 28–35% lower response. Leucine Tmax for two blends were similar to WPI (#1: 0.94 [0.73–1.18]; #2: 1.56 [1.28–1.92]; #3: 1.19 [0.95–1.48]). The plant-based protein blends were not bio-equivalent. However, blood leucine kinetic data across the blends approximately doubled from fasting concentrations, whereas blood Tmax data across two blends were similar to WPI. This suggests evidence of rapid hyperleucinemia, which correlates with a protein’s anabolic potential.
Published:
December 6, 2019
Title:
Differential Responses of Blood Essential Amino Acid Levels Following Ingestion of High-Quality Plant-Based Protein Blends Compared to Whey Protein—A Double-Blind Randomized, Cross-Over, Clinical Trial
Authors:
Brennan, Jessica L.; Keerati-u-rai, Maneephan; Yin, Huaixia; Daoust, Julie; Nonnotte, Emilie; Quinquis, Laurent; St-Denis, Thierry; Bolster, Douglas R.
Abstract:
This study assessed the bio-equivalence of high-quality, plant-based protein blends versus Whey Protein Isolate (WPI) in healthy, resistance-trained men. The primary endpoint was incremental area under the curve (iAUC) of blood essential Amino Acids (eAAs) 4 hours after consumption of each product. Maximum concentration (Cmax) and time to maximum concentration (Tmax) of blood leucine were secondary outcomes. Subjects (n = 18) consumed three plant-based protein blends and WPI (control). An analysis of Variance model was used to assess for bio-equivalence of total sum of blood eAA concentrations. The total blood eAA iAUC ratios of the three blends were [90% CI]: #1: 0.66 [0.58–0.76]; #2: 0.71 [0.62–0.82]; #3: 0.60 [0.52–0.69], not completely within the pre-defined equivalence range [0.80–1.25], indicative of 30–40% lower iAUC versus WPI. Leucine Cmax of the three blends was not equivalent to WPI, #1: 0.70 [0.67–0.73]; #2: 0.72 [0.68–0.75]; #3: 0.65 [0.62–0.68], indicative of a 28–35% lower response. Leucine Tmax for two blends were similar to WPI (#1: 0.94 [0.73–1.18]; #2: 1.56 [1.28–1.92]; #3: 1.19 [0.95–1.48]). The plant-based protein blends were not bio-equivalent. However, blood leucine kinetic data across the blends approximately doubled from fasting concentrations, whereas blood Tmax data across two blends were similar to WPI. This suggests evidence of rapid hyperleucinemia, which correlates with a protein’s anabolic potential.
Published:
December 6, 2019
Title:
Lixisenatide attenuates advanced glycation end products (AGEs)-induced degradation of extracellular matrix in human primary chondrocytes
Authors:
Li, Xin; Jia, Fangteng; Zhu, Zhengqing; Huang, Lanfeng
Abstract:
Osteoarthritis (OA) poses a growing threat to the health of the global population. Accumulation of advanced glycation end-products (AGEs) has been shown to upregulate expression of degradative enzymes such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in chondrocytes, which leads to excessive degradation of type II collagen and aggrecan in the articular extracellular matrix (ECM). In the present study we investigated the effects of the GLP-1 agonist lixisenatide, a widely used type II diabetes medication, on AGEs-induced decreased mitochondrial membrane potential (MMP), degradation of ECM, oxidative stress, expression of cytokines including interleukin (IL)-1β and IL-6, and activation of nuclear factor kappa B (NF-κB). Our findings indicate that lixisenatide significantly ameliorated the deleterious effects of AGEs in a dose-dependent manner. Thus, lixisenatide has potential as a safe and effective treatment for OA and other AGEs-induced inflammatory diseases.
