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Rationale We propose narrative evidence-based medicine as a necessary elaboration of the NIH translational research roadmap. The roadmap defined two complex obstacles, T1 and T2, to the progress of research from the 'bench' or basic laboratory science to the 'bedside' or clinical application, the traversal of which requires emergence of complex transformative relationships between the parties and stakeholders. It fails to encompass patient interactions, hesitancies and alliances with medical care.Aims and Objectives We suggest a third transformative or translational step, T3, that begins at the point that practitioners have themselves elected to adopt and recommend strategies and interventions based on high-level evidence and guidelines. In our model, T3 encompasses all aspects of care that converge on the practitionerDSpatient relationship and ultimately determine what therapies and choices patients actually make regarding their care.Results Learning from the biopsychosocial model, patient-centred care and shared decision making while attending to the ethical injunction of Emmanuel Levinas to know the other, we have developed a medical practice and theory that unites the local and specific concerns of narrative medicine with the generalizability and power of evidence-based medicine.Conclusions We offer innovative approaches to study, teach and improve the therapeutic intimacy and integrative effectiveness of the practitioner-patient relationship. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This open clinical trial examined the efficacy of treating obese patients with binge eating disorder (BED) with phentermine and fluoxetine in the setting of cognitive-behavioral therapy (CBT). METHOD: Sixteen obese women received individual CBT along with phentermine/fluoxetine. Treatment goals included elimination of binge eating, weight loss, and reduced psychological distress. Following active treatment, patients were offered once-monthly maintenance treatment for 3 years. RESULTS: Patients showed significant reduction in binge frequency, weight loss, and psychological distress at the end of active treatment, but regained most of the weight within 1 year. At 18-month follow-up, there was an ongoing reduction in binge eating for patients who continued maintenance. DISCUSSION: Treatment produced comparable binge suppression and more weight loss than most reported studies of CBT alone. However, there is significant weight regain, particularly following medication discontinuation. This study does not support the long-term clinical utility of adding phentermine/fluoxetine to CBT for BED. Copyright 2000 by John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE: While most individuals with bulimia nervosa begin dieting prior to the onset of binge eating, some individuals begin binge eating prior to dieting. The purpose of this study was to assess the differences between these two groups. METHODS: Participants (N = 120) in a treatment study for bulimia nervosa were separated into two groups (Binge First vs. Diet First) based on the ages they reported for the onset of binge eating and of dieting and then compared across a number of variables. RESULTS: Individuals in the Binge First group reported higher weight, higher shape and weight concern, lower age of onset of eating disorder symptoms, and an altered relationship of binge eating to vomiting when compared to individuals in the Diet First group. DISCUSSION: The differences between the two groups suggest that there may be subgroups of individuals with purging bulimia nervosa and that individuals in the Binge First group more closely resemble individuals with binge eating disorder than do those in the Diet First group. [ABSTRACT FROM AUTHOR]

Objective: To revisit the merits and problems inherent in considering obesity, or some aspect of obesity, as a mental or behavioral disorder. Method: The author suggests shifting the focus from the state of obesity to the process of nonhomeostatic overeating that results in obesity. Studies are reviewed that pertain to various models of nonnormative overeating including eating disorder models that stress the form of overeating, substance use disorder models focusing on its consequences, and affect regulation or stress response models focusing on its function. Results: Studies focusing on abnormal eating patterns, including binge eating and night eating suggest that such patterns may be related to the development of obesity. While the literature pertaining to substance use and other models of nonhomeostatic overeating is beginning to mount, current evidence is mostly preliminary and indirect. Conclusion: An attempt to devise diagnostic criteria based on the above models raises multiple difficulties, since the phenomena central to each model are dimensional, common, and variably associated with distress or dysfunction. A detailed understanding of the neurobiological relationships among eating behavior, reward systems, and affect regulation systems will enable a more meaningful consideration of these models and will facilitate specific treatment for disorders of overeating. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2007 [ABSTRACT FROM AUTHOR]

