The legacy of hope summit: a consensus-based initiative and report on eating disorders in the U.S. and recommendations for the path forward.

BACKGROUND: Several unsuccessful attempts have been made to reach a cross-disciplinary consensus on issues fundamental to the field of eating disorders in the United States (U.S.). In January 2020, 25 prominent clinicians, academicians, researchers, persons with lived experience, and thought leaders in the U.S. eating disorders community gathered at the Legacy of Hope Summit to try again. This paper articulates the points on which they reached a consensus. It also: (1) outlines strategies for implementing those recommendations; (2) identifies likely obstacles to their implementation; and (3) charts a course for successfully navigating and overcoming those challenges. METHODS: Iterative and consensual processes were employed throughout the Summit and the development of this manuscript. RESULTS: The conclusion of the Summit culminated in several consensus points, including: (1) Eating disorder outcomes and prevention efforts can be improved by implementing creative health education initiatives that focus on societal perceptions, early detection, and timely, effective intervention; (2) Such initiatives should be geared toward parents/guardians, families, other caretakers, and frontline healthcare providers in order to maximize impact; (3) Those afflicted with eating disorders, their loved ones, and the eating disorders community as a whole would benefit from greater accessibility to affordable, quality care, as well as greater transparency and accountability on the part of in-hospital, residential, and outpatient health care providers with respect to their qualifications, methodologies, and standardized outcomes; (4) Those with lived experience with eating disorders, their loved ones, health care providers, and the eating disorders community as a whole, also would benefit from the establishment and maintenance of treatment program accreditation, professional credentialing, and treatment type and levels of care guidelines; and (5) The establishment and implementation of effective, empirically/evidence-based standards of care requires research across a diverse range of populations, adequate private and government funding, and the free exchange of ideas and information among all who share a commitment to understanding, treating, and, ultimately, markedly diminishing the negative impact of eating disorders. CONCLUSIONS: Widespread uptake and implementation of these recommendations has the potential to unify and advance the eating disorders field and ultimately improve the lives of those affected. A cross-disciplinary group of eating disorder professionals, thought leaders, and persons with lived experience have come together and reached a consensus on issues that are fundamental to the battle against the life-threatening and life-altering illnesses that are eating spectrum disorders. Those issues include: (1) the need for early detection, intervention, prevention, and evidenced-based standards of care; (2) the critical need to make specialized care more accessible and affordable to all those in need; (3) the importance of developing uniform, evidenced-based standards of care; (4) the need for funding and conducting eating spectrum disorder research; and (5) the indispensability of advocacy, education, and legislation where these illnesses are concerned. During the consensus process, the authors also arrived at strategies for implementing their recommendations, identified likely obstacles to their implementation, and charted a course for successfully navigating and overcoming those challenges. Above all else, the authors demonstrated that consensus in the field of eating spectrum disorders is possible and achievable and, in doing so, lit a torch of hope that is certain to light the path forward for years to come.

In vitro and in vivo effects of kinin B(1) and B(2) receptor agonists and antagonists in inbred control and cardiomyopathic hamsters.

The aims of this study were to examine the possible alterations occurring in the effects of kinins on isolated aortae of inbred control (CHF 148) and cardiomyopathic (CHF 146) hamsters of 150 - 175 and 350 - 375 days of age. Bradykinin (BK) and desArg(9)BK contracted isolated aortae (with or without endothelium) of hamsters of both strains and ages. After tissue equilibration (90 min), responses elicited by both kinin agonists were stable over the time of experiments. The patterns of isometric contractions of BK and desArg(9)BK were however found to be different; desArg(9)BK had a slower onset and a longer duration of action than BK. Potencies (pEC(50) values) of BK in all groups of hamsters were significantly increased by preincubating the tissues with captopril (10(-5) M). No differences in the pEC(50) values and the E(max) values for BK or desArg(9)BK were seen between isolated vessels from inbred control and cardiomyopathic hamsters. The myotropic effect of BK was inhibited by the selective non peptide antagonist, FR 173657 (pIC(50) 7.25+/-0.12 at the bradykinin B(2) receptor subtype (B(2) receptor)). Those of desArg(9)BK, at the bradykinin B(1) receptor subtype (B(1) receptor) were abolished by either R 715 (pIC(50) of 7. 55+/-0.05; alpha(E) = 0), Lys[Leu(8)]desArg(9)BK (pIC(50) of 7.21+/-0. 01; alpha(E) = 0.22) or [Leu(8)]desArg(9)BK (pIC(50) of 7.25+/-0.02; alpha(E) = 0.18). FR 173657 had no agonistic activity, exerted a non competitive type of antagonism and was poorly reversible (lasting more than 5 h) from B(2) receptor. In vivo, FR 173657 (given per os at 1 and 5 mg kg(-1), 1 h before the experiment) antagonized the acute hypotensive effect of BK in anaesthetized hamsters. It is concluded that aging and/or the presence of a congenital cardiovascular disorder in hamsters are not associated with changes in the in vitro aortic responses to either BK or desArg(9)BK.

