date: 2020
title: IN WHO GLOBAL PULSE SURVEY, 90% OF COUNTRIES REPORT DISRUPTIONS TO ESSENTIAL HEALTH SERVICES SINCE COVID-19 PANDEMIC

**31 August 2020 News release** - WHO to roll out learning and monitoring tools to improve service provision during pandemic

The World Health Organization (WHO) today published a first indicative survey on the impact of COVID-19 on health systems based on 105 countries' reports. Data collected from five regions over the period from March to June 2020 illustrate that almost every country (90%) experienced disruption to its health services, with low- and middle-income countries reporting the greatest difficulties. Most countries reported that many routine and elective services have been suspended, while critical care - such as cancer screening and treatment and HIV therapy – has seen high-risk interruptions in low-income countries.

"The survey shines a light on the cracks in our health systems, but it also serves to inform new strategies to improve healthcare provision during the pandemic and beyond," said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. "COVID-19 should be a lesson to all countries that health is not an 'either-or' equation. We must better prepare for emergencies but also keep investing in health systems that fully respond to people's needs throughout the life course."

Services hit across the board: Based on reports from key informants, countries on average experienced disruptions in 50% of a set of 25 tracer services. The most frequently disrupted areas reported included routine immunization – outreach services (70%) and facility-based services (61%), non-communicable diseases diagnosis and treatment (69%), family planning and contraception (68%), treatment for mental health disorders (61%), cancer diagnosis and treatment (55%).

Countries also reported disruptions in malaria diagnosis and treatment (46%), tuberculosis case detection and treatment (42%) and antiretroviral treatment (32%). While some areas of health care, such as dental care and rehabilitation, may have been deliberately suspended in line with government protocols, the disruption of many of the other services is expected to have harmful effects on population health in the short- medium- and long-term.

Potentially life-saving emergency services were disrupted in almost a quarter of responding countries. Disruptions to 24-hour emergency room services for example were affected in 22% of countries, urgent blood transfusions were disrupted in 23% of countries, emergency surgery was affected in 19% of the countries.

Disruption due to a mix of supply and demand side factors. 76% of countries reported reductions in outpatient care attendance due to lower demand and other factors such as lockdowns and financial difficulties. The most commonly reported factor on the supply side was cancellation of elective services (66%). Other factors reported by countries included staff redeployment to provide COVID-19 relief, unavailability of services due to closings, and interruptions in the supply of medical equipment and health products.

Adapting service delivery strategies. Many countries have started to implement some of the WHO recommended strategies to mitigate service disruptions, such as triaging to identify priorities, shifting to on-line patient consultations, changes to prescribing practices and supply chain and public health information strategies. However, only 14% of countries reported removal of user fees, which WHO recommends to offset potential financial difficulties for patients.

The pulse survey also provides an indication of countries' experiences in adapting strategies to mitigate the impact on service provision. Despite the limitations of such a survey, it highlights the need to improve real-time monitoring of changes in service delivery and utilization as the outbreak is likely to wax and wane over the next months, and to adapt solutions accordingly.

To that end, WHO will continue to work with countries and to provide supportive tools to address the fallout from COVID-19. Given countries' urgent demand for assistance during the pandemic response, WHO is developing the COVID19: Health Services Learning Hub, a web-based platform that will allow sharing of experiences and learning from innovative country practices that can inform the collective global response. WHO is also devising additional surveys at the sub-national level and in health facilities to gauge the longer-term impact of disruptions and help countries weigh the benefits and risks of pursuing different mitigation strategies.

Available from: <https://www.who.int/news-room/detail/31-08-2020-in-who-global-pulse-survey-90-of-countries-report-disruptions-to-essential-health-services-since-covid-19-pandemic>


author: Joshua P. Thaler; Stephan J. Guyenet; Mauricio D. Dorfman; Brent E. Wisse; Michael W. SchwartzCorresponding author: Michael W. Schwartz, <email@example.com>.
date: 2013-08
references:
title: Hypothalamic Inflammation: Marker or Mechanism of Obesity Pathogenesis?

Obesity and its associated metabolic and cardiovascular disorders are among the most challenging health problems confronting developed countries. Not only is obesity remarkably common, affecting more than one-third of U.S. adults, and very challenging to treat, but it is also tightly linked to type 2 diabetes and related metabolic disorders. A major obstacle to effective obesity treatment is that lost weight tends to be regained over time (1). Although the mechanisms underlying recovery of lost weight are incompletely understood, a large literature suggests that body fat stores are subject to homeostatic regulation, and that this process occurs in obese as well as normal-weight individuals. From this perspective, obesity can be viewed as a disorder in which the biologically defended level of body fat mass is increased. Recent findings implicate inflammation in key hypothalamic areas for body weight control in this process. In this review, we present an overview of energy homeostasis—the biological process that underlies the control of body fat mass—and describe evidence that defects in this regulatory system contribute to obesity pathogenesis. We then address molecular characteristics of hypothalamic inflammation and their implications for obesity pathogenesis (detailed more extensively in refs. 2,3), followed by evidence linking high-fat diet (HFD) feeding to neuropathological alteration of key hypothalamic areas controlling energy balance. We conclude by considering how cell-cell interactions may contribute to this deleterious hypothalamic response and the implications of these interactions for obesity pathogenesis.

# The case for energy homeostasis

## Homeostatic response to weight loss.

Following a period of caloric restriction, lost weight is gradually but inexorably recovered in most individuals. This effect involves the capacity of the brain to sense the reduction of body energy stores and activate responses to compensate for this deficit. In simple terms, voluntary weight loss triggers increases of both appetite and energy efficiency, such that both sides of the energy balance equation shift in favor of weight gain (4,5). Perhaps the clearest example of this compensatory response to lost weight comes from the large clinical literature of diet studies in human subjects. Some 20 years ago, Safer (6) reported that the vast majority (\>90%) of weight lost through hypocaloric dieting in humans is regained over a 5-year period. Even with the addition of exercise (which slows the rate of weight regain \[7\]), caloric restriction through lifestyle modification is a Sisyphean task over the long term. As an example, obese subjects enrolled in the lifestyle intervention arm of the landmark Diabetes Prevention Program (DPP) study averaged ∼7% weight loss during the trial but regained virtually all of the weight lost over the full 10 years of postintervention monitoring (8). Lifestyle intervention in the follow-up Look AHEAD trial similarly failed to produce durable weight loss (9).

Robust defense of body energy stores is similarly observed in conditions that promote weight loss by increasing energy expenditure rather than reducing intake, such as housing mice in a cold environment. To survive, a marked increase of energy expenditure is required to support thermogenesis and maintain core body temperature. Increased heat production occurs initially at the expense of modest body fat depletion, but as fat loss proceeds, food intake increases in a commensurate manner to offset further loss of body fat stores (10). Consequently, graded decreases of environmental temperature trigger proportionate increases of energy expenditure that are compensated by increased energy intake so as to maintain body fat stores.

## Adaptive responses to weight gain.

From the foregoing, it is evident that the energy homeostasis system responds robustly to states of negative energy balance, whether secondary to caloric restriction or increased energy expenditure. Does the energy homeostasis system also protect against weight gain? Available data from both animal models and humans support this possibility. A classic demonstration of this phenomenon was provided by the "Experimental Obesity in Man" studies performed at the University of Vermont almost 50 years ago (11). In these experiments, lean human volunteers were challenged to increase their body weight by 20% through overeating for a period of up to 6 months. Although overeating was initially accomplished without difficulty, the subjects' capacity to do so soon began to wane, presumably because counterregulatory mechanisms were engaged that reduce appetite. After reaching the prescribed 20% increase of body weight and being released from the experimental mandate to overeat, the subjects displayed several weeks of profound anorexia that caused the excess pounds to be shed. Only when body weight began to converge on preintervention values did food intake also return to normal levels. Similar observations were made in subsequent human overfeeding studies (12), and across a variety of animal models as well (13).

In the face of a challenge to body fat stores in either direction, therefore, robust homeostatic responses drive the return of body weight to its original, biologically defended level (sometimes referred to as a set-point). If normal-weight individuals defend against experimentally induced changes of body fat mass in either direction, it follows that obesity pathogenesis should involve impairment of the energy homeostasis system. Since overweight individuals appear, by and large, to defend their body fat mass as robustly as normal weight individuals (14), obesity does not appear to reflect a failure of energy homeostasis so much as the biological defense of an elevated level of body fat mass.

# Obesity and energy homeostasis

An important strength of the homeostasis model for understanding obesity pathogenesis is that it offers a plausible explanation for why conservative approaches to weight loss fail over time. To understand how a slow, progressive increase in the defended level of body fat stores might occur, it is helpful to consider how the energy homeostasis system operates in normal-weight individuals.

## How does energy homeostasis work?

Energy homeostasis involves an adiposity negative feedback system through which circulating signals such as the hormone leptin inform key brain centers about body energy stores (15). In response to a change of body fat mass, corresponding changes of plasma leptin levels and hence of leptin signaling in these brain areas elicit changes of both energy intake and energy expenditure that favor the return of body weight to preintervention levels. In response to weight loss due to caloric restriction, this model predicts that falling plasma levels of leptin and other adiposity negative feedback signals (e.g., insulin) elicit brain responses that minimize further weight loss and promote the eventual recovery of lost weight. Leptin also responds robustly to short-term changes of energy balance, prior to major changes in adiposity, and therefore integrates information about both long-term and short-term energy status (16,17).

