"That childhood obesity could inflict considerable pain of the emotional kind on its sufferers was, in fact, a new belief in the twentieth century. It was sufficiently radical an idea that doctors felt the need to tell patients that the jolly fat child was a figment of popular imagination. "I was an obese child myself, and I know that there is genuine mental suffering in being an obese child," said , a famous diet doctor and newspaper columnist. "The fat child is not a happy child." In 1921, this was revelatory and had big implications for how Americans saw themselves and the issue of obesity in childhood."

"We have shown previously that a maternal diet during pregnancy and lactation plays a role in predisposing offspring to obesity. Here we show that rat offspring born to mothers fed the same junk food diet rich in fat, sugar and salt develop exacerbated adiposity accompanied by raised circulating glucose, insulin, triglyceride and/or cholesterol by the end of adolescence (10 weeks postpartum) compared with offspring also given free access to junk food from weaning but whose mothers were exclusively fed a balanced chow diet in pregnancy and lactation. Results also showed that offspring from mothers fed the junk food diet in pregnancy and lactation, and which were then switched to a balanced chow diet from weaning, exhibited increased perirenal fat pad mass relative to body weight and adipocyte hypertrophy compared with offspring which were never exposed to the junk food diet."

"We repeatedly measured 24-hour total energy expenditure, resting and nonresting energy expenditure, and the thermic effect of feeding in 18 obese subjects and 23 subjects who had never been obese. The subjects were studied at their usual body weight and after losing 10 to 20 percent of their body weight by underfeeding or gaining 10 percent by overfeeding. ... The thermic effect of feeding and nonresting energy expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kilogram of fat-free mass per day, respectively, after weight gain. These changes in energy expenditure were not related to the degree of adiposity or the sex of the subjects. ... Maintenance of a reduced or elevated body weight is associated with compensatory changes in energy expenditure, which oppose the maintenance of a body weight that is different from the usual weight. These compensatory changes may account for the poor long-term efficacy of treatments for obesity."

"Obesity is a double victory for consumerism. Instead of eating little, which will lead to economic contraction, people eat too much and then buy diet products - contributing to economic growth twice over."

"We know that 25 per cent of women in the UK are carriers of the APOE4 gene and that almost two thirds of Alzheimer's patients are women."

"All the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall"

"Some birth defects can be prevented. Vaccination, adequate intake of folic acid or iodine through fortification of staple foods or supplementation, and adequate care before and during a pregnancy are examples of prevention methods."

"The most common severe birth defects are heart defects, neural tube defects and Down syndrome."

"Although birth defects may be the result of one or more genetic, infectious, nutritional or environmental factors, it is often difficult to identify the exact causes."

"An estimated 240,000 newborns die worldwide within 28 days of birth every year due to birth defects. Birth defects cause a further 170 000 deaths of children between the ages of 1 month and 5 years."

"Nine of ten children born with a serious birth defect are in low- and middle-income countries."

"As neonatal and under-5 mortality rates decline, birth defects become a larger proportion of the cause of neonatal and under-5 deaths."

"Birth defects can contribute to long-term disability, which takes a significant toll on individuals, families, health care systems and societies."

"Let's avoid those unnecessary antibiotics. Let's not feed the antimicrobial-resistance demon."

"Antimicrobial resistance (AMR) has developed as one of the major urgent threats to public health causing serious issues to successful prevention and treatment of persistent diseases. In spite of different actions taken in recent decades to tackle this issue, the trends of global AMR demonstrate no signs of slowing down. Misusing and overusing different antibacterial agents in the health care setting as well as in the agricultural industry are considered the major reasons behind the emergence of antimicrobial resistance. In addition, the spontaneous evolution, mutation of bacteria, and passing the resistant genes through horizontal gene transfer are significant contributors to antimicrobial resistance. Many studies have demonstrated the disastrous financial consequences of AMR including extremely high healthcare costs due to an increase in hospital admissions and drug usage."