Chronic AT1 receptor blockade and angiotensin-converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters: effects on cardiac hypertrophy and survival.

OBJECTIVE: We have reported that angiotensin II AT1 receptors are upregulated and that there are no AT2 receptors in the ventricles of cardiomyopathic hamsters. Since the upregulation was present even when no histological lesions were detectable, these results suggested that angiotensin II plays a role in the genesis/maintenance of this pathology. A survival study was conducted to compare the effects of an angiotensin II AT1 receptor antagonist, losartan (L), to those of a placebo (P). Since the angiotensin-converting enzyme (ACE) inhibitor quinapril (Q) has been shown to have beneficial effects in this animal model, a Q group was included. METHODS: Male Syrian cardiomyopathic hamsters (CHF 146, n = 360) were orally administered P, low- (30 mg/kg/day) or high-dose (100 mg/kg/day) L, or Q (100 mg/kg/day), starting at day 50 of life. Inbred control hamsters (CHF 148, n = 180) were treated with P or L (100 mg/kg/day) as controls. Animals were sacrificed at intervals to evaluate cardiac hypertrophy. Kaplan-Meier analysis was performed to assess differences in survival. RESULTS: High-dose L had no effects on the survival of control hamsters. There was an unexpected dose-dependent decrease in the survival of cardiomyopathics treated with L (low-dose, P = 0.14; high-dose, P = 0.0015) compared to an increase with Q (P = 0.0003). Cardiac hypertrophy compared to P was increased with L but significantly decreased with Q in cardiomyopathics. CONCLUSIONS: In this model, losartan did not improve survival compared to placebo and quinapril and, if anything, increased mortality. Our results suggest that AT1 receptor antagonists and ACE inhibitors are not necessarily equivalent or interchangeable in terms of their effects on cardiac hypertrophy and survival in selected progressive heart failure models.

Localization of BRCA1 gene expression in adult cynomolgus monkey tissues.

The breast and ovarian cancer susceptibility gene BRCA1 encodes a phosphoprotein of 1863 amino acids containing a highly conserved N-terminal RING finger domain and a C-terminal acidic region typical of several transcription factors. BRCA1 acts as a tumor suppressor that may inhibit the proliferation of breast and ovarian cancer cells. To gain knowledge and to further understand the biological function of BRCA1, we examined its localization and expression in various tissues from 20-year-old male and female cynomolgus monkeys (Macaca fascicularis) by in situ hybridization using a 35S-labeled human BRCA1 DNA probe fragment derived from exon 11. In mammary glands, BRCA1 expression was primarily located in the duct and acinar epithelial cells. In the ovary, strong BRCA1 expression was detected in granulosa cells in maturing follicles and in luteal cells of the corpus luteum, as well as in the epithelial cells overlying the tunica albuginea. Specific signal was also observed in epithelial cells of the oviduct, endometrium, cervix, and vagina. Moreover, BRCA1 was strongly expressed in the germinal epithelium of the seminiferous tubules as well as over interstitial cells of the testis, in the epithelium of the epididymis, and in epithelial cells bordering the glandular lumen of the seminal vesicles. Signal was also detected in both the anterior and posterior lobes of the pituitary. In the adrenal glands, the signal was greater in the zona glomerulosa compared to the two other cortical zones, whereas the medullary cells were weakly labeled. In the stomach, and in small and large intestine, epithelial cells of the crypts usually exhibited stronger positive reaction than that observed over surface epithelial lining cells. BRCA1 expression was also found in diverse types of epithelial cells of the thyroid, pancreas, salivary glands, trachea, urinary bladder, and kidneys. In addition to demonstrating widespread tissue- and cell-specific expression of the BRCA1 gene in primate tissues, primarily in the epithelia, we observed a weaker but specific signal in various other cell types, suggesting a generalized biological function of BRCA1.

