Association between gastrointestinal phenotypes and weight gain in younger adults: a prospective 4-year cohort study.

BACKGROUND/OBJECTIVES: Gastrointestinal phenotypes have previously been associated with obesity, however it is unknown if these phenotypes are a cause or a consequence of obesity and weight gain. Our aim was to assess whether these gastrointestinal phenotypes are associated with future weight gain in younger adults. SUBJECTS/METHODS: At baseline, 126 adult participants under the age of 35 were weighed and underwent measurement of gastrointestinal phenotypes including gastric emptying (GE), gastric volume, satiation, satiety, and gastrointestinal hormones. Patients were reappraised after median 4.4 years unless, during the period of follow-up, they participated in a formal weight loss program, received obesity-weight loss interventions, or developed a health condition likely to affect weight. Participants were dichotomized into two groups for each phenotype at the median of each phenotype. RESULTS: In total, 60 participants met criteria for inclusion and were evaluated after a median of 4.4 years [IQR: 3.5-5], 36 participants were excluded due to conditions that would abnormally affect weight during study period including pregnancy and weight loss treatment, and 30 participants were lost to prospective follow-up. Faster GE was significantly associated with weight gain. Those with faster GE at baseline (n = 30) gained a median of 9.6 kg [3.1-14.9] compared with those with slower GE at baseline (n = 30) who gained a median of 2.8 kg [-4.6 to 9.2] (p = 0.03), over the follow-up period. There was no association between the other phenotypes and weight gain. CONCLUSIONS: In adults ≤35 years old, faster gastric emptying is associated with significantly increased weight gain over the medium term. This provides supportive evidence for the role of gastric emptying in weight gain and development of obesity.

Effects of Lower-Body Muscular Fatigue on Vertical Jump and Balance Performance.

Cooper, CN, Dabbs, NC, Davis, J, and Sauls, NM. Effects of lower-body muscular fatigue on vertical jump and balance performance. J Strength Cond Res 34(10): 2903-2910, 2020-Lower-body fatigue can lead to a decline in vertical jump (VJ) and balance performance due to decreased motor control and coordination. The purpose is to determine the effects of lower-body fatigue on VJ and balance performance. Twenty-four recreationally trained individuals participated in a single 1-hour familiarization and testing session. Participants were familiarized with balance, countermovement vertical jump (CMVJ), and static vertical jump (SVJ) using the Vertec. Three trials of static and dynamic balance tests were completed. Three trials of a SVJ and CMVJ were completed in a randomized order pre/post fatigue protocol. Three trials of double-leg and single-leg tests were performed. Dependent t tests analyzed differences between pre/post fatigue protocol for jumping and balance measures. There was a significant (p < 0.001) difference between pre/post measures for SVJ-H (height), CMVJ-H, and CMVJ peak power (PP). Results showed an interaction (p < 0.05) for group by time for CMVJ-H, CMVJ-peak force (PF), SVJ-PF, and SVJ-PP. There were no main effects (p > 0.05) for time or group for SVJ-rate of velocity development and SVJ-impact force (IF). There were no interactions, time effects, and group effects for balance variables (p > 0.05). Bosco protocol decreased VJ height and PF in SVJ, and VJ height and PF, IF, peak velocity, and PP for CMVJ potentially due to decreased muscle control, coordination, and force-generating capacity after fatigue. Practitioners should consider fatiguing effects on individuals performing jumping motions but it seems that fatigue has no effect on balance.

Index of mechanical efficiency in competitive and recreational long distance runners.

The purpose of this investigation was to compare external work and net energy expenditure during a bout of repetitive stretch-shortening cycles between competitive and recreational long-distance runners. Participants were divided into either competitive or recreational runners based on their maximal oxygen consumption and self-reported 1600 m times. The stretch-shortening cycle involved a repetitive hopping protocol on a force plate while measuring oxygen consumption and lactate accumulation for a total of 10 min. External work and net energy expenditure were calculated for 3 min after steady state was achieved and the ratio between these variables was utilised as an index of mechanical efficiency. Lower extremity stiffness was calculated during this interval as well. Net energy expenditure was significantly lower in competitive runners (152.6 ± 33.3 kJ) in comparison to recreational runners (200.6 ± 41.4 kJ) (P = 0.02) given similar amounts of external work performed in both groups (competitive runners = 65.6 ± 20.1 kJ, recreational runners = 68.8 ± 12.1 kJ) (P = 0.67). Index of mechanical efficiency was significantly different between competitive runners (43.2 ± 9.0%) and recreational runners (34.8 ± 5.3%) (P = 0.03). No significant differences were found in lower extremity stiffness (P = 0.64). Competitive distance runners can perform similar levels of external work with lower net energy expenditure and thus a higher index of mechanical efficiency during repetitive stretch-shortening cycles in comparison to recreational runners with similar values of lower extremity stiffness. This ability could possibly be due differences in muscle-tendon length changes, muscle pre-activation, cross-bridge potentiation and short-latency reflex responses as a result of training which should be considered for future investigation.