"The cost of antimicrobial resistance is immense, both economically as well as for human health and lives. The Organisation for Economic Co-operation and Development (OECD) has released a new report (Stemming the superbug tide, 7 Nov 2018), which predicts that 2.4 million people in Europe, North America and Australia will die from infections with resistant microorganisms in the next 30 years and could cost up to US$3.5 billion per year. Southern European countries are predicted to have the highest mortality rate due to resistant infections among countries included in the study. Furthermore, many low and middle-income countries already have high resistance rates, which are predicted to increase disproportionately. For example, in Brazil, Indonesia and Russia 40–60% of infections are already caused by resistant microorganisms, and resistance is predicted to rise 4–7 times faster in these countries than in other OECD countries."

"The development of antibiotics is considered among the most important advances of modern science. Antibiotics have saved millions of lives. However, antimicrobial resistance (AMR) threatens this progress and presents significant risks to human health. ... The increase in AMR has been driven by a diverse set of factors, including inappropriate antibiotic prescribing and sales, use of antibiotics outside of the health care sector, and genetic factors intrinsic to bacteria. The problem has been exacerbated by inadequate economic incentives for pharmaceutical development of new antimicrobial agents. A range of specific AMR concerns, including carbapenem- and colistin-resistant gram-negative organisms, pose a clinical challenge. Alternative approaches to address the AMR threat include new methods of antibacterial drug identification and strategies that neutralize virulence factors."

"Quantitative estimation of an individual's risk of infection due to airborne pathogens requires knowledge of the pathogen's infectious dose, in addition to estimates of the pathogen's airborne concentration and the person's exposure duration. Based on our review of the published literature on Q fever, we conclude that the infectious dose of Coxiella burnetii is likely one rickettsia, and that the probability of a single organism initiating infection is approximately 0.9. Findings in experiments exposing guinea pigs to C. burnetii via intraperitoneal injection and inhalation of respirable aerosols firmly support a “one-hit” Poisson model of infection."

"The 21 August 1937 issue of the Medical Journal of Australia contained two articles on a hitherto unknown disease affecting abattoir workers and farmers — Q fever (with the “Q” standing for query). The first of these was by Edward Holbrook Derrick, Director of the Laboratory of Microbiology and Pathology, Queensland Health Department, Brisbane, and comprised his meticulous clinical descriptions and subsequent experiments to isolate the causative organism. ... During his research, Derrick sought the help of Frank Macfarlane Burnet, and the second article by Burnet and Mavis Freeman from the Walter and Eliza Hall Institute of Medical Research in Melbourne described their identification of the causative agent."

"This disease typically manifests as a self-limiting, febrile illness known as acute Q fever. Due to the aerosol transmissibility, environmental persistence, and infectivity of C. burnetii, this pathogen is a notable bioterrorism threat."

"The cows were heavily infected with rickettsiae, and we were getting cases of Q fever in people who were drinkers of raw milk, and in dairy workers who were surrounded by a contaminated atmosphere. We mentioned how artificial dairy husbandry is down there in the Los Angeles area. You've got these enclosure where the cattle are kept, and of course, as manure accumulates, the cattle get higher and higher off the ground, to the point they can probably step over the fence. At that time, the dairy people bring in bulldozers and clean out the premises, and that's when you begin to get a few cases of Q fever, either amongst the employees or amongst the neighbors."

"We also don’t know yet what role other factors may play, such as environmental exposures, medications, or other infections that the children might have"

"But you never know, it might be fun to do it covered in shit."

"I’ve done research, this is what they do: number one, you can see a man here, having sucked the other person’s rectum, and the other person is poo-pooing, and this one is eating the poo-poo all over the place! Tell me, when you have a law against homosexuality, do you say, “except eating poo-poo?” I mean look at this guy sincerely! Bishop? [Bishop groans and leans away in disgust]"

"Now it's time for my breakfast."