Tick-raccoon associations and the potential for Lyme disease spirochete transmission in the coastal plain of North Carolina.

Raccoons (Procyon lotor) were live-trapped and examined for ticks from July 1990 to July 1993 in the coastal plain of North Carolina on Marine Corps Base, Camp Lejeune, North Carolina (USA). Five species of ixodid ticks were found on 351 (78%) of 449 raccoons. Amblyomma americanum was the most abundant tick found on raccoons. Dermacentor variabilis, Ixodes texanus, and Ixodes scapularis were frequently collected, while Ixodes cookei were rarely collected from raccoons. Tick burdens were not affected by the age, sex, or trap location of captured raccoons. Ticks parasitizing raccoons had varying seasonal patterns of abundance. Amblyomma americanum were generally collected from raccoons year around, but infestation intensities were greatest in summer from June to September. Dermacentor variabilis adults were most abundant in mid-summer while peak numbers of larvae were collected in the fall. Infestation intensities of Ixodes texanus larvae were greatest in fall and winter months while nymphs were most abundant in winter and spring. No males were collected from raccoons, but females were most frequently collected in the spring and declined in abundance in the summer with no specimens collected in the fall or winter. Numbers of 1. scapularis adults appeared to reach peak numbers in the fall while larvae and nymphs were most abundant on raccoons in winter. Spirochetes, Borrelia burgdorferi, were identified in a small percentage (0.2%) of host-seeking A. americanum nymphs and adults, and I. scapularis adults by immunofluorescent antibody assays. Similarly, a small percentage (1.9%) of host-associated A. americanum, D. variabilis, I. texanus and I. cookei contained B. burgdorferi. Borrelia burgdorferi spirochetes were cultured from the blood of 23 (26%) of 87 raccoons.

Determinants of success and failure of EMLA.

Although EMLA is known to be an effective topical anesthetic, its rate of success is unknown. Indeed, researchers have suggested that EMLA may fail with young and apprehensive children. Therefore, the objectives of this study were to assess EMLA's rate of success as well as factors which predict success. A double-blind, placebo-controlled design was utilized. The sample included 258 children and adolescents aged 5-18 years who were having venipuncture or intravenous (i.v.) cannulation. After having their anxiety assessed, subjects were randomly assigned to have EMLA or placebo applied over the procedure site for 90 min. The visual analogue scale was used to assess pain caused by removal of the semi-permeable dressing and by the procedure. Other information that was collected included: duration of drug application, interval between drug removal and procedure, skin changes at bandage and drug sites and rated difficulty of the procedure. EMLA was successful 84% of the time for venipuncture and 51% of the time for i.v. cannulation. Factors which predicted success of EMLA included type of procedure, duration of drug application and anxiety. EMLA was less successful for i.v. cannulation compared to venipuncture even with duration of drug application controlled. Those who had a poor outcome were more anxious than those with a good outcome. Age of child was not a factor. Strategies for improving efficient use of EMLA were recommended.

Minority influence: a meta-analytic review of social influence processes.

A meta-analytic review of 97 minority influence experiments evaluated the processes by which sources advocating deviant, minority opinions exert influence. Minority impact was most marked on measures of influence that were private from the source and indirectly related to the content of the appeal and less evident on direct private influence measures and on public measures. This attenuated impact of minorities on direct private and public measures suggests that in response to normative pressures, recipients avoided aligning themselves with a deviant source. Mediator analyses revealed that minorities perceived as especially consistent in the advocacy of their views were especially influential. The relation between normative and informational pressures in the minority influence paradigm was discussed.

Placebo-controlled comparative study of the anxiolytic activity and of the pharmacokinetics of oral and sublingual lorazepam in generalized anxiety.