The golden pig, reflections as ancestral blessings: the reflecting process in teaching family therapy.

This is an example of a postmodern, dialogical approach to teaching family therapy based on the work of such practitioners as Tom Andersen, Michael White, and Lynn Hoffman, among others. It demonstrates the way in which the reflecting process connects all of the participants in a web of meanings both educational and transformational. This particular consultation, which includes the author, her graduate students, the client, and guest participant Lynn Hoffman, ends with an unexpected ritual of intergenerational appreciation. Privileging the transcript, it is presented as a kind of theatre where the learning is revealed more through the dialogue than through authorial analysis. The experience is embedded in an "ethics of participation" (Hoffman, 1992) where social connectedness and attunement are key.

Physical activity is associated with accelerated gastric emptying and increased ghrelin in obesity.

BACKGROUND: Rapid gastric emptying, increased food intake, and alterations in gastrointestinal hormones are associated with obesity. The effect of regular physical activity (PA) on food intake, gastric emptying (GE), gastric accommodation, and gastrointestinal (GI) hormones in adults with obesity remains unclear. Our aim was to compare, at time of presentation, weight trends, eating behavior, GE, and GI hormone levels among individuals with obesity who engage in regular PA compared to those who do not. METHODS: In 270 participants with obesity, we performed validated measurements of GI phenotypes: GE of solids and liquids, gastric volume (GV) during fasting and after consumption of 200 mL Ensure®, satiety by kcal intake (T-kcal) during a buffet meal, satiation (volume to fullness [VTF] and maximal tolerated volume [MTV]) of a liquid nutrient, and plasma levels of fasting and postprandial GLP-1, PYY, CCK, and ghrelin. Physical Activity Stages of Change Questionnaire was used to assess whether participants were regularly PA or not. KEY RESULTS: PA was associated with lower BMI (Δ 2.01 kg/m2 , P = .001) and body weight (Δ 4.42 kg, P = .0278). GE of solids (T-50% Δ 7.54 min, P = .021) and liquids (T-50% Δ 2.99 min, P = .029%) was significantly more rapid in physically active participants. PA was also associated with relatively higher postprandial ghrelin AUC (Δ 10.4 pg/mL, P = .015). There was no significant difference in postprandial satiation, satiety, GV, or other GI hormones (CCK, PYY, or GLP-1) between groups. CONCLUSIONS & INFERENCES: Physical activity is associated with lower BMI, but faster GE and higher postprandial ghrelin levels, two factors that are also associated with obesity.

Ileo-colonic delivery of conjugated bile acids improves glucose homeostasis via colonic GLP-1-producing enteroendocrine cells in human obesity and diabetes.