Published:
December 4, 2019
Title:
Insulin as an immunomodulatory hormone
Authors:
van Niekerk, Gustav; Christowitz, Claudia; Conradie, Daleen; Engelbrecht, Anna-Mart
Abstract:
Insulin plays an indispensable role in the management of hyperglycaemia that arises in a variety of settings, including Type I and II diabetes, gestational diabetes, as well as is in hyperglycaemia following a severe inflammatory insult. However, insulin receptors are also expressed on a range of cells that are not canonically implicated in glucose homeostasis. This includes immune cells, where the anti-inflammatory effects of insulin have been repeatedly reported. However, recent findings have also implicated a more involved role for insulin in shaping the immune response during an infection. This includes the ability of insulin to modulate immune cell differentiation and polarisation as well as the modulation of effector functions such as biocidal ROS production. Finally, inflammatory mediators can through both direct and indirect mechanisms also regulate serum insulin levels, suggesting that insulin may be co-opted by the immune system during an infection to direct immunological operations. Collectively, these observations implicate insulin as a bona fide immune-modulating hormone and suggest that a better understanding of insulin’s immunological function may aid in optimising insulin therapy in a range of clinical settings.
Published:
December 3, 2019
Title:
Late life metformin treatment limits cell survival and shortens lifespan by triggering an aging-associated failure of energy metabolism
Authors:
Espada, Lilia; Dakhovnik, Alexander; Chaudhari, Prerana; Martirosyan, Asya; Miek, Laura; Poliezhaieva, Tetiana; Schaub, Yvonne; Nair, Ashish; Döring, Nadia; Rahnis, Norman; Werz, Oliver; Koeberle, Andreas; Kirkpatrick, Joanna; Ori, Alessandro; Ermolaeva, Maria A.
Abstract:
Summary The diabetes drug metformin is to be clinically tested in aged humans to achieve health span extension, but little is known about responses of old non-diabetic individuals to this drug. By in vitro and in vivo tests we found that metformin shortens life span and limits cell survival when provided in late life, contrary to its positive early life effects. Mechanistically, metformin exacerbates aging-associated mitochondrial dysfunction towards respiratory failure, aggravated by the inability of old cells to upregulate glycolysis in response to metformin, leading to ATP exhaustion. The beneficial dietary restriction effect of metformin on lipid reserves is abrogated in old animals, contributing to metabolic failure, while ectopic stabilization of cellular ATP levels alleviates late life metformin toxicity in vitro and in vivo . The toxicity is also suspended in nematodes carrying diabetes-like insulin receptor insufficiency and showing prolonged resilience to metabolic stress induced by metformin. In sum, we uncovered an alarming metabolic decay triggered by metformin in late life which may limit its benefits for non-diabetic elderly patients. Novel regulators of life extension by metformin are also presented. Highlights Late life metformin treatment limits cell survival and shortens lifespan. Metformin exacerbates aging-associated mitochondrial dysfunction causing fatal ATP exhaustion. Old cells fail to upregulate glycolysis as a compensatory response to metformin. The dietary restriction (DR) mimetic response to metformin is abrogated in old animals. PKA and not AMPK pathway instigates the early life DR response to metformin. Stabilization of cellular ATP levels alleviates late life metformin toxicity in vitro and in vivo .
Published:
December 3, 2019
Title:
Data set for characterization of the glycosylation status of hepatic glycoproteins in mice fed a low-carbohydrate ketogenic diet
Authors:
Okuda, Tetsuya
Abstract:
The data presented herein pertain to a research article entitled “A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes” [1]. The present article provides additional structural analysis data for the characterization of hepatic glycoproteins in mice fed a low-carbohydrate ketogenic diet (LCKD). Analysis of hepatic glycoproteins by enzyme-linked assay using the lectins UEA-I, ConA, LCA, and WGA showed that the LCKD decreased mature forms of complex-type glycans but increased immature forms of glycans on glycoproteins. An enzyme-linked immunosorbent assay using an anti–α2,6-sialyl LacNAc antibody also supported this result, indicating that dietary carbohydrate restriction results in aberrant glycosylation of tissue glycoproteins. These structural alterations of hepatic glycoproteins were not correlated with the expression levels of glycosyltransferase genes but were correlated with down-regulated expression of the Gale gene, which encodes a rate-limiting enzyme for the synthesis of sugar nucleotide donors for protein glycosylation in the liver. This property differed from glycosphingolipid metabolism in the liver of LCKD-fed mice.
