| NHS Choices: Behind the headlines “Low levels of the stress hormone cortisol marks out children at higher risk of developing chronic fatigue syndrome as adults,” reported the BBC today. It said that if children with low levels of cortisol are exposed to trauma, such as sexual abuse, they are six times more likely to develop the condition. Contrary to the impression that might be gained from parts of the news report, this study did not assess cortisol levels in childhood, but only in adults with or without CFS. Although it found that more people who had CFS reported childhood trauma, this does not conclusively prove that trauma itself causes CFS. This study contributes to knowledge about potential risk factors for CFS, but much more research is needed into the causes of this condition. Where did the story come from?Christine Heim and colleagues from the Emory University School of Medicine and Centers for Disease Control and Prevention (CDC) carried out this research. The work was funded by the CDC. The study was published in the peer-reviewed medical journal Archives of General Psychiatry. What kind of scientific study was this?This case control study looked at whether experiences of childhood trauma differed between people with chronic fatigue syndrome (CFS) and those without it. The causes of CFS are not known, but several risk factors, including childhood trauma, have been suggested. One theory suggests that trauma in childhood may affect how people respond to stress, and that this could increase the risk of developing CFS. The researchers wanted to investigate this by looking at levels of the hormone cortisol, which is involved in the body’s stress response, in people with and without CFS. The study involved 113 people with CFS and 124 people without the condition. The participants with CFS were found through a larger population-based survey of CFS carried out by telephone in Georgia, USA between September 2004 and July 2005. In this larger survey, household telephone numbers were randomly selected and called, and one adult aged 18 to 59 years of age (average age 44) from each household was asked to take part. This survey identified 469 people who had felt fatigued for six months or more, did not feel better after rest, did not report any medical or psychiatric conditions that might explain their fatigue, and who had at least four out of eight typical symptoms of CFS (suspected cases). These people were invited for a clinical interview. Of these, 292 people attended the interview and 113 were confirmed as having CFS, based on standard criteria. The researchers identified a control group by carrying out clinical examinations on people who were believed to not have CFS and who were matched to the suspected CFS cases in terms of age, gender, race, and the area where they lived. Of these people, 124 people were confirmed as being healthy, and acted as controls. All participants had a psychiatric examination , and the researchers excluded anyone who had certain conditions, such as manic depression (bipolar disorder) or psychosis. The participants then answered a standard questionnaire about childhood trauma, which assessed five areas including emotional and physical neglect, and emotional, physical, and sexual abuse. Each area was assessed using five statements which the participants rated from “never true” (one point) to “very often true” (five points). Scores for each area (i.e. emotional and physical neglect, and emotional, physical, and sexual abuse) were added together, giving a total ranging from 5 to 25. People who scored above a specified amount were classed as having had childhood trauma of moderate or greater severity. The participants’ cortisol levels were measured using samples of their saliva taken immediately upon waking in the morning, and 30, 45, and 60 minutes later. The researchers then compared levels of childhood trauma between the cases and controls. They used statistical methods to look at whether the levels of psychological symptoms a person reported in the psychiatric examination affected the link between childhood trauma and CFS. The researchers also looked at the relationship between cortisol levels, childhood trauma, and CFS. What were the results of the study?The researchers found that higher levels of childhood trauma were reported by people with CFS than in people without it. About 62% of people with CFS reported childhood trauma in at least one of the five areas compared with about 24% of those without CFS. Experiencing childhood trauma increased the risk of CFS 5.6-fold. In particular, levels of sexual abuse, emotional abuse and emotional neglect showed the greatest differences between cases and controls, after adjusting for (taking into account) the other areas. People with CFS showed more mental health symptoms, including depression, anxiety and post-traumatic stress disorder. However, the link between childhood trauma and CFS remained even after adjusting for these symptoms. The researchers also found that people with CFS had lower levels of cortisol on awakening than controls. If the participants were split into those with and without trauma, only those with CFS and childhood trauma had reduced levels of cortisol. What interpretations did the researchers draw from these results?The researchers conclude that their results “confirm childhood trauma as an important risk factor of CFS”. They suggest that reduced levels of cortisol, which is a “hallmark feature of CFS, appears to be associated with childhood trauma”. This may indicate the biological mechanism behind how childhood trauma could affect risk of CFS. They say that their findings “are critical to inform pathophysiological research and to devise targets for the prevention of CFS”. What does the NHS Knowledge Service make of this study?This was a relatively small study, which may provide some early evidence of a link between psychological and biological risk factors for CFS. There are some limitations to note, however:
Although this study cannot prove that childhood trauma itself “causes” CFS, or that childhood cortisol levels can predict CFS in adulthood, this study contributes to knowledge about potential risk factors for CFS. Much more research is needed to fully understand the causes of this complex condition. “Parents who limit their smoking to the garden could still be harming their children,” warns The Daily Telegraph. The newspaper says this is because children can inhale toxins which remain on the clothes, hair and skin after smoking, which it terms as ‘third-hand smoke’. The story is based on a US study. The research behind this story did not actually assess the dangers of “third-hand” smoke, but instead surveyed people’s beliefs about these dangers, and whether this was related to the likelihood of banning smoking in their own homes. Only 43% of non-smokers thought third-hand smoking was harmful to children, compared with 65% of non-smokers. People who believed third-hand smoke was harmful were also more likely to have a no-smoking rule in their homes. Consequently, the researchers suggest that public information on third-hand smoke might encourage home smoking bans. Stopping smoking completely is the best way to avoid the dangers of smoking for individuals and those around them. However, while working towards quitting smoking, banning it in the home is a good way to protect children from the dangers of tobacco smoke. Where did the story come from?This research was conducted by Dr Jonathan Winickoff and colleagues from Massachusetts General Hospital and other research centres in the US. The study was funded by the Flight Attendant Medical Research Institute, the National Cancer Institute, the Office of Rural Health Policy of the Department of Health and Human Services. It was published in the peer-reviewed medical journal Pediatrics. What kind of scientific study was this?This was a cross-sectional survey about adults’ beliefs about third-hand smoking, and whether these varied between smokers and non-smokers. Third-hand smoke was defined as “residual tobacco smoke contamination that remains after the cigarette is extinguished”. This includes toxins that settle on surfaces in the home, and remain even after a cigarette has been smoked. The authors quote the US Surgeon General’s 2006 report on involuntary smoking, which concludes that there is no “safe” level of exposure to tobacco smoke. The researchers say that “the majority of adults are aware that visible [second-hand smoke] is harmful to health” and that some smokers take measures to avoid exposing others, for example by avoiding smoking around non-smokers in the home. The researchers believe that people who were aware of the dangers of third-hand smoke would be more likely to ban smoking inside their own homes. These results come from the 2005 annual nationwide telephone survey The Social Climate Survey of Tobacco Control. Computer programmes randomly selected a nationally representative sample of telephone numbers to dial, and researchers asked to speak with the adult in the home whose next birthday was nearest to the time of the phone call, and asked if they would take part in the survey. Those who agreed were asked questions about whether they currently smoked (defined as having smoked 100 cigarettes or more in their lifetime, and now smoking every day or some days). They were also asked what smoking policy they maintained in their homes, e.g. was smoking allowed in the whole house, part of the house, none of the house, or the respondents were unsure or didn’t know. Other questions assessed how strongly they agreed or disagreed with two statements about second and third-hand smoke;
The researchers then looked at what proportion of people believed that second and third-hand smoke was harmful. They also looked at whether this varied among smokers and non-smokers, those with different home smoking policies, and different levels of knowledge about smoking policies in local restaurants and bars. The results also took into account factors that might also affect the results, such as educational achievement and race. What were the results of the study?1,478 adults completed the survey, and almost a fifth of these people were current smokers. About one quarter of participants lived in a house with a smoker. The majority of participants (93%) believed that second-hand smoke was harmful to children, but only 61% believed that third hand smoke was harmful. About a fifth of people reported that they did not know if third-hand smoke was harmful for children, compared with only about 3% not knowing if second-hand smoke was harmful. A strict smoking ban in the home was more common among non-smokers (88%) than among smokers (27%). People with a strict home smoking ban were more than twice as likely to report that third-hand smoking was harmful than those who did not have such a ban. What interpretations did the researchers draw from these results?The authors concluded that there is an association between the belief that third-hand smoke is dangerous and strict home smoking bans. They suggest that “emphasising that third-hand smoke harms the health of children may be an important element in encouraging home smoking bans”. What does the NHS Knowledge Service make of this study?This large survey highlights the fact that a considerable proportion of people are not aware of the dangers of lingering toxins from cigarette smoke. There are some points to note when interpreting this research:
Contrary to The Daily Telegraph’s message (which highlights the dangers of smoking even outside the house), the main conclusion of the authors of this paper is that that knowledge about the dangers of third hand smoke is associated with home smoking bans. They say that informing people about the dangers may motivate them to take the positive step of having a smoking ban in their homes. The authors acknowledge that toxins may still be found on clothes, or enter via windows and doors, and that a home smoking ban should ideally be accompanied by efforts to stop smoking altogether. Golfers face the risk of hearing problems if they use the latest generation of golf clubs, says the Daily Mail. The newspaper claims the “sonic boom” noise from titanium drivers had damaged the hearing of a 55-year-old man, and suggests that golfers should wear earplugs to help protect their hearing. The story is based on a study in the Christmas edition of the British Medical Journal in which doctors describe a golfing patient’s ear damage and tinnitus. The doctors believe these problems came from repeated use of a particular titanium driver. Researchers measured the noise levels produced when a golf ball was hit with different drivers, and suggested that newer titanium clubs may expose players to quite high sound levels. This study uses low-level evidence and appears to be written in a light-hearted spirit in keeping with other articles in the festive issue of the British Medical Journal. As the study is based on anecdotal evidence, the results should be interpreted with caution, and it remains to be seen whether hearing loss will become endemic among golfers. However, it is sensible to limit exposure to uncomfortably loud noises wherever possible. Where did the story come from?This research was conducted by doctors M.A. Buchanan and P.R. Prinsley and