"Crazier things have happened on the road."

"I thought [naming a sex act after Rick Santorum] was a super idea and asked my readers to nominate sex acts for the honor of being known as a "santorum." Nominations poured in--more than 3,000! I rejected some of the suggested sex acts for being too broad (oral sex), others for being too rare (manrimming-dog), still others for being completely fictional (donkey punching, dirty sanchez). I also eliminated nominated sex acts that already have perfectly good names (fisting, felching, rimming, scat)."

"I don’t speak with a stupid filmmaker about his poop fetish!"

"I have taken time to do a little research to know what homosexuals do in the privates [sic] of their bedroom. One of the thing [sic] they do is called anal licking, where a man’s anus [imitates] is licked [kissing noise] like this by the other person [man says “like ice cream”] like ice cream. And then what happens, even poo-poo comes out [demonstrates using hands]— the other person poo-poos out, and then they eat the poo-poo!"

"Type 2 diabetes accounts for almost 90% of all cases of diabetes in adults worldwide. In general, as countries become richer, people eat a more sugar- and fat-rich diet and are less physical active — and the incidence of diabetes rises. On average, nearly 8% of adults living in high-income countries (see map for country classification) have diabetes. It is, however, upper-middle and middle-income countries that have the highest prevalence of diabetes; over 10% of adults in these countries have the condition."

"Believing that the want of success to prepare extracts of uniform potency as due to the destruction of the antidiabetic hormone by the digestive enzymes also present in the gland, F. G. Banting suggested preparing them from duct-ligated pancreas, and with the aid of C. H. Best, and under my direction, he succeeded in 1922 in showing that such extracts reduced the hyperglycaemia and glycosuria in depancreatized dogs. The general symptoms of diabetes were also found to be alleviated and the duration of life of the depancreatized animal prolonged, by the repeated injection of alcoholic extracts of foetal, as well as of adultox pancreas. Later it was shown, in collaboration with Collip, that other symptoms of diabetes, namely the ketonuria and the absence of glycogen from the liver, were favourably influenced by the extracts and, with Hepburn, that the respiratory quotient became raised. These results on depancreatized dogs showed beyond doubt that the antidiabetic hormone was present in potent form in the extracts, and the time seemed ripe to investigate their action on the clinical forms of diabetes. This was done by Banting in a severe case under the care of W. R. Campbell, with the result that the hyperglycaemia and glycosuria were diminished. At the same time, however, it was found that it would be necessary to rid the extracts of irritating substances before the value of their repeated injection in the treatment of diabetes in man could be adequately put to the test. This was accomplished by Collip, and the name insulin was decided upon for the purified extract."

"The susceptibility and severity of is made more severe by diabetes, with the impact on the disease process inversely proportional to the level of glycemic control. Although type 1 diabetes mellitus and type 2 diabetes mellitus have different etiologies, and their impact on bone is not identical, they share many of the same complications. Studies in animals and humans agree that both forms of diabetes increase inflammatory events in periodontal tissue, impair new bone formation, and increase expression of in response to bacterial challenge. High levels of glucose, reactive oxygen species, and advanced glycation end-products are found in the periodontium of diabetic individuals and lead to increased activation of nuclear factor-kappa B and expression of inflammatory cytokines such as tumor necrosis factor and interleukin-1. Studies in animals, moreover, suggest that there are multiple cell types in periodontal tissues that are affected by diabetes, including leukocytes, vascular cells, mesenchymal stem cells, periodontal ligament fibroblasts, osteoblasts, and osteocytes."