BACKGROUND: The bile acid (BA) pathway plays a role in regulation of food intake and glucose metabolism, based mainly on findings in animal models. Our aim was to determine whether the BA pathway is altered and correctable in human obesity and diabetes. METHODS: We conducted 3 investigations: 1) BA receptor pathways were studied in NCI-H716 enteroendocrine cell (EEC) line, whole human colonic mucosal tissue and in human colonic EEC isolated by Fluorescence-activated Cell Sorting (ex vivo) from endoscopically-obtained biopsies colon mucosa; 2) We characterized the BA pathway in 307 participants by measuring during fasting and postprandial levels of FGF19, 7αC4 and serum BA; 3) In a placebo-controlled, double-blind, randomised, 28-day trial, we studied the effect of ileo-colonic delivery of conjugated BAs (IC-CBAS) on glucose metabolism, incretins, and lipids, in participants with obesity and diabetes. FINDINGS: Human colonic GLP-1-producing EECs express TGR5, and upon treatment with bile acids in vitro, human EEC differentially expressed GLP-1 at the protein and mRNA level. In Ussing Chamber, GLP-1 release was stimulated by Taurocholic acid in either the apical or basolateral compartment. FGF19 was decreased in obesity and diabetes compared to controls. When compared to placebo, IC-CBAS significantly decreased postprandial glucose, fructosamine, fasting insulin, fasting LDL, and postprandial FGF19 and increased postprandial GLP-1 and C-peptide. Increase in faecal BA was associated with weight loss and with decreased fructosamine. INTERPRETATIONS: In humans, BA signalling machinery is expressed in colonic EECs, deficient in obesity and diabetes, and when stimulated with IC-CBAS, improved glucose homeostasis. ClinicalTrials.gov number, NCT02871882, NCT02033876. FUNDING: Research support and drug was provided by Satiogen Pharmaceuticals (San Diego, CA). AA, MC, and NFL report grants (AA- C-Sig P30DK84567, K23 DK114460; MC- NIH R01 DK67071; NFL- R01 DK057993) from the NIH. JR was supported by an Early Career Grant from Society for Endocrinology.

Considerations for laboratory animal imaging center design and setup.

In vivo animal imaging is an outstanding noninvasive tool to study the pathophysiology of disease or response to therapy; additionally, serial imaging reduces the required number of experimental animals. Because of the tremendous capital investment, we recommend the imaging center be a shared resource to facilitate innovative and productive cross-disciplinary scientific collaborations. A shared center also enables a broader range of imaging, as equipment is often cost prohibitive for smaller facilities. A multitude of factors will determine the architectural design, facility efficiency, and functionality. Important considerations to determine during the planning stages include the types of animals to be imaged, types of imaging studies to be performed, types of imaging equipment and related services to be offered, and the location of the imaging center. Architects must work closely with manufacturers to accommodate equipment-related building specifications; facility planners and veterinarians can provide a practical logistical design that will ensure efficient functionality. Miscellaneous considerations include biosecurity levels, use of radioisotopes, and personnel safety in the imaging environment. The ideal imaging center will include space to house animals and perform necessary preimaging procedures, state-of-the-art in vivo imaging devices and the most up-to-date anesthesia, physiological support, and monitoring equipment. The center staff should include imaging specialists for technical development and data analysis. As it is difficult to provide a comprehensive manual for setting up an in vivo animal imaging center, we offer advice based on our experiences with the National Institutes of Health Mouse Imaging Facility. Because magnetic resonance imaging (MRI) is the most expensive imaging tool, requires specific building design considerations, and poses unique occupational health and safety risks, we focus on MRI as the foundation for an imaging facility design.

Gender influences infectivity in C57BL/6 mice exposed to mouse minute virus.

Two natural outbreaks of mouse minute virus (MMV) are described. Observations during management of the naturally infected colonies led to a study in which 4-wk-old C57BL/6NCr and C57BL/6Tac mice were inoculated oronasally with an immunosuppressive variant of MMV (MMVi), as were adult C57BL/6NCr lactating dams or their pups (age, 10 d). By day 28 postinoculation, 100% of the 4-wk-old male C57BL/6NCr and C57BL/6Tac mice, 56.2% of 4-wk-old C57BL/6NCr female and 62.5% of 4-wk-old C57BL/6Tac female mice, 100% of adult lactating C57BL/6NCr dams, and 100% of inoculated pups (10 d) had seroconverted. Serologically positive nursing dams did not infect their nursing pups. In contrast, when nursing pups were inoculated, 100% of their dams seroconverted by 28 d postinoculation. Only 1 of 4 facility sentinels (Tac:SW female mice) seroconverted to MMVi and none of the 4 research sentinels (Tac:SW female mice) seroconverted under a once-weekly bedding transfer program. Consequently, 4 new research Tac:SW sentinels of each gender (n = 8) were placed in known-positive cages at cage-change; 100% of the male mice but 0% of the females seroconverted by day 48. Study results suggest gender influences both infectivity and the ability to detect subclinical infections of MMVi. Other factors that may influence detection of MMV include mouse strain or stock, short shedding period, and prolonged time between cage changes. In light of the data from both the natural infections and the experimental cases, cessation of breeding likely will be beneficial when trying to eradicate this virus.

The role of the veterinary staff in mouse breeding colony management.