colleagues from Norfolk and Norwich University Hospital. There is no information on any external funding, and the authors declare they have no competing interests. The study was published in the peer-reviewed British Medical Journal. What kind of scientific study was this?This publication combines a case report of a golfer with hearing problems, and a descriptive study of noise levels attained during tests of different golf drivers. In the case report, the doctors describe the 55-year-old man who had presented to an ear, nose and throat outpatient clinic with tinnitus and reduced hearing in his right ear. His hearing problems were diagnosed as relating to exposure to loud noise. History revealed that the golfer had been using a King Cobra LD titanium golf club three times a week for 18 months, and he reported that the noise was “like a gun going off”. The man had stopped using the club because it had become so unpleasant. Other than this, he had no significant exposure to loud sound in his work or recreation time. The researchers go on to discuss the energy transfer between the head of the golf club and the ball, which is measured as the ‘coefficient of restitution’, or COR. The United States Golf Association stipulates that clubs for competition use should have a COR value of 0.83 or less. A COR value of 0.83 means that if the club connects with the ball at 100mph, the ball will travel 83mph. Two of the titanium clubs tested (including the club used by the patient) had a COR value greater than 0.83. The researchers then assessed the noise levels produced by 12 golf clubs: six thin-faced titanium drivers and six thicker-faced stainless steel drivers. They used a ‘modular precision sound level meter’ to record the noise levels generated when a professional golfer hit two-piece golf balls with these clubs. The sound meter was positioned 1.7m away from the club as this was the estimated distance between the contact with the ball and a golfer’s ear. The researchers then presented the different noise levels from the different drivers. What were the results of the study?Following an examination and medical history, the doctors attributed the man’s hearing problems to exposure to noise through the use of his titanium golf club. Their investigation into the noise produced by different types of drivers showed that the thin-faced titanium golf drivers “all produced greater sound levels than the stainless steel clubs”. What interpretations did the researchers draw from these results?The doctors conclude that their study provides “anecdotal evidence that caution should be exercised by golfers who play regularly with thin-faced titanium drivers” in order to avoid damaging their hearing. What does the NHS Knowledge Service make of this study?This small study does provide some anecdotal evidence that golf clubs produce a high level of noise when hit. There are several points to note:
The article appears to have been written in a light-hearted spirit, and given that it is based on a single case study and statistically non-comparative evidence, the results should be interpreted as such. It is doubtful that golfers as a group are at a particularly increased risk of hearing loss. “Adults with diabetes may find their mental abilities slowing down soon after the disease appears,” The Times reported. The newspaper said that a study found that people with type 2 diabetes were noticeably worse than healthy adults in their semantic speed (working out meaning) and higher thought processes, such as planning, organising and paying attention to detail. The newspaper added that age did not seem to have an effect on mental deterioration, which suggests that the damage is done early on in the disease and then stabilises. The story is based on a study of a small group of relatively healthy Canadian adults with mild type 2 diabetes. It found that, compared to healthy people, the patients performed worse in parts of some neuropsychological tests. However, its design means that it cannot prove that diabetes is the cause of the difference in performances. The claim that diabetics are at risk of a progressive mental slow-down are not supported by the results of this study. This question can only be answered by larger, prospective studies, which take into account the range of other factors that might be involved. Where did the story come from?Drs Sophie Yeung, Ashley Fischer and Roger Dixon carried out the research. Their work was funded with a grant from the National Institutes of Health. The study was published in the peer-reviewed medical journal Neuropsychology. What kind of scientific study was this?The researchers in this cross-sectional study compared how people with and without diabetes of different ages performed on a range of neuropsychological tests. The study compared people between 53 and 70 years of age with 71 to 90-year-olds. The participants in this study were selected from the first wave of an ongoing larger study – the Victoria Longitudinal Study (VLS). From this group, the researchers selected all 44 people with type 2 diabetes, and a control group of 522 healthy people. The researchers then further excluded anyone who had been diagnosed with Alzheimer’s or vascular dementia, mild to moderate cognitive impairment (scoring less than 26 on the mini mental state examination), neurological conditions including Parkinson’s, cardiovascular disease or psychiatric conditions. This left them with a final sample for analysis of 41 relatively healthy adults with diabetes and 424 controls. The researchers compared the results from various cognitive and neuropsychological tests between the people with and without diabetes, and then investigated whether age had any effect on the differences. These tests had been performed as part of the first wave of the VLS study, and included memory tests, verbal fluency, and tests of executive function (such as speed of responses, ability to suppress a first response, and inhibiting automatic responses). What were the results of the study?The researchers found no difference between the diabetes groups and healthy control groups in terms of episodic memory (assessed by immediate word recall tests). As expected, the younger adults performed better than the older adults. There were also no differences between the groups in terms of their semantic memory (assessed by tests of vocabulary and fact recall), verbal fluency, reaction time or perceptual speed. In terms of executive functioning, the controls performed better in two of four tests. The controls also performed better on semantic speed tests, though not on other neurocognitive speed tests. Although the younger groups tended to outperform the older groups, diabetes did not affect different ages in different ways. What interpretations did the researchers draw from these results?The researchers conclude that their study has contributed to the literature on deficits associated with mild type 2 diabetes in older adults. They say that their results show that healthy controls “significantly outperformed the diabetes group only on markers of executive functioning and speed”. What does the NHS Knowledge Service make of this study?According to the authors, several studies have shown that mental performance is affected by diabetes. However, there is some conflict in the published research about which neuropsychological domains are affected. The purpose of this study was to investigate which domains are involved, and which of them appear to contribute to the difference. There are several points to note when interpreting this study:
Overall, there is a need for larger, prospective studies to confirm whether people with diabetes experience a decline in cognitive function and, in particular, which aspects of their function are affected. These studies will also need to take into account other potential confounding factors. “Playing ball games as a teenager can cut the chances of going on to suffer from brittle bones,” says The Daily Telegraph. The newspaper says weight-bearing sport strengthens the bones and keeps them healthy for a further 40 years. The newspaper’s claims are based on a Japanese study on 46 post-menopausal women. Researchers asked the women to recall what types of exercise they did during adolescence and compared the results to bone scans. They found that women who had performed weight-bearing sports had a higher mineral content in their bones. This size and design of this study mean it cannot prove that exercise has caused the differences in the womens’ bones. There are many other factors that might be responsible for improving bone health including diet, that the researchers did not take into account when analysing their data. However, apart from the risk of injuries that can occur during ball sports (and other vigorous exercise), it seems sensible to suggest that weight bearing exercise can improve bone strength and many other aspects of health. Where did the story come from? This research was conducted by Dr T. Kato and colleagues from Suzuka University of Medical Science, the Japan Institute of Sports Sciences and Chukyo University in Japan. Their work was funded by the Japanese Ministry of Education and Sciences.The study was published in a peer-reviewed medical journal, the British Journal of Sports Medicine. What kind of scientific study was this?This was a cross sectional study in which 46 post-menopausal women were asked what sports they participated in between the ages of 12 and 18 years. From their responses, they were grouped as either participating in weight-bearing sports or not. The health of the women’s bones was assessed by measuring bone mineral density (BMD) in their lower back and hip regions. This was done using a painless, non-invasive scan. They also measured the area and the perimeter of the mid thigh bone. Researchers then compared the BMD and other bone measurements between the two exercise groups and discussed any differences. What were the results of the study?The researchers report that those in the weight bearing group had significantly greater bone mineral density in the lumbar spine (lower back) and femoral neck (hip) than those women in the non-weight bearing sport group. What interpretations did the researchers draw from these results?The researchers conclude that their results suggest that weight-bearing activities during adolescence can affect bone structure and that these effects may be preserved for up to 40 years. What does the NHS Knowledge Service make of this study?This is a very small study with several shortcomings including its design. As it was a cross sectional study, it cannot prove causation (that one thing causes another). Many other factors, aside from what sport the women did when they were young, may play a part in bone health. Shortcomings to note about this study:
The study essentially compared bone characteristics between 16 women who reported participating in ‘weight-bearing sports’ in their youth with 30 who had not. The association that was found is not surprising as participation in vigorous activity may just mean that they generally have better health. The design and analyses of this study cannot prove this. Many factors are involved in bone health, including genetics, diet (importantly calcium intake) and lifestyle. This study advocates participation in sports when young, which is no bad thing given that the benefits of exercise on health throughout life are well known. “Being just a little overweight dramatically raises the risk of heart attacks,” reports the Daily Express. The paper claims that it is not only the obese who have a higher risk of heart attacks, but that “podgy” people also face an 11% increase in the risk of coronary disease. The large study behind this story assessed data on 21,000 male doctors, which was collected over 20 years on average. Researchers wanted to see whether the doctors’ body mass index (BMI) and physical activity levels at the beginning of the study were linked to their risk of developing heart failure. They found that risk of heart failure increased in relation to excess weight. The study has some shortcomings, but in general the findings are not unexpected: that there is an optimum weight for health (not underweight or overweight), and that physical activity is good for the circulatory system. The researchers sensibly conclude that public health initiatives which promote these facts may go some way to limiting the “scourge of heart failure”. Where did the story come from? This research was conducted by Dr Satish Kenchaiah, Dr Howard Sesso and Dr J. Michael Gaziano from Brigham and Women’s Hospital, Harvard Medical School, Massachusetts Veterans Epidemiology Research and the Veteran Affairs Boston Healthcare System. The study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute in the US, and it was published in the peer-reviewed medical journal Circulation. What kind of scientific study was this? This was a prospective cohort study investigating how BMI and physical activity levels might contribute to the risk of developing heart failure by following up 21,094 male doctors between 1982 and 2007. Heart failure occurs when the heart becomes less efficient at pumping blood around the body. It can have severe consequences and may lead to death. Several problems can lead to heart failure, including