A growing number of leptin-responsive neuronal subsets have been identified, and their roles in adaptive changes of energy balance are increasingly well understood. Perhaps best studied of these are two leptin-sensitive neuronal subsets situated in the hypothalamic arcuate nucleus (ARC). Activation of neuropeptide Y and agouti-related peptide (NPY/AgRP) neurons potently increases food intake and reduces energy expenditure through the paracrine action of the neuropeptides NPY and AgRP themselves and through inhibition of downstream neuronal activity via GABAergic signaling (15,18,19). Conversely, reduced intake and increased expenditure occurs with activation of proopiomelanocortin (POMC) neurons largely through the action of the anorexigenic neuropeptide α-melanocyte–stimulating hormone (15) (although direct neurotransmitter action likely contributes as well \[20\]). Weight loss reduces leptin levels causing activation of NPY/AgRP neurons and inhibition of POMC neurons (15). This combination potently favors positive energy balance and is sustained until lost weight has been regained.

A large literature now indicates that proper functioning of these neurocircuits is required for normal energy homeostasis in rodent models, and many models of obesity caused by impairment of the leptin-melanocortin pathway now exist. A similar role was recently invoked for a distinct subset of leptin-sensitive ARC neurons containing neuronal nitric oxide synthetase. Deletion of leptin receptors from these neurons causes hyperphagia and obesity even more severe than that induced by defective melanocortin signaling (21). Neurons in other hypothalamic areas, including the ventromedial, lateral hypothalamic, and paraventricular nuclei, and in extrahypothalamic areas, including hindbrain (e.g., nucleus of the solitary tract), midbrain (ventral tegmental area), and forebrain (nucleus accumbens), are also critical for normal energy homeostasis.

That the aforementioned hypothalamic neurocircuits are essential for normal energy homeostasis in humans is supported by insights gained from rare monogenic forms of human obesity. Loss-of-function mutations affecting the leptin-melanocortin pathway, including genes encoding leptin, melanocortin-4 receptor (Mc4r), leptin receptor, and the prohormone convertase enzyme that processes POMC, together constitute the most prevalent, highly penetrant genetic causes of human obesity (22). However, ∼95% of human obesity is due not to a single, highly penetrant mutation but rather to complex interactions between genetic and environmental factors that favor both weight gain and the defense of elevated body weight. Impaired leptin responsiveness is a feature of these more common forms of obesity as well and hence may contribute to obesity pathogenesis in susceptible individuals.

## Hypothalamic inflammation and leptin resistance.

Leptin resistance can be defined simply as an acquired or inherited defect in the response to leptin. This simplistic definition is problematic, however, since such leptin resistance can potentially arise from a long list of defects—not only those affecting leptin receptor signal transduction, but at innumerable points downstream of or in parallel to leptin-mediated effects (23). For example, obesity due to Mc4r mutation, the most common monogenic form of human obesity, is characterized by leptin resistance, since leptin action on energy balance requires that it activate the melanocortin pathway. From this perspective, the term leptin resistance is easily misused, since a blunted feeding response to leptin is present in virtually all forms of obesity, save for that caused by leptin deficiency (23). This conundrum has to some extent confounded efforts to delineate underlying mechanisms.

Despite this caveat, growing evidence suggests a causal role for leptin resistance in obesity pathogenesis and that obesity-associated hypothalamic inflammation can underlie this resistance. This hypothesis originated following clear evidence that inflammatory signaling contributes to obesity-associated insulin resistance in peripheral tissues such as liver, muscle, and adipose tissue (24). Among neuronal consequences of proinflammatory signaling is a disruption of intracellular signal transduction downstream of both insulin and leptin receptors via the insulin receptor substrate–phosphatidylinositol 3-kinase pathway (2). Leptin signaling via the janus kinase–signal transducer and activator of transcription pathway can also be impaired by cellular inflammation (25,26), suggesting that this mechanism may contribute not only to obesity-associated leptin and insulin resistance, but also to the associated increase in the defended level of body fat stores. However, dissociating cause and effect has been challenging, and evidence of leptin resistance caused by inflammation independently of obesity is lacking (though studies of aging, injury, and endotoxin-induced leptin resistance are suggestive of this possibility \[27–29\]). We favor the hypothesis that a vicious cycle exists involving obesity, leptin resistance, and inflammation. According to this model, diet-induced increases of inflammation beget a state of leptin resistance that promotes weight gain, which in turn triggers further inflammation and leptin resistance, eventually resulting in the biological defense of an elevated level of body fat. This perspective highlights the challenges inherent in determining the extent to which leptin resistance and inflammation are causes or consequences of weight gain, a challenge that cannot be met without methodologies that can distinguish cellular responses to diet from metabolic alterations induced by obesity itself.

## Does hypothalamic inflammation cause obesity?

The first report of obesity-associated hypothalamic inflammation was in a rat model of diet-induced obesity (DIO) published in 2005 (30), and many investigators have since replicated this finding (2,3,31–36). The observation that genetic interventions that disrupt neuronal inflammation can block both obesity and hypothalamic leptin resistance during HFD feeding implicates this inflammation in obesity pathogenesis. For this to be the case, however, hypothalamic inflammation would have to occur prior to obesity onset, unlike the later onset of inflammation in peripheral tissues. This hypothesis is supported by our recent observation that in rats predisposed to DIO, expression of proinflammatory biomarkers increases in the mediobasal hypothalamus within 24 h of HFD onset (37). The mediobasal hypothalamus level of these markers increases more by day 3 and is followed by a transient normalization of inflammation, only to rise again in 2–3 weeks and remain elevated thereafter. Interestingly, this initial rise and fall of hypothalamic inflammatory markers follows a temporal pattern similar to that of caloric intake following the switch to an HFD.

Several molecules and pathways have been identified as candidate mediators of hypothalamic inflammation during HFD feeding. Among these are the serine kinases c-Jun N-terminal kinase (Jnk) and inhibitor of nuclear factor-κB kinase (IKKβ) as well as Toll-like receptor 4 (TLR4), the ceramide biosynthesis pathway, and the endoplasmic reticulum (ER) stress pathway (30–36). Each of these is upregulated in the rodent hypothalamus during DIO (30,36,38), and Jnk and IKKβ can inhibit insulin and leptin signaling by at least two mechanisms: induction of the signal termination molecule suppressor of cytokine signaling-3 and serine phosphorylation of the essential pathway intermediate insulin receptor substrate (3,24). Targeted disruption of each of these pathways in a hypothalamus-specific manner (by pharmacologic, viral gene transfer, or genetic means) limits the extent of HFD-induced obesity, hypothalamic leptin resistance, and systemic insulin resistance (30–36), implying a contributory role for these mechanisms of hypothalamic inflammation in the pathogenesis of DIO and its metabolic sequelae. Conversely, although acute or robust central nervous system inflammation is typically associated with anorexia and weight loss, interventions that generate more modest levels of hypothalamic inflammation (e.g., virally mediated neuronal expression of constitutively active IKKβ, or central administration of either low-dose tumor necrosis factor-α or the ER stress inducer thapsigargin) can produce mild obesity/metabolic syndrome phenotypes (34,36,39,40). These data collectively suggest that in some contexts, hypothalamic inflammation is both necessary and sufficient for DIO. As such, an important research priority is to determine the relative importance of the many inflammatory signaling molecules and pathways implicated in promoting leptin resistance and obesity.

Although these findings collectively offer evidence of a causal role for hypothalamic inflammation in the pathogenesis of DIO in rodent models, there are conflicting results that cast doubt on this hypothesis. First, several models of increased tissue inflammation (e.g., fasting in adipose tissue \[41\] and p50 knockout in liver \[42\]) show improved rather than worsened insulin sensitivity, suggesting that the relationship between hormone signaling and inflammation is context dependent. More importantly, a number of total-body proinflammatory cytokine and cytokine receptor knockout models (e.g., interleukin \[IL\]-1, IL-6, IL-1 receptor, and tumor necrosis factor-α receptors \[43–46\]) display obesity phenotypes rather than being protected from DIO. Conversely, IL-1 receptor antagonist–deficient mice show a lean, hypermetabolic phenotype with increased leptin sensitivity despite higher levels of IL-1 activity (47). Reconciling these results with the literature supporting a role for hypothalamic inflammation in DIO is inherently difficult because these are largely whole-body gene knockouts that affect multiple tissues and may cause developmental compensation. In many instances, the degree of change in inflammatory signaling in these models is much greater than that observed with HFD-induced obesity. Lastly, the hypothalamus was not specifically examined in these models. However, two recent studies have demonstrated dissociation between weight changes and alterations in hypothalamic inflammation. In the first, DIO-sensitive HFD-fed rats switched back to regular chow for 8 weeks were observed to lose all their excess weight despite sustained elevations in hypothalamic inflammatory gene expression (48). Conversely, neuronal peroxisome proliferator–activated receptor-δ knockout mice are resistant to HFD-induced hypothalamic inflammation yet are more susceptible to DIO than wild-type controls (49). Thus, the evidence supporting a direct role of hypothalamic inflammation in promoting weight gain is clearly mixed. These considerations raise the possibility that HFD-induced hypothalamic inflammation is but one element of a more comprehensive injury process that itself contributes to obesity pathogenesis, a hypothesis that we explore further below.

# Hypothalamic gliosis and neuron injury

At the cellular level, exposure of neurons to nutrient excess represents a significant stress that not only engages adaptive mechanisms such as autophagy and ER stress that limit neuronal damage, but also involves neighboring cell populations. More than 50% of the cellular composition of the brain is nonneuronal, including glial, vascular, and periventricular constituents (50). Astrocytes and microglia are the most abundant of these specialized cell types and, in addition to comprising much of the basic architecture of brain parenchyma, they maintain the blood-brain barrier, support neuronal metabolism, and both guard against and react to local tissue injury. To accomplish these various functions, both astrocytes and microglia are capable of remarkable plasticity, altering both their genetic programs and cellular morphologies (called reactive gliosis) to combat infection, support or consume damaged neurons, and direct the restorative process (51,52). Interestingly, rats receiving systemic leptin administration 3 h prior to cerebral ischemia had reduced infarct volume with signal transducer and activator of transcription-3 activation in astrocytes of the ischemic penumbra (53). Similarly, leptin administration and fasting reciprocally modulate glucose and glutamate transporter expression in hypothalamic astrocytes. These observations are suggestive of an interaction between nutritional status and glial cell function (54).