Published:
December 1, 2019
Title:
Factors Impacting Adherence to Diabetes Medication Among Urban, Low Income Mexican-Americans with Diabetes
Authors:
Baghikar, Sara; Benitez, Amanda; Fernandez Piñeros, Patricia; Gao, Yue; Baig, Arshiya A.
Abstract:
Mexican-Americans carry a high burden of type 2 diabetes and are disproportionately affected by diabetes related mortality and morbidity. Poor adherence to medication is an important barrier to achieving metabolic control and contributes to adverse health outcomes and health disparities. Little is known about barriers and facilitators to medication adherence among Mexican-Americans with diabetes. This is a qualitative study of semi-structured interviews with a sample of 27 adults (25 Mexican-Americans and 2 Latinos of other origin) with self-reported type 2 diabetes who were recruited as part of a church-based, randomized controlled trial for diabetes self-management education in a low-income, immigrant neighborhood of Chicago. Face-to-face, in-depth interviews were conducted (one in English and 26 in Spanish), audio-recorded, transcribed verbatim, and professionally translated. Systematic qualitative methods were used to analyze interviews. All 27 participants were Latino, and 25 were of Mexican descent. Participants’ mean age was 57 years, 81% were female, 69% had an annual income less than $20,000 and 48% had no health insurance. Mean A1C level was 8.6% and mean systolic blood pressure was 125 mmHg. The majority of participants (85%) reported using oral diabetes medication and 35% reported taking insulin. 76% reported being affiliated with one of the two partnering catholic churches based in the South Lawndale neighborhood of Chicago, also known as Little Village. Concerns regarding effectiveness and negative impact of diabetes medication were prevalent and expressed by 13 (48%) of 27 participants. Dissatisfaction with ineffective provider communication and not being able to pay for medication were other important barriers to adherence and were expressed by 7% and 11% of participants, respectively. Family support, for example, family members assisting in organizing medications in boxes and reminding participants to take them, was reported by 15% of participants and emerged as an important facilitator to medication adherence. There is a gap in research on factors influencing adherence to diabetes medication among Mexican-Americans. Our study suggests that concerns regarding negative impact of diabetes medication and concerns regarding effectiveness are prevalent barriers to adherence. These barriers can be addressed through educational efforts targeting patients and clinicians by specifically including content on beliefs that lead to poor adherence in diabetes self-management interventions for patients and continuing medical education for providers and by developing interventions that engage family members as a support system for medication adherence.
Published:
December 1, 2019
Title:
First use of anatomical networks to study modularity and integration of heads, forelimbs and hindlimbs in abnormal anencephalic and cyclopic vs normal human development
Authors:
Diogo, Rui; Ziermann, Janine; Smith, Christopher; Alghamdi, Malak; Fuentes, Jose; Duerinckx, Andre
Abstract:
The ill-named “logic of monsters” hypothesis of Pere Alberch - one of the founders of modern evo-devo - emphasized the importance of “internal rules” due to strong developmental constraints, linked teratologies to developmental processes and patterns, and contradicted hypotheses arguing that birth defects are related to a chaotic and random disarray of developmental mechanisms. We test these hypotheses using, for the first time, anatomical network analysis (AnNA) to study and compare the musculoskeletal modularity and integration of both the heads and the fore- and hindlimbs of abnormal cyclopic trisomy 18 and anencephalic human fetuses, and of normal fetal, newborn, and adult humans. Our previous works have shown that superficial gross anatomical analyses of these specimens strongly support the “logic of monsters” hypothesis, in the sense that there is an ‘order’ or ‘logic’ within the gross anatomical patterns observed in both the normal and abnormal individuals. Interestingly, the results of the AnNA done in the present work reveal a somewhat different pattern: at least concerning the musculoskeletal modules obtained in our AnNA, we observe a hybrid between the “logic of monsters” and the “lack of homeostasis” hypotheses. For instance, as predicted by the latter hypothesis, we found a high level of left-right asymmetry in the forelimbs and/or hindlimbs of the abnormal cyclopic trisomy 18 and anencephalic human fetuses. That is, a network analysis of the organization of/connection between the musculoskeletal structures of these fetuses reveals a more “chaotic” pattern than that detected by superficial gross anatomical comparisons. We discuss the broader developmental, evolutionary, and medical implications of these results.