The rapid increase in the production and use of transgenic mice has been a boon for biomedical research and a challenge for the animal care and use programs responsible for providing housing and medical care to these animals. The authors suggest ways in which the veterinary staff can successfully organize and manage transgenic mouse breeding programs to reduce uncontrolled breeding and the problems associated with it.

The impact of laryngopharyngeal reflux on patient-reported quality of life.

OBJECTIVES/HYPOTHESIS: The objectives were to assess patient-reported outcomes, specifically, the health-related quality of life of patients with laryngopharyngeal reflux, and to compare those reported levels with the health-related quality of life of patients with gastroesophageal reflux disease and a general population. STUDY DESIGN: Prospective study. METHODS: As part of a prospective study to validate a health-related quality of life instrument for laryngopharyngeal reflux, patient-reported data were collected before the initiation of therapy. Use of the Short Form-36 (SF-36), a generic instrument, allowed the health-related quality of life of the patients with laryngopharyngeal reflux to be compared with benchmarks existing for patients with gastroesophageal reflux disease and a general U.S. population. RESULTS: The 117 patients with laryngopharyngeal reflux often reported multiple symptoms, most frequently, chronic throat-clearing (85.5%), globus (82.1%), and hoarseness (80.3%). Their mean health-related quality of life was statistically significantly worse than that of a general U.S. population in seven of the eight SF-36 domains. The most dramatic differences between patients with laryngopharyngeal reflux and the general population were in social functioning and bodily pain (P <.001). Mean scores for patients with laryngopharyngeal reflux were significantly lower than those for patients with gastroesophageal reflux disease in social functioning (P <.001) and vitality (P =.0017). In five of the six remaining domains, patients with laryngopharyngeal reflux reported lower mean scores than did patients with gastroesophageal reflux disease, but those differences were not statistically significant. CONCLUSION: The study's assessment of health-related quality of life suggests that laryngopharyngeal reflux has a significant negative impact on the lives of patients. Although its impact is similar in some respects to that of gastroesophageal reflux disease, laryngopharyngeal reflux has a more significant impact on patients' social functioning and vitality.

Euthanasia of mouse fetuses and neonates.

We sought to determine whether any of the common methods of euthanasia for adult rodents would lead to an acceptable death for fetuses or neonates. We wanted to identify a method that was rapid, free of signs of pain or distress, reliable, and minimally distressful to the person performing the procedure and that minimized the amount of handling required to perform the procedure. We evaluated six methods of euthanasia, with and without anesthesia, in three age groups of mice: gravid mice (E14-20) and neonatal pups (P1-P7 and P8-P14). Euthanasia methods included: halothane inhalation, carbon dioxide inhalation, intraperitoneal sodium pentobarbital, intravenous potassium chloride, and cervical dislocation with and without anesthesia. Noninvasive echocardiography was used to assess heartbeat during euthanasia. With cardiac arrest as the definition of death, no method of euthanasia killed fetal mice. Halothane inhalation (5% by vaporizer) was not an acceptable method of euthanasia for mice of the age groups tested. Intraperitoneal administration of sodium pentobarbital for euthanasia required a higher dose than the previously established dose, and there is a risk of reduced efficacy in pregnant animals due to potential intrauterine injection. Carbon dioxide asphyxiation was the most efficient method of euthanasia for neonatal mouse pups P1-14. For pregnant adult mice, intravenous potassium chloride under anesthesia, carbon dioxide asphyxiation, and cervical dislocation alone or under anesthesia were excellent methods of euthanasia.

Spontaneous Rhabdomyosarcomas in (A/J x CBA/J)Fl Mice.

Spontaneous rhabdomyosarcoma is rare in laboratory rodents. Incidence was estimated as 2.4/100,000 in BALB/c mice; incidence of <0.5% for rodents is generally accepted. We describe spontaneous rhabdomyosarcoma in 2 aged, female ([A/J x CBA/ J]F1) mice. Part of a small breeding colony, these mice were experimentally naive; incidence was estimated as 12.5%. Tumors were located in the muscles of the thoracic wall and muscles of the dorsolumbar region. Cross-striations were detected, using phosphotung- stic acid hematoxylin stain; presence of cross-striations within the neoplasm are diagnostic for rhabdomyosarcoma.

Urinary Bladder Catheterization of Female Mice and Rats.

