Homeostatic Factors Research Articles

Assessment of calcium homeostasis after total thyroidectomy in differentiated thyroid carcinoma

Background: After total thyroidectomy, hypocalcaemia can be transient or permanent. Most of the patients are being prescribed long term calcium supplementation despite preserving parathyroid glands. We have tried to study the various calcium homeostatic factors to predict the long term calcium levels in differentiated thyroid carcinoma following total thyroidectomy. Method: Study was conducted in a tertiary care centre and a total number of 28 patients of differentiated thyroid carcinoma were retrospectively analysed who underwent surgery from 2013 - 2015. Post surgery patients were given thyroxine and calcium supplementation with regular monitoring of thyroid function test and serum calcium. Serum Parathormone(PTH) levels were recorded after minimum of one year of completion of surgery. Results: Out of 28 patients, 26 patients have serum parathormone within normal range (15-65 pg/ml). Only two patients have low serum PTH values ( Conclusion: Our study reveals optimum calcium homeostasis in patients undergoing total thyroidectomy. A long term follow up of these patients is required so that many patients with normal PTH levels may not require calcium supplementation.

Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: a nested case-control study.

BackgroundRecent research suggests that several pathogenetic factors, including aging, genetics, inflammation, dyslipidemia, diabetes, and infectious diseases, influence cognitive decline (CD) risk. However, no definitive candidate causes have been identified. The present study evaluated whether certain serum parameters predict CD.MethodsA total of 151 participants were assessed for CD using the Mini-Mental State Examination (MMSE), and 34 participants were identified as showing CD.ResultsAmong CD predictive risk factors, Helicobacter pylori seropositivity was significantly predictive of CD risk, more so than classical risk factors, including white matter lesions and arterial stiffness [adjusted odds ratio (OR) = 4.786, 95% confidence interval (CI) = 1.710–13.39]. A multivariate analysis indicated that the albumin to globulin (A/G) ratio was the only factor that significantly lowered CD risk (OR = 0.092, 95% CI = 0.010–0.887). A/G ratio also was positively correlated with MMSE scores and negatively correlated with disruption of homeostatic factors (i.e., non-high-density lipoprotein, hemoglobin A1c, and high-sensitive C-reactive protein).ConclusionsThe current study results suggest that the A/G ratio is related to cognitive decline and may reflect homeostatic alterations.

Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption.

BackgroundSleep disruptions are common in epilepsy patients. Our previous study demonstrates that homeostatic factors and circadian rhythm may mediate epilepsy-induced sleep disturbances when epilepsy occurs at different zeitgeber hours. The proinflammatory cytokine, interleukin-1 (IL-1), is a somnogenic cytokine and may also be involved in epileptogenesis; however, few studies emphasize the effect of IL-1 in epilepsy-induced sleep disruption. We herein hypothesized that IL-1 receptor type 1 (IL-1R1) mediates the pathogenesis of epilepsy and epilepsy-induced sleep disturbances. We determined the role of IL-1R1 by using IL-1R1 knockout (IL-1R1 −/− KO) mice.ResultsOur results elucidated the decrease of non-rapid eye movement (NREM) sleep during the light period in IL-1R −/− mice and confirmed the somnogenic role of IL-1R1. Rapid electrical amygdala kindling was performed to induce epilepsy at the particular zeitgeber time (ZT) point, ZT13. Our results demonstrated that seizure thresholds induced by kindling stimuli, such as the after-discharge threshold and successful kindling rates, were not altered in IL-1R −/− mice when compared to those obtained from the wildtype mice (IL-1R +/+ mice). This result suggests that IL-1R1 is not involved in kindling-induced epileptogenesis. During sleep, ZT13 kindling stimulation significantly enhanced NREM sleep during the subsequent 6 h (ZT13-18) in wildtype mice, and sleep returned to the baseline the following day. However, the kindling-induced sleep alteration was absent in the IL-1R −/− KO mice.ConclusionsThese results indicate that the IL-1 signal mediates epilepsy-induced sleep disturbance, but dose not participate in kindling-induced epileptogenesis.