In a randomized crossover study, twelve patients presenting a generalized anxiety disorder received either a 1 mg oral tablet or a 1 mg sublingual tablet of lorazepam three times daily for 7 days. After a 7-day washout period, each patient received a 7-day treatment with the other tablet form. Treatments were administered in a double-blind manner using placebos of both the oral and sublingual tablets. Psychiatric evaluations were carried out before and following each of the three periods. Blood samples were drawn at intervals for 48 h following the last dose of each treatment. The plasma concentrations of lorazepam were measured by gas chromatography using an electron-capture detector. Both the oral and sublingual lorazepam produced a significant anxiolytic effect; there was no statistically significant difference between the therapeutic effectiveness of the two forms of lorazepam. The main pharmacokinetic parameters for the oral and sublingual tablets were, respectively: elimination half-life 15.6h and 11.7h; maximal concentration 40.8 ng ml-1 and 42.2 ng ml-1; time to reach maximal concentration 1.2h and 1.4h; corrected area under the curve 310.6 ng hml-1 and 313.6 ng hml-1. There was no statistically significant difference between the oral and sublingual tablets for any of the pharmacokinetic parameters measured.

A comparative double-blind controlled study of trimipramine and amitriptyline in major depression: lack of correlation with 5-hydroxytryptamine reuptake blockade.

Thirty-four hospitalized patients with major depression were enrolled in a 3-week double-blind parallel comparative study of trimipramine and amitriptyline. Following a 1-week washout period, patients randomly received one of the two drugs up to 100 mg twice daily on a fixed increment dosage schedule. Both treatments produced a rapid significant clinical improvement that occurred in a predominantly linear fashion. The pattern of improvement was very similar with both drugs. There was no significant correlation between plasma levels of trimipramine and desmethyl-trimipramine and clinical improvement. A negative correlation between amitriptyline plasma levels and clinical improvement was found, whereas a positive correlation occurred with the nortriptyline levels. Amitriptyline, and to a lesser extent trimipramine, prolonged intracardiac conduction. In the amitriptyline group only, this effect was accompanied by significant increases of heart rate and blood pressure. Platelet serotonin content was decreased by 57% by the amitriptyline treatment but remained unchanged in the trimipramine group. This finding constitutes the first clinical evidence that trimipramine does not exert its antidepressant effect through 5-hydroxytryptamine reuptake blockade. It is proposed that neuronal sensitization to 5-hydroxytryptamine might mediate the therapeutic effect of tricyclic antidepressant drugs.

Reduced excitatory effect of kainic acid on rat CA3 hippocampal pyramidal neurons following destruction of the mossy projection with colchicine.

Rats were injected unilaterally with colchicine in the dentate gyrus of the dorsal hippocampus. Two weeks later, under urethane anesthesia, extracellular recordings were obtained on both sides from pyramidal neurons of the CA1 and of the CA3 regions of the dorsal hippocampus. Microiontophoresis was used to assess the responsiveness of these neurons to kainate, glutamate and ibotenate. The colchicine injection produced a nearly complete destruction of the granule cells of the ipsilateral dentate gyrus and of their mossy fiber projections to CA3 without apparently affecting other hippocampal neurons. On the lesioned side, the potency of kainate in activating CA3 pyramidal neurons was reduced by 94% compared to the same neurons on the intact side. However, the excitatory effect of glutamate was unchanged and that of ibotenate only slightly reduced. Kainate was 80 times more potent in activating CA3 than CA1 pyramidal neurons on the intact side, whereas this ratio had dropped to 2.6 on the lesioned side. The selective decrease of the effectiveness of kainate in activating CA3 pyramidal neurons following the colchicine lesion suggests that this amino acid, but not glutamate and ibotenate, produces most of its excitatory effect in the intact CA3 region by releasing (an) excitatory neurotransmitter(s) from mossy fibers terminals, the nature of which remains to be identified.

Low-back pain: an orthopedic medicine approach.

Many patients suffering from low-back pain present to a family physician. This paper will deal specifically with the moving parts of the lumbar spine as the source of low-back pain: muscles, discs, ligaments, apophysial (facet) joints. A detailed systematic approach is suggested to facilitate the identification of the particular tissues involved. Various modes of treatment-manipulations, tractions, epidural injections and sclerotherapy-are discussed.