Catheterization of the urinary bladder of rats and mice is necessary for a variety of clinical and experimental reasons. The anatomy of the female mouse and rat is unique in that the urinary orifice is external and just anterior to the vaginal opening. This characteristic makes the bladder of these species easier to catheterize than that of other species. Methods cited in the literature do not adequately describe techniques that facilitate ease of urinary bladder catheterization (1). We describe a simple technique for urinary catheterization in adult female mice and rats.

Inoculation of Staphylococcus xylosus in SJL/J mice to determine pathogenicity.

An experimental study was performed to investigate whether intradermal tail inoculations of Staphylococcus xylosus would result in pathologic lesions in the SJL/J strain of mice (Mus musculus). This organism historically has been classified as a nonpathogenic, commensal bacterium associated with skin and mucous membranes and rarely implicated in infections. In this study, SJL/J mice inoculated with S. xylosus developed cutaneous tail lesions post-inoculation, and the organism was recovered from those lesions. Inoculation was accomplished by surgically inserting silk suture impregnated with the concentrated suspension of bacteria. In addition, a superficial abrasion was created adjacent to the suture, and a bacterial suspension was applied. Approximately 80% of the mice in the inoculated groups developed dermatologic lesions, compared with 0% in the control group. Mice with lesions were treated with Sulfamethoxazole-Trimethoprim in the drinking water continuously for 28 days. For the mice assigned to the treatment group, this treatment resulted in resolution of the cutaneous tail lesions.

Mouse and rat anesthesia and analgesia.

Many animal models used in neuroscience research must be surgically created and/or anesthetized for imaging studies. The purpose of this unit is to review the advantages and disadvantages of various anesthetic and analgesic agents in rodents; to discuss state-of-the-art methods for monitoring anesthesia; and to provide tips for troubleshooting problems with anesthesia.

Effect of housing density on reproductive parameters and corticosterone levels in nursing mice.

The Guide for the Care and Use of Laboratory Animals (Guide) recommends minimum floor space per mouse based on weight, with no other factors considered. We conducted a randomized experiment to evaluate the effect of housing density on reproductive indices and corticosterone levels in lactating mice. Female mice matched for age, strain, and date-of-pregnancy were housed individually. At parturition the dams were randomly allocated to have litters culled or remain intact. The experimental group had litters culled to meet the Guide's space density requirement. Litters of the second group were maintained as the numbers born to each dam. Fecal corticosterone levels (first-generation mice only), growth, and weaning weights were measured for mice in all cages; in addition, the reproductive behavior of progeny generated under both housing conditions was assessed to determine whether a space x litter size interaction affected subsequent reproduction. The growth rates for pups from culled litters were significantly greater than those from intact litters. The first-generation pups showed no statistically significant differences in fecal corticosterone or reproductive parameters. The second-generation pups showed no statistically significant differences in growth rates. The results of the study suggest that a strict interpretation of space requirements as listed in Table 2.1 of the Guide is not warranted for lactating dams with litters.

Validity of gout diagnoses in administrative data.

OBJECTIVE: To determine the utility of using administrative data for epidemiologic studies of gout by examining the validity of gout diagnoses in claims data. METHODS: From a population of approximately 800,000 members from 4 managed care plans, we identified patients who had at least 2 ambulatory claims for a diagnosis of gout between January 1, 1999 and December 31, 2003. From this group, a random sample of 200 patients was chosen for medical record review. Trained medical record reviewers abstracted gout-related clinical, laboratory, and radiologic data from the medical records. Two rheumatologists independently evaluated the abstracted information and assessed whether the gout diagnosis was probable/definite or unlikely/insufficient information. Discordant physician ratings were adjudicated by consensus. Based on record reviews, patients were also classified according to the American College of Rheumatology (ACR), Rome, and New York gout criteria and these results were compared with the physician global assessments. RESULTS: There were 121 patients rated as having probable/definite gout by physician consensus, leading to a positive predictive value of >or=2 coded diagnoses of gout of 61% (95% confidence interval 53-67). There was low concordance between physician assessments and established gout criteria including ACR, Rome, and New York criteria (kappa = 0.17, 0.16, and 0.20, respectively). CONCLUSION: Use of administrative data alone in epidemiologic and health services research on gout may lead to misclassification. Medical record reviews for validation of claims data may provide an inadequate gold standard to confirm gout diagnoses.