valve diseases, high blood pressure or disease of the heart muscle itself. Previous research has established that obesity (BMI of more than 30) increases the risk of heart failure. However, less is known about how physical activity and being overweight (or preobese) affect the risk of heart failure. In this study, researchers followed up doctors already participating in the larger Physicians' Health Study (PHS), which was evaluating the use of low-dose aspirin and beta carotene for primary prevention of cardiovascular disease and cancer. As part of the PHS study, baseline information on the doctors’ weight and height was taken. Their average age at entry into the study was 53 years. The doctors’ level of physical activity was also determined at baseline through a single question, which asked how often the doctors did sweat-inducing exercise each week. Possible answers were: rarely/never; one to three times a month; once a week; two to four times a week, five to six times a week or daily. Through the PHS, the doctors reported health outcomes (including signs and symptoms of heart failure) every six months in the first year, and annually thereafter. For this subsequent publication, researchers included those doctors who had participated in the PHS study and had information available on BMI and physical activity at baseline. Researchers excluded men who reported heart failure before baseline, or were missing other information, including age, family history of heart disease, smoking status, alcohol consumption, and history of various conditions such as high blood pressure, diabetes mellitus and high cholesterol. This group comprised the 21,094 men included in this analysis. The researchers determined whether the men’s baseline BMIs and their levels of reported physical activity was linked to their risk of heart failure during follow-up. They made several different calculations but took into account other factors that may be linked to heart failure risk, including age, smoking, alcohol, parental history of heart disease, treatment received during the original study, levels of exercise and health history. What were the results of the study? During the 20-year follow-up, 1109 men developed heart failure. The risk of heart failure increased in accordance with increasing BMI, with each 1kg/m2 associated with a 13% increase in the risk of heart failure. When compared with lean men, preobese men were 1.49 times more likely to experience heart failure, while obese men were 2.8 times more likely. This pattern did not change when taking into account the amount of physical activity each man did. The study also found that vigorous physical activity at least one to three times a month reduced the risk of heart failure by 18% after accounting for other factors that might explain this reduction. These factors included BMI, high blood pressure, diabetes and high cholesterol. What interpretations did the researchers draw from these results?The researchers conclude that a higher BMI was associated with a greater risk of heart failure in men. Vigorous physical activity was conversely associated with reduced risk of heart failure. Lean, active individuals had the lowest risk of heart failure, while obese, inactive people had the highest risk. The authors say that while the majority of their findings are consistent with those of previous research, the link between preobesity and heart failure is significant, and has not been seen before in previous large studies. What does the NHS Knowledge Service make of this study?This large prospective cohort study followed male doctors for 20 years on average, and linked their baseline levels of physical activity and BMI with their risk of developing heart failure during that time. The researchers have taken into account the fact that other variables such as cardiac symptoms, age and family history might be responsible for the increased risk of outcome, and they have adjusted accordingly for these. However, this study has its shortcomings, some of which the researchers acknowledge:
In general, the findings from this study are not unexpected: there is an optimum healthy weight (between underweight and preobese), and physical activity benefits the circulatory system. The researchers sensibly conclude that public health initiatives which promote these facts may go some way to limiting the “scourge of heart failure”. “A man who was left completely blind by multiple strokes has been able to navigate an obstacle course using only his "sense" of where hazards lie,” The Daily Telegraph reported. It said that researchers had already found that the man used ‘blindsight’ to react to facial expressions in other people such as fear, anger and joy. They tested the extent of this ability by constructing an obstacle course for him to navigate, which he did without striking any of the objects in his path. This story is based on a case report of a man demonstrating ‘blindsight’, an ability that has previously only been described in monkeys. The man’s blindness was caused by strokes and was a result of damage to the brain rather than his eyes. The researchers say that this shows there are pathways in the brain other than those known to be involved in vision that give humans navigational skills in the absence of sight. This finding is intriguing and may lead to future study. When evaluating a piece of research, it is important to consider how strong the evidence for it is. In this case, this type of study is often thought of as the lowest level of evidence. Further research that demonstrates this ability in others is needed. Where did the story come from?The research was carried out by Professor Beatrice de Gelder from the University of Tilburg in the Netherlands, and colleagues from the Netherlands, USA, Italy, Switzerland and Scotland. It was partly funded by grants from several sources including the European Union. The study was published in the peer-reviewed science journal Current Biology. What kind of scientific study was this?In this case report, the researchers described a single patient, referred to as patient TN, who had had at least two strokes which had damaged both sides of his brain. After the two main strokes, he was left with clinical blindness over his whole visual field. The researchers say this was caused by the loss of nerve cells in the areas of brain where the nerve signals from the eyes eventually end up, known as the primary visual (striated) cortex, and in the pathways that lead to these, known as the geniculostriate pathways. This loss of function in the visual cortex was confirmed by brain imaging assessments using advanced functional MRI scans. The researchers