Whereas the link between hypothalamic inflammation and obesity pathogenesis is the focus of a sizeable literature, the role of astrocytes and microglia in energy homeostasis is comparatively unexplored. Both cell types play crucial roles in synaptic remodeling (55), metabolic coupling at active synapses (56), and neurotransmitter reuptake (57), functions that ultimately influence neuronal activity and behavior. Astrocytes and microglia play central roles in the central nervous system response to injury but can provide either neuroprotection or perpetuate neurotoxicity depending on the nature of the underlying insult (51,58). In neurodegenerative conditions such as Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis, microglia and astrocytes often accelerate the disease process by generating cytokines, reactive oxygen species, and other toxic mediators involved in clearing degenerating cells. By amplifying inflammatory signals in the hypothalamus analogously to the recruitment and activation of proinflammatory immune cells in adipose and other peripheral tissues (59,60), both cell types have the potential to impair neuronal function in ways that favor leptin resistance and associated weight gain. Lending support to this argument, TLR4, a putative mediator of saturated fatty acid–induced inflammatory signaling, is abundantly expressed by microglia (33), and acute inactivation of TLR4 by central administration of an anti-TLR4 antibody can reduce weight gain during HFD feeding (33). In addition, reactive astrocytes and microglia accumulate in the hypothalamus during long-term HFD consumption at times when hypothalamic inflammation is clearly evident (33,37). In contrast, HFD-fed mice subjected to an involuntary exercise regimen exhibit modest improvements in glucose tolerance along with reduced hypothalamic microglial activation (61), suggesting a link between microglial phenotype and obesity-associated metabolic impairment. Finally, in a nonhuman primate model, microglial activation along with increased expression of inflammatory pathway genes was observed in fetuses from HFD-fed mothers, raising the possibility that hypothalamic microglia contribute to the effect of intrauterine programming to influence the adult phenotype (62).

Other studies, however, suggest a more complex picture in which microglia and astrocytes play a protective role by limiting the deleterious hypothalamic consequences of consuming an HFD. First, mice with moderately increased production of IL-6 from astrocytes were protected from DIO, rather than being more susceptible (63). Moreover, adult rats overfed during the neonatal period manifest hypothalamic microglial activation (as evidenced by major histocompatibility complex class II expression) without local inflammation (64), and hypothalamic microglia from mice fed an HFD accumulate the generally anti-inflammatory molecule IgG (65). Finally, our recent work suggests that effects of short-term HFD feeding on hypothalamic inflammation and reactive gliosis are separable from one another (37). Specifically, whereas both processes were evident within the first week of HFD consumption, hypothalamic inflammation subsided over the next 2 weeks despite accumulation of enlarged microglia in the ARC that continued unabated.

Although definitive answers are still awaited, these results are consistent with a model (<a href="#F1" data-ref-type="fig">Fig. 1</a>) in which gliosis develops initially as a neuroprotective response to cope with neuronal stress induced by HFD feeding. In this scenario, glial responses initially constrain hypothalamic inflammatory signaling. With prolonged exposure to an HFD, however, astrocytes and/or microglia may eventually convert to a more proinflammatory, neurotoxic phenotype. Detailed cellular phenotyping and carefully timed functional interventions should help clarify these possibilities.

# Integrated model of neuronal injury and obesity pathogenesis

Like cells in peripheral tissues of animals fed an HFD, hypothalamic neurons confronted by nutrient excess are proposed to respond by engaging mechanisms that limit excessive hormone- and nutrient-related signaling, manage organellar stress, and maintain structural integrity. At the same time, these neurons also integrate signaling inputs from neurons in other brain regions that may themselves be reacting to the change in diet. These various challenges to neuronal function are compatible with evidence that in rats predisposed to DIO, hypothalamic neurons initiate a stress response (as measured by up-regulation of the chaperone protein hsp72) within the first week of HFD exposure, close to the onset of hypothalamic inflammation (37). The accumulation of reactive astrocytes and microglia in the mediobasal hypothalamus occurs around the same time and precedes a subsequent reduction in the level of inflammation (<a href="#F1" data-ref-type="fig">Fig. 1</a>).

With prolonged HFD exposure, however, POMC neurons exhibit increased autophagic activity and eventually (after 8 months) appear to decrease in number by 25% (37), consistent with prior reports of apoptosis of these neurons in mice with DIO (66). Based on these considerations, we speculate that hypothalamic inflammation during HFD feeding originates primarily within neurons rather than glial cells, and that the associated gliosis occurs in response to neuron injury and is initially neuroprotective. This hypothesis does not exclude the possibility that glial cells that respond directly to dietary components and/or nutrient excess are also drivers of inflammation and/or neuronal injury, but to date we are unaware of data that directly support this view. If chronic exposure to an HFD causes permanent damage to or death of neurons comprising energy balance neurocircuits, obesity susceptibility and other phenotypic outcomes may depend on the degree to which these neuronal subsets are susceptible to this type of stress. For example, if neuron injury and loss occur preferentially in POMC over AgRP neurons, the balance of functional anorexigenic to orexigenic inputs should shift so as to favor leptin resistance, excess weight gain, and an upward resetting of the defended level of body fat mass.

Although the extent to which obesity and/or HFD feeding impacts various hypothalamic cell populations in humans remains uncertain, early insights from brain imaging studies are beginning to support this type of neuropathological model. A retrospective analysis of magnetic resonance images from 34 subjects (BMI range 17.7–44.1 kg/m^2^) revealed evidence of gliosis in the mediobasal hypothalamus that correlated with BMI (37), and a separate study reported an inverse correlation between systemic inflammation (measured as serum fibrinogen) and the integrity of brain structures involved in food reward and feeding behavior measured by magnetic resonance imaging in 44 overweight/obese subjects (67). Brain imaging (including new approaches to the use of PET imaging to detect microglial activation) and other modalities have important potential to ascertain whether human obesity involves cumulative ARC neuronal damage and whether such an effect is reversible and/or predictive of either future weight gain or weight regain following voluntary weight loss.

# Summary

Our understanding of obesity-associated hypothalamic inflammation—its underlying causes, the contributions made by distinct cell types, the extent to which it is reflective of tissue injury versus repair, and its implications for obesity pathogenesis and treatment—remains incomplete, but the field is evolving rapidly. Although hypothalamic inflammation shares several features with responses observed in peripheral tissues (e.g., comparable increases of some of the same inflammatory biomarkers, activation of local immune cells), its many unique features identify it as a fundamentally distinct process. For one, inflammation occurs much more rapidly in the hypothalamus than in peripheral tissues following the switch to an obesogenic HFD, such that it precedes weight gain. Available data are compatible with a model in which the initial cause of hypothalamic inflammation induced by HFD feeding involves injury to neurons that comprise energy balance neurocircuits. In turn, this injury may undermine homeostatic responses that protect against weight gain, thereby contributing to obesity pathogenesis. Additional studies are warranted to critically test this model and determine if therapeutic interventions targeting this process have a role in the future of obesity treatment.

## ACKNOWLEDGMENTS

This work was supported by a National Institutes of Health (NIH) Fellowship Training Program Award (T32DK007247), NIH National Research Service Award (F32DK091989), the NIH-funded University of Washington Nutrition Obesity Research Center and the Diabetes Research Center, and NIH grants to M.W.S. (DK090320, DK083042, and DK052989) and J.P.T. (DK088872). J.P.T. was also supported by a Beginning Grant-in-Aid from the American Heart Association.

M.W.S. has consulted for Santarus and Pfizer. No other potential conflicts of interest relevant to this article were reported.

J.P.T. and M.W.S. wrote the manuscript. S.J.G. and B.E.W. reviewed and edited the manuscript. M.D.D. contributed the figure and reviewed and edited the manuscript.

# REFERENCES


author: PH Remans; JM van Laar; ME Sanders; P-P Tak; KA Reedquist
date: 2005
institute: 1AMC, Amsterdam, The Netherlands; 2LUMC, Leiden, The Netherlands
title: Synovial monocytes mediate Rap1-dependent oxidative stress in rheumatoid arthritis T lymphocytes

# Background

Transient production of reactive oxygen species (ROS) plays an important role in optimizing transcriptional and proliferative responses to T-cell receptor signaling. Conversely, chronic oxidative stress leads to mitogenic hyporesponsiveness and enhanced transcription of inflammatory gene products. It has recently been demonstrated that constitutive activation of the small GTPase Ras and simultaneous inhibition of Rap1 in synovial fluid (SF) T cells results in high intracellular ROS production, which is thought to underlie many of the functional abnormalities observed in these cells in rheumatoid arthritis.

# Objectives

To identify the factor(s) responsible for modulation of intracellular ROS production in synovial T lymphocytes.

# Methods

Purified rheumatoid arthritis peripheral blood (PB) T cells were incubated in the presence of different cytokines, in 50% autologous SF, or with autologous SF monocytes for 72 hours. Activation status of Ras and Rap1 GTPases were determined using activation-specific probes for these GTPases. Oxidation of the dye DCF by FACS analysis was used to measure intracellular ROS production.

# Results

Chronic stimulation of PB T cells for 72 hours with tumor necrosis factor alpha (TNF-α) or 50% autologous SF resulted in a slight increase in basal ROS production, but did not increase intracellular ROS production to levels found in SF T cells. Exposure of PB T cells to SF (but not PB) monocytes for 72 hours, however, led to a strong increase in ROS production in PB T cells, comparable with ROS levels in SF T cells. Moreover, similar Rap1 inhibition as found in SF T cells were observed in PB T cells after exposure to SF monocytes. To demonstrate that the inhibition of Rap1 is critical in the subsequent increase in ROS production, PB T cells were nucleofected with the constitutive active isoform of Rap1 (RapV12). In RapV12 nucleofected PB T cells the SF monocyte-induced ROS production was prevented. Cell–cell contact is critical, since in PB T cells separated from SF monocytes by a transwell membrane, the inhibition of Rap1 was relieved, concomitant with an absence in excess ROS production. Additionally, we found that addition of 10 μg/ml recombinant CTLA-4-Ig fusion protein also prevented oxidative stress in PB T cells exposed to SF monocytes, which suggested a central role for CD28. PB T cells were therefore stimulated with TNF-α, interferon gamma, IL-1β, or transforming growth factor beta, in the presence or absence of anti-CD28. Here we found that stimulation with anti CD28 by itself was sufficient to induce Rap1 inhibition and induce a moderate increase in ROS production. Co-incubation of PB T cells with TNF-α strongly enhanced the intracellular ROS production.