Clinical Assessment of Fatigability in Multiple Sclerosis: A Shift from Perception to Performance.

Multiple sclerosis (MS) is a neurodegenerative disorder characterized by an inflammatory autoimmune disease process in the central nervous system (CNS) (1). MS presents with clinical impairments based on location and severity of CNS lesions. Fatigue is the most common reported symptom of people with MS (PwMS) (2), and 80–85% of individuals describe it as the most disabling feature of the disease (3, 4). Decreased quality of life (5), limited physical activity (6, 7), and increased rates of depression and anxiety (8, 9) are associated with higher levels of reported fatigue among PwMS. The specific etiology of fatigue in MS is unknown, and it is likely the product of multiple factors rather than a single cause (1). There is a need for development of a unified taxonomy to help define what people experience when they report fatigue (10, 11). An early attempt to define fatigue was published from the 1981 CIBA Foundation Symposium in “Human Muscle Fatigue: Physiological Mechanisms” by Edwards (12) as “a failure to maintain the required or expected force.” While Edwards provided a simple and direct operational definition, it failed to convey subjective feelings described by PwMS. Enoka and Stuart (13) expanded Edwards’ definition to include perception, stating that fatigue is “an acute impairment of performance that includes both an increase in the perceived effort necessary to exert a desired force and the eventual inability to produce this force.” This definition features Mosso’s dichotomy and is now a commonly used framework within the realm of fatigue research (13). Within this taxonomy, force decrements are considered distinct from sensations that arise from prolonged muscular activity. However, as investigators began to uncover multiple mechanistic causes for fatigue, they began to label fatigue with descriptors consisting of the independent variables studied. Examples of this trend include cognitive fatigue, peripheral fatigue, and central fatigue among others. Beyond cohesive operational definitions, the limited ability to isolate components of Enoka and Stuart’s expanded definition explains, in part, why so little progress has been made in addressing clinically reported fatigue symptoms (14). Kluger et al. (10) presented a taxonomy that attempts to reunite the developing silos of fatigue work by returning to Enoka and Stuart’s definition. He calls for the common language of fatigue to be divided into two well-defined categories, distinguishing between the perception of fatigue and fatigability. “Perception of fatigue” defines subjective sensations related to an individual’s symptom complaint and is the result of homeostatic and psychological factors. “Fatigability” relates to task performance and is defined by a change in performance relative to an objective criterion. Enoka and Duchateau (11) presented additional framework for viewing fatigue as a symptom that has a trait characteristic and can be influenced by state variables. This view of fatigue allows researchers to measure the effects of short-term and modifiable state variables on the long-term trait characteristic of fatigue (i.e., the perception of fatigue or fatigability). The approach of Enoka and Duchateau (11) encourages investigators to emphasize their assessment methodology and the task dependency of fatigue, while minimizing use of obtuse modifiers or descriptors that lack clarity and yield little insight into causative factors. Developing and conceptualizing unified operational definitions of fatigue holds ramifications for clinical practice. It is our view that a combination of poorly defined taxonomies, unknown etiology, and vague clinical descriptions have made fatigue difficult to quantify during clinical assessment. Therefore, it is not surprising that current treatments are non-specific and yield unsatisfactory outcomes. The purpose of this paper is to convey the limitations of current fatigue assessments for evaluating task performance fatigability in rehabilitative settings for PwMS. Additionally, we call for the development of clinical tests which can measure the influence of state variables on the trait characteristic of performance fatigability as it relates to function and quality of life.