say that the first indication that patient TN had ‘affective blindsight’ was when they noticed that he reacted to facial expressions that he could not see. To confirm this, they tested him with brain scans to show that parts of his brain reacted to the emotional expressions he was exposed to in other people including fear, anger and joy. The researchers also tested TN with an electroencephalograph (EEG), which detects the electrical currents within the brain from electrodes placed on the surface of the scalp. This identified which parts of the brain activated when objects or flashing lights were placed in various parts of the man’s visual fields. Patient TN’s ability to navigate was then tested as he was asked to walk down a long corridor in which various barriers such as waste paper baskets, tripods and small boxes had been placed. What were the results of the study?The MRI and EEG tests showed that the man completely lacked any functional visual cortex. The abilities he retained did allow him to successfully navigate down the corridor. A video shows him avoiding six or seven blockages. What interpretations did the researchers draw from these results?The researchers say this demonstrates that pathways other than the usual geniculostriate pathways are being used and means that humans can retain navigational skills in the absence of sight. This is similar to what has been previously reported in monkeys. They conclude that “it remains to be determined which other pathways account for the retained navigational skill”. They say that the scans showed that, when TN’s visual field was stimulated, there was a different type of activation pattern in the left hemisphere compared to the right one. This suggests that part of the explanation might lie in how the nerve signals are transferred from one side of the brain. What does the NHS Knowledge Service make of this study?Case reports are often the first study type in humans. As an observational study, they provide preliminary information and can be the starting point for future studies. If more people develop the condition, a case series can be formed or alternatively other observational studies with control groups can be designed. Case reports are the lowest level of evidence commonly referred to in a hierarchy of study types. This is because without a comparison group or even the ability to make recordings in similar patients it's not possible to draw general conclusions. For example, it's not possible to know what aspects of these findings would be the same or different for anyone else with this type of blindness or pattern of brain damage. In this type of study, it is also important for repeat tests to be conducted, preferably using a new group of researchers, independent of the original observers. This is so that the lack of function in the visual cortex can be confirmed as this is critical to the idea that the man has no sight. The researchers have done this using several different techniques themselves, but say that it was difficult as the patient was unable to keep his eyes still for testing. They say that in one test “one could not be certain that absolutely all visual cortex had been destroyed or inactivated.” The exciting thing about this observation, is that ‘blindsight’ in humans is now known to be possible. Using currently available imaging techniques, such as the advanced MRI-scanner, more of the specific visual pathways in the brain can be mapped. Newspapers report today that researchers have recreated a genetic disease in a laboratory. The Times said that scientists created stem cells and nerve cells with characteristics of spinal muscular atrophy using skin cells from a child with the most severe form of the genetic condition. This enabled them to observe its early progress, which could eventually lead to new therapies to treat this condition. This important study illustrates the rapid advances being made in stem cell research. Prior to this, researchers have had to rely on animal models of the condition to study this disease. These models are limited by the fact that they may not accurately reflect what happens in the human body. The practical application of this early research is to give researchers a more accurate model through which to test potential treatments. Where did the story come from?Alison Ebert from the Waisman Center and The Stem Cell and Regenerative Medicine Center, with colleagues from other departments at the University of Wisconsin-Madison in the US, conducted this research. The work was funded by grants from the Amyotrophic Lateral Sclerosis Association and National Institutes based in the US. It was published online in the peer-reviewed science journal Nature. What kind of scientific study was this?In this laboratory study, the researchers wanted to see if they could use a type of stem cell to model the specific pathology of spinal muscular atrophy, a genetically inherited disease. Human stem cells can come from different sources, such as embryos or the umbilical blood. The stem cells that were examined in this study, human induced pluripotent stem cells, are different in that they can be derived from developed cells such as skin cells. These can be 'induced', or forced, to take on some of the characteristics of stem cells, such as the ability to become specialised nerve cells. The researchers say that fibrous skin cells (fibroblasts) have already been used extensively in studying spinal muscular atrophy. They felt, however, that as the nerve cells that control muscles are unique, they could better study the disease process by developing a technique of producing these nerve cells from the pluripotent stem cells from fibroblasts. Spinal muscular atrophy is a commonly inherited neurological disease with a range of severities. Children with it begin to lose nerve cells outside the brain (for example in the spinal cord), which leads to progressive muscle weakness, paralysis and often death. The cause of the disease has been tracked back to mutations of genes on chromosome 5, the SMN1 or SMN2 genes. In order for a child to have the condition, they must inherit two copies of the defective genes. As yet there is no known cure, though the protein produced by this gene has been identified. In this research, the scientists took a sample of fibrous skin cells from a child with spinal muscular atrophy. They succeeded in producing pluripotent stem cells from these, which were then grown further until they divided and finally changed into nerve cells. When they analysed the genes in the nerve cells, they found the same selective deficits as found in the child's unaffected mother. What were the results of the