Objectives: Bone is a dynamic organ under continual turnover influenced by life history stage, energy dynamics, diet, climate, and disease. Bone turnover data have enormous potential in biological anthropology for testing evolutionary and biocultural hypotheses, yet few studies have integrated these biomarkers. In the present article we systematically review the current availability, future viability, and applicability of measuring bone turnover markers (BTMs) in dried blood spot (DBS) samples obtained from finger prick whole blood., Methods: Our review considers clinical and public health relevance, biomarker stability in DBS, assay availability, and cost. We consider biomarkers of bone formation such as osteocalcin (bone matrix protein), PINP (N-terminal propeptide of type I collagen), and alkaline phosphatase (osteoblast enzyme), as well as biomarkers of bone resorption such as CTX (marker of collagen breakdown) and TRACP5b (tartrate-resistant acid phosphatase 5b; osteoclast enzyme)., Results: Two BTMs have been validated for DBS: osteocalcin (formation) and TRACP5b (resorption). Prime candidates for future development are CTX and PINP, the formation and resorption markers used for clinical monitoring of response to osteoporosis treatment., Conclusion: BTMs are a field-friendly technique for longitudinal monitoring of skeletal biology during growth, reproduction and aging, combining minimized risk to study participants with maximized ease of sample storage and transport. This combination allows new insights into the effects of energy availability, disease, and physical activity level on bone, and questions about bone gain and loss across life history and in response to environmental factors; these issues are important in human biology, paleoanthropology, bioarchaeology, and forensic anthropology., (© 2022 The Authors. American Journal of Human Biology published by Wiley Periodicals LLC.)

Objectives: Investigating factors that contribute to bone loss and accretion across populations in remote settings is challenging, particularly where diagnostic tools are scarce. To mitigate this challenge, we describe validation of a commercial ELISA assay to measure osteocalcin, a biomarker of bone formation, from dried blood spots (DBS)., Methods: We validated the Osteocalcin Human SimpleStep ELISA kit from Abcam (ab1951214) using 158 matched plasma and DBS samples. Passing-Bablok regression analysis assessed the relationships between plasma and DBS osteocalcin concentrations. Dilutional linearity and spike and recovery experiments determined if the DBS matrix interfered with osteocalcin measurement, and intra- and inter-assay coefficients of variation (CVs) were calculated. Limit of detection, analyte stability, and specific forms of osteocalcin measured by the kit were also investigated., Results: Mean plasma osteocalcin value was 218.2 ng/mL (range 64.6-618.1 ng/mL). Linear relationships existed between plasma and DBS concentrations of osteocalcin, with no apparent bias in plasma vs DBS concentrations. There was no apparent interference of the DBS matrix with measurement of osteocalcin in DBS. Intra-assay CV for DBS was ~8%, while average inter-assay CV was 14.8%. Limit of detection was 0.34 ng/mL. Osteocalcin concentrations were stable in DBS stored at -28°C and room temperature, but not those stored at 37°C. This ELISA kit detects total osteocalcin., Conclusions: Osteocalcin, a bone formation biomarker, can be measured from DBS. Combined with a previously validated DBS assay for TRACP-5b, a bone resorption biomarker, these assays have the potential to help researchers disentangle the many factors contributing to bone strength., (© 2020 Wiley Periodicals, Inc.)