Teratological evaluation of picloram potassium salt in rabbits.

The embryotoxic and teratogenic potential of orally administered picloram potassium salt was evaluated in New Zealand white rabbits. Artificially inseminated rabbits were given 0, 40, 200 or 400 mg picloram acid equivalent/kg body weight/day in the form of picloram potassium salt in aqueous solution on days 6 to 18 of gestation. The foetuses were removed for examination on day 29 of gestation. Transient weight loss was observed among rabbits given 200 or 400 mg/kg/day of the test material, though the total weight gain of the treated groups during gestation was comparable to that of controls. A few isolated, sporadic cases of foetal malformations were observed in the dosed groups, but there was no indication of a dose-related embryotoxic or teratogenic response to treatment.

A confound in the standard control condition of the Stroop experiment.

Two experiments were performed to investigate the magnitude of the confound in the standard control condition of the Stroop experiment. The confound resides in the fact that only color changes from one item to the next in the control condition, whereas both color and configuration of the items that represent color change in the usual experimental conditions. The results of both experiments showed small but significant increases in color-naming time when both colors and non-verbal shapes changed from one item to the next. These findings are discussed in the context of the role of factors in selective attention in the color-naming task. While response competition appears to be the more substantial source of interference in Stroop color-word effects, a smaller but more general source of interference due to selective attention appears in whole-list tasks with more than one dimension of item-to-item change.

Short-term efficacy trial and twenty-four-month follow-up of flunisolide nasal spray in the treatment of perennial rhinitis.

Seventy-eight patients with perennial rhinitis underwent a double-blind, placebo-controlled. 12-wk trial with flunisolide nasal spray, a new potent topical steroid. Eighteen of these patients were followed in an open study and evaluated at intervals for side effects and dosage of spray used. Baseline and plasma cortisol concentrations were performed before and at the end of the 12-wk, double-blind period. Adrenocorticotropic hormone (ACTH) stimulation testing was performed on six patients after 1 yr of flunisolide therapy at 300 micrograms/day or less. Flunisolide was found to be safe and effective over a short period. Over a 2-yr follow-up there were no serious side effects or evidence of adrenal suppression. Ten patients with perennial rhinitis continue to obtain subjective benefit after 2 yr of therapy with flunisolide nasal spray.

Multicenter study of flunisolide aerosol in adult patients with steroid-dependent asthma.

Seventy-three adult, steroid-dependent asthmatic patients participated in a 16-wk, double-blind study testing the efficacy of flunisolide aerosol. Forty received flunisolide, and 33 received placebo. The mean daily prednisone requirement of patients receiving flunisolide fell 59.2% during the testing period, and that of the patients receiving placebo fell 19.7%. The median daily prednisone dose dropped 74.4% in the flunisolide group and 4.2% in the placebo group (p = 0.006). In the flunisolide group 75% tapered use of oral steroids 50% or more, and 27.5% stopped taking oral steroids completely. In the placebo group 36% tapered use of oral steroids 50% or more, and only 12% stopped taking them completely. Despite their reduction in systemic steroids, those patients receiving flunisolide achieved significantly greater reduction in the daily severity of wheezing (p = 0.014) and frequency of asthma attacks (p = 0.049) than did those receiving placebo. In the final evaluation of therapeutic response, 70% of patients receiving flunisolide were rated as having a very good or good response, and 30% were rated as having a fair or poor response. In contrast 33% of patients receiving placebo were rated as very good or good, and 67% were rated as fair or poor (p = 0.0009). No serious reactions were reported. Plasma cortisols showed an average increase of 42.9% in the flunisolide group but no change in the placebo group. Flunisolide aerosol is a well-tolerated and effective agent in the treatment of steroid-dependent asthma.

Brainstem evoked potentials to tonepips in notched noise.

Notched noise can be used to mask the frequency spread of acoustic energy in the brief tonepips that are used to elicit brainstem evoked potentials. Brainstem responses to tonepips and notched noise can therefore be used to evaluate auditory thresholds at particular frequencies. These thresholds are more frequency-specific than those obtained using tonepips alone, and are accurate to within 20 dB of the conventional audiometric thresholds.