study?The researchers claim to be the first to have used human induced pluripotent stem cells to demonstrate the changes in cell survival or function typical of this disease. They report that they grew stem cells from both the affected child (with two defective genes) and from his unaffected mother (with only one gene), and showed that these cells could develop into nerve tissue and motor nerve cells. The cells retained the gene defect, a lack of the gene SMN1 expression, and the cells eventually died in a way that was typical for the disease. What interpretations did the researchers draw from these results?The researchers conclude that their main results, “will allow disease modelling and drug screening for spinal muscular atrophy in a far more relevant system”. In other words, using a disease model that more closely resembles what actually happens in humans. They claim that “this is the first study to show that human induced pluripotent stem cells can be used to model… a genetically inherited disease.” They say their research is important because it provides a new way of studying how diseases develop. This could lead to early ways of testing new drug compounds, which in turn may lead to the development of new therapies. What does the NHS Knowledge Service make of this study?This important study illustrates the rapid advances being made in stem cell research. Although there are animal models of spinal muscular atrophy in mice, flies and worms that can be made to model a similar disease state, they are limited as they are only models and they are not in human cells. Research that used this new technique would be more likely to accurately reflect what would happen in a human body. In addition, as this study used human cell culture that did not come from animals or human embryos, it avoids some of the ethical issues related to this sort of research. “Olive oil contains tumour-killing chemicals that may help us to win the war against breast cancer,” the Daily Express reported. The newspaper suggested that premium extra virgin olive oil contains tumour-killing chemicals that make breast cancer cells self-destruct. According to the report, a study has shown that the substances in the oil work in a similar way to the drug Herceptin by reducing the concentration of HER2 protein that helps HER2-positive breast cancer to grow. The story is based on a laboratory study in which researchers extracted phenols from commercially available extra virgin olive oil and assessed their effects on HER2-positive breast cancer cells. They found that the phenols from the oil reduced the levels of HER2 protein and also increased tumour cell death. These findings will be of interest to the scientific community, but it is important for large, epidemiological studies (in humans) to establish whether a Mediterranean diet – including high intake of olive oil – can protect against breast cancer. Where did the story come from?Dr Javier Menendez and colleagues from the Catalan Institute of Oncology and other medical and academic institutions in Catalonia, Spain, carried out this study. The research was supported by a grant from the Instituto de Salud Carlos III. A provisional version of the study is available in the BMC Cancer medical journal. What kind of scientific study was this?HER2 is a protein found on the surface of some cancer cells, including breast cancer. This protein can bind to another molecule (known as human epidermal growth factor), which then encourages the growth and division of the tumour cells. Not all breast cancers have the HER2 protein on their surface; it is estimated that one in five women with breast cancer will have HER2 receptors. In this study, the researchers investigated the effects of olive oil on breast cancer cells grown in laboratory cultures. Using a method called solid phase extraction, they removed and purified certain chemicals called phenols from commercially available extra virgin olive oil. These were then added to the growth medium for HER2-positive and HER2-negative breast cancers to see what effect they had on the tumour cells. Several laboratory tests were then carried out to determine how fast the tumour cells were growing, their metabolic activity, whether the phenol caused cell death, whether the phenol had an effect on levels of HER2 protein and whether or not HER2 protein was activated in the presence of the phenol. The results from these tests were compared with those from tests performed on breast cancer cells that were not cultured with the phenols. What were the results of the study?The researchers found that some single phenolic compounds (including hydroxytyrosol, tyrosol and others) and all the polyphenols (several phenols joined together) from extra virgin olive oil induced “strong tumouricidal effects” in breast cancer cells that had HER2 protein on their surface. The phenols also reduced the levels of HER2 protein and its activation. What interpretations did the researchers draw from these results?The researchers conclude that the phenols in extra virgin olive oil have the ability to cause degradation of the HER2 protein on breast cancer cells. This may mean they can be used as a basis for the design of new HER2-targeting agents. What does the NHS Knowledge Service make of this study?This study found that phenols extracted from extra virgin olive oil have an effect on HER2-positive breast cancer cells grown in culture in the laboratory. When purified, the phenols that had been extracted from commercially available extra virgin olive oil affected breast cancer cell proliferation and survival in cultures. This property may partly help to explain why an olive oil-rich Mediterranean diet may offer some protection from malignancies, although the researchers report that the results about this protective effect are conflicting. This is an important point: the researchers acknowledge that large, epidemiological studies (in human populations) have found conflicting results about whether a Mediterranean diet can protect against breast cancer. When considering how these findings can be used in a practical application, it should be noted that there may be differences in how tumour cells react to chemicals applied directly in the laboratory and how they respond to lower concentrations in real life. There is also the possibility that these chemicals may have other side effects in humans. These findings will be of interest to the scientific community, but there remain several important steps in researching this approach before it is confirmed that a diet rich in olive oil can protect against breast cancer. “Childhood obesity is determined before the age of five,” says