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Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota, and may be the primary dietary cause of leptin resistance and obesity
Due to the complexity of a phenomenon like obesity, it is inevitable that most study assumes a “bottom-up” approach, working to elucidate detailed knowledge of the systems believed to be involved. During the assembly of such detailed knowledge into a working whole, a measure of conformity to prevailing views is natural, as researchers work in detail on their part of the puzzle and seek to integrate that work into the network of existing knowledge. Bottom-up approaches do not lend themselves to rapid paradigm shifts in understanding, as each novel contribution is an incremental advancement. This is especially true in research into the dietary causes of obesity and Western diseases, where implicating the wrong cause and advocating widespread dietary changes on the basis of that could lead to a significant worsening of the epidemiological situation.
With obesity and diabetes incidence and severity now at truly disconcerting rates, it is time to consider the possibility that implicating dietary fat as the primary cause and advocating that it be minimized has been a fundamental error, despite the large body of evidence supporting mechanisms by which high-fat diets might produce obesity.
The present paper attempts a “top-down” approach to obesity and provides a hypothesis that is not only consistent with available detailed mechanisms but also with some of the most confusing widely observed dietary phenomena. By comparing “ancestral diets,” which appear to promote universally effective homeostatic energy balance, with Western diets, a sharp delineation is found in the proportional mass of carbohydrate found in Western foods versus the locked-in low carbohydrate density of cellular plant foods. Since this characteristic does not correlate with glycemic index, the primary “organ” likely to be directly affected by such luminal concentration changes, and one already implicated in leptin resistance and obesity, is the gastrointestinal (GI) microbiota.
Background to the hypothesis
Energy homeostasis in the absence of Western foods
Obesity and non-insulin dependent diabetes are growing global phenomena, extending into the developing world following the spread of Westernized dietary patterns.1 The tendency toward overeating in the modern world is so common that it has led to the widely held belief that human energy homeostasis is maladapted to food excess and a sedentary lifestyle,2 and that constant voluntary caloric restriction is important to maintain healthy weight. Most epidemiological overviews of obesity examine Western populations, and it is often overlooked that even nominally healthy Westerners have leptin levels many times higher than those eating a non–Westernized diet, even in the presence of food abundance. For example, the Kitavan Islanders of Melanesia live as horticulturists with levels of activity comparable to manual workers who take moderate exercise; their dietary staples are root vegetables and fruit, with some consumption of meat and fish, but with little availability of Western foods. Hence as a population they consume virtually no grains or refined foods such as flour, sugar, or refined oils.3,4 Their carbohydrate intake is high, in the order of 60%–70% of energy intake, much of it root tubers or fruit with a moderately high glycemic index,5 while their saturated fat intake is also high (17% – largely from coconut). Despite food abundance and a clear overlap of macronutrients and glycemic index with Western diets, Kitavans are reported to possess leptin levels, fasting insulin, and blood glucose levels dramatically lower than those in Western populations deemed healthy,6,7 and appear to have a virtual absence of overweight, diabetes, and atherosclerotic disease.3,4,8,9 Environmental or genetic explanations for this metabolic health appear unlikely, since islanders who leave for the mainland and eat Western foods become overweight.7 People of this region may in fact be more susceptible to the effects of Western diet than Europeans, which may include increased susceptibility to effects subsequent to leptin resistance.10,11 Similar leanness and low leptin concentrations have also been recorded in the Ache hunter-gatherers of Paraguay, and in Shuar people of the Amazon who retain a traditional lifestyle.12–14 Those Shuar who have taken the initial steps toward agriculture have significant increases in leptin levels.15 Although leptin levels have not been recorded for other people eating traditional diets, it has been widely reported that unless grains or refined foods had arrived, all bore remarkably low incidences of “Western diseases,” including obesity (Table 1).3,4,6–9,16–29 Also notable is the apparent macronutrient-independence of the health associated with ancestral diets. The Kitavan case appears to argue against a primary causal role for carbohydrates or glycemic index in the genesis of obesity, at least when carbohydrates are in the form of root vegetables or fruit. Their diet is higher in carbohydrates than the estimated intake for our East African ancestors30 or modern hunter-gatherers,31,32 who tend to have carbohydrates provide around 35% of energy, ranging from 3% to 50% of energy intake, the proportion falling with northern latitude. Similarly, other analyses of modern hunter-gatherers33 have suggested that intake of unprocessed meat does not produce poor metabolic or cardiovascular health, in agreement with the reported historical diets and health of the Masai, Kavirondo, and Turkhana (Table 1).
Those populations that transitioned to a Westernized diet invariably developed Western metabolic diseases,1,34 while sustaining high levels of physical activity appears to offer only a degree of protection against obesity,35,36 as would be expected if a perturbation of homeostatic set point were responsible. It is unlikely that environmental factors could effect an absence of overweight in non-Westernized populations by means of effectively enforcing caloric-restriction even in good times, and such an improbable constant food-shortage or increased physical exertion would not be sufficient explanation for the dramatically different leptin levels seen in hunter-gatherers and non-cereal horticulturists, which in the case of the Ache of Paraguay are significantly lower than Western distance runners despite the lower adiposity of the latter.13
Moreover, even small amounts of Western influence in diet are associated with significant adverse alterations in metabolic and physiological markers, often before any substantial lifestyle changes.15,26 The relationship between health and ancestral or Western diets is reviewed in detail by Lindeberg.37 The effects of Western diet and lifestyle do appear to be reversible, at least in part. The metabolic health of diabetic Australian Aborigines has been shown to be markedly improved by even a 7-week return to a hunter-gatherer lifestyle and diet.38 In addition, Westerners have also been shown to benefit from similar dietary changes.
Grain-free whole-food diet: early results in Westerners
Whole grains are mooted to be healthier than refined grains,39 yet comparisons between grain consumption habits in industrialized societies indicate the effects of replacing refined grains with whole grains yield only modest improvements to health.40 These studies inevitably compare differing patterns of grain consumption against a background of almost universal flour, sugar, refined starches, and oils in the modern diet. Health patterns during nutrition transitions indicate that obesity, diabetes, and cardiovascular disease have characteristic incubation periods, but were virtually absent prior to the arrival of Western foods.18,21,37 The interindividual variability in “Western disease” incidence in a population eating Western foods is affected by genetic and other factors, but it is mostly these secondary factors that the epidemiology of industrialized populations would be studying if the root causes of metabolic disorders were now present throughout the population.
Removal of grains and all refined foods is one of the hallmarks of the “Paleolithic” diet, a modern way of eating that attempts to approximate the characteristics of ancestral diets. Although the literature of clinical studies of this dietary pattern in Westerners is currently small, it is also unanimous. Each published experimental comparison of a diet containing grains with one excluding grains has found significant favorable metabolic effects in the grain-restricted groups, with beneficial effects large enough to render the studies adequately powered despite their small test groups. The randomized clinical trials have shown significantly greater reductions in weight and waist circumference in an ad libitum Paleolithic-style diet compared with the consensus “Mediterranean” or “Diabetes” diets41,42 and significant improvements over the Mediterranean diet in blood glucose control, independently of the superior waist-circumference reduction.42 All three diets emphasize whole foods, but the restriction of grains in the Paleolithic diet is a principal difference, which correlated well with the reduced waist measurement42 and the 20%–30% increased satiety per calorie seen in the Paleolithic-diet groups. Importantly this increased satiety did not correlate with energy density, fiber, or macronutrient content,43 and significant spontaneous decreases in energy intake have been reported in all the ad libitum studies to date.41,42,44 However, the benefits of this dietary pattern do not appear dependent on this altered satiety or weight change; consumed in a calorie-matched manner to prevent weight loss, a Paleolithic-style diet produced significantly greater improvements in blood pressure, glucose tolerance, insulin sensitivity, and lipid profiles in a small group of healthy volunteers, with each individual participant showing improvements, indicating that these metabolic improvements occur independently of reduced caloric intake.45 Both the spontaneous 20%–30% decrease in caloric intake and the other metabolic improvements produced by a Paleolithic style of eating would be consistent with an increase in leptin sensitivity. Leptin levels dropped by 31% after 12 weeks of ad libitum Paleolithic diet, and were found to correlate best with consumption of cereals excluding rice.43 It is not known whether continued adherence to the regimen would produce leptin levels comparable to those reported in hunter-gatherers and noncereal horticulturists.
On the balance of evidence from the dietary patterns of non–Western populations and the initial findings of the modern Paleolithic diet, grains and refined foods therefore stand implicated as potential dietary causes of the Western obesity problem. It has been hypothesized that insulin receptor, epidermal growth factor receptor, or interleukin-2 receptor activities of cereal-grain lectins may be responsible for producing leptin resistance;46 the present paper proposes an alternative or additional mechanism with broad applicability to almost all Western foods.
Food-related inflammation and obesity
It is increasingly recognized that obesity is a disorder characterized by systemic low-level inflammation,47 with multiple elements of the metabolic syndrome strongly correlating with circulating bacterial lipopolysaccharide (LPS) concentrations.48 LPS levels are also significantly higher in nonalcoholic fatty-liver patients than controls, in conjunction with elevated GI permeability,49,50 while in metabolic syndrome, elevated downstream expression and activation of TLR4 and TLR2 on circulating monocytes is seen.51 After successful Roux-en-Y gastric bypass surgery, the reductions in weight and insulin resistance are associated with reductions in circulating LPS and inflammation.52 The source of the LPS is thought to be the GI tract, with ingestion of high-fat and high-carbohydrate Western-style meals found to produce postprandial “metabolic endotoxemia”: an increase in circulating LPS levels and other inflammatory changes.53 LPS and other gastrointestinally derived pathogen-associated molecular patterns (PAMPs) have also been suggested to play a role in the etiology of many “Western diseases,” including obesity. The small intestine has been implicated as a primary source for their systemic absorption, with possible PAMP sources including swallowed oral bacteria, small intestinal commensals, or PAMPs harbored inside foodstuffs. The far larger populations of Gram-negative bacteria in the large intestine are suggested to be less likely to act as a source for systemic PAMPs, due to the relatively small surface area of the bowel compared to the small intestine, the presumed evolutionary adaptations of the bowel to high concentrations of bacteria, and the fact that colonic translocatory PAMPs would undergo clearance by the liver, rather than bypassing hepatic detoxification via the lymphatic system, as small intestinal PAMPs would (reviewed by Erridge).54 The precise GI location of the alterations in microbiota underlying metabolic endotoxemia and inflammation in diet-induced obesity is not fully understood. The present hypothesis makes suggestions regarding the dietary triggers of these changes, wherever they are ultimately found to be located.