Defining Conditions for Optimal Inhibition of Food Intake in Rats by a Grape-Seed Derived Proanthocyanidin Extract

Food intake depends on homeostatic and non-homeostatic factors. In order to use grape seed proanthocyanidins (GSPE) as food intake limiting agents, it is important to define the key characteristics of their bioactivity within this complex function. We treated rats with acute and chronic treatments of GSPE at different doses to identify the importance of eating patterns and GSPE dose and the mechanistic aspects of GSPE. GSPE-induced food intake inhibition must be reproduced under non-stressful conditions and with a stable and synchronized feeding pattern. A minimum dose of around 350 mg GSPE/kg body weight (BW) is needed. GSPE components act by activating the Glucagon-like peptide-1 (GLP-1) receptor because their effect is blocked by Exendin 9-39. GSPE in turn acts on the hypothalamic center of food intake control probably because of increased GLP-1 production in the intestine. To conclude, GSPE inhibits food intake through GLP-1 signaling, but it needs to be dosed under optimal conditions to exert this effect.

Abstract 2372: The genetic evolution of melanoma

Abstract The pathogenic mutations in melanoma have largely been catalogued, but the order of their occurrence is not known. We identified 82 cases of melanocytic neoplasia with two or more histopathologically distinct precursor and descendent portions. These portions spanned several histopathologic stages including benign nevi, intermediate neoplasms such as dysplastic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. In total, 277 histopathogically distinct areas were microdissected and sequenced using a panel of several hundred cancer-genes at an average of 275-fold coverage. In all cases precursor lesions harbored mutations known to activate the MAPK pathway, most commonly affecting BRAF or NRAS, and thus these were considered initiating mutations. TERT promoter mutations were the earliest secondary mutations to occur, emerging in intermediate neoplasms and in situ melanomas. Bi-allelic CDKN2A mutations and/or deletions arose predominantly at the transition to invasive melanoma. TP53 and PTEN mutations occurred comparatively later in thicker primary melanomas. In the 12 cases in which matched primaries and metastases were sequenced, no pathogenic mutations were specifically associated with the transition to metastatic melanoma, suggesting that metastatic capability was already present in the primary tumors. Unequivocally benign neoplasms, which mostly consisted of conventional nevi, disproportionately harbored BRAFV600E mutations as the only apparent pathogenic alteration. Lesions that were histopathologically intermediate, such as dysplastic nevi, had two or more pathogenic mutations and were enriched for NRAS mutations. These findings provide genetic support for the existence of an intermediate stage of melanocytic neoplasia, resolving a long-standing controversy. We also found that melanomas with different initiating mutations evolve through distinct evolutionary trajectories linked to specific histopathologic precursors. A mutational signature of UV-radiation-induced DNA damage predominated in lesions from all histopathologic stages, implicating UV-radiation in both the initiation and progression of melanoma. The point mutation burden increased steadily from one progression stage to the next, stabilizing once melanomas became invasive. By contrast, copy number alterations only became prevalent at the transition to invasive melanoma. Melanomas evolve from benign lesions linearly, whereas, they show patterns of branched evolution when they evolve from intermediate lesions; this indicates that evolution may accelerate once a melanocytic neoplasm reaches an intermediate stage. In summary, our study outlines a framework of the genetic evolution of melanocytic neoplasms from precursor lesions and unveils the rate-limiting homeostatic factors that become disrupted as neoplasms progress from one stage to the next, as well as the pathogenic factors driving this evolution. Citation Format: Alan H. Shain, Richard Yu, Iwei Yeh, Jamal Benhamida, Ivanka Kovalyshyn, Aravindhan Sriharan, Eric Talevich, Reinhard Dummer, Jeffrey North, Laura Pincus, Beth Ruben, William Rickaby, Corrado D’Arrigo, Alistair Robson, Robert Judson, Nancy Joseph, Boris Bastian. The genetic evolution of melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2372.

Targeted Delivery of Shear Stress-Inducible Micrornas by Nanoparticles to Prevent Vulnerable Atherosclerotic Lesions.