"Evidence from observational studies and randomized trials suggests that prediabetes and type 2 diabetes mellitus (T2DM) can develop in genetically susceptible individuals in parallel with weight (that is, fat) gain. Accordingly, studies show that weight loss can produce remission of T2DM in a dose-dependent manner. A weight loss of ~15 kg, achieved by calorie restriction as part of an intensive management programme, can lead to remission of T2DM in ~80% of patients with obesity and T2DM. However, long-term weight loss maintenance is challenging. Obesity and T2DM are associated with diminished glucose uptake in the brain that impairs the satiating effect of dietary carbohydrate; therefore, carbohydrate restriction might help maintain weight loss and maximize metabolic benefits. Likewise, increases in physical activity and fitness are an important contributor to T2DM remission when combined with calorie restriction and weight loss."

"On October 30th, 1920, I was attracted by an article by , in which he pointed out the similarity between the degenerative changes in the cells of the pancreas following experimental ligation of the duct, and the changes following blockage of the duct with s. Having read this article, the idea presented itself that by ligating the duct and allowing time for the degeneration of the acinus cells, a means might be provided for obtaining an extract of the islet cells free from the destroying influence of trypsin and other pancreatic enzymes."

"Even for most of us who spend our time working in the field of experimental diabetes, the primary concern is the disorder which occurs in the human subject. To stimulate our thoughts in this field, I will attempt, briefly, to list the possible causes of this disorder. ... Some Possible Causes of Diabetes 1. Defects in the pancreas as a whole, including the beta cells. 2. Defects in the formation of insulin. 3. Defects in the liberation of insulin. 4. Abnormal destruction of insulin. 5. Genetic defects involving insulin-dependent reactions. 6. Excess of diabetogenic agents. 7. Genetic defects making tissues abnormally suspectible to diabetogenic substances. 8. Genetic defects independent of hormonal actions."

"The modern era of diabetes knowledge began with the accidental discovery by a European research physiologist, , that in its most severe manifestation, now called type I diabetes, the disorder is generated with the pancreas, not, as had been previously believed, the liver or the stomach."

"The lesions of atherosclerosis are responsible for changes in the heart that can lead to myocardial infarction, in the brain to cerebral infarction or stroke, and in the peripheral vasculature to gangrene and loss of function. Lesions of atherosclerosis represent the principal cause of death in the United States, Europe, and part of Asia ... The advanced lesions of atherosclerosis, the sources of these potentially disastrous clinical events, consist of an extensive inflammatory, fibroproliferative response that intrudes into the lumen of the affected artery, compromises the flow of blood and, thus, oxygen to the affected part, and leads to clinical sequelae. The lesions represent a culmination of interactions between two types of leukocytes, circulating blood monocytes and T lymphocytes, that interact with the lining endothelium, enter into the artery wall, and have the potential to release various bioactive molecules. Ultimately, these interactions result in the migration and proliferation of smooth muscle cells, which elaborate connective tissue within the intima of the affected artery and produce the advanced lesions of atherosclerosis. Platelet mural thrombi and, later, occlusive thrombi can markedly affect the progress of the disease and lead to sudden death. Thus three cellular components in the circulation—monocytes, T lymphocytes, and platelets—together with two cells of the artery wall—endothelium and smooth muscle—interact in multiple ways to generate the lesions of atherosclerosis."

"The clinical manifestations of atherosclerosis are nowadays the main cause of death in industrialized countries, but atherosclerotic disease was found in humans who lived thousands of years ago, before the spread of current risk factors. Atherosclerotic lesions were identified on a 5300-year-old mummy, as well as in Egyptian mummies and other ancient civilizations. For many decades of the twentieth century, atherosclerosis was considered a degenerative disease, mainly determined by a passive lipid storage, while the most recent theory of atherogenesis is based on endothelial dysfunction. The importance of inflammation and immunity in atherosclerosis’s pathophysiology was realized around the turn of the millennium, when in 1999 the famous pathologist Russell Ross published in the New England Journal of Medicine an article entitled “Atherosclerosis – an inflammatory disease”. In the following decades, inflammation has been a topic of intense basic research in atherosclerosis, albeit its importance has ancient scientific roots. In fact, in 1856 Rudolph Virchow was the first proponent of this hypothesis, but evidence of the key role of inflammation in atherogenesis occurred only in 2017. It seemed interesting to retrace the key steps of atherosclerosis in a historical context: from the teachings of the physicians of the Roman Empire to the response-to-injury hypothesis, up to the key role of inflammation and immunity at various stages of disease."

"Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. Unraveling the roles of cytokines as inflammatory messengers provided a mechanism whereby risk factors for atherosclerosis can alter arterial biology, and produce a systemic milieu that favors atherothrombotic events. The discovery of the immune basis of allograft arteriosclerosis demonstrated that inflammation per se can drive arterial hyperplasia, even in the absence of traditional risk factors. Inflammation regulates aspects of plaque biology that trigger the thrombotic complications of atherosclerosis. Translation of these discoveries to humans has enabled both novel mechanistic insights and practical clinical advances."

"Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation."

"Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors that regulate lipid and lipoprotein metabolism, glucose homeostasis and inflammation. The PPAR family consists of three proteins, α, β/δ and γ. Recent data suggest that PPARα and γ activation decreases atherosclerosis progression not only by correcting metabolic disorders, but also through direct effects on the vascular wall. PPARs modulate the recruitment of leukocytes to endothelial cells, control the inflammatory response and lipid homeostasis of monocytes/macrophages and regulate inflammatory cytokine production by smooth muscle cells. Experiments using animal models of atherosclerosis and clinical studies in humans strongly support an anti-atherosclerotic role for PPARα and γ in vivo. Thus, PPARs remain attractive therapeutic targets for the development of drugs used in the treatment of chronic inflammatory diseases such as atherosclerosis. Future research will aim for the development of more potent drugs with co-agonist activity on PPARα, PPARβ/δ and/or PPARγ as well as tissue and target gene-selective PPAR receptor modulators (SPPARMs)."

"Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis. Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance."

"Elevated blood pressure (BP) remains an extraordinarily common and important risk factor for cardiovascular and renal diseases, including stroke, coronary heart disease, heart failure, and kidney failure. According to the most recent NHANES survey (1999 to 2000), 27% of adult Americans have hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or use of antihypertensive medication), and another 31% have prehypertension (systolic BP of 120 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg, not on medication). ... Prehypertensive individuals have a high probability of developing hypertension and carry an excess risk of cardiovascular disease as compared with those with a normal BP (systolic BP <120 mm Hg and diastolic BP <80 mm Hg). ... It has been estimated that among adults >50 years of age, the lifetime risk of developing hypertension approaches 90%. ..."

"In this systematic review and meta-analysis, including 74 trials and more than 300 000 patients, treatment to lower blood pressure was associated with a reduced risk for death and cardiovascular disease if baseline systolic blood pressure was 140 mm Hg or above. Below 140 mm Hg, the treatment effect was neutral in primary preventive trials, but with possible benefit on nonfatal cardiovascular events in trials of patients with coronary heart disease. ... High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated."

"Abnormal sodium metabolism may be critical in the causation of certain forms of hypertension, particularly salt-sensitive hypertension. Long-term restriction of sodium intake in patients at high risk for the development of hypertension may reduce the chances of established hypertension occurring later. These high-risk patients in whom subsequent hypertension may be prevented include normotensive patients with family histories of hypertension, elderly patients, black patients, and those with low-renin hypertension. Treatment of hypertension with moderate sodium restriction to 70 mEq/day will significantly reduce blood pressure in a large percentage of patients, particularly known salt-sensitive hypertensive patients. This degree of restriction is also an effective adjunctive therapy for patients receiving antihypertensive medications. There is convincing experimental, epidemiologic, and clinical evidence that moderate sodium restriction helps prevent and assists in the treatment of hypertension in those patients who are genetically predisposed to develop primary hypertension or who already have hypertension. There is no evidence that this degree of sodium restriction is harmful."