Dietary fat also appears able to facilitate translocation of PAMPs from the gut lumen into the circulation by promoting a microbiota that reduces the expression of tight-junction proteins.55 In humans, test drinks of cream (70% fat) produce a postmeal spike in circulating LPS, while a glucose drink does not. However, suppressor of cytokine signalling-3 (SOCS3) protein signaling and nuclear factor kappa B (NFκB) activation in circulating mononuclear cells were markedly elevated by both cream and glucose drinks, and were still elevated at 5 hours.56 The finding that glucose consumption elevates NFκB and inflammatory pathways57 without producing changes in LPS or TLR4 levels is important evidence that a glucose-induced non-LPS/TLR4 inflammatory pathway exists. SOCS3 has been implicated in leptin and insulin resistance, and both it and NFκB are significantly elevated in the obese.58 In animal studies, when conventional mice are compared with germ-free mice over 12 weeks, a saturated fat-free diet of ordinary rodent chow interacts with the microbiota of conventional mice to produce elevated LPS, increased white adipose tissue mass, increased levels of leptin, blood glucose and insulin, and increased infiltration of white adipose tissue by macrophages.59 In the same study, germ-free mice were monocolonized with either a wild-type Escherichia coli or a mutant form with less immunogenic penta-acylated LPS. The less immunogenic bacterium produced lower LPS levels in the portal vein, and was associated with lower macrophage infiltration and inflammation of white adipose tissue, indicating a role for LPS in this effect. However, leptin and insulin levels were even higher in mice monocolonized with the mutant E. coli, suggesting non-LPS PAMPs play a considerable role in leptin and insulin resistance.
Differing profiles of inflammation and PAMP translocation appear to be produced by different monosaccharides. In mice whose chow diet was supplemented with 30% glucose solution, larger weight gain and visceral adiposity were seen, but with no significant changes in hepatic portal LPS concentration. Conversely, fructose produced smaller changes in adiposity but markedly worse markers of hepatic inflammation, and significantly elevated hepatic portal LPS.60 Fructose is thought to have direct toxic effects on the liver,61,62 and its ability to generate circulatory LPS may be an important contributor to non-alcoholic fatty liver disease.
Inflammation of the gut itself plays a potential role, with early GI inflammation preceding and predicting obesity in diet-induced obesity models.63 This inflammation is associated with increased gastrointestinal permeability and changes in microbiota.64 Leptin resistance of the vagal afferent neurons innervating the upper GI tract is seen in diet-induced obese mice, apparently via SOCS3 signaling to inhibit STAT3 activation by leptin, with LPS shown to be able to increase SOCS3 in isolated nodose neurons (the cell bodies of the vagal afferents) in vitro.65,66 The onset of increased food intake in diet-induced obese animals coincides with this onset of leptin resistance, and substantially reduces the role of leptin in maintaining vagal afferent sensitivity to satiety mediators including cholecystokinin and peptide YY, by reducing the functional expression of their receptors, and increasing the expression of appetite-increasing receptors such as melanin-concentrating hormone 1 receptor and cannabinoid receptors.66 In similar diet-induced obesity models, central leptin resistance occurs some time later,67 with SOCS3 signaling again implicated.68 Modulation of the gastrointestinal microbiota in diet-induced obese and Ob/Ob mice with antibiotics is able to reduce the levels of LPS, inflammatory markers, and oxidative stress, along with reduced glucose intolerance, visceral fat, and body-weight gain.55,69 TLR4 and CD14 knockout mice are also protected from these effects, interestingly with subtly different effects on adipose tissue macrophage infiltration, indicating differing roles for these receptors in mediating LPS effects.70–72
The capacity for dysregulation of insulin, blood glucose, and other metabolic markers as a result of intestinal microbiotal changes may be highly conserved, with altered microbiota strongly affecting metabolism and growth patterns in the fruit fly Drosophila.73 In addition, microbiotal alterations appear able to influence the severity of myocardial infarction in a rodent model in a leptin-dependent manner.74 In humans, the species of bacteria that are present in fecal microbial communities appear to be relatively varied between individuals, with greater similarities between closely related people. However, the bacterial genes present across human populations appear to be more conserved, hence we possess a “core microbiome” composed more of similar bacterial genes rather than similar bacterial species. The microbiota of obese individuals showed alterations in the expression of bacterial genes, many involved in metabolism of carbohydrates, lipids, and amino acids.75 There is evidence that less Westernized diets can produce microbial communities with marked differences from those seen in industrialized countries. Children from rural Burkina Faso have a considerably different microbiota to those from Europe, a difference thought to be primarily dietarily mediated. With a lifestyle comparable to early Neolithic subsistence farmers, these children carry a large representation of Bacteroidetes, with an unusual prevalence of species suggested to bear genes for hydrolysis of dietary fiber.76
It is also known that the GI microbiota is also able to make use of fiber to affect the efficiency of energy absorption from the gut, which has been the subject of much study (reviewed by Backhed).77 By fermenting fiber into absorbable short-chain fatty acids, colonic bacteria are able to provide energy from fiber to the host that would otherwise not be available, and affect signaling via GPR41 and GPR43 receptors. Despite the trend toward reduced fiber intake in Western diets, the relevance of fermentable fiber mechanisms to obesity is questionable. The addition of supplementary fiber to Western diets has been studied extensively, without any improvements of the order of magnitude required for fiber to represent a significant part of the causal difference between ancestral and modern diets.78 While fermentable fiber is able to effect certain changes in colonic gastrointestinal microbiota, these currently seem unlikely to represent a useful intervention for obesity or metabolic disease.
Dietary fat is an exacerbatory but not primary cause of human obesity
There is no question that fat has a role in obesity. The rodent diet-induced obesity models discussed above predominantly make use of high-fat chows to produce their effects, which for a proportion of dietary fat of 72% (lard and corn oil) produced around a 2.7-fold increase in circulating LPS, while 40% fat chows produced 1.4-fold changes in LPS.79 It has also been shown that diets of differing fatty acids are able to differentially produce endotoxemia and complex patterns of inflammatory processes.80 Saturated fatty acids themselves are also able to activate the LPS receptor TLR4; this appears to require concentrations in the high micromolar range.81–83 These data appear consistent with the dominant body of dietary belief since the late 1970s that overconsumption of dietary fats is one of the primary nutritional problems of the industrialized world. However, despite all the mechanistic evidence that has been amassed condemning dietary fat, two broader considerations nonetheless suggest fat is unlikely to be the most pertinent factor in human obesity and metabolic syndrome.
Firstly, if dietary fat were the primary determinant of leptin resistance in humans, one would expect a low-fat diet to produce meaningful spontaneous reductions in weight in the obese. Reduced dietary fat intake would substantially reduce vagal and central leptin resistance, correcting the appetite and energy-expenditure “set point,” increasing the effectiveness of satiety signals, reducing appetite, and correcting metabolic markers. However, instead it is low-carbohydrate diets that are reported to produce the greatest weight loss in ad libitum diets, while ad libitum low-fat diets perform less well and produce less improvement to metabolic markers.84–88 Low-fat diets work as effectively as low-carbohydrate diets only when caloric restriction is enforced in both regimens.89,90 A recent small study of a “prudent” reduced-fat diet produced a 38% reduction in endotoxin activity.91 However, despite having a similar sample size to some Paleolithic-diet studies, there were no significant differences in blood glucose or insulin levels between the “prudent” diet and an elevated-fat diet that increased circulating endotoxin activity by 71%, consistent with the modest metabolic improvements from reducing fat.86,88
The second consideration against dietary fat is the evidence of ancestral diets where some populations historically ate high levels of meat and/or fat, and some ate high levels of carbohydrates, but no overweight or poor metabolic health markers were reported (see Table 1). Similarly, modern hunter-gatherers do not have a gradient of metabolic health or overweight outcomes based on either fat or carbohydrate consumption,32,33 as would be expected to be manifest if simple increased proportions of one of these macronutrients were the primary causes of obesity.
These observations are consistent with some factor present in Westernized foods being responsible for obesity, with the macronutrient ratios of unprocessed foods having no obesogenic effects.
Elevating dietary fat in a Western diet can cause obesity. However, the effects of low-carbohydrate diets and the failure of low-fat diets to match their ad libitum weight loss and metabolic effects indicate that carbohydrates somehow play a central role as initiators of leptin resistance in humans. However, the Kitavan Islanders, one of the metabolically healthiest populations yet studied, eat a high-glycemic-index, high-carbohydrate diet with staples of starchy tubers and fruits. A unified theory of obesity should (somehow) be consistent with all these observations.
Carbohydrate density and diet-related inflammation
To find the cause of the modern obesity epidemic, the properties of modern foods that perturb the homeostatic energy set point should be sought. The universality of the negative effects of Western foods on indigenous populations indicates that these properties must be similarly widespread in modern foods.