# Conclusion

*In vitro* exposure of PB T cells from rheumatoid arthritis patients to synovial monocytes leads to a strong increase in intracellular ROS production. This is mediated by simultaneous Ras activation and inhibition of Rap1. Where Ras can be activated by a variety of stimuli, Rap1 inhibition is induced by SF monocytes through CD28 costimulatory signaling.


abstract: A report on the Cold Spring Harbor Laboratory meeting 'Systems Biology: Global Regulation of Gene Expression', Cold Spring Harbor, USA, 27-30 March 2008.
author: Stein Aerts; Stefanie Butland
date: 2008
institute: 1Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, VIB, Leuven B-3000, Belgium; 2Centre for Molecular Medicine and Therapeutics, CFRI, University of British Columbia, Vancouver, V5Z 4H4, Canada
title: Sequencing the regulatory genome

The line between the biological and computational research communities has disappeared in the field of gene regulation. The group of regulatory biology researchers represented at the recent meeting at Cold Spring Harbor on systems biology shares the same goal: develop and apply experimental and computational technologies to decipher the genomic regulatory code and the gene regulatory networks that are the driving forces of development and evolution. As in previous years, important gaps in solving the complex problem of gene regulation were bridged. This year featured the emerging massively parallel sequencing technologies, which are now being applied to every conceivable step in the gene regulation process, from gene annotation and alternative splicing, to transcription factor binding, and chromatin structure. Topics covered at the meeting ranged widely and in this report, we give our impressions of some highlights in two dominant themes: gene regulation in a nuclear context and transcription factor binding specificity.

# Genome geography in three dimensions

When transcription factors are reading the genomic regulatory code to determine the complement of active genes in a cell at a given time, they can be aided, guided, or obstructed by the chromatin they operate on. To catch chromatin in the regulatory act, laboratories are sequencing the sites associated with histone modifications that mark repressive, activating, and bivalent chromatin states, high-resolution DNase I hypersensitive sites (DHSs) that mark accessible chromatin, possible insulator sites, sites bound by transcription factors and RNA polymerase II, and *in vivo* cross-linked sites that represent long-range regulatory interactions in a locus. In an increasing number of laboratories, the regulatory geography of the genome is now being assessed within the three-dimensional context of the nucleus.

Bas van Steensel (Netherlands Cancer Institute, Amsterdam, the Netherlands) provided an elegant picture of human gene regulation in three dimensions by identifying nuclear-lamina-associated domains (LADs) in interphase chromosomes. LADs range from 100 kb to 10 Mb and have sharp borders that define chromatin regions with distinctive characteristics: they tend to have fewer genes with lower expression levels compared with genes outside LADS, low RNA polymerase II occupancy, and enrichment of the repressive histone mark H3 trimethylated on lysine 27 (H3K27me3) at their borders. Thirty percent of LAD borders have at least one of three other marks: binding sites for the transcription factor CTCF (commonly held to act as insulators), a CpG island, or a promoter directing transcription away from the LAD.

Sites of chromatin accessibility across the human genome were precisely delineated by John Stamatoyannopoulos (University of Washington School of Medicine, St Louis, USA) in nine cell types by 'digital DNase I', an *in vivo* assay of DNase I hypersensitive sites identified by single-molecule sequencing. Stamatoyannopoulos has identified around 400,000 DHSs genome-wide, of which around 170,000 were highly regulated cell-type specific elements. A subset of these are organized into approximately 2,000 tissue 'regulons', each comprising a large cluster of lineage-specific elements spread out over tens or even hundreds of kilobases. Genes that were marked by these regulons in a given cell type showed striking over-representation of Gene Ontology terms for processes associated with the cell lineage in which they were observed. In addition to accessibility to DNase, active enhancers show specific histone modifications. Gary Hon (Ludwig Institute for Cancer Research, San Diego, USA) was able to distinguish cell-type specific enhancers from promoters by their enrichment for H3K4me1 over H3K4me3 modifications. He proposed that these enhancers are what drive cell-type specific patterns of gene expression.

With such data it is critical to determine how different regulon elements interact with each other to elicit a response. Job Dekker (University of Massachusetts Medical School, Worcester, USA) described his 'chromosome conformation capture carbon copy' (5C) method to detect many-by-many chromatin interactions for a picture of spatial conformation of genomic regions. His analysis of a 1 Mb region around the human beta-globin locus showed that an alternative promoter 250 kb upstream physically interacts with the globin locus control region. Dekker pointed out that "simple models are insufficient" for gene regulation, as CTCF sites, usually considered as insulators, at the beta-globin locus actually facilitate long-range interactions between promoters and enhancers.

# Transcription factor binding specificity

We were reminded by Kevin Struhl (Harvard Medical School, Boston, USA) that the epigenetic states of chromatin cannot explain the specificity of gene expression, but are rather instructed by the sequence-specific transcription factors that translate the regulatory code and recruit chromatin-modifying activities. A cornerstone of our understanding of the regulatory language is the knowledge of a transcription factor's DNA-binding specificity. Significant progress has been achieved in deriving high-quality DNA-binding profiles through a variety of approaches with a large dose of collaboration, particularly with Martha Bulyk (Brigham & Women's Hospital and Harvard Medical School, Boston, USA) for protein-binding microarrays (PBMs). Scot Wolfe (University of Massachusetts Medical School, Worcester, USA) reported new binding profiles for 84 homeodomain transcription factors for *Drosophila melanogaster* through a bacterial one-hybrid system, while Gong-Hong Wei (University of Helsinki, Finland) described binding profiles for all 27 human and 26 mouse ETS family members using a microwell-based high-throughput assay and PBMs, and Christian Grove (University of Massa-chusetts Medical School, Worcester, USA) reported profiles for most of the basic helix-loop-helix (bHLH) dimers in *Caenorhabditis elegans* using a novel version of assay by PBMs. Timothy Hughes (University of Toronto, Canada) described profiles for 300 human and mouse transcription factors across 23 structural classes, including 168 profiles (of 175 total) for homeodomain transcription factors using PBMs.

All these profiles are highly conserved across species and can be ported between orthologous transcription factors when the DNA-contacting amino acids are conserved. This implies that a full compendium of transcripton factor binding specificities across all animals can be accomplished in the near future, with about one third being finished and released by these groups very soon. A question that remains is precisely how other contributors to specificity, such as transcription factor cooperativity, cell-type specific expression, variant or 'weak' recognition sites, and chromatin state together distinguish between correct target sites of related transcription factors that have virtually identical position weight matrices (PWMs).

While the relationship between transcription factors and their binding profiles is well conserved, independent data from various speakers showed yet again that the locations of *bona fide* regulatory elements are not always conserved in an alignment between orthologous regions. This plasticity of transcription factor recognition sites between functionally conserved regulatory regions is still posing a challenge for their computational prediction. Pouya Kheradpour (Massa-chusetts Institute of Technology, Cambridge, USA) presented a pragmatic solution by allowing for movement of a predicted site in an alignment, which for many motifs resulted in increased recovery of conserved sites (sensitivity) at a given specificity. Furthermore, many nonconserved sites are located in transposable elements that are generally not under selection and are usually masked before sequence analysis. For example, Guillaume Bourque (Genome Institute of Singapore, Singapore) found that 43% of nonconserved p53-binding sites are repeat-associated. Ting Wang (University of California, Santa Cruz, USA) identified a similar proportion of p53-binding sites in human endogenous retrovirus long terminal repeats, and Stamatoyanno-poulos noted that around 10% of his DHSs map to transposable elements. Mobile elements thus provide an additional substrate for evolution of species-specific gene regulation.

# What's next in transcriptional regulation?

The key challenge will be to combine the two topics highlighted in this report, namely determination of the specific binding sites for multiple transcription factors and the genome-scale characterization of chromatin states, and to link these with spatial and temporal differences in gene expression. Advances in measuring cell-type specific gene expression were shown by Bob Waterston (University of Washington, St Louis, USA), who is using automated image-processing tools to analyze three-dimensional movies of fluorescent-marker tagged transcription factors in *C. elegans* embryos. Comparing massive numbers of images, they can make direct quantitative comparisons of expression patterns of different transcription factors "cell-by-cell, minute-by-minute". On the same topic, Philip Benfey (Duke University, Durham, USA) has leveraged a compendium of gene-expression data at cell-type specific resolution for an entire organ. His group performed microarray experiments on diverse cell lineages across the radial and longitudinal axes of the *Arabidopsis* root. A complementary set of experiments on six different cell types showed that specific cell types respond uniquely to high-salt or low-iron stress conditions in terms of which genes are up- or down-regulated.

Robert Kingston (Harvard Medical School, Boston, USA) is developing technologies for locus-specific chromatin isolation to get the complete list of players that bind *in vivo* to a regulatory locus. He presented a convincing proof of principle by isolating 95% of known telomere interactors and identifying new biologically relevant ones. A more classical way of determining the input of multiple transcription factors to a specific locus is by genetic screens. Results of a high-throughput assay were presented by Pinay Kainth (University of Toronto, Canada), who tested the input contributions of all nonessential yeast transcription factors and their potential regulators on 27 cell-cycle-specific promoters using quantitative fluorescence measurements. Although genetic perturbations that alter a promoter's output are not limited to the transcription factors that physically bind to the promoter, such data can approximate direct interactions, especially when combined with PWM-based motif predictions.