Objectives: A number of basic questions about bone biology have not been answered, including population differences in bone turnover. In part, this stems from the lack of validated minimally invasive biomarker techniques to measure bone formation and resorption in field-based population-level research. The present study addresses this gap by validating a fingerprick dried blood spot (fDBS) assay for tartrate-resistant acid phosphatase 5b (TRACP-5b), a well-defined biomarker of bone resorption and osteoclast number., Methods: We adapted a commercially available enzyme-linked immunosorbent assay (ELISA) kit from MyBiosource for the quantitative determination of TRACP-5b levels in serum and plasma for use with DBS. We used a rigorous process of assay modification and validation, including the use of a matched set of 189 adult plasma, fDBS, and venous DBS (vDBS) samples; parameters evaluated included precision, reliability, and analyte stability., Results: Plasma and DBS TRACP-5b concentrations showed a linear relationship. There were no systematic differences in TRACP-5b levels in fDBS and vDBS, indicating no significant differences in TRACP-5b distribution between capillary and venous blood. Parallelism and spike-and-recovery results indicated that matrix factors in DBS do not interfere with measurement of TRACP-5b levels from DBS using the validated kit. Intra- and interassay CVs were 5.0% and 12.1%, respectively. DBS samples should preferably be stored frozen but controlled room temperature storage for up to a month may be acceptable., Conclusions: This DBS-based ELISA assay adds to the methodological toolkit available to human biologists and will facilitate research on bone turnover in population studies., (© 2019 Wiley Periodicals, Inc.)

Objectives: Humans exhibit significant ecogeographic variation in bone size and shape. However, it is unclear how significantly environmental temperature influences cortical and trabecular bone, making it difficult to recognize adaptation versus acclimatization in past populations. There is some evidence that cold-induced bone loss results from sympathetic nervous system activation and can be reduced by nonshivering thermogenesis (NST) via uncoupling protein (UCP1) in brown adipose tissue (BAT). Here we test two hypotheses: (1) low temperature induces impaired cortical and trabecular bone acquisition and (2) UCP1, a marker of NST in BAT, increases in proportion to degree of low-temperature exposure., Methods: We housed wildtype C57BL/6J male mice in pairs at 26 °C (thermoneutrality), 22 °C (standard), and 20 °C (cool) from 3 weeks to 6 or 12 weeks of age with access to food and water ad libitum (N = 8/group)., Results: Cool housed mice ate more but had lower body fat at 20 °C versus 26 °C. Mice at 20 °C had markedly lower distal femur trabecular bone volume fraction, thickness, and connectivity density and lower midshaft femur cortical bone area fraction versus mice at 26 °C (p < .05 for all). UCP1 expression in BAT was inversely related to temperature., Discussion: These results support the hypothesis that low temperature was detrimental to bone mass acquisition. Nonshivering thermogenesis in brown adipose tissue increased in proportion to low-temperature exposure but was insufficient to prevent bone loss. These data show that chronic exposure to low temperature impairs bone architecture, suggesting climate may contribute to phenotypic variation in humans and other hominins., (© 2018 Wiley Periodicals, Inc.)

Limited data are available on the characteristics of adolescents with obesity who seek bariatric surgery. Existing data suggest that adolescent surgery candidates have a higher body mass index (BMI) than comparison adolescents with obesity, but the limited findings regarding psychosocial functioning are mixed. This study aimed to compare BMI and psychosocial functioning among adolescent bariatric surgery candidates, outpatient medical-treatment-seeking adolescents with obesity (receiving lifestyle modification), and adolescents in the normal-weight range. All adolescents completed self-report measures of impulsivity, delay discounting, depression, anxiety, stress, eating pathology, family functioning and quality of life, and had their height and weight measured. Adolescent surgical candidates had higher BMIs than both comparison groups. Surgical candidates did not differ from medical-treatment-seeking adolescents with obesity on any measure of psychosocial functioning, but both groups of adolescents with obesity reported greater anxiety and eating pathology and poorer quality of life than normal-weight adolescents. Quality of life no longer differed across groups after controlling for BMI, suggesting that it is highly related to weight status. Adolescents with obesity may experience greater anxiety, eating pathology, and quality of life impairments than their peers in the normal-weight range regardless of whether they are seeking surgery or outpatient medical treatment. Clinical implications and directions for future research are discussed., (© 2017 World Obesity Federation.)