Among the most common elements of Westernized foods are the nonperishable products flour and sugar. A fundamental distinction between modern foods containing these and ancestral foods is carbohydrate density. Figure 1A shows the carbohydrate density of a broad selection of foods, with modern foods in grey (USDA data). Foods that would be permitted on a Paleolithic or “primal” diet – the “ancestral foods” – are those in the categories of root tubers, leafy vegetables, fruit, nuts, meats, eggs, and fish, and are shown in white. Tubers, fruits, or functional plant parts such as leaves and stems store their carbohydrates in organelles as part of fiber-walled living cells. These are thought to remain largely intact during cooking, which instead mostly breaks cell-to-cell adhesion.92,93 This cellular storage appears to mandate a maximum density of around 23% non-fibrous carbohydrate by mass, the bulk of the cellular weight being made up of water. The acellular carbohydrates of flour,94 sugar and processed plant-starch products are considerably more dense. Grains themselves are also highly dense, dry stores of starch designed for rapid macroscopic enzymic mobilization during germination.95 Whereas foods with living cells will have their low carbohydrate density “locked in” until their cell walls are breached by digestive processes, the chyme produced after consumption of acellular flour and sugar-based foods is thus suggested to have a higher carbohydrate concentration than almost anything the microbiota of the upper GI tract from mouth to small bowel would have encountered during our coevolution. This may stimulate differing bacterial species to prosper or be outcompeted, or increase some microbial metabolic pathways and waste products in preference to others. It is proposed that the effects of these enhanced carbohydrate concentrations will include a more inflammatory GI microbiota, initially causing leptin resistance, hence the greatly elevated leptin levels seen in Western populations when compared to those eating a wholly cellular diet.7,12–15
Figure 1B shows that the nutrient densities of ancestral foods have a good degree of overlap with those of modern food, with nuts, meats, and eggs having higher nutrient densities, but still retaining low carbohydrate density. Figure 1C shows a similar overlap of glycemic index between ancestral and modern foods for which data were available,5 with little correlation between carbohydrate density and glycemic index. Hence ancestral diets are strongly distinct from modern diets with regard to carbohydrate density, but not by either nutrient density or glycemic index.
Once an inflammatory microbiota is in place, consumption of refined dietary fats and oils may effect a double hit by increasing the absorption of inflammatory PAMPs including LPS into the circulation (Figure 2), or stabilizing and preserving the inflammatory microbiota itself. This would make a diet rich in both acellular carbohydrates and fat highly obesogenic, promoting a self-sustaining cycle of hyperphagia in an environment where such foods are abundant. Upon withdrawal of all acellular carbohydrates, the GI microbiota is proposed to return to a less inflammatory form consistent with our evolutionary experience, and one much more resistant to the exacerbatory effects of dietary fats, consistent with the interplay between fructose and fats seen in rats.96 From the sensitivity of ancestral peoples’ health markers to even small influences of Western foods,15,26 there may be a nonlinear relationship between the degree of diet-related inflammation and the amount of acellular carbohydrate in diet, with even small amounts of sugar or flour able to produce significant leptin resistance. This is also likely influenced by the concentration and nature of dietary fats present and heritable factors.
In people of European descent, relatively high resistance to the diabesogenic effects of Western diet is seen.1,34 This is proposed to be due to thousands of years of exposure to the acellular carbohydrates from cereal agriculture, allowing limited adaptive mechanisms to evolve. People of non-European descent hence appear more susceptible to the effects of flour, sugar, and refinement, develop worse adipokine profiles from Western diets,10 and show higher incidences of obesity and diabetes. In Europeans, overt obesity or diabetes is minimal unless consumption of bread is compounded by replacement of remaining cellular carbohydrate sources (fruit and vegetables) with sugar, flour, and refined oil-bearing processed foods.
Archaeological evidence from Paleolithic African and European tools indicates that some groups of people did supplement their diet with ground plant starches from roots or gathered wild grass seeds.97–99 The pestle-and-mortar scale of this food preparation would likely have made the contribution of acellular carbohydrates to diet an order of magnitude smaller than that seen in the modern diet, where for many the overwhelming majority of plant foods consumed year-round are acellular processed products. Hence it is argued that any evolutionary pressures evoked by prior hand preparations of wild seeds was dwarfed by the advent of cereal agriculture, which in turn provided only a partial evolutionary preparation for the modern Western diet.
Dietary carbohydrate-density: a link between periodontal health and metabolic health?
When indigenous people adopted flours and sugars into their diets, along with the adverse metabolic effects they experienced a substantial downturn in their dental health.100,101 It is widely accepted that consumption of refined carbohydrates can cause tooth decay and gingival inflammation through bacterial means. While an inflammatory oral microbiota may alter oral inflammation, it increasingly appears that analogous microbial changes in the upper GI tract appear able to produce leptin resistance in vagal afferent endings, attenuating satiety signaling.65,66 The present hypothesis suggests that it is a diet of high-density carbohydrates that produces inflammatory microbiotal changes in both areas. Periodontal disease has long been known to associate with obesity,102 while elevated levels of a particular Gram-negative oral bacterium was found to predict 98.4% of obesity in one study.103 A 4-week experiment in “Stone Age” lifestyle, including removal of refined foods and consumption of reduced levels of whole cereal grains, produced significant reductions in markers of gingival inflammation despite an absence of modern oral hygiene practices during the study.104 Over the last decade, interest in the association between periodontal disease and systemic diseases has increased markedly, along with some reconsideration of the possibility of a role for dietary carbohydrate as a cause of both (reviewed by Hujoel).100 However, elsewhere this link was misrepresented, and some were marketing dental treatments as a means to improve cardiovascular health. This led to a recent American Heart Association scientific statement emphasizing the lack of evidence indicating a causal link between periodontal disease and heart disease, and suggesting independent causative factors were causing both.105 If the high carbohydrate density of modern foods produces an inflammatory microbiota in both the mouth and small bowel, it may be this that is the root cause of both periodontal and atherosclerotic disease, as well as obesity and other metabolic syndrome-linked “diseases of affluence.”
The hypothesis and existing dietary patterns
The consensus “prudent” or Mediterranean dietary patterns could be expected to offer slight improvements over an unrestrained Western diet, due to the inclusion of more cellular plant foods at the expense of some acellular carbohydrate and fat, and an emphasis on some less refined and thus very slightly less carbohydrate-dense breads (see Figure 1). However, enough breads and baked goods with acellular dense carbohydrate are retained to keep an inflammatory microbiota and prevent substantial correction to the endemic Western leptin resistance. This is consistent with the continued requirement for conscious caloric restriction when eating these consensus diets if a steady weight is to be maintained.
Low-carbohydrate diets will reduce acellular carbohydrate consumption as a by-product of markedly reducing all carbohydrates. This is suggested to result in a larger reduction in the inflammatory nature of the GI microbiota, weight loss without conscious caloric restriction, and improved metabolic syndrome markers.86,88,106 However, low-carbohydrate diets retain some carbohydrates (usually less than 20–50 g per day), often with no regard to their density. This means what little carbohydrate is eaten may still lay the basis for an inflammatory microbiota, which is proposed to receive a second hit via additional energy for bacteria and increased LPS translocation from the elevated fat content that often accompanies a low-carbohydrate diet. This is suggested to explain the “stall” process, where low-carbohydrate dieters can lose large amounts of weight, but then cease weight loss while still overweight or begin to slowly regain weight.84,85
Severe caloric restriction for 8 weeks with a diet of refined-liquid meal-replacement formula supplemented with some vegetables (510 kcal Optifast with vegetables to a total of 600 kcal per day) was reported to normalize beta-cell function and insulin sensitivity in a small group of type II diabetics (<4 years from diagnosis).107 This represents an intake of acellular carbohydrates of around 237 kcal per day (the liquid diet was 46.4% carbohydrate), which might represent a sufficient reduction to avoid adverse metabolic microbial effects. It is of note that a Paleolithic-style diet also normalized type II diabetic glucose tolerance in a randomized trial with a similar small group, but crucially these patients were eating ad libitum.42 Both 237 kcal per day of acellular carbohydrate and an ad libitum Paleolithic style of eating may produce similarly sparse concentrations of carbohydrate in the upper GI tract, but only the Paleolithic diet is practical or sustainable in the long term. Time of intervention may be of the essence due to beta-cell damage; in a later study, longer-established type II diabetics (mean = 8 years postdiagnosis) still showed greater improvements with Paleolithic eating than with a consensus diet, but they did not obtain fully normalized blood glucose regulation.41
Hence a grain-free whole-food diet would be predicted to restore the GI microbiota to the less inflammatory state that humans coevolved with. This is consistent with the larger falls in blood glucose response and leptin/insulin-resistance, and the 20%–30% spontaneous reduction in caloric intake seen in the Paleolithic diet when eating to satiety,41–43 as well as the population-wide maintenance of healthy weight in Kitava6,7 and in other grain-free whole food-eating populations.16,20,22,29,108,109 Upon initial adoption of dietary change, overweight Westerners with higher insulin resistance might initially benefit from a low-carbohydrate form of Paleolithic-style eating. However, over time (and assuming no permanent diabetes-related damage) the resulting restoration of insulin sensitivity should mean a diet with a higher level of unrefined whole fruit and starchy root vegetables should be compatible with maintaining optimal metabolic health and stable healthy weight. This is now being reported anecdotally by Paleolithic-diet eaters, and is consistent with the condition of the Kitavan Islanders. The proposed importance of the cellularity and low carbohydrate density of fruit and vegetables in maintaining an evolutionarily appropriate microbiota might explain the failure of supplementary fiber, vitamins, or antioxidants to replicate the health effects of a diet of fruit and vegetables when taken with a Western diet.110
Suggestions for the future
The available evidence suggests that whole-food grain-free diets are substantially metabolically healthier than modern diets. How generalizable these findings are to differing populations and to what extent Western diseases such as obesity, diabetes, and atherosclerosis can be reversed by adoption of this dietary pattern should now be assessed in large-scale clinical trials. Whether the means of action is as proposed in this paper should also be tested in humans, measuring levels of inflammation, SOCS3, NFκB and leptin with titrated intake of acellular carbohydrate and fat. Whether any effects of carbohydrate density are found to be dependent on cellularity will be a crucial determinant of whether processed foods can be made safer by reformulation. Potential interactions of the Paleolithic dietary pattern with common medications should be studied carefully.23 Whether the advice of some variants of the diet regarding exclusion of legumes or dairy products have demonstrable metabolic or anti-inflammatory roles should also be evaluated.
The complexity of the microbiome and its interplay with the host is hard to overstate. Detailed 16S RNA bacterial profiles from multiple levels of the GI tract, of both the luminal contents and mucosa, may be needed to identify any bacteria or bacterial genes that vary while carbohydrate density or cellularity are altered (holding macronutrient ratios as constant as possible). Putative microbiota-related signaling molecules and metabolic effectors such as fasting-induced adipocyte factor and adenosine monophosphate-activated protein kinase should also be monitored for correlations with carbohydrate density and fat. It may be possible to establish an index system for assessing the obesogenic potential of foods, based upon the rate of proliferation of relevant bacteria either in the gut or under simulated conditions in vitro.