Once the transcription-factor-specific regulatory sites, chromatin accessibility, and long-range interactions are determined for a given cell state, one must still determine the *cis*-regulatory logic and the rate of transcription initiation that it produces. This is still a difficult problem addressed by only few groups, including that of Jason Gertz (Washington University School of Medicine, St Louis, USA), who reported the use of libraries of synthetic regulatory regions to examine putative roles of combinations of *cis*-elements even before they have been discovered in real enhancers. This approach provides a possible solution to the sparse sampling of sets of *in vivo* validated regulatory regions that produce a similar output.

This high-quality meeting of regulatory biology researchers indicates that we are taking important steps toward the construction of a powerful toolkit to identify and model *in vivo* regulatory interactions and networks. The strong proofs of principle demonstrated at this meeting, together with increased access to massively parallel sequencing platforms, anticipate an era in which systems geneticists will collaborate to perform gene-regulation experiments in unprecedented detail and scale to characterize their pet 'regulome', and niche biologists will apply these technologies to address specific hypotheses about development, health and disease.


author: Gregory A Petsko
date: 2010
institute: 1Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110, USA
title: A Faustian bargain

# An open letter to George M Philip, President of the State University of New York At Albany

Dear President Philip,

Probably the last thing you need at this moment is someone else from outside your university complaining about your decision. If you want to argue that I can't really understand all aspects of the situation, never having been associated with SUNY Albany, I wouldn't disagree. But I cannot let something like this go by without weighing in. I hope, when I'm through, you will at least understand why.

Just 30 days ago, on October 1st, you announced that the departments of French, Italian, Classics, Russian and Theater Arts were being eliminated. You gave several reasons for your decision, including that 'there are comparatively fewer students enrolled in these degree programs.' Of course, your decision was also, perhaps chiefly, a cost-cutting measure - in fact, you stated that this decision might not have been necessary had the state legislature passed a bill that would have allowed your university to set its own tuition rates. Finally, you asserted that the humanities were a drain on the institution financially, as opposed to the sciences, which bring in money in the form of grants and contracts.

Let's examine these and your other reasons in detail, because I think if one does, it becomes clear that the facts on which they are based have some important aspects that are not covered in your statement. First, the matter of enrollment. I'm sure that relatively few students take classes in these subjects nowadays, just as you say. There wouldn't have been many in my day, either, if universities hadn't required students to take a distribution of courses in many different parts of the academy: humanities, social sciences, the fine arts, the physical and natural sciences, and to attain minimal proficiency in at least one foreign language. You see, the reason that humanities classes have low enrollment is not because students these days are clamoring for more relevant courses; it's because administrators like you, and spineless faculty, have stopped setting distribution requirements and started allowing students to choose their own academic programs - something I feel is a complete abrogation of the duty of university faculty as teachers and mentors. You could fix the enrollment problem tomorrow by instituting a mandatory core curriculum that included a wide range of courses.

Young people haven't, for the most part, yet attained the wisdom to have that kind of freedom without making poor decisions. In fact, without wisdom, it's hard for most people. That idea is thrashed out better than anywhere else, I think, in Dostoyevsky's parable of the Grand Inquisitor, which is told in Chapter Five of his great novel, *The Brothers Karamazov*. In the parable, Christ comes back to earth in Seville at the time of the Spanish Inquisition. He performs several miracles but is arrested by Inquisition leaders and sentenced to be burned at the stake. The Grand Inquisitor visits Him in his cell to tell Him that the Church no longer needs Him. The main portion of the text is the Inquisitor explaining why. The Inquisitor says that Jesus rejected the three temptations of Satan in the desert in favor of freedom, but he believes that Jesus has misjudged human nature. The Inquisitor says that the vast majority of humanity cannot handle freedom. In giving humans the freedom to choose, Christ has doomed humanity to a life of suffering.

That single chapter in a much longer book is one of the great works of modern literature. You would find a lot in it to think about. I'm sure your Russian faculty would love to talk with you about it - if only you had a Russian department, which now, of course, you don't.

Then there's the question of whether the state legislature's inaction gave you no other choice. I'm sure the budgetary problems you have to deal with are serious. They certainly are at Brandeis University, where I work. And we, too, faced critical strategic decisions because our income was no longer enough to meet our expenses. But we eschewed your draconian - and authoritarian - solution, and a team of faculty, with input from all parts of the university, came up with a plan to do more with fewer resources. I'm not saying that all the specifics of our solution would fit your institution, but the process sure would have. You did call a town meeting, but it was to discuss your plan, not let the university craft its own. And you called that meeting for Friday afternoon on October 1st, when few of your students or faculty would be around to attend. In your defense, you called the timing 'unfortunate', but pleaded that there was a 'limited availability of appropriate large venue options.' I find that rather surprising. If the President of Brandeis needed a lecture hall on short notice, he would get one. I guess you don't have much clout at your university.

It seems to me that the way you went about it couldn't have been more likely to alienate just about everybody on campus. In your position, I would have done everything possible to avoid that. I wouldn't want to end up in the 9th Bolgia (ditch of stone) of the 8th Circle of the Inferno, where the great 14th century Italian poet Dante Alighieri put the sowers of discord. There, as they struggle in that pit for all eternity, a demon continually hacks their limbs apart, just as in life they divided others.

The *Inferno* is the first book of Dante's *Divine Comedy*, one of the great works of the human imagination. There's so much to learn from it about human weakness and folly. The faculty in your Italian department would be delighted to introduce you to its many wonders - if only you had an Italian department, which now, of course, you don't.

And do you really think even those faculty and administrators who may applaud your tough-minded stance (partly, I'm sure, in relief that they didn't get the axe themselves) are still going to be on your side in the future? I'm reminded of the fable by Aesop of the Travelers and the Bear: two men were walking together through the woods, when a bear rushed out at them. One of the travelers happened to be in front, and he grabbed the branch of a tree, climbed up, and hid himself in the leaves. The other, being too far behind, threw himself flat down on the ground, with his face in the dust. The bear came up to him, put his muzzle close to the man's ear, and sniffed and sniffed. But at last with a growl the bear slouched off, for bears will not touch dead meat. Then the fellow in the tree came down to his companion, and, laughing, said 'What was it that the bear whispered to you?' 'He told me,' said the other man, 'Never to trust a friend who deserts you in a pinch.'

I first learned that fable, and its valuable lesson for life, in a freshman classics course. Aesop is credited with literally hundreds of fables, most of which are equally enjoyable - and enlightening. Your classics faculty would gladly tell you about them, if only you had a Classics department, which now, of course, you don't.

As for the argument that the humanities don't pay their own way, well, I guess that's true, but it seems to me that there's a fallacy in assuming that a university should be run like a business. I'm not saying it shouldn't be managed prudently, but the notion that every part of it needs to be self-supporting is simply at variance with what a university is all about. You seem to value entrepreneurial programs and practical subjects that might generate intellectual property more than you do 'old-fashioned' courses of study. But universities aren't just about discovering and capitalizing on new knowledge; they are also about preserving knowledge from being lost over time, and that requires a financial investment. There is good reason for it: what seems to be archaic today can become vital in the future. I'll give you two examples of that. The first is the science of virology, which in the 1970s was dying out because people felt that infectious diseases were no longer a serious health problem in the developed world and other subjects, such as molecular biology, were much sexier. Then, in the early 1990s, a little problem called AIDS became the world's number 1 health concern. The virus that causes AIDS was first isolated and characterized at the National Institutes of Health in the USA and the Institute Pasteur in France, because these were among the few institutions that still had thriving virology programs. My second example you will probably be more familiar with. Middle Eastern Studies, including the study of foreign languages such as Arabic and Persian, was hardly a hot subject on most campuses in the 1990s. Then came September 11, 2001. Suddenly we realized that we needed a lot more people who understood something about that part of the world, especially its Muslim culture. Those universities that had preserved their Middle Eastern Studies departments, even in the face of declining enrollment, suddenly became very important places. Those that hadn't - well, I'm sure you get the picture.

I know one of your arguments is that not every place should try to do everything. Let other institutions have great programs in classics or theater arts, you say; we will focus on preparing students for jobs in the real world. Well, I hope I've just shown you that the real world is pretty fickle about what it wants. The best way for people to be prepared for the inevitable shock of change is to be as broadly educated as possible, because today's backwater is often tomorrow's hot field. And interdisciplinary research, which is all the rage these days, is only possible if people aren't too narrowly trained. If none of that convinces you, then I'm willing to let you turn your institution into a place that focuses on the practical, but only if you stop calling it a university and yourself the President of one. You see, the word 'university' derives from the Latin 'universitas', meaning 'the whole'. You can't be a university without having a thriving humanities program. You will need to call SUNY Albany a trade school, or perhaps a vocational college, but not a university. Not anymore.

I utterly refuse to believe that you had no alternative. It's your job as President to find ways of solving problems that do not require the amputation of healthy limbs. Voltaire said that no problem can withstand the assault of sustained thinking. Voltaire, whose real name was François-Marie Arouet, had a lot of pithy, witty and brilliant things to say (my favorite is 'God is a comedian playing to an audience that is afraid to laugh'). Much of what he wrote would be very useful to you. I'm sure the faculty in your French department would be happy to introduce you to his writings, if only you had a French department, which now, of course, you don't.

I guess I shouldn't be surprised that you have trouble understanding the importance of maintaining programs in unglamorous or even seemingly 'dead' subjects. From your biography, you don't actually have a PhD or other high degree, and have never really taught or done research at a university. Perhaps my own background will interest you. I started out as a classics major. I'm now Professor of Biochemistry and Chemistry. Of all the courses I took in college and graduate school, the ones that have benefited me the most in my career as a scientist are the courses in classics, art history, sociology, and English literature. These courses didn't just give me a much better appreciation for my own culture; they taught me how to think, to analyze, and to write clearly. None of my sciences courses did any of that.