Atherosclerosis is a chronic inflammatory vascular wall disease, and endothelial cell dysfunction plays an important role in its development and progression. Under the influence of laminar shear stress, however, the endothelium releases homeostatic factors such as nitric oxide and expresses of vasoprotective microRNAs that are resistant to atherosclerosis. Adhesion molecules such as E-selectin, exhibited on the endothelial surface, recruit monocytes that enter the vessel wall to form foam cells. Accumulation of these foam cells form fatty streaks that may progress to atherosclerotic plaques in the blood vessel wall. Interestingly, E-selectin may also serve as an affinity moiety for targeted drug delivery against atherosclerosis. We have recently developed an E-selectin-targeted platform that enriches therapeutic microRNAs in the inflamed endothelium to inhibit formation of vulnerable atherosclerotic plaques.

Individual Differences in Post-exercise Ad Libitum Energy Intake in Children

Previous studies have shown individual differences in the energy intake (EI) response to exercise, but homeostatic or cognitive mechanisms underlying these differences are unclear, particularly in youth. Fat-free mass is a known predictor of daily EI in adolescents and adults, predominantly through its effects on resting metabolic rate and total energy expenditure. In addition, studies in adults have shown that increased perceived difficulty of exercise is associated with caloric over-compensation through greater EI. However, the influence of these biological and psychological factors in children is unknown. PURPOSE: To examine the predictors of post-exercise EI in children. METHODS: Healthy-weight children ages 9–12 years (n = 18) reported to the laboratory for 1 baseline and 2 experimental visits (EX = exercise, SED = sedentary) each separated by 1 week in a randomized crossover design. Percent body fat (bioelectrical impedance analysis), weight (kg), and height (m) were used to calculate fat-mass index (FMI) and fat-free mass index (FFMI; kg/m2). On the EX day, children exercised at 70% estimated VO2peak for 30 minutes on a cycle ergometer and gave ratings of perceived exertion (RPE). Objective EI (kcal) was measured at identical meals on the EX and SED days: standard breakfast and ad libitum lunch, snack, and dinner. Paired t-tests, Pearson’s correlations, and multiple linear regressions were performed using SPSS. RESULTS: Total EI was not statistically different between the EX and SED days (t = 0.47, p = 0.64). However, FFMI was positively associated with EI on the EX day (r = 0.50, p < 0.05), but not the SED day (p = 0.25). RPE was also positively associated with EI on the EX day (r = 0.78, p < 0.01). Together, FFMI and RPE explained 71% of the variability in EI on the EX day (F(2,15) = 17.14, p < 0.01). CONCLUSIONS: Fat-free mass was associated with EI on the EX day but not the SED day, suggesting better homeostatic regulation of EI with imposed exercise. Despite experiencing the same 70% relative exercise intensity, children varied in their perceived difficulty of the exercise. Increased perceived difficulty predicted greater EI on the EX day. These findings demonstrate a role for both homeostatic and cognitive factors in post-exercise EI regulation in children. Supported by USDA/NIFA Grant #2011-67001-30117 Program A2121.

Evidence of stable insulin and its increased efficacy during oral administration with Desmodium gangeticum extract in rats

ObjectiveTo find the efficacy of administering insulin orally with Desmodium gangeticum (DG) extract in diabetes induced rats. MethodsDiabetes was induced in Wistar male rats by streptozotocin and subsequently treated with the mixture of DG/insulin/DG + insulin and compared with diabetic rats. Standard glucose estimation assay described elsewhere was used to determine the diabetic levels. The effects of homeostatic factors (the effect of temperature, gastric juices, pH, trypsin, and mercaptoethanol) on insulin and insulin-DG were analyzed. ResultsThe test results proved that the reported combination of insulin-DG was effective in maintaining glucose homeostasis. More interestingly, insulin-DG was stable against all the degrading parameters while insulin without DG suffered degradation. A molecular interaction was suggested between DG and insulin through nuclear magnetic resonance and Fourier transform infrared spectroscopy analysis. ConclusionsInsulin-DG mix is a potent anti-diabetic agent and importantly, DG extract is protective to insulin when used in prescribed combination and delivered orally. This could be a possible solution for painful subcutaneous injections.

Gender and chronological age affect erythrocyte membrane oxidative indices in citrate phosphate dextrose adenine-formula 1 (CPDA-1) blood bank storage condition.