A simple start could be made by profiling the microbiota of Kitavan Islanders, and investigating whether comparable profiles can be produced by a Paleolithic diet in Westerners after a month or a year. Due to population constraints, we are currently dependent on grains to feed the world. Hence another question of importance is the relative obesogenic effects of different grains, and how much impact minimally processed rice, maize, millet, sorghum, or sprouting grains have on metabolism and microbiota.
Should carbohydrate density be found to correlate with increased appetite under experimental conditions, how rapidly a sugar- or flour-containing meal (against a background of otherwise constant grain-free whole foods) acts may be mechanistically and practically informative; how rapidly does a switch to flour or sugar produce leptin resistance in humans, is the localization pattern (vagal afferents, then central) the same as in rodents, and what is the duration of this effect? This will have implications for how strictly modern foods have to be avoided in order to maximize health. Whether acellular sugary drinks have similar effects, the nature of their concentration–inflammation relationships, and whether they undergo concentration or dilution in the gut lumen would likely also be of interest. The possibility that some effects of increased luminal carbohydrate density may be directly conveyed via enterochromaffin cell signaling to vagal afferents should be considered.
One complexity with the current hypothesis is that some effects that may be attributable to microbiota and carbohydrate density are hard to extricate from effects attributable to food reward. Changes in both have inevitably been present in many previous studies of food reward; for example, in the use of the highly refined and highly rewarding cafeteria diet in rodents.111 With such foods, both hypotheses predict central mechanisms to increase caloric intake, one through increased reward when a palatable food is encountered and eaten, the other through increased appetite and delayed satiety from microbiota-driven central mechanisms. One possible way to dissociate the contributions of the two might be to look at the effects of antibiotics on trials of cellular and acellular foods, while looking for correlations of microbiotal change with inflammatory and metabolic markers. A key difference to attempt to tease out may be the nature of intermeal hunger. People eating a grain-free whole-food diet anecdotally report a satiety that precludes intrusive thoughts about food, often until after a scheduled mealtime has passed. This is qualitatively different to the craving for almost anything to “fill the gap” so familiar to Westerners sensing a need for a snack between meals. An informative experiment might be one that tested whether refined diets increase subsequent intake of all foods, or only of highly palatable foods. Since all behaviors are expressed with input from the brain’s reward centers, food reward must naturally play a role in food intake, but surely so must homeostatic control of energy balance. At extremes of reward, it likely does affect meal size and short-term caloric intake. Otherwise, it certainly plays a major role in the choice between refined foods (with carefully tailored palatability) and the whole-food alternatives. That, of course, may be the most important choice of all.
The increased storage life and convenience of some of our oldest agricultural products may come with a hitherto unrecognized metabolic cost. The foods eaten by hunter-gatherers, non-cereal horticulturalists, and those following a modern Paleolithic or “primal” diet are sharply delineated from modern foods by their lower carbohydrate densities. Consumption of exclusively low-density carbohydrates is suggested to produce a less inflammatory GI microbiota, and may explain the apparent absence of overweight and metabolic disease in two of these groups, and the promising early data from the third. This hypothesis may also explain (1) why obesity incidence scales with refined food intake, but has such confusing correlatory patterns with macronutrients; (2) why calorie-controlled diets of Westernized foods require a perpetual fight with homeostatic correction mechanisms; (3) the link between periodontal disease and systemic atherosclerotic disease and obesity; (4) why the benefits of a diet of fruit and vegetables have not been replicated by supplements of the constituent antioxidants, vitamins, minerals, and fiber alongside a Western diet; (5) why low-carbohydrate diets produce ad libitum weight loss, but low-fat diets do not; and (6) the relative resistance of European people to obesity and diabetes from Westernized diets.
We should not settle for the meager improvements attainable from the consensus dietary advice when it is already clear that so much more might be achieved. Our sights should be set high, to see how close we can move levels of industrialized metabolic health toward those enjoyed by non-Westernized populations. While many will resist making dietary changes of such magnitude, official advice must nonetheless point in the correct direction, allowing individuals to make informed decisions.
The social and financial burden of the epidemic of obesity and metabolic syndrome threatens the long-term viability of our health-care systems and perniciously undermines the other benefits of modern civilization, including redirection of scarce financial resources. If this dietary pattern is confirmed to work, practical policy solutions must be sought. Some grain cultivars may be found to produce less inflammation, sprouting techniques may be found to be of benefit, or grain production may be replaced with root-vegetable cultivation where practical. Over time, the interplay between market forces, attainable agricultural yields, and the practicalities of food-distribution networks may allow shifting demand from a newly informed populace to reshape global agribusiness.
A dietary pattern with carbohydrates exclusively from cellular low-density sources may remove the root cause of a range of our most prevalent diseases. The potential savings in health-care costs should be borne in mind, and the hypothesis tested.
|People||Diet||Macronutrient summary||Acellular foods or grains||Overweight or obesity||Other health markers||Reference|
|Kitava 1990s||Starchy root vegetables, fruit, some fish and meat, coconuts. Food abundance||~65% carbohydrate, high fibre, 17% saturated fat||−||0% overweight||No stroke, diabetes or heart disease. No increase in weight or blood pressure in middle age||3,4,6–9|
|Machiguenga 1982||Mostly root vegetables, fruit and nuts, very small amount of meat and fish. Food abundance||High carbohydrate, high fibre||−||None reported||Healthy teeth and gums, good general health, except for parasites and infections||22|
|Masai 1971||Cow’s milk and blood, meat||66% fat, similar cholesterol intake to US||−||Lean||Atherosclerosis rare at autopsy||16|
|Kavirondo Kenyans 1929||Mostly meat||High protein, high fat||−||Lean||Aortic atheroma at autopsy rarer than in Westerners. No increase in blood pressure through middle age||20|
|!Kung 1972||~70% plant matter (mongongo nuts, fruits, roots, bulbs, leaves), some meat||Mongongo nuts: ~60% fat, 25% protein||−||Lean||No increase in blood pressure through middle age||29|
|Solomon Islanders 1974||Root vegetables, fruit, fish, limited meat, tinned fish||Varied||−/+||Lean (Western-influenced islands were heavier)||No hypertension or cardiovascular disease. Islands with Western influence showed increased blood pressure||26|
|Turkana 1980–83||Mostly milk, blood, meat, but by 1983 also some traded sorghum, maize, millet, and sugar||High protein, high fat||+||Lean (<5th percentile of Western weight)||No increase in weight in middle age||24,25|
|Tarahumara 1978–79||90% from pinto beans and maize tortilla. Remainder from squash and other vegetables||High carbohydrate, high fibre, fat 12%, animal sources 6%, refined sugar 1%||++||5% BMI > 26||No hypertension, no rise in blood pressure with age||17,19|
|Mexican Pima 2006||Beans, wheat-flour tortillas, corn tortillas, and potatoes||62% carbohydrate, 25% fat, high fibre||+++||Males: 7% obese|
Females: 20% obese
|7% diabetes incidence||27|
|Arizona Pima 1996–2006||Refined Western diet, including fried breakfasts, processed meats, hamburgers, pork chops, beans, white bread, flour tortillas, fried or baked dough, cereals, canned foods, fruit juices||49% carbohydrate, 15% protein, 34% fat, >10% saturated fat||++++||Males: 64% obese|
Females: 75% obese
Note: −, −/+, +,++, +++ and ++++: Approximate contribution of acellular foods or grains to diet, ranked from ‘absent’ (−), to ‘major component of diet’ (++++).
The author reports no conflicts of interest in this work.
This work was not supported by funding. Thanks to Dr Francisco Bautista Cruz and Dr Andrew Samis for useful discussions over a long period, and to Dr Mike Beyak, Dr Japie Louw and Dr Philip Sherman for feedback on the evolving hypothesis.
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The Boeing Company [NYSE: BA] has reached an agreement with the Royal Australian Air Force (RAAF) to provide logistics support services for Australia's C-17 fleet.
Australia is buying four Globemaster III aircraft with the first delivery planned for December 2006. Under the $80.7 million contract, Boeing will manage spare parts for the Australian fleet. The RAAF will be responsible for flight line maintenance with Boeing performing heavier, depot-level maintenance. Boeing has similar responsibilities for the U.S. Air Force and the United Kingdom's Royal Air Force C-17 fleets through the Globemaster III Sustainment Partnership (GSP).
By joining the global C-17 support network, Australia will take advantage of the economy of scale for the purchase of spare parts and materials for a fleet of nearly 200 aircraft compared to a fleet of four. Support Systems, a business of Integrated Defense Systems, also will provide technical support, engineering services, engine maintenance and management, technical publications and support equipment management for the RAAF anywhere the aircraft are located.
The RAAF joins the existing performance-based logistics contract where Boeing is paid for an agreed upon level of aircraft availability. Boeing shares part of the risk for maintaining the aircraft and has incentive to sustain the fleet as efficiently as possible.
"By joining the partnership, Australia is significantly reducing its costs," said Bud Matlock, Boeing director of International Product Support for the C-17. "The advantage comes not only in the synergies gained by joining the virtual C-17 fleet, but also in Boeing's experience and infrastructure in sustaining the C-17 around the world for all our customers. We are excited about the RAAF joining the C-17 GSP and encouraged about our international growth opportunities."
The contract to maintain the Australian C-17s mirrors Boeing's agreement with the United Kingdom. Similar partnerships are available to foreign military services that purchase C-17s. Denmark recently signed a letter of intent to join a team of NATO nations that will share a pool of C-17s. The Canadian Department of National Defence in early July said it intends to acquire four C-17s.
A unit of The Boeing Company, Boeing Integrated Defense Systems is one of the world's largest space and defense businesses. Headquartered in St. Louis, Boeing Integrated Defense Systems is a $30.8 billion business. It provides network-centric system solutions to its global military, government and commercial customers. It is a leading provider of intelligence, surveillance and reconnaissance systems; the world's largest military aircraft manufacturer; the world's largest satellite manufacturer; a foremost developer of advanced concepts and technologies; a leading provider of space-based communications; the primary systems integrator for U.S. missile defense; NASA's largest contractor; and a global leader in sustainment solutions and launch services.