One of the things I do now is write a monthly column on science and society. I've done it for over 10 years, and I'm pleased to say some people seem to like it. If I've been fortunate enough to come up with a few insightful observations, I can assure you they are entirely due to my background in the humanities and my love of the arts.

One of the things I've written about is the way genomics is changing the world we live in. Our ability to manipulate the human genome is going to pose some very difficult questions for humanity in the next few decades, including the question of just what it means to be human. That isn't a question for science alone; it's a question that must be answered with input from every sphere of human thought, including - especially including - the humanities and arts. Science unleavened by the human heart and the human spirit is sterile, cold, and self-absorbed. It's also unimaginative: some of my best ideas as a scientist have come from thinking and reading about things that have, superficially, nothing to do with science. If I'm right that what it means to be human is going to be one of the central issues of our time, then universities that are best equipped to deal with it, in all its many facets, will be the most important institutions of higher learning in the future. You've just ensured that yours won't be one of them.

Some of your defenders have asserted that this is all a brilliant ploy on your part - a master political move designed to shock the legislature and force them to give SUNY Albany enough resources to keep these departments open. That would be Machiavellian (another notable Italian writer, but then, you don't have any Italian faculty to tell you about him), certainly, but I doubt that you're that clever. If you were, you would have held that town meeting when the whole university could have been present, at a place where the press would be all over it. That's how you force the hand of a bunch of politicians. You proclaim your action on the steps of the state capitol. You don't try to sneak it through in the dead of night, when your institution has its back turned.

No, I think you were simply trying to balance your budget at the expense of what you believe to be weak, outdated and powerless departments. I think you will find, in time, that you made a Faustian bargain. Faust is the title character in a play by Johann Wolfgang von Goethe. It was written around 1800 but still attracts the largest audiences of any play in Germany whenever it's performed. Faust is the story of a scholar who makes a deal with the devil. The devil promises him anything he wants as long as he lives. In return, the devil will get - well, I'm sure you can guess how these sorts of deals usually go. If only you had a Theater department, which now, of course, you don't, you could ask them to perform the play so you could see what happens. It's awfully relevant to your situation. You see, Goethe believed that it profits a man nothing to give up his soul for the whole world. That's the whole world, President Philip, not just a balanced budget. Although, I guess, to be fair, you haven't given up your soul. Just the soul of your institution.

Disrespectfully yours,

Gregory A Petsko


abstract: # Background
  .
  Of concern to health educators is the suggestion that college females practice diet and health behaviors that contradict the 2005 dietary guidelines for Americans. In this regard, there remain gaps in the research related to dieting among college females. Namely, do normal weight individuals diet differently from those who are overweight or obese, and are there dieting practices used by females that can be adapted to promote a healthy body weight? Since it is well recognized that females diet, this study seeks to determine the dieting practices used among normal, overweight, and obese college females (do they diet differently) and identify dieting practices that could be pursued to help these females more appropriately achieve and maintain a healthy body weight.
  .
  # Methods
  .
  A total of 185 female college students aged 18 to 24 years participated in this study. Height, weight, waist and hip circumferences, and skinfold thickness were measured to assess body composition. Surveys included a dieting practices questionnaire and a 30-day physical activity recall. Participants were classified according to body mass index (BMI) as normal weight (n = 113), overweight (n = 35), or obese (n = 21). Data were analyzed using JMP IN® software. Descriptive statistics included means, standard deviations, and frequency. Subsequent data analysis involved Pearson *X*^2^ and one-way analysis of variance with comparison for all pairs that were significantly different using Tukey-Kramer honestly significant difference test.
  .
  # Results
  .
  Outcomes of this study indicate the majority of participants (83%) used dieting for weight loss and believed they would be 2% to 6% greater than current weight if they did not diet; normal weight, overweight, and obese groups perceived attractive weight to be 94%, 85%, and 74%, respectively, of current weight; 80% of participants reported using physical activity to control weight, although only 19% exercised at a level that would promote weight loss; only two of 15 dieting behaviors assessed differed in terms of prevalence of use among groups, which were consciously eating less than you want (44% normal weight, 57% overweight, 81% obese) and using artificial sweeteners (31% normal weight and overweight, 5% obese); and the most prevalent explicit maladaptive weight loss behavior was smoking cigarettes (used by 9% of participants) and most unhealthy was skipping breakfast (32%).
  .
  # Conclusion
  .
  Collectively, results indicate female college students, regardless of weight status, would benefit from open discussions with health educators regarding healthy and effective dieting practices to achieve/maintain a healthy body weight. The results are subject to replication among high school, middle-aged, and older females.
author: Brenda M Malinauskas; Thomas D Raedeke; Victor G Aeby; Jean L Smith; Matthew B Dallas
date: 2006
institute: 1Department of Nutrition and Hospitality Management, East Carolina University, Greenville, North Carolina, USA; 2Department of Exercise and Sport Science, East Carolina University, Greenville, North Carolina, USA; 3Department of Health Education, East Carolina University, Greenville, North Carolina, USA
references:
title: Dieting practices, weight perceptions, and body composition: A comparison of normal weight, overweight, and obese college females

# Background

Tens of thousands of high school graduates will be heading out on their own this fall. Many will be confronting the rigors of higher education while adjusting to a new environment and new pressures. With all the changes, gaining weight is common. When you consider that more than 1.5 million students are entering U.S. colleges and universities each fall, by the following spring the weight gain entering collegians encounter is epidemic. Gaining weight during freshman year is so common that the phenomenon has its own nickname the "Freshman 15" and has been associated with the freshman experience for many years. Although unwanted weight gain can occur at any age, the transition from high school to college is a time of increased risk of weight gain among females.

Females, at a very young age, are concerned about body weight and place high importance on appearance, which is dramatically influenced by the media. A major messaging theme of teen magazine websites is the necessity to be beautiful \[1\]. Mooney et al \[2\] conducted interviews with home economic teachers and teen focus groups in Ireland and found that adolescent females are very conscious of their body image, are strongly influenced by high profile celebrities, and the primary motivations for wanting to be thin are to gain attention from males, approval from friends, and self confidence. Unfortunately, the desire to be beautiful may result in unwanted outcomes. For example, in a study by Monro et al \[3\] the authors reported an increase in appearance anxiety among female college students that resulted from viewing advertisements of idealized images. Wilson et al \[4\] reported that non-athlete college students reported more stress than athlete counterparts in areas of satisfaction with physical appearance, decisions about education, social conflicts regarding smoking, and financial burdens. Lastly, there are unique experiences of college females that may promote dieting, including fear of gaining weight, increased sense of independence that may promote experimenting with dieting (food restriction, use of supplements and fad diets), and changes to daily schedule that affect eating and exercise habits ("pulling all-nighters" to study for exams or complete course projects).

Emergence of dieting among girls is most prevalent at 13 and 14 years of age and remains prevalent throughout adulthood \[5\]. Dieting has been reported among normal and underweight individuals, in addition to those who are overweight \[6\]. Despite the finding that dieting to control weight is often times ineffective; dieting remains popular among females \[7\]. When compared to college males, college females are more likely to actively diet, place high importance on appearance and the benefits of maintaining an ideal weight, and engage in unsafe dieting \[8\].

Given our culture, which suffers from a pathological emphasis on weight as a measure of a woman's worth, and given the continuing epidemic in our society of disordered eating, there are significant problems stemming from the idea of the "Freshman 15". The first problem is the assumption that excessive weight gain is inevitable during the college years. Second, for the many females already struggling with disordered eating, the construct of the "Freshman 15" becomes a terrifying probability that exacerbates an already difficult problem. For example, Patton \[9\] reported that girls with a history of severe dieting were 18 times more likely to develop eating disorders than girls with no history of dieting, and girls with a history of moderate dieting were five times more likely to develop eating disorders than girls who did not diet. Third, even for the college females who may not have significant issues with food or weight, the idea of the "Freshman 15" can play a significant role in solidifying the oppressive ideathat a female must be thin in order to qualify for success and happiness in our society. Such mentality can contribute significantly to the development of disordered eating throughout college.

At the core of what makes the "Freshman 15" concept so problematic is the reduction of female students to a single-dimension: body type. Given the myriad life issues that are relevant to women at the onset of the college years, to have a concept referring to the single superficial issue of body weight be so widespread and so influential is indicative of a larger cultural pathology. What is needed is a more aggressive message to the culture that contradicts this reductionistic message.

In this regard, there remain gaps in the research related to dieting among college females. Namely, do normal weight individuals diet differently from those who are overweight or obese, and are there dieting practices used by females that can be adapted to promote a healthy body weight? Because it is well recognized that females diet, this study seeks to determine the dieting practices used among normal, overweight, and obese college females (do they diet differently) and identify dieting practices that could be pursued to help these females more appropriately achieve and maintain a healthy body weight.

Of concern to health educators is the suggestion that college females practice diet and health behaviors that contradict the 2005 dietary guidelines for Americans \[10\]. For example, physical exercise plays a role in weight management \[10,11\]. In an executive summary regarding treatment of overweight and obesity in adults, the National Heart, Lung, and Blood Institute in cooperation with the National Institutes of Diabetes and Digestive and Kidney Diseases report that an increase in physical activity is an important component of weight loss therapy and that sustained physical activity is helpful in prevention of weight regain \[11\]. Importantly, the Dietary Guidelines recommend adults engage in 60 to 90 minutes of daily moderate- to vigorous-intensity physical activity \[10\]. It is questionable if college females adhere to the public health message of higher intensity and longer duration physical activity to promote a healthy body weight \[10,11\]. The relationship between smoking and weight concerns has been explored. Potter et al \[12\] reported in a comprehensive review of smoking among adolescents that dieting behaviors, disordered eating symptoms, and general weight concerns were related to smoking among females.