The discovery that metabolically active brown fat is present in humans throughout ontogeny raises new questions about the interactions between thermoregulatory, metabolic, and skeletal homeostasis. Brown adipose tissue (BAT) is distinct from white adipose tissue (WAT) for its ability to burn, rather than store, energy. BAT uniquely expresses uncoupling protein-1 (abbreviated as UCP1), which diverts the energy produced by cellular respiration to generate heat. While BAT is found in small mammals, hibernators, and newborns, this depot was thought to regress in humans during early postnatal life. Recent studies revealed that human BAT remains metabolically active throughout childhood and even in adulthood, particularly in response to cold exposure. In addition to the constitutive BAT depots present at birth, BAT cells can be induced within WAT depots under specific metabolic and climatic conditions. These cells, called inducible brown fat, "brite," or beige fat, are currently the focus of intense investigation as a possible treatment for obesity. Inducible brown fat is associated with higher bone mineral density, suggesting that brown fat interacts with bone growth in previously unrecognized ways. Finally, BAT may have contributed to climatic adaptation in hominins. Here, I review current findings on the role of BAT in thermoregulation, bone growth, and metabolism, describe the potential role of BAT in moderating the obesity epidemic, and outline possible functions of BAT across hominin evolutionary history., (© 2014 American Association of Physical Anthropologists.)

Objective: Best practice guidelines for adolescents considering bariatric surgery recommend a pre-operative mental health evaluation. However, only general information about these assessments appears in the literature, which makes consistency of administration challenging. This review proposes a specific empirically-derived format for pre-surgical mental health evaluations and summarizes currently available data on the psychiatric functioning of adolescents seeking bariatric surgery., Design: Studies of mental health evaluations for adults preparing for bariatric surgery are reviewed, as is the limited literature relevant to adolescent evaluations. A specific and detailed example of an evaluation (clinical interview, self-report questionnaires, cognitive assessment) used for younger patients at a major metropolitan hospital center is presented, followed by data from an initial group of adolescents completing this evaluation., Subjects: 200 adolescents (n=139 female; age: 14-18 y, BMI: 35.4-83.3 kg/m 2 ) presenting for bariatric surgery., Results: A notable subset of adolescents reported current Axis I conditions (31.5%) and current mental health treatment (29.5%), but reports of current illicit drug use (1.5%) and regular alcohol use (0.5%) were relatively rare. Procedures for using the completed evaluation and post-surgery monitoring of psychosocial issues are discussed., Conclusions: Adolescents considering weight loss surgery should receive comprehensive pre-surgical mental health evaluations, but additional data are needed to develop specific recommendations the use of these evaluations in post-operative care.

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. This review considers several possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? These possibilities are evaluated in terms of the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance., (Copyright © 2011 Wiley-Liss, Inc.)

How reliable are reconstructions of body mass and joint function based on articular surface areas? While the dynamic relationship between mechanical loading and cross-sectional geometry in long bones is well-established, the effect of loading on the subchondral articular surface area of epiphyses (hereafter, articular surface area, or ASA) has not been experimentally tested. The degree to which ASA can change in size and shape is important, because articular dimensions are frequently used to estimate body mass and positional behavior in fossil species. This study tests the hypothesis that mechanical loading influences ASA by comparing epiphyses of exercised and sedentary sheep from three age categories: juvenile, subadult, and adult (n = 44). ASA was measured on latex molds of subchondral articular surfaces of 10 epiphyses from each sheep. Areas were standardized by body mass, and compared to diaphyseal cross-sectional geometrical data. Nonparametric statistical comparisons of exercised and control individuals found no increases in ASA in response to mechanical loading in any age group. In contrast, significant differences in diaphyseal cross-sectional geometry were detected between exercised and control groups, but mostly in juveniles. The conservatism of ASA supports the hypothesis that ASA is ontogenetically constrained, and related to locomotor behavior at the species level and to body mass at the individual level, while variations in diaphyseal cross-sectional geometry are more appropriate proxies for individual variations in activity level., (Copyright 2001 Wiley-Liss, Inc.)