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Rattlesnakes are one of the most feared creatures on the planet, known for their venomous bite and deadly reputation. However, what many people don’t know is that these snakes are also a delicacy in some parts of the world.
While the thought of consuming a rattlesnake may seem repulsive to some, others swear by its unique flavor and nutritional benefits. So, are rattlesnakes really edible? Let’s dive deeper into this fascinating topic and explore the surprising culinary world of these slithering creatures.
Yes, Rattlesnakes are edible and considered a delicacy in some parts of the world. However, it is important to note that consuming rattlesnakes can be dangerous as they may carry diseases and toxins. Therefore, it is recommended to only consume rattlesnakes that have been properly prepared and cooked by a trained professional.
Are Rattlesnakes Edible?
Rattlesnakes, known for their venomous bites and rattling tails, are found in various parts of the world, including North and South America. However, what many people may not know is that some cultures consider rattlesnakes to be a delicacy and even incorporate them into their cuisine. But are rattlesnakes really edible? Let’s find out.
History of Eating Rattlesnakes
Eating rattlesnakes is not a new phenomenon. In fact, Native Americans have been consuming rattlesnakes for centuries. They believe that rattlesnakes have medicinal properties and are good for treating various ailments. Rattlesnake meat was also a source of protein for them when other food sources were scarce.
In modern times, some cultures still eat rattlesnakes. In China, for instance, rattlesnake meat is believed to have aphrodisiac properties and is sold in some restaurants and markets. In the United States, rattlesnakes are hunted and eaten in some parts of the country, particularly in the South and Southwest.
Is Rattlesnake Meat Safe?
Before considering eating rattlesnake meat, it’s important to know if it’s safe to consume. Rattlesnakes are known to carry various diseases, including salmonella and E. Coli. Therefore, it’s crucial to handle and cook the meat properly to avoid any health risks.
The best way to ensure that rattlesnake meat is safe to eat is to purchase it from a reputable supplier who has properly handled and processed the meat. Additionally, it’s important to cook the meat thoroughly to kill any harmful bacteria that may be present.
How to Prepare Rattlesnake Meat
If you’re interested in trying rattlesnake meat, you may be wondering how to prepare it. The most common way to cook rattlesnake meat is to grill or fry it. Before cooking, the meat should be marinated to add flavor and tenderize it.
Another popular way to cook rattlesnake meat is to make a stew. The meat is usually slow-cooked with vegetables and seasonings to create a flavorful and hearty dish.
Benefits of Eating Rattlesnake Meat
Apart from its cultural significance, some people believe that rattlesnake meat has health benefits. It’s said to be high in protein and low in fat, making it a healthier alternative to other meats.
Additionally, some people believe that rattlesnake meat has medicinal properties and can help with various health conditions, such as arthritis and joint pain. However, more research is needed to confirm these claims.
Rattlesnake Meat Vs. Other Meats
Compared to other meats, rattlesnake meat has a unique taste and texture. It’s often described as similar to chicken or fish, but with a slightly gamey flavor.
In terms of nutrition, rattlesnake meat is lower in fat and calories than beef, pork, and chicken. It’s also high in protein, making it a good option for those who are looking for a protein-rich diet.
In conclusion, rattlesnakes are indeed edible, but it’s important to handle and cook the meat properly to avoid any health risks. Rattlesnake meat has a unique taste and texture and is a good source of protein. However, it’s not a common meat and may not be easily accessible in some areas. If you’re interested in trying rattlesnake meat, be sure to purchase it from a reputable supplier and cook it thoroughly.
Frequently Asked Questions
Here are some commonly asked questions about rattlesnakes and their edibility.
What parts of a rattlesnake can be eaten?
While some people may eat the entire rattlesnake, including the head and internal organs, it is recommended to only consume the meat. Additionally, it is important to remove the skin, which can contain toxins and is difficult to digest.
The meat of the rattlesnake is lean and has a texture similar to chicken or fish. It can be cooked in a variety of ways, such as grilling, frying, or baking.
Is it safe to eat rattlesnakes?
While consuming rattlesnake meat is not inherently dangerous, there are some risks associated with handling and preparing the snake. Rattlesnakes are venomous, so care should be taken when removing the skin and meat to avoid being bitten.
Additionally, it is important to make sure the snake is fully cooked to avoid any potential bacterial infections. It is recommended to cook the meat to an internal temperature of 165°F.
Are there any health benefits to eating rattlesnakes?
Rattlesnake meat is high in protein and low in fat, making it a healthy choice for those looking to incorporate more lean protein into their diet. It also contains a variety of vitamins and minerals, such as iron and zinc.
However, it is important to note that consuming rattlesnake meat should be done in moderation, as it can be high in cholesterol and sodium.
What does rattlesnake meat taste like?
Many people describe the taste of rattlesnake meat as similar to chicken or fish, with a slightly gamey flavor. The texture is also similar to these meats, with a firm and slightly chewy texture.
Some people also note a slightly sweet or nutty flavor, which may be due to the snake’s diet of rodents and small animals.
How do I prepare rattlesnake meat?
Rattlesnake meat can be prepared in a variety of ways, such as grilling, frying, or baking. Before cooking, it is important to remove the skin and internal organs, as well as any remaining venom glands.
Once the meat is cleaned, it can be marinated or seasoned to impart flavor. It is important to cook the meat to an internal temperature of 165°F to avoid any potential bacterial infections.
In conclusion, while it is possible to eat rattlesnakes, it is not something that is recommended for the average person. The dangers associated with handling and preparing the meat, as well as the potential for contracting diseases from the snake, make it a risky choice. However, for those with experience and knowledge in handling and preparing wild game, rattlesnake meat can be a unique and flavorful addition to their diet. Ultimately, the decision to eat rattlesnakes should be made with caution and careful consideration of the risks involved.