The purpose of this study was to determine differences in dieting practices, weight perceptions, and body composition of normal weight, overweight, and obese female college students. The research questions under investigation seek to first, determine body composition, weight perceptions, and physical activity differences of normal weight, overweight, and obese college females. Second, identify perceived sources of pressure to be a certain weight among these groups. Third, identify weight loss behaviors ever used to consciously lose or control weight among groups. Fourth, identify the most prevalent weight control products and commercial diets used by female college students.

# Methods

## Design and sample

The study is a quasi-experimental design. The sample of convenience included students from five introductory nutrition courses taught by two instructors and invited to participate during the spring semester of 2005. The total sample recruited included 230 females, which represented 51% of all females who were enrolled in introductory nutrition courses spring 2005. Overall, 208 female participants completed the study, which was a 90% participation rate for females in the nutrition courses surveyed. The final sample size was 185, as 23 were excluded for the following reasons: age greater than 24 years (n = 14), BMI less than 18.5 kg/m^2^ (n = 7), and reported pregnancy (n = 2).

Course enrollment ranged from 49 to 100 students. A scripted description of the study (read by the instructor at the beginning of a class period which highlighted the study protocol) and an electronic course announcement posted on Blackboard were the means used to inform students about the study. For the purpose of this study Blackboard is defined as a web-based education platform that aids course delivery; students are accustomed to checking Blackboard frequently for course information. Extra credit was available to students who completed the study. Males, females greater than 24 years of age, and females reporting current pregnancy were excluded from analysis.

## Data collection and research instruments

Data collection occurred on two occasions. During the first meeting, students completed a survey regarding dieting practices, weight perceptions, and level of physical activity participation. During the second meeting, body composition assessments were completed. The university-affiliated institutional review board approved the project (University and Medical Center Institutional Review Board number 04–0487), and the project was carried out in compliance with the Helsinki Declaration. Signed informed consent was obtained from all participants.

Prior to survey administration, one of two research assistants met with students during a class period, using a script to describe the study and provide instruction for completing the survey. The key points of the script were to provide uniform instruction for completing the study survey, encourage participants to answer all questions completely and truthfully, and to remind participants of the body composition assessment schedule. The survey took approximately 15 minutes to complete.

The survey included a dieting practices questionnaire that assessed demographic, dieting practices, weight perceptions, and perceived sources of pressure to be a certain weight, and a 30-day physical activity recall. The dieting practices questionnaire was developed by a Registered Dietitian and reviewed for content validity by two Registered Dietitians who practice in eating disorder treatment and nutrition counseling of college students. The questionnaire was adapted from one developed by Calderon et al \[13\] that investigated dieting practices among high school students. As a measure of physical activity, a 30 day self-report measure developed by Jackson et al \[14\] was used. To complete this measure, participants rate how active they have been over the past 30 days on a scale ranging from zero to seven. In general, scores of zero and one indicate that the person does not participate in regular activity. Participants who score two or three participate in some moderate activity whereas those who score four or above participate in some vigorous exercise. Baumgartner et al \[15\] reported that values four or above generally indicate that a person participates in physical activity on a regular basis. Regular activity participation, particularly vigorous exercise, often results in increased aerobic capacity. In support of the scale's validity, researchers have found that self-reported physical activity was a significant predictor of VO~2~ max \[15\].

To pilot test the survey, a small sample of 12 undergraduate female students completed the questionnaires. Minor syntax and formatting modifications were made to the dieting practices questionnaire based on their responses.

On the second occasion, participants reported to the lab for anthropometric measurements. Females with the first letter of their last name A to L reported after completing the second exam in their respective nutrition course, females with last name M to Z after the third. The lab was organized into two measurement stations that were separated by privacy screens. Weight and height were measured at the first station, circumference (waist and hip) and skinfold thickness (triceps, biceps, and thigh) measurements were obtained at the second station. Four research assistants (two for each station) were trained by a single anthropometrist. The same research assistant took all measurements for that "station" on each participant. Weight was measured to the nearest 0.1 kg (Tanita body composition analyzer, Arlington, IL), height (Seca portable height stadiometer, Leicester, England) and circumferences (non-flexible tape measure) to 0.1 cm, and skinfolds to 0.1 mm (Harpenden skinfold caliper, Vital Signs model 68875, Country Technology, Inc., Gays Mills, WI) using American College of Sports Medicine \[16\] procedures. Shoes, and as much clothing as was socially acceptable to the participant, were removed preceding body composition measurements. Participants were classified according to body mass index (BMI); BMI 18.5 to 24.9 kg/m^2^ were classified as normal weight, 25 to 29.9 kg/m^2^ as overweight, and 30 kg/m^2^ or greater as obese \[17\].

## Data analysis

Analyses were performed using JMP IN® software \[18\]. Descriptive statistics included means, standard deviations, and frequency. Subsequent data analysis involved Pearson *X*^2^ and one-way analysis of variance with comparison for all pairs that were significantly different using Tukey-Kramer honestly significant difference test. A significant level of .05 was used for statistical analysis.

# Results

Overall, 208 female participants completed the study, which was a 90% participation rate for females in the nutrition courses surveyed. However, 23 were excluded for the following reasons: age greater than 24 years (n = 14), BMI less than 18.5 kg/m^2^ (n = 7), and reported pregnancy (n = 2). BMI less than 18.5 kg/m^2^ is classified by the Center for Disease Control and Prevention \[17\] as an underweight condition. The final sample size was 185. Mean age of participants was 19.7 years (SD = 1.4). A majority (78%) of participants were White, 18% were Black, and 4% were American Indian, Asian, or Hispanic. Participants were predominantly freshmen and sophomores (70%), as expected because they were recruited from introductory nutrition courses.

Regarding question one, body composition, weight perceptions, and physical activity of normal weight, overweight, and obese groups are reported in Table 1. Despite significant differences among groups for weight, F(2, 166) = 171, p \< .01, BMI, F(2, 166) = 272, p \< .01, body fat, F(2, 166) = 96, p \< .01, and waist-to-hip ratio, F(2, 166) = 53, p \< .01, mean physical activity was similar among groups, F(2, 165) = 0.5, p = .61. Significant differences were found among groups for perceived healthy weight, F(2, 163) = 76, p \< .01, and attractive weight, F(2, 160) = 74, p \< .01, compared to current weight. Mean perceived healthy weight was 5% (normal weight), 13% (overweight), and 23% (obese) lower than current weight. Mean perceived attractive weight followed the same trend, and was 6%, 15%, and 26% lower than current weight for normal weight, overweight, and obese groups, respectively. All groups perceived natural weight to be greater than current weight, meaning if no attempt was made to control weight then weight would be 2% to 6% greater than current weight. The majority (80%) of participants reported using physical activity to control their weight. However, 32% did not participate in regularly programmed recreation, sport, or heavy physical activity, and only 19% of participants (21% normal weight, 21% overweight, and 5% obese groups) reported spending over 3 hours per week in vigorous aerobic activity.

Mean body composition, weight perceptions, and physical activity among normal weight, overweight, and obese female college students.

|  | Weight classification |  |  |
|----|----|----|----|
|  |  |  |  |
|  | Normal weight | Overweight | Obese |
|  | n = 113 | n = 35 | n = 21 |
| Variable | M ± SD | M ± SD | M ± SD |
| Body composition |  |  |  |
| Weight (pounds) | 130^a^ ± 13 | 160^b^ ± 18 | 213^c^ ± 39 |
| BMI (kg/m^2^) | 21.9^a^ ± 1.8 | 27.3^b^ ± 1.3 | 35.3^c^ ± 5.7 |
| Body fat (%) | 28^a^ ± 4 | 33^b^ ± 4 | 38^c^ ± 3 |
| Waist-to-hip ratio | 0.72^a^ ± 0.01 | 0.76^b^ ± 0.05 | 0.83^c^ ± 0.07 |
| Weight perceptions |  |  |  |
| Perceived healthy weight (pounds) | 123^a^ ± 10 | 138^b^ ± 17 | 164^c^ ± 26 |
| Perceived attractive weight (pounds) | 122^a^ ± 11 | 136^b^ ± 17 | 158^c^ ± 29 |
| Perceived natural weight (pounds) | 138^a^ ± 18 | 169^b^ ± 25 | 216^c^ ± 42 |
| Perceived healthy weight (% of current) | 95^a^ ± 7 | 87^b^ ± 6 | 77^c^ ± 6 |
| Perceived attractive weight (% of current) | 94^a^ ± 7 | 85^b^ ± 6 | 74^c^ ± 8 |
| Perceived natural weight (% of current) | 106 ± 9 | 106 ± 10 | 102 ± 2 |
| Physical activity | 4.1 ± 2.5 | 3.8 ± 2.5 | 3.5 ± 2.5 |

Note: Means in the same row having letters that do not share subscripts differ at *p* \< .01 in the Tukey-Kramer honestly significant difference test. The higher the physical activity score, the greater intensity and amount of reported exercise over the past 30 days using a scoring system of 0 (do not participate regularly in planned exercise) to 7 (spend over 3 hours weekly in heavy exercise).

Concerning question two, 83% of participants reported ever consciously trying to lose or control their weight, including 80% of normal weight, 91% of overweight, and 86% of obese participants. Mean age when dieting was initiated was 15.7 years (SD = 2.3), which was similar among groups, F(2, 137) = 1, p = .30. Fifty eight percent of participants reported pressure to be a certain weight; the primary sources were self (54%), media (37%), and friends (32%). Frequency distributions of "yes" response to these sources were similar among groups (see Table 2). Other sources of pressure included significant other (reported as a source of pressure by 13% of participants), colleagues at work (5%), other athletes (3%), coach (2%), and family members (2%).