Published:
December 1, 2019
Title:
Voltage-gated sodium channel inhibitor reduces atherosclerosis by modulating monocyte/macrophage subsets and suppressing macrophage proliferation
Authors:
Sun, Haiying; Jiang, Jipeng; Gong, Lei; Li, Xiao; Yang, Yang; Luo, Yuechen; Guo, Zhaozeng; Lu, Ruiyi; Li, Hongxia; Li, Jinlong; Zhao, Jihong; Yang, Ning; Li, Yuming
Abstract:
Inflammatory monocyte and macrophage subset accumulation during the inflammatory response that drives atherosclerosis can exacerbate the extent of atherosclerosis. It has been demonstrated that voltage-gated sodium channels (VGSCs) can regulate cell bioactivities in monocytes/macrophages. We hypothesized that blockade of mononuclear phagocyte VGSCs was atheroprotective through monocyte/macrophage subset modulation and macrophage proliferation suppression in atherosclerotic lesions. In this experimental study, when VGSCs were knocked down with RNA interference plasmid transfection in mouse peripheral blood monocytes and monocyte-macrophage lineage RAW264.7 cells in vitro, the biological characteristics of proliferation, phagocytosis, and migration in RAW264.7 cells declined. In addition, suppression of LPS-induced M1 polarization and facilitation of IL-4-induced M2 polarization were also observed. In an in vivo study, ApoE knockout (ApoE−/−) mice were fed a standard chow diet (CD) or a western diet (WD). After feeding with phenytoin (PHT), no significant differences were detected in plasma lipids, and the anti-inflammatory phenotypes of both monocytes and macrophages were elevated and proinflammatory phenotypes declined. The local proliferation of macrophages was also distinctly suppressed, along with a significant reduction in atheromatous plaques. In conclusion, blockade of VGSCs in the mononuclear phagocyte system reduced atherosclerotic lesions, which may occur through altering monocyte/macrophage subsets and suppressing macrophage proliferation in atherosclerotic plaques. Blockage of VGSCs may play an important role in cardiovascular protection.
Published:
December 1, 2019
Title:
The role of exposome in acne: results from an international patient survey
Authors:
Dreno, Brigitte; Shourick, Jason; Kerob, Delphine; Bouloc, Anne; Taïeb, Charles
Abstract:
Background: Acne severity and its response to treatment may be influenced by internal and external factors: the exposome. Objectives: The aim of this international real-life survey was to assess the most involved exposome factors in acne. Methods: 11000 individuals, aged between 15 and 39 years, with clinically confirmed acne or without acne, defined by age, gender and prevalence, were invited to participate in an internet survey of 63 questions in order to assess the frequency of identified acne exposome factors. Results: Data from 6679 questionnaires were used for statistical analysis purposes: 2826 from the acne group and 3853 from the control group. Nibbling, consumption of dairy products, sweets, alcohol, or whey proteins, as well as exposure to pollution, stress, certain mechanical factors and humid or hot weather or sun exposure, were significantly (all P≤0.05) more frequently reported for the acne group than for the control group. This was not the case for tobacco consumption. Data regarding the impact of cannabis consumption were insufficient for drawing any conclusions. Conclusions: Data from this international, anonymized internet questionnaire conducted with more than almost 6700 participants add new arguments to assumptions made that certain exposome factors have an impact on acne. Nutrition, pollution, stress and harsh skin care, as well as climate and sun exposure may be considered the most frequent factors related to acne.