It is well known that in vitro storage lesions lead to membrane dysfunction and decreased number of functional erythrocytes. As erythrocytes get older, in storage media as well as in peripheral circulation, they undergo a variety of biochemical changes. In our study, the erythrocytes with different age groups in citrate phosphate dextrose adenine-formula 1 (CPDA-1) storage solution were used in order to investigate the possible effect of gender factor on oxidative damage. Oxidative damage biomarkers in erythrocyte membranes such as ferric reducing antioxidant power, pro-oxidant-antioxidant balance, protein-bound advance glycation end products, and sialic acid were analyzed. Current study reveals that change in membrane redox status during blood-bank storage condition also depends on both gender depended homeostatic factors and the presence of CPDA-1. During the storage period in CPDA-1, erythrocytes from the male donors are mostly affected by free radical-mediated oxidative stress but erythrocytes obtained from females are severely affected by glyoxidative stress.

Inflammation Controls Sensitivity of Human and Mouse Intestinal Epithelial Cells to Galectin-1.

Galectins play key roles in the inflammatory cascade. In this study, we aimed to analyze the effect of galectin-1 (Gal-1) in the function of intestinal epithelial cells (IECs) isolated from healthy and inflamed mucosa. IECs isolated from mice or patients with inflammatory bowel diseases (IBD) were incubated with different pro-inflammatory cytokines, and Gal-1 binding, secretion of homeostatic factors and viability were assessed. Experimental models of food allergy and colitis were used to evaluate the in vivo influence of inflammation on Gal-1 binding and modulation of IECs. We found an enhanced binding of Gal-1 to: (a) murine IECs exposed to IL-1β, TNF, and IL-13; (b) IECs from inflamed areas in intestinal tissue from IBD patients; (c) small bowel of allergic mice; and (d) colon from mice with experimental colitis. Our results showed that low concentrations of Gal-1 favored a tolerogenic micro-environment, whereas high concentrations of this lectin modulated viability of IECs through mechanisms involving activation of caspase-9 and modulation of Bcl-2 protein family members. Our results showed that, when added in the presence of diverse pro-inflammatory cytokines such as tumor necrosis factor (TNF), IL-13 and IL-5, Gal-1 differentially promoted the secretion of growth factors including thymic stromal lymphopoietin (TSLP), epidermal growth factor (EGF), IL-10, IL-25, and transforming growth factor (TGF-β1 ). In conclusion, we found an augmented binding of Gal-1 to IECs when exposed in vitro or in vivo to inflammatory stimuli, showing different effects depending on Gal-1 concentration. These findings highlight the importance of the inflammatory micro-environment of mucosal tissues in modulating IECs susceptibility to the immunoregulatory lectin Gal-1 and its role in epithelial cell homeostasis.

Sleepiness and Cognitive Performance among Younger and Older Adolescents across a 28-Hour Forced Desynchrony Protocol.

Quantify the homeostatic and circadian effects on sleepiness and performance of adolescents. Examine age-related changes in homeostatic and circadian regulation of sleepiness and performance by comparing younger and older adolescent groups. Three-week laboratory study including 12 cycles of a 28-h forced desynchrony protocol. Controlled laboratory environment with individual sleep and performance testing rooms and shared common areas. Twenty-seven healthy adolescents including 16 females. Ages ranged from 9.6-15.2 years and participants were split into younger (n = 14 ages 9-12) and older (n = 13 ages 13-15) groups based on median age split of 13.0 years. N/A. Testing occurred every 2 h during scheduled wake periods. Measures included sleep latency during repeated nap opportunities and scores from a computerized neurobehavioral assessment battery including a 10-min psychomotor vigilance task, a digit symbol substitution task, and the Karolinska Sleepiness Scale. Significant main effects of circadian and homeostatic factors were observed, as well as several circadian and homeostatic interaction effects. Age group did not have a significant main effect on sleep and performance data. A significant interaction of circadian phase and age group was found for sleep latency, with younger adolescents showing greater circadian modulation than older teens during the circadian night. Adolescents demonstrated a similar pattern of response to forced desynchrony as reported for adults. Sleepiness and performance were affected by homeostatic and circadian factors, and age group did not interact with homoeostatic and circadian factors for subjective sleepiness and most performance metrics. Younger adolescents had a shorter latency to sleep onset than older during the circadian bin spanning 4 to 8 h after the onset of melatonin secretion.