"The importance of white coat hypertension rests on a curious haemodynamic phenomenon, which has quite profound clinical relevance: patients—let us call them people, because they may not be ill—who appear to have hypertension when their blood pressure is measured by the traditional Riva-Rocci/KorotkoV method, have normal blood pressures when ambulatory techniques are used to record their blood pressures away from the medical environment. Put another way, conventional blood pressure measurement is misleading in people with white coat hypertension (and most of us have some degree of white coat reaction), and if decisions are based on these measurements inappropriate diagnosis and treatment may result."

"The effect of induced hypertension on the blood-brain barrier (BBB) change in Mongolian gerbils exposed to various periods of ischemia was studied. Evans blue dye was used to determine the BBB change in animals subjected to different levels of hypertension after 3 h ischemia. Horseradish peroxidase (HRP) was used in electronmicroscopic studies of animals subjected to 30 min, 1, 3 or 6 h ischemia and subsequently exposed for 30 min to varying periods and sequences of normo- and hypertension. Furthermore, HRP-labeled vesicle counts were performed in animals from the 30-min ischemia group. Our findings revealed that hypertension, after blood flow restoration following ischemia, induces and/or accelerates BBB damage by enhancing endothelial vesicular and/or tubulo-channel transport."

"Thirteen years after Sabin and Olitsky’s success with growing poliovirus in brain tissue, researchers at the lab of John Enders at the Children’s Hospital in Boston successfully grew the virus in a culture of skin and muscle tissue from a human embryo—in a fortunate happenstance. At the time, the researchers were focused on trying to isolate and grow varicella, the chickenpox virus. They had already succeeded in growing mumps and influenza viruses, and had moved on to varicella, which they knew grew in human cells. After preparing flasks with human embryonic tissue, they inoculated four flasks with throat washings from chickenpox patients. Another four flasks were inoculated with a strain of poliovirus as a control group. The chickenpox virus did not grow in this case, but to the researchers’ great surprise, poliovirus did. They went on to grow two other strains of poliovirus, and in many types of human embryonic tissue, without using nervous system tissue. They were able to grow the virus rapidly and to very high concentrations using the “roller tube” apparatus created by researcher George Otto Gey in the 1930s."

"Hopes of growing poliovirus in the lab without the use of live animals drove many researchers in the 1930s and 1940s. Cell cultures involve growing cells in a culture dish, often with a supportive growth medium like collagen. They offer a level of control unavailable using live animals, and can also support large-scale virus production. (For more about cell cultures and cell lines, as well as cell lines made using human cells, see our article “Human Cell Strains in Vaccine Development.”) Early efforts to grow poliovirus in culture, however, repeatedly ended in failure. In 1936, Albert Sabin and Peter Olitsky at the Rockefeller Institute successfully grew poliovirus in a culture of brain tissue from a human embryo. The virus grew quickly, which was promising, but Sabin and Olitsky were concerned about using this as starting material for a vaccine, fearing nervous system damage for vaccine recipients. They tried to grow poliovirus in cultures using tissue taken from other sources, but were unsuccessful."

"For demonstrating that poliovirus could be reliably grown without using nervous tissue, Enders and his colleagues Thomas Weller and Frederick Robbins were awarded the Nobel Prize in Physiology or Medicine in 1954. Their discovery proved to be the breakthrough needed to develop a polio vaccine. In 1951, Jonas Salk and his colleagues at the University of Pittsburgh found that poliovirus could also be propagated on a large scale in monkey kidney cells. Over time, most vaccine development efforts shifted to cell strains—cultures made up of only a single type of cell. These strains can be derived from tissue cultures, which contain multiple types of cells. While viruses can be grown in tissue cultures, cell strains allow continuous observation and control that may not be possible in cultures containing multiple types of cells. This same transition was made in the development of polio vaccines. A monkey kidney cell strain is used to grow poliovirus for the inactivated polio vaccine made today."