domain: food


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Registered Clinical Officer Job, Current Medical Jobs In Kenya,
- Be a Kenyan citizen.
- Be a holder of Diploma in Clinical Medicine and Surgery or Clinical Medicine and Community Health from Recognized institution
- Be a registered member of the Clinical Officers Council
- Possess a valid practicing license from the Clinical Officers’ Council
- Certificate in Computer Application Skills from a recognized institution
- Satisfy the requirements of Chapter Six of the Constitution of Kenya 2010
- Taking history, examining, diagnosing and treating patients’ common ailments at an outpatient or inpatient health facility;
- Implementing Community Health Care activities in liaison with other health workers;
- Guiding and counseling patients, clients and staff on health issues;
- Sensitizing patients and clients on preventive and promotive health;
- Carrying out minor surgical procedures as per training and skill;
- Collecting and compiling clinical data;
- Referring to patients and clients to appropriate health facilities.
- Teaching and Mentorship of Human resources for health at various levels
- Performing any other duties as may be assigned by the immediate supervisor
How To Apply
Written applications enclosing current Curriculum Vitae, Copies of academic and professional certificates and ID card should be submitted in a sealed envelope and addressed to;
Makueni County Public Service Board
P.O. Box 49 – 90300
Or delivered by hand at the reception desk at Makueni County Public Service Board Offices located past Makueni Girls, Opposite Wote Technical Training Institute to be received on or before Monday, 13th October, 2020.
- The Makueni County Job Application Form can be downloaded here.(click here to download)
- Candidates should attach relevant professional Certificates, National Identity Card, Professional registration Certificate, and Practice License where necessary.
- Only shortlisted candidates will be contacted.
- Shortlisted candidates will be required to produce their original National Identity cards, Certificates and Testimonials at the interview.
- The Makueni County Government is an equal opportunity employer; Youth, Women, Persons with Disabilities and other disadvantaged personsare encouraged to apply.
- Affirmative action as stipulated in the constitution shall be applied.
- Canvassing in any form will lead to automatic disqualification
- The Board does not charge a fee at any stage of the recruitment process. Payment of any form of fee will lead to automatic disqualification

domain: medical


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If you’ve just welcomed a new pet into your household, there’s no doubt you’ll want to give them the very best start to life. There may be some nerves (from both human and animal) as well as plenty to think about and be prepared for.
You’ll need to think about nutrition, how to make them feel safe and comfortable, how to gain understanding to make sure you are creating a trusting and loving relationship with your new companion, not to mention navigating vaccination, microchipping and desexing needs! Above all, we recommend being patient throughout the process and keeping their environment a consistent and calm one.
Behaviour and socialisation
Focussing on behaviour and socialisation of our new pets should be a priority. All animals have a period of learning at the start of their lives that affects lifelong behaviour. During this time, they learn to accept the things around them so that they are not afraid of them. This period is between 3-12 weeks in puppies and 2-7 weeks in kittens. Puppy socialisation involves having pleasant encounters (with humans, other animals and noises/experiences). Puppies that are well socialised tend to grow up to be friendly and happy, taking different situations in their stride. Current thinking is that many dogs are put down because of issues that could be prevented by early socialisation. Puppy classes are a great first step in becoming a responsible dog owner. Make sure you also have plenty of toys and treats on hand to help with training. And remember, although puppies and kittens seem to have endless energy, it’s vital to give them plenty of downtime for their physical and mental health.
Some puppy owners have described the few first weeks of having a puppy similar to having a newborn baby. Be prepared for sleepless nights! Establishing a routine is important, as is making sure your puppy has a safe and cosy place to sleep. Crate training is highly recommended. Get it right and your puppy will seek out their crate for times they want rest. Kittens will need lots of sleep when they are young, even more so that adult cats. However, they will not always sleep through the night.
It won’t take long to realise that puppies pee a lot! Up to 12 times a day. It’s your job to read your puppy’s behaviour and learn when they ‘need to go’. Walking in circles and looking around anxiously are common behaviours. Calmly walking with them outside and waiting patiently until they are finished, then rewarding them with praise or treats are good actions. Be consistent with your approach and don’t punish your puppy for accidents, this can slow progress, so keep positive! Kittens require less work when it comes to toilet training and most are already trained by the time they come to their new home (those who haven’t are helped by a strong instinct to bury their evidence!).
Putting some thought into what you are feeding your pet is part of giving them a great start to life. At the puppy or kitten stage, getting the correct balance of nutrients, vitamins and minerals is essential. If fed poor quality foods they may fail to thrive, be more susceptible to disease, and could have ongoing permanent issues. Whatever diet you choose to feed your pet, it is important to introduce new foods slowly, avoiding any sudden changes as this may cause gastrointestinal upsets.
Other important things to note:
Desexing: If you don’t plan to breed your pet, there are good medical and behavioural reasons for desexing, which we strongly recommended.
Vaccination: We strongly recommended that puppies and kittens be fully vaccinated, as this will help protect them from potentially fatal diseases. They will require rounds of vaccinations, at 8 weeks, 12 and 16 weeks.
Council requirements: Microchipping and registration is a council requirement for dogs. The microchipping procedure is quick and painless and means that if your pet goes missing, they can be identified.
Parasite control: Regular flea and worm treatments are important for all animals, but particularly in the young. If untreated, pets will almost certainly suffer from parasitism, which can make them seriously ill.
Puppy and Kitten Promotion now on!
Tauranga, Te Puna, Katikati and Papamoa Village Vets’ Puppy and Kitten Promotion is now on! If you have a new puppy or kitten, give us a call or come in – let us help you make providing the best care for your puppy or kitten simple and more affordable. Our Kitten and Puppy packs include discount vouchers for 20% off de-sexing, vouchers on food and flea treatment plus lots more!