Perceived sources of pressure to be a certain weight among normal weight, overweight, and obese female college students.

| Variable         | Frequency "yes" response (%) | *X*^2^ | p (weight status) |
|------------------|------------------------------|--------|-------------------|
| Self             |                              | 2.5    | .29               |
| Normal weight^a^ | 50                           |        |                   |
| Overweight^b^    | 62                           |        |                   |
| Obese^c^         | 43                           |        |                   |
| Media            |                              | 0.9    | .63               |
| Normal weight^a^ | 39                           |        |                   |
| Overweight^b^    | 34                           |        |                   |
| Obese^c^         | 29                           |        |                   |
| Friends          |                              | 3.4    | .18               |
| Normal weight^a^ | 31                           |        |                   |
| Overweight^b^    | 37                           |        |                   |
| Obese^c^         | 14                           |        |                   |

Note: *X*^2^ (2, *N* = 166).

^a^n = 113; ^b^n = 35; ^c^n = 21.

Referring to question three, 15 dieting behaviors were assessed to determine if use differed among normal weight, overweight, and obese participants. Nine of the 15 behaviors had large enough sample size of "yes" response to analyze frequency distribution differences among groups; these are reported in Table 3. The five most common behaviors used by all participants were exercising (80%), eating or drinking low fat or fat free versions of foods/drinks (59%), consciously eat less than you want (51%), eating or drinking sugar free versions of foods/drinks (43%), and count calories (40%). Eating less than you want and use of artificial sweeteners were the only behaviors for which frequency of use was significantly different among groups (see Table 3). The other behaviors assessed, which had low frequency of use reported, included not eating foods with high glycemic index (used by 4% normal weight, 6% overweight, and 0% obese), smoke cigarettes (8%, 14%, and 5%), use laxatives after you eat (2%, 6%, and 5%), vomit after you eat (4%, 6%, and 5%), skip lunch (10%, 9%, 10%), and skip dinner (4%, 9%, 0%). Explicit maladaptive weight loss practices included smoking cigarettes (used by 9% of all participants), vomiting (5%) and use of laxatives (3%) after eating.

Weight loss behaviors ever used to consciously lose or control weight of normal weight, overweight, and obese female college students.

| Variable | Frequency "yes" response (%) | *X*^2^ | p (weight status) |
|----|----|----|----|
| Consciously eat less than you want |  | 10.1 | \< .01 |
| Normal weight^a^ | 44 |  |  |
| Overweight^b^ | 57 |  |  |
| Obese^c^ | 81 |  |  |
| Count grams of fat |  | 1.0 | .60 |
| Normal weight^a^ | 23 |  |  |
| Overweight^b^ | 31 |  |  |
| Obese^c^ | 24 |  |  |
| Count net carbs |  | 2.3 | .32 |
| Normal weight^a^ | 18 |  |  |
| Overweight^b^ | 17 |  |  |
| Obese^c^ | 5 |  |  |
| Count calories |  | 0.2 | .89 |
| Normal weight^a^ | 39 |  |  |
| Overweight^b^ | 43 |  |  |
| Obese^c^ | 43 |  |  |
| Eat or drink low fat or fat free versions of foods/drinks |  | 2.9 | .24 |
| Normal weight^a^ | 57 |  |  |
| Overweight^b^ | 71 |  |  |
| Obese^c^ | 52 |  |  |
| Eat or drink sugar free versions of foods/drinks |  | 2.2 | .33 |
| Normal weight^a^ | 43 |  |  |
| Overweight^b^ | 49 |  |  |
| Obese^c^ | 29 |  |  |
| Exercise |  | 2.2 | .33 |
| Normal weight^a^ | 77 |  |  |
| Overweight^b^ | 89 |  |  |
| Obese^c^ | 81 |  |  |
| Use artificial sweeteners |  |  |  |
| Normal weight^a^ | 31 | 6.3 | .04 |
| Overweight^b^ | 31 |  |  |
| Obese^c^ | 5 |  |  |
| Skip breakfast |  |  |  |
| Normal weight^a^ | 27 | 4.9 | .09 |
| Overweight^b^ | 40 |  |  |
| Obese^c^ | 48 |  |  |

Note: *X*^2^ (2, N = 166).

^a^n = 113; ^b^n = 35; ^c^n = 21.

In terms of question four, over-the-counter meal replacement drinks were used by 35% of participants, supplements (Hydroxycut, Stacker II, Xenadrine, CortiSlim, Trim Spa, Hot Rox) by 26%, meal replacement bars by 18%, dieter's tea, green tea, and green tea pills by 11%, and chromium picolinate by 3%. Physician prescribed weight loss pills were used by 3% of participants. In examining commercial diets, the most popular ones were Atkins or South Beach (20%) and Weight Watchers® (11%). Subway, Sugar Busters, and The Zone diet combined had been used by 7% of participants.

# Discussion

The purpose of this study was to investigate dieting practices, weight perceptions, and body composition among normal weight, overweight, and obese college females. Findings from this study support the general belief that dieting by college females is a common weight management strategy, irrespective of weight status. Abraham and O'Dea \[19\] reported that females as young as 12 years of age had tried to lose weight, including 44% who dieted using food restriction and 78% who exercised to lose weight. Findings from the present study indicate that females continue to diet through college. Calderon et al \[13\] reported a greater prevalence of dieting among overweight (67% prevalence) versus at risk for overweight (25%) high school females, which is in contrast to the findings from the present study. We found 83% of college females reporting ever consciously trying to lose or control their weight, with similar prevalence between normal weight, overweight, and obese participants. The discrepancy between findings could be due to how dieting is defined by researchers and interpreted by study participants. Dieting strategies have become so "main stream" in our society, that one may not be aware, unless explicitly stated, behaviours that are being used to consciously lose or control ones' weight. For example, someone may have been drinking diet sodas to control/lose their weight for so many years that they do not recognize this behaviour as a weight loss strategy unless it is pointed out to them. We classified dieting as any method of food restriction, use of supplements, or behaviours used to control one's weight. Although our questionnaire was adapted from the survey of Calderon and colleagues \[13\], we expanded upon behaviours and methods marketed for weight control that were popular at the time our study was conducted, including counting net carbs, eating/drinking sugar free versions of foods/drinks, avoiding foods with high glycemic index, and use of artificial sweeteners. Furthermore, a limitation of the study is that being a cross-sectional study design, we do not know if there exists a causal relationship between dieting and weight control. Longitudinal studies would be the best way to measure if dieting frequency among females and methods of dieting choices change throughout the lifespan and if there exists a causal relationship between dieting and weight control.

We found females perceive healthy and attractive weights to be lower than current weight, and that media influence contributes pressure to be a certain weight. Klesges et al \[8\] reported that college females are more likely than male counterparts to engage in healthy and unhealthy physical activity and food restriction behaviours and place higher importance on appearance benefits of maintaining an ideal body weight. Of great concern are the findings of Bacon et al \[20\] that indicated a significant negative correlation between bone mineral content and number of times on a weight loss diet among obese adult females. Additionally, Gingras et al \[21\] reported that adult female chronic dieters had low body satisfaction and suggested that it is important to address body image dissatisfaction with chronic dieting to improve health, regardless of body size of the dieter. Clearly, chronic dieting can have physical and emotional ramifications.

Most important, many of the weight loss practices reported to be used by participants of the current study, if used appropriately, could promote healthy weight loss and be used long term to maintain a healthy weight. For example, the majority (80%) of participants reported using physical activity to control their weight. However, 32% did not participate in regularly programmed recreation, sport, or heavy physical activity, which is similar to the Behavioral Risk Factor Surveillance system finding that 15% to 34% of adults reported no leisure-time physical activity \[22\]. Holcomb et al \[23\] reported that body mass index, body fat, and waist-to-hip ratio were significantly lower as physical activity increases among premenopausal females. The researchers suggested that ability to increase daily physical activity to minimize fat accumulation could be a strong incentive to become more physically active. Strategies to improve nutrient intake and physical activity to promote health and weight control among females are warranted.

The current study makes an important contribution to the literature by narrowing the gap in research related to dieting among females. Namely, do normal weight individuals diet differently from those who are overweight or obese, and are there dieting practices used by females that can be adapted to promote a healthy body weight? Outcomes of interest to the health educator include: First, dieting practices are prevalent among female college students, regardless of body weight; Second, there were a number of dieting practices used that could promote effective weight loss and healthy weight maintenance if employed appropriately; Third, although many dieters stated they used physical activity for weight loss, the majority who used this method were not meeting physical activity goals for weight loss; and Fourth, the most prevalent explicit maladaptive weight loss behavior identified was smoking cigarettes and the most unhealthy dieting practice was skipping breakfast.

# Conclusion

These findings suggest that health educators should promote education and intervention strategies for females that encourage appropriate weight control practices and dispel unhealthy and ineffective weight loss myths (using laxatives and skipping breakfast are effective weight control methods). Implications from this study are numerous. Female college students, regardless of weight status, would benefit from open discussions with health educators to identify healthy and unhealthy dieting practices they use. Throughout these discussions, females could identify healthy dieting practices that could be expanded upon to promote a healthy weight status and recognize the health consequences associated with using unhealthy dieting practices. Because this study involved only female college students at a state university the implications discussed here are subject to replication of the results. Beyond replication with other participants, researchers can consider how to effectively target specific dieting practices among females to promote healthy eating and exercise to promote and maintain a healthy weight. Future research should identify which dieting practices dieters report most content with and believe are most successful to promote short- and long-term weight management.

# Competing interests

The author(s) declare that they have no competing interests.

# Authors' contributions

BMM conceived of the study, participated in its design, performed the statistical analysis, and drafted the manuscript. TAR participated in the design of the study and drafted the manuscript. VGA drafted the manuscript. JLS and MBD participated in coordination and data collection and helped to draft the manuscript. All authors read and approved the final manuscript.

### Acknowledgements

This research was supported in part by undergraduate research assistantships, East Carolina University Honors Program. We thank Emily R. Bennett and Lauren B. Manning for their assistance with data acquisition.