Hypothalamic control of brown adipose tissue thermogenesis.

It has long been known, in large part from animal studies, that the control of brown adipose tissue (BAT) thermogenesis is insured by the central nervous system (CNS), which integrates several stimuli in order to control BAT activation through the sympathetic nervous system (SNS). SNS-mediated BAT activity is governed by diverse neurons found in brain structures involved in homeostatic regulations and whose activity is modulated by various factors including oscillations of energy fluxes. The characterization of these neurons has always represented a challenging issue. The available literature suggests that the neuronal circuits controlling BAT thermogenesis are largely part of an autonomic circuitry involving the hypothalamus, brainstem and the SNS efferent neurons. In the present review, we recapitulate the latest progresses in regards to the hypothalamic regulation of BAT metabolism. We briefly addressed the role of the thermoregulatory pathway and its interactions with the energy balance systems in the control of thermogenesis. We also reviewed the involvement of the brain melanocortin and endocannabinoid systems as well as the emerging role of steroidogenic factor 1 (SF1) neurons in BAT thermogenesis. Finally, we examined the link existing between these systems and the homeostatic factors that modulate their activities.

The fetal programming of food preferences: current clinical and experimental evidence.

Increased energy consumption is one of the major factors implicated in the epidemic of obesity. There is compelling evidence, both clinical and experimental, that fetal paucity of nutrients may have programming effects on feeding preferences and behaviors that can contribute to the development of diseases. Clinical studies in different age groups show that individuals born small for their gestational age (SGA) have preferences towards highly caloric foods such as carbohydrates and fats. Some studies have also shown altered eating behaviors in SGA children. Despite an apparent discrepancy in different age groups, all studies seem to converge to an increased intake of palatable foods in SGA individuals. Small nutrient imbalances across lifespan increase the risk of noncommunicable diseases in adult life. Homeostatic factors such as altered responses to leptin and insulin and alterations in neuropeptides associated with appetite and satiety are likely involved. Imbalances between homeostatic and hedonic signaling are another proposed mechanism, with the mesocorticolimbic dopaminergic pathway having differential reward and pleasure responses when facing palatable foods. Early exposure to undernutrition also programs hypothalamic-pituitary-adrenal axis, with SGA having higher levels of cortisol in different ages, leading to chronic hyperactivity of this neuroendocrine axis. This review summarizes the clinical and experimental evidence related to fetal programming of feeding preferences by SGA.

Food for Thought: Revisiting the Complexity of Food Intake

The ability of hormones such as insulin, leptin, and cholecystokinin to alter food intake is influenced by intricate interactions between homeostatic and non-homeostatic factors. Consequently, when administered exogenously, the likelihood of these hormones influencing food intake is probabilistic, leading to difficulties replicating previously reported outcomes both within and between labs.

Wolff's law in action: a mechanism for early knee osteoarthritis.

There is growing interest in the role of bone in knee osteoarthritis. Bone is a dynamic organ, tightly regulated by a multitude of homeostatic controls, including genetic and environmental factors. One such key environmental regulator of periarticular bone is mechanical stimulation, which, according to Wolff’s law, is a key determinant of bone properties. Wolff’s law theorizes that repetitive loading of bone will cause adaptive responses enabling the bone to better cope with these loads. Despite being an adaptive response of bone, the remodeling process may inadvertently trigger maladaptive responses in other articular structures. Accumulating evidence at the knee suggests that expanding articular bone surface area is driven by mechanical stimulation and is a strong predictor of articular cartilage loss. Similarly, fractal analysis of bone architecture provides further clues that bone adaptation may have untoward consequences for joint health. This review hypothesizes that adaptations of periarticular bone in response to mechanical stimulation cause maladaptive responses in other articular structures that mediate the development of knee osteoarthritis. A potential disease paradigm to account for such a hypothesis is also proposed, and novel therapeutic targets that may have a bone-modifying effect, and therefore potentially a disease-modifying effect, are also explored.

Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states.

A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt) neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP) can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT) can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools has greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

Buddhism and Subjective Wellbeing: Do Self-Esteem, Optimism and Perceived Control Play a Role?

This study investigated the relationship between Buddhism and subjective wellbeing within the theoretical framework of a revised homeostatic model of subjective wellbeing (SWB). This model integrates the affective (homeostatically protected mood: content, happy and excited), cognitive (self-esteem, optimism and perceived control: primary control and secondary control) and experiential factors in relating to SWB. Given that the religious doctrine of Buddhism advocates selflessness and self-attained liberation from suffering, it is predicted that, among the cognitive factors, primary control and optimism will predict more significant SWB variance beyond the other homeostatic model factors than self-esteem. Additionally, compared with those without religious belief, the Buddhists would be higher in SWB, primary control and optimism, but lower in self-es- teem. Chinese samples were drawn in Hong Kong comprising 153 Buddhists and 240 participants without religious belief. Through the use of questionnaire, it was found that, quite contrary to prediction, secondary control and self-esteem explained significant SWB variance for the Buddhists while none was provided by primary control and optimism. Also, no significant intergroup difference was found on SWB and all cognitive factors. The results were discussed in terms of difficulty in the eradication of egocentric mentality.

Linking the future of anticancer metal-complexes to the therapy of tumour metastases.

Cancer chemotherapy is almost always applied to patients with one or more diagnosed metastases and is expected to impact these lesions, thus providing significant benefits to the patient. The outcome of metastasis is determined by the interplay between the specific subpopulation of metastatic cells and host homeostatic factors in specific microenvironments. In clinical practice, metal-based drugs are represented by platinum compounds, which are constituents of a wide variety of chemotherapeutic regimens, and are only rarely active against tumour metastases unless they are combined with drugs that target specific pathways characterizing the malignancy of the tested tumour. On experimental grounds, a number of complexes based on ruthenium and other metals have been frequently studied in vitro using models and experimental conditions mimicking one or more steps of the metastatic process, such as invasion and migration. The ruthenium-based drug, NAMI-A, is the only one to have been subject to clinical testing for the treatment of metastatic tumours. The capacity of NAMI-A to modulate the relationship established between metastatic cells and their microenvironment suggests that metal-based drugs shall be viewed as an opportunity for the treatment of tumour metastases.

Brain function predictors and outcome of weight loss and weight loss maintenance

Obesity rates are associated with public health consequences and rising health care costs. Weight loss interventions, while effective, do not work for everyone, and weight regain is a significant problem. Eating behavior is influenced by a convergence of processes in the brain, including homeostatic factors and motivational processing that are important contributors to overeating. Initial neuroimaging studies have identified brain regions that respond differently to visual food cues in obese and healthy weight individuals that are positively correlated with reports of hunger in obese participants. While these findings provide mechanisms of overeating, many important questions remain. It is not known whether brain activation patterns change after weight loss, or if they change differentially based on amount of weight lost. Also, little is understood regarding biological processes that contribute to long-term weight maintenance. This study will use neuroimaging in participants while viewing food and non-food images. Functional Magnetic Resonance Imaging will take place before and after completion of a twelve-week weight loss intervention. Obese participants will be followed though a 6-month maintenance period. The study will address three aims: 1. Characterize brain activation underlying food motivation and impulsive behaviors in obese individuals. 2. Identify brain activation changes and predictors of weight loss. 3. Identify brain activation predictors of weight loss maintenance. Findings from this study will have implications for understanding mechanisms of obesity, weight loss, and weight maintenance. Results will be significant to public health and could lead to a better understanding of how differences in brain activation relate to obesity.