Published:
November 30, 2019
Title:
The Space Between: Transformative Learning and Type 2 Diabetes Self-Management
Authors:
Smith-Miller, Cheryl A.; Berry, Diane C.; Miller, Cass T.
Abstract:
Introduction:Immigrant populations experience higher type 2 diabetes mellitus (T2DM) prevalence rates and worse health outcomes secondary to T2DM than native-born populations. But as the largest immigrant population in the United States, the experience of T2DM diagnosis and self-management among Spanish-speaking, limited English-language proficient Latinx immigrants remains largely unexamined. This study used semistructured interviews to explore these phenomena among a cohort of 30 recent Latinx immigrants.Method:All aspects of data collection were conducted in Spanish. Quantitative and qualitative data were collected. Data analysis included descriptive statistical procedures. Qualitative data analysis was conducted using a grounded theory approach.Results:Patterns in the data analysis of 30 interviews identified accepting T2DM as a common transitional process that required significant changes in individuals? self-perspective and ways of being. Accepting T2DM was identified by the participants as a precursor to treatment initiation. And while for most participants this transition period was brief, for some it took months to years. Distinct transitional stages were identified, categorized, and considered within the context of several theoretical orientations and were observed to align with those in transformative learning.Conclusion:Understanding differing responses and processing of a T2DM diagnosis could be leveraged to better support patients? acceptance and transition into treatment.
Published:
November 26, 2019
Title:
The fate of dietary advanced glycation end products in the body: from oral intake to excretion
Authors:
Liang, Zhili; Chen, Xu; Li, Lin; Li, Bing; Yang, Zhao
Abstract:
Advanced glycation end products (AGEs), which are closely associated with various chronic diseases, are formed through the Maillard reaction when aldehydes react with amines in heated foods or in living organisms. The fate of dietary AGEs after oral intake plays a crucial role in regulating the association between dietary AGEs and their biological effects. However, the complexity and diversity of dietary AGEs make their fate ambiguous. Glycated modifications can impair the digestion, transport and uptake of dietary AGEs. High and low molecular weight AGEs may exhibit individual differences in their distribution, metabolism and excretion. Approximately 50–60% of free AGEs are excreted after dietary intake, whereas protein-bound AGEs exhibit a limited excretion rate. In this article, we summarize several AGE classification criteria and their abundance in foods, and in the body. A standardized static in vitro digestion method is strongly recommended to obtain comparable results of AGE digestibility. Sophisticated hypotheses regarding the intestinal transportation and absorption of drugs, as well as calculated physicochemical parameters, are expected to alleviate the difficulties determining the digestion, transport and uptake of dietary AGEs. Orally supplied AGEs with low or high molecular weights must be supported by welldefined amounts in investigations of excretion. Furthermore, unequivocal evidence should be obtained regarding the degradation and metabolism products of dietary AGEs.
Published:
November 25, 2019
Title:
Climate-human interaction associated with southeast Australian megafauna extinction patterns
Authors:
Saltré, Frédérik; Chadoeuf, Joël; Peters, Katharina J.; McDowell, Matthew C.; Friedrich, Tobias; Timmermann, Axel; Ulm, Sean; Bradshaw, Corey J. A.
Abstract:
Whether Australia’s Pleistocene megafauna extinctions were caused by climate change, humans, or both is debated. Here, the authors infer the spatio-temporal trajectories of regional extinctions and find that water availability mediates the relationship among climate, human migration and megafauna extinctions.
Published:
November 22, 2019
Title:
The double-edged role of neutrophil extracellular traps in inflammation
Authors:
Euler, Maximilien; Hoffmann, Markus H.
Abstract:
While there are numerous studies showing that neutrophil extracellular traps (NETs) contribute to autoimmune inflammation and cause bystander tissue injury, human individuals with genetic impairments in NET formation curiously often suffer from exacerbated autoimmune diseases and/or chronic inflammatory conditions. These findings are confirmed in some mouse models of systemic lupus erythematosus (SLE) and gouty arthritis, where an absence of neutrophils or impairment of NET formation leads to exacerbation of autoimmunity and chronic inflammation. Thus, aside from their role as archetypical pro-inflammatory cells, neutrophils in general, and NETs in particular, can also interrupt the self-amplifying loop of cell activation and cell recruitment that characterizes neutrophilic inflammation. Here, we review the current state-of-the-science regarding anti-inflammatory and immune-regulatory action of NETs. We give an overview about the mechanistic involvement of NET-associated neutrophil serine proteases and suggest how tailored induction of NET formation could be exploited for the treatment of chronic autoinflammatory disorders.
Published:
November 22, 2019
Title:
Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine
Authors:
Wang, Yalong; Song, Wanlu; Wang, Jilian; Wang, Ting; Xiong, Xiaochen; Qi, Zhen; Fu, Wei; Yang, Xuerui; Chen, Ye-Guang
Abstract:
The intestine plays an important role in nutrient digestion and absorption, microbe defense, and hormone secretion. Although major cell types have been identified in the mouse intestinal epithelium, cell type–specific markers and functional assignments are largely unavailable for human intestine. Here, our single-cell RNA-seq analyses of 14,537 epithelial cells from human ileum, colon, and rectum reveal different nutrient absorption preferences in the small and large intestine, suggest the existence of Paneth-like cells in the large intestine, and identify potential new marker genes for human transient-amplifying cells and goblet cells. We have validated some of these insights by quantitative PCR, immunofluorescence, and functional analyses. Furthermore, we show both common and differential features of the cellular landscapes between the human and mouse ilea. Therefore, our data provide the basis for detailed characterization of human intestine cell constitution and functions, which would be helpful for a better understanding of human intestine disorders, such as inflammatory bowel disease and intestinal tumorigenesis.
Published:
November 21, 2019
Title:
Cerebral blood flow rates in recent great apes are greater than in Australopithecus species that had equal or larger brains
Authors:
Seymour, Roger S.; Bosiocic, Vanya; Snelling, Edward P.; Chikezie, Prince C.; Hu, Qiaohui; Nelson, Thomas J.; Zipfel, Bernhard; Miller, Case V.
Abstract:
Brain metabolic rate (MR) is linked mainly to the cost of synaptic activity, so may be a better correlate of cognitive ability than brain size alone. Among primates, the sizes of arterial foramina in recent and fossil skulls can be used to evaluate brain blood flow rate, which is proportional to brain MR. We use this approach to calculate flow rate in the internal carotid arteries (𝑄˙ICA)(Q˙ICA)(Q˙ICA), which supply most of the primate cerebrum. 𝑄˙ICAQ˙ICAQ˙ICA is up to two times higher in recent gorillas, chimpanzees and orangutans compared with 3-million-year-old australopithecine human relatives, which had equal or larger brains. The scaling relationships between 𝑄˙ICAQ˙ICAQ˙ICA and brain volume (Vbr) show exponents of 1.03 across 44 species of living haplorhine primates and 1.41 across 12 species of fossil hominins. Thus, the evolutionary trajectory for brain perfusion is much steeper among ancestral hominins than would be predicted from living primates. Between 4.4-million-year-old Ardipithecus and Homo sapiens, Vbr increased 4.7-fold, but 𝑄˙ICAQ˙ICAQ˙ICA increased 9.3-fold, indicating an approximate doubling of metabolic intensity of brain tissue. By contrast, 𝑄˙ICAQ˙ICAQ˙ICA is proportional to Vbr among haplorhine primates, suggesting a constant volume-specific brain MR.
Published:
November 20, 2019
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