domain: pet


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The FY2010 roller-coaster ride is just about over, and many a library advocate is undoubtedly glad to see the back of it. There’s a curious symmetry about the timing: Thousands of tenacious front-line library supporters are taking stock of their finalized local budgets even as a swarm of library boosters descended on Capitol Hill June 29 to speak up for full library funding at the federal level—with another 1,061 making themselves heard online.
New York Public Library staff members heaved a sigh of relief June 24 with the announcement that the system had dodged a catastrophic $37-million budget cut. “You spoke out loud and clear,” read a poignant thank-you message on the NYPL website. The open letter credited “the 130,000 who wrote letters, donated more than $144,000 online, called elected officials, and raised their voices on the steps of City Hall” with convincing Mayor Bloomberg and the City Council to restore enough funding to ensure five-day-a week service. Queens Library offered public thanks to elected officials and supporters alike for restoring $17 million to the budget, thus “making libraries a priority, for ensuring every one of our libraries remains open an average of five days a week.” A pragmatic Brooklyn Public Library indicated nothing as of the evening of June 28, maintaining its “save the library” web page. Among the variables still in play is the amount of state aid public libraries will receive; a contentious struggle at the state capitol makes the outcome anyones guess.
The New Jersey Library Association heralded a budget agreement between Gov. Chris Christie and the legislature that restores FY2010 funding levels for resource sharing and the New Jersey State Library. “We can breath a sigh of relief, but it doesn't mean it won’t happen again next year,” NJLA Executive Director Pat Tumulty said in the June 24 Vineland Daily Journal. Instead of suffering a $10.4-million cut. New Jersey’s public libraries are counting themselves lucky to contend with a $6-million reduction. And even though Gov. Christie signed the state budget June 29, many community libraries are vulnerable to the fiscal woes of their municipalities and a 2.9% annual property-tax cap. However, a bill that passed the state senate unanimously June 28 may offer some hope; if enacted, S. 2068 would give municipal libraries a dedicated line on property-tax bills and remove them from the cap.
While New York and New Jersey libraries (as well as those in Boston, Los Angeles, Charlotte, and countless points in between), have fought off draconian cuts for months, South Carolina’s library community had a narrow window of opportunity to win an override of Gov. Mark Sanford’s devastating veto of $4.65 million in state aid and $1.172 million in stimulus funds for public libraries. However, State Librarian David Goble marshalled advocates through traditional and social-network channels, and they connected with lawmakers so persuasively that Sanford’s veto was overturned five days later.

domain: finance


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Lily is on summer vacation and you can travel with her! Pack your bags and create a beautiful summer outfit for her in this new dress up title!
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Impress your friends and design your own stylish fidget spinner toy!
Tea - you can't only drink it, but use it for a refreshing makeover as well! Choose from different tea extracts and start the beauty adventure!
Have fun with surfer girl Nina on the beach! Help her design a new surf board and give her stunning makeover!
The school year is about to begin but this princess isn’t even close to being ready for it. Can you help her choose tons of awesome outfits and accessories in this online dress up game for girls? mobile
Stroll around Japan's fashion mecca Harajuku and create some truly kawaii outfits for Lily in this fun Manga dress up game!
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domain: artistic


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Everyone, it seems, is angry at Mayor Antonio Villaraigosa over his stalled bid to raise utility rates in the service of ending the city's fossil fuel addiction.
Local business leaders said the higher rates from the Department of Water and Power would have forced them to lay off workers. Outraged citizens complained in droves. And the City Council, reluctant to impose steep rate increases during a recession, rejected the mayor's proposal Friday, kicking it back to the DWP's board for reconsideration.
The proposed charges, designed to balance the DWP's ledger while underwriting the mayor's $648-million renewable energy trust fund, would have added anywhere from a few dollars to $50 a month to residential customers' bills. Now, they almost certainly will be revised downward. The department's past shenanigans on Measure B, and its seeming unwillingness to deliver a cost-efficient and verifiable green power roster, have made council members and the public understandably skeptical about whether the agency can be trusted to spend money wisely.
If the rate hikes are cut drastically, the mayor's ambitious promise to unplug the city from dirty energy will be put on hold. But softening the blow today is only postponing a sobering reckoning for tomorrow. Pain, and lots of it, is about to be visited on Los Angeles' electricity customers. The cost of power is going up, and nothing is going to halt the climb.
Here are the facts. Right now, Los Angeles gets more than 40% of its power from coal-fired plants in Arizona and Utah. These plants blanket the Grand Canyon in sulfurous haze, pour carbon fumes and deadly coal ash into the atmosphere, drain billions of gallons of precious Colorado River water, deposit mercury in the soil and leave a legacy of disease on Navajo and Hopi lands. Coal used to be cheap and dirty power. But it's about to become expensive and dirty power.
An independent review of the DWP's rate hike proposal prepared for the City Council estimated that the utility's cost of generating electricity from coal will rise at a rate of $175 million a year from 2009 to 2014 -- more money than would be raised annually by the mayor's carbon surcharge.
And that's not all. The DWP's cost for nuclear power is projected in the review as likely to rise from $61 million to $86 million from 2009 to 2011. And although no one can predict for certain , there is a fair chance that natural gas prices will inch back up toward their historic highs of just three years ago.
As the council's independent analysis makes clear, with or without a transition plan to renewable sources, the cost of generating electricity will continue to jump year after year just to keep fossil fuel power flowing over the transmission lines.
And then there's the really bad news: looming penalties for carbon emissions. While it's not yet entirely clear what the impact will be, laws aimed at curbing global warming are likely to result in stiff federal and state penalties if Los Angeles continues to rely so heavily on coal. One reason DWP rates historically have been lower than those of most other utilities is our dependence -- the heaviest among California utilities -- on all those train loads of bituminous black rock.
But that reliance is likely to result in new costs, estimated at between $330 million and $749 million a year, for emissions permits or carbon taxes. On the other hand, as the independent analysis notes, the introduction of a carbon tariff would make converting 20% of the city's power to renewable sources seem far less costly, since every dollar invested in a clean-energy grid would mean less money spent on carbon penalties.
A recession certainly isn't a convenient time to raise utility rates, and even a hefty hike won't wean the city any time soon from its reliance on coal. But even if the DWP Board of Commissioners scales back its proposal, as is likely, the utility still will be forking over larger and larger sums to continue our unnecessary and immoral consumption of dirty power -- and one way or another, Los Angeles ratepayers will foot the bill. We will be paying a hefty, self-administered tax to maintain a diet of 19th century fuel when we could have begun the admittedly arduous and expensive transition to clean energy.
And what would have been the price? For the vast majority of the city's residents, significantly less than the cost of a tank of gas a month.
Greg Goldin is the architecture critic for Los Angeles magazine.

domain: economics


Top 10 Richest Kpop Idols 2016. Most American pop stars see international success and tour around the world. He is legendary as a King of YouTube as his music album Gangnam Style created an enormous bustle on YouTube by having a couple of billion views.
K-Pop has become a popular genre of music all over the world and these bands are the ones whove earned the most from it. Top 10 Richest Korean Pop Idols 2020 2021 Popular Richest K-Pop Idols. Prime Minister and I 2013 The K2 2016 and also The King In Love 2017.
Lee Ji-Eun Lee Ji-eun better known by her stage name IU.
Top 10 Men K-pop Singer Idols of Asian Girls in 2016 The battle for the best K-pop singer idol is not ending soon. The popular genre originating in South Korea. Top 10 Richest KPop Idols Salary Net Worth UPDATED 2018 The idol competitions and shows give a chance to these talented pop stars to delight their fans with their singing skills. The business magazines Asia edition also listed him in its 30 under 30 in 2016.