The Daily Telegraph. The newspaper says a new study has found that the majority of seriously overweight children gained much of their excess weight before they started school. This study is part of ongoing diabetes research investigating a range of health indicators in children including changes in weight. Researchers looked at the weight of 223 children at birth, then at ages five and nine. Today’s children had birth weights similar to babies born 25 years ago, but were found to gain far more weight by the time they started school. The research also found that at puberty, most of a child’s excess weight had been gained before they started school. Over 90% of girls’ excess weight and 70% of boys', was found to have been 'carried over' from age five. The researchers say this provides a good reason for dealing with obesity early. This study provides an early indication that programmes for managing the weight of pre-school children might be successful in preventing obesity in older children. Where did the story come from?This research was conducted by Dr Daphne Gardner and colleagues from the department of Endocrinology and Metabolism at the Peninsula Medical School in Plymouth. It is not clear from the available draft report what sources of funding where used for this research. The study has been peer-reviewed and is awaiting full official publication in the medical journal Pediatrics. What kind of scientific study was this?This is the 36th publication from a prospective cohort study known as the EarlyBird Diabetes Study. This ongoing study is investigating the factors relating to the emergence of insulin resistance in a group of over 300 healthy children from school entry (four or five years old) to 16 years. The study also has access to the weight data (retrospective data) collected at birth on these children, who by 2008 were approaching puberty. For this study (EarlyBird36), the researchers wanted to find out when the children who put on excess weight began to do so. They also looked at how this weight gain affected body composition and insulin resistance later in life. Insulin resistance (IR) is a metabolic condition in which normal amounts of insulin are inadequate to produce the normal responses from fat, muscle and liver cells in the body. In healthy people, the release of insulin will cause these cells to act in different ways to reduce blood glucose levels, e.g. muscle cells will take in glucose and store it. This leads to a fall in the overall level of glucose in the blood as the level of insulin rises. However, in children and adults who are insulin resistant, a rise in insulin leads to less glucose take-up by muscles and the liver increases its glucose production. Together these lead to an unhealthy rise in the level of glucose, despite the higher levels of the hormone insulin. Excess weight gain contributes to IR and the metabolic link is thought to be one of the main factors underlying diabetes and cardiovascular disease. Early weight gain, from birth to five years is thought to be an important contributor to diabetic risk. Between 2000 and 2001, 307 healthy, mostly Caucasian children (170 boys, 137 girls) were recruited from randomly selected schools around Plymouth. The children were an average of 4.9 years old at this time. They were weighed at ages five and nine and their birth weights were obtained from birth records. As children continually grow throughout childhood, it was necessary to use a method called a weight standard deviation score (SDS), to get an idea of how different each child was from the expected weight for their age. The researchers also calculated the weight change between weighings, relative to that expected for their age (the change in SDS). They called this the excess weight. They then used a recognised technique called the HOMA2-IR to measure insulin resistance and scanned the children to measure fat mass and calculate the fat mass index (FMI) by adjusting for height. The lean mass index is calculated from the lean mass in the same way. The researchers used complex statistics (known as multiple regression modelling) to see if it was the current weight, or the weight gain (change in SDS) that was associated most strongly with IR at nine years. What were the results of the study?Excess weight gain (the change in weight SDS) was substantial from birth to five years but smaller from five to nine years. While weight SDS at five years correlated poorly with weight SDS at birth, it strongly predicted weight SDS at nine years. When assessing how well their models predicted IR the researchers say that, “importantly, predictive strength was little different, whether the change in weight SDS over the time period (excess weight gain) was used in the analysis, or simply the weight SDS recorded at the end of the time period (current weight).” This means that the single measures of current weight are as strongly predictive of IR as weight gain, and supports their claim that future policy could be based on a school entry weight at about five years of age. What interpretations did the researchers draw from these results?The researchers claim these findings are important because a single measure of weight (or BMI) on school entry at five years provides both a record of the long term trends in the population (prevention), and an accurate pointer to future risk for the child (treatment). They go on to say that the data implies that the successful prevention of excess weight gain early in childhood will be maintained, at least into puberty. They say that diabetes prevention strategies might better focus on pre-school children rather than older children, as “the die appears to be cast by five years”. What does the NHS Knowledge Service make of this study?The researchers claim that the current UK Department of Health guidelines are correct in proposing the routine measurement of children’s weight and height at school entry, around the age of five years. They say this is important for monitoring what is happening in the population, and for alerting parents, schools or healthcare professionals about the children that need more intensive treatments. They also say that taking action at even earlier ages would be better. The researchers do note some limitations to the study:
It may be easier for parents to modify preschool diets than the diets of older children. If weight gain and insulin resistance can be prevented from developing at young ages this may play an important role in reducing the record levels of obesity and the current epidemic of diabetes and heart disease that threaten health the developed world. |
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