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July 4, 2019
Happy 243rd birthday America! Today, Americans will be celebrating nationwide with barbecues, fireworks, parades and more. We’ll be travelling to visit family and friends at beaches, parks, pools and destinations around the country.
AAA estimates that this summer more than 41 million of us will be travelling, thanks to lower gas prices, strong consumer spending and rising disposable incomes. The July 4th Holiday is also the traditional kickoff of summer travel. We’ll be loading families and pets into our cars for a quick weekend trip nearby or maybe even an extended family road trip for a longer holiday. What that in mind, here are some tips on ensuring a safe and fun trip with your four-legged friend.
Before you leave
- Medication. Don’t forget to bring any and all prescriptions for you AND your dog.
- Exercise. This goes without saying, but don’t forget a brisk walk/jog/hike before you leave. This gives your dog a chance to “eliminate” before jumping in your vehicle and will likely reduce any excess energy.
- Snacks. Consider feeding your pooch a small treat with ginger or sugar. Studies have shown this will reduce nausea in your pup.
For the Road
- Water. Bedding. Wipes. Poo bags, and toys! Consider a collapsible water bowl for your dog. It saves more space than you think.
- Don’t forget a Travall Guard and/or Liner for your car. They will keep your dog secure and make cleanup quick if your dog has, er, an “accident”.
Plan for everything
- Know your route and potential places to stop for a quick walk or pee-break for your dog.
- Have a leash. You might be stopping unexpectedly in an unfamiliar area.You don’t want Fido chasing a squirrel!
- Fireworks! July 4th is a traditional fireworks extravaganza, but on the East Coast they happen throughout the summer. Know where and when they might be happening!
Happy Fourth of July from all of us and “Enjoy the Journey”.

domain: travel


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The University of North Carolina at Chapel Hill (UNC) HIV Cure Center and Cell Microsystems, a provider of instruments for the sorting and isolation of single cells, have received an approximately $283,000, 12-month Phase I Small Business Innovation and Research contract from the National Institutes of Health to develop an automated platform to quantify the latent HIV reservoir.
As researchers develop therapies to reverse HIV latency—a step toward clearing the virus from the body—an accompanying diagnostic test is also needed to accurately measure the viral reservoir and judge the efficacy of these new latency reversal agents.
The collaboration between UNC and Cell Microsystems aims to fill this need by using Cell Microsystem’s automated images analysis tools, the CytoSort Array and CellRaft AIR system, to screen and isolate thousands of patient-derived cells to detect emergence of HIV after exposure to potential therapeutics. If Cell Microsystem’s solutions accurately quantify the viral reservoir, the company along with UNC will apply for Phase II funding to explore the project’s commercial and scientific viability.
“We are very excited the CellRaft Technology will be utilized by a world-class team of investigators toward a historically intractable problem,” said Nick Trotta, PhD, Cell Microsystem’s director of product applications and market development. “As we talk to more HIV investigators, it’s clear that the platform has a lot of advantages that uniquely address the latency reversal drug screening process. We are also eager to contribute our genomics capabilities to better understand the precursors of HIV latency reversal.”
Prescient Medicine, Metabiomics to Develop Microbiome-Based GI Health Tests
Prescient Medicine and Meta-biomics are collaborating to develop a microbiome diagnostics platform for detecting precancerous colon polyps and diagnosing other types of gastrointestinal (GI) diseases including Crohn’s, colitis, and irritable bowel syndrome. These assays will apply Metabiomics’ MultiTag next-generation sequencing and microbiome analytics platform to detect warning signs of polyps and carcinogenesis in the colon. The partnership is currently aiming for the new tests to be available in 2020.
“The interrogation of the gut microbiome in order to assess GI health and predict colon cancer risk is a total game changer,” said Greg Kuehn, chief operating officer of Metabiomics. “Gastroenterologists have known for a long time that gut microbes are associated with GI disease. Now we’re finally applying these new metagenomics tools to analyze gut microbial DNA and bringing our understanding of GI disease to a new level.”
Qiagen to Acquire NeuMoDx, Commercialize NeuMoDx PCR Systems
Qiagen has signed an agreement to acquire the remaining 80.1% of NeuMoDx shares that it does not currently own at a predetermined price of approximately $234 million. Separately, the two companies also entered a strategic partnership to commercialize two of NeuMoDx’s new fully integrated systems for automation of polymerase chain reaction testing, the NeuMoDx 288 (high-throughput version) and NeuMoDx 96 (mid-throughput version).
These next-generation systems are designed to help clinical molecular diagnostics’ laboratories process increasing test volumes and deliver more rapid insights on a broad range of diseases. Under the terms of the agreement, Qiagen will initially distribute the NeuMoDx 288 and NeuMoDx 96 in Europe and other major markets outside of the U.S., while NeuMoDx will cover the U.S. directly.
Qiagen intends to begin commercialization of the NeuMoDx systems with an initial assay menu including the systems’ first two CE marked assays, which are for Group B Streptococcus and Chlamydia trachomatis/Neisseria gonorrhoeae infections.
Bristol-Myers Squibb, Natera to Evaluate ctDNA Lung Cancer Co-Diagnostic
Bristol-Myers Squibb has entered an agreement with Natera to use the company’s Signatera circulating tumor DNA (ctDNA) assay in a study to determine whether the test can serve as a co-diagnostic for adjuvant non-small cell lung cancer therapy.
Led by Charles Swanton, MD, PhD, of the Francis Crick Institute, the study will use the Signatera ctDNA assay to select patients who have minimal residual disease after surgical resection to receive adjuvant standard of care with or without Bristol-Myers Squibb’s drug Opdivo (nivolumab).
The first patient is expected to enroll in 2019 once Natera completes validation of the Signatera ctDNA assay under CLIA. “Our goal is to potentially use the learnings from this study to serve as Natera’s framework with other companies to investigate novel approaches from the metastatic setting in early-stage treatment,” said Matthew Rabinowitz, PhD, Natera CEO. “We believe that our technology will potentially enable treatment selection for patients most likely to benefit.”
Seven Bridges, e-NIOS Team to Improve Biomarker Extraction From Omics Data
The biomedical data platform and analytics company Seven Bridges has joined forces with the start-up e-NIOS in an effort to improve derivation of robust biomarkers from next-generation sequencing and multi-omic data. Together, the two companies will leverage machine learning and physiology to partially automate interpretation of potential biomarkers.
The partnership will use e-NIOS’ technology, which enables unsupervised translation of omics data through BioInfoMiner, a cloud platform that resolves biological complexity and derives molecular signatures suitable for data-driven interpretation. “e-NIOS’ technology has the unique ability to combine biological network information with data-driven models,” said Brandi Davis-Dusenbery, CEO of Seven Bridges. “Our strategic partnership supports Seven Bridges’ mission to connect the world’s biomedical information and rapidly transform it into actionable information.”
The project will also leverage the Seven Bridges Platform, a high-performance cloud computing service for streamlined processing of massive genomic datasets.
Merck, Definiens Partner on Immuno-Oncology Biomarker Discovery
Definiens will support Merck’s exploratory and clinical immunotherapy development programs with the Definiens TissuePhenomics solutions, which quantify biomarkers for immunoprofiling and enable users to share data via web-based collaboration software. Based in Munich, Germany, Definiens focuses on tissue-based biomedical digital imaging and data visualization, mining, and analysis.
“This partnership agreement is a testament to Definiens’ ability to transform tissue image data into valuable insights using our proprietary data mining methods for biomarker discovery,” said Oliver Lehner, vice president of Definiens business development and partnering.
In addition to providing Merck with digital tissue analysis tools, Definiens will provide a dedicated team to help Merck maximize synergies between its immuno-oncology projects. Merck believes that the tissue diagnostics and biomarker data gained through this collaboration will enable the company to make more informed decisions about its immuno-oncology product